“Combating Antibiotic Drug

Resistance in Pakistan”
Speaker: Amir Afzal Khan (Ph. D)
Contents of the Presentation

Antibiotic

Mechanism of action of Antibiotics

Origion Of Antibiotic Resistance

Types of Antimicrobial Resistance

Factor Diriving Antimicrobial resistance

Antimicrobial resistance in Pakistan

Interventions stratagies for Antimicrobial Resistance

• Microbes
• Microorganisms, are a collective term for bacteria, viruses, fungi, and
protozoa.
• They are ubiquitous
• Either in a
• Commensal (non-disease causing)
• Pathogenic (infection causing) relationship
• Antimicrobials
• kill or prevent the growth of microbes, and are used to treat infections in
humans, animals, and plants
• Antimicrobials can either be
• Broad – targeting a commonly shared trait within a group of microbes, or
• Narrow – affecting a trait only present in a (few) species, within a group.
 Mechanism of Antimicrobial

Antimicrobials often target

destroying a microorganism or
preventing its growth by either

1) Disrupting the cell membrane,

2) Inhibiting cell wall synthesis,
3) Inhibiting protein synthesis,
4) Inhibiting nucleic acid (DNA or
RNA) synthesis, or
5) Inhibiting metabolism
(Rani et al., 2021)
Origins and evolution of Antimicrobial Resistance
• Developing resistance to
antimicrobials is an element of the
natural evolution of microorganisms.
• Two main ways

1. Intrinsic resistance

2. Acquisition of genetic material

a) Transformation (Incorporated DNA)

b) Transduction (Phages)

c) Conjugation
Antimicrobial Resistance (AMR)
• AMR is a naturally occurring process
• For example, antibiotic resistance, also called bacterial AMR, occurs when
bacteria become resistant to antibiotic medicine
• The resistant strain therefore survives exposure to the antibiotic, where other
strains without this mutation do not
• The genetic advantage can then be passed on when the resistant microbe
replicates and divides itself or, in some instances, between species through
horizontal gene transfer
• Overuse, misuse, and underuse of antimicrobials for various applications,
including therapeutic uses, and continuous exposure of antimicrobials in the
environment (such as in healthcare settings, wastewater treatment facilities,
and the built environment) further increase the resistant acquisition
 How Germs Can Spread in Community
Germs, including resistant germs, can spread between people, animals, and food,
through common activities.
For example, germs can spread from food to people and between people and
animals without appropriate hand hygiene.
People can also get an infection when traveling, then spread these germs when
they return. Other examples include gonorrhea, a common sexually transmitted
disease (STD)
However, harmful microorganisms, notably the pathogens that cause infections
among humans and animals, have developed resistance to antimicrobials
(WHO 2021a).
 AMR threatens the effective use of antimicrobials.
CDC is concerned about antimicrobial-resistant germs
 Centers for Disease Control and Prevention (CDC) is concerned about antimicrobial-
resistant germs in the community for several reasons.

Community-associated infections can happen to healthy people who have not had a recent
interaction with health care

Infections in the community can be difficult to identify and control spread

New forms of resistance can emerge and spread quickly, especially resistance shared among
germs through mobile genetic elements

Antimicrobial-resistant germs can share their resistance genes with other germs, making
them more difficult to treat
MDR, XDR, and PDR Organisms

• Multidrug resistance (MDR) arises

when a microbe is resistant to multiple
antimicrobial medicines that are
normally effective against it.
• Extensively drug resistant (XDR)
• With the exposure to a broader array of
antimicrobials, some microorganisms
have developed resistance not only to a
single antimicrobial targeting them but
to multiple antimicrobials.
• The microorganisms are referred to as
“superbugs”(Davies & Davies 2010).
Drivers of AMR

Whilst AMR is a naturally occurring process, certain human activities can hasten
its occurrence.
Inappropriate (self-medication), and overuse of antimicrobials;
Inadequate infection prevention and control measures;
Poor farming husbandry (breeding of crops and animals),
Foodprocessing, and distribution practices;
 inadequate sewage and waste management,
including in the
Production and disposal of antimicrobials.
Combating (Fight, Prevent) antibiotic Resistance
• Antibiotics Fight Bacteria, Not Viruses

• Antibiotics are meant to be used against bacterial infections.

