Aaron Oladipo Aboderin

Background: Antimicrobial resistance disproportionally affects low- and middle-income countries. We calculated the burden of resistant and susceptible Escherichia coli and Staphylococcus aureus bloodstream infections (BSIs) in ACORN2, a prospective clinical surveillance study in adults and children. Methods: Patients with culture-confirmed community-acquired susceptible and resistant E. coli (third-generation cephalosporin susceptible [3GC-S] and resistant [3GC-R]) and S. aureus (methicillin-resistant [MRSA] and methicillin-susceptible [MSSA]) BSIs were compared against blood culture–negative patients (controls). Cause-specific hazard ratios (HRs) were calculated for competing events of in-hospital mortality and discharge alive. Length of hospital stay (LOS) was calculated. Results: From 22 802 blood cultures taken, there were 329 E. coli (177 [53.8%] 3GC-R) and 363 S. aureus (132 [36.4%] MRSA) BSIs. In-hospital mortality was 8.4% for controls, 20.1% for E. coli (20.3% 3GC-R; 19.7% 3GC-S), and 13.1% for S. aureus (12.2% MRSA; 13.7% MSSA). 3GC-S but not 3GC-R E. coli BSI cases had higher adjusted hazard of death than controls (HRs, 1.73 [95% confidence interval {CI}, 1.20–2.49] and 1.38 [95% CI, .99–1.94]); risk of dying was the same for 3GC-S compared with 3GC-R infections (P = .882). Neither MSSA nor MRSA BSI patients were more likely to die than controls (HRs, 1.33 [95% CI, .91–1.93] and 1.00 [95% CI, .61–1.66]) nor MSSA versus MRSA (P = .891). The hazard of discharge alive for both resistant and susceptible S. aureus and E. coli decreased significantly when compared with controls. LOS was 2 (95% CI, 0–3) days and 1 (95% CI, −1 to 3) day longer for resistant compared with susceptible infections, for E. coli and S. aureus. Conclusions: Antimicrobial-resistant infections were not associated with increased mortality in ACORN2. Drug-resistant BSI had longer LOS compared with susceptible infections, but CIs encompassed 0 days.

Background To inform training strategies for the ACORN2 (“A Clinically Oriented antimicrobial Resistance surveillance Network”) project, a knowledge-attitudes-practices (KAP) survey was conducted among physicians to understand bacterial culture practices and views on antimicrobial resistance (AMR), diagnostic stewardship and surveillance. Methods A cross-sectional, self-administered, structured questionnaire survey, was done in 19 hospitals in Cambodia, Indonesia, Laos, Nepal, Vietnam (Asia) and Ghana, Kenya, Malawi, Nigeria (Africa) from Oct-2022 to Apr-2023. There were 586 respondents, 52% from sites in Africa and 48% from sites in Asia. Results Physicians in both regions acknowledged the problem of AMR in their hospital and country, the importance of diagnostic stewardship and AMR surveillance. More respondents from sites in Asia, compared to Africa, (78% vs 44%) had received training on AMR, and more hospitals in Asia (84% vs. 51%) had guidelines for culture specimen collection. Physician defined suspected sepsis or septic shock was the most frequent reason given for ordering a blood culture specimen in sites in both regions (28% Africa, 19% Asia). As part of diagnostic work up, most respondents requested microbiology testing for most or all patients with suspected bacterial infections (71% Africa, 85% Asia), sepsis/bloodstream infections (77% Africa, 97% Asia), bacterial pneumonia (38% Africa, 75% Asia), urinary tract infections (77% Africa, 89% Asia) and when starting parenteral antibiotics (38% Africa, 75% Asia). Conclusions Despite good awareness and knowledge of AMR at ACORN surveillance sites, heterogeneity in practices between sites and regions indicated the need for context-specific, tailored training related to AMR surveillance and diagnostic stewardship.

Enterobacter spp. are an important cause of healthcare-associated bloodstream infections that are uncommonly reported in Africa. This study utilized whole-genome sequencing to characterize Enterobacter spp. from hospitals in Nigeria’s antimicrobial resistance surveillance system. Bloodstream Enterobacter spp. isolates from six sentinel tertiary-care hospitals recovered between 2014 and 2020 were re-identified and antimicrobial susceptibility-tested using VITEK 2 system. Illumina technology provided whole-genome sequences for genome nomenclature, antimicrobial resistance gene prediction, SNP phylogeny and multi-locus sequence typing via publicly available bioinformatics pipelines. Initial biochemical delineation often misclassifies Enterobacter, necessitating whole-genome sequencing for accurate classification. Among 98 Enterobacter received, Enterobacter hormaechei subspecies xiangfangensis predominated (43), followed by other E. hormaechei subspecies (18) and Enterobacter spp. such as Enterobacter cloacae (26), Enterobacter roggenkampii (4), Enterobacter bugandensis (3), Enterobacter kobei (2), Enterobacter asburiae (1) and Enterobacter cancerogenus (1). Resistance to extended-spectrum cephalosporins, aminoglycosides, phenicols, macrolides and carbapenems in E. hormaechei was attributed to known resistance genes. E. hormaechei isolates belonged to clusters III, IV and VIII based on hsp60 typing and clades A, B, C and D according to Sutton and Co’s nomenclature. This and other recent reports from Nigeria reveal the extensive diversity of E. hormaechei, as well as clusters representing potential outbreaks. E. hormaechei, often misidentified and rarely reported from Nigeria, is the most common Enterobacter spp. isolated from blood culture in this study. Uncovering underappreciated species as important bloodstream pathogens and retrospective detection of likely outbreaks emphasize the value of genomic surveillance in resource-limited settings.

Background: Enteropathogenic Escherichia coli (EPEC) are etiological agents of diarrhea. We studied the genetic diversity and virulence factors of EPEC in southwestern Nigeria, where this pathotype is rarely characterized. Methodology/Principal findings: EPEC isolates (n = 96) recovered from recent southwestern Nigeria diarrhea case-control studies were whole genome-sequenced using Illumina technology. Genomes were assembled using SPAdes and quality was evaluated using QUAST. Virulencefinder, Ectyper, and ResFinder were used to identify virulence genes, serotypes, and resistance genes. Multilocus sequence typing was done by STtyping. Single nucleotide polymorphisms (SNPs) were called out of whole genome alignment using SNP-sites and a phylogenetic tree was constructed using IQtree. Thirty-nine of the 96(40.6%) EPEC isolates were from diarrhea cases diarrhea. Nine isolates from diarrhea patients and four from healthy controls were typical EPEC, harboring bundle-forming pilus (bfp) genes whilst the rest were atypical EPEC. There were 15 EPEC-EAEC hybrids. Atypical serotypes O71:H19 (16, 16.6%), O108:H21 (6, 6.3%), O157:H39 (5, 5.2%), and O165:H9 (4, 4.2%) were the most prevalent; only 8 (8.3%) isolates belonged to classical EPEC serovars. The largest, ST517 clade harbored multiple siderophore and serine protease autotransporter genes and included an O71:H19 subclade <10 SNPs apart, representing a likely outbreak involving 15 children, four with diarrhea. Likely outbreaks, of typical O119:H6(ST28) and atypical O127:H29(ST7798) were additionally identified. Conclusion/Significance: EPEC circulating in southwestern Nigeria are diverse and differ substantially from well-characterized lineages seen previously elsewhere. EPEC carriage and outbreaks could be commonplace but are largely undetected, hence, unreported, and require genomic surveillance for identification.

Background: Enteropathogenic Escherichia coli (EPEC) are etiological agents of diarrhea. We studied the genetic diversity and virulence factors of EPEC in southwestern Nigeria, where this pathotype is rarely characterized. Methodology/ Principal findings: EPEC isolates (n=96) recovered from recent southwestern Nigeria diarrhea case-control studies were whole genome-sequenced using Illumina technology. Genomes were assembled using SPAdes and quality was evaluated using QUAST. Virulencefinder, SeroTypefinder, and Resfinder were used to identify virulence genes, serotypes, and resistance genes, while multilocus sequence typing was done by STtyping. Single nucleotide polymorphisms (SNPs) were called out of whole genome alignment using SNP-sites and a phylogenetic tree was constructed using IQtree. Thirty-nine of the 96 (40.6%) EPEC isolates were from cases of diarrhea. Nine isolates from diarrhea patients and four from healthy controls were typical EPEC, harboring bundle-forming pilus ( bfp ) genes whilst the rest were atypical EPEC. Fifteen isolates were EPEC-EAEC hybrids. Atypical serotypes O71:H19 (16, 16.6%), O108:H21 (6, 6.3%), O157:H39 (5, 5.2%), and O165:H9 (4, 4.2%) were most prevalent; only 8(8.3%) isolates belonged to classical EPEC serovars. The largest clade comprised ST517 isolates, of O71:H19 and O165:H9 serovars harboring multiple siderophore and serine protease autotransporter genes. An O71:H19 subclade comprised isolates <10 SNPs apart, representing a likely outbreak involving 15 children, four presenting with diarrhea. Conclusion/ Significance: Likely outbreaks, of typical O119:H6(ST28) and atypical O127:H29(ST7798) were additionally identified. EPEC circulating in southwestern Nigeria are diverse and differ substantially from well-characterized lineages seen previously elsewhere. EPEC carriage and outbreaks could be commonplace but are largely undetected, hence, unreported, and require genomic surveillance for identification.

Background: Surveillance of drug-resistant infections is crucial for antimicrobial resistance (AMR) control. Implementing surveillance in low- and middle-income countries (LMICs) is challenging. Aim: To investigate bacteraemia and describe AMR surveillance. Setting: Tertiary healthcare facility. Methods: Case finding was by WHO Global AMR and Use Surveillance System (GLASS). Blood samples were processed between May 2017 and June 2018, using BACTEC blood culture system. Bacterial identification, antibiotic susceptibility testing and detection of AMR genes followed standard protocols. Results: Aerobic blood cultures were conducted in a third of clinical sepsis cases (n = 601/1851), of which 114 (19.0%) were true positives, with a 2.2% contamination rate. Pathogens recovered included six priority blood pathogens reportable to WHO GLASS. Sixteen (30.2%) of 53 Gram-negative isolates were extended-spectrum beta-lactamase producers, predominantly harbouring blaCTX-M, three (5.7%) were AmpC beta-lactamase producers, and 20 (37.7%) were carbapenem-resistant, predominantly harbouring blaKPC. Twenty-nine (50.9%) of 57 Staphylococcus aureus isolates were methicillin-resistant; 17 (58.6%) of these harboured mecA genes. Hospital-acquired infection (odds ratio [OR] = 0.3, 95% confidence interval [CI]=0.1–0.7, p = 0.004) was identified as a predisposing factor for the development of multidrug-resistant (MDR) bacteraemia. Bacteraemia with MDR organisms was significantly associated with mortality (OR = 3.8, 95% CI = 1.6–9.1, p = 0.001). Conclusion: A wide variety of bacteria are responsible for bacteraemia in our setting, with more than half being multidrug-resistant. Bacteraemia with multidrug-resistant organisms was significantly associated with mortality, hence, the need for this AMR surveillance initiative. Contribution: Implementing healthcare facility-based surveillance of AMR in LMICs is achievable despite limited microbiological laboratory capacity.

Introduction In low- and middle-income countries (LMICs), the persistent lack of access and high inappropriate use of antibiotics, which are fuelled by gender-related factors, continue to facilitate antimicrobial resistance. This in turn reduces the capacity to treat infectious diseases. However, there is a lack of clarity on the nature and extent of the available evidence on gender influence on access to antibiotics and antibiotic use behaviour. This proposed study will systematically review the available literature to map out the scope of evidence on gender differences and, importantly, the related factors influencing antibiotic use and access to antibiotics in LMICs. Methods and analysis This scoping review will be conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for scoping reviews. Major databases (MEDLINE, PsycINFO and CINAHL) will be searched via the EBCOhost and Web of Science platforms for peer-reviewed articles. Title and abstract screening, as well as full paper review, will be conducted by a single reviewer, with 20% of identified citations reviewed independently by two other reviewers. A predefined excel spreadsheet will be used for data extraction and analysis. Findings will be presented thematically in a narrative summary and tables. Ethics and dissemination Obtaining ethics approval is not required for this study. The findings will contribute to understanding gender health inequalities and areas for further research on strategies to incorporate gender considerations in antimicrobial stewardship efforts in LMICs. The study findings will be disseminated through presentations in seminars, scientific conferences and publications in peer-reviewed journals.

Enterobacter spp. are an important cause of healthcare-associated bloodstream infections uncommonly reported in Africa. This study used whole genome sequencing (WGS) to characterise Enterobacter spp. from hospitals in Nigeria’s antimicrobial resistance (AMR) surveillance system. Blood-culture isolates of Enterobacter from six such tertiary-care hospitals recovered between 2014 and 2020 were re-identified and antimicrobial susceptibility-tested using VITEK2. Illumina technology provided whole genome sequences for genome nomenclature, antimicrobial resistance gene prediction, Single Nucleotide Polymorphism (SNP) phylogeny, and multi-locus sequence typing via publicly available bioinformatics pipelines. Initial biochemical delineation often misclassified Enterobacter , necessitating whole-genome sequencing for accurate classification. Among 98 Enterobacter received, Enterobacter hormaechei subspecies xiangfangensis predominated (43), followed by other E. hormachei subspecies (18), E. cloacae (26), E. roggenkampii (4), E. bugandensis (3), E. kobei (2), E. asburiae (1) and E. cancerogenous (1). Cephalosporins, aminoglycoside, chloramphenicol, macrolide, and carbapenem resistance in E. hormaechei was attributed to known resistance genes. They belonged to clusters III, IV, and VIII based on hsp60 typing and clades A, B, C, and D according to Sutton and Co’s nomenclature. These isolates and other Enterobacter species recently reported from Nigeria reveal extensive E. hormaechei diversity, as well as clusters representing potential outbreaks . Enterobacter hormaechei , often misidentified and rarely reported from Nigeria, is this study’s most common blood culture isolated Enterobacter spp. Uncovering underappreciated species as important bloodstream pathogens and retrospective detection of likely outbreaks emphasise the value of genomic surveillance in resource-limited settings. DATA SUMMARY: All sequence reads were submitted to the European Nucleotide Archive (ENA) under the project ID PRJEB29739 ( https://www.ebi.ac.uk/ena/browser/view/PRJEB29739 ). Accessions can be found in Table S1. IMPACT STATEMENT: Accurate identification of Enterobacter is essential in healthcare settings as misidentification can lead to selecting antimicrobials to the genus is intrinsically resistant resistant before susceptibility testing results are available. Also, misidentification can compromise microbiology support for infection prevention and control. We show that E. hormaechei , which is never reported from clinical laboratories in Nigeria, is frequently misidentified using conventional methods like tube- or strip biochemical testing and VITEK systems. Whole genome sequence data demonstrates that E. hormaechei and E. cloacae are the most common Enterobacter isolated from bloodstream infections in Nigeria. Enhanced identification methods for surveillance play pivotal roles in improving patient care, optimising antibiotic stewardship, and combating the evolving challenges posed by this pathogen. Overall, this study reveals the effectiveness of WGS in correctly identifying this important pathogen.

Nigeria instituted the National Health Insurance Scheme (NHIS) for universal health coverage. This study compared the NHIS and out-of-pocket (OOP) antibiotic prescribing with the World Health Organization (WHO) optimal values. A total of 2190 prescription forms from the NHIS and OOP were included in this study conducted at Obafemi Awolowo University Teaching Hospitals Complex, Nigeria from January 2021 to December 2022 and analysed using WHO drug prescribing guidelines. The average number of drugs per encounter was higher in the NHIS prescribing (χ²=58.956, p=0.00) than in OOP prescribing. The percentage of encounters with an antibiotic prescribed is higher in NHIS prescribing (χ²=46.034, p=0.000) than in OOP prescribing. The percentage of parenteral antibiotic prescribing is higher in OOP prescribing (χ²=25.413, p=0.000) than in NHIS prescribing. The percentage of antibiotic prescribed from the National Essential Medicine List is higher in NHIS prescribing (χ²=8.227, p=0.000) as well as the antibiotics prescribed from the Access category of the WHO Access, Watch and Reserve (AWaRe) Classification of antibiotics (χ²=23.946, p=0.000) when compared with OOP prescribing. Prescribing indicators show better performances with NHIS antibiotic prescribing and are closer to the WHO-recommended optimal values than in OPP prescribing. Hence NHIS prescribing can be an easy target for hospital antibiotic stewardship intervention for optimal antibiotic prescribing.

This review documents the status of AMR education and awareness in the WHO African region, as well as specific initiatives by its member states in implementing education and awareness interventions, as a strategic objective of the Global Action Plan on AMR, i.e., improve knowledge and understanding on AMR through effective communication, education, and training. A systematic search was conducted in Google Scholar, PubMed, and African Journals Online Library according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, for articles published in English. Retrieval and screening of articles was performed using a structured search protocol following a pre-set inclusion/exclusion criterion. Eighty-five published articles reporting 92 different studies from 19 Member States met inclusion criteria and were included in the final qualitative synthesis. Nigeria (21) and Ethiopia (16) had most of the studies, while the rest were distributed across the remaining 17 Member States. The majority of the articles were on knowledge, attitude, and practices with regard to AMR and antimicrobial use and most of them documented a general lack and suboptimal knowledge, poor attitude and practices, and widespread self-medication. This review shows low levels of knowledge of AMR coupled with extensive misuse of antimicrobial medicines by different target audiences. These findings underscore the urgent need for enhanced and context-specific educational and positive behavioural change interventions.