JAC-Antimicrobial Resistance

Antimicrobial resistance (AMR) threatens global health. Understanding resistance patterns aids in treatment and promotes responsible antimicrobial use. This review and meta-analysis assessed the prevalence of antimicrobial resistance among clinically relevant pathogens in Tanzania. A total of 18,265 studies identified from Google Scholar (18,000), PubMed (13), and Science Direct (252) underwent screening and full article review. Finally, 28 studies were included. A subgroup analysis was performed to evaluate the resistance patterns within antibiotic classes for specific pathogens. Descriptive statistics were used to describe the characteristics of the studies and the prevalence of antibiotic resistance. Heterogeneity was assessed using forest plots and the I{superscript 2} statistic. Among the included studies, most isolates (25.0%) were obtained from urine samples. Of these studies, 75% were cross-sectional studies and 92.9% were conducted in hospital settings. The analysis revealed high resistance to penicillin, particularly amoxicillin-clavulanic and ampicillin, with Klebsiella pneumoniae (0.96 [0.83-0.99]), Acinetobacter baumannii (0.94 [0.67-0.99]) and Escherichia coli (0.90 [0.81-0.95]). Similarly, erythromycin resistance was most prevalent in Campylobacter spp. (0.85 [0.80-0.89]). Ciprofloxacin resistance was highest in Acinetobacter baumannii (0.54 [0.33-0.73]), whereas amikacin resistance was highest in Proteus spp. (0.86 [0.35-0.99]). Ceftriaxone resistance was particularly high in Acinetobacter baumannii (0.91 [0.70-0.98]) and Pseudomonas aeruginosa (0.85 [0.74-0.92]). Resistance to meropenem was lowest among Escherichia coli (0.04 [0.01-0.10]) and Klebsiella spp. (0.07 [0.03-0.15]), with an overall pooled resistance to the ESKAPE-E pathogen of (0.11[0.06-0.19]). Imipenem and clindamycin each had an overall pooled resistance of (0.06[0.02-0.14]) against both Escherichia coli and Klebsiella pneumoniae. The findings highlight widespread resistance among key bacterial pathogens, ESKAPE-E, particularly in the Access and Watch groups of antibiotics. The variability in resistance patterns underscores the need to re-evaluate empirical treatment protocols (STG/NEMLIT) to ensure effective treatment regimens, strengthen antimicrobial stewardship, enhance surveillance systems, and promote rational antibiotic use.

BackgroundThe never-ending emergence of superbugs casts a shadow over the victorious age of antibiotics. In fact, the triumph of antibiotics was previously viewed in retrospection as our final victory over bacteria. Bacteria like Klebsiella pneumoniae, Acinetobacter baumannii, and Escherichia coli are now raising an alarming number of infections across hospitals and communities around the globe. The objective was to evaluate the implications for antimicrobial stewardship based on identifying the antibiotic resistance profiles, genotype mechanisms, and trends in common pathogenic bacteria found in various hospitals across Iraq. MethodsWe used a two-fold approach that was comprehensive in scope and involved both efficient multicenter surveillance as well as cutting edge genetic analysis to unravel the complex topography of antibiotic resistance. We provided a geographically heterogeneous but diverse set of clinically obtained isolates to participate in hospitals for a period of 24 months and concentrated our efforts on prioritized pathogens K. pneumoniae, A. baumannii, E. coli, P. aeruginosa, and S. aureus that are well known to pose serious threats. Beginning with clinically obtained isolates sourced across the entire globe, we used standardized techniques such as broth microdilution to first undertake phenotyping in a central reference lab to establish microbial identity based on resistance phenotypes to a set of prioritized antibiotics that include carbapenems, third generation cephalosporins, or fluoroquinolones. Finally, we derived data concerning the emergence patterns and geographic distribution of resistant microbes such as MRSA or CRE. We used genome-wide sequencing to unlock information concerning the genetic blueprints for a set of specifically chosen isolates based on their representational diversity across geographic locales, resistance phenotypes, and specific times. ResultsThe sample was made up of Escherichia coli (n = 225), Klebsiella pneumoniae (n = 185), Staphylococcus aureus (n = 135), Pseudomonas aeruginosa (n= 90), and Acinetobacter baumannii (n = 125). Ceftriaxone resistance was found in 80.4% of E. Coli, ciprofloxacin resistance in 45.6%, and meropenem resistance in 15.1%. K. pneumoniae exhibited 38.9% resistance to aminoglycosides and 70.2% resistance to carbapenems. The percentage of MRSA in S. aureus was 55.5%. P. aeruginosa showed 22.2% resistance to colistin, 37.8% resistance to piperacillin tazobactam, and 50.0% resistance to ceftazidime. Imipenem resistance was found in 85.6% of A. baumannii isolates, whereas colistin resistance was found in 28.8% of isolates. In all, 3.4% of isolates are pan-drug-resistant (PDR), 14.6% are extensively drug-resistant (XDR), and 52.1% are multidrug-resistant (MDR). WGS identified common genes such bla_NDM-1, bla_OXA-48, mcr-1, aac (6)-Ib, and plasmid replicons IncF, IncL/M, and IncI2. Carbapenem resistance in Gram-negative bacteria rose by around 18% over the course of five years. ConclusionsThis study shows that the rapid spread of complex genetic information in bacteria causes antibiotic resistance problems. High-level resistance represents an expected consequence of the spread of resistance genes and successful bacteria within healthcare systems. We demonstrate in our results that our expertise in overcoming resistance at a molecular level will play a crucial role in combating infectious diseases in the coming years.

