Impact Of Different Antimicrobial Stewardship

Strategies For Reducing Antimicrobial Resistance

And Antimicrobial Uses- A Systematic Literature
Review
Tarun Singh1, Munawwar Hussain2, Manish Kumar Maity3, Kapil Shandilya4, Khushi Wazir5, Anuj Malik6*, Maheipeube Ndang7,
Parneet Kaur8, Aayush Kumar9, Prashant Das10, Bimal K Agrawal11
1,2,3,4,5,6*,7,8,9,10
Department of Pharmacy Practice, MM College of Pharmacy, Maharishi Markandeshwar (Deemed to be University),
Mullana - 133207, Ambala, India
11
MM Institute of Medical Sciences and Research, Maharishi Markandeshwar (Deemed to be University), Mullana - 133207, Ambala,
India

*Corresponding author:- Dr. Anuj Malik

*Department of Pharmacy Practice, MM College of Pharmacy, Maharishi Markandeshwar (Deemed to be University), Mullana -
133207, Ambala, India. Email id- [email protected]
Doi: 10.47750/pnr.2022.13. S05.206

Antimicrobial resistance (AMR) is a serious global warning to social wellbeing. Antimicrobial stewardship Intervention is evident
to provide a good effect on AMR. Antimicrobial Stewardship Programs (ASPs) have been established to minimize the usage of
antibiotics, antibiotic resistance, and healthcare expenditure. Prospective audits with feedback, formulary restriction/pre-
authorization along with many other supportive elements are found effective techniques of antimicrobial stewardship programme.
However, the proportional effect of different techniques is unclear. This ASP strategies utilization is compared in hospital setting
and adult hospital units implementing ASP have provided much evidence demonstrating their value. This study includes the
effectiveness of various explicit AMS strategies, measuring the outcome in various clinical setups such as reducing antibiotic
resistance and antibiotic use.The death toll from COVID-19 is the highest of any other respiratory virus outbreak but Multiple Drug
Resistant (MDR) and deadly resistant pathogens outbreaks could be at any point of time.Even in this present antibiotic era required
primarily require combat it andstrong vigilance is also desired. The primary objective of this study is to enhance patient care and
to lower medical expenses, but the ultimate objective is to safeguard already available and newly developed antibiotics against the
threat of AMR. It has been noted that Prospective Audit and Feedback (PAF) intervention is one of the most often employed
strategies among all other interventions of AMS. Although this is time-taking, it is accepted by physicians for more than formulary
restrictions and pre-authorization procedures. There have been several digital initiatives to support antimicrobial stewardship
(AMS), while they have been concentrated on individual interventions.Pre-authorization or recommended formulary limitation was
found in 31% of all trials. 20% of these studies implemented this intervention independently, and many trials were also undertaken
in conjunction with other interventions mostly in addition to training and education. Using the available pool information, we
observed in various strategies a significant reduction in antimicrobial resistance and a reduced Days of Therapy (DOT)/Length of
Treatment (LOT) ratio. Formulary restriction limited the use of broad-spectrum antibiotics without any major causality.

Keywords: Antimicrobial Stewardship Programme (ASP), Prospective Audit and Feedback (PAF), Pre-authorization,
Antimicrobial Resistance (AMR), Antibiotic Resistance (AR), Define Daily Dose (DDD), Days of Therapy (DOT).

