Interprofessional education in antimicrobial stewardship, a collaborative effort.

Introduction: Antimicrobial stewardship (AMS) education and interprofessional collaboration are integral to the success of a stewardship programme. An interactive interprofessional AMS workshop, designed to encourage workplace interprofessional collaboration was piloted in a tertiary hospital. Objectives: To obtain feedback to determine the suitability and sustainability of the AMS workshop. Methods: Feedback was elicited through a predesigned questionnaire containing both open-ended and closed questions on the content and structure of the workshop. Results: The survey had a 70% (n = 16) overall response rate. All participants agreed that the goals of the workshop were met and that the knowledge and skills gained from the workshop would help them in their AMS roles. All participants indicated that the workshop content, and the level at which it was pitched, met their expectations and that it had improved their knowledge and skills. All agreed that they found it advantageous and enjoyed learning as an interprofessional group. Open feedback showed that the workshop was found to be useful and would potentially result in improved patient care, dissemination of knowledge, improved teamwork and organizational culture. Conclusions: The positive feedback and changes made following the workshop demonstrated that a targeted AMS educational workshop adds value to an antimicrobial stewardship programme.

Evidence review and recommendations for the implementation of genomics for antimicrobial resistance surveillance: reports from an international expert group.

Nearly a century after the beginning of the antibiotic era, which has been associated with unparalleled improvements in human health and reductions in mortality associated with infection, the dwindling pipeline for new antibiotic classes coupled with the inevitable spread of antimicrobial resistance (AMR) poses a major global challenge. Historically, surveillance of bacteria with AMR typically relied on phenotypic analysis of isolates taken from infected individuals, which provides only a low-resolution view of the epidemiology behind an individual infection or wider outbreak. Recent years have seen increasing adoption of powerful new genomic technologies with the potential to revolutionise AMR surveillance by providing a high-resolution picture of the AMR profile of the bacteria causing infections and providing real-time actionable information for treating and preventing infection. However, many barriers remain to be overcome before genomic technologies can be adopted as a standard part of routine AMR surveillance around the world. Accordingly, the Surveillance and Epidemiology of Drug-resistant Infections Consortium convened an expert working group to assess the benefits and challenges of using genomics for AMR surveillance. In this Series, we detail these discussions and provide recommendations from the working group that can help to realise the massive potential benefits for genomics in surveillance of AMR.

Exploiting genomics for antimicrobial resistance surveillance at One Health interfaces.

The intersection of human, animal, and ecosystem health at One Health interfaces is recognised as being of key importance in the evolution and spread of antimicrobial resistance (AMR) and represents an important, and yet rarely realised opportunity to undertake vital AMR surveillance. A working group of international experts in pathogen genomics, AMR, and One Health convened to take part in a workshop series and online consultation focused on the opportunities and challenges facing genomic AMR surveillance in a range of settings. Here we outline the working group's discussion of the potential utility, advantages of, and barriers to, the implementation of genomic AMR surveillance at One Health interfaces and propose a series of recommendations for addressing these challenges. Embedding AMR surveillance at One Health interfaces will require the development of clear beneficial use cases, especially in low-income and middle-income countries. Evidence of directionality, risks to human and animal health, and potential trade implications were also identified by the working group as key issues. Addressing these challenges will be vital to enable genomic surveillance technology to reach its full potential for assessing the risk of transmission of AMR between the environment, animals, and humans at One Health interfaces.

Multidrug-resistant Gram-negative bacterial colonization in patients, carriage by healthcare workers and contamination of hospital environments in Ghana.

