Development of a cross-sectoral antimicrobial resistance capability assessment framework.

Antimicrobial resistance (AMR) is an urgent and growing global health concern, and a clear understanding of existing capacities to address AMR, particularly in low-income and middle-income countries (LMICs), is needed to inform national priorities, investment targets and development activities. Across LMICs, there are limited data regarding existing mechanisms to address AMR, including national AMR policies, current infection prevention and antimicrobial prescribing practices, antimicrobial use in animals, and microbiological testing capacity for AMR. Despite the development of numerous individual tools designed to inform policy formulation and implementation or surveillance interventions to address AMR, there is an unmet need for easy-to-use instruments that together provide a detailed overview of AMR policy, practice and capacity. This paper describes the development of a framework comprising five assessment tools which provide a detailed assessment of country capacity to address AMR within both the human and animal health sectors. The framework is flexible to meet the needs of implementers, as tools can be used separately to assess the capacity of individual institutions or as a whole to align priority-setting and capacity-building with AMR National Action Plans (NAPs) or national policies. Development of the tools was conducted by a multidisciplinary team across three phases: (1) review of existing tools; (2) adaptation of existing tools; and (3) piloting, refinement and finalisation. The framework may be best used by projects which aim to build capacity and foster cross-sectoral collaborations towards the surveillance of AMR, and by LMICs wishing to conduct their own assessments to better understand capacity and capabilities to inform future investments or the implementation of NAPs for AMR.

The Impact of COVID-19 on Knowledge, Beliefs, and Practices of Ni-Vanuatu Health Workers Regarding Antibiotic Prescribing and Antibiotic Resistance, 2018 and 2022: A Mixed Methods Study.

Antimicrobial resistance (AMR) is included in the ten most urgent global public health threats. Global evidence suggests that antibiotics were over prescribed during the early waves of the COVID-19 pandemic, particularly in low- and middle-income countries. Inappropriate use of antibiotics drives the emergence and spread of antibiotic resistance. This study aimed to examine the impact of COVID-19 on Ni-Vanuatu health worker knowledge, beliefs, and practices (KBP) regarding antibiotic prescribing and awareness of antibacterial AMR. A mixed methods study was conducted using questionnaires and in-depth interviews in 2018 and 2022. A total of 49 respondents completed both baseline (2018) and follow-up (2022) questionnaires. Knowledge scores about prescribing improved between surveys, although health workers were less confident about some prescribing activities. Respondents identified barriers to optimal hand hygiene performance. More than three-quarters of respondents reported that COVID-19 influenced their prescribing practice and heightened their awareness of ABR: "more careful", "more aware", "stricter", and "need more community awareness". Recommendations include providing ongoing continuing professional development to improve knowledge, enhance skills, and maintain prescribing competency; formalising antibiotic stewardship and infection, prevention, and control (IPC) programmes to optimise prescribing and IPC practices; and raising community awareness about ABR to support more effective use of medications.

Antibiotic Consumption in Vanuatu before and during the COVID-19 Pandemic, 2018 to 2021: An Interrupted Time Series Analysis.

The study objectives were to examine antibiotic consumption at Vila Central Hospital (VCH), Vanuatu between January 2018 and December 2021 and the influence of the COVID-19 pandemic on antibiotic consumption during this period. Data on antibiotic usage were obtained from the Pharmacy database. We used the WHO's Anatomical Therapeutic Classification/Defined Daily Dose (ATC/DDD) index, VCH's inpatient bed numbers and the hospital's catchment population to calculate monthly antibiotic consumption. The results were expressed as DDDs per 100 bed days for inpatients (DBDs) and DDDs per 1000 inhabitants per day for outpatients (DIDs). Interrupted time series (ITS) was used to assess the influence of COVID-19 by comparing data before (January 2018 to January 2020) and during (February 2020 to December 2021) the pandemic. Ten antibiotics were examined. In total, 226 DBDs and 266 DBDs were consumed before and during COVID-19 by inpatients, respectively with mean monthly consumption being significantly greater during COVID-19 than before the pandemic (2.66 (p = 0.009, 95% CI 0.71; 4.61)). Whilst outpatients consumed 102 DIDs and 92 DIDs before and during the pandemic, respectively, the difference was not statistically significant. Findings also indicated that outpatients consumed a significantly lower quantity of Watch antibiotics during COVID-19 than before the pandemic (0.066 (p = 0.002, 95% CI 0.03; 0.11)). The immediate impact of COVID-19 caused a reduction in both inpatient and outpatient mean monthly consumption by approximately 5% and 16%, respectively, and this was followed by an approximate 1% monthly increase until the end of the study. By mid-2021, consumption had returned to pre-pandemic levels.

Strategies Used for Implementing and Promoting Adherence to Antibiotic Guidelines in Low- and Lower-Middle-Income Countries: A Systematic Review.

Containing antimicrobial resistance and reducing high levels of antibiotic consumption in low- and lower middle-income countries are a major challenge. Clinical guidelines targeting antibiotic prescribing can reduce consumption, however, the degrees to which clinical guidelines are adopted and adhered to are challenging for developers, policy makers and users. The aim of this study was to review the strategies used for implementing and promoting antibiotic guideline adherence in low- and lower middle-income countries. A review of published literature was conducted using PubMed, Cochrane Library, SCOPUS and the information systems of the World Health Organization and the Australian National University according to PRISMA guidelines and our PROSPERO protocol. The strategies were grouped into five broad categories based on the Cochrane Effective Practice and Organization of Care taxonomy. The 33 selected studies, representing 16 countries varied widely in design, setting, disease focus, methods, intervention components, outcomes and effects. The majority of interventions were multifaceted and resulted in a positive direction of effect. The nature of the interventions and study variability made it impossible to tease out which strategies had the greatest impact on improving CG compliance. Audit and feedback coupled with either workshops and/or focus group discussions were the most frequently used intervention components. All the reported strategies are established practices used in antimicrobial stewardship programs in high-income countries. We recommend interrupted time series studies be used as an alternative design to pre- and post-intervention studies, information about the clinical guidelines be made more transparent, and prescriber confidence be investigated.

Quality microbiological diagnostics and antimicrobial susceptibility testing, an essential component of antimicrobial resistance surveillance and control efforts in Pacific island nations.

PROBLEM: Emerging bacterial antimicrobial (antibiotic) resistance (AMR) is a global threat to human health. However, most lower income countries do not have microbiological diagnostic testing for prompt, reliable confirmation of bloodstream infection and identification of AMR. CONTEXT: Clinicians in Pacific island nations are increasingly challenged by patients who have infection due to antimicrobial-resistant bacteria. Treatment of infection remains empirical because of a lack of diagnostic testing capacity and may follow guidelines that were formulated without reference to local measures of AMR prevalence. There is limited understanding among clinicians of microbiology testing and test interpretation. ACTION: Examine the lessons learnt from pilot laboratory development programmes in two Pacific island nations that focused on establishing standard procedures for micrological diagnostics and antimicrobial susceptibility testing (AST) and on improving the training of clinicians to increase their use of laboratory services. OUTCOME: The pilot programmes addressed a range of logistical difficulties and evaluated two blood culture systems. They also examined and improved internal QC implementation and evaluated the prevalence of AMR. DISCUSSION: Continued development of microbiological diagnostic capability in the Pacific region is paramount. Pacific Island nations need to develop the capability of at least one central laboratory to culture AMR pathogens and subject them to quality-controlled AST or arrange for suitable referral to a nearby country. DISCUSSION: This study demonstrated a persistently high prevalence of three major bacterial STIs across four countries in WHO's Western Pacific Region during nearly two decades. Further strengthening of strategies to control and prevent STIs is warranted.

Bacteriology and Antimicrobial Resistance in Vanuatu: January 2017 to December 2019.

Keywords: drug resistance; antimicrobial; public health surveillance; Pacific Islands; bacteriology; epidemiology.

Liver abscess: diagnostic and management issues found in the low resource setting.

INTRODUCTION: Liver abscesses are mainly caused by parasitic or bacterial infection and are an important cause of hospitalization in low-middle income countries (LMIC). The pathophysiology of abscesses is different depending on the etiology and requires different strategies for diagnosis and management. This paper discusses pathophysiology and epidemiology, the current diagnostic approach and its limitations and management of liver abscess in low resource settings. SOURCES OF DATA: We searched PubMed for relevant reviews by typing the following keywords: 'amoebic liver abscess' and 'pyogenic liver abscess'. AREAS OF AGREEMENT: Amoebic liver abscess can be treated medically while pyogenic liver abscess usually needs to be percutaneously drained and treated with effective antibiotics. AREAS OF CONTROVERSY: In an LMIC setting, where misuse of antibiotics is a recognized issue, liver abscesses are a therapeutic conundrum, leaving little choices for treatment for physicians in low capacity settings. GROWING POINTS: As antimicrobial resistance awareness and antibiotic stewardship programs are put into place, liver abscess management will likely improve in LMICs provided that systematic adapted guidelines are established and practiced. AREAS TIMELY FOR DEVELOPING RESEARCH: The lack of a quick and reliable diagnostic strategy in the majority of LMIC makes selection of appropriate treatment challenging.

Antimicrobial resistance in Cambodia: a review.

OBJECTIVES: Following the launch of the Global Antimicrobial Resistance Surveillance System (GLASS), antimicrobial resistance (AMR) rates in many countries remain poorly described. This review provides an overview of published AMR data from Cambodia in the context of recently initiated national human and food-animal surveillance. METHODS: PubMed and the Cochrane Database of Systematic Reviews were searched for articles published from 2000 to 2018, which reported antimicrobial susceptibility testing (AST) data for GLASS specific organisms isolated from Cambodia. Articles were screened using strict inclusion/exclusion criteria. AST data was extracted, with medians and ranges of resistance rates calculated for specific bug-drug combinations. RESULTS: Twenty-four papers were included for final analysis, with 20 describing isolates from human populations. Escherichia coli was the most commonly described organism, with median resistance rates from human isolates of 92.8% (n=6 articles), 46.4% (n=4), 55.4% (n=8), and 46.4% (n=5) to ampicillin, 3rd generation cephalosporins, fluoroquinolones, and gentamicin respectively. CONCLUSIONS: Whilst resistance rates are high for several GLASS organisms, there were insufficient data to draw robust conclusions about the AMR situation in Cambodia. The recently implemented national AMR surveillance systems will begin to address this data gap.

Antibiotic Resistance in Pacific Island Countries and Territories: A Systematic Scoping Review.

Several studies have investigated antimicrobial resistance in low- and middle-income countries, but to date little attention has been paid to the Pacific Islands Countries and Territories (PICTs). This study aims to review the literature on antibiotic resistance (ABR) in healthcare settings in PICTs to inform further research and future policy development for the region. Following the PRISMA-ScR checklist health databases and grey literature sources were searched. Three reviewers independently screened the literature for inclusion, data was extracted using a charting tool and the results were described and synthesised. Sixty-five studies about ABR in PICTs were identified and these are primarily about New Caledonia, Fiji and Papua New Guinea. Ten PICTs contributed the remaining 21 studies and nine PICTs were not represented. The predominant gram-positive pathogen reported was community-acquired methicillin resistant S. aureus and the rates of resistance ranged widely (>50% to <20%). Resistance reported in gram-negative pathogens was mainly associated with healthcare-associated infections (HCAIs). Extended spectrum beta-lactamase (ESBL) producing K. pneumoniae isolates were reported in New Caledonia (3.4%) and Fiji (22%) and carbapenem resistant A. baumannii (CR-ab) isolates in the French Territories (24.8%). ABR is a problem in the PICTs, but the epidemiology requires further characterisation. Action on strengthening surveillance in PICTs needs to be prioritised so strategies to contain ABR can be fully realised.

Leptospirosis: An important zoonosis acquired through work, play and travel

BACKGROUND: Leptospirosis is one of the most common zoonotic diseases worldwide. Infection occurs through contact with infected animals, or soil or water that has been contaminated by the urine of infected animals. Risk factors include occupational and recreational exposures, contact with floodwaters, and travel to areas with a high risk of leptospirosis, particularly tropical, developing countries. With climate change, flood-related outbreaks are becoming more common. OBJECTIVE: This article aims to improve awareness of leptospirosis, and provide an update for general practitioners on its epidemiology, risk factors, clinical presentation, laboratory diagnosis, management and prevention. DISCUSSION: Leptospirosis is sometimes misdiagnosed because clinical presentation can be non-specific and overlap with many other causes of acute febrile illnesses. In patients with risk factors for leptospirosis, a high index of clinical suspicion is important to ensure early diagnosis and treatment. Delays in treatment could increase the risk of severe complications, including pulmonary haemorrhage, acute renal failure and acute liver failure.

Mycetoma in Timor-Leste and first report of nocardiosis.

Mycetoma is a neglected tropical disease with an unknown global burden. Although considered endemic to South-east Asia, it has not previously been reported from Timor-Lest. We describe two cases in Timor-Leste, highlighting the challenges surrounding microbiological diagnosis and management shared by many low to middle-income countries. As characteristically described, both patients lived rurally and presented late with marked soft tissue involvement and multiple draining sinuses following a prolonged period of high morbidity. Nocardia brasiliensis, a beadedbranched, modified acid-fast, gram-positive bacilli, was isolated and confirmed by molecular testing in the first case. The causative organism in the second case could not be confirmed due to limited microbiological capabilities. Due to limited local laboratory capabilities, Nocardia spp. infection cannot be routinely confirmed in Timor- Leste. However, the microbiology laboratory is essential for the successful diagnosis and management of Mycetoma. In both cases, medical therapy alone resulted in cure and favorable outcomes, although supply of antibiotic remains an ongoing resource issue.

Dominance of IMP-4-producing enterobacter cloacae among carbapenemase-producing Enterobacteriaceae in Australia.

The prevalence of carbapenemase-producing Enterobacteriaceae (CPE) has been increasing worldwide. blaIMP has been reported to be the predominant carbapenemase-encoding gene within Enterobacteriaceae in Australia. However, there are limited data currently available on CPE from Queensland, Australia. A total of 58 CPE isolates were isolated between July 2009 and March 2014 from Queensland hospitals. The clonality of isolates was determined by Diversilab repetitive sequence-based PCR. The isolates were investigated for the resistance mechanisms carbapenemase, extended-spectrum ß-lactamase, and AmpC ß-lactamase and for aminoglycoside resistance and plasmid-mediated quinolone resistance genes by PCR. The plasmid types associated with carbapenemase-encoding genes were characterized. The majority of the CPE were Enterobacter cloacae (n = 29). The majority of Queensland CPE isolates were IMP producers and comprised 11 species (n = 48). Nine NDM-producing Enterobacteriaceae were identified. One NDM-producing Klebsiella pneumoniae isolate coproduced OXA-48. One K. pneumoniae isolate was an OXA-181 producer. The incidence of IMP producers increased significantly in 2013. blaIMP-4 was found in all IMP-producing isolates. blaTEM, qnrB, and aacA4 were common among IMP-4 producers. The HI2 (67%) and L/M (21%) replicons were associated with blaIMP-4. All HI2 plasmids were of sequence type 1 (ST1). All but one of the NDM producers possessed blaCTX-M-15. The 16S rRNA methylase genes found among NDM producers were armA, rmtB, rmtC, and rmtF. The substantial increase in the prevalence of CPE in Queensland has been associated mainly with the emergence E. cloacae strains possessing HI2 plasmids carrying blaIMP-4 over the past 2 years. The importation of NDM producers and/or OXA-48-like producers in patients also contributed to the increased emergence of CPE.

Parenteral nutrition-associated bloodstream infection in an Australian teaching hospital--an 8-year retrospective study of over 11,000 PN-days.

BACKGROUND: Bloodstream infections (BSIs) are a well-recognized complication of parenteral nutrition (PN). However, their epidemiology and clinical consequences are incompletely described. METHODS: A retrospective cohort study was performed, from 2002 to 2009, of all hospital inpatients who were administered PN, outside the intensive care setting, at a major tertiary hospital in Queensland, Australia. RESULTS: In 780 episodes of PN administration, 120 BSIs occurred, giving an incidence of 10.0/1000 PN-days. The majority of PN-associated BSIs were classified as central line-associated (n = 98, 81.7%). Candida spp. were the most frequent pathogens. Observed BSI management revealed that over 8% of intravascular devices were inappropriately retained, over 30% of empirical antibiotic therapy was inappropriate, and 62% of antifungal therapy was delayed ≥ 48 h. All-cause hospital mortality was over 2-fold greater in patients with a PN-associated BSI compared to those without (17.9% vs 8.3%, crude odds ratio (OR) 2.4, 95% confidence interval (CI) 1.29-4.35, p = 0.002). BSI was identified as an independent risk factor for mortality (adjusted OR 3.54, 95% CI 1.76-7.12, p < 0.001). Low baseline albumin levels and a requirement for intravenous insulin infusion (a marker of sustained hyperglycaemia) were independent risk factors for the development of PN-associated BSIs. CONCLUSIONS: PN-associated BSI in hospital inpatients is common and is associated with mortality. The implementation of standardized evidence-based infection prevention strategies, particularly targeting IVD maintenance, is a priority. PN-associated BSI management pathways require optimization, with timely IVD removal and appropriate antimicrobial therapy. Depending on local epidemiology patterns, empirical antifungal therapy should be considered.

Relapse of imported Plasmodium vivax malaria is related to primaquine dose: a retrospective study.

BACKGROUND: Relapsing Plasmodium vivax infection results in significant morbidity for the individual and is a key factor in transmission. Primaquine remains the only licensed drug for prevention of relapse. To minimize relapse rates, treatment guidelines have recently been revised to recommend an increased primaquine dose, aiming to achieve a cumulative dose of ≥6 mg/kg, i.e. ≥420 mg in a 70 kg patient. The aims of this study were to characterize the epidemiology of P. vivax infection imported into Queensland Australia, to determine the rates of relapse, to investigate the use of primaquine therapy, and its efficacy in the prevention of relapse. METHODS: A retrospective study was undertaken of laboratory confirmed P. vivax infection presenting to the two major tertiary hospitals in Queensland, Australia between January 1999 and January 2011.Primaquine dosing was classified as no dose, low dose (<420 mg), high dose (≥420 mg), or unknown. The dose of primaquine prescribed to patients who subsequently relapsed that prescribed to patients who did not relapse. RESULTS: Twenty relapses occurred following 151 primary episodes of P. vivax infection (13.2%). Relapses were confirmed among 3/21 (14.2%), 9/50 (18.0%), 1/54 (1.9%) and 7/18 (38.9%) of patients administered no dose, low dose, high dose and unknown primaquine dose respectively. High dose primaquine therapy was associated with a significantly lower rate of relapse compared to patients who were prescribed low dose therapy (OR 11.6, 95% CI 1.5-519, p = 0.005). CONCLUSIONS: Relapse of P. vivax infection is more likely in patients who received low dose primaquine therapy. This study supports the recommendations that high dose primaquine therapy is necessary to minimize relapse of P. vivax malaria.

Community-associated methicillin-resistant Staphylococcus aureus endocarditis 'down under': case series and literature review.

Infective endocarditis is a common complication of Staphylococcus aureus bacteraemia, but literature reports of community-associated methicillin-resistant S. aureus (CA-MRSA) endocarditis are relatively uncommon and mostly comprise intravenous drug users (IVDUs) with the USA300 strain. We report 5 cases of CA-MRSA endocarditis in previously healthy young Australian adults, 4 in IVDUs. Morbidity was high with frequent septic emboli; 3 patients required cardiac surgery and 1 patient died. Typing revealed the 2 most common Australian strains, the Panton-Valentine leukocidin (PVL)-positive ST93 (Queensland) strain and the PVL-negative ST1 (WA-MRSA-1) strain.