INTRODUCTION
AMR is a significant warning threat to global health, economy, and social well-being. AMR occurs when the
appropriate antimicrobial drug is not used promptly as per the requirement of the patient; therefore, medication turned
into irrational for human consumption.[1] Despite popular opinion, community members such as healthcare facilities
and agricultural production (source of food) are the main source of resistance in hospitals (antimicrobials are
commonly used in agricultural production). By choosing antibiotics with minimal resistance potential, every attempt
should be taken in the hospital to prevent the spread of resistance. There are several misconceptions concerning
resistance, such that it is only based on usage type, volume, or duration. But, in many types, it may be due to
underutilization or the quality of antibiotics. This can be categorized as having a low or high potential for antimicrobial
resistance. Antimicrobials with limited potential for resistance, like doxycycline, can cause less to no resistance
regardless of the quantity or frequency of usage. On the other hand, high-resistance-potential drugs, like ampicillin,
may produce resistance even with sparing usage and probably increase resistance if used extensively. There are
antimicrobials with low and high resistance potentials within each antimicrobials class. For instance, ceftazidime, a
third-generation cephalosporin, has a high resistance potential, while ceftriaxone, a cephalosporin, has a low resistance
potential, demonstrating that resistance is not necessarily related to antimicrobials class. [2, 3, 4] Several irrational uses
of antimicrobial drugs increase the risk of prolonged disease several folds, higher treatment costs, and increase
Journal of Pharmaceutical Negative Results ¦ Volume 13 ¦ Special Issue 5 ¦ 2022 1307
morbidity/mortality rates.[5, 6] Among various medical errors, Hospital Acquired Infection (HAI) is among the most
usual unintended events during healthcare delivery and is mostly due to AMR. Between 7% - 10% of HAI cases will
germinate in overall healthcare delivery with a minimum of one incidence of HAI at a time in developed and
developing countries.[7, 8] Various global approaches have been developed to combat antimicrobial
resistance.[9]Among these guidelines implementation of Antimicrobial Stewardship (AMS), has been counted as
efficient to fulfill the aim of the Global action plan (GAP) for proper usage of antimicrobial drugs in human beings
and animals.[10, 11]AMS is outlined as a coordinated strategy to promote choosing an appropriate antibiotic treatment
plan, as well as the dose, length of treatment, and method of management, to optimize but also monitor the proper use
of antimicrobial medicines.[12, 13] This review is designed to analyze and calculate the potential implementation
potential of AMS and its different strategies in a clinical setup. Safety and efficacy of AMS were also assessed on
infected of novel coronavirus-2 (SARS-CoV-2) and accountable for a recent pandemic worldwide.[14, 15, 16]The
mortality and morbidity rate from COVID-19 has the most elevation compared to respiratory virus epidemics and
pandemics, even in this modern antibiotics age and like this, many MDR and deadly resistant pathogens can outbreak
anytime, whose control is crucial.[17, 18, 19]Antimicrobials can be prescribed and monitored in healthcare settings with
digital initiatives, which will reduce antimicrobial resistance. Many AMS program obstacles could be improved with
the help of digital interventions. These issues can be handled by computerized provider order entry (CPOE) systems
or electronic medical records (eMRs), which permit Antimicrobial Stewardship Programme (AMSP) personnel to
quickly identify individuals on antimicrobials and document and make suggestions to prescribers.[20]

