Journal of Clinical Sciences

REVIEW ARTICLE
Year
: 2021  |  Volume : 18  |  Issue : 2  |  Page : 74--80

Roles and challenges of clinical microbiology laboratories in antimicrobial stewardship in resource-limited countries: A narrative review


Mohammed Ibrahim Tahir1, Abdurrahman El-Fulaty Ahmad1, Temidayo Oluwafemi Ige2, Idris Nasir Abdullahi1, Yahaya Usman1, Ahmed Babangida Suleiman3,  
1 Department of Medical Laboratory Science, Ahmadu Bello University, Zaria, Nigeria
2 Department of Medical Microbiology, Kaduna State University, Kaduna, Nigeria
3 Department of Microbiology, Ahmadu Bello University, Zaria, Nigeria

Correspondence Address:
Dr. Abdurrahman El-Fulaty Ahmad
Department of Medical Laboratory Science, Zaria
Nigeria

Abstract

Antimicrobial resistance (AMR) is a major global health challenge, especially in low- and middle-income countries (LMIC). Programs that appropriate antibiotic use such as antimicrobial stewardship, is a global health strategy adopted by the World Health Organization to contain threats posed by AMR. Unfortunately, many LMICs are at best left behind in the process of developing antimicrobial stewardship programs (ASP). We highlighted the roles of the clinical microbiology laboratory in antimicrobial stewardship and challenges associated with the program in LMICs. We further suggested ways forward in the adoption and implementation of existing programs in resource-limited settings. There is generally nonexistent or at best, fewer ASP in the LMICs. More efforts need to be channeled toward fighting the AMR scourge, primarily by adopting ASP while utilizing the little resources available.



How to cite this article:
Tahir MI, Ahmad AE, Ige TO, Abdullahi IN, Usman Y, Suleiman AB. Roles and challenges of clinical microbiology laboratories in antimicrobial stewardship in resource-limited countries: A narrative review.J Clin Sci 2021;18:74-80


How to cite this URL:
Tahir MI, Ahmad AE, Ige TO, Abdullahi IN, Usman Y, Suleiman AB. Roles and challenges of clinical microbiology laboratories in antimicrobial stewardship in resource-limited countries: A narrative review. J Clin Sci [serial online] 2021 [cited 2021 May 15 ];18:74-80
Available from: https://www.jcsjournal.org/text.asp?2021/18/2/74/314451


Full Text



 Introduction



The World Health Organization (WHO) defines Antimicrobial resistance (AMR) as the ability of microorganisms to withstand (resist) or reduce the action of antimicrobial drugs (such as antibiotics, antifungals, antivirals, antimalarials, and anthelmintics) to which they were ab initio susceptible.[1] Simply put, it is the ability of microorganisms (such as viruses, bacteria, fungi, and some parasites) to stop or reduce antimicrobials (such as antibiotics, antivirals, antifungals, antiparasitic agents) from working against them.[1] Consequently, standard treatment modalities are rendered ineffective, infections persist and tendencies to spread to others increase. It is a global multifaceted phenomenon, a Pandora box of unprecedented evil, threatening to revert the entire world back to the preantimicrobial era and even worse, with horrendous consequences. The development of antibiotics is one of the greatest breakthroughs in the field of medicine and in a span of about 70 years 14 new classes of antibiotics were introduced.[2] This did not happen without unintended negative consequences as AMR emerged and resulted in setbacks in infection management and control. AMR emerged from treating trivial and viral infections with broad-spectrum antibiotics.[3]

At present, AMR has emerged as one of the major public health concerns of the 21st century that threatens the effective prevention and treatment of a growing range of infections caused by microorganisms no longer susceptible to the common medications used to treat them.[4] The problem of AMR, especially with regards to antibacterial resistance requires urgent attention. In Nigeria, there are a lot of data that reported cases of multidrug-resistant (MDR) bacteria from many clinical and epidemiological studies. For instance, in the intensive care units of University College Hospital Ibadan, 59.3% of bacterial isolates were MDR strains;[5] among poultry workers in Abuja 16.7% and 79.2% of Escherichia coli isolated were extended-spectrum beta-lactamase (ESBL) and MDR strains, respectively;[6] in Port Harcourt 46.7% MDR tuberculosis (TB) was reported;[7] in Kano 100% MDR bacterial isolated were reported;[8] and 35% ESBL E. coli isolates were reported in Enugu.[9] In a National AMR report in Nigeria, it was shown that all the bacteria causing urinary tract infections (UTIs) are resistant to all antimicrobial drugs commonly prescribed.[10] In particular, there was high resistance to ceftriaxone, ampicillin, and cotrimoxazole. Many of the bacterial isolates had 100% resistance to ampicillin and cotrimoxazole (first-line drugs for UTIs).[10] In addition, the Center for Disease Control and Prevention (CDC) estimated that >2 million people in the US are affected with AMR each year, with more than 35,000 deaths as a result.[11] In Europe, more than 400,000 people were affected and about 25,000 deaths were reported in 2007.[12] A systematic review of AMR in Africa revealed that recent AMR data are not available for >40% of the countries and the level of resistance to commonly prescribed antibiotics was significant.[13] The burden of AMR in Nigeria is difficult to quantify due to the diversity of sources and lack of properly coordinated surveillance.[14]

 Factors Contributing to The Emergence of Antimicrobial Resistance



The overuse of antibiotics obviously drives the evolution of resistance.[15] Studies show that there is a direct relationship between antibiotic use and the emergence and spread of resistant bacterial strains.[15],[16] Erroneously prescribed antibiotics also promote resistance development by bacteria. Studies have also shown that treatment modalities, choice of and duration of antibiotic therapy are done incorrectly in 30%–50% of cases.[4],[17]

Some physicians also contributed due to limited knowledge of the basic principle of antibiotic therapy.[18],[19] Uncontrolled commercial output of broader spectrum and newer generation antibiotics by pharmaceutical industries has immensely contributed to the scourge. In low- and middle-income countries (LMICs), under-utilization of antimicrobial agents due to poverty has resulted in the emergence of resistance. The systematic misuse and overuse of antimicrobials in human medicine and food production have put the entire human race at risk.[20],[21],[22] AMR has increased potential in LMICs to cause more morbidity and mortality considering the burden of bacterial disease in the regions, poor access to diagnosis and below the bar availability of second-line antibiotics.[23] Other factors causing the antibiotic crisis include extensive agricultural use. Treating livestock with antimicrobials is believed to improve the overall health of the animals, producing larger yields and a higher-quality product. The antibiotics used in livestock are eventually ingested by humans.[24] Agricultural use of antibiotics also has significant effects on the environmental microbiome. A greater proportion of antibiotics administered to livestock are excreted in stool and urine, and so are widely dispersed through groundwater, fertilizer, and surface runoff.[4]

At present, resistant organisms which pose the greatest global threat include Methicillin-resistant Staphylococcus aureus,[25] vancomycin-resistant enterococci,[26] drug-resistant Streptococcus pneumoniae, drug-resistant Mycobacterium TB,[27] fluconazole-resistant candida, carbapenem-resistant enterobacteriaceae, MDR Pseudomonas aeruginosa, acinetobacter, ESBL-producing enterobacteriaceae, drug-resistant strains of Neisseria gonorrhoeae, Salmonella typhimurium, nontyphoidal Salmonella, shigella, campylobacter, and Clostridium difficille.[28]

The CDC, WHO, as well as other organizations and experts recommend steps that healthcare practitioners and healthcare facilities (HCFs) can pursue to reduce antibiotic resistance. These include adopting an antibiotic stewardship program, preventing infection transmission, encouraging innovative approaches required for the development of new antibiotics, and global surveillance of AMR.[4],[17],[29]

Antimicrobial stewardship program

Antimicrobial stewardship was defined by the Infectious Disease Society of America (IDSA) as a “rational, systematic approach to the use of antimicrobial agents to achieve optimal outcomes.”[30] In another term, it refers to coordinated interventions designed to measure and improve the appropriate use of antimicrobial agents by promoting the selection of optimal antimicrobial drug regimens including dosing, duration of therapy and route of administration.[31]

Successful implementation of an antimicrobial stewardship program (ASP) requires an interdisciplinary team, system innovation, education, and feedback provided to health care workers. Promoting the appropriate use of antibiotics is intended to improve clinical outcomes by reducing AMR, limiting drug-related failures, and minimizing the risk of unintended consequences arising from antimicrobial use and misuse.[32] Tactics employed in antimicrobial stewardship include:

Formulary restriction and preauthorization

This involves limiting the use of particular antimicrobial agents to certain approved indications. The approach leads to direct control over antimicrobial use and misuse for prescribers when making requests.[31]

Prospective audit with intervention and feedback

Involves a daily review of targeted antimicrobial agents for appropriateness. Follow up intervention may be necessary by contacting the prescriber to recommend alternative antimicrobial agents.[31]

Supplemental strategies

Other strategies which play pivotal roles in ASP include education, guidelines, and clinical pathways, streamlining or de-escalation, antimicrobial order forms, IV-to-PO switch (that is switching from giving drugs intravenously to oral), and antimicrobial cycling.[31]

The IDSA/The Society for Healthcare Epidemiology of America guideline recommends that two core members of the team should include an infectious disease physician and a clinical pharmacist. Other critical members of the team can include a hospital epidemiologist, a clinical microbiologist, infection control professional, and an information system analyst.[33] It is necessary to acquire support from the hospital management, who should give core team members the permission to administer stewardship tactics. However, everyone in an HCF has a role to play in this battle against microbes.

Clinical microbiology laboratories in the HCFs of low-/middle-income countries need to rise to the challenge and appreciate the fact that they also can play a cardinal role in the hospital ASP in guiding the antimicrobial choice to support the successful patient outcome and minimize the adverse impacts in terms of cost of healthcare, toxicity and antimicrobial selective pressure. Surveillance is the basis for any infection control and ASP; the clinical microbiology laboratory, on its own, is key surveillance and early warning system.

 Roles of Clinical Microbiology Laboratory in Antimicrobial Stewardship Program



Institutionalized ASP helps the physicians to offer the most favorable treatment to patients through appropriate prescription of antimicrobial regimen to the right patient for the right period. The program has conventionally been implemented mainly by pharmacists and supervised by an infectious disease physicians until the last decade where rapid diagnostic microbiology technologies offered more opportunities for ASP in the clinical microbiology laboratory.[33] Prescribing physicians and ASP rely on guidance and information from the clinical microbiology laboratory to achieve the stewardship objectives, and this prerequisite has included the laboratory as an integral component to patient care and the success of ASPs.[30]

 Antibiotic Resistance Surveillance



Surveillance is defined as the ongoing and systematic collection, analysis, and interpretation of health data necessary to the planning, implementation, and assessment of public health practice. AMR surveillance is expected to present updated and appropriate information to ratify therapy guidelines, antibiotic formulary, public health interventions, infection control policies, antimicrobial development, and ASPs.[34] All countries, including LMIC, are mandated to develop strategies for suppressing AMR as part of the WHO Global Action Plan for AMR.[35] Surveillance can be detected passively through normal laboratory pathways or workflow and alerting on an individual basis or actively when specific targets are followed by informatics models and processes and acted upon when thresholds are crossed.[36] There are several approaches to surveillance of AMR which include population-, sentinel-and laboratory-based surveillance. However, the general current perception is that the laboratory-based is the most efficient though it is accused of skewed surveillance generated data.[35]

One of the fundamental requirements for ASP is the surveillance for the most prevalent and type of circulating resistant bacteria species in a hospital or a community. Clinical microbiology laboratories spearhead the antimicrobial susceptibility testing to depict the antibiogram of the tested organisms which helps to illustrate a clear resistant pattern to the antimicrobials. This promotes the restriction of testing to only known organisms or at least thought to be of possible clinical significance.[37] Antibiograms also known as Cumulative Antimicrobial Susceptibility Report, is essential in helping prescribers choose efficient therapy while awaiting culture result, revising local guidelines for empirical treatment of common infection and perioperative prophylaxis. It provides the basis for antimicrobial formulary selection.[36]

The creation of the antibiogram involves the collection, organization, and communication of resistance data. Antibiograms provide critical information to ASPs and prescribing physicians on institutional susceptibility patterns.[30] The antibiogram profile generated serves as a guide for prescribing clinicians on the most likely antimicrobial to treat given pathogens, in so doing optimizing empiric antimicrobial therapy. Created antibiogram helps in developing institution's drug formulary and can be created specifically to address distinct patient's care location or clinical condition such as medical intensive care units or UTI respectively.[30]

 Rapid Diagnostic Tests For Organism Identification And Resistance Testing



Many rapid diagnostic test assays have been developed over the past two decades. The tests remarkably reduce turnaround time for organism identification when compared with the traditional cultural methods. This lead to faster susceptibility results through detecting resistance marker.[38] Rapid identification of blood pathogens for example is important as mortality from sepsis is reported to increase by 8% with every hour of delay of antibiotic administration.[39] Therefore, laboratories must establish a reliable alerting system to promptly communicate the results of high-risk infections to the prescribers.[36] Rapid diagnostic assays are essential in the prompt identification of pathogens that are difficult to identify by the standard microbiology methods. Rapid diagnostic assays currently in use for detecting different resistance markers include peptide nucleic acid fluorescence In situ hybridization, matrix-assisted laser desorption ionization time-of-flight mass spectrometry, real-time polymerase chain reaction, gram-positive blood culture (BC) nucleic acid microarray, gram-negative BC nucleic acid microarray, and multiplex nucleic acid amplification test with varying turnaround time of 0.2–2 h.[38]

 Antimicrobial Susceptibility Reporting



The Clinical and Laboratory Standards Institute (CLSI) defines cascading microbiology laboratory reporting as a “strategy of reporting antimicrobial susceptibility test results in which secondary (e.g., broader-spectrum, more costly) agents may only be reported if an organism is resistant to primary agents within a particular drug class (cascade reporting is one type of selective reporting).”[40]

Although data that demonstrate the direct impact of those strategies on prescribing are limited, some form of selective or cascaded reporting is reasonable.[41] By this, narrow-spectrum antimicrobials (primary agents) are reported from the antimicrobial panel while holding back the susceptibilities of the broad-spectrum agents, higher-cost agents or high-toxicity agents (secondary agents). Cascade or selective reporting provides susceptibility reports based on formulary availability and antibiograms.[35] Cascade reporting is important because if secondary agents are not reported, they are less likely to be prescribed. The susceptibilities of the secondary agents can be reported on a request from the microbiology laboratory.[36],[40]

 Quality Management System



Implementation of the quality management system is key toward achieving sustainable ASP. In medical laboratories, quality is defined as accuracy, reliability, and promptness of reporting a result while a quality management system involves coordinated activities put in place to achieve the said quality.[42] International Organization for Standardization (ISO) and CLSI are the most widely adopted standardization bodies for the medical laboratory quality management system. ISO 15,189 provides medical laboratories with particular requirements for quality and competence while CLSI QMS01-A4 is tagged as a model for laboratory services approved guidelines.[43],[44] These enshrined requirements for medical laboratory quality services cover the preanalytical, analytical, and post-analytical phases of sample workflow.

All quality programs for culture media used in clinical microbiology laboratories must in the final analysis assure that a medium will support the growth of the organisms likely to be in the specimen.[45] It must specifically inhibit the growth of commensal microbes, exhibit ideal biochemical response, and should be relatively stable with appreciable shelf life.[45] For the quality assurance purpose of culture media, the presence of turbidity an indication of precipitation of the constituents of the medium;[45] color alteration may indicate overheating of sugar-containing media, incorrect pH or incorrect mixture of ingredients.[45] Importantly and on preparation, culture media must be sterile before use. Each batch of newly prepared medium (whether prepared in the laboratory or received from a commercial source), must be sampled for sterility. This is best done by removing 1%–5% of the batch and placing it in a bacteriologic incubator at 35°C for 48 h.[46] It is also ideal to determine the ability of the medium to support the growth of suspected organisms by inoculating the medium with a typical stock culture isolate.[46] When testing for the ability to support growth, it is ideal to prepare a dilute suspension to use as the inoculum.[45] This suspension confers greater assurance that the medium is adequate for the growth of a minimal amount of organisms in the specimen.[45]

 Challenges Associated With Antimicrobial Stewardship Programs In The Low-And Middle-Income Countries