BACKGROUND: Patients already colonized with multidrug-resistant (MDR) Gram-negative bacteria (GNB) on admission to critical care units may be an important source of transmission of these bacteria in hospitals. We sought to determine the prevalence of MDR GNB colonization in patients, staff and the ward environment and to assess the risk factors for colonization of patients in wards. METHODS: The study was conducted from April 2021 to July 2021 in a teaching hospital in Ghana. MDR GNB were isolated from rectal, and hand swabs were taken from patients on admission and after 48 h. Swabs from HCW's hands and the ward environment were also taken. Risk factors for colonization with MDR GNB were assessed using univariate and multivariate analysis. RESULTS: MDR GNB rectal colonization rate among patients was 50.62% on admission and 44.44% after 48 h. MDR GNB were isolated from 6 (5.26%) and 24 (11.54%) of HCW's hand swabs and environmental swabs, respectively. Previous hospitalization (p-value = 0.021, OR, 95% CI= 7.170 (1.345-38.214) was significantly associated with colonization by MDR GNB after 48 h of admission. Age (21-30 years) (p-value = 0.022, OR, 95% CI = 0.103 (0.015-0.716) was significantly identified as a protective factor associated with a reduced risk of rectal MDR GNB colonization. CONCLUSION: The high colonization of MDR GNB in patients, the carriage of MDR GNB on HCW's hands, and the contamination of hospital environments highlights the need for patient screening and stringent infection prevention and control practices to prevent the spread of MDR GNB in hospitals.

Impact of Environmental Sub-Inhibitory Concentrations of Antibiotics, Heavy Metals, and Biocides on the Emergence of Tolerance and Effects on the Mutant Selection Window in E. coli.

Bacteria's ability to withstand the detrimental effects of antimicrobials could occur as resistance or tolerance with the minimum inhibitory concentration, the mutant prevention concentration, and the mutant selection window as salient concepts. Thus, this study assessed the impact of exposure to extremely high doses of ampicillin on the level of persistence and tolerance development in isolates previously exposed to different concentrations of selected antibiotics, biocides, and heavy metals. These isolates were previously exposed to oxytetracycline (OXYTET), amoxicillin (AMX), copper (Cu), zinc (Zn), benzalkonium chloride (BAC) 10, dimethylammonium chloride (DADMAC) 12 and a combination of all the individual pollutants (ALL). The isolates were exposed to very high concentrations (25 × MIC) of ampicillin, and their tolerance was calculated as the time required to kill 99.9% of the bacterial population (MDK99.9). The MDK99.9 increased by 30 to 50% in test isolates (DADMAC, OXYTET, Zinc = 28 h; BAC, Copper = 30 h; amoxycillin, ALL = 26 h) compared to the untreated control. BAC-exposed isolates decreased from 2.5 × 108 CFU/mL to 2.5 × 104 CFU/mL on the second day, displaying the highest tolerance increase. The tolerance appeared to originate from two sources, i.e., stochastic persistence and genetic-induced persistence, involving multiple genes with diverse mechanisms. The mutant selection window of the isolates to ampicillin, amoxicillin, and oxytetracycline also slightly increased compared to the control, indicating the selective survival of persister cells during the 30-day exposure. These findings indicate that bacterial exposure to sub-inhibitory concentrations of environmental chemical stressors may not always result in the development of antimicrobial resistance but could initiate this process by selecting persisters that could evolve into resistant isolates.

Evaluation of intermittent antimicrobial infusion documentation practices in intensive care units: A cross-sectional study.

OBJECTIVE: To observe nurse administration of carbapenem antibiotics, in the context of medication safety measures, in intensive care units. RESEARCH METHODOLOGY/DESIGN: A quantitative study was conducted using observation principles. SETTING: Three adult private and public Intensive Care Units in the health district of a capital city in KwaZulu-Natal, South Africa. MAIN OUTCOME MEASURES: Nurse practices were observed for double-checking of the medication order, medication vial, and method of preparation and administration. Infusion bags were inspected for nurse labelling of medication and patient details. Patient medication treatment charts were inspected for nurse signature. RESULTS: Carbapenem infusion administrations (n = 223) to twenty patients were observed. Adherence to the scheduled time occurred in 34.9% administrations, 5.4% doses were not given, and an incorrect dose given on 1.4% administrations. One hundred and forty-four (64.6%) infusion bags were inspected during the administrations: there was no medication label affixed to 21.5% bags, and only 8.3% of bags were labelled with essential details; the patient's name, drug, dose, date, time, signature of the nurse mixing and administering the dose, and signature of the secondary nurse. CONCLUSION: There was a lack of compliance with accepted medication risk mitigation measures. Sub-optimal double-checking resulted in the incorrect dose given, missed dose, and non-adherence to scheduled administration time. This has implications for the optimal administration of antimicrobial medications, raising concerns about the efficacy of treatment for critically ill patients. IMPLICATIONS FOR CLINICAL PRACTICE: Parenteral administration errors pose a challenge in acute care areas. Risk mitigation measures include double-checking of medications. If antimicrobial treatment is not administered at the prescribed dosing intervals, this may have implications for the efficacy of time-dependent broad-spectrum antibiotics such as carbapenems. Medication administration errors involving antimicrobial medications should therefore be considered as high-risk errors, with the potential to contribute towards antimicrobial resistance.