Antimicrobial stewardship
An AMSP is a clinical-based program, designed to make sure that the right patient receives proper antimicrobial
medication at the right dose, for the right amount of time. An effective program is one with strong management and
provision of required people, monetary and informatics capabilities. [21, 22] Literature suggests that the success of this
program requires a strong determination as well as an alliance between well-prepared physicians and clinical
pharmacists.[23, 24] Different countries have issued guidelines for AMS for their respective countries. [25]The guidelines
issued by the SHEA, IDSA, and WHO are also followed around the world. Interventions for the management of AMS
are categorized into three parts; pharmacy-driven, comprehensive, and disease-specific.[26, 27, 28]Integrated
antimicrobial management is essentially desired for the One Health approach. [29 - 34] Recommendations for the
reduction of AMR in hospitals were released by the IDSA and SHEA. These recommendations establish the standards
for implementing infection control systems in hospitals for the first time. The suggested standards comprised (1) a
surveillance system adopting CDC Guidelines for Infection Control measures in Hospitals; (2) creating practices
guidelines for regulating and utilization of antimicrobials; (3) utilizing hospital committees to promote new policies;
and (5) holding hospital management liable for the establishment and enforcing policies. Accepted by health
authorities, and (6) tracking results to analyze the success of implemented policies. [35, 36] The adoption of an
antimicrobial stewardship program (ASP) to control AMR has addressed the need to find a solution to enhance
antimicrobial prescription practices.[37]The AMSP includes actions to encourage the proper use of antibiotics. To
enhance competency, such steps include teaching AMS to all healthcare personnel, evidence-based effective treatment
for common infections, communicating concerns connected to the use of antibiotics to contributors, and ultimately
monitoring the impact of changes in clinical practice. [38 - 41]The ultimate goals of ASMP are to increase effectiveness,
reduce side effects, and restrict AMR. Compared to infections generated by resistant bacteria, which may result in low
clinical outcomes (mortality and morbidity), a longer hospital stay, and greater costs. It is easier to treat illnesses
brought on by sensitive organisms.[42 - 44]To decrease the unnecessary usage of antimicrobials, the IDSA has
implemented two key ASP strategies: prospective audit with intervention & feedback and Pre-authorization. The
primary benefit of the PAF technique is that recommendations are accepted voluntarily, preserving the independence
of physicians' prescription decisions. As a result, physicians are more inclined to accept and support it. In reality, this
kind of intervention may be seen as institutional because of the feedback mechanism. The approach used for such
program implementation and assessment should also be considered. The choice of audit cases basis on medical or
surgical specialties and the basis on pre-specified antimicrobials are a few of the alternatives.[45, 46]

MATERIALS AND METHOD

This review followed the standards and methodology statement of the Cochrane Collaboration Framework.

Search strategies and study selection

Genuine research publications were found using the databases listed as: PubMed; Cochrane Central Register of
Clinical Trial; ClinicalTrials.gov; and inflibnet databases. Included RCTs investigating clinical effects of
Antimicrobial Stewardship, core elements as well as supportive elements of this approach on Antimicrobial resistance,
from the beginning through May 2022, searches for drug utilization were conducted without regard to time or
language. The following Boolean format was used with carefully chosen search keywords: [‘‘Antimicrobial
Stewardship (MeSH)’’ OR ‘‘AMSP’’ OR “Prospective Audit and Feedback” OR “ Pre-authorization” OR “Restricted
Antibiotics” OR “IV to PO” OR “De-escalation”] AND [‘‘Drug Utilization (MeSH)’’ OR ‘‘Antimicrobial
Resistance’’ OR ‘‘AMR’’ OR ‘‘Defined Daily Dose” OR ‘‘DDD’’ OR ‘‘Days of Therapy’’ OR “DOT” OR “Patients
Safety” OR “Infection Control”] AND (‘‘randomized controlled trial’’ OR ‘‘clinical controlled trial’’). A search was

1308 Journal of Pharmaceutical Negative Results ¦ Volume 13 ¦Special Issue 5 ¦ 2022

also done by searching individual elements of antimicrobial stewardship as an intervention on patient safety, infection
control, drug utilization, and the effect on antimicrobial resistance.
❖ Inclusion criteria - If the research articles were randomized controlled trials investigating clinical results of any
elements of Antimicrobial stewardship on Antimicrobial resistance, drug utilization, patient safety, and infection
treatment. The list of links to articles found was manually analyzed and identified research if the report was
published in English; it included a minimum of one intervention of the antimicrobials stewardship program as
described in SHEA, IDSA, and ICMR guidelines. Populations were included as adults, pediatrics/neonates, elderly,
critically ill patients, disease-specific, and extensively included physician training and pharmacist training. We
analyzed various systematic reviews and meta-analyses as well but for data analysis, in this review, we included
only clinical trials and RCTs.
❖ Exclusion criteria - Research was done in a community setting, without AMS intervention, addressing
prescribing patterns for common drugs that do not emphasize antibiotics, and no defined local institutional or
national policies were excluded from the search. The study investigated non-human interventions such as
antimicrobial use, and antimicrobial new indications were also excluded.
A total of 35 papers are included in the systematic review after being assessed under the inclusion criteria. Data were
retrieved and compiled from the studies that were found with consideration of Preferred Reporting Items for
Systematic Reviews and Meta-Analyses (PRISMA) Guideline and segregated as Patient / Population, Intervention,
Comparison, and Outcomes (PICO) included study design and setting. Various drug utilization evaluation method
comparison and the outcome was assessed qualitatively. All recovered articles' titles and abstracts were initially
checked by one researcher (S.T.) and then confirmed by a different researcher (M.A). Then, two investigators (H.M.
and S.G.) independently reviewed each article's entire content to determine whether it met the eligibility requirements.
Discussions with the investigators helped to clarify any differences of opinion (A.B and B.S).

5603 articles identifies through database search

5522 excluded by screening and filtering

81 eligible for full text review 46 excluded after full review

35 studies eligible after quality assessment

Qualitative assessment for System Review

Figure 1 Flowchart for inclusion in a systematic review

Antimicrobial stewardship techniques

There are several AMS interventions described in SHEA, IDSA, WHO, and ICMR guidelines. It has been proposed
that these interventions are effective in reducing antibiotic use and AMR. Mainly used core elements of AMS
interventions were: prospective audit with intervention and feedback (PAF) and pre-authorization. Whereas supportive
elements included: infectious disease counseling, education, clinical pathway development, antibiotic cycling,
streamlined or medical de-escalation, separate antibiotic orders form, switch from intravenous route to oral, biomarker
derived AMA prescription, delayed prescribing; physician and patient educational support; communication training;
Close and commitment of patient testing with the policy-setting practice for antibiotics.

Core elements of AMS

Prospective audits with intervention and feedback (PAF)
Among most studies, 54% of studies have used intervention and prospective audits with feedback.[47 - 57] Out of these,
58% of trials have used this intervention independently or in comparison, [58 - 63]remaining 42% of trials conducted a
combined intervention with education and training, infectious disease consultation or any other
intervention.[64]Prospective audits with intervention and response include evaluation of antimicrobial therapy by
professionals, who makes suggestions in real-time to determine service when treatment is deemed sub-optimal. Most
of the time, clinical pharmacists conduct these audits.[65]Prospective audit with intervention and feedback includes
trained personnel (often doctors and pharmacists) evaluating antibiotic treatment. Infectious disease education is
preferable but not required and educated pharmacists frequently carry out audits. In more complicated instances, it is
ideal to have access to physicians with infectious disease experience for advice. [66 - 70] Doctor support is crucial for
pharmacists, especially at the start of the program and if the physician is not familiar with AMS pharmacists. This will
boost the credibility of the pharmacist and enable prescribers to take recommendations more seriously. [71, 72]Examples
of medical support include:
(1) Pharmacist introducing the antimicrobial stewardship program to practitioners,
Journal of Pharmaceutical Negative Results ¦ Volume 13 ¦ Special Issue 5 ¦ 2022 1309
(2) Constantly being accessible to the pharmacist for advice and meeting with practitioners as necessary,
(3) Supporting the advice of pharmacists.
Program designs differ depending on who conducts audits and offer feedback, when, how frequently, and for which
patients they are carried out.[73]One or more of the following factors may be used to choose patients:
(1) Several infectious diseases.
(2) The ward or service (such as ICU, surgery, medicine, or critical care) where the patient is located. Particular
antibiotics, such as (Narrow spectrum, broad-spectrum and restricted), or high-use antimicrobials.Vancomycin,
carbapenems, linezolid, and piperacillin/tazobactam are typical examples.
(3) Length of treatment; often available alternatives include additional antibiotic prescriptions, particular days of
treatment (such as day 3 or day 7), or extended periods (e.g., day 7 or day 10).
(4) Patients who are in the possibility of comorbidities (e.g., for Clostridium difficile infection).
This recommendation helps to improve quality prescriptions and also increases the credibility of pharmacists in the
healthcare system.[74, 75]