• For example, they are used to treat strep throat, which is caused by streptococcal
bacteria, and skin infections caused by staphylococcal bacteria.

• Although antibiotics kill bacteria, they are not effective against viruses.

• Therefore, they will not be effective against viral infections such as colds, most
coughs, many types of sore throat, and influenza (flu).
Using antibiotics against viral infections

will not cure the infection

will not keep other individuals from catching the virus

will not help a person feel better

May cause unnecessary, harmful side effects

May contribute to the development of antibiotic-resistant bacteria

Follow Directions for Proper Use

• Take the antibiotics as prescribed

• Do not skip doses
• Do not save antibiotics
• Never take leftover medicine
• Do not take antibiotics prescribed for someone else
• Talk with your health care professional.
• All drugs have side effects.
What Food and Drug Administration (FDA) Is Doing

•Approval of certain new antibiotics.

•Since 2015, FDA approved new antibiotics that can treat certain resistant
bacteria.
•Labeling regulations addressing proper use of antibiotics.
•Antibiotic labeling contains required statements in several places advising
health care professionals
•Partnering to promote public awareness.
•FDA is partnering with the Centers for Disease Control and Prevention
(CDC) on "Get Smart: Know When Antibiotics Work," a campaign that
offers Web pages, brochures, fact sheets, and other information sources
•Encouraging the development of new antibiotics.
•Evaluate how an antibacterial drug works for the treatment of different
types of infections.
Main reason of increasing antibiotic resistance in Pakistan

• Major reason for antibiotic resistance is overuse and misuse

• Antibiotic therapy duration were not medically correct in 30%-50% of the cases

• Irrational antibiotics use does not only indicate lack of patient compliance towards
physicians’ instructions, but inappropriate antibiotic prescription from the
physicians is also not uncommon.

• Correct indication, right drug and dosage, drug of first choice, appropriate period
of use, and lower treatment cost, all contribute to rational (appropriate to their
clinical needs) and judicious antibiotic prescription (only when necessary)
Antimicrobial Resistance in Pakistan

• Antibiotic resistance of any World Health Organization (WHO) enlisted priority pathogens in
Pakistan (published onward 2009 till March 2020), were collected from PubMed, Google
scholar, and PakMedi Net search engines.

• That most of the pathogens Staphylococcus aureus (MRSA), Escherichia coli and klebsiella
pneumoniae in Pakistan show high resistance to commonly used antibiotics (Bilal et al., 2022).
• Pakistan consists of four provinces and capital territory, i-e, Islamabad.

• Most studies (31.6%) were reported from Karachi (Sindh), followed by Lahore (Punjab)
16.7%. 11.95% of studies were reported from Khyber Pakhtunkhwa province and 10.86% from
the Islamabad region.

• However, no study was reported from Baluchistan province

Number of AMR studies from different
cities of Pakistan included in this study
(Bilal et al., 2021) Review article
Pakistan's national action plan for antimicrobial resistance
Antimicrobial resistance has appeared as a global health crisis that could lead to 10
million deaths every year by 2050.

WHO instituted a global action plan to tackle antimicrobial resistance in the 68th World
Health Assembly in 2015.

This global action plan was endorsed by all countries, including Pakistan—the world's
sixth most populous country, and which is expected to rise to fourth place by 2050.

By participating in the Global Antimicrobial Surveillance System (GLASS), the

Pakistan National Institute of Health is the custodian of antimicrobial resistance
surveillance in Pakistan
• In April, 2018, the Pakistan Global Antibiotic Resistance Partnership launched a situation
analysis report about antimicrobial resistance in Pakistan
• The major challenges and issues

1) Unnecessarily large number of registered products,

2) Misleading advertisements,
3) Polypharmacy, irrational prescribing by physicians,
4) Availability of over-the-counter drugs without prescription,
5) Bias towards costly broad-spectrum antibiotics,
6) Lack of surveillance systems and experts,
7) Widespread use of antibiotics in poultry, animals, and agriculture

https://www.nih.org.pk
Interventions stratagies in Pakistan

World Health Organization (WHO) Global Action Plan (GAP) to combat antimicrobial
resistance, and started antibiotic stewardship program (ASP) in hospital settings
Wash your hands frequently, use gloves, ensure your instruments are clean, and
exercise good patient contact precautions are interventions to prevent antibiotic
resistance.
Antibiotic stewardship
is the effort to measure and improve how antibiotics are prescribed by clinicians and
used by patients.
Improving antibiotic prescribing and use is critical to effectively treat infections,
protect patients from harms caused by unnecessary antibiotic use, and combat
antibiotic resistance.
Basic Infection Prevention and Control Guidelines
Disinfection and sterilization

Hand hygiene

Environmental infection control

Isolation precautions
 Pakistan Antimicrobial Surveillance Program

• Antimicrobial surveillance refers to efforts to monitor changes in populations of microbes

to help understand evolving patterns of resistance to anti-infectives (treat infections).

• Self-medication in more than 50% of the population according to different studies/ surveys

• The Pakistan National AMR Action Plan identifies identified the lack of nationwide
surveillance to as a principle factor limiting the ability of Pakistan to control the growing
threat of AMR.

• GLASS is adapted by NIH in 2016, and it has led to development of Pakistan

AMRSurveillance system in 2018 (PASS)
Objectives
• 1. Conduct routine culture and standardized antimicrobial susceptibility testing
(AST)

• 2. Establish regular and systematic communication of all AST results from

identified laboratories to clinical providers as described in this document

• 3. Establish regular and systematic reporting of country defined priority AST

results and patient level data from surveillance hospitals to the National AMR
Surveillance Coordinating Center (NCC)

• 4. Analyze, interpret, and publicly report annual AMR surveillance data in a

written report
• Antibiogo is a mobile app that supports
non-expert laboratory technicians in low
resource settings in measuring and
interpreting Antibiotic Susceptibility
Tests (AST), to help clinicians prescribe
accurate antibiotics.

Whole genome sequencing (WGS)

 Matrix-assisted laser
desorption/ionization time-of-flight
(MALDI-TOF) spectrometry
Scientists discover new approach to fighting
antibiotic resistance
Researchers, including experts from Imperial College London, have found a way to
impair antibiotic-resistant bacteria that cause human disease, such as E. coli, K.
pneumoniae and P. aeruginosa, by inhibiting a protein that drives the formation of
resistance capabilities within the bacteria.

Dr Mavridou’s research team found that a protein in bacteria called DsbA helps fold
resistance proteins into the right shapes to neutralise antibiotics.

The researchers inhibited DsbA, using chemicals that cannot be used directly in human
patients, to prevent the formation of resistance proteins.

Now planning to work on developing inhibitors that can be safely used in humans while
also achieving the same protective effect.
Conrad Duncan, 24 February 2022
New Antibiotics for Multidrug-Resistant Bacterial
Strains
• The most recently approved antibiotics include

• Dalbavancin (semisynthetic lipoglycopeptide derivative of teicoplanin)

• Tedizolid (inhibits bacterial protein synthesis)

• Oritavancin (Peptidoglycan synthesis)

• Delafloxacin (DNA topoisomerase IV and DNA gyrase (topoisomerase II)

Selected Methods to Combat Zoonotic Foodborne
Bacterial Infections
• Antimicrobial Proteins

• Bacteriocins (proteinaceous or peptidic toxins)

• Bacteriophages

• Plant-Derived Antimicrobial Compounds

• Probiotics and Prebiotics

• "Since the discovery of new antibiotics is challenging,
it is crucial to develop ways to prolong the lifespan of
existing antimicrobials."

Dr Chris Furniss
Department of Life Sciences, Imperial College London