ANTIMICROBIAL USE PRACTICES IN MBAGATHI HOSPITAL, NAIROBI-KENYA:

A POINT PREVALENCE SURVEY

MUYU MWENDE GRATIA (BPharm)

U51/7177/2017

A thesis submitted in partial fulfillment for the requirements for the award of Master’s Degree in
Pharmacoepidemiology and Pharmacovigilance

Department of Pharmacology and Pharmacognosy

School of Pharmacy

University of Nairobi

JUNE 2020
UNIVERSITY OF NAIROBI DECLARATION OF ORIGINALITY

Name of Student: Muyu Mwende Gratia

Reg. Number: U51/7177/2017

College: College of Health Sciences

School: School of Pharmacy

Department: Department of Pharmacology and Pharmacognosy

Course Name: Master of Pharmacy, Pharmacoepidemiology and Pharmacovigilance

Title of the work: Antimicrobial use patterns in Mbagathi Hospital, Nairobi-Kenya: A

point prevalence survey

DECLARATION

1. I understand what Plagiarism is and I am aware of the University’s policy in this regard.
2. I declare that this thesis is my original work and has not been submitted elsewhere for examination,
the award of a degree or publication. Where other people's work or my own work has been used,
this has properly been acknowledged and referenced in accordance with the University of Nairobi's
requirements.
3. I have not sought or used the services of any professional agencies to produce this work.
4. I have not allowed, and shall not allow anyone to copy my work with the intention of passing it off
as his/her own work.
5. I understand that any false claim in respect of this work shall result in disciplinary action, in
accordance with University anti-Plagiarism Policy.

Signature _____________________ Date ________________________

Muyu Mwende Gratia (B. Pharm)
U51/7177/2017

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APPROVAL BY SUPERVISORS

This is to certify that this thesis has been submitted for examination with our approval as University
supervisors.

Dr. Eric M. Guantai, PhD

Department of Pharmacology and Pharmacognosy
School of Pharmacy, University of Nairobi

Signature:………………………………………………….. Date……………………….

Prof. Faith A. Okalebo, PhD

Department of Pharmacology and Pharmacognosy
School of Pharmacy, University of Nairobi

Signature:………………………………………………….. Date……………………….

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 DEDICATION

I dedicate this work to my family who have constantly encouraged me throughout the study
period. My dear husband, George Moturi, for allowing me to read during family time.

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 ACKNOWLEDGEMENTS

First and foremost to God for giving me the knowledge, strength and zeal to pursue this
course.

Secondly special thanks to Dr. Eric Guantai and Professor Faith Okalebo for the support,
guidance, advise, mentorship and invaluable time offered towards completing this work.

Thirdly, Mbagathi Hospital Research Committee, headed by Dr Kimutai, who granted me

permission to carry out research in the facility.

Lastly the research assistants who devoted their time to data collection.

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TABLE OF CONTENTS

UNIVERSITY OF NAIROBI DECLARATION OF ORIGINALITY .................................... ii

APPROVAL BY SUPERVISORS .............................................................................................. iii

DEDICATION .............................................................................................................................. iv

ACKNOWLEDGEMENTS.......................................................................................................... v

TABLE OF CONTENTS............................................................................................................. vi

LIST OF TABLES ....................................................................................................................... ix

LIST OF FIGURES ...................................................................................................................... x

LIST OF ABBREVIATIONS AND ACRONYMS .................................................................. xii

DEFINITIONS OF OPERATIONAL TERMS ...................................................................... xiv

ABSTRACT ................................................................................................................................ xvi

Chapter 1 : INTRODUCTION .................................................................................................... 1

1.1 Background ................................................................................................................................... 1
1.2 Statement of the problem ............................................................................................................... 2
1.3 Research Questions ....................................................................................................................... 3
1.4 Study Objectives............................................................................................................................ 4
1.4.1 General objective ................................................................................................................... 4
1.4.2 Specific objectives ................................................................................................................. 4
1.5 Study Justification ......................................................................................................................... 4

Chapter 2 : LITERATURE REVIEW .................................................................................... …6

2.1 Types of antimicrobials ................................................................................................................. 6
2.1.1.Antibacterials .............................................................................................................................. 6
2.1.2 Antifungals .................................................................................................................................. 7
2.1.3 Antivirals..................................................................................................................................... 8
2.1.4 Anti-parasitic agents ................................................................................................................... 8
2.2 Types of Misuse of Antimicrobials ............................................................................................... 8
2.3 Factors that contribute to antimicrobial misuse ................................................................................ 9
2.3.1 Poor quality antimicrobials ......................................................................................................... 9
2.3.2 Poor regulatory framework ......................................................................................................... 9
2.3.3 Health facility factors ................................................................................................................ 10
2.3.4 Prescriber related factors ........................................................................................................... 10
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 2.3.5 Patient related factors ................................................................................................................ 10
2.3.6 Increasing consumption of antimicrobials in the agriculture and animal industry .................. 10
2.4 Antimicrobial Resistance (AMR) ................................................................................................ 11
2.4.1 Prevalence of Antimicrobial Resistance .............................................................................. 13
2.5 Clinical and Economic Impact of Antimicrobial Resistance ...................................................... 14
2.6 Strategies to mitigate Antimicrobial resistance ........................................................................... 15
2.7 Protocols for studying antimicrobial use ..................................................................................... 16
2.8 Conceptual Framework on Types of Antimicrobial Misuse and their Causes ............................ 17

Chapter 3 : METHODS .............................................................................................................. 19

3.1 Study design ................................................................................................................................ 19
3.2 Study site ..................................................................................................................................... 19
3.3 Study Population ......................................................................................................................... 20
3.4 Eligibility criteria ........................................................................................................................ 20
3.4.1 Inclusion criteria .................................................................................................................. 20
3.4.2 Exclusion criteria ................................................................................................................. 20
3.5 Sampling ...................................................................................................................................... 20
3.6 Data Collection instruments and procedures ............................................................................... 21
3.7 Quality Assurance ....................................................................................................................... 22
3.8 Data Management........................................................................................................................ 22

Chapter 4 : RESULTS ................................................................................................................ 25

4.1 Participants Recruitment and Enrollment ........................................................................................ 25
4.2 Bed capacity and occupancy in the wards surveyed ........................................................................ 25
4.3 Socio-demographic Characteristics of Study Participants. .............................................................. 26
4.4 Medical characteristics of study participants .................................................................................. 26
4.5 Prior Antimicrobial Use by Participants of the Study...................................................................... 27
4.6 Antimicrobials prescribed during admission at Mbagathi Hospital ................................................ 28
4.6.1 Types of antimicrobials prescribed ........................................................................................... 28
4.6.2 Distribution of number of antimicrobials prescribed per patient .............................................. 29
4.6.3 Frequency of individual antimicrobials prescribed at Mbagathi Hospital ................................ 30
4.7 Duration, Frequency and Route of antimicrobial use ...................................................................... 31
4.8 Indications for antimicrobial use...................................................................................................... 32
4.8.1 Indications in medical, maternity and surgical wards ............................................................... 32
4.8.2 Indications in the nursery and paediatric wards ........................................................................ 33
4.9 Leading indications for antimicrobial use in Mbagathi Hospital ..................................................... 34
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 4.10 Prescribed Daily Doses and associated Defined Daily Doses in Patients above 18 Years ............ 35
4.10.1 Association Between Prescribed Daily Doses and Gender .................................................... 36
4.10.2 Comparison of Prescribed Daily Doses and Ward Type ........................................................ 37
4.11 Prophylactic use of the antimicrobials. .......................................................................................... 38
4.12 Culture and sensitivity testing ........................................................................................................ 39
4.13 Compliance with WHO indicators and specific guidelines for antimicrobial prescribing at
Mbagathi Hospital .................................................................................................................................. 39
4.14 Linear regression for risk factors for number of antimicrobials prescribed per patient................. 40

Chapter 5: DISCUSSION, CONCLUSION AND RECOMMENDATIONS ........................ 42

5.1 General Discussion .......................................................................................................................... 42
5.2 Strengths and Limitations of the Study ........................................................................................... 47
5.3 Conclusion ....................................................................................................................................... 47
5.4 Recommendations ............................................................................................................................ 48
5.4.1 Recommendations for practice................................................................................................. 48
5.4.2 Recommendations for policy .................................................................................................... 49
5.4.3 Recommendations for future research ...................................................................................... 49

REFERENCES ............................................................................................................................ 50

APPENDICES ............................................................................................................................. 57

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LIST OF TABLES

Table 4.1: Bed capacity and occupancy in Mbagathi Hospital .................................................................. 26

Table 4.2. Social Demographic Characteristics of survey Participants ..................................................... 26

Table 4.3. Medical characterisics of study participants ............................................................................. 27

Table 4.4. Prior Antimicrobial Use by the Participants in the Study ......................................................... 28

Table 4.5. Frequency of individual antimicrobials prescribed at Mbagathi Hospital ............................... 31

Table 4.6. Duration Frequency and Route of administration of antimicrobials ........................................ 32

Table 4.7. Indications in medical, maternity and surgical wards ............................................................... 33

Table 4.8. Indications in nursery and paediatrics....................................................................................... 34

Table 4.9. Prescribed and Defined Daily Doses in Patients above 18 Years ............................................ 35

Table 4.10. Comparison of Prescribed Daily Doses by Gender ................................................................ 37

Table 4.11. Comparison of Prescribed Daily Doses and Ward Type ........................................................ 38

Table 4.12. Prophylactic use of the antimicrobials .................................................................................... 38

Table 4.13. Compliance with WHO indicators for antimicrobial prescribing at Mbagathi Hospital ........ 40

Table 4.14. Linear regression for risk factors for number of antimicrobials prescribed per patient ......... 41

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LIST OF FIGURES

Figure 2.1. Factors that contribute to antimicrobial misuse (22). .............................................................. 11

Figure 2.2. Conceptual Framework on Types of Antimicrobial Misuse and their Causes. ....................... 18

Figure 4.1. Consort diagram of participants in the study ........................................................................... 25

Figure 4.2: Classes of antimicrobials prescribed ....................................................................................... 29

Figure 4.3: Frequency polygon of number of antimicrobials prescribed ................................................... 30

Figure 4.4: Leading indications in Mbagathi Hospital .............................................................................. 34

Figure 4.5: Proportion of patients that received doses above or below WHO defined daily doses ........... 36

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LIST OF APPENDICES

Appendix 1. Global Point Prevalence Survey (GLOBAL-PPS) Ward Form (55)..................................... 57

Appendix 2 . Antimicrobial Use Point Prevalence Survey - Patient Data collection form ....................... 60

Appendix 3. Diagnostic codes (what the clinician aims at treating) (55). ................................................. 77

Appendix 4. Indication Codes for antimicrobials given (55)..................................................................... 81

Appendix 5. ATC codes for antimicrobials given (55). ............................................................................. 83

Appendix 6. Letter of KNH-UON ERC approval...................................................................................... 85

Appendix 7. Mbagathi Hospital Research Committee Approval Letter .................................................. 877

Appendix 8. Co-efficients of determination for each of the bivariable models ......................................... 88

xi
LIST OF ABBREVIATIONS AND ACRONYMS

ADR Adverse Drug Reactions

AMR Antimicrobial Resistance

AMU Antimicrobial Use

ASP Antimicrobial Stewardship Programme

ATC Anatomical Therapeutic Chemical Classification

AZT Zidovudine

BJ Bone and Joint Infections

ENT Ear, Nose, Throat

CNS Central Nervous System

CST Culture and Sensitivity Test

CVS Cardio Vascular System

DDD Daily Defined Dose

DTG Dolutegravir

ESBL Extended Spectrum Beta lactamase

ESKAPE Enterococcus spp, S. aureus, K. pneumonia, Acinetobacter baumannii,

Pseudomonas aeruginosa and Enterobacter spp.

GI Gastrointestinal

GLOBAL PPS Global Point Prevalence Survey

HAART Highly Active Antiretroviral Therapy

HIV Human Immuno-Deficiency Virus

ICU Intensive Care Unit

INN International Non-Proprietary Name

KEML Kenya Essential Medicines List

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MDR TB Multi Drug Resistant Tuberculosis

MP-GEN Medical Prophylaxis in General

MRSA Methicillin Resistant Staphylococcus Aureus

NVP Nevirapine

NICU Neonatal Intensive Care Unit

OBGY Obstetric and Gynecological Infections

Proph BJ Prophylaxis for Bone or Joint Infections

Proph OBGY Prophylaxis for Obstetric or Gynecological Infections

PDD Prescribed Daily Dose

PPS Point Prevalence Survey

RHZE Rifampicin Isoniazid Pyrazinamide Ethambutol

SST Soft Tissue Infections

TB Tuberculosis

TDF/3TC/EFV Tenofovir Lamivudine Efavirenz

WHO World Health Organization

XDR TB Extensively drug resistant Tuberculosis

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 DEFINITIONS OF OPERATIONAL TERMS

Adverse drug reactions: harmful or unpleasant reactions, which result from an intervention related to the
use of a medicinal product.

Antibiotic: A substance that can either be produced or derived from a microorganism. Antibiotics destroy
or inhibit growth of microorganisms.

Antimicrobial: An agent that kills microorganisms or stops their growth. Antimicrobial medicines can
be grouped according to the microorganisms they act primarily against. For example, antibiotics are used
against bacteria and antifungals act against fungi. Antivirals work against viruses whereas anti-malarials
are used for malaria parasites.

Antimicrobial resistance: This is resistance of a microorganism to an antimicrobial agent that was

originally effective for treatment of infections caused by this microorganism. Bacteria, viruses, fungi and
parasites adapt to antimicrobial drugs, resulting in drug inefficacy and persistent infections, with a
subsequent increase in the risks of severe disease and transmission.

Antimicrobial stewardship: Well co-ordinated set of actions which are aimed at promoting responsible
use of antimicrobials. They range from actions at the individual level as well as the national and global
levels. This cuts across human health, animal health and the environment.

Daily defined dose: defined by World Health Organization as the assumed average maintainance dose per
day for a drug used for its main indication in adults. It is a statistical measure of drug consumption that is
used to standardize the comparison of drug usage between different drugs or between different health care
environments.

Empiric therapy: therapy based on experience or clinical guesses in the absence of diagnostic
confirmatory tests.

Irrational use of antimicrobials: Irrational use refers to prescribing that does not conform to prescribed
standards of care. This is manifested by : under or over prescribing ,wrong prescribing, extravagant
prescribing, and poly pharmacy.

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Prescribed daily dose: The average daily amount of a drug that is actually prescribed. This can vary
according to severity of illness or even amongst different countries.

Poly pharmacy: Occurs when patients use more medicines than required for their illness.

Rational use of antimicrobials: Refers to giving the right medicine, for the right recipient, at the right
dose, within the right duration and at the right and lowest cost to them and their community.

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ABSTRACT

Background: Antimicrobials are indispensable in the practice of medicine. Their misuse is one of the
great forces behind the rapid growth of resistance. Antibiotics are the most frequently prescribed class of
antimicrobials, locally and globally. However this use is very often irrational. This increases risk of serious
untoward drug reactions, poor treatment outcomes, waste of resources as well as antimicrobial resistance.
Antimicrobial resistance is a grave and growing public health threat today. Inappropriate and unnecessary
use of antimicrobials is a big contributor to the growth of resistant pathogens. Advocating and promoting
rational use of antimicrobial agents through antimicrobial stewardship programs is pivotal in curbing
increasing growth of resistance. The World Health Organization recommends that each facility drafts its
antimicrobial use policy.

Study objective: The main objective of this study was to establish patterns of antimicrobial use in
Mbagathi Hospital, Nairobi County, Kenya.

Methods: A Point Prevalence Survey was conducted in all wards of Mbagathi Hospital, in Nairobi County.
Universal sampling was employed, whereby all patients who met the inclusion criteria were included in
the study. Participants were included in the study if they met the following criteria: Age ranged from 0
days to 100 years and were admitted before 8 am on the survey day. This is in line with the Global point
prevalence survey protocol, 2018. Patient demographic and clinical data were extracted from the patient
files, treatment sheets, laboratory culture and sensitivity reports. All raw data collected was entered into
EPI info version 7 and a database created. Descriptive and linear regression data analysis was conducted.

Results: A total of 185 patient records were sampled of whom 146 (78.9%) received at least one
antimicrobial. Overall, 363 antimicrobials were prescribed during current admission and on average each
participant was prescribed for 2 antimicrobials. The most important risk factors for number of
antimicrobials used were HIV status, prior hospitalization in the last 90 days, catheterization and
nutritional status. Antibiotics formed the biggest proportion of antimicrobials prescribed in Mbagathi
Hospital ( n=294, 81%) followed by antivirals ( n=48, 13%) and the least prescribed were antimalarials
and antifungals at 3% each. Most commonly prescribed antimicrobial was ceftriaxone at 46% while the
commonest indication for antimicrobial use was pneumonia with a prevalence of 33%. Culture and
sensitivity tests were only ordered in 7 (3.8%) of the cases.

Conclusion: The prevalence of antimicrobial use was above the World Health Organization (WHO)
reference value of 30% or less. Ceftriaxone was used to a great extent. Empiric prescribing of
antimicrobials was mainly the practice as culture and sensitivity testing were not routinely done in
xvi
Mbagathi hospital. The hospital medicines and therapeutics committee should set up an antimicrobial
stewardship committee to help in judicious antimicrobial use.

xvii
Chapter 1 : INTRODUCTION

1.1 Background

Majority of medicines are sub-optimally prescribed, dispensed or marketed especially in the

developing world where drug regulatory mechanisms are in their infancy stages of development
or not available, according to World Health Organization (WHO) (1). In lower income countries,
pharmaceuticals contribute a high percentage of family and overall healthcare expense.
Betterment in the way medicines are utilized is of great significance in increasing quality of life
and reducing premature deaths. This helps to build public confidence as well as reinforce health
system credibility. Scarce resources will also be optimally utilized and most of all help to curb
the growing menace of antimicrobial resistance (AMR) (2).

Antimicrobial resistance occurs when microorganisms resist the effects of antimicrobial agents.
Resistant microbes increase or endure even in high concentrations of an antimicrobial in relation
to the sensitive counterpart of an identical species. Microbes such as bacteria, fungi, viruses, and
parasites undergo change when exposed to antimicrobial drugs such as antibacterials,
antimycotics, antimalarials, antivirals and anthelmintics. The medicines consequently become
ineffective and infections continue to exist in the body, increasing the risk of dissemination to
others. If these trends continue then simple infections will be no longer treatable (3).

AMR is a serious global concern and is considered one of the greatest dangers to human existence.
According to World Health Organization (WHO) AMR Global Resistance Report on
Surveillance, April 2014, AMR is a grave phenomenon in many parts of the world (4). The report,
which focused on antibacterial resistance, noted that there were soaring rates of resistance among
bacteria such as Klebsiella pneumonia, Escherichia coli and Staphyloccocus aureus, which cause
upper respiratory tract, urinary tract and wound infections (3). These immense rates of resistance
were observed across all WHO regions globally. Resistance has been associated with poor
clinical end results in patients with pneumococcal meningitis and blood infections due to
Streptococcus pneumoniae strains with diminished sensitivity to penicillin (3).

The rapidly increasing levels of AMR are strongly associated with using antibiotics
inappropriately. Overusing and misusing antimicrobials increases AMR rates (5) , and hence there
is crucial requirement to control as well as monitor the use of the existing antimicrobials (6).
Multidimensional interventions rather than single initiatives have been found more effective to
reduce overuse of antimicrobials. These include prohibiting over the counter sale of
1
 antimicrobials, delayed antimicrobial prescribing strategies, develop and implement treatment
guidelines, and institute Antimicrobial Stewardship Programmes (ASPs).

Antimicrobial Stewardship Programmes are broad quality enhancement activities to rationalize

prescribing and reduce antimicrobial resistance. Some activities include regular clinical audits,
use of valid rapid diagnostic tests, pragmatic studies on complications and clinical outcomes and
improvement of communication proficiency with patients (1, 5). Such initiatives to improve
rational use of antibiotics have been implemented across continents including some African
countries like Botswana (7).

In Kenya , the antimicrobial use policy has objectives geared to improving awareness and
understanding of antimicrobial resistance by effective communication, education and training. In
addition, strengthening the knowledge and evidence base on antimicrobials through surveillance
and research. Reduction of the incidence of infection through effective sanitation, hygiene and
infection prevention and control is also targeted. Another objective aims to optimize the use of
antimicrobials in human, animal and plant health. Increasing investment in new medicines,
diagnostic tools, vaccines and other interventions (8).

1.2 Statement of the problem

Antimicrobials are today indispensable in all healthcare systems for the treatment and prevention
of infections. Even major surgeries, cancer chemotherapy, organ transplantation cannot be
performed without effective microbial infections treatment. The consequences of antimicrobial
resistance are far-reaching. Unless real global coordinated actions including antimicrobial
prevalence surveys are immediately taken, we might be faced with setbacks. Describing global,
regional and local antimicrobial resistance helps to detect crucial areas where some action can be
put into place within the shortest time possible (9).

The 2011 European Commission Action plan emphasized the importance of surveillance data in
antimicrobial use and resistance and the role of antimicrobial stewardship (10).

It is estimated that in Europe and the United States, resistant infections are causing roughly 50,000
deaths annually (11). When other countries are included the figure escalates to many hundred
thousands. Infections that are resistant to antimicrobials will become a number one cause of
mortality by 2050, due to overuse of antimicrobials and AMR. This ultimately will significantly
impact on the wealth of nations, potentially costing up to US$100 trillion/year by 2050 (7).

2
 There is a compelling obligation to lower misuse of antimicrobials. Penicillins and cephalosporins
account for around 60% of total global antibiotic consumption. Between 2000 and 2010 their
usage increased by around 40% as did carbapenems, a reserve group of antibiotics. This increase
in carbapenem use along with a 13% increase in the last resort agents, polymixins including
colistin, and a doubling use of glycopeptides, like vancomycin, is attributed to the rising rates of
antibiotic resistance and development of multi drug resistant organisms (12).

Overusing and misusing antimicrobials increases AMR rates (5). Antibiotic overuse and misuse
results from unsuitable prescribing, widespread use in agriculture, lack of new antibiotics from
the research world as well as very poor regulatory practices where prescribing antibiotics is not
controlled at all (13).

A previous study on medicine use practices in Mbagathi hospital showed that up to 68% of the
prescriptions issued at the outpatient department had an antibiotic prescribed and some contained
more than one antibiotic (14). The previous study only involved out-patients. This study focused
on in-patient antimicrobial use which had not been studied. This particular study was broader and
looked broadly at antimicrobials as opposed to only antibiotics.

1.3 Research Questions

The study sought to answer the following questions:-

1. What is the prevalence of antimicrobial use among in-patients at Mbagathi Hospital?

2. What are the most common indications for antimicrobials in Mbagathi Hospital in-patients?

3. Are antimicrobials prescribed and used according to existing antimicrobial use guidelines?

4. What is the prevalence of use of culture and sensitivity tests to guide the choice of
antimicrobials?

3
1.4 Study Objectives

1.4.1 General objective

To identify the patterns of antimicrobial use among patients admitted at Mbagathi Hospital in
Nairobi County, Kenya.

1.4.2 Specific objectives

The specific objectives of the study were to:

1. Determine the prevalence of antimicrobial use among in-patients at Mbagathi Hospital

2. Describe the indications and extent of use of the different classes and groups of
antimicrobials in the different wards.

3. Evaluate whether the antimicrobials were prescribed and used according to existing
antimicrobial use guidelines

4. Examine the frequency and results of culture and sensitivity tests to guide the choice of
antibiotics.

1.5 Study Justification

Information regarding consumption of antimicrobials from this Point Prevalence Survey (PPS)
will be used to draw and implement antimicrobial guidelines at this facility (15). The findings of
this study would highlight areas that the hospital is doing well as well as areas for improvement.
This is expected to provide the basis for the formulation of an antimicrobial use policy for the
facility that would reinforce the appropriate use of antimicrobials for the in-patients at Mbagathi
Hospital. This will ultimately curb the emergence of antimicrobial resistance and preserve
treatments for the future. This study also aimed to provide important information on trends and
antimicrobial resistance (9).

Data is inadequate to inform policy on matters of antimicrobial use practices in hospitals in low
income settings including Kenya. Very limited studies have evaluated the rationality of
antimicrobial consumption among in-patients in the county hospitals in Kenya. Only two studies
have been conducted in Kisii Level 5 and Jaramogi Odinga Oginga Teaching and Referral
hospitals (20, 21). No studies have examined the appropriateness of antimicrobial use among in-
patients at Mbagathi Hospital, a public Level 4 hospital in Nairobi that serves a large spectrum of

4
patients, mostly the urban poor. This study therefore aimed at determining patterns of
antimicrobial use among in-patients in Mbagathi Hospital. The findings can be used to identify
gaps in use and develop an antimicrobial stewardship policy.

The study is expected to help the facility Medicines and Therapeutics Committee to identify
feasible targets to improve the standards of antimicrobial prescribing, thereby contributing to
designing of hospital interventions to promote prudent antimicrobial use and ultimately combat
antimicrobial resistance and improve patient outcomes.

5
 Chapter 2 : LITERATURE REVIEW

2.1 Types of antimicrobials

An antimicrobial is a product that kills or slows down the spread of microorganisms. Anti microbials
act against bacteria, viruses, protozoans, and fungi such as mold and mildew. Antimicrobials are
classified into antibacterials, antifungals, antivirals and anti-parasitic agents (18).

2.1.1.Antibacterials

Pathogenic bacteria cause diseases and infections. Antibacterial agents are used to fight infectious
diseases. These agents can be classified into 5 major groups based on the following characteristics
(1).

Classification Description Examples

Type of action Can be bacteriostatic or bactericidal. The former Bacteriostatic-

target the cell wall or membrane to destroy bacteria tetracyclines, macrolides
whereas the latter inhibit or slow down the growth
Bactericidal –beta lactams
of bacteria

Their source They can either be naturally obtained example from Natural –Penicillins
fungal sources or plants, semi-synthetic or fully
Semi synthetic-sulfur
synthetic.
based antibiotics

Synthetic-
fluoroquinolones

Spectrum of Here we have narrow or broad spectrum Narrow spectrum-

activity antibacterials. Narrow spectrum work against gram macrolides
positive only or gram negative only but not both.
Broad spectrum-
Broad spectrum work on a wide range of
aminoglycosides, second,
antibacterials, both gram negative and positive
third and fourth generation
bacteria
cephalosporins

6
 Chemical This arises from different skeletons to form different Group A-beta lactams,
structure structrulal units. beta lactamase inhibitor
combinations

Group B-
Aminoglycosides,
macrolides, quinolones,
fluoroquinolones

Function This classification is based on mode of action or how Cell wall synthesis
the antibacterial works. This results to four groups inhibitors-beta lactams,
of antibacterials. Cell wall synthesis inhibitors, penicillins
inhibitors of membrane function, protein synthesis
Cell membrane function
inhibitors and nucleic acid synthesis inhibitors
inhibitors-polymyxins

Protein synthesis
inhibitors- tetracyclines,
aminoglycosides,
chloramphenicol

Nucleic acid synthesis

inhibitors-quinolones

2.1.2 Antifungals
Antifungals selectively eliminate fungal pathogens from hosts. There are different classes including
polyene antifungals that interact with sterols in the in the cell membrane making the membrane leaky.
Amphotericin B and nystatin are examples. Azoles like fluconazole which inhibit cytochrome p450
depended enzymes, which are needed in structure and function of fungal cell membrane. Allylamines
and morpholine antifungals- blocks ergosterol biosynthesis at the level of squalene epoxidase. Include
terbinafine. Antimetabolite antifungals like 5-fluorocytosine inhibit both DNA( De-oxyribo Nucleic
Acid) and RNA (Ribo-Nucleic Acid) synthesis (19).

7
2.1.3 Antivirals

There are two classes here. Non retroviral antivirals include anti herpes virus agents-acyclovir, anti-
influenza agents and anti hepatitis drugs. Anti-retroviral agents include nucleoside reverse
transcriptase inhibitors, non-nuceoside reverse transcriptase inhibitors, protese inhibitors, entry
inhibitors and integrase strand transfer inhibitors (20).

2.1.4 Anti-parasitic agents

This is a class of medications indicated for the management of parasitic diseases, such as those caused
by helminths, amoeba, ectoparasites, parasitic fungi, and protozoa, among others. Some anti-parasics
include antimalarials. Other agents include those used for trypanosomiasis, leishmaniasis, amebiasis,
giardiasis and trichomoniasis (21).

2.2 Types of Misuse of Antimicrobials

Issues regarding inappropriate use of antimicrobials bear international importance. Despite the rapid
growth of resistance to current antimicrobials, there is little or no investment into novel
antimicrobials. It is postulated that one million fatalities globally will occur by 2025 due to multiple
drug resistance (22).

Misuse occurs when antimicrobials for humans are given to animals and applying antibiotic sprays
on plants in agriculture. In addition, when the incorrect antimicrobial is utilized at inappropriate
doses and unsuitable durations of therapy constitutes misuse. Expansive utilization of items like
soaps, detergents, toys, mattress pads stuffed with antibacterials like triclosan and triclocarban all
account for misuse. Misuse of antimicrobials and antibacterials destroy the susceptible microbes but
the immune ones are left unperturbed. According to the World Health Organization (WHO) 50% of
prescriptions globally are illogical. This entails polypharmacy, inadequate prescribing, and
unwarranted antibiotic combinations. The leading irrational uses include polypharmacy, suboptimal
dosage of the antimicrobials, non-adherence to established clinical guidelines, unsuitable routes of
administration and self-medication (23).

Antimicrobial misuse is on the rise, and forms the basis of the menace. Misuse includes underuse,
unnecessary use, suboptimal use and inappropriate use. Underuse is caused by lack of access to
healthcare services. Unnecessary use is where an antimicrobial is not indicated and there is no health
benefit for the patient. Inappropriate or suboptimal use includes incorrect timing, antimicrobial
8
choice, dose and route, frequency of intake or period of treatment. An example of incorrect timing is
delayed administration to a critically ill patient. Choosing an antimicrobial with an unnecessarily
broad or too narrow a spectrum as well as drug-agent mismatch. The use of intravenous route when
oral can be used is also misuse. When the dose is too high or too low compared to what is indicated
for that patient or duration is too long or too short all constitute misuse (24).

Inappropriate use of antimicrobials often includes use of antibiotics for non-infectious conditions,
unnecessary initiation or even continued use of broad spectrum antimicrobials. Suboptimal dosing
and duration of therapy that is inappropriate also account to inappropriate use (25).

2.3 Factors that contribute to antimicrobial misuse

2.3.1 Poor quality antimicrobials

Poor quality antimicrobials to sub-inhibitory concentrations which consequently increase chances of

resistant strains. The most common counterfeited antimicrobials include beta-lactams, chloroquine
and artemisinin derivatives. Until 2009, 50% of substandard antibiotics were beta lactams, 12%
quinolones, 11% macrolides, 7% cyclins, and 20% other antibiotics. Poor quality anti-tuberculosis
agents have been reported in 28 different countries, mostly in Asia and Africa. In 2003, WHO
reported that Cote d’Ivoire a triple antiretroviral contained only zidovudine. In 2004, antiretrovirals
were found to containing antidepressants in Congo (14). In one study in Tanzania, counterfeit
oseltamivir and interferon were reported. Antimalarials were found to be of low quality in 90% of the
time in African studies. Azole antifungals were not spared either in the America, Ukraine, and West
Africa, Sierra Leone and Nigeria (26).

2.3.2 Poor regulatory framework

This has led to antimicrobials being dispensed and sold over the counter without any diagnostic
guidance. When it comes to regulatory affairs most countries fail to enforce policies on manufacturing
and distribution of medicines due to poor funding and even lack of necessary skills and personnel.
Variations and lack of skills in prescribers is also a big contributor to antimicrobial misuse.
Dispensing on the other hand has been infiltrated by quacks that apart from making profits have no
other patient safety knowledge. The patients themselves are not spared by this menace as they fail to
adhere to their antimicrobials, buy medicines over the counter and do not take their courses to

9
completion. The Agriculture industry remains an enormous challenge when it comes to antimicrobial
misuse. The food chain is responsible for transferring resistance from the animals and environment
to humans (27).

2.3.3 Health facility factors

Health facility factors which lead to antimicrobial misuse include inadequate supply of certain
antimicrobials leading to over-prescription of the available ones. Lack of diagnostic capability in the
health facilities also lead to empiric prescribing leading to misuse. Other factors are health facility
related. Poorly equipped facilities with no diagnostic facilities, lack of skilled staff, patient overloaded
facilities (28).

2.3.4 Prescriber related factors

Lack of skills and knowledge about antimicrobials. Some prescribers due to lack of continuous
medical education stick to old information and prescribe what is thought not to be evidence based.
Some prescribers are drven by selfish gains like prescriptions for pay whereby medical
representatives gift them to prescribe certain antimicrobials (28).

2.3.5 Patient related factors

Some lack resources whereby they cannot afford to pay for laboratory investigations therefore force
prescribers to prescribe empirically. Furthermore still due to limited resources , some patients do not
buy the complete dose for antimicrobials and end up using sub optimal doses. In this error of internet
connectivity some patients go to hospitals with already the perceived prescription they should get
therefore forcing prescribers to prescribe them (29).

2.3.6 Increasing consumption of antimicrobials in the agriculture and animal industry

Up to 40-80% of antimicrobials used on farm animals is highly questionable. Global

antimicrobial use in agriculture is set to increase by 67% by 2030 due to the increasing demand of
animal protein leading to intesive farming systems. In Kenya, studies done by the Global antibiotic
resistance partnership(GARP) , report that, up to 70% of the antibiotics imported for use in the
country are given to poultry, pigs and cattle for prophylaxis against infections (30).

10
 Adopted with some changes from Goo et al, 2016.

Figure 2.1. Factors that contribute to antimicrobial misuse (22).

2.4 Antimicrobial Resistance (AMR)

Antimicrobial resistance arises when bacteria, parasites, viruses and fungi adjust to antimicrobial
agents. This results to the drugs becoming ineffective hence the infections persist subsequently
increasing risks of severe disease (31). Bacteria are able to identify and eject toxins from within the
cell through efflux pumps before they even reach their targets. This is an important mechanism
leading to AMR. These pumps can be selective or poly specific to many drugs (32).

Resistance can also develop naturally over time via genetic modifications. Emergence and spread of
new mechanisms of resistance can be facilitated by inappropriate use of antimicrobials. In many
countries antibiotics are dispensed without any professional guidance in both livestock and humans.
Poor infection control, inadequate sanitary conditions and unsuitable food handling all lead to spread
of AMR within populations (3).

Antimicrobial Resistance (AMR) is of great public health interest. Growing resistance is a threat in
treatment of many infections. Using antibiotics judiciously is essential in slowing the development
of antibacterial resistance and extending the lifetime of effective antibiotics. AMR occurs through

11
several mechanisms such as, modified antimicrobial target, efflux, impermeability or enzymatic
degradation (33).

According to AMR Global Resistance Report on Surveillance 2014, there is high prevalence of
resistance to third generation cephalosporins by Esherichia coli and Klebsiella pneumonia. This
therefore means that severe infections by these bacteria have to rely on carbapenems which are
reserved as the last resort for treating serious infections acquired in the community and hospital
settings. Carbapenems are costly, and may be unavailable in poor settings. Of very worrying concern
is that up to 54% of K. pneumoniae are resistant to carbapenems (3).

AMR directly threatens future patient safety. About 25 000 patients die every year in Europe alone
due to infections resulting from resistant bacteria. The global estimate is approximately 700 000
deaths yearly. If the current AMR patterns are not changed, then ten million deaths annually are
projected by 2050. Out of these only 0.7 million will happen in North America or Europe, with Africa
and Asia topping the list (34). Methicillin Resistant Staphyloccus aureus (MRSA) kills more
Americans yearly than HIV/AIDS, Parkinson’s disease, pulmonary emphysema and manslaughter
put together (3).

There are highly resistant organisms that cause urinary tract infections (UTIs) especially to common
first line regimens like penicillins and sulfamethoxazole/trimethoprim. When a failing regimen is
used to manage a UTI there is a danger of progression to kidney disease and high blood pressure. In
the same way, with such resistance profiles, neonatal sepsis caused by E. coli, K. pneumonia and S.
aureus will not be adequately eliminated with the preferred first line medicines such as penicillins,
aminoglycosides and cephalosporins. This will escalate deaths of patients with severe infections. The
increased levels of resistance to penicillins in S. pneumonia and Haemophyllus influenza are
worrying since pneumonia is a main cause of mortality in children (35).

The world is unable to keep abreast with increasing AMR to current treatments. This sabotages the
success of fundamental and new medicines in treating infections. Furthermore, the number of new
classes of antibiotics has also dramatically declined over the past four decades. This means that the
prospects of getting into a post antibiotic period are real, where ordinary infections will not be
contained by accessible antibiotics (36). AMR must be treated as a global problem since it is not
limited to national borders. Efforts are needed to change social norms and health system
strengthening. AMR needs to be redefined broadly under agricultural, environmental and health
security and not only concentrating on human health (36).

12
Antimicrobial resistance is not only a concern with antibiotics but affects all antimicrobials. It poses
a danger in the successful prevention and care of a continuously growing variety of bacterial, viral,
fungal and parasitic infections (9). Widespread resistance among A(H1N1) and A(H3N2) viruses to
adamantanes have rendered neuraminidase inhibitors as the primary antivirals for preventing and
treating influenza (3). Resistance to the first-line management for Plasmodium falciparum malaria,
artemisinin-based combination therapies, has been established in five countries in the Greater
Mekong. Worse still , approximately 7% of patients beginning highly active antiretroviral therapy in
middle income countries were drug-resistant (9). Azoles on the other hand have been effective in
managing fungal infections but recently resistance in Candida spp has set in posing a great challenge
(37).

2.4.1 Prevalence of Antimicrobial Resistance

Multi drug resistant Tuberculosis (MDR TB) is increasing. It is both challenging and costly to treat.
Extensively drug resistant TB (XDR TB) has been reported in many countries according to WHO
First Global Antibiotic Resistance Surveillance Report in 2014. It showed that five out of six WHO
regions had more than 50% resistance to fluoroquinolones and third generation cephalosporins in
Escherichia coli and methicillin resistance in Staphylococcus aureus in health care settings. Over
50% resistance to carbapenems and third generation cephalosporins was observed in Klebsiella
pneumonia. In Africa and South East Asia, 45% of fatalities were associated with multi drug resistant
bacteria. Up to 77% deaths in Africa are associated with Klebsiella pneumonia resistant to third
generation cephalosporins. The rates of MRSA in hospital settings are high. In South Africa it is at
52% and in Nigeria 29.6%. Methicillin Resistant Staphylococcus aureus prevalences in Cameroon,
Ethiopia , Morocco and Kenya are 72%, 42.8%, 14.4% and 27.7% respectively (33).

Antimicrobial resistance is a big menace in Sub Saharan Africa, in line with other world trends, E.
coli resistance to third-generation cephalosporins presents a disturbing scenario, especially in urinary
tract infections (UTIs). Fluoroquinolone resistance among E. coli also appeared to be increasing in
UTIs to 28%, as well as amongst community-acquired febrile illness/bacteremia to 8% (38).

Many middle income countries do not have robust surveillance systems. In Rwanda, Kigali University
Teaching Hospital, 31.4% and 58.7% of Escherichia coli and Klebsiella isolates, respectively, were
not responding to at least one of the third generation, last resort cephalosporins. Eight percent of E.
coli isolates were non responsive to imipenem and 82% and 6% of Staphylococcus aureus isolates
were resistant to oxacillin and vancomycin respectively. Antimicrobial resistance is soaring in
Rwanda and presents a grave challenge in treatment of basic infections (39).
13
There is increased resistance to earlier approved quinolones and extended-spectrum cephalosporins.
The surveillance for AMR in Kenya was carried out to establish the prevalence and variety of AMR
of gonococcal isolates from Sex Workers Outreach Program (SWOP) Clinic. Forty one isolates in
2012, 119 isolates in 2013, 24 isolates in 2014 and 54 isolates in 2015 showed up to 100%
susceptibility to cefixime, ceftriaxone and spectinomycin, with a mean susceptibility of 82%, 37.7%,
19.5%, 1.6% and 0% for azithromycin, erythromycin, ciprofloxacin, penicillin and tetracycline
respectively. Resistance against ciprofloxacin rose from 56% in 2012, 58.8% in 2013, 66.7% in 2014
and 68.5% in 2015 (40). Ciprofloxacin a widely prescribed quinolone is no longer dependable for
management of gonorrhea. Worsening gonococcal drug resistance will affect effective treatment and
demean disease control attempts (40).

An evaluation of antimicrobial resistance in East Africa showed soaring levels of AMR to first line
antimicrobial agents including 50-100% resistance to ampicillin and cotrimoxazole. Non response to
gentamicin was at 20-47% in gram negative isolates. Up to 100% and 50-100% of gram positive
isolates were resistant to gentamicin and ceftriaxone respectively (41).

In a study conducted in Pumwani Maternity Antenatal Clinic, Kenya, on treatment of urinary tract
infections (UTIs) in pregnancy, more than 49% of all gram-negative organisms were resistant to third
generation cephalosporins, sulfamethoxazole-trimethoprim, fluoroquinolones, cefoxitin, amoxicillin-
clavulanic acid and nitrofurantoin. Gram-positive strains were susceptible to nitrofurantoin,
amoxicillin-clavulanic acid, linezolid and ofloxacin. The frequency of multi-drug resistance in the
study isolates was at 96%. This suggests a serious resistance trend among UTI strains. Expectant
mothers therefore need screening by urine culture testing and therapy should be informed by
antimicrobial susceptibility laboratory results (42).

2.5 Clinical and Economic Impact of Antimicrobial Resistance

Antimicrobial resistance is associated with increased overall health care costs, both direct and
indirect. It is also associated with increased hospital stay, mortality and morbidity in both developed
and middle income countries. It is approximated that by 2050, AMR will be responsible for up to 10
million deaths. Its estimated 100 trillion USD will go to waste if substantial efforts are not made to
avert this danger (33). A study published by the World Bank in March 2017 roughly estimated that
AMR would exert a lag on global GDP of between 1.1 and 3.8 percentage points by the year 2050
(8).

Soaring antimicrobial resistance would also bring about shocking secondary consequences on aspects
childbirth safety, including caesarean sections, with resulting increases in maternal and infant
14
mortality. Previous health scares such as severe acute respiratory syndrome (SARS), have revealed
that travel and trade really have a tangible effect on the economy. If there is no successful treatment
for malaria, people from non-malaria countries may not be ready to visit malaria endemic zones. This
poses great trouble for most economies, especially those depending on tourism, foreign direct
investment or global trade (44).

Resistant bacteria particularly Enterococcus spp, S. aureus, K. pneumoniae, Acinetobacter

baumannii, Pseudomonas aeruginosa and Enterobacter spp. jointly referred as ESKAPE have been
classified by WHO as important antibiotic resistant bacteria. They are used as target organisms in
research, discovery and designing of novel antibiotics. These ESKAPE bacteria and their resistant
counterparts are passed over in health care facilities in high and middle income countries. Multi drug
resistant ESKAPE bacteria have also been identified in ICUs (29).

Cancer treatments often suppress patients’ immune systems. This makes these patients more
vulnerable to infections. Without efficacious antimicrobials for prevention and treatment of
infections, chemotherapy would turn out to be a very risky affair (46). Caesarean sections contribute
almost 2% to world GDP. The broad cancer chemotherapeutics add more than 0.75% while organ
grafts add approximately 0.1%. These milestones in modern medicine risk being sabotaged if
effective antibiotics are not available in the future. Together they add almost 4% to the world’s GDP,
worth over 120 trillion USD by 2050. The effects of AMR could lead to lose of more than 7% of
GDP by 2050 or a total of 210 trillion USD over the next 35 years. These are not problems of high
income countries only but also have dire and undesirable effects on developing countries expected to
achieve universal health coverage over the future decades. Procedures such as bowel surgery and
bone marrow transplants, might be undertaken less often or not even at all (47).

2.6 Strategies to mitigate Antimicrobial resistance

There is pressing need to get answers in fighting antimicrobial resistance. Legislation, political
agendas, educational initiatives and development of treatments have been suggested amongst other
strategies in combating antimicrobial resistance. Monitoring, continuous watch of practice and policy
provide answers in human and agricultural sectors. There is need for a multidimensional approach if
health care outcomes are to be scaled up (48).

Antimicrobial stewardship programs, (ASPs) , revolves around selecting the best antimicrobial, at its
optimum dose and sufficient period of therapy that results in the best clinical outcome for the
treatment or prophylaxis against an infection, with the least harm to the user and posing minimum

15
impact on future resistance (49). They are also geared on bettering clinical end results and safety, at
minimal related costs and ultimately lower treatment related costs. The end goal is usually the
reduction of antimicrobial resistance. Antimicrobial stewardship programs rely on education together
with front end interventions like restriction of some selected antimicrobials. Development of
guidelines and formularies and education of prescribers constitute good ASP practices. Others include
accurate organism identification, selection of optimal dose and correct duration of treatment. These
include reviewing or streamlining treatment on the basis of antimicrobial sensitivity testing. Reducing
antibiotic use in agriculture is also important (50).

The populace needs to be educated on antimicrobial overuse and how to mitigate it and the use of
analytic tools for monitoring development and spread of AMR. Vaccinations promote herd immunity
and their use is also a strategy of minimizing antimicrobial use and ultimately resistance (51).

The growing AMR challenge can also be addressed by immunization and vaccination programmes.
These can reduce prevalence of AMR pathogens as has been achieved with Haemophilus influenza
and pneumococcal vaccines. Research has been on top gear to come up with HIV, malaria and
universal influenza vaccines (47).

Antimicrobial surveillance together with ASP ensures quality use of antimicrobials. It means using
as little as possible and as much as necessary to ensure welfare and high levels of health (11).

2.7 Protocols for studying antimicrobial use

Several protocols have been developed to study antimicrobial use. The Global Point Prevalence
survey, is one of these (52). European Centre for Disease Prevention and Control (ESAC) has
developed a protocol to guide point prevalence surveys. Data on antimicrobial consumption is
collected at product level (53).

The Global Point Prevalence Survey of Antimicrobial Consumption and Resistance (GLOBAL-PPS)
regulates surveillance of antimicrobial prescribing and resistance in hospitalized adults, children and
neonates worldwide. The GLOBAL-PPS creates awareness across the world regarding the use and
antimicrobial resistance. It is instrumental in planning and supporting international and local
stewardship interventions in various resource and geographical settings. The first Global-PPS was
conducted in 2015 and included 335 hospitals in 53 countries in six continental regions, using a
standardized and validated method (54).

16
Some prevalence surveys that have been performed include; A point prevalence survey of healthcare-
associated infections (HAIs) and antimicrobial consumption organized by European Centre for
Disease Prevention and Control (ECDC-PPS). Global Point Prevalence Survey of antimicrobial use
(Global-PPS). These studies were done in succession in Belgian acute care hospitals in 2017 (55).
First was antimicrobial consumption in acute care hospitals: A national point prevalence survey on
healthcare-associated infections and antimicrobial consumption in Switzerland, 2017 (56), then the
Global Point Prevalence Survey (G-PPS) of antimicrobial use and antimicrobial resistance among
hospitalized children in Georgia (57).

Medicine use surveys in partnership with Management sciences for Health. The activities herein
include pharmacovigilance, rational medicine use, good dispensing practices and also medicines and
therapeutics information (58).

Strengthening Pharmaceutical Systems organization (SPS), has also come up with ways of
investigating antimicrobial consumption in hospitals (59). Surveillance of antimicrobial use identifies
both rational and irrational use. This informs treatment and management decisions and also evaluates
impact of resistance.

2.8 Conceptual Framework on Types of Antimicrobial Misuse and their Causes

The contribution of various facets and attendant reasons for irrational use of antimicrobials is
illustrated in the conceptual framework shown in Figure 2.2 (60).

17
(Adopted with some adjustments from Mao W et al ;2015).

Figure 2.2. Conceptual Framework on Types of Antimicrobial Misuse and their Causes

Some indicators of irrational antimicrobial use are average number of drugs per prescription set at an
optimum level between 1.6-1.8. Percent of drugs prescribed by generic name should be at 100%.
Encounters with an antibiotic should range between 20.0 to 26.8%. An injection should be prescribed
13.4 to 24.1 % of the time. Up to 100% of total drugs prescribed should be from the essential medicine
list (61)

18
Chapter 3 : METHODS

3.1 Study design

The study was a descriptive cross sectional Point Prevalence Survey (PPS) of antimicrobial use at
Mbagathi Hospital. A point prevalence survey is a cross sectional study. It estimates the prevalence
of a parameter at a specific point in time. Point Prevalence Surveys are the commonest population
based epidemiological studies (54). Prevalence surveys can also be used to investigate relationships
between risk factors and disease. A PPS offers a standardized tool which can be used to choose
indicators for quality improvement in health care settings. Furthermore PPSs are less time consuming,
less costly and easy to conduct.

A point prevalence survey is a practical surveillance tool for providing information about antibiotic
use and assessing effects of antibiotic stewardship interventions. This study borrowed it’s
methodology from, and ultimately contributed to, the Global PPS of Antimicrobial Consumption and
Resistance (GLOBAL-PPS, http://www.global-pps.com/).

3.2 Study site

The study was conducted at Mbagathi Hospital. It is situated in Golf Course location, Dagoretti
District of Nairobi County. It was originally known as Infectious Diseases Hospital. It was built in
the 1950s to offer health care services mainly for infectious diseases which required isolation such as
TB, measles, meningitis and leprosy. In 1995 it was carved from Kenyatta National Hospital and
transformed into an autonomous district hospital for Nairobi.

Mbagathi hospital is the largest public health facility under Nairobi county. It is a 200 bed capacity
facility with several wards. These include a medical TB ward, general medicine, surgical, paediatric,
post natal wards and a newborn unit. The bed occupancy rate is usually over 75% most of the time.
Mbagathi Hospital serves mainly the urban poor and the informal settlements in south, west and North
of Nairobi County, Kenya. Up to 1 000 patients are admitted in Mbagathi Hospital monthly. The
outpatient department serves an average of 700 patients daily and admits an average 20 patients daily.

19
3.3 Study Population

The study population was all inpatients admitted to the wards of Mbagathi Hospital during the survey.
The survey was carried out in the internal medicine, paediatric, surgical (both male and female), post
natal wards and the new born unit. The study was conducted between March and April, 2019.

3.4 Eligibility criteria

3.4.1 Inclusion criteria

Participants were included in the study if they met the following criteria:

1. Age ranged from 0 days to 100 years.

2. Were of either sex.
3. Were admitted before 8 am on the survey day.

3.4.2 Exclusion criteria

Participants were excluded if they,

1. Were admitted for same-day procedures such as dialysis and day surgeries.
2. Had files missing from the ward for more than 24 hours on the day of the specific ward’s
survey.
3. Their treatment sheets were missing from their files.
4. Had files with incomplete data.

3.5 Sampling

Universal sampling was done therefore a minimum sample size was not computed. All patients
admitted before 8 am on the day of the survey were sampled. According to the Global Point
Prevalence Protocol of 2018, in hospitals with <500 bed capacity, all patients who meet the inclusion
criteria should be included in the study (62).

Data was collected in a single day for each ward. Major ward rounds are done on Mondays and
Thursdays. These two days were avoided for surveillance except for paediatric ward, new born unit
and maternity where ward rounds are conducted daily. Data was mainly collected on Tuesdays,
Wednesdays and Fridays. The total time frame for data collection for all wards was three weeks.
Survey of surgical wards was carried out on weekdays that allowed retrospective data collection on
surgical prophylaxis. These wards were not surveyed on a weekday immediately after a weekend or
holiday.
20
3.6 Data Collection instruments and procedures

The Global Point Prevalence Survey (G-PPS) data collection forms (Appendices 1, 2, 3 and 4) were
adapted (63). A Ward Data Collection Form (Appendix 1) was used to record information on the
name of the ward and type of patients admitted therein. The Patient Data Collection Form (Appendix
2) was used to record the patient’s bio-data, medicines prescribed, duration and all accompanying
information on any antimicrobials prescribed.

This study involved extraction of data from the patient files, treatment sheets and laboratory culture
and sensitivity reports. Antimicrobial interventions after 8 am on the survey day were not included in
the survey (63).

Data on patients’ age, weight and gender were collected. The antimicrobial agent used, dose per
administration, number of doses per day, and route of administration were recorded. The anatomical
site of infection or target for prophylaxis (according to provided reasons for treatment) as well as the
admitting ward, admitting diagnosis and indication for therapy (community acquired versus hospital
acquired infection or prophylaxis) were also determined. Availability of microbiological or biomarker
data in determining choice of antimicrobial was very key in this study and laboratory reports were
sought to establish this.

Bed occupancy was determined by dividing the total number of patients by the total number of beds
in the hospital. Data on compliance to guidelines, documentation of reasons warranting antimicrobial
use and stop/review date of prescriptions was also collected. Data on the route of administration, the
type and class of antimicrobial used for an indication and whether there were antimicrobials
prescribed with no indication were collected using the patient data collection tool (Appendix 2).

The antimicrobial agents were listed by generic name and classified according to the WHO ATC
(Anatomic Therapeutic Chemical Classification). This is illustrated in appendix 5. In the ATC
classification system, the drugs are divided into different groups according to the organ or system on
which they act and their chemical, pharmacological and therapeutic properties. Drugs are classified
into five different levels. The first level is the organ class, the second level main therapeutic class,
third level pharmacological action, fourth level chemical class and the last level is the chemical
compound itself. It is a hierarchical level classification and provides a convenient way of presenting
drug use consumption statistics (64).

Based on the ATC classification system, data was collected for the following antimicrobial agents:
Antibacterials (J01), antimycotics (D01BA) and antifungals (J02) for systemic use, antibiotics used
21
as drugs for treatment of tuberculosis (J04A), intestinal anti infectives (A07AA), antiprotozoals used
as antibacterial agents, nitroimidazole derivatives (P01AB) and antimalarials (P01B). Antimicrobials
for topical use were excluded from the survey.

Information on the diagnosis as well as indication for antimicrobial use was classified and coded
according to the classes/ codes presented in Appendix 3 and Appendix 4. These classes and codes
have been adapted from GLOBAL PPS data collection tools (63).

Adherence to guidelines was inferred by comparing the collected data to what is stipulated in the
guidelines: WHO (World Health Organization) drug use indicators (65), Basic Paediatric Protocols
(66), Clinical Management and Referral Guidelines Volume 111 (67), National guidelines for the
Diagnosis ,Treatment and Prevention of Malaria in Kenya (68).

3.7 Quality Assurance

Data collection tools, the ward data collection tool (Appendix 1) and the patient data collection tool
(Appendix 2) was pre-tested before the study commenced. Research assistants constituted two
registered pharmacists and one registered medical officer working at Mbagathi Hospital at the time
of the study. They were trained on how to fill the data tools and also taken through the Global Point
Prevalence Protocol of 2018 of conducting a point prevalence survey. They were also taken through
the various national antimicrobial guidelines mentioned in sub section 3.10.

3.8 Data Management

Patient information was coded and no real names or patient identifiers were used. Data was
counterchecked after entering into the research instruments and missing information sought. Data
collection instruments were kept under key and lock and the computer files password protected. Data
was entered within 24 hours of data collection. Regular backup of the database was done to guarantee
data integrity.

All raw data was entered into Epi info version 7 software and a database created. The data was then
exported to STATA version 14.2 software for analysis.

3.9 Study Variables

The primary outcomes of interest were the occurrence of antimicrobial use and its prevalence, the
various classes of antimicrobial agents prescribed, the indications for antimicrobial use, posology of
antimicrobials prescribed and whether antibiotic prescribing was informed by culture and sensitivity

22
results. For multilinear regression analysis the outcome variable was number of antimicrobials used.
The predictor variables were age category, ward type, catheterization status, prior hospitalization in
the last 90 days, HIV status, intubation status , gender, nutritional status and referral from another
facility.

3.10 Data Analysis

Data was extracted from the patient’s files and analyzed using STATA version 14.2 (StataCorp,
USA). Descriptive statistics such as prevalence, frequencies, means and standard deviations were
used to summarize the antimicrobial use patterns. The socio-demographic variables, indications of
irrational use and prescribing patterns were compared across wards. Given that these variables were
a mix of categorical and continuous variables, different inferential methods were used. The
distribution of categorical variables were compared across wards using the Fischers exact and
Pearsons chi-squared tests. Variables that were normally distributed were compared using one way
analysis of variance. Continuous variables that were not normally distributed were compared using
Kruskal Wallis test. Total number of patients admitted formed the denominator variable for the
calculation of the overall prevalence of antimicrobial use. Summative WHO indicators of
antimicrobial use were computed and compared with the ideal levels.

Bivariable linear regression analysis was done to identify risk factors for prescribing multiple
antimicrobials which is a major problem. The outcome variable was number of antimicrobials
prescribed. The predictor variables were, ward type, catheterization status, age category, intubation
status, gender, HIV status, nutritional status, previous hospitalization or referral from another facility
were the potential co-variates considered. Multivariable regression was done to adjust for
confounders. Model building was done using a forward stepwise approach. The level of significance
was set at 0.05.

3.11 Ethical Considerations

Approval to carry out this study was sought from the Kenyatta National Hospital/University of
Nairobi Ethics and Research Committee (KNH/UoN-ERC) in February 2019 (Ref.no.KNH-

23
ERC/RR/48, Appendix 6). To implement the study, permission was sought from the Mbagathi
Hospital research committee in March 2019, (NO. MDH/RS/1/VOL.1) Appendix 7.

Utmost care to ensure maximum privacy and confidentiality of the information obtained during the
study was exercised. Patient codes were used instead of patient identifier information. The data
instruments were stored in a password-protected database only accessible to the principal researcher.
The data collection instrument and any other materials that were used during the study were kept
under lock and key. The requirement for consent from the patients was waived since only medical
records were used.

24
Chapter 4 : RESULTS

4.1 Participants Recruitment and Enrollment

Data was collected over three weeks. A total of 205 patients were screened for eligibility of which
185 met the criteria. Twenty patients were excluded for reasons presented in Figure 4.1. Nine patients
had already been discharged on the day of the survey, another five patient files were in theatre or not
available while six others had been admitted after 8 a.m. on the day of survey.

Total number of patients admitted during period of study n=205

Reasons for exclusion

- Discharged already (n=9)

- Patient files in theatre/
missing (n=5)
- Patients admitted after 8
a.m. on day of study (n=6)
Patient files included n=185

Figure 4.1. Consort diagram of participants in the study

4.2 Bed capacity and occupancy in the wards surveyed

The total number of patients admitted in the hospital at the time of the survey was 205. The total
number of beds were 169 with medical ward having the most number ( n=84, 49.7%). Percentage bed
occupancy per ward was given by number of patients in a ward divided by the number of beds in the
respective ward. The overall bed occupancy was 121%. Nursery had the highest bed occupancy at
450% followed by maternity with 263.2%. Medical ward had the lowest occupancy at 63.1%. This
is summarized in Table 4.1.

25
Table 4.1: Bed capacity and occupancy in Mbagathi Hospital

Number of patients Bed occupancy per

Ward Number of beds
admitted in ward ward (%)
Maternity 19 50 263.2
Medical 84 53 63.1
Nursery 6 27 450
Paediatrics 40 50 125
Surgery 20 25 125
Totals 169 205 121.3

4.3 Socio-demographic Characteristics of Study Participants.

Table 4.2 is a summary of the baseline characteristics of the 185 participants who met the inclusion
criteria. Majority of the participants were above 18 years (n=108, 58%) and the fewest were children
between 1 and 17 years (n=19, 10.3%). More than half of the participants were female (n=110, 59%).
A large proportion of patients came from medical ward (n=51, 28%) followed by paediatrics (n=48,
26%). The least number of patients were from the surgical wards (n=21, 11%).

Table 4.2. Social Demographic Characteristics of survey Participants

Characteristic n (%)
Age in years Adult (≥ 18 Years) 108 (58.4)
Child (≥ 1 and ≤ 17 Years) 28 (15.1)
Infant (≥ 1 and ≤ 11 Months) 19 (10.3)
Neonate (≤ 28 Days) 30 (16.2)

Gender Female 110 (59.5)

Male 75(40.5)
Ward type Maternity 40 (21.6)
Medical 51 (27.6)
Nursery 25 (13.5)
Paediatrics 48 (26.0)
Surgery 21 (11.4)

4.4 Medical characteristics of study participants

There were significant correlations between the ward type and most of the medical characteristics
observed. Out of the 185 patients sampled, 79 (42.7%) had been referred from other facilities and the
bulk 33 (64.7%) were in the medical ward . A total of 145 patients were catheterized at some point

26
during their hospital stay. This constituted 78% of total patients surveyed. Almost half of the patients
n=91 (49%) were malnourished and 38 (74.5%) were in the medical ward. Thirty four (18.4%) were
HIV positive of which 29 (56.9%) were admitted in the medical ward. Most of the patients on TB
treatment were also from medical ward 27 (52.9%). This is summarized in Table 4.3.

Table 4.3. Medical characterisics of study participants

Variable Maternity Medical Nursery Paediatric Surgery p-value

Referred from 3 33 3 26 14 <0.001
another facility(7.5) (64.7) (12) (54.2) (66.7)
Catheterized 15 46 23 46 15 <0.001
(37.5) (90.2) (92.0) (95.8) (71.43)
Intubated 0 4 2 3 2 0.473
(0.0) (7.8) (8.0) (6.3) (9.5)
Malaria test 1 13 0 38 0 <0.001
done (2.5) (25.5) (0.0) (79.2) (0.0)
Malnourished 2 38 18 28 5 <0.001
(5.0) (74.5) (72.0) (58.3) (23.8)
HIV +ve 2 29 0 2 1 <0.001
(5.0) (56.9) (0.0) (4.17) (4.8)
On TB 0 27 0 3 1 <0.001
treatment (0.0) (52.9) (0.0) (6.25) (4.76)

4.5 Prior Antimicrobial Use by Participants of the Study

Table 4.4 summarises the number of participants who had used an antimicrobial in the last 90 days
preceding current admission. Nearly 1 out of 4 patients had used an antimicrobial before admission.
Prior use was particularly high amongst paediatric patients. In this sub-population, slightly over 80%
had been treated with an antimicrobial before admission. Amoxicillin was the commonly used
antimicrobial. Only 2 patients reported to have used ceftriaxone in the last 90 days. It was noted that
unlike other wards, the paediatric ward was consistent in the recording of prior use of antimicrobials.
There were no records of antimicrobial use amongst patients admitted in maternity ward.

27
Table 4.4. Prior Antimicrobial Use by the Participants in the Study

Maternit Medical Nursery Paediatri Surger p-value

y c y
Prevalence of 0(0%) 5(11.1% 2(4.4%) 37(82.2% 1(2.2) <0.001
prior use ) )
Common antimicrobial used prior to admission
Amoxicillin 0(0) 0(0) 2(8.3) 22(91.7) 0(0) <0.001
Co- 0(0) 5(35.7) 0(0) 9(64.3) 0(0) 0.157
trimoxazole
Benzathine 0(0) (0) 0(0) 0(0) 1(100.0 <0.001
penicillin )
RHZE 0(0) (0) 0(0) 4(100.0) 0(0) <0.001
Ceftriaxone 0(0) (0) 0(0) 2(100.0) 0(0) <0.001

4.6 Antimicrobials prescribed during admission at Mbagathi Hospital

Of the 185 patient records sampled, 146 prescriptions had one or more antimicrobial translating to a
prevalence of antimicrobial use of 78.9%. A total of 363 antimicrobials were prescribed during
admission. There were statistically significant differences in the patterns of prior antimicrobial use.
Paediatric ward had the highest prevalence of use.

4.6.1 Types of antimicrobials prescribed

Antibiotics formed the biggest proportion of antimicrobials prescribed during admission in Mbagathi
Hospital, n=294(81%). Antivirals n=48(13%) followed and the least prescribed were antimalarials
and antifungals at 3% each. This is displayed in Figure 4.2.

28
 Antimalarials
3%

Antivirals
Antifungals 13%
3%

Antibiotics
81%

Figure 4.2: Classes of antimicrobials prescribed

4.6.2 Distribution of number of antimicrobials prescribed per patient

The number of antimicrobials prescribed per patient ranged from 1 to 8. On average 2 antimicrobials
were prescribed per patient, though extremes of up to 6 and 8 antimicrobials prescribed to a single
patient were noted. Figure 4.3 shows the overall frequency distribution of the number of
antimicrobials per patient. Six patients from medical ward and one from paediatric ward had six
antimicrobials each. These patients had many co-morbities among them pneumonia, retroviral disease
and opportunistic infections. One patient from medical ward was on 8 antimicrobials. This patient
was also intubated and quite sick and had been put on wide empirical antimicrobial cover.

29
 80
70

Number of patients 60
50
40
30
20
10
0
0 1 2 3 4 5 6 8
Number of antimicrobials prescribed

Figure 4.3: Frequency polygon of number of antimicrobials prescribed

4.6.3 Frequency of individual antimicrobials prescribed at Mbagathi Hospital

The most commonly prescribed antimicrobial was ceftriaxone at 23.7% (n=86) followed by
gentamicin (10.2%), metronidazole (9.4%), RHZE (9.1%) and co-trimoxazole (8.5%). The top five
antimicrobials were all antibiotics. Some low frequency antimicrobials included dolutegravir,
amphotericin-B, norfloxacin and vancomycin. This is illustrated in Table 4.5

30
Table 4.5. Frequency of individual antimicrobials prescribed at Mbagathi Hospital

Antimicrobial n (%) Antimicrobial n (%)

Ceftriaxone 86 (23.7) Clindamycin 3 (0.8)
Gentamicin 37 (10.2) NVP* 3 (0.8)
IV Metronidazole 34 (9.4) Oral Metronidazole 3 (0.8)
RHZE* 33 (9.1) Benzathine penicillin 2 (0.6)
Co-trimoxazole 31 (8.5) Clarithromycin 2 (0.6)
TDF/3TC/EFV* 31 (8.5) Cefuroxime 2 (0.6)
Benzyl penicillin 28 (7.7) Meropenem 2 (0.6)
Acyclovir 10 (2.8) Nystatin 2 (0.6)
Ceftazidime 8 (2.2) DTG* 1 (0.3)
Fluconazole 8 (2.2) TDF/3TC* 1 (0.3)
Amikacin 7 (1.9) Amphoterin B 1 (0.3)
AL* 6 (1.7) AZT* 1 (0.3)
Flucloxacillin 6 (1.7) ABC/3TC/AZT* 1 (0.3)
Erythromycin 5 (1.4) Norfloxacin 1 (0.3)
Artesunate 4 (1.1) Vancomycin 1 (0.3)
Amoxicillin 3 (0.8)
RHZE*- Rifampicin Isoniazid Pyrazinamide Ethambutol, TDF/3TC/EFV*-Tenofovir Lamivudine Efavirenz, AL*
Artemether Lumefantrine, NVP* Nevirapine, DTG* Dolutegravir, TDF/3TC* Tenofovir Lamivudine, AZT* Zidovudine,
ABC/3TC/AZT* Abacavir Lamivudine Zidovudine.

4.7 Duration, Frequency and Route of antimicrobial use

Most of the antimicrobials were prescribed once a day (46%), followed by twice daily at 29% as
shown in Table 4.6. The most common route of administration was intravenous at 59%. Oral route
accounted for 41% of prescribed antimicrobials.

Most of the antimicrobials were prescribed over a period of 4-7 days (26.4%). Several antimicrobials
accounting for 53.2%, had no duration of use on the treatment sheet. This meant that the nurses
administered them daily until discharge. A stop review date was available for 60.9% (221) of the
antimicrobials prescribed but 39.1% (142) had no documentation on when to stop or review treatment.
Almost half of the patients admitted (45.5%) missed at least one dose during their hospitalization
with some missing up to 30 doses. This is illustrated in Table 4.6.

31
Table 4.6. Duration Frequency and Route of administration of antimicrobials

Variable Parameter n(%)

Frequency Weekly 2(0.5)
Five times a day 9(2.5)
Four times a day(QID) 20(5.5)
Thrice a day(TID) 54(14.8)
Twice a day (BID) 106(29.0)
Once a day(OD) 166(45.5)
Not indicated 8(2.2)
Route Intravenous 214(58.5)
Intramuscular 2(0.5)
Oral 147(40.2)
Not indicated 3(0.8)
Duration of use Yes 170(46.8)
indicated No 193(53.2)
Duration of use 1-3 days 35(9.6)
(days) 4-7 days 96(26.4)
8-10 days 28(7.7)
More than 10 days 11(3.0)
Not indicated 193(53.2)
Is there a stop
review for the Not indicated 142(39.1)
antimicrobial?
Missed doses
during course of Yes 165(45.5)
therapy

4.8 Indications for antimicrobial use

The leading indication of antimicrobial use in maternity ward was prophylaxis for obstetric
gynecology surgical infections. In medical wards it was pneumonia, while in the surgical ward it was
soft tissue infections.

4.8.1 Indications in medical, maternity and surgical wards

In medical ward approximately one in four of the antimicrobials prescribed was an antiretroviral.
Pneumonia was the second highest indication (18.4%) for antimicrobial use in the medical ward. In
the maternity ward slightly over 80% of the time antimicrobials were used for prophylaxis for
obstetric gynecology surgical cases as shown in Table 4.7.

32
Table 4.7. Indications in medical, maternity and surgical wards

Medical Indication n (%) Maternity Indication n (%)

Antiretroviral 35(23.0) Proph OBGY 29(82.9)
therapy
Pneumonia 28(18.4) OBGY 3(8.6)
Tuberculosis 27(17.8) Antiretroviral Therapy 2(5.7)
General medical 25(16.4) Pneumonia 1(2.9)
prophylaxis
Gastrointestinal 8(5.3) Surgical Skin and soft tissue 11(30.6)
infections infections
Central Nervous 7(4.6) Prophylaxis for bone 7(19.4)
System infections and joint infections
Unknown 6(3.9) Bone and Joint 6(16.7)
infections
PROPH CNS 3(2.0) Sepsis 4(11.1)
Sepsis 3(2.0) Proph OBGY 3(8.3)
Bacteremia 2(1.3) Proph CVS 1(2.8)
Cysturia 2(1.3) Unknown 1(2.8)
Malaria 2(1.3) Anti Retroviral Therapy 1(2.8)
Upper respiratory 2(1.3) Ear Nose Throat 1(2.8)
tract infections infections
Lung infection 1(0.7) Tuberculosis 1(2.8)
Proph RESP 1(0.7)
Key: PROPH OBGY-Prophylaxis for obstetric gynecology surgical cases. OBGY-therapy for obstetric gynecology cases.
PROPH CNS-prophylaxis for central nervous system conditions, Proph RESP-Prophylaxis for respiratory infections,
Proph CVS-prophylaxis for cardio-vascular infections.

4.8.2 Indications in the nursery and paediatric wards

In the nursery, neonatal jaundice and sepsis were the most prevalent indications of antimicrobial use.
There were more co-morbidities in the paediatric ward as compared to the nursery. Pneumonia was
the main indication in paediatrics as shown on Table 4.8.

33
 Table 4.8. Indications in nursery and paediatrics

Indication Nursery Paediatrics

Pneumonia - 49(50)
Neonatal jaundice and sepsis 27(64.4) 6(6.1)
Malaria - 8(8.2)
Gastrointestinal infections - 8(8.2)
Respiratory distress 7(16.7) -
Cental nervous system infections - 6(6.1)
Bacteremia - 6(6.1)
Upper respiratory tract infections 1(2.4) 6(6.1)
Medical prophylaxis for neonatal 4(9.5) -
infections
General medical prophylaxis - 3(3.1)
Anti retroviral therapy 3(7.1) 3(3.1)
Tuberculosis - 3(3.1)
Skin and soft tissue infections - 1(1.0)

4.9 Leading indications for antimicrobial use in Mbagathi Hospital

Pneumonia was the most common indication for antimicrobial use across the wards (n=78) followed
by, prophylaxis for obstetric gynecology surgical cases (n=32). Tuberculosis was third, (n=31),
general medical prophylaxis fourth n=28, and sepsis n=21. This is illustrated in Figure 4.4.

78
Number of patients

33 32 31 28

Pneumonia Sepsis and Prophylaxis Tuberculosis General

Neonatal for obstetric medical
Jaundice gynecology prophylaxis
surgery
Leading Indications of antimicrobial use

Figure 4.4: Leading indications in Mbagathi Hospital

34
4.10 Prescribed Daily Doses and associated Defined Daily Doses in Patients above 18 Years

Most of the antimicrobials were prescribed within the World Health Organization (WHO)
recommended Daily Defined Doses (DDDs). The exceptions were acyclovir whereby only 2 (18%)
got the recommended DDDs and the rest 82% were prescribed lower doses. Only 2 (28%) got the
recommended defined daily dose of fluconazole while 71% got higher doses. The recommended
DDD for RHZE is 4 tablets but only 31% got this. The remaining 69% got lower doses. This is
presented in Table 4.9

Table 4.9. Prescribed and Defined Daily Doses in Patients above 18 Years

Antimicrobial PDDa in mg/ DDDb n (%) Daily Cumulative

DDDs
tabs
Ceftriaxone 1000 0.5 5 (8.5) 68.5
(DDD=2g) 2000 1 42 (71.2)
4000 2 12 (20.3)
Metronidazole 1000 0.67 1 (3.1) 31.47
(DDD=1.5g) 1200 0.8 1 (3.1)
1500 1 30 (93.8)
Acyclovir (DDD=4g) 400 0.1 1 (9.1) 5.4
800 0.2 1 (9.1)
1000 0.25 2 (18.2)
2000 0.5 5 (45.5)
4000 1 2 (18.2)
Fluconazole 200 1 2 (28.6) 18
(DDD=0.2g) 400 2 3 (42.9)
800 4 1 (14.3)
1200 6 1 (14.3)
Flucloxacillin 1500 0.75 1 (16.7) 5.75
(DDD=2g) 2000 1 5 (83.3)
Erythromycin 2000 1 2 (100.0) 2
(DDD=2g)
Cotrimoxazole 960 1 24 (92.3) 30
(DDD=960mg) 1920 2 1 (3.85)
3840 4 1 (3.85)
RHZE 1tab 0.25 1 (3.5) 23.25
(DDD=4 Tabs) 2 tabs 0.5 1 (3.5)
3 tabs 0.75 18 (62.1)
4 tabs 1 9 (31.0)
RHZE-Rifampicin Isoniazid Pyrazinamide Ethambutol, -Defined Daily Doses, a-Prescribed Daily
b

Doses

35
The total daily prescribed doses have been compared to the World Health Organization’s defined
daily doses in figure 4.5.

100%
90%
80%
Proportion

70%
60%
50%
40%
30%
20%
10%
0%

Antimicrobial Prescribed
Consumption<DDD Consumption=DDD Consumption>DDD

Figure 4.5: Proportion of patients that received doses above or below WHO defined daily
doses

4.10.1 Association Between Prescribed Daily Doses and Gender

There was a statistically significant difference in prescribed daily doses of ceftriaxone across males
and females whereby females received more quantities (p=0.016). Among the twelve patients who
received a prescribed daily dose of 4000mg of ceftriaxone, 11(91.7%) were female and only 1(8.3%)
was male. Forty two patients got the recommended daily dose of 2000 mg per day, females being
more at n=28 while males were 14. This is summarized in Table 4.10.

36
Table 4.10. Comparison of Prescribed Daily Doses by Gender

Antimicrobial PDDs Female Male p-value

Ceftriaxone 1000 1 (2.5) 4 (21.1) 0.016

2000 28 (70.0) 14 (73.7)
4000 11 (27.5) 1 (5.3)
Metronidazole 1000 1 (3.7) 0 (0) 1.000
1200 1 (3.7) 0 (0)
1500 25 (92.6) 5 (100)
Acyclovir 400 1 (12.5) 0 (0) 0.636
800 0 (0.0) 1 (33.3)
1000 2 (25.0) 0 (0.0)
2000 4 (50.0) 1 (33.3)
4000 1 (12.5) 1 (33.3)
Fluconazole 200 0 (0) 2 (100) 0.095
400 3 (60) 0 (0)
800 1 (20.0) 0 (0)
1200 1 (20.0) 0 (0)
RHZE 1 0 (0) 1 (7.1) 0.232
2 1 (6.7) 0 (0)
3 11 (73.3) 7 (50.0)
4 3 (20.0) 6 (42.9)

4.10.2 Comparison of Prescribed Daily Doses and Ward Type

Prescribed daily doses were not affected by the type of the ward patient was admitted to as illustrated
in Table 4.11. There was possible association between PDDs of flucloxacillin and ward type but the
number of patients was too small to demonstrate it.

37
Table 4.11. Comparison of Prescribed Daily Doses and Ward Type

Antimicrobial PDDs Maternity Medical Surgery p-value

Ceftriaxone 1000 1 (7.1) 4 (11.1) 0(0.0) 0.740
2000 11 (78.6) 23 (63.9) 8 (88.9)
4000 2 (14.3) 9 (25.0) 1 (11.1)
Metronidazole 1000 0 (0) 0 (0) 1 (14.3) 0.486
1200 1 (6.7) 0 (0) 0 (0)
1500 14 (93.3) 10 (100) 6 (85.7)
Flucloxacillin 1500 0 (0) 1 (100) 0 (0) 0.167
2000 0 (0) 0 (0) 5 (100.0)
RHZE 1 0 (0) 1 (3.6) 0 (0) 0.379
2 0 (0) 1 (3.6) 0 (0)
3 0 (0) 18 (64.3) 0 (0)
4 0 (0) 8 (28.6) 1 (100.0)
RHZE (Rifampicin, Isoniazid, Pyrazinamide, Ethambutol) PDD-Prescribed Daily Dose

4.11 Prophylactic use of the antimicrobials.

Of the total 185 sampled study participants, 146 had an antimicrobial prescribed. Out of 146 patients
on antimicrobials, 86 (59%) were for prophylaxis, of which medical prophylaxis constituted 51.2%
while surgical prophylaxis formed 48.8%. This is presented in Table 4.12.

All the prophylaxis administered either surgically or medically was given for more than one day.
Antimicrobials used for prophylaxis constituted ceftriaxone, co-trimoxaxole, flucloxacillin,
fluconazole and metronidazole. The most commonly used antimicrobial for surgical prophylaxis was
ceftriaxone and co-trimoxazole was used widely for medical prophylaxis.

Table 4.12. Prophylactic use of the antimicrobials

Maternity Medical Nursery Paediatrics Nursery p-value

Antimicrobial 30 (34.9) 32 (37.2) 7 (8.1) 4 (4.7) 13 (15.1) <0.001
used for
prophylaxis
Medical 1 (2.3) 32 (72.7) 7 (15.9) 4 (9.1) 0 (0.0) <0.001
prophylaxis
Surgical 29 (69.0) 0 (0.0) 0 (0.0) 0 (0.0) 13 (31.0) <0.001
prophylaxis

38
4.12 Culture and sensitivity testing

There were only 7 culture and sensitivity requests (3.8%). The highest number of requests
n=4(57.1%) came from nursery. Medical and maternity wards did not have any requests. Out of the
seven requests, results were available for only 4 requests. The other three were still being processed.

4.13 Compliance with WHO indicators and specific guidelines for antimicrobial prescribing
at Mbagathi Hospital

Nearly 80% of patients studied were on one or more antimicrobials. The reference WHO value is
30% hence antimicrobial use was quite high in this study. The average number of antimicrobials
prescribed was approximately 2 which is within the reference range of 1.3 to 2.2. Proportion of
medicines prescribed by generic name was 80%. The ideal should be 100%. Almost 50% of patients
missed one or more doses during their course of treatment. Over 50% of prescribed antimicrobials
did not have duration of use specified.

None of the patients received surgical prophylaxis as per the guidelines in our study. Guidelines
stipulate no more than 24 hours antimicrobial prophylaxis for caesarian sections but all the patients
received prophylaxis for a minimum of 72 hours. The paediatric protocols suggest all patients with
pneumonia be treated with dispersible amoxicillin but none of the paediatric patients was on this
formulation. They had all been started on ceftriaxone. For malaria management 10% were put on
second line treatment without a positive malaria test which is a leading cause of antimalarial drug
resistance. These indicators are summarized in Table 4.13.

39
Table 4.13. Compliance with WHO indicators for antimicrobial prescribing at Mbagathi
Hospital

Measure Indicator Mbagathi WHO

Hospital optimal
score values
Extent of Percentage of prescriptions with an 78.9% <30%
antimicrobial use antimicrobial

Polypharmacy Average number of antimicrobials 1.96 1.3-2.2

per encounter
Compliance to Percentage of antimicrobials 80% 100%
generic prescribing prescribed by generic name

Guideline Proportion of patients who received 0.0% >70%

compliance surgical prophylaxis as per guideline

Proportion of patients with 40% >70%

pneumonia who received antibiotic
treatment as recommended in the
treatment guidelines
Proportion of patients who received 90% 100%
second line antimalarials after a
positive malaria test
Percentage of drugs prescribed from 100% 100%
the essential drugs list
Irrational use of Percentage of encounters with 100% -
surgical prophylaxis Surgical prophylaxis exceeding 24
hours
Prescribing errors Frequency not indicated on 2.2% Errors
prescription should be
Route not indicated 0.8% avoided
Duration of use lacking 53.2% 100% of the
No stop review for antimicrobial 39.1% time
Missed doses during course of 45.5%
treatment

4.14 Linear regression for risk factors for number of antimicrobials prescribed per patient

Bivariable linear regression was carried out by regressing the number of antimicrobials prescribed
against each of the covariates. A parsimonious model of the most important predictors of number of
antimicrobials prescribed was also conducted. The co-efficients of determination for each of the
bivariable models are summarized in appendix 8. The co-efficients showed that the most important
40
determinants of the number of antimicrobials prescribed were HIV status, nutritional status, presence
of catheterization and previous hospitalization. These variables were retained in the most
parsimonious model. The most powerful predictor for number of antimicrobials prescribed was HIV
status with adjusted β co-efficient of 2.187. This meant that, on average, HIV positive patients had
an addition 2 antimicrobials prescribed. On average, catheterization increased the number of
prescribed antimicrobials by 1. This is as shown in Table 4.14

Table 4.14. Linear regression for risk factors for number of antimicrobials prescribed per
patient

Variable Crude β coefficient Adjusted β coefficient

β (95% CI) p-value β (95% CI) p-value
HIV status 2.867 (2.436 - 3.297) <0.001 2.187 (1.617 - 2.759) <0.001
Catheterization 2.089 (1.740 - 2.438) <0.001 1.317(1.055 - 1.580) <0.001
Previous 1.307 (.848 - 1.766) <0.001 0.516 (.183 - .850) 0.003
hospitalization in
the last 90 days
Nutritional status 1.510 (1.101 - 1.920) <0.001 0.264(-.0314 - .560) 0.080
Referred from 1.193 (.747 - 1.639) <0.001 - -
another facility
Age group -0.124 (-.294 - .0460) 0.152 - -
Ward type 0.642 (-.087 - .215) 0.402 - -
Intubation 0.137 (-.862 - 1.135) 0.787 - -
Sex -0.026 (-.480 .428) 0.91 - -

41
Chapter 5: DISCUSSION, CONCLUSION AND RECOMMENDATIONS

5.1 General Discussion

This prevalence survey found that 79.8% of patients admitted in Mbagathi hospital received one or
more antimicrobials. This is comparable with a previous study done in Kenyatta Referral Hospital in
Kenya where 67.7% of patients surveyed were on antimicrobials (17). Similar outcomes were
observed in a study done in Ethiopia where 86% participants prescribed with one or more
antimicrobials (69). However hospitals in Ghana and South Africa had lower antimicrobial use
prevalences of 51.4% and 31% respectively (70). World Health Organization (WHO), optimal value
is 30% or less. The deviation from the WHO norm could be due to many co-morbidities including
retroviral disease, tuberculosis and several opportunistic infections. Empiric therapy was adminstered
to cover all these infections and any other that had not been diagnosed. Secondly, most low and
middle income countries have a higher prevalence of infectious disease.

On average each participant was prescribed two (2) antimicrobials which was within the WHO
permissible levels. The optimum number of antimicrobials as per WHO guidelines is 1.3-2.2. In a
study of antimicrobial assessment at a tertiary hospital in north-western Nigeria, 22% of prescriptions
contained more than one antimicrobial (71). Similar findings were observed in Gujarat, India with an
average of 1.8 antimicrobials per patient (72).

In this study the most important risk factor for number of antimicrobials prescribed was HIV status.
The others were previous hospitalization, catheterization and nutritional status. In a point prevalence
survey in Botswana some risk factors associated with number of antimicrobials used included age-
group, prior admission, referral from another facility, being malnourished, having tuberculosis and
HIV infection (73).

Prior antimicrobial use in our study was noted in 45(24.3%) of participants. The bulk of these patients
were in paediatric ward and this was attributed to thorough history taking of prior use. It could also
be attributed to increased prevalence of parents self medicating their children. This proportion could
have been actually higher if all wards routinely sought this information from patients.The commonest
antimicrobial among the adults was co-trimoxazole while amoxillin was commonest among the
children. Similar results were observed in an outpatient study conducted in Kiambu County, Kenya,
the most prescribed antibiotic was amoxicillin 46(36%). This corroborates with other studies in Accra
Ghana and United Arab Emirates which both had amoxicillin use prevalence of 46% (29). In a point
prevalence study in Botswana (18.85) patients had prior exposure in the last 90 days, cefotaxime at

42
28.4% and amoxicillin 26.1% (73). This is in tandem with our study whereby amoxicillin was widely
used pre-admission. Self medication especially with amoxicillin has led to extensive antimicrobial
resistance. In a study done in Kakamega town, Kenya, amoxicillin had the highest resistance at 72%
(74).

A total of 363 antimicrobials were prescribed during hospitalization at Mbagathi Hospital. Antibiotics
formed the biggest proportion of antimicrobials prescribed in Mbagathi Hospital n=294(81%).
Antivirals n=48(13%) followed and the least prescribed were antimalarials and antifungals at 3%
each. The bulk of prescribed antivirals were antiretroviral drugs. Similar results were obtained in
another study conducted among 53 countries, 41,213 antimicrobials were prescribed. Antibacterials
constituted 36,792 (89.3%), both antimalarials and antifungals were 1,724(4.2%) (75). Results from
the first global point prevalence study showed that out of 48,565 antimicrobials prescribed, 43,513
(89.6%) were antibacterials, 2,062 antifungals for systemic use (76). These findings are consistent
with our study and in all the studies antibiotics were the leading antimicrobials prescribed.

In our study, third generation cephalosporin ceftriaxone topped the list of prescribed antimicrobials
86(23.7%) followed by gentamicin 37(10.2%) and metronidazole 34(9.4%). These values are
consistent with reports in the literature. In a study conducted at Kenyatta referral Hospital, Kenya,
ceftriaxone was the commonest antimicrobial prescribed (55%). This was followed by metronidazole
(41.8%) and broad spectrum penicillins (41.8%) (17). Comparable findings were seen in a
retrospective observational analysis of antimicrobials (20) where ceftriaxone was the commonest
prescribed antimicrobial at (32.5%) of the time. Amikacin was second at 25.0% and metronidazole
third at 22%. In the contrast in an Ethiopian study, the most prescribed antimicrobial was penicillin
G crystalline at (20)%, followed by gentamicin at (19%) and third ampicillin(16%) (77).
Cephalosporins particularly third generation are very popular. They have wide spectrum of activity,
minimal toxicity, are easy to administer and readily available as well. In an antimicrobial use review
by Verspoten et al; (75), vancomycin and carbapenems were highly utilized in both North and Latin
American hospitals unlike our study where they were minimally used. Reasons could be high
prevalence of methicillin resistant Staphylococcus aureus (MRSA) in Latin American Hospitals (75).
The high cost of these antibacterials is also an inhibition to their use especially in low and middle
income countries like Kenya. Most studies on antimicrobial have found a high prevalence of
ceftriaxone use . A study conducted in India had 48.5% prevalence and in Tehran 34% (78). In a
study conducted in a Kenyan referral hospital ceftriaxone was the most common prescribed antibiotic
(39.7%) followed by benzyl penicillin (29.0%) and metronidazole (25.1%) (16). overuse may be
attributed to non-adherence to guidelines as well as a weak medicines and therapeutics committee to
43
reinforce good prescribing practices. The implications of overuse of ceftriaxone are dire. With the
dwindling pipeline of new antibiotics and growing risk of resistance to ceftriaxone mortality rates
from simple infections is expected to increase. Empowering the hospitals medicines and therapeutics
committee as well as establishing an antimicrobial stewardship programme (ASP) might help to curb
this menace. Other point prevalence surveys are suggested in future to compare and evaluate impact
of established ASP.

Our study did not find any association of use of ceftriaxone with age but there was some association
with gender (p-value 0.016). This was consistent with a study in Thailand which found out that there
was a higher incidence of ceftriaxone use in females compared to males (78). However a US based
study had 86.2% males on ceftriaxone as opposed to only 13.8% females (79). This may have resulted
from the larger proportion of females in the Mbagathi study 59.5% versus 40.5%. Most of ceftriaxone
was consumed for surgical prophylaxis for obstetric gynecology surgical cases and all the patients
here are female. This could also have been due to unavailability of alternative less broad spectrum
antimicrobials. Restricting ceftriaxone use and antimicrobial stewardship programs would be of
benefit in adding life to antimicrobials. Future studies should be conducted to establish if there are
any differences in ceftriaxone consumption across the genders.

Parenteral route was the commonest accounting for 216 (58.5%) while oral route took 147 (40.2%).
Some 3 (0.8%) prescriptions had no route indicated. Our study had no transition from parenteral to
oral formulations which is a critical requirement of judicial antimicrobial use. In one Ugandan study,
81% of patients on antimicrobials during their hospital stay got at least one parenteral formulation of
their antimicrobial(s) (70). In Ghana antimicrobials were majorly administered parenterally (54%)
than orally at 46% (80). In Gujarat, India however things were different and most common route of
administration was oral at 73% (20). Early switch during treatment from intravenous to oral
antimicrobials has many benefits, including reductions in catheter-related complications, health-care
costs, and duration of hospital stays, and is recognized as a key facet for stewardship processes in
hospitals. Switching to oral medication also enables faster discharge from hospital further lowering
hospital costs associated with long hospital stay (70).

Several antimicrobials accounting for 22.6% did not have accompanying duration of use in the
treatment sheet. In a study conducted in Uganda, the prescriber omitted duration in 7%–8% of
prescriptions (70). A stop review date was available for 60% (221) of the antimicrobials but 40%
(142) had no indication on when to stop or review treatment. This means that the nurses will
administer them daily until discharge. This is serious misuse and leads to high costs and resistance.

44
A big proportion of patients 45.5% missed at least one dose during their hospitalization with some
missing up to 30 doses. Missing doses aggravates resistance since efficacy is already compromised.
This is comparable to a study done among hospitalized patients in Uganda where 44% (243/558)
missed at least one dose of their antimicrobial treatment (70). In Botswana, 1923 doses from 437
prescriptions failed to be administered, with a mean of 1.96 doses (73). Missed doses may have been
occasioned some system related problems including stock-outs, understaffing especially since most
were parenteral and a nurse is needed for administration and poor communication between the health
care providers and the patients.

In our study the most common indication was pneumonia (n=76) followed by neonatal sepsis and
neonatal jaundice n=33, prophylaxis for obstetric gynecology surgeries third (n=32), tuberculosis
(n=31) and general medical prophylaxis n=28. Similar findings in Ethiopia were reported indicating
pneumonia and sepsis as top indications where ceftriaxone was indicated (81). Similarly in an internet
based study among 53 countries pneumonia was the commonest overall indication n=5722(19.2%)
of patients treated (75). However in a survey at Kenyatta referral hospital, Kenya, the most prevalent
indication was medical prophylaxis (29%) (17). Contrary to our study, in a point prevalence survey
in Ethiopia, the biggest indications were associated with obstetrics and gynecology in 94(13.22%)
participants (73).

Out of 146 antimicrobial episodes observed, 86(59%) were for prophylaxis. Medical prophylaxis
constituted 44(51.2%) while surgical prophylaxis was at 42(48.8%). The most widely used
antimicrobial for surgical prophylaxis was ceftriaxone and co-trimoxazole for medical prophylaxis.
This is comparable with another study in Barcelona whereby sulfamethoxazole –trimethoprim was
most prevalent in medical prophylaxis accounting for 63·4% (59 of 93 patients). In Northern Europe
surgical prophylaxis constituted 17·8% and cefazolin was commonly used accounting for 1801
(27·5%). In Eastern Europe ceftriaxone was used 49(39.5%) times and 28% (559) for Southern
Europe. In Africa ceftriaxone was used 78 [27·7%] of the times (75).

Surgical prophylaxis was administered for>24 hours in 100% of the surgical cases in this study. In
an antimicrobial use survey, surgical prophylaxis lasting>24 hours was very rampant ranging from
40.6% in Oceania to 86.3% in eastern Europe (82). In an Australian study, surgical antimicrobial
prophylaxis rates greater than the benchmark of 24 hours was high (36%) (83). In a point prevalence
survey among 4 Nigerian hospitals only 4.1% surgical prophylaxis was in tandem with institutional
guidelines (84). According to one African study prophylaxis for more than 24 hours for most surgical
indications does not prevent development of postoperative infections compared with surgical

45
prophylaxis for 24 hours or less, but increases the risk of antimicrobial resistance, elevated odds of
acute kidney injury coupled with Clostridium difficile infestation (75). Inappropriate surgical
prophylaxis entails use of broad spectrum agents, like in our study use of ceftriaxone, and prolonged
duration> 24 hours. Duplicate doses are only advocated if blood loss is more than 2 liters during the
procedure, hypotension occurs or if surgery goes on for more than thrice the half-life of antimicrobial
administered. All these can lead to resistance and increased costs. There is also an emphasis from
reports that the most of irrational antibiotic prescriptions in surgical units are due to inappropriate
prophylaxis (69).

In our study generic prescribing was done 80% of the times. The rest 20% were prescribed in their
brand names. All medicines prescribed were from the essential medicine list. WHO optimal values
for generic prescribing is 100% as well as 100% for prescribing from the essential medicine list.
Almost similar findings were observed in an Ethiopian study where 97% of the drugs were prescribed
using their generic name while 92% were from the Ethiopian Essential Medicine List (85). In a study
in four governmental hospitals at United Arab Emirates (UAE) 100% was prescribed from the
essential medicine list for all hospitals surveyed as per WHO recommendations. In India 90.3% were
from the essential list while in Nepal only 42.3% was from essential medicine list (86). In a Tanzanian
study, East Africa, 96.7% were prescribed from essential medicine list while generic prescribing was
at 95.7% (87). Sub-optimal generic prescribing was noted in North west Nigeria where only 57%
antimicrobials were prescribed using their generic names (71). Some prescribers use brand names
due to pressure from medical representatives. Economic gains are usually the motivation at the
expense of the patient. Brand prescribing is expensive therefore bad practice. Some clinicians may
be unaware of the dangers associated with it for example It can also lead to adverse drug events where
look alike or sound alike medicines are confused. Strict regulation and oversight should be done by
the medicines and therapeutics committee to ensure prescribing by generic name. Prescribing audits
should also be encouraged time to time.

The proportion of patients with pneumonia who received antibiotic treatment as recommended in the
treatment guidelines was only 40%. None of the paediatric patients got dispersible amoxicillin which
is the recommended first line treatment for pneumonia in this population. In a systematic review in
Indian children aged below 5 years, oral antibiotics may be used in children with tachypnea and chest
indrawing but who do not have signs of severe pneumonia (88). Most patients with pneumonia were
started intravenous therapy. When a patient reaches clinical stability switch to orals should be
considered. Less severe pneumonia is treated for 5 days while 7 days is permissible for more severe
cases. Biomarkers are then utilized to guide on duration of antibiotic use (82). Many clinicians avoid
46
 oral antibiotics because of greater faith in intravenous administration. Secondly most paediatric
patients had already been on amoxil prior to admission. Regulatory framework needs to really look
into over the counter sale of antimicrobials without definitive diagnosis. Studies on the proportion of
antimicrobials sold without prescriptions should be done and such outlets deregistered.

Out of the sampled 185 records there were only 7 culture and sensitivity requests (3.8%). Similarly,
in a point prevalence survey in Botswana, culture and sensitivity was rarely requested and mostly in
specialized hospitals (73). In Ghana only 14 out of 382 patients on antibiotics ( 4% ) had a biomarker
test done (80). This compares poorly to a study done in The Gambia where approximately 50%
participants managed with antibiotics had at least one biomarker test requested. Empirical antibiotic
use was very common and clinical judgement was very rampant especially among neonatal
admissions. Laboratory utilization for microbiology is very limited at Mbagathi Hospital. This may
be due to unavailability of the services, delays in processing results, clinical suspicions of septicemia
warranting immediate antimicrobial use. Molecular methods of testing can be adopted which may be
cheaper and cost effective to the patients.

5.2 Strengths and Limitations of the Study

The use of a standardized protocol is a big strength for this study. This allows for comparability
nationally and internationally. Since it was a retrospective study it had several limitations. The small
number of patients hence caution is to be observed while generalizing the results. The study was done
over three weeks therefore a different pattern could also have been noted had the study period been
prolonged over other months or seasons.

This study did not measure severity of illness hence it was not feasible to relate drug use patterns
with severity of patients sicknessnesses. The quality of the records was also poor and lots of
observations had to be done since the study design did not allow for interviews. Nevertheless it is a
feasible design for surveillance in limited resource settings since this data is beneficial and pin-points
prevailing antimicrobial prescribing practices in Mbagathi Hospital.

5.3 Conclusion

This prevalence point study found several areas of concern regarding antimicrobial use. Increased
rates of antimicrobial use both prior to hospitalization as well as during admission were observed. Of
47
 note was the high prevalence (78.9%) of antimicrobial use. This was almost three times higher
compared to WHO optimal value of 30%. Ceftriaxone was extensively prescribed in this study.

The commonest indication for antimicrobial use in our study was pneumonia. Other top indications
included neonatal sepsis, tuberculosis and prophylaxis for obstetric gynecology surgery.

Adherence to guidelines was a great concern especially in surgical prophylaxis where all the patients
received doses lasting more than 24 hours as opposed to the recommended WHO permissible less
than 24 hours. Only 40% of the patients receiving pneumonia treatment adhered to the standard
treatment guidelines and paediatric protocols on pneumonia treatment.

Culture and sensitivity was rarely requested. Only seven patients out of the sampled 185 patients had
a culture and sensitivity requested. Patient management was largely empiric.

5.4 Recommendations

5.4.1 Recommendations for practice

All hospitals and health facilities should have antimicrobial stewardship committees to assist in
judicious antimicrobial use. The hospital pharmacist in-charge should set up such a committee which
should have representation from all members of the hospital medicines and therapeutics team. More
data is needed on the cost and outcomes of antimicrobial stewardship programmes (ASPs) for
decision makers to make a strong case for venturing in ASPs since there are other competing
preferences to invest in. Such data in middle and low income countries is unavailable (89)

The antimicrobial stewardship committee should make it a policy in the hospital to conduct culture
and sensitivity testing before commencing antimicrobial therapy. The hospital should facilitate
development of appropriate guidelines recommending targeted therapy guided by culture and
sensitivity results.

Hospital medicine and therapeutics committee chair should assign continuous medical education
sessions touching on proper prescribing habits. This include prescribers sensitization to indicate
antimicrobial treatment frequency, duration and stop review. Dangers of missed doses should be
emphasized. Attention could also be directed on facilitating intravenous to oral switch of
antimicrobials as well as focus on improving adherence to surgical prophylaxis guidelines. This
should form the orientation package for all interns and newly employed health care workers.

48
5.4.2 Recommendations for policy

Government needs to empower the drug regulatory authority to carry out its mandate and enforce
illegal practice of buying antimicrobials without a prescription.

Continuous medical education by the national and county medicines and therapeutics committee to
educate and supervise prescribers on rational use of antimicrobials .

Special attention could be directed at reducing overall use of ceftriaxone in the hospital when possible
and this should be taken up by the hospital medicine and therapeutics committees.

Pharmacist Interventions on antimicrobial prescriptions may be effective in enhancing appropriate

use of antimicrobials, reducing their toxicity, reducing the use of special-vigilance drugs and reducing
overall antimicrobial cost. Hospital management teams should ensure that all ward rounds have a
pharmacist in the team all the time (77).

This data forms a very good indication of antimicrobial use in public facilities in Nairobi county and
policy makers could use it for formulating policies and guidelines to improve antimicrobial use.

5.4.3 Recommendations for future research

Arising from this study the following are suggestions for future research.

1. Our study could not identify antimicrobial resistance patterns because of the few number of
culture and sensitivity tests ordered. A study should therefore be conducted to determine
resistance patterns so as to develop an antibiogram for the facility.
2. We found that culture and sensitivity testing was not routinely done. This could be avoided
by adoption of molecular techniques of identification of positive organisms and their
antimicrobial susceptibility . A cost effectiveness study comparing molecular diagnostics with
the current culture and sensitivity practices is also highly recommended.
3. A follow up study to quantify extent of economic burden due to antimicrobial resistance is
also recommended.

49
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56
APPENDICES

Appendix 1. Global Point Prevalence Survey (GLOBAL-PPS) Ward Form (62)

Global Point Prevalence Survey

Please fill in one form for each ward included in the PPS

Date of survey
(dd/mm/year) ___________/________/________________
Person completing form
(Auditor code)

Hospital name

Ward Name

Paediatric Adult
departments: departments:
Department Type:
Place a tick against the type AMW (Adult
of department PMW (Paediatric Medical Ward) Medical Ward)
HO-AMW
(Haematology-
HO-PMW (Haematology-Oncology PMW) Oncology AMW)
T-AMW (Transplant
T-PMW (Transplant (BMT/Solid) PMW) (BMT/solid) AMW)
P-AMW
PSW (Paediatric Surgical Ward) (Pneumology AMW)
ASW (Adult Surgical
PICU (Paediatric Intensive Care Unit) Ward)

57
 Neonatal AICU ([Adult]
departments: Intensive Care Unit)
NMW (Neonatal Medical Ward)
NICU (Neonatal Intensive Care Unit)

Mixed Department Yes No

Activity: Tick as
appropriate.

In case of mixed
departments, tick all the Medicine Surgery Intensive Care
encountered
activities/specialties
Total number of admitted
patients on the ward present
at 8.00 am on day of PPS
split up by activity.
For mixed
departments, fill the
total number of patients
corresponding to
each of the
encountered
activities.
Total number of beds on
the ward present at 8:00 am
on
day of PPS split up by
activity.

58
 For mixed
departments fill in the
total number of beds
corresponding to
each of the
encountered
activities.

Include only patients admitted before 8am on the day of study

59
Appendix 2 . Antimicrobial Use Point Prevalence Survey - Patient Data collection form

Participant Code
__________________________________

Research Assistant code __________________________________

Date of data collection

__________________________________

Name of the Hospital Mbagathi District Hospital (MDH)

Name of the ward group: surgery, medical, paediatrics, maternity, nursery

Ward Name

Inpatient file number (IP)/ code

__________________________________

Admission date
__________________________________

Age Group Adult (≥ 18 Years)

Child (≥ 1 and ≤ 17 Years)
Infant (≥ 1 and ≤ 11 Months)
Neonate (≤ 28 Days)
(For adults, state in Years (e.g. 34))
__________________________________
(For children, state in Years (e.g. 14))
__________________________________
(For infants, state in Months (e.g. 9))
__________________________________

60
(For neonates, state in days (e.g. 16))

Sex Male Female

Any hospitalization in the last 90 days, excluding current hospitalization

Yes No Not documented

Was participant transferred from another hospital for this admission?

Yes No Not documented

Any catheterization on participant during this admission? Yes No

Urinary ,

Peripheral (IV Cannula)

Central
Peritoneal
Haemodialysis
Unspecified
Other
Not documented
Other, Specify_____________________

Any intubation on participant during current admission? Yes No

Endotracheal
Gastro duodenal
Tracheostomy
Nasogastric/ Feeding
Suction
Unspecified
Not documented

61
Other, Specify _____________________
Has the participant undergone any surgery during this admission? Yes No

If yes, which type (most recent surgery)? Invasive

Minimally Invasive Procedure
Non-Invasive

Was a malaria test done? Yes , No

What was the result? Positive , Negative

Is the participant malnourished/wasted? Yes

No
Undocumented

HIV Status Positive

Negative
Undocumented

Is the participant on HAART? Yes

No
Undocumented

Is the participant on TB treatment? Yes No

Is antimicrobial use prior to current admission documented (within past 90 days)?

Yes No

How many antimicrobials were used before current admission (within 90 days)? 1, 2, 3, 4, 5

Antimicrobial 1
ATC Code for Antimicrobial 1 (See Appendix 5)
62
Duration of use indicated Yes No

Duration (Number of days on any antimicrobial)

Antimicrobial 2
ATC Code for Antimicrobial 2 (See Appendix 5)

Duration of use indicated Yes No

Duration (Number of days on any antimicrobial)

Antimicrobial 3
ATC Code for Antimicrobial 3 (See Appendix 5)

Duration of use indicated Yes No

Duration (Number of days on any antimicrobial)

How many antimicrobials have been used and already stopped during current admission 1, 2, 3,
4, 5
ATC Code for Antimicrobial 1 (See Appendix 5)

Duration of use indicated Yes no

Duration (Number of days on the antimicrobial)

ATC Code for Antimicrobial 2 (See Appendix 5)

Duration of use indicated Yes no

63
Duration (Number of days on the antimicrobial)

ATC Code for Antimicrobial 3 (See Appendix 5)

Duration of use indicated Yes no

Duration (Number of days on the antimicrobial)

SECTION 2

To be completed only for participant currently on Antimicrobial therapy other than for TB (Do
not proceed further if the participant is treated only for TB)

Indications for which antimicrobials were given

Number of indications
1
2
3
4
5

Indication Code 1 (See Appendix 4)

Type of indication Community Acquired Infection
Hospital Acquired Infection
Not documented
Other, specify ______________________

64
Indication Code 2 (See Appendix 4)
Type of indication Community Acquired Infection
Hospital Acquired Infection
Not documented
Other, specify ______________________
Indication Code 3 (See Appendix 4
Type of indication Community Acquired Infection
Hospital Acquired Infection
Not documented
Other, specify ______________________
Indication Code 4 (See Appendix 4)
Type of indication Community Acquired Infection
Hospital Acquired Infection
Not documented
Other, specify ______________________
Indication Code 5 (See Appendix 4
Type of indication Community Acquired Infection
Hospital Acquired Infection
Not documented
Other, specify ______________________
Number of antimicrobials given
Number of antimicrobials participant is on
1
2
3
4
5

Antimicrobial 1
ATC code for Antimicrobial: 1 (See Appendix 5)

65
Start date
__________________________________

Dose per administration __________________________________

Unit of measure
g
mg
IU
MU
Not documented
Other, specify ______________________

Route of administration Oral (PO)

Intravenous (IV)
Intramuscular (IM)
Other, specify ______________________

Frequency of administration STAT dose

Once a day (OD)
Twice a day (BID)
Thrice a day (TID)
Four times a day (QID)
Every 4 hours (Q4H)
Other, specify ______________________

Is a stop/review date for the antimicrobial documented? Yes No

Is the antimicrobial being used for Prophylaxis? Yes No Not documented

Was it Medical or Surgical prophylaxis? Medical Prophylaxis Surgical

Prophylaxis

66
Prophylaxis duration One single dose
Multiple doses within 24 hours
More than 1 day

For which indication/diagnosis is the antimicrobial being given?

Indication 1
Indication 2
Indication 3
Indication 4
Indication 5
Not documented
(These are the indications selected earlier)

Was the antimicrobial prescribed using the INN (generic name)? Yes No

Is the antimicrobial on the Kenya Essential Medicines List (KEML)? Yes No

No. of missed doses since antimicrobial started __________________________________

(Count from the date of initiation to current
date how many doses were missed and state
it as simple count. If 6 doses missed capture
as 6; if none state 0.)
Antimicrobial 2
ATC code for Antimicrobial 2: (See Appendix 5)

Start date
__________________________________

Dose per administration

__________________________________

67
Unit of measure g
mg
IU
MU
Not documented
Other, specify ______________________

Route of administration Oral (PO)

Intravenous (IV)
Intramuscular (IM)
Other, specify ______________________

Frequency of administration STAT dose

Once a day (OD)
Twice a day (BID)
Thrice a day (TID)
Four times a day (QID)
Every 4 hours (Q4H)
Other, specify ______________________

Is a stop/review date for the antimicrobial documented? Yes No

Is the antimicrobial being used for Prophylaxis? Yes No Not documented

Was it Medical or Surgical prophylaxis? Medical Prophylaxis Surgical

Prophylaxis

Prophylaxis duration One single dose

Multiple doses within 24 hours
More than 1 day

For which indication/diagnosis is the antimicrobial being given?

68
 Indication 1
Indication 2
Indication 3
Indication 4
Indication 5
Not documented
(These are the indications selected earlier)

Was the antimicrobial prescribed using the INN (generic name)? Yes No

Is the antimicrobial on the Kenya Essential Medicines List (KEML)? Yes No

No. of missed doses since antimicrobial started
__________________________________

Antimicrobial 3
ATC code for Antimicrobial 3: (See Appendix 5)

Start date
__________________________________

Dose per administration

__________________________________

Unit of measure g
mg
IU
MU
Not documented
Other, specify ______________________

Route of administration Oral (PO)

69
 Intravenous (IV)
Intramuscular (IM)
Other, specify ______________________

Frequency of administration STAT dose

Once a day (OD)
Twice a day (BID)
Thrice a day (TID)
Four times a day (QID)
Every 4 hours (Q4H)
Other, specify ______________________

Is a stop/review date for the antimicrobial documented? Yes No

Is the antimicrobial being used for Prophylaxis? Yes No Not documented

Was it Medical or Surgical prophylaxis? Medical Prophylaxis Surgical

Prophylaxis

Prophylaxis duration One single dose

Multiple doses within 24 hours
More than 1 day

For which indication is the antimicrobial being given?

Indication 1
Indication 2
Indication 3
Indication 4
Indication 5
Not documented
(These are the indications selected earlier)

70
Was the antimicrobial prescribed using the INN (generic name)? Yes No

Is the antimicrobial on the Kenya Essential Medicines List (KEML)? Yes No

No. of missed doses since antimicrobial started
__________________________________

Antimicrobial 4
ATC code for Antimicrobial 4 (See Appendix 5)

Start date
__________________________________

Dose per administration

__________________________________

Unit of measure g
mg
IU
MU
Not documented
Other, specify ______________________

Route of administration Oral (PO)

Intravenous (IV)
Intramuscular (IM)
Other, specify ______________________

Frequency of administration STAT dose

Once a day (OD)
Twice a day (BID)
Thrice a day (TID)
Four times a day (QID)

71
 Every 4 hours (Q4H)
Other, specify ______________________

Is a stop/review date for the antimicrobial documented? Yes No

Is the antimicrobial being used for Prophylaxis? Yes No Not documented

Was it Medical or Surgical prophylaxis? Medical Prophylaxis Surgical

Prophylaxis

Prophylaxis duration One single dose

Multiple doses within 24 hours
More than 1 day

For which indication/diagnosis is the antimicrobial being given?

Indication 1
Indication 2
Indication 3
Indication 4
Indication 5
Not documented
(These are the indications selected earlier)

Was the antimicrobial prescribed using the INN (generic name)? Yes No

Is the antimicrobial on the Kenya Essential Medicines List (KEML)? Yes No

No. of missed doses since antimicrobial started

__________________________________

72
Antimicrobial 5
ATC code for Antimicrobial 5: (See Appendix 5)

Start date
__________________________________

Dose per administration

__________________________________

Unit of measure g
mg
IU
MU
Not documented
Other, specify ______________________

Route of administration Oral (PO)

Intravenous (IV)
Intramuscular (IM)
Other, specify ______________________

Frequency of administration STAT dose

Once a day (OD)
Twice a day (BID)
Thrice a day (TID)
Four times a day (QID)
Every 4 hours (Q4H)
Other, specify ______________________

Is a stop/review date for the antimicrobial documented? Yes No

73
Is the antimicrobial being used for Prophylaxis? Yes No Not documented

Was it Medical or Surgical prophylaxis? Medical Prophylaxis Surgical

Prophylaxis

Prophylaxis duration One single dose

Multiple doses within 24 hours
More than 1 day
For which indication/diagnosis is the antimicrobial being given?
Indication 1
Indication 2
Indication 3
Indication 4
Indication 5
Not documented
(These are the indications selected earlier)

Was the antimicrobial prescribed using the INN (generic name)? Yes No

Is the antimicrobial on the Kenya Essential Medicines List (KEML)? Yes No

No. of missed doses since antimicrobial started
__________________________________

Culture Tests
Culture and Sensitivity (CST) ordered Yes No

How many culture tests were done during the current admission? 1 2 3
Culture Test 1
Which specimen was used Blood
Pus swab
Urine

74
 Stool
Tracheal aspirate
Tissue
Cerebrospinal fluid
High vaginal swab(HVS)
Pleural fluid
Peritoneal fluid
Joint aspirate
Other, specify ______________________

Culture results available Yes No

Culture Test 2
Which specimen was used Blood
Pus swab
Urine
Stool
Tracheal aspirate
Tissue
Cerebrospinal fluid
High Vaginal Swab (HVS)
Pleural fluid
Peritoneal fluid
Joint aspirate
Other, specify ______________________

Culture results available Yes No

Culture Test 3
Which specimen was used Blood
Pus swab
Urine

75
 Stool
Tracheal aspirate
Tissue
Cerebrospinal fluid
High Vaginal Swab (HVS)
Pleural fluid
Peritoneal fluid
Joint aspirate
Other, specify ______________________

Culture results available Yes No

76
Appendix 3. Diagnostic codes (what the clinician aims at treating) (62).

Site Codes Examples

CNS Proph CNS Prophylaxis for CNS (neurosurgery, meningococcal)

CNS Infections of the Central Nervous System

EYE Proph EYE Prophylaxis for Eye operations

EYE Therapy for Eye infections e.g., Endophthalmitis

ENT Proph ENT Prophylaxis for Ear, Nose, Throat (Surgical or Medical prophylaxis=SP/MP)

ENT Therapy for Ear, Nose, Throat infections including mouth, sinuses, larynx

RESP Proph RESP Pulmonary surgery, prophylaxis for Respiratory pathogens

LUNG Lung abscess including aspergilloma

URTI Upper Respiratory Tract viral Infections including influenza but not ENT

Bron Acute Bronchitis or exacerbations of chronic bronchitis

Pneu Pneumonia or LRTI (lower respiratory tract infections)

TB Pulmonary TB (Tuberculosis)

77
CVS Proph CVS Cardiac or Vascular Surgery, endocarditis prophylaxis

Cardiovascular System infections: endocarditis, endovascular prosthesis or

CVS device

e.g. pacemaker, vascular graft

GI Proph GI Surgery of the Gastro-Intestinal tract, liver or biliary tree, GI prophylaxis in

neutropaenic patients or hepatic failure

GI GI infections (salmonellosis, Campylobacter, parasitic, C.difficile, etc.)

IA Intra-Abdominal sepsis including hepatobiliary, intra-abdominal abscess etc.

SSTBJ Proph BJ Prophylaxis for plastic or orthopaedic surgery (Bone or Joint)

Skin and Soft Tissue: Cellulitis, wound including surgical site infection, deep
SST soft

tissue not involving bone e.g., infected pressure or diabetic ulcer, abscess

BJ Bone/Joint Infections: Septic arthritis (including prosthetic joint), osteomyelitis

Prophylaxis for urological surgery (SP) or recurrent Urinary Tract Infection

UTI Proph UTI (MP)

Cys Lower UTI

Pye Upper UTI including catheter related urinary tract infection, pyelonephritis

78
GUOB Proph OBGY Prophylaxis for Obstetric or Gynecological surgery

Obstetric/Gynaecological infections, Sexual Transmitted Diseases (STD) in

OBGY women

GUM Genito-Urinary Males + Prostatitis, epididymo-orchitis, STD in men

No BAC Bacteremia with no clear anatomic site and no shock

defined SEPSIS Sepsis, sepsis syndrome or septic shock with no clear anatomic site

Site Malaria

Pyrexia of Unknown Origin - Fever syndrome with no identified source or site

(NDS) PUO of

infection

Fever syndrome in the non-neutropaenic Haematology–Oncology patient with

PUO-HO no

identified source of pathogen

FN Fever in the Neutropaenic patient

LYMPH Infection of the lymphatics as the primary source of infection e.g.suppurative

79
 lymphadenitis

Antibiotic prescribed with documentation for which there is no above diagnosis

Other group

Drug is used as Medical Prophylaxis in general, without targeting a specific site,

MP-GEN e.g.

antifungal prophylaxis during immunosuppression

UNK Completely Unknown Indication

PROK Antimicrobial (e.g. erythromycin) prescribed for Prokinetic use

Neonatal MP-MAT Drug is used as Medical Prophylaxis for MATERNAL risk factors e.g. maternal

prolonged rupture of membranes

Drug is used as Medical Prophylaxis for NEWBORN risk factors e.g. VLBW
NEO-MP (Very

Low Birth Weight) and IUGR (Intrauterine Growth Restriction)

80
Appendix 4. Indication Codes for antimicrobials given (62)

 CNS - refers to infections of the central nervous system(e.g. Meningitis, brain

abscess)
 EYE - refers to eye infections, e.g. endophthalmitis
 ENT - refers Infections of ear, nose, throat, larynx and mouth (Upper respiratory
tract excluding bronchus)
 BRON - Acute bronchitis or exacerbations of chronic bronchitis
 PNEU - Pneumonia (other than TB; if TB see below for different code)
 CVS - Cardiovascular infections: (e.g. endocarditis, vascular graft.)
 GI - Gastrointestinal infections (e.g. salmonellosis, antibiotic-associated diarrhoea)
 IA - Intra-abdominal sepsis (between diaphragm and pelvic floor) including
hepatobiliary and peritoneal cavity infections
 SST - Soft tissue infections (e.g. cellulitis, wound, and deep soft tissue) not
involving bone
 BJ - Bone and Joint Infections (e.g. septic arthritis, prosthetic joint infections,
osteomyelitis...)
 CYS - Symptomatic lower urinary tract infection (urethra and bladder) e.g. cystitis
 PYE - Symptomatic upper urinary tract infection (ureter and kidney)e.g.
pyelonephritis
 ASB - Asymptomatic bacteriuria (Presence of bacteria in urine without symptoms)
 OBGY - Obstetric or gynaecological infections (e.g. STDs in women, abortion
related sepsis, post-partum sepsis etc...)
 GUM - Prostatitis, epididymo-orchitis, and STD in men
 BAC - Laboratory-confirmed bacteraemia (Positive blood culture with isolated
bacteria)
 CSEP - Clinical sepsis (suspected bloodstream infection without lab
confirmation/results are not available, no blood cultures collected or negative blood
culture), excluding febrile neutropenia
 FN - Febrile neutropenia or other form of manifestation of infection in
immunocompromised host, e.g. HIV, chemotherapy, etc., with no clear
anatomical site

81
 SIRS - Systemic Inflammatory Response Syndrome with no clear anatomical site
of infection.
 UND - Completely undefined; site with no systemic inflammation
 NA - Not applicable; for antimicrobial use other than treatment

82
Appendix 5. ATC codes for antimicrobials given (62)

Antimicrobial Code Antimicrobial Code

Amikacin J01GB06 Amoxicillin J01CA04
Amoxicillin and enzyme Ampicillin, J01CA51
inhibitor J01CR02 combinations

Artesunate P01BE03 Artemether and P01BF01

Lumefantrine

Artesunate and Mefloquine P01BF02 Artesunate and P01BF02

Amodiaquine

Albendazole P02CA03 Mebendazole P02CA01

Quinine P01BC01 Azithromycin J01FA10

Benzathinebenzylpenicillin J01CE08 Benzyl penicillin J01CE01

Cefaclor J01DC04 Cefadroxil J01DB05

Cefalexin J01DB01 Cefepime J01DE01
Cefixime J01DD08 Cefazolin J01DB04
Cefotaxime J01DD01 Cefpodoxime J01DD13
Ceftazidime J01DD02 Ceftriaxone J01DD04
Cefuroxime J01DC02 Chloramphenicol J01BA01
Ciprofloxacin J01MA02 Clarithromycin J01FA09
Cefoxitin J01DC01 Cefprozil J01DC10
Clindamycin J01FF01 Cloxacillin J01CF02
Doxycycline J01AA02 Erythromycin J01FA01
Flucloxacillin J01CF05 Gentamicin J01GB03
Griseofulvin D01BA01 Imipenem and enzyme J01DH51
inhibitor
Kanamycin A07AA08 Kanamycin J01GB04

83
Levofloxacin J01MA12 Linezolid J01XX08
Meropenem J01DH02 Metronidazole (oral, P01AB01
rectal)
Metronidazole (parenteral) J01XD01 Minocycline J01AA08
Moxifloxacin J01MA14 Nalidixic acid J01MB02
Nitrofurantoin J01XE01 Norfloxacin J01MA06
Nystatin A07AA02 Ofloxacin J01MA01
Ornidazole (oral) P01AB03 Penicillins,combinations J01RA01
with other antibacterials

Rifampicin J04AB02 Secnidazole P01AB07

P01AB07 Sulfadiazine J01EC02
Secnidazole
Sulfadiazine and J01EE02 Sulfamethoxazole J01EC01
trimethoprim
Sulfamethoxazole and J01EE01 Sulfonamides, J01RA02
trimethoprim combinations with other
antibacterials (excl.
trimethoprim)
Tigecycline J01AA12 Tinidazole (oral, rectal) P01AB02
Vancomycin (parenteral) J01XA01

84
Appendix 6. Letter of KNH-UON ERC approval

85
86
Appendix 7. Mbagathi Hospital Research Committee Approval Letter

87
Appendix 8. Co-efficients of determination for each of the bivariable models

Variable Crude β co-efficient P-value R-Squared

(95% CI)
Ward type 0.642 (-.0867 - .215) 0.402 0.0030
Age group -0.124 (-.294 - .046) 0.152 0.0080
Sex -0.026 (-.480 - .428) 0.91 0.0001
Previous hospitalization 1.307 (.846 - 1.766) <0.001 0.1624
Referred from another facility 1.193 (.747 - 1.639) <0.001 0.1386
Catheterization 2.089(1.739 - 2.438) <0.001 0.2943
Intubation 0.137(-.862- 1.135) 0.787 0.0004
HIV status 2.867(2.436 - 3.297) <0.001 0.5002
Nutritional status 1.510 (1.101 1.920) <0.001 0.2277

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