In a trial with intervention prospective audit and feedback on patients with pathogen-positive blood, culture improves
both activity and appropriateness of antimicrobial treatment. Whereas another trial with positive blood culture of 617
patients group was stratified into 3 different study groups and underwent randomization. The primary outcome of this
study group in which antimicrobial order was audited by the Antimicrobial Stewardship Team was found to reduce
the duration of antimicrobial therapy. These were also found to be associated with de-escalation, Length of stay,
mortality, and cost of treatment. Whereas another study brought with 69% of suggestions for a prospective audit were
accepted[76]and 12% of suggestions were accepted with modification resulting in a remarkable decline in total
antibiotics use. In a recent study, it is observed with ASI time required to give definitive therapy to patients was
reduced.[77] This intervention also found a major change in a complete boost in adherence to guidelines from 60 % to
66 % for all intervention wards. Another study found that broad-spectrum antibiotic prescribing reduced from 26.8 %
to 14.3 % when audit and feedback intervention was used and whereas it is observed broad-spectrum antibiotic
prescribing increases again with immediate effect after the intervention ends. This intervention concluded that along
with a reduction in antimicrobial use, it can also lead to a cost reduction of up to 10.5%. Moreover, implementation
in daily use of intervention has significantly reduced intravenous antimicrobials used to treat bloodstream infections
treatment duration (P = 0.022), and the rate of de-escalation was greatly increased (P < 0.001). It is found that using
this intervention along with any other intervention of AMS gives much better results. Moreover study found, broad-
spectrum antibiotic prescribing reduced from 26.8 % to 14.3 % as a result of on-site physician education sessions and
prospective audits and feedback. Intensive aggregation of on-site pharmacist intervention and off-site infectious
diseases is connected with a decrease in antimicrobial use. A trial comparing the response of antimicrobial
management between core elements of AMS pre-authorization and prospective audits, where pre-authorization
intervention consequential resulted in reductions in overall systemic antibiotics usage (9.75 DOT / 1,000-PD / month)
and broad-spectrum antibiotic usage (4.00 DOT / 1,000-PD) were observed. A recent study with intervention PAF
utilizing on COVID - 19 patients using measure scale of 7-point ordinal scale on a total of 530 patients has shown a
statistically significant impact on patient safety. [78]Implementation of this intervention along with education even on
any one infection, then good results can be observed. As this study found that the execution of this intervention along
with prescriber education for ARIs is feasible and effective. Additionally, there has been a reduction in the use of
antibiotics for ARIs and illnesses, going from 6.2 % to 2.4 %. Outcome measures of this intervention have resulted in
a decrease in antimicrobial daily defined doses, days of therapy, duration of therapy, and broad-spectrum antibiotic
use. [79 – 87] Major selection criteria used for AMS intervention are shown in figure 2.

PATIENT SELECTION DURATION OF THERAPY

• Certain infection conditions • New antimicrobials prescriptions
• Place of the patient or ward • Particular or fixed DOT
• Admitting services (e.g. Medicine, (eg. Day 3 – 7)
surgery , critical care) • Longer durations (e.g. Day 7 – 10)

Major selection criteria of AMS intervention

STRATEGIES FOR OUTCOME MEASURES

COMMUNICATION • Decrease in Antimicrobial DDD
• In person or telephonic conversations • Days of therapy
• Daily planned stewardship rounds • Duration of therapy
• Notes and consult. • Reduction in broad spectrum
antibiotics use.

Figure 2 Major selection criteria of AMS intervention

Pre-authorization/formulary restriction
Out of total studies, 31% studies used pre-authorization / formulary restriction.[88 - 94] Out of these, 64% of trial
interventions used this intervention independently or in combination. 36% of trials have been conducted together with
combined initiatives such as education, training, prospective audit feedback. [47, 95 - 100]

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Several antimicrobials included in a hospital's formulary may be subject to restrictions. Such restrictions may be based
on who is qualified to administer an antibiotic (for example, certain services or expertise) or accepted standards for
using the antibiotic at the institution. One technique to guarantee adherence to such limits is a formulary restriction
with pre-authorization. Pre-authorization is used in conjunction with formulary restriction to pre-approve orders before
prescription distribution. Consultation between the prescriber and the person tasked with determining if the request is
suitable (often an infectious disease expert or infectious disease pharmacist) is a common method for obtaining
approval.[101 - 106]
There are several ways that implementation may happen:
(1) When a request for a restricted antibiotic is received, the prescriber (or, in some institutions, the pharmacist)
directly contacts a member of the antimicrobial stewardship program (typically through a pager or phone). If the
restriction criteria show that the antibiotic is necessary, it is then approved; otherwise, substitutes are suggested.
(2) It is possible to take a similar course of action as described above, but through consultation with an expert in
infectious diseases.
(3) It is possible to utilize a preauthorization form (or computerized physician order entry), in which the doctor must
explain why the antibiotic is necessary. After that, the paperwork is examined before the medication is given out. [107]
(4) When the use of an antibiotic does not comply with limits, clinical pharmacists (instead of an expert team member
of the AMS team) get in touch with the prescriber in a less formal program. [101]
(5) A short course may be supplied until the request can be assessed, or permission may only be granted during peak
working hours. Some institutions have staff available for 24 hours per day × 7 days per week for medication approval
(e.g., on the next work day). [108]
Preauthorization combined with formulary limitation is referred to as a "front-end" method since it involves an
intervention before the medicine is made accessible. Additionally, it is viewed as a "limiting" stewardship strategy (as
opposed to "educational/persuasive"). [109, 110] An approach that has been used for centuries in reducing antibiotic
formulary and limiting the use of specified antibiotics. Due to the high cost and broad spectrum of activity of newly
developed antibiotics, rather with AMS results could be inclining for utilization of narrow-spectrum antibiotics.[111,
112]
One of the reasons for frequently longer duration use of broad-spectrum antibiotics is the fact that antibiotics are
generally easily available to all prescribers.[113]So, it becomes imperative that certain broad-spectrum antimicrobials
be designated as restricted as per AMS. Restricted broad-spectrum antibiotics are drugs "whose high cost warrants
some restriction on their use as well as the potential for toxicity or emergence of resistance among hospitalized
organisms". Parenteral carbapenems, piperacillin-tazobactam, glycopeptides, colistin, and antifungals (excluding
fluconazole) have all been classified as restricted under this program. Antimicrobials such as 3rd generation
cephalosporins, quinolones, and amikacin can be prescribed by doctors of all specialties for the first 72 hours, but after
that, IDS permission is required. Although it has been observed in research that strict pre-authorization was not feasible
in hospitals. [114 - 121] The monthly mean of DDD / 100 bed-days was reduced from 96 ± 7 to 65 ± 6 (p < 0.001) as
reported with pre-authorization intervention in the hospital. The percentage of patients inoculated or infected with
MDR organisms has dropped from 36 % to 13 %. The time to admit to ICU and time to discharge ICU decreased from
48 % to 29% (both P < 0.001). Short-term antimicrobial therapy reduced antibiotic exposure in seriously unwell ICU
patients. It was also found that continuation of treatment for up to 15 hours was not able to produce any significant
clinical benefits. Moreover, the duration of hospital stays was significantly reduced in the short-term treatment group
by restricting antibiotics (61 ± 34 hrvs 81 ± 40 hr, P = 0.005).

Supportive elements of AMS

Our study found that 45 %[47, 57, 58, 59, 60, 61, 62, 64, 94, 122, 123, 124] most commonly used educational interventions as adjuncts
to AMS. Various studies have been carried out by training physicians, pharmacists, nursing, and other healthcare
professionals about AMS for infectious diseases. In some studies, management training was also included. The
efficacy of ASPs in diverse healthcare settings relies on intervention studies that enhance practitioners' and patients'
understanding of proper antibiotic usage. Antibiotic prescriptions for certain illnesses and asymptomatic bacteriuria
can be reduced by educating healthcare providers. Educational approaches have also been found useful in improving
adherence to prescribed guidelines. Its usefulness is more efficient in prescribing certain categories of drugs (eg, third-
generation cephalosporins, fluoroquinolones) General compliance with some recommendations as a particular therapy
and desired to have further research for finding more efficiency. A best practice alert (BPA) was established in one
study to efficiently utilize this intervention and found that several for the objective of de-escalation, BPAs were
developed and acted on within 72 hours: (69%) were approved, (12%) with revisions, and (18%) were refused. When
the advice was followed, overall antibiotic use and broad-spectrum antimicrobial use both decreased statistically
significantly. Oral administration is the simplest and most suitable mode of medication delivery. There is a moderate
therapeutic distinction between IV and PO medicines if an oral drug reaches tissue and blood concentration to the
same extent as an IV medication. Activities for antimicrobial stewardship run by pharmacists can help with the
transition from IV to PO switch therapy. [125 - 129]Newer injectable antimicrobial agents are generally expensive and
broad-spectrum.[51, 53] When examining the use of infectious disease advisory interventions in a study, it was found
that mean of monthly usage calculated as DDD decreased from 96 ± 7 to 65 ± 6 (P < 0.001) in 100 bed-days throughout
the hospital. The percentage of patients inoculated or infected with multi-drug resistant organisms has dropped from
36 % to 13 %. Moreover, ICU admitting time and Intensive Care Unit (ICU) discharge time decreased from 48 % to
29% (both P < 0.001). Daily infectious disease consultations were found to be efficient in lowering antimicrobial
usage while there was no change in in-hospital mortality.[89] Restricted antibiotics led by an IDS significantly reduced
Journal of Pharmaceutical Negative Results ¦ Volume 13 ¦ Special Issue 5 ¦ 2022 1311
carbapenem use in general wards of - 4.57 DOT / 1,000 patient days/month from - 6.69 to - 2.46. Intensive aggregation
of on-site pharmacist intervention and off-site infectious a decrease in the usage of antibiotics was linked to certain
disorders. Pre-intervention, intervention, and post-intervention periods, while adopting antibiotic cycling, showed a
significant reduction in resistance to AMC (- 31.85 % change).[64, 130, 131]In a recent trial it is found that the length of
treatment per patient days was decreased from 6.5 days to 4.8 days in the intervention time.[132] The streamlined
guideline "Implementing an Antibiotic Stewardship" suggests for places with the highest antibiotic usage, a facility-
specific clinical approach to enhance prescription practices has been developed. Our search did not find any studies
using clinical pathways as interventions. Besides, many of the core and supporting elements of AMS such as infectious
disease counseling, and prospective audits require specific institutional clinical pathways. Clinical pathway
implementation outcome measures also found observed in decline inappropriate antibiotic use. The general
characteristics of the criticized studies characteristic are shown in Table 1.

Table 1 General characteristics of the reviewed studies

Characteristic
Numbers (%)Percentages
Geography (N = 35)
USA 15 42.86
China 3 8.57
Germany 2 5.71
England 3 8.57
Canada 1 2.86
Australia 2 5.71
France 3 8.57
Netherlands 2 5.71
Norway 1 2.86
Thailand 1 2.86
Singapore 1 2.86
Publication Year (N = 35)
<2011 0 0.00
2012–2014 7 20.00
2015–2017 10 28.57
2018-2021 18 51.43
Study Design (N = 35)
Clinical Trials 1 2.86
RCT 34 97.14
Unclear 0 0.00