Antimicrobial resistance (AMR) is a rising global health threat and estimated to cause 700,000 deaths annually. Although blood cultures (BCs) are the reference standard to diagnose bloodstream infections and inference of antimicrobial susceptibility testing (AST), the method could fail to differentiate bacteria with similar biochemical characteristics. This study evaluated the utility of whole genome sequencing (WGS) in complimenting BCs in bacteria identification and assessing AMR. Blood samples came from septicemic patients attending county referral hospitals in western Kenya and around the Lake Victoria region. BCs and AST were performed on BD Bactec 9050 and Phoenix 100 respectively. Out of the 960 BCs, 17 had uncontaminated growth and were evaluated by WGS on the Oxford Nanopore PromethION platform. BD Phoenix system identified the 17 bacteria isolates as: 4 Escherichia coli, 8 Salmonella enterica serovar Typhi, 1 unspeciated Salmonella, 3 Staphylococcus aureus and 1 Streptococcus pneumoniae. WGS results differed from BCs in identifying Salmonella species, with WGS identifying the species as Salmonella enterica serovar Typhimurium. Conversely, WGS detected AMR genes in bacteria that AST had classified as susceptible. In conclusion, we caution that BCs may not be providing correct identity of Salmonella species. The observed discrepancies between phenotypic and genotypic markers of drug resistance highlight the challenges in interpreting and predicting the functional utility of AMR genes.

BackgroundSystematic evidence on antimicrobial selection for antimicrobial resistance (AMR) is scarce. We estimated the effect of prescribing key antibiotic classes on AMR across U.S. Veterans Affairs Medical Centres (VAMC). MethodsWe analysed clinical isolates of Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa from 138 VAMC from Feb 1, 2007 to Dec 31, 2021. Antimicrobial prescribing was measured as inpatient days of therapy per 1000 patient-days; multidrug resistance as number of resistant phenotypes per 1,000 admissions. Temporal trends were modelled using generalized estimating equations and average annual percentage changes (AAPC). Multilevel multinomial logistic regression related facility-level antibiotic prescribing (days of therapy per 100 patient-days in the last 14d) to the relative odds of resistant phenotypes. FindingsHospital-onset infection incidence declined for all pathogens, except third-generation cephalosporin (3GC)-resistant E coli. Antimicrobial prescribing remained stable or decreased, except 3GC prescribing, which increased from 2007 until 2019 (AAPC=2{middle dot}4%, 95% CI 1{middle dot}3%-3{middle dot}5%, p-value<0.0001). Fluoroquinolone (FQL) use was associated with resistance across all pathogens. In S aureus, each day of FQL treatment was linked to a 4{middle dot}6% (95CI: 1{middle dot}5, 7{middle dot}7, p-value=0.0127) increase in the relative odds of isolating FQL-resistant, macrolide-susceptible, methicillin-resistant S aureus. Anti-staphylococcal beta-lactams were not linked to MRSA. Each day of 3GC treatment increased the odds of isolating 3GC- and beta-lactam/beta-lactamase-resistant E coli by 5{middle dot}2% (95%CI: 1{middle dot}3%, 9{middle dot}4%, p-value=0.0079) and K pneumoniae by 3{middle dot}0% (95% CI: -0{middle dot}1%-6{middle dot}2%, p-value=0.0600). Each day of carbapenem treatment increased the odds of carbapenem-resistant, FQL- and BL/BLI-susceptible P aeruginosa by 15{middle dot}7% (95%CI: 9{middle dot}4%, 22{middle dot}4%, p-value<0.0001). InterpretationHigher facility-level antimicrobial use increased the odds of corresponding resistant phenotypes, with important exceptions. FQLs selected for resistance across multiple pathogens. Increased 3GC prescribing likely offset reductions in FQLs and was associated with co-resistance in E coli. These findings underscore the need for comprehensive stewardship that coordinates strategies across antimicrobials.

BackgroundWhile associations of antibiotic resistance traits are not random in multidrug-resistant (MDR) bacteria, clinically relevant resistance patterns remain relatively underexplored. This study used machine learning, specifically association-set mining, to explore resistance associations within E. coli isolates from community-acquired urinary tract infections (UTIs). MethodsWe analysed antibiograms of community-acquired E. coli UTI isolates collected from 2018 to 2022 by Frances national surveillance system. Association-set mining was applied separately to extended-spectrum beta-lactamase-producing E. coli (ESBL-EC) and non-ESBL-EC. MDR patterns that had expected support (reflecting pattern frequency) and conditional lift (reflecting association strength) higher than expected by chance (p-value[&le;]0.05) were used to construct resistance networks, and analysed according to time, age and gender. FindingsThe number of isolates increased from 360 287 in 2018 (10 150 ESBL-EC, 350 137 non-ESBL-EC) to 629 017 in 2022 (18 663 ESBL-EC, 610 354 non-ESBL-EC). More MDR patterns were selected in ESBL-EC than non-ESBL-EC (2022: 1770 vs 93 patterns), with higher respective network densities (2022: 0.230 vs 0.074). Fluoroquinolone, third-generation cephalosporin and penicillin resistances were strongly associated in ESBL-EC. The median densities of resistance association networks increased from 2018 to 2022 in both ESBL-EC (0.238 to 0.302, p-value=0.06, Pearson test) and non-ESBL-EC (0.074 to 0.100, p-value=0.04). Across all years, median network densities were higher in men than women in both ESBL-EC (2022: 0.305 vs 0.276) and non-ESBL-EC (2022: 0.128 vs 0.094); they were also higher in individuals over 65 years old than under 65 in ESBL-EC (2022: 0.289 vs 0.275) and non-ESBL-EC (2022: 0.103 vs 0.088). InterpretationThese findings, which show increasing MDR associations, especially in men and older individuals, highlight the importance of ongoing resistance surveillance to understand the future evolution of resistance patterns. FundingThis work received funding from the French government through the National Research Agency project COMBINE ANR-22-PAMR-0003. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched Pubmed for previously published articles without any date or language restrictions using the search terms (multiresistan* OR "multidrug-resistan*") AND ("data mining" OR "machine learning" OR "artificial intelligence") AND (pattern* OR associat*). We found three studies that used machine learning to identify multiresistance patterns in various pathogens (chicken-associated Escherichia coli, human-associated Staphylococcus aureus and cattle-associated Salmonella enterica) in the United States. However, to our knowledge, no machine-learning studies to date have explored multiresistance patterns in human-associated Enterobacterales, especially within European contexts. Added value of this studyOur study provided a novel and detailed analysis of multiresistance patterns in community-acquired E. coli urinary tract infection collected from a French national surveillance system. Our findings confirmed that association-set mining is effective for identifying resistance associations in antibiotic resistance surveillance data. We explored the temporal evolution of resistance associations, gender-specific and age-specific differences, which to our knowledge, had not been previously analysed. Implications of all the available evidenceOur results suggest a temporal increase of resistance associations in community-acquired E. coli UTI and identify key patterns in different subpopulations. In the context of rising antibiotic resistance, optimizing the use of current medications is crucial, as few new antibiotics have been developed in the past two decades. With further research, this work could provide insight for targeted antibiotic stewardship strategies.

BackgroundAntimicrobial resistance (AMR) surveillance is essential for quantifying and monitoring the burden of AMR among World Health Organization (WHO) priority pathogens. We analysed Tunisian AMR surveillance system (TARSS) data across five sentinel hospitals from 2014 to 2022. MethodsWe conducted a retrospective isolate-level analysis for Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter spp. Temporal, ward, and specimen associations were quantified using multivariable logistic regression models. Sex and age categories were explored in secondary models due to missingness. Temporal trends were assessed using Cochran-Armitage test, and co-resistance was summarised for third-generation cephalosporin and carbapenem phenotypes. We also evaluated temporal dynamics of 3GCR and CR profiles. ResultsA total of 35,525 E. coli, 14,325 K. pneumoniae, 9,679 P. aeruginosa, and 5,597 Acinetobacter spp. were reported to TARSS between 2014 and 2022. Mean annual MDR prevalence was high for Acinetobacter spp. (85.1%), moderate for K. pneumoniae (45.5%) and for P. aeruginosa (27.1%), and lower for E. coli (17.5%). Adjusted models indicated increased odds of resistance to several antibiotics, whereas E. coli showed decreased odds. Intensive care unit (ICU) and blood isolates were associated with higher odds of resistance in all pathogens. ConclusionThis nine-year multi-hospital analysis reveals a high prevalence of AMR across the four WHO priority pathogens, settings, and specimen types, with increasing resistance for some pathogen-antibiotic combinations. The higher odds of clinically important resistance amongst ICU and blood isolates support the use of ward-level antibiograms and stratified stewardship and infection prevention measures.

BackgroundThe overuse and misuse of antimicrobials contribute significantly to antimicrobial resistance (AMR), which is a global public health concern. India has particularly high rates of antimicrobial resistance, posing a threat to effective treatment. The WHO AWaRe classification system was introduced to address this issue and guide appropriate antibiotic prescribing. However, there is a lack of studies examining the prescribing patterns of antimicrobials using the AWaRe classification, especially in North India. Therefore, this study aimed to assess the prescribing patterns of antimicrobials using the WHO AWaRe classification in a tertiary care centre in North India. AimTo study the prescribing patterns of antimicrobials using WHO AWaRe classification through a cross-sectional study in AIIMS Rishikesh. MethodsA descriptive, cross-sectional study was conducted from July 2022 to August 2022 at a tertiary care hospital. Prescriptions containing at least one antimicrobial were included in the study. Data on prescriptions, including patient demographics, departments, types of antimicrobials prescribed, and duration of treatment, were collected. A questionnaire-based survey was also conducted to assess the knowledge and practices of prescribing doctors regarding the utility of AWaRe classification. ResultsA total of 123 patients were included in the study, with antibiotic prescriptions being written for all of them. Most prescriptions were for inpatients, evenly distributed between Medicine and Surgical departments. Metronidazole and Ceftriaxone were the most prescribed antibiotics. According to the AWaRe classification, 57.61% of antibiotics fell under the Access category, 38.27% in Watch, and 4.11% in Reserve. The majority of Access antibiotics were prescribed in the Medicine department, while Watch antibiotics were more common in the Medicine department as well. The questionnaire survey showed that only a third of participants were aware of the AWaRe classification, and there was a lack of knowledge regarding antimicrobial resistance and the potential impact of AWaRe usage. ConclusionThis study highlights the need for better antimicrobial prescribing practices and increased awareness of the WHO AWaRe classification and antimicrobial resistance (AMR) among healthcare professionals. The findings indicate a high proportion of prescriptions falling under the Access category, suggesting appropriate antibiotic selection. However, there is a significant difference between the WHO DDD and the prescribed daily dose in the analysed prescriptions suggesting overuse and underuse of antibiotics. There is room for improvement and educational interventions and antimicrobial stewardship programs should be implemented to enhance knowledge and adherence to guidelines, ultimately contributing to the containment of antimicrobial resistance.

BackgroundAntimicrobial Resistance (AMR), a major global public health threat causing 1.2 million deaths, calls for immediate action. Antimicrobial stewardship (AMS) promotes judicious antibiotic use, but the COVID-19 pandemic increased AMR by 15%. Our study evaluated AMS implementation and inappropriate antibiotic prescribing before-the-pandemic (PD) and during-the-pandemic (DP). MethodsThis retrospective study examined medical records of adult patients (age 25 and above) admitted to an NHS Foundation Trust in England for respiratory tract infections (RTIs) or pneumonia in 2019 and 2020. Our objective was to evaluate antibiotic prescribing practices BP and DP in 2019 and 2020. Primary outcomes included evaluating the prevalence of inappropriate antibiotic prescribing and assessing the implementation of AMS using Public Health Englands Start Smart, Then Focus (SSTF) toolkit. Reliable data extraction was ensured by two independent reviewers using a validated data extraction tool. ResultsA total of 640 patient records (320 from 2019 and 320 from 2020) were analysed. The mean age of enrolled adults was 74.3 years in 2019 and 76.2 years in 2020. COVID pneumonia showed a significantly higher odds ratio (OR) of 20.24 (95% CI 5.82 to 128.19, p-value<0.001). Inappropriate antibiotic prescribing, as per local guidelines, increased from 36% in 2019 to 64% in 2020 for the second course of antibiotics DP. Differences were observed in AMS interventions, with an OR of 3.36 (95% CI 1.30-9.25, p=0.015) for Continue Antibiotics and an OR of 2.77 (95% CI 1.37-5.70, p=0.005) for De-escalation. ConclusionThe COVID-19 pandemic significantly impacted antibiotic prescribing, increasing inappropriate use and posing risks of antimicrobial resistance. Factors influencing prescribing practices must be considered, and proactive measures, including updating the SSTF toolkit and developing an AMS roadmap, are needed to address the challenges of AMR in the context of evolving infectious diseases. KEY MESSAGESO_ST_ABSWHAT IS ALREADY KNOWN ON THIS TOPICC_ST_ABSO_LI{Rightarrow} AMR is a major global health threat, called a silent pandemic, with the potential for 10 million annual deaths by 2050, equivalent to one death every three seconds. C_LIO_LI{Rightarrow} Antimicrobial stewardship (AMS), promoting judicious antibiotic use, plays a pivotal role in combating AMR. C_LIO_LI{Rightarrow} The COVID-19 pandemic led to a 15% rise in AMR and hospital-associated deaths during 2020. C_LI WHAT THIS STUDY ADDSO_LI{Rightarrow} Evaluated the implementation of AMS before and during the COVID-19 pandemic in 2019 and 2020 across four seasonal time points. C_LIO_LI{Rightarrow} Estimated the prevalence of inappropriate antibiotic prescribing in 2019 and 2020. C_LIO_LI{Rightarrow} Identified factors influencing antibiotic prescribing upon admission and during the hospital stay. C_LI HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE AND/OR POLICYO_LI{Rightarrow} Our study offered a comprehensive analysis of AMS implementation and identified the key factors that influence antibiotic prescribing and AMS application BP and DP. This critical understanding will be instrumental in shaping a strategic plan intended to improve antibiotic prescribing practices in acute care settings, thereby directing necessary updates and revisions in current policies. C_LI

Antibiotic-resistant Pseudomonas aeruginosa is a common nosocomial pathogen all over the world. We detected the presence of P. aeruginosa in 22% (53 out of 238) of the test samples collected from patients with infections including secondary wound infections, abscesses and urinary tract infections admitted to two academic hospitals in Bangladesh. Resistance to carbapenems (imipenem, and meropenem) was present among 30% (16 out of 53) of these clinical P. aeruginosa isolates, which is more than 2-fold higher compared to that of previous studies. Such a rapid increase in carbapenem resistance was mediated by metallo-{beta}-lactamase (MBL). Expression of MBL was detected in 90% (14 out of 16) of these resistant isolates. Molecular analyses revealed that the carbapenem-resistant isolates carried at least one of the MBL variants, either bla-VIM or bla-NDM-1. All the bla-NDM-1 positives carried a 0.5 MDa plasmid. ERIC-PCR revealed the highly heterogeneous nature of the P. aeruginosa isolates indicating multiple sources of infection within the hospital. However, the majority of XDR isolates belonged to a single cluster of drug-resistant bacterial infections. These findings indicate that Metallo-{beta}-lactamase (MBL) mediated resistance to carbapenem in P. aeruginosa poses a serious threat to the spread of infections among hospitalized patients.

ObjectiveRoutine use of whole genome sequencing (WGS) has been shown to help identify transmission of pathogens causing healthcare-associated infections (HAIs). However, the current gold standard of short-read, Illumina-based WGS is labor and time-intensive. In light of recent improvements in long-read Oxford Nanopore Technologies (ONT) sequencing, we sought to establish a low resource utilization approach capable of providing accurate WGS-based comparisons of HAI pathogens within a time frame allowing for infection prevention and control (IPC) interventions. MethodsWGS was prospectively performed on antimicrobial-resistant pathogens at increased risk of potential healthcare transmission using the ONT MinION sequencer with R10.4.1 flow cells and Dorado basecalling algorithm. Potential transmission was assessed via Ridom SeqSphere+ for core genome multilocus sequence typing and MINTyper for reference-based core genome single nucleotide polymorphisms using previously published cut-off values. The accuracy of our ONT pipeline was determined relative to Illumina-based WGS data generated from the same genomic DNA sample. ResultsOver a six-month period, 242 bacterial isolates from 216 patients were sequenced by a single operator. Compared to the Illumina gold-standard data, our ONT pipeline achieved a Q score of 60 for assembled genomes, even with a coverage rate of as low as 40X. The mean time from initiating DNA extraction to complete genetic analysis was 2 days (IQR 2-3.25 days). We identified five potential transmission clusters comprising 21 isolates (8.7% of all sequenced strains). Combining ONT WGS data with epidemiological data, >70% (15/21) of the isolates originated from patients with potential healthcare transmission links. ConclusionsVia a stand-alone ONT pipeline, we detected potentially transmitted HAI pathogens rapidly and accurately, aligning closely with epidemiological data. Our low-resource method has the potential to assist in the efficient detection and deployment of preventative measures against HAI transmission.

BackgroundAntimicrobial resistance (AMR) is a major global health threat, with sub-Saharan Africa bearing a disproportionate burden. Community-level antibiotic dispensing practices remain poorly described in Kenya outside Nairobi. MethodsA total of 504 antibiotic dispensing events were prospectively recorded across 22 community pharmacies in Kakamega County, western Kenya, between 3rd and 22nd August 2025. Data collected included dispensing source (over-the-counter [OTC] versus prescription), clinical indication, antibiotics dispensed, course completion, and self-reported repeat antibiotic use within the preceding month. Descriptive analyses were performed, and {chi}2 tests were used to examine associations between dispensing source and selected non-antibiotic dispensing characteristics. ResultsOf the 504 dispensing events, 224 (44.4%) involved OTC dispensing and 278 (55.2%) were prescription-based. The most frequent indications for antibiotic dispensing were upper respiratory tract infections (URTI; n = 156, 31.0%), lower respiratory tract infections (LRTI; n = 95, 18.8%), gastrointestinal infections (n = 65, 12.9%), and skin or soft-tissue infections (n = 55, 10.9%). Across all events, amoxicillin, azithromycin, and metronidazole were the most frequently dispensed antibiotics, with broad-spectrum agents--including fluoroquinolones and cephalosporins--commonly used for lower respiratory tract infections, urinary tract infections, and sepsis. Partial antibiotic courses were supplied in 33 (6.5%) dispensing events, most commonly due to financial constraints (15/33, 45.5%). Self-reported antibiotic use within the preceding month occurred in 156 (31.0%) cases. ConclusionsOTC antibiotic access remains widespread in Kakamega County, with substantial use of broad-spectrum agents across multiple clinical indications. Financial barriers contribute to incomplete antibiotic courses. These findings highlight the importance of incorporating community pharmacy dispensing data into county-level antimicrobial stewardship programmes and informing national strategies to optimise antibiotic use.

Antimicrobial stewardship (AMS), the evidence-based use of antimicrobials, is an effective strategy in controlling antimicrobial resistance (AMR) in humans by reducing the irrational use of antimicrobials. Stewardship in children is less studied. This study assessed the knowledge, attitude, and practice of physicians prescribing antibiotics to children in Bayelsa State, Nigeria to identify gaps in AMS and possible solutions. Following ethical approval, a semi-structured questionnaire was distributed among 40 paediatricians and gynaecologists at the two public tertiary healthcare facilities in Bayelsa State - the Niger Delta University Teaching Hospital and the Federal Medical Centre - for self-completion. Responses were expressed as percentages and analyzed using Blooms cutoffs. The Capability, Opportunity, Motivation, and Behaviour (COM-B) model was employed to identify gaps for intervention in prescribing behavior with gaps in each component identified by aggregate scores <80%. Perceived approaches to improve prescribing among 14 selected options were assessed using 5-point Likert scales and options with scores >90% rated the most acceptable. Questionnaires were administered from August to September 2021. The response rate was 68% (27/40). Participants were paediatricians (81%, 22/27) and gynaecologists (19%, 5/27). Antimicrobial Susceptibility Testing (AST) was not performed before antibiotic selection nine times out of 10 (89%, 24/27). In a third (37%, 10/27) of cases, 2-3 antibiotics were prescribed. The top three antibiotics, in rank order, were: cefuroxime or amoxicillin 41% (11/27); ciprofloxacin or amoxicillin 30% (8/27), and azithromycin (33%, 9/27). Aggregate COM-B scores were: capability, 74%; opportunity, 78%; and motivation, 87%. The most acceptable (100%, 27/27) options to improving antibiotic prescribing were: availability of resistance data, availability of guidelines, readily accessible microbiological data, and easy access to infectious disease physicians. There are gaps in knowledge of AMR and opportunity for rational prescribing. There is need for antimicrobial resistance data to promote pediatric AMS at the surveyed healthcare facilities.

BackgroundThe World Health Organization (WHO) (AWaRe (Access/Watch/Reserve) book gives detailed guidance on the optimal use of antibiotics across primary care and hospitals for adults and children with the aim of improving the quality of use. ObjectivesTo develop universally applicable, model sets of appropriate and feasible quality indicators based on the WHO AWaRe system for primary care, hospital, and general indicators for optimal antibiotic use. MethodsIndicators from a scoping review were revised to focus on clinical infections in the AWaRe book. They were assessed using consensus techniques through two rounds each of the Global Delphi Technique and RAND/UCLA Appropriateness Method, evaluating appropriateness and feasibility at national and global levels respectively. In Round 1 of each method, panellists rated clarity and suggested revisions or new indicator. Round 2 results are reported. FindingsThere were 102 quality indicators (Primary Care: 46; Hospital: 39; General: 17) included in Round 2 of the Delphi Technique and 136 indicators (Primary Care: 56; Hospital: 60; General: 20) in Round 2 of the RAND/UCLA method, which are presented as model sets of indicators. From these broad sets, 12 indicators from the Delphi Technique and 31 indicators from the RAND/UCLA method were rated both appropriate and feasible with agreement respectively. ConclusionThese model AWaRe-based, universally applicable quality indicators can be locally adapted to improve the optimal use of antibiotics and inform global and country specific antimicrobial stewardship programs (AMS).

BackgroundPromoting the responsible use of antimicrobials is essential in tackling antimicrobial resistance. However, data on consumption and usage of antibiotics in Sub-Saharan Africa are still limited. MethodsThis was a prospective cross-sectional time series study conducted to investigate the consumption and use of third-and fourth-generation cephalosporins and fluoroquinolones in North Western Tanzania. We collect stock records from outpatient pharmacies in the hospital and conducted exist interviews each month from April to September 2021.We did descriptive analysis in Stata and Ms Excel. ResultsA total of 982586.2 DDD were consumed with a daily consumption of 1198.5 DDD per 1000 inhabitants per day over the six months. Five classes of antibiotics accounted for 70% of consumption. Beta lactams penicillins (J01C) are the most consumed at 329.25 DDD followed tetracyclines(J01A) 243.85 DDD. By WHO AWaRe Access antibiotics constituted 75%. Of the 253 interviews conducted 131 (51.8%) of the patients were male, 192 (75.9%) patients had bacterial infection as an indication. Ceftriaxone, was the most used cephalosporin and was used mostly to treat pneumonia while ciprofloxacin was the most used fluoroquinolone and was widely but mostly used for UTI and gastrointestinal infections. Up to 44% of prescriptions do not adhere to treatment guidelines. ConclusionWe report that antibiotic consumption is in concordance WHO recommendation to have >60% of antibiotics consumed from the access group. However, there is relatively high consumption of ciprofloxacin and ceftriaxone in this hospital. Additionally, there, was significant non-adherence to treatment guidelines which underscores the need to establish functioning and robust antimicrobial stewardship programs. Posted historyNONE

Antimicrobial resistance (AMR) to all antibiotic classes has been found in the pathogen Staphylococcus aureus. The reported prevalence of these resistances vary, driven by within-host AMR evolution at the patient level, and between-host transmission at the hospital level. Without dense longitudinal sampling, pragmatic analysis of AMR dynamics at multiple levels using routine surveillance data is essential to inform control measures. We explored S. aureus AMR diversity in 70,000 isolates from a UK paediatric hospital between 2000-2020, using electronic datasets containing multiple routinely collected isolates per patient with phenotypic antibiograms, hospitalisation information, and antibiotic consumption. At the hospital-level, the proportion of isolates that were meticillin-resistant (MRSA) increased between 2014-2020 from 25 to 50%, before sharply decreasing to 30%, likely due to a change in inpatient demographics. Temporal trends in the proportion of isolates resistant to different antibiotics were often correlated in MRSA, but independent in meticillin-susceptible S. aureus. Ciprofloxacin resistance in MRSA decreased from 70% to 40% of tested isolates between 2007-2020, likely linked to a national policy to reduce fluoroquinolone usage in 2007. At the patient level, we identified frequent AMR diversity, with 4% of patients ever positive for S. aureus simultaneously carrying, at some point, multiple isolates with different resistances. We detected changes over time in AMR diversity in 3% of patients ever positive for S. aureus. These changes equally represented gain and loss of resistance. Within this routinely collected dataset, we found that 65% of changes in resistance within a patients S. aureus population could not be explained by antibiotic exposure or between-patient transmission of bacteria, suggesting that within-host evolution via frequent gain and loss of AMR genes may be responsible for these changing AMR profiles. Our study highlights the value of exploring existing routine surveillance data to determine underlying mechanisms of AMR. These insights may substantially improve our understanding of the importance of antibiotic exposure variation, and the success of single S. aureus clones.

BackgroundThere has been an increment in the resistance of microorganisms to various antibiotics used in regional hospitals in the Ashanti region of Ghana and the country. This has led to difficulty in selecting agents to treat patients without the associated increment in side effects, the astronomical increase in the cost of medical care and a longer duration of hospitalization. In this study, we analyze the pattern of antibiotic use in a district hospital using the WHO AWaRe recommendation. ObjectivesTo ascertain the general pattern of antibiotic use with reference to the Access, Watch and Reserve Classes using the selected parameters (year of visit and patient demographics) and to confirm if the standard set by the WHO with respect to Access Class antibiotics is met. MethodFiles of patients, in 2021 and 2022, were systematically sampled from the database of SDA Hospital - Kwadaso (the hospital involved), and data concerning the visits for which antibiotics were administered were extracted to carry out the analysis required. The data extracted included the year of visit, demographics of the patients involved (patient status, age and sex) and the antibiotics that were administered. ResultsThis study seeks to ascertain the distribution of antibiotics used across the two years in the hospital of interest using the 2021 WHO AWaRe (Access, Watch and Reserve Antibiotics) Classification. Ultimately, the value, in percentage, of the distribution of the antibiotics used in the Access class will be compared to the target of at least 60% of the total antibiotic consumption being Access group antibiotics as recommended by WHO.

BackgroundAntimicrobial drug resistance is of public health importance due to its potential to reduce treatment options and increase healthcare expenditure. There is, however, a paucity of studies that have examined antimicrobial resistance in countries with poor to moderate income. The present study examined the patterns and predictors of antimicrobial resistance in Staphylococcus isolates collected from humans at diagnostic laboratories in South Africa between 2012 and 2017. Method and materialsA cross-sectional study design using retrospective data of 404 217 diagnostic laboratory records of staphylococcal isolates collected between 2012 and 2017 was adopted in this study. Isolates were assessed for antimicrobial drug resistance against 24 antimicrobials. Descriptive statistics, and binary logistic regression models were used to analyse the data. Significance was assessed at < 0.05. ResultsThe highest resistance was observed against Cloxacillin (70.3%), while the lowest resistance was against Colistin (0.1%). A significant (p < 0.05) decreasing trend in AMR was observed over the study period, while a significant increasing temporal trend (p < 0.05) was observed for MDR over the same period. A Significant (p < 0.05) association was observed between specimen type, species of organism, and year of isolation with AMR outcome. Significant (p < 0.05) associations were observed between specimen type and season, with MDR. Discussion and recommendationsThe observed high levels of AMR and the increasing temporal trend in MDR is of public health concern. Clinicians should consider these findings when deciding on therapeutic options. Continued monitoring of AMR among Staphylococcus spp. and judicious use of antimicrobials in human medicine should be promoted.

Linezolid resistance has become a focal point worldwide, particularly as linezolid stands as one of the last resort antibiotics against multiple-drug resistant bacterial strains. Despite its critical importance, the situation in Egypt remains relatively unexplored. As various linezolid resistance mechanisms have been identified in staphylococci, our investigation aims to uncover the molecular characteristics of staphylococci showing reduced susceptibility to Linezolid at Kasr-El-Eini Teaching Hospital. Thirty isolates were investigated in this study. The selected samples, identified by Vitek 2 system and confirmed by 16S rRNA, were examined by disc diffusion method. Of the 30 isolates, two were confirmed as linezolid resistant and screened for the presence of cfr gene and mutations in the Domain V of the 23S rRNA gene. Both of the studied strains, identified as Staphylococcus haemolyticus, SZ-2 and SZ-7 harbored two point mutations G2576T and G2602T in the Domain V of the 23S rRNA gene. A novel G2694C mutation reported for the first time was detected in strain SZ-7. The presence of cfr gene was confirmed in both isolates. Linezolid-resistant Staphylococcus haemolyticus had emerged in ICU patients with prior antibiotic exposure. The exact role of the novel G2694C mutation in linezolid resistance needs further investigations. The study underscores the importance of proper surveillance of cfr-carrying strains in the healthcare settings in Egypt.

BackgroundHospital-acquired infections (HAIs) remain a global public-health concern, particularly in low- and middle-income countries where infection-prevention resources are limited. Surgical-site infections (SSIs) and urinary-tract infections (UTIs) are among the most frequent HAIs and contribute to increased morbidity and healthcare costs. Genomic surveillance provides insights into the diversity, antimicrobial resistance (AMR), and virulence potential of causative bacteria. MethodsFour bacterial isolates collected from Tanzanian healthcare facilities were analysed: Pseudomonas aeruginosa SS01 and SS89 (from SSIs), Alcaligenes faecalis UP17 (from a UTI), and Lysinibacillus sphaericus SS48 (from an SSI). Genomic DNA was extracted and sequenced on the Illumina platform. Reads were quality-filtered and assembled de novo using SPAdes. Genomes were annotated with Prokka. AMR genes were identified using AMRFinderPlus, CARD-RGI, and ResFinder. Virulence determinants were detected using VFDB. P. aeruginosa isolates were typed by multilocus sequence typing (MLST). Phylogenetic analysis based on single-nucleotide polymorphisms (SNPs) was performed using Snippy and IQ-TREE, and trees were visualised with iTOL. ResultsGenome sizes ranged between approximately 6.0 and 6.7 Mb with GC contents consistent with species references. MLST revealed two distinct P. aeruginosa sequence types: SS01 was closest to ST2317 (incomplete ppsA locus) and SS89 matched ST4714, indicating non-clonal origins. AMR screening detected {beta}-lactamase, aminoglycoside-modifying enzyme, and efflux-pump genes in P. aeruginosa, multidrug-efflux genes in A. faecalis, and intrinsic resistance determinants in L. sphaericus. Virulence-factor profiling identified type III-secretion, quorum-sensing, and biofilm-formation genes in P. aeruginosa; adhesion and stress-tolerance genes in A. faecalis; and sporulation and surface-adhesion genes in L. sphaericus. Phylogenetic analysis positioned the Tanzanian isolates as unique local lineages distinct from global references. ConclusionsThis study demonstrates the genomic diversity and complex AMR mechanisms of clinically important bacteria in Tanzania. The coexistence of resistance and virulence determinants underscores the need for routine genomic surveillance and strengthened antimicrobial-stewardship programs.

We investigated the genomic epidemiology of Ambler class C (AmpC-type) {beta}-lactamases in Enterobacter spp. and Klebsiella aerogenes in the national carbapenemase-producing Enterobacterales (CPE) surveillance of the Netherlands between 2012 and 2023. A total of 399 E. cloacae complex and K. aerogenes isolates from 399 patients were analyzed using whole-genome sequencing to assess genetic relatedness, resistance gene profiles, plasmid replicons, and the genomic location of AmpC-genes, respectively. Of the 399 patients, 217 were male (54%), and the median age was 67 years. Carbapenemase production was assessed using the carbapenem inactivation method (CIM) and CarbaNP-test. Considerable proportions of Enterobacter spp. (32%) and K. aerogenes (52%) isolates produced carbapenemase, without detectable major carbapenemase genes (IMP, KPC, NDM, OXA-48-like, VIM), a phenotype termed CIM+Carba-. These isolates were mostly (82%) susceptible (EUCAST [&le;]2mg/L) to meropenem. The majority of CIM+Carba+ isolates with major carbapenemase genes were gained from pre-emptive screening, while CIM+Carba-isolates were mainly taken for diagnostic purposes. Genomic analysis identified 18 genogroups, with E. kobei, E. roggenkampii, E. ludwigii, and K. aerogenes showing the CIM+Carba-phenotype, correlating with chromosome-encoded AmpC-type {beta}-lactamases like blaACT-28, blaACT-52, blaMIR-3, blaMIR-11 or ampC of which the majority (63%) yielded a positive CarbaNP. These CIM+Carba-isolates carried only few plasmids, and there was limited nosocomial spread. CIM+Carba-E. kobei carrying blaACT-28 overproduced ACT-28 protein in the CIM. Overall, the Enterobacter and K. aerogenes population in the Netherlands is genetically diverse, with most isolates carrying species-specific AmpC-type {beta}-lactamases with putative carbapenemase activity and represent a low-risk for public health. ImportanceCPE represents an important healthcare problem worldwide. This study highlights the diverse genetic Enterobacter spp. population in the Dutch CPE surveillance with E. hormaechei subsp. steigerwaltii as the most common carbapenemase-producing (CIM+Carba+) species. However, a significant proportion of E. kobei, E. roggenkampii, E. ludwigii, and K. aerogenes obtained in the Netherlands carry chromosomal AmpC-type {beta}-lactamases with putative carbapenemase activity in the absence of major carbapenemases (CIM+Carba-), were mostly susceptible for meropenem, and showed limited nosocomial spread. We recommend whole-genome sequencing for accurate Enterobacter/K. aerogenes species classification, and AmpC-type {beta}-lactamase gene identification. Despite limited carbapenem resistance and dissemination, proper infection control measures are necessary. The work outlined here underscores the importance of distinguishing E. kobei, E. roggenkampii, E. ludwigii, and K. aerogenes isolates and its AmpC-type {beta}-lactamases from true CPE by whