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.

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.

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: 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.

Objectives: This study determined the profile of spontaneous bacterial peritonitis (SBP) and its variants in patients with decompensated liver cirrhosis and hepatocellular carcinoma (HCC).Design: A descriptive cross-sectional studySetting: The study was conducted in a tertiary hospital.Participants: Patients with decompensated liver cirrhosis and HCC above 18 years.Interventions: Ascitic fluid (AF) samples were taken for cell count and culture using a BACTEC culture bottle. Sensitivity patterns and ascitic fluid total protein and albumin levels were also assessed.Main outcome measures: Clinical profile of SBP, organisms isolated from the ascitic fluid and sensitivity of isolated organisms to antibiotics.Results: One hundred and six (106) participants were recruited. Seventy (66%) had liver cirrhosis, and 36 (34%) had HCC. The mean age was 50.08±12.66years. Eighty-nine (84%) were males and 17(16%) were females. The overall prevalence of SBP was 29.2% (n = 31). Classical SBP was 5(4.7%), CNNA 20(18.9%) and monobacterial ascites 6(5.7%). The Gram-positive isolates were Staphylococcus aureus 5(45.5%) – [2(18.2%) MRSA, 3(27.3%) MSSA] while the Gram-negative organisms were E. coli 3(27.3%), Acinectobacter 2(18.2%) and Bulkholderia cepacia 1 (9.1%). Gram-negative bacteria showed absolute resistance to cephalosporins but were all susceptible to meropenem. Gram-positive bacteria showed 100% susceptibility to linezolid, vancomycin and daptomycin. Gram-positive bacteria also showed low resistance to fluoroquinolones (20%). Multi-drug resistance pattern was reported for MRSA, Acinetobacter baumannii and Bulkholderia cepacia.Conclusion: SBP is a common complication in patients with decompensated CLD. Guided antibiotic treatment should be encouraged, particularly in light of the emergence of multidrug resistance patterns.

BACKGROUND:Antimicrobial resistance (AMR) is a major global health threat, but there is scarcity of laboratory surveillance data linked to clinical information to determine burden and inform interventions, especially from low-income and middle-income countries. The ACORN2 study sought to address this through prospective case-based surveillance in 19 hospitals across Africa and Asia to characterise drug-resistant infections by origin, clinical syndrome, patient age, outcome, and geographical location. METHODS:Patients were enrolled on selected wards and clinical data were collected daily for community-acquired infections (CAIs). Point prevalence surveys for hospital-acquired infections (HAIs) were conducted weekly. Mortality was assessed at discharge and after 28 days. Linked microbiology data were extracted from local laboratory databases. Primary descriptive analyses focused on WHO Global Antimicrobial Resistance and Use Surveillance System pathogen (target organism) bloodstream infections (BSIs). Comparisons were adjusted for clustering by site using random effects models. FINDINGS:Over 31 months, 41 907 infections were characterised from 41 032 admissions. Two-thirds were children (19 351; 47·2%) or neonates (6649; 16·2%). There were marked differences in pathogen incidence and antibiotic resistance when clinical infections were stratified by patient age category and infection origin (CAI/HAI). The highest rates of target organism AMR BSI were third-generation cephalosporin-resistant (3GC-R) Escherichia coli (718·56/100 000 blood cultured infection episodes), meticillin-resistant Staphylococcus aureus (586·89/100 000 blood cultured infection episodes), and 3GC-R Klebsiella pneumoniae (364·92/100 000 blood cultured infection episodes). In-hospital mortality was 13·1% (166/1265) in patients with target organism BSI versus 6·2% (1357/21 845) in those with negative blood cultures, p<0·0001. INTERPRETATION:ACORN2 has shown practical implementation of collecting linked clinical-laboratory AMR data in low-income and middle-income countries and identified a significant burden of WHO GLASS BSI. Adoption of the ACORN2 approach at scale might enhance use of diagnostic microbiology and improve the volume of clinical data included in national and global AMR surveillance datasets. FUNDING:Wellcome.

BackgroundEnteropathogenic 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 findingsEPEC 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/significanceEPEC 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.

