Control of multidrug-resistant Gram-negative bacteria in low- and middle-income countries—high impact interventions without much resources

Open ArchivePublished:March 05, 2017DOI:https://doi.org/10.1016/j.cmi.2017.02.034
      Multidrug-resistant Gram-negative rods (MDR-GNR) are emerging as a major challenge to human health, especially in low- and middle-income countries (LMIC). MDR-GNR bacteraemia is common in neonates and young infants in Asia and Africa [
      • Investigators of the Delhi Neonatal Infection Study (DeNIS) collaboration
      Characterisation and antimicrobial resistance of sepsis pathogens in neonates born in tertiary care centres in Delhi, India: a cohort study.
      ,
      • Le Doare K.
      • Bielicki J.
      • Heath P.T.
      • Sharland M.
      Systematic review of antibiotic resistance rates among gram-negative bacteria in children with sepsis in resource-limited countries.
      ]. Klebsiella pneumoniae, Acinetobacter spp., Pseudomonas aeruginosa and Escherichia coli have alarming degrees of antimicrobial resistance and are associated with high mortality and morbidity due to scarcity of effective antibiotics. This commentary elaborates the IDEAL framework:
      • Implement programmes for infection prevention and control
      • Develop antimicrobial and diagnostic stewardship based on local data
      • Enhance interventions based on relevant technical and behavioural factors to improve impact
      • Accreditation of healthcare institutions to improve quality and safety of care
      • Legislation to ensure compliance with accreditation standards.

      Implement infection prevention and control (IPC) programme

      Measuring the burden of disease due to antimicrobial resistance (AMR) organisms in patients is the initial step. A conceptual framework for local, national, regional and global collaboration to generate the needed surveillance data to guide interventions and assess their impact is presented in Fig. 1. Hospital-acquired infection (HAI) surveillance should be carried out initially for patients hospitalized in high-intensity units, those with a high volume of surgical procedures, and in labour and delivery rooms. Although surveillance reveals the magnitude of the challenge of HAI, healthcare professionals (HCPs) must also identify key stakeholders, especially powerful members of the organization and enhance communication with them formally through infection control committees. Representatives of the infection control committee should report to healthcare administrators committed to improving patient safety and health outcomes based on allocation of adequate resources to the programme. IPC professionals should assess and monitor compliance with WHO and CDC core components of IPC and standard precautions. If all the core components are not in place, the institution must take incremental steps to implement them as resources become available. Infection control assessment tools can be used in LMIC to establish baseline compliance with (a) Hand hygiene and sanitation, (b) disinfection and sterilization, (c) safe drinking water and (d) waste disposal [
      • Weinshel K.
      • Dramowski A.
      • Hajdu Á.
      • Jacob S.
      • Khanal B.
      • Zoltán M.
      • et al.
      Gap analysis of infection control practices in low- and middle-income countries.
      ]. These four components have been major challenge areas for places with scarce resources. Depending upon the findings, interventions should be prioritized and resources should be allocated by securing funding.
      Fig. 1
      Fig. 1Conceptual framework for global antimicrobial resistance surveillance. Adapted from Singh/Stelling https://www.folkhalsomyndigheten.se/amr-stockholm-2014/

      Develop stewardship programmes based on local data

      Many professional societies and organizations in resource-rich countries have developed guidelines for management of infectious diseases and compendia to prevent HAI that serve as an important resource.

       Antimicrobial stewardship

      HCPs should make daily assessments of whether invasive device or antibiotics are needed. Inter-professional collaboration between clinician, clinical pharmacist and microbiologist can help with optimizing use of antimicrobials. When resources are scarce, the IPC team can share responsibility for the antimicrobial stewardship programme. The microbiology laboratory should prepare annual antibiograms to assist HCPs with the choice of empiric antibiotic therapy based on local susceptibility patterns and de-escalation to definitive therapy as the microbiology results are known. HCPs should be educated to distinguish between colonization and infection and to limit unnecessary continuation of prescribed antibiotics. They should be educated about the pyramid of infectious diseases that includes complex interactions between the patient, the drug and the pathogens that are colonizing a patient's microbiome [
      • Pulcini C.
      • Inge C.
      • Gyssens I.
      How to educate prescribers in antimicrobial stewardship practices.
      ]. On-line free modules with examples from successful implementation of antimicrobial stewardship in LMIC could be helpful in educating clinicians and infectious disease (ID) HCPs [

      Antimicrobial stewardship: managing antibiotic resistance. Available at: https://www.futurelearn.com/courses/antimicrobial-stewardship.

      ]. Structured face-to-face education as well as incidental interventions are also helpful. Evidence-based guidelines for timely administration of perioperative prophylaxis and meticulous skin disinfection will prevent surgical site infections. Corrective measures should be promptly taken when such lapses occur.

       Diagnostic stewardship

      Availability of adequate infrastructure and trained manpower has been a major challenge in scare resource laboratories. Poor quality supplies further compound the problems. The value of a functional microbiology laboratory, rapid identification of pathogens and reporting of resistant organisms with external quality assurance cannot be emphasized enough. Several global health initiatives are underway to build laboratory capacity. Accurate and timely identification of organisms and their susceptibilities to antibiotics is important to implement strategies to optimally treat the infected patients. Effective communication between laboratory personnel and IPC professionals is needed for prompt institution of precautions and de-escalation of antibiotic therapy. A spoke-and-hub model and point-of-care tests by peripheral laboratories and high end test/costly tests being conducted in a centralized manner can help by sharing of resources and knowledge and can enhance laboratory capacity to detect new and emerging resistance that may be reportable under international health regulations.

      Enhance interventions based on relevant technical and behavioural factors to improve impact

      Each societal and healthcare institution has a set of core values that bring groups of people together. Treatment of infectious diseases, antimicrobial stewardship and IPC practices are rooted in the culture of a healthcare institution. Inter-professional collaboration is needed for effective IPC and stewardship programmes, which could be challenging in LMIC [
      • Borg M.A.
      Lowbury Lecture 2013. Cultural determinants of infection control behaviour: understanding drivers and implementing effective change.
      ]. The focus of such collaboration must placed on non-infectious disease specialties to engage with the issue of behaviour change towards antimicrobial use [
      • Rawson T.M.
      • Moore L.S.P.
      • Tivey A.M.
      • Tsao A.
      • Gilchrist M.
      • Charani E.
      • et al.
      Behaviour change interventions to influence antimicrobial prescribing: a cross-sectional analysis of reports from UK state-of-the-art scientific conferences.
      ]. Most evidence-based interventions from developed countries can be implemented only in an outbreak crisis scenario in LMIC. For sustainable results, interventions need to be adapted within the context of underlying core cultural values. The common behavioural interventions that can be used include education, persuasion and enablement [
      • Rawson T.M.
      • Moore L.S.P.
      • Tivey A.M.
      • Tsao A.
      • Gilchrist M.
      • Charani E.
      • et al.
      Behaviour change interventions to influence antimicrobial prescribing: a cross-sectional analysis of reports from UK state-of-the-art scientific conferences.
      ].

      Accreditation of healthcare institutions to improve quality and safety of care

      In LMIC accreditation is often limited to large hospitals catering to medical tourism whereas many primary and district hospitals lag behind. In developed nations, transparency has helped to generate public interest to prevent HAI, and support has led law makers and politicians to pay greater attention to the issues with penalties incurred for deficient practices or outcomes. Accreditation has played an active role in improving patient safety, initiating surveillance of HAI and antimicrobial stewardship [
      • Smits H.
      • Supachutikul A.
      • Mate K.S.
      Hospital accreditation: lessons from low- and middle-income countries.
      ]. Health insurance (from both public sector and private sector) companies have taken initiatives through requirement of accreditation for enhanced payment, which has been a key driver in improving safety in this area [
      • Smits H.
      • Supachutikul A.
      • Mate K.S.
      Hospital accreditation: lessons from low- and middle-income countries.
      ]. Public sharing of HAI data is still a challenge in LMIC that will require sensitization of broadcasting and print media along with other stakeholders including judiciary and public at large.
      Policies with wider coverage using targeted resources from donor and philanthropic organizations can have sustainable impact in reducing the burden of MDR-GNR. Public–private partnerships would also be needed for safe healthcare delivery in the inherently challenging situations prevailing in LMIC.
      • 1
        Limited diagnostic ability of the laboratories compounds the issue and makes it difficult to detect AMR as the patients have similar clinical presentation whether they are infected with susceptible or resistant pathogens. Integration of laboratories and pooling of scarce resources through strong referral systems can strengthen diagnostic capabilities. A spoke-and-hub model and the use of point-of-care tests has already been described above.
      • 2
        The situation is further complicated by the lack of trained infectious diseases HCP and IPC professionals in these countries. Introduction of formal training programmes for infectious diseases and IPC is urgently needed.
      • 3
        The risk of acquisition of MDR-GNR is high in LMIC where people often live in close proximity to each other and to animals and polluted waterways, and may lack access to hygienic and sanitary conditions. Overall sanitary conditions and safe drinking supplies can help to mitigate the risk. Continuous engagement of leaders, environmentalists and help groups is required. The roles of community participation and engagement must be contemplated.
      • 4
        In many of the LMIC, antibiotics are relatively inexpensive and have saved many lives but their over-the-counter use has contributed to the build up of a large reservoir of MDR-GNR in the gut microbiome that can cause endogenous infections when these patients are hospitalized. This leads to considerable out-of-pocket expenses and loss of earnings due to extended hospital stays and treatment. In the era of global travel MDR-GNR can also be transmitted in distant countries from person-to-person when breach of IPC practices occurs. Prescriber education for rational use of antibiotics along with implementation and monitoring of regulations regarding over-the-counter restriction of sales of antibiotics can help to reduce out-of-pocket expenses. When not to use antimicrobials, ill effects of overuse of antibiotics, completion of duration of antibiotic therapy and restraining from self-medication can be focus areas for community and prescriber education.
      • 5
        Widespread sharing of information in professional society meetings, discussion on avoidable costs of inaction and large benefits of coordinated interventions through enhanced transparency can help to drive this change. As those working with these various tools in global health, a partnership through the framework of IDEAL is presented here.
      • 6
        Legislation to ensure compliance with accreditation standards: Resource-rich countries are proposing legislation at state and national level that will mandate healthcare institutions to implement programs as outlined above.

      Conclusion

      We have identified five key focus areas to help mitigate AMR in LMIC. Motivated team leaders are a prerequisite to design, implement and monitor the building of the pillars for success of the AMR containment strategies in LMIC. We clarify the identification and prioritization of key activities, diagnostic methods and policy areas within the hospital and the larger local and regional health systems to enhance the effectiveness of policies to address AMR within resource-constrained countries. Inter sectoral collaboration, as a part of one health approach, is integral for successfully decreasing the prevalence of AMR globally.

      Transparency declaration

      The authors declare no conflicts of interests.

      Funding

      No funding was received.

      Acknowledgements

      The authors are grateful for the helpful suggestions of Sanjay Saint, Jorge Matheu and John Stelling Thanks are due to the Society of Health Care Epidemiology's International ambassadors, Angela Dramowski from South Africa, Ágnes Hajdu from Hungary, Maria Inés Staneloni from Argentina for sharing the AMR initiatives of their respective countries.

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