Metal Ions and their Effects on Antimicrobial Resistance Development in Wastewater.

Antimicrobial resistance (AMR) is a global health challenge and there is increasing recognition of the role of the environment, particularly wastewater, in the development and spread of AMR. Although trace metals are common contaminants in wastewater, the quantitative effects of trace metals on AMR in wastewater settings remain understudied. We experimentally determined the interactions between common antibiotic residues and metal ions found in wastewater and investigated their effects on the development of antibiotic resistance in Escherichia coli over time. These data were then used to expand on a previously developed computational model of antibiotic resistance development in continuous flow settings to incorporate the effects of trace metals acting in combination with multiple antibiotic residues. We found that the common metal ions, copper and iron, interact with both ciprofloxacin and doxycycline at wastewater relevant concentrations. This can significantly affect resistance development due to antibiotic chelation of the metal ions causing a reduction in the antibiotics' bioactivity. Furthermore, modeling the effect of these interactions in wastewater systems showed the potential for metal ions in wastewater to significantly increase the development of antibiotic resistant E. coli populations. These results demonstrate the need to quantitatively understand the effects of trace metal-antibiotic interactions on AMR development in wastewater.

Antibiotic, Heavy Metal, and Biocide Concentrations in a Wastewater Treatment Plant and Its Receiving Water Body Exceed PNEC Limits: Potential for Antimicrobial Resistance Selective Pressure.

Although the rise in antimicrobial resistance has been attributed mainly to the extensive and indiscriminate use of antimicrobials such as antibiotics and biocides in humans, animals and on plants, studies investigating the impact of this use on water environments in Africa are minimal. This study quantified selected antibiotics, heavy metals, and biocides in an urban wastewater treatment plant (WWTP) and its receiving water body in Kwazulu-Natal, South Africa, in the context of the predicted no-effect concentrations (PNEC) for the selection of antimicrobial resistance (AMR). Water samples were collected from the WWTP effluent discharge point and upstream and downstream from this point. Heavy metals were identified and quantified using the United States Environmental Protection Agency (US EPA) method 200.7. Biocides and antibiotic residues were determined using validated ultra-high-performance liquid chromatography with tandem mass spectrometry-based methods. The overall highest mean antibiotic, metal and biocide concentrations were observed for sulfamethoxazole (286.180 µg/L), neodymium (Nd; 27.734 mg/L), and benzalkonium chloride (BAC 12) (7.805 µg/L), respectively. In decreasing order per sampling site, the pollutant concentrations were effluent > downstream > upstream. This implies that the WWTP significantly contributed to the observed pollution in the receiving water. Furthermore, most of the pollutants measured recorded values exceeding the recommended predicted no-effect concentration (PNEC) values, suggesting that the microbes in such water environments were at risk of developing resistance due to the selection pressure exerted by these antimicrobials. Further studies are required to establish such a relationship.

Environmental concentrations of antibiotics, biocides, and heavy metals fail to induce phenotypic antimicrobial resistance in Escherichia coli.