Introduction: Diarrhoea is a major public health concern in developing countries, usually exacerbated by poor water, sanitation and hygiene but it’s aetiology is under-studied, particularly away from capital cities. We identified diarrheagenic Escherichia coli (DEC) from stools collected in Ile-Ife and Ilesa, Osun state, Nigeria and determined their antibiotic resistance profiles. Methods: Stool samples from 167 children with diarrhoea and 334 controls under the age of 5 years were cultured for E. coli and Salmonella. Bacterial isolates were identified biochemically and DEC were identified by PCR. Antimicrobial susceptibility testing was by modified Kirby-Bauer disc diffusion method in accordance with the CLSI guidelines. Data were analyzed using Chi-square and Fisher’s exact tests. Result: Risk factors associated with diarrhoea included age under 12 months (p = 0.002), caregivers without at least primary school education (p = 0.006), breastfeeding for under 6 months (p˂0.001), and care-givers who were siblings (p = 0.004). DEC was detected in 69(41.3%) cases but only 86(25.7%) controls (p < 0.001) and more commonly recovered during wet season (p < 0.001). Enterotoxigenic E. coli (p = 0.031), enteropathogenic E. coli (p = 0.031) and Shiga-toxin producing E. coli (p = 0.044) were recovered more commonly from cases than controls. DEC from patients with diarrhoea were commonly resistant to sulphonamides (91.3%), trimethoprim (82.6%), and ampicillin (78.3%) but were largely susceptible to quinolones (%) and carbapenems (%). Conclusion: Enteropathogenic, enterotoxigenic and Shiga toxin-producing E. coli are associated with diarrhoea in our setting, and show considerable resistance to first line antimicrobials. Risk factors for DEC diarrhoea include infancy, inadequate breast feeding and caregivers with education below primary school.

COVID-19 pandemic changed the face of global health and brought about new issues in global health security and economy. The World Health Organization published guidelines for clinical management of COVID-19 four months after declaration of COVID-19 as a pandemic. Scholarly reviews and studies from member states within WHO AFRO reveals significant deviation from the WHO published protocols on COVID-19. Assessment of national treatment protocols of 30 of 47 WHO AFRO member states showed widespread inappropriate use of antimicrobial agents for patients, which may worsen the global and concerning threat of antimicrobial resistance. There is need for adopting interventions that optimize antimicrobial use in the context of pre- and post-pandemic preparedness to ensure long-term effectiveness and sustainability for antimicrobials. Treatment guidelines are to be adopted or adapted depending on best clinical evidence available. Non-compliance with guidelines might lead to mismanagement of infectious diseases with attendant negative consequences including antimicrobial resistance and misdirection of critical resources and supplies amongst others.

INTRODUCTION: The value of medicines is lost when these resources are not used rationally. Out of 12 developing countries, Nigeria has the third highest percentage of antibiotic prescriptions, at 48%. Antibiotic misuse results in limited efficacy, which can lead to the emergence of antimicrobial resistance. We conducted a systematic review to synthesise the evidence on antibiotic use in humans in Nigeria. METHODS: We conducted a systematic review of medicine use behaviour by patients and prescription behaviour by health workers, which were searched for in articles published in English from 2000 to 2017. Data was entered into purpose-built templates. Key quantitative indicators were extracted and summarised as frequencies and proportions, while free-text responses were synthesised. RESULTS: The systematic review determined that the median prevalence of persons using antibiotics without prescription is 46.7%. The drivers of irrational antibiotic use included poor regulation of medicines and premises, a chaotic medicine distribution system, limited licensed medicine prescribers, over-the-counter (OTC) sales of antibiotics, patients’ demand for antibiotics, and access to health insurance. DISCUSSION: Irrational antibiotic use is widespread in humans and animals. We recommend that the government enforce regulations on antibiotic sales to humans and animals and increase awareness of irrational antibiotic use and AMR in Nigerian communities through a whole-of-society approach. The collated information was used to develop a National Action Plan on AMR in 2017.

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.

Abstract Introduction Diarrhoea is a major public health concern in developing countries, usually exacerbated by poor water, sanitation and hygiene but its aetiology is under-studied, particularly away from capital cities. We identified diarrhoeagenic Escherichia coli (DEC) from stools collected in Ile-Ife and Ilesa, Osun state, Nigeria and determined their antibiotic resistance profiles. Methods Stool samples from 167 children with diarrhoea and 334 controls under the age of 5 years were cultured for Escherichia coli and Salmonella. Bacterial isolates were identified biochemically and DEC were identified by PCR. Antimicrobial susceptibility testing was by modified Kirby-Bauer disc diffusion method in accordance with the CLSI guidelines. Data were analyzed using Chi-square and Fisher’s exact tests. Result Diarrhoea infection is significantly high among children under 12 months (p = 0.002), caregivers without at least primary school education (p = 0.006), breastfeeding for under 6 months (p˂0.001), and caregivers who were siblings (p = 0.004). DEC was detected in 69(41.3%) cases but only 86(25.7%) controls (p < 0.001) and more commonly recovered during the wet season (p < 0.001). Enterotoxigenic E. coli (p = 0.031), enteropathogenic E. coli (p = 0.031) and Shiga-toxin-producing E. coli (p = 0.044) were recovered more commonly from cases than controls. DEC from patients with diarrhoea were commonly resistant to sulphonamides (91.3%), trimethoprim (82.6%), and ampicillin (78.3%) but were largely susceptible to quinolones and carbapenems (97.1%). Conclusion Enteropathogenic, enterotoxigenic and Shiga toxin-producing E. coli are associated with diarrhoea in our setting, and show considerable resistance to first-line antimicrobials. Risk factors for DEC diarrhoea include infancy, inadequate breastfeeding and caregivers with education below primary school.

Background 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. Methods 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. Results 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. Conclusions 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.

Background Acinetobacter baumannii cause difficult-to-treat infections mostly among immunocompromised patients. Clinically relevant A. baumannii lineages and their carbapenem resistance mechanisms are sparsely described in Nigeria.Objective This study aimed to characterise the diversity and genetic mechanisms of carbapenem resistance among A. baumannii strains isolated from hospitals in southwestern Nigeria.Methods We sequenced the genomes of all A. baumannii isolates submitted to Nigeria’s antimicrobial resistance surveillance reference laboratory between 2016 – 2020 on an Illumina platform and performed in silico genomic characterisation. Selected strains were sequenced using the Oxford Nanopore technology to characterise the genetic context of carbapenem resistance genes.Results The 86 A. baumannii isolates were phylogenetically diverse and belonged to 35 distinct sequence types (STs), 16 of which were novel. Thirty-eight (44.2%) isolates belonged to none of the known international clones (ICs). Over 50% of the isolates were phenotypically resistant to 10 of 12 tested antimicrobials. Majority (n=54) of the isolates were carbapenem-resistant, particularly the IC7 (100%) and IC9 (>91.7%) strains. bla OXA-23 (34.9%) and bla NDM-1 (27.9%) were the most common carbapenem resistance genes detected. All bla OXA-23 genes were carried on Tn 2006 or Tn 2006 -like transposons. Our findings suggest that the mobilisation of a 10kb Tn 125 composite transposon is the primary means of bla NDM-1 dissemination.Conclusion Our findings highlight an increase in bla NDM-1 prevalence and the widespread transposon-facilitated dissemination of carbapenemase genes in diverse A. baumannii lineages in southwestern Nigeria. We make the case for improving surveillance of these pathogens in Nigeria and other understudied settings.Importance Acinetobacter baumannii are increasingly clinically relevant due to their propensity to harbour genes conferring resistance to multiple antimicrobials, as well as their ability to persist and disseminate in hospital environments and cause difficult-to-treat nosocomial infections. Little is known about the molecular epidemiology and antimicrobial resistance profiles of these organisms in Nigeria, largely due to limited capacity for their isolation, identification, and antimicrobial susceptibility testing. Our study characterised the diversity and antimicrobial resistance profiles of clinical A. baumannii in southwestern Nigeria using whole-genome sequencing. We also identified the key genetic elements facilitating the dissemination of carbapenem resistance genes within this species. This study provides key insights into the clinical burden and population dynamics of A. baumannii in hospitals in Nigeria and highlights the importance of routine whole-genome sequencing-based surveillance of this and other previously understudied pathogens in Nigeria and other similar settings.

Acinetobacter baumannii bacteria are increasingly clinically relevant due to their propensity to harbor genes conferring resistance to multiple antimicrobials, as well as their ability to persist and disseminate in hospital environments and cause difficult-to-treat nosocomial infections. Little is known about the molecular epidemiology and antimicrobial resistance profiles of these organisms in Nigeria, largely due to limited capacity for their isolation, identification, and antimicrobial susceptibility testing.

AbstractBackgroundAcinetobacter baumanniicause difficult-to-treat infections mostly among immunocompromised patients. Clinically relevantA. baumanniilineages and their carbapenem resistance mechanisms are sparsely described in Nigeria.ObjectiveThis study aimed to characterise the diversity and genetic mechanisms of carbapenem resistance amongA. baumanniistrains isolated from hospitals in southwestern Nigeria.MethodsWe sequenced the genomes of allA. baumanniiisolates submitted to Nigeria’s antimicrobial resistance surveillance reference laboratory between 2016 – 2020 on an Illumina platform and performedin silicogenomic characterisation. Selected strains were sequenced using the Oxford Nanopore technology to characterise the genetic context of carbapenem resistance genes.ResultsThe 86A. baumanniiisolates were phylogenetically diverse and belonged to 35 distinct sequence types (STs), 16 of which were novel. Thirty-eight (44.2%) isolates belonged to none of the known international clones (ICs). Over 50% of the isolates were phenotypically resistant to 10 of 12 tested antimicrobials. Majority (n=54) of the isolates were carbapenem-resistant, particularly the IC7 (100%) and IC9 (>91.7%) strains.blaOXA-23(34.9%) andblaNDM-1(27.9%) were the most common carbapenem resistance genes detected. AllblaOXA-23genes were carried on Tn2006or Tn2006-like transposons. Our findings suggest that the mobilisation of a 10kb Tn125composite transposon is the primary means ofblaNDM-1dissemination.ConclusionOur findings highlight an increase inblaNDM-1prevalence and the widespread transposon-facilitated dissemination of carbapenemase genes in diverseA. baumanniilineages in southwestern Nigeria. We make the case for improving surveillance of these pathogens in Nigeria and other understudied settings.ImportanceAcinetobacter baumannii are increasingly clinically relevant due to their propensity to harbour genes conferring resistance to multiple antimicrobials, as well as their ability to persist and disseminate in hospital environments and cause difficult-to-treat nosocomial infections. Little is known about the molecular epidemiology and antimicrobial resistance profiles of these organisms in Nigeria, largely due to limited capacity for their isolation, identification, and antimicrobial susceptibility testing. Our study characterised the diversity and antimicrobial resistance profiles of clinical A. baumannii in southwestern Nigeria using whole-genome sequencing. We also identified the key genetic elements facilitating the dissemination of carbapenem resistance genes within this species. This study provides key insights into the clinical burden and population dynamics of A. baumannii in hospitals in Nigeria and highlights the importance of routine whole-genome sequencing-based surveillance of this and other previously understudied pathogens in Nigeria and other similar settings.

Introduction Antibiotic-resistant bacteria complicate treatment options in neonatal sepsis, especially in developing countries. This study determined the epidemiology and bacteriological characteristics of neonatal sepsis at a tertiary hospital, in southwest Nigeria.Methods This was a cross-sectional study from December 2017 to April 2019 among admitted babies with clinical neonatal sepsis. Blood culture was performed by semi-automated system, sepsis biomarker assay (serum procalcitonin) by a semi-quantitative kit while proforma was used to capture clinico-demographic data. Bacterial identification, antibiotic susceptibility patterns, determination of genetic elements mediating resistance, were performed by standard methods and polymerase chain reaction protocols, respectively. Quantitative data were expressed as frequencies, mean; bivariate and multivariate analyses were performed by Chi-square or Fishers' exact test and logistic regression.Results Of the 192 cases of neonatal sepsis enrolled, 42.7% (82/192) were blood culture positive. Factors associated with blood culture positivity included respiratory rate >60 bpm (60/82; p<0.03), lethargy/unconsciousness (59/82; FE=7.76; p<0.001), grunting respiration (54/82; p=0.04), meconium passage before birth (17/82; p=0.03) and prolonged rupture of membranes >24 hours (50/82; FE=6.90; p=0.01). On the other hand, mortality in the neonates was associated with elevated serum procalcitonin assay (>0.5 ng/mL) chi 2=13.58; p=0.03] and Gram-negative bacteremia (chi 2=24.64; p<0.001). The most common bacterial isolates were Staphylococcus aureus (42/82), coagulase-negative Staphylococcus spp. (17/82), Enterobacter spp. (8/82), and Acinetobacter spp. (6/82). Methicillin resistance was present in 85.7% (36/42) of Staphylococcus aureus and 52.9% (9/17) of coagulase-negative Staphylococcus, while extended-spectrum beta-lactamase (ESBL) and AmpC enzymes were present in (21.1%; 4/19) of the Gram-negative bacilli.Conclusions Almost half of the cases of clinically diagnosed neonatal sepsis have bacterial etiologic confirmation of sepsis. Gram-negative bacteremia and high serum procalcitonin predict mortality in neonatal sepsis. There was high resistance to common antibiotics for the treatment of neonatal sepsis in our settings.

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.

BackgroundAntimicrobial resistance (AMR) has emerged as a leading global health and economic threat of the 21st century, with Africa bearing the greatest burden of mortality from drug-resistant infections. Optimization of the use of antimicrobials is a core strategic element of the response to AMR, addressing misuse and overuse as primary drivers. Effectively, this requires the whole society comprising not only healthcare professionals but also the public, as well as the government, to engage in a bottom-up and a top-down approach. We determined the progress of African national governments in optimizing antimicrobial drug use.MethodsFrom September 2021 to June 2022, all 47 member states of the World Health Organization African region (WHO AFRO) were invited to participate in a survey determining the implementation of strategies to optimize antimicrobial use (AMU). We used the WHO antimicrobial stewardship (AMS) assessment tool, National core elements—A checklist to guide the country in identifying existing national core elements for the implementation of AMS Programs, to obtain information from national AMR focal persons. The tool consists of four sections—national plans and strategies; regulations and guidelines; awareness, training, and education; and supporting technologies and data—with a total of 33 checklist items, each graded from 0 to 4. The responses were aggregated and analyzed using Microsoft Excel 2020®.ResultsThirty-one (66%) of the 47 countries returned completed forms. Only eight (25.8%) countries have developed a national AMS implementation policy incorporating defined goals, targets, and operational plans. There are no budget lines for AMS activities in 23 (74.2%) countries. The WHO Access, Watch, Reserve (AWaRe) classification of optimizing AMU has been integrated into the national essential medicines list or formulary in 19 (61.3%) countries, while the incorporation of the AMS principles and WHO AWaRe classification into national clinical guidelines for the management of infections is present in only 12 (38.7%) and 11 (34.5%) countries, respectively. Although regulations on the prescription-only sale/dispensing of antibiotics are present in 68% of countries, their enforcement is poor. Systems identifying pathogens and antibiotic susceptibility for optimal use of antibiotics are lacking in 38% of countries.ConclusionIn Africa, wide gaps exist in the governments’ implementation of the core elements of optimizing antimicrobial drug use. Responding to AMR constitutes a long journey, and technical and financial support needs to be deployed to optimize the use of antimicrobials.

Background: Pulmonary aspergillosis (PA) is common among patients with tuberculosis (TB). With both infections presenting with similar clinical and radiologic features, diagnosis of PA is often made too late or missed completely due to lack of clinical suspicion and poor diagnostic laboratory capacity for mycotic infections prevalent in our settings. We present a case of preventable mortality caused by delayed diagnosis and treatment of PA in a patient with pulmonary TB (PTB). Case presentation: A 13-year-old female was diagnosed and treated for PTB, having received anti-TB regimen for 8 months in a mission hospital from where she was referred due to worsening cough, chest pain and progressive breathlessness. The patient was re-assessed and investigated, with GeneXpert detecting Mycobacterium tuberculosis, susceptible to rifampicin. Diagnosis of pulmonary tuberculosis complicated by right pneumothorax was made indicating an emergency thoracotomy and chest tube insertion and continuation of the first line anti-TB regimen. At about 2 weeks into admission, patients had features of superimposed acute bacterial sepsis with fever becoming high grade, marked neutrophilia with toxic granulation and elevated sepsis biomarker, and this necessitated empiric antibiotic treatment with parenteral meropenem and vancomycin. However, the patient only had mild clinical improvement following which there was progressively worsening respiratory symptoms and massive haemoptysis. Result of sputum fungal study was available on admission day 20 and revealed a growth of Aspergillus flavus. Treatment with intravenous voriconazole was however commenced rather late when the fungal respiratory disease could no longer be remedied. The patient died on admission day 23. Conclusion: Diagnosis of PA in patients with background TB is often made too late to guarantee timely and effective antifungal treatment with negative consequences on patients’ outcomes. Improving clinical and laboratory capacities is essential to reducing mortality from PA in healthcare facilities.