RESULT AND DISCUSSION

The study's goal is to evaluate antimicrobial stewardship in tertiary care hospitals. When AMR becomes a grave danger
to the potential goal of reducing infection-related deaths in the past century, it renders all modern antibiotics ineffective
against resistant organisms. The Antimicrobial Stewardship Program (ASP) has become a prime instrument in the
battle against AMR as fewer drugs are under development shortly. CDC has identified major 18 resistant pathogens.
These threats are classified according to their level of risk: acute, relevant, and severe. The WHO recently released a
list of 12 bacteria that are resistant to antibiotics and represent the biggest threats to human health. Various
interventions in Antimicrobial Stewardship Program are expected to improve patient protection against AMR,
especially from hospital-borne infections. Implementation of this initiative reduced the usage of antibiotics and the
development of antibiotic resistance. When prescribing antimicrobials, there is a rising awareness of the significance
of establishing an indication. Several studies have demonstrated that comprehensive techniques may be used to
improve antimicrobial indication reporting, despite the fact it is not routinely administered. Recent studies have
demonstrated to shows Antimicrobial indication recording appears to be linked to better prescription and patient
outcomes in both clinical and community settings. Various elements of AMS are followed at the national or
institutional level as per requirements on identified resistant pathogens. Hospital ASPs focused on providing high
outcomes for patients through the implementation of a variety of interventions, with cost described because the fitness
effects are additionally achieved. Patients, insurers, clinicians, and manufacturers can all gain if AMR is improved,
and the healthcare system's financial stability will also increase. For this evaluation, we looked at all of the outcomes
from qualified quality research and discovered that the majority of hospitals' ASPs are aimed at reducing AMR and
DUR. Most ASPs, on the other hand, are focused on changing antimicrobial usage practices and lowering costs. While
concluding this review several important contributing elements of ASP elements were also observed which could not
be fully quantified in this review such as biomarker-derived AMA prescriptions such as PCT, CRP, IL-1, IL-8, and
others. Their potential contributions to the improvement of ASP-appropriate properties for clinical usage in acute
infections include CRP and PCT delay setting; physician and patient educational support; communication training;
Close patient testing and commitment with the policy-setting practice for antibiotics; streamlined or medical de-
escalation; antibiotic order form. These aspects are cost-effective, even if they require a lot of resources and money,

1312 Journal of Pharmaceutical Negative Results ¦ Volume 13 ¦Special Issue 5 ¦ 2022

but the outcomes are quantifiable. Antimicrobial management principles and aspects may be applied effectively in
any care hospital to increase patient safety and antibiotic safety.
CONCLUSION
Our findings suggest that antimicrobial use is sub-optimal in this area, as evidenced by the data we analyzed. We
encourage those functioning in this field to establish AMS as a prime concern for their organizations and to evaluate
suggestions in areas where new techniques are being developed and implemented. In this way, efforts may be made
to enhance the usage of antimicrobial drugs within that area and finally improve the health of this patient. Overall, this
study found that ASP has a moderate impact on antimicrobial usage and that AMS can reduce AMR, DUR, length of
stay, and cost while improving patient outcomes. Antibiotic protection has been proven to benefit from a variety of
components. However, if we utilize key components and a dedicated Pharmacist in conjunction with another adjuvant,
we can see a considerable reduction in AMR and antibiotic usage. Instead of generalizing an illness, AMS has proven
the relevance of a specific disease as well as its extent. Positive perceptions and practices regarding antimicrobial
stewardship were observed in this study. However, several aspects need to be strengthened, such as the integration of
the antimicrobial stewardship program into community pharmacies, the need for inter-professional collaboration, and
the distribution of antimicrobials without a valid prescription. Interventions to enhance antimicrobial stewardship
perceptions and behaviours must be designed to address the gaps identified in this study. The data also indicated that
the costs of introducing and implementing ASP may outweigh the cost savings of the latter. In addition, multiple
systematic reviews and meta-analyses have shown that such programs improve hospital LOS, resistance strategies,
and infection occurrence. These findings support the importance of ASP with infection control methods. Moreover,
the findings are universally applicable. While further study is still needed. This would enable us to not only design
high-value customized ASP models based on robust medical and financial data but also to observe benchmarking,
which is a difficult task.

Funding: None

Conflict of interests: None

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