Most anthropogenically affected environments contain mixtures of pollutants from different sources. The impact of these pollutants is usually the combined effect of the individual polluting constituents. However, how these stressors contribute to the development of antimicrobial resistance in environmental microorganisms is poorly understood. Thus, a 30-day exposure experiment to environmental and sub-inhibitory concentrations of oxytetracycline, amoxicillin, zinc, copper, BAC (benzalkonium chloride) 10 and DADMAC (diallyldimethylammonium chloride) 12, was conducted using fully susceptible E. coli ATCC 25922 to ascertain any development of phenotypic or genotypic resistance. Furthermore, wild-type isolates were collected from the same aquatic environment as the stressors, analysed for phenotypic resistance using the disk diffusion method and genotypically through whole genome sequencing. Exposure to the various concentrations and combinations of the stressors did not trigger phenotypic resistance in the experimental bacteria. Furthermore, genotypic analysis of the WGS on the exposed isolates only found the macrolide resistance mdf(A) gene (also present in the control strain) and the disinfectant resistance gene sitABCD. With further analysis for single nucleotide variants (SNV), mutations were detected for 19 genes that encoded for oxidative stress, DNA repair, membrane proteins efflux systems, growth and persister formations except for the robA, a transcription protein subset of the ArcC/XylS family of proteins, which confer multidrug resistance in E. coli. This indicates that exposure to sub-inhibitory concentrations of antibiotics, heavy metals and biocide residues in the aquatic environmental concentrations of the stressors identified in the current study could not induce phenotypic or genotypic resistance but encoded for genes responsible for the development of persistence and tolerance in bacteria, which could be a precursor to the development of resistance in environmental bacteria.

Evidence-Based Interventions to Reduce the Incidence of Common Multidrug-Resistant Gram-Negative Bacteria in an Adult Intensive Care Unit.

Background Multidrug-resistant Gram-negative bacteria (MDR-GNB) present a significant and escalating hazard to healthcare globally. Context-specific interventions have been implemented for the prevention and control of MDR-GNB in several healthcare facilities. The objective of this study was to implement and evaluate the effectiveness of evidence-based interventions in the incidence and dissemination of MDR-GNB. Methods This was a pre-and post-intervention study conducted in three phases at King Abdulaziz Medical City Jeddah, Saudi Arabia. During Phase-1, the data on each of the four MDR-GNB (Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Escherichia coli) were collected prospectively. Genomic fingerprinting was performed on isolates using enterobacterial repetitive intergenic consensus-polymerase chain reaction (ERIC-PCR) to determine clonality and establish a link between different strains within and between the hospital wards/units. In the second phase, targeted interventions were implemented in the adult intensive care unit (ICU) based on previously determined risk factors and included the education of healthcare workers on hand hygiene, disinfection of patients' surrounding, daily chlorhexidine baths, and disinfection rooms on discharge with hydrogen peroxide fogging after MDR-GNB patients were discharged. An antibiotic restriction protocol was simultaneously implemented as part of the hospital antibiotic stewardship program. In the third phase, the effectiveness of the interventions was evaluated by comparing the incidence rate and clonality (using ERIC-PCR genetic fingerprints) of MDR-GNB before and after the intervention. Results A significant reduction of MDR-GNB was observed in Phase-2 and Phase-3 compared with Phase-1. The mean incidence rate of MDR-GNB per 1000 patient days in Phase-1 (pre-intervention) was 11.08/1000, followed by 6.07 and 3.54/1000 in Phase-2 and Phase-3, respectively. A statistically significant reduction was observed in the incidence rate of MDR-GNB in the adult ICU (P=0.007), whereas no statistically significant decrease (P=0.419) was observed in areas other than the adult ICU. Two A. baumannii strains appear to be circulating within the ICU environment with reduced frequency in Phase-2 and Phase-3 compared to Phase-1. Conclusion  There was a significant reduction in the incidence of MDR-GNB in the adult ICU due to the successful implementation of both infection control and stewardship interventions, albeit challenging to ascertain the relative contribution of each.

Addressing Consumer Misconceptions on Antibiotic Use and Resistance in the Context of Sore Throat: Learnings from Social Media Listening.