The recognition that misuse of antimicrobials affects the society of patients and not just an individual patient and increased risk of transmission of resistant organisms empowered ASP development. In LMICs, there are significant challenges in antibiotics prescription; although not all individuals have access to adequate antibiotic therapy, the usage of these drugs is high and is reflected in high rates of bacterial resistance. The execution of the strategic models within ASP is promising and good results have been achieved, with a decline in antimicrobial usage.[47]

The institution of ASP is a global need, and there are global initiatives for its development and implementation. There are special challenges faced by the LMICs, as there is a need for them to allow access to their population, but the use must be made appropriately. Currently, high rates of AMR are reported in-hospital services, but in some countries, the implementation of ASP begins to yield valuable results.[47] The challenges of ASPs are many, and their impact on improving patient outcomes, limiting the spread of pathogenic-resistant organisms, and decreasing costs are profound in the current health care environment. Clearly, a multidisciplinary approach fosters the success of ASPs. Indeed, achieving ASP has been bedeviled by a lot of challenges that include:

Greater percentage of pathogens are MDR, both hospital and community acquired;[14] inadequate laboratory testing facilities for the detection of MDR pathogens;[48] poor regulatory policies on the use of antimicrobials in humans and for animals;[49] poor regulation of antibiotics in the food industry such as in poultry animals; and lack of healthcare workers training and leadership willpower in implementation and sustenance of ASP.[50] However, there are emerging efforts that try to curtail global AMR such as the recent one proposed by the WHO. Some nations have documented success in the implementation of some of the key aspects of ASPs. These can serve as a guide for adaptation in local conditions. This forms the rationale for the protection of antimicrobials, for present and future use.

 Going Against The Tides: Antimicrobial Stewardship Programs In The Low- And Middle-Income Countries



No doubt that fighting the scourge of AMR which is promoted by lack of resources and attitude towards public health is a serious challenge in the LMICs.[51] That would not however, warrant complete disregard of processes and programs that aim at mitigating the menace. The first step of addressing this is adopting the initiatives that are already role-played elsewhere in the developed and even developing countries.[51] Despite resource limitations in these settings, the most expensive resources, human resources, endowed with multidisciplinary specialties and qualifications in addition to requisite knowledge of existing ASP programs are available.[52] These resources should be stimulated to understand the risks at hand, appreciate the feasibility of adoption of ASP and be willing to be part of the solution rather than the problem. It may be a general belief that structured programs that are adopted from developed countries come with incentives and monetary rewards, but there are just certain problems that foreign donor agencies may not spearhead. Locally, certain programs may require minimal or no gross funding, which, if spearheaded by a few interested professionals, a lot of success will be recorded and by extension, will contribute hugely to addressing global public health concerns.[53]

Another major setback is the bureaucratic process with which structured programs are handled. Certain time-consuming bureaucratic processes that discourage volunteering professionals from actively participating in positively-impacting programs should be circumvented while devising alternate means of administrative auditing and overseeing roles.[54] Lowering the bars of organizational processes in structured programs such as ASP will not only set a plain and smooth ground for pioneer interested professionals, but it will also encourage others to contribute to the overall success of the program.

Finally, public campaigns, focus group training and retraining, and constant updates on the subjects of immediate public health threats is a requirement to keep stakeholders abreast of challenges facing the general population, which requires the participation of each stakeholder.[55] Complementing synergy and collaborative efforts from individuals, nonprofit organizations and government agencies would naturally drive the workforce to neutralize the threat with minimal pressure, thus requiring less funding with hugely positive results.

 Conclusion



The clinical microbiology laboratory performs crucial roles in the successful implementation of an ideal ASP by providing essential data for the choice and correct use of antimicrobials for the treatment of infected patients. Antibiograms data from various institutions, regions, and countries assist in decision making when selecting empirical antimicrobial therapy, and prompt and accurate personalized medicine with respect to isolated pathogens and antimicrobial susceptibility.

In resource-limited settings where the scourge of AMR has its greatest impacts, all efforts need to be utilized to tame the menace. Adoption of ASPs in the healthcare system is more convenient given that literate and enlightened people are the major stakeholders in the program. It is no secret that the need for developing and implementing suitable ASPs are required the most in the LMICs where the AMR scourge has its roots due partly to limited resources. The commitment of the healthcare workers and the hospital administrations are required for successful adoption and implementation of stewardship for the national and global collaborative fight against AMR.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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