A misunderstanding of the mechanism of action and bacterial targets of antibiotics by consumers may drive inappropriate antibiotic use and antimicrobial resistance (AMR). Tackling AMR requires an in-depth understanding of consumer beliefs and misconceptions. We explored consumer conversations on a number of social media platforms on antibiotic use and AMR in the context of sore throat and how coronavirus disease 2019 (COVID-19) affected online conversations between 1 January 2018 and 25 November 2021 across eight countries. Five distinct consumer groups were identified (antibiotic-preserving peer educators, antibiotic-cautious consumers, medication-resistant antibiotic opponents, believers in the strength of antibiotics, determined pro-antibiotic consumers) with a wide spectrum of beliefs around antibiotics in sore throat. Many opinions were based upon misconceptions, the most prominent of which was that antibiotics are strong medications that can treat all types of sore throat. COVID-19 had a multifaceted effect on the sore throat and AMR conversation. Sore throat triggered anxiety as consumers feared it may be a COVID-19 symptom while engagement in conversations around antibiotics for COVID-19 increased. Finally, consumers sought multiple routes to access antibiotics, such as directly from the pharmacy or by attempting to persuade physicians to prescribe. Knowledge obtained from this study could be used to develop focused approaches to dispel consumer misconceptions and mitigate AMR.

A Genomic Snapshot of Antibiotic-ResistantEnterococcus faecalis within Public Hospital Environments in South Africa.

Enterococci are among the most common opportunistic hospital pathogens. This study used whole-genome sequencing (WGS) and bioinformatics to determine the antibiotic resistome, mobile genetic elements, clone and phylogenetic relationship of Enterococcus faecalis isolated from hospital environments in South Africa. This study was carried out from September to November 2017. Isolates were recovered from 11 frequently touched sites by patients and healthcare workers in different wards at 4 levels of healthcare (A, B, C, and D) in Durban, South Africa. Out of the 245 identified E. faecalis isolates, 38 isolates underwent whole-genome sequencing (WGS) on the Illumina MiSeq platform, following microbial identification and antibiotic susceptibility tests. The tet(M) (31/38, 82%) and erm(C) (16/38, 42%) genes were the most common antibiotic-resistant genes found in isolates originating from different hospital environments which corroborated with their antibiotic resistance phenotypes. The isolates harboured mobile genetic elements consisting of plasmids (n = 11) and prophages (n = 14) that were mostly clone-specific. Of note, a large number of insertion sequence (IS) families were found on the IS3 (55%), IS5 (42%), IS1595 (40%), and Tn3 transposons the most predominant. Microbial typing using WGS data revealed 15 clones with 6 major sequence types (ST) belonging to ST16 (n = 7), ST40 (n = 6), ST21 (n = 5), ST126 (n = 3), ST23 (n = 3), and ST386 (n = 3). Phylogenomic analysis showed that the major clones were mostly conserved within specific hospital environments. However, further metadata insights revealed the complex intraclonal spread of these E. faecalis major clones between the sampling sites within each specific hospital setting. The results of these genomic analyses will offer insights into antibiotic-resistantE. faecalis in hospital environments relevant to the design of optimal infection prevention strategies in hospital settings.

Risk Factors for Infection With Multidrug-Resistant Gram-Negative Bacteria in a Tertiary Care Hospital in Saudi Arabia: A Case-Control Study.

Background The increase in the incidence of multidrug-resistant (MDR) organisms especially Gram-negative bacteria (GNB) in healthcare facilities is a serious cause of concern. This study identified risk factors for the infection with these MDR GNB, such as Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Escherichia coli to inform healthcare workers about strategies for their containment. Methods A case-control study was carried out at a tertiary care hospital where 100 patients with healthcare-associated infections (infections arising 48 hours after admission) caused by MDR GNB were compared with two control groups, i.e., 100 patients with healthcare-associated infections caused by non-MDR GNB (not meeting the criteria of MDR) and 100 patients without infection caused by GNB. MDR bacteria were defined as the ones that were non-susceptible to at least one antibiotic in three or more classes of antibiotics. The data were analyzed using descriptive statistics (frequency and percentage of categorical variables). Multivariate regression analysis was undertaken to identify significant predictors of MDR GNB. Odds ratios with 95% confidence intervals were calculated, and the level of significance was determined at p-value < 0.05. Results A total of 388 organisms were isolated during four months (January-April 2015) from 332 patients. Fifty-six (17%) of the patients were infected with more than one organism. Among the MDR bacteria, the most dominant MDR organism was A. baumannii (38%), followed by K. pneumoniae (31%), P. aeruginosa (20%), and E. coli (11%). Among the non-MDR organisms, the most dominant was P. aeruginosa (47%), followed by E. coli (32%), K. pneumoniae (18%), and A. baumannii (3%). Patients with MDR organisms compared with the first control group (patients with non-MDR organisms) showed that prior antibiotic use (p-value: 0.001), intensive care unit (ICU) admission (p-value: 0.001), and indwelling medical devices (p-value: 0.005) were significant risk factors for MDR infections. It was also found that the risk factors for MDR GNB infection were the same in the second control group (patients without infection): prior antibiotic use (p-value: 0.002), ICU admission (p-value: 0.001), and indwelling medical devices (p-value: 0.03). Based on the comparison of the two control groups, prolonged hospital stays of more than five days (p-value: 0.001), immunosuppressive therapy (p-value: 0.02), and over 60 years of age (p-value: 0.02) were significant risk factors for non-MDR infection. Conclusion  The risk factors identified in our study provide guidance to healthcare workers for the prevention and containment of MDR GNB.

Barriers to implementing National Action Plans on antimicrobial resistance using a One Health Approach: policymakers' perspectives from South Africa and Eswatini.

OBJECTIVES: Antimicrobial resistance poses a global public health concern that threatens human, animal, and environmental health. If it is not addressed, it is estimated to cost the global economy between USD 90 trillion and USD 210 trillion, and the death burden could balloon to 10 million lives per year by 2050. This study aimed to explore policymakers experiences on barriers to implementing National Action Plans on antimicrobial resistance using a One Health approach in South Africa and Eswatini. METHODS: Thirty-six policy makers were recruited using purposive and snowballing sampling in South Africa and Eswatini. Data were collected between November 2018 and January 2019 in South Africa, and February to March 2019 in Eswatini. Data was then analysed based on Creswell methods. RESULTS: Three themes and five subthemes emerged from our findings. The themes were resource barriers, political barriers, and regulation barriers to the implementation of National Action Plans on antimicrobial resistance in South Africa and Eswatini. CONCLUSION: South African and Eswatini governments should commit funds to their One Health sector budgets to enable the implementation of National Action Plans on antimicrobial resistance. Specialized human resources issues need to be prioritized to unlock barriers of implementation. A renewed political commitment is needed to combat antimicrobial resistance in a One Health approach, as it plays a significant role in resource mobilization from regional and international organizations to support the resource-constrained countries to successfully implement policies.

Mitigating antimicrobial resistance (AMR) using implementation research: a development funder's approach.

Despite the escalating burden of antimicrobial resistance (AMR), the global response has not sufficiently matched the scale and scope of the issue, especially in low- and middle-income countries (LMICs). While many countries have adopted national action plans to combat AMR, their implementation has lagged due to resource constraints, dysfunctional multisectoral coordination mechanisms and, importantly, an under-recognized lack of technical capacity to adapt evidence-based AMR mitigation interventions to local contexts. AMR interventions should be tailored, context-specific, cost-effective and sustainable. The implementation and subsequent scale-up of these interventions require multidisciplinary intervention-implementation research (IIR). IIR involves both quantitative and qualitative approaches, occurs across a three-phase continuum (proof of concept, proof of implementation and informing scale-up), and across four context domains (inner setting, outer setting, stakeholders and the implementation process). We describe the theoretical underpinnings of implementation research (IR), its various components, and how to construct different IR strategies to facilitate sustainable uptake of AMR interventions. Additionally, we provide real-world examples of AMR strategies and interventions to demonstrate these principles in practice. IR provides a practical framework to implement evidence-based and sustainable AMR mitigation interventions.

Antibiotic prescribing amongst South African general practitioners in private practice: an analysis of a health insurance database.

Objectives: To investigate the appropriateness of antibiotic prescribing among GPs in the private primary healthcare sector in South Africa. Methods: An anonymized national database of claims for antibiotic prescriptions was obtained from a large medical insurer. Antibiotic prescriptions were categorized based on International Classification of Diseases (ICD-10) codes as 'appropriate', 'potentially appropriate' and 'inappropriate' using a classification scheme developed by Chua et al. (BMJ 2019; 364: k5092). Further assessments of antibiotic choice, dosage and duration of treatment were carried out to determine the appropriateness of 'appropriate' and 'potentially appropriate' prescriptions in comparison with treatment guidelines. Results: In February 2018, 188 141 antibiotics were prescribed for 174 889 patients who consulted GPs in the private sector. Penicillins were the most frequently prescribed antibiotic class, making up 40.7% of all antibiotics prescribed. Amoxicillin/clavulanic acid was the most frequently prescribed antibiotic, making up 28.6% of all antibiotics prescribed. Diseases of the respiratory system generated the highest number of prescriptions, making up 46.1% of all diagnoses. Of all prescriptions, 8.8% were appropriate, 32.0% were potentially appropriate, 45.4% were inappropriate and 13.8% could not be assessed. Of the appropriately and potentially appropriately prescribed antibiotics, 30.8% were correct antibiotic selections. Of the correctly selected antibiotics for adults, 57.7% had correct doses. Of the antibiotics prescribed with correct doses for adults, 76.7% had correct dosage frequencies and durations of treatment. Conclusions: The study revealed that antibiotics were frequently prescribed inappropriately by GPs in the private primary healthcare sector. There is thus a need to develop stewardship interventions in the sector.

Molecular Epidemiological Characterisation of ESBL- and Plasmid-Mediated AmpC-Producing Escherichia coli and Klebsiella pneumoniae at Kamuzu Central Hospital, Lilongwe, Malawi.

The global rise in infections caused by multidrug resistant (MDR) Enterobacterales poses a public health problem. We have performed a molecular epidemiological characterisation of representative plasmid-mediated AmpC (pAmpC) and ESBL-positive clinical isolates of Escherichia coli (n = 38) and Klebsiella pneumoniae (n = 17) from a tertiary hospital in Malawi collected in 2017. BlaCTX-M-15 was the most prevalent ESBL-determinant in E. coli (n = 30/38) and K. pneumoniae (n = 17/17), whereas blaCMY-2 was detected in nearly all AmpC-phenotype E. coli (n = 15/17). Whole genome sequencing revealed dominant globally disseminated E. coli sequence types (STs); ST410 (n = 16), ST131 (n = 7), and ST617 (n = 6). The ST distribution in K. pneumoniae was more diverse but included ST101 (n = 2), ST14 (n = 2), and ST340 (n = 2), all considered high-risk MDR clones. The isolates expressed an MDR profile, including resistance against commonly used antibiotics, such as fluoroquinolones, aminoglycosides, and/or trimethoprim-sulfamethoxazole, and harboured corresponding resistance determinants. Clonal analyses of the major STs of E. coli revealed closely related genetic clusters within ST410, ST131, and ST617 supporting within-hospital transmission between patients and/or via a common reservoir. The overall findings add to the limited knowledge on the molecular epidemiology of MDR E. coli and K. pneumoniae in Malawi and may help health policy makers to identify areas to target when addressing this major threat of antibiotic resistance.

Antimicrobial Stewardship in Public-Sector Hospitals in KwaZulu-Natal, South Africa.

Antimicrobial resistance (AMR) is a serious global public-health threat. Evidence suggests that antimicrobial stewardship (AMS) is a valuable tool to facilitate rational antibiotic use within healthcare facilities. A cross-sectional situational analysis using a questionnaire was conducted to determine the current status of antimicrobial stewardship (AMS) activities in all public-sector hospitals in KwaZulu-Natal (KZN). The survey had a 79% (57, N = 72) response rate. A total of 75% of hospitals had an antimicrobial stewardship committee (AMSC), 47% (20, N = 43) had a formal written statement of support from leadership, and 7% (3, N = 43) had budgeted financial support. Only 37% (16, N = 43) had on-site or off-site support from a clinical microbiologist, and 5% (2, N = 43) had an on-site infectious disease (ID) physician. Microbiologist input on pathogen surveillance data (aOR: 5.12; 95% CI: 4.08-22.02; p-value = 0.001) and microbiological investigations prior to the commencement of antibiotics (aOR: 5.12; 95% CI: 1.08-42.01; p-value = 0.041) were significantly associated with having either on- or off-site microbiology support. Respondents that had a representative from microbiology on the AMSC were significantly associated with having and interrogating facility-specific antibiograms (P = 0.051 and P = 0.036, respectively). Those facilities that had access to a microbiologist were significantly associated with producing an antibiogram (aOR: 4.80; 95% CI: 1.25-18.42; p-value = 0.022). Facilities with an ID physician were significantly associated with having a current antibiogram distributed to prescribers within the facility (P = 0.010) and significantly associated with sending prescribers personalized communication regarding improving prescribing (P = 0.044). Common challenges reported by the facilities included suboptimal hospital management support; a lack of clinicians, pharmacists, nurses, microbiologists, and dedicated time; the lack of a multidisciplinary approach; low clinician buy-in; inadequate training; a lack of printed antibiotic guidelines; and financial restrictions for microbiological investigations. The survey identified the need for financial, IT, and management support. Microbiology and infectious disease physicians were recognized as scarce human resources.

Salmonella Yoruba: A rare serotype revealed through genomic sequencing along the farm-to-fork continuum of an intensive poultry farm in KwaZulu-Natal, South Africa.

Salmonella enterica is a zoonotic pathogen of worldwide public health importance. We characterised Salmonella isolates from poultry along the farm-to-fork continuum using whole genome sequencing (WGS) and bioinformatic analyses. Three multilocus sequence types (MLSTs), i.e., ST15 (1.9%), ST152 (5.9%) and ST1316 (92.2%) and three serotypes, i.e., S. Heidelberg (1.9%), Kentucky (5.9%) and Yoruba (92.2%) were detected. The rare serotype, S. Yoruba, was detected among the farm and abattoir isolates and contained resistance and virulence determinants. Resistome analysis revealed the presence of the aac(6')-Iaa gene associated with aminoglycoside resistance, a single point mutation in the parC gene associated with fluoroquinolone and quinolone resistance, and a single isolate contained the fosA7 gene responsible for fosfomycin resistance. No antibiotic resistance genes (ARGs) were identified for isolates phenotypically non-susceptible to azithromycin, cephalosporins, chloramphenicol and nitrofurantoin and resistance was thought to be attributable to other resistance mechanisms. The fully susceptible profiles observed for the wastewater isolates suggest that the poultry environment may receive antibiotic-resistant strains and resistance determinants from poultry with the potential of becoming a pathway of Salmonella transmission along the continuum. Six plasmids were identified and were only carried by 92.2% of the S. Yoruba isolates in varying combinations. Four plasmids were common to all S. Yoruba isolates along the continuum; isolates from the litter and feces on the farm contained two additional plasmids. Ten Salmonella pathogenicity islands (SPIs) and 177 virulence genes were identified; some were serotype-specific. Phylogenetic analysis of S. Heidelberg and Kentucky showed that isolates were related to animal and human isolates from other countries. Phylogenetic analysis among the S. Yoruba isolates revealed four clades based on the isolate sources along the farm-to-fork continuum. Although the transmission of Salmonella strains along the farm-to-fork continuum was not evident, pathogenic, resistant Salmonella present in the poultry production chain poses a food safety risk. WGS analysis can provide important information on the spread, resistance, pathogenicity, and epidemiology of isolates and new, rare or emerging Salmonella strains to develop intervention strategies to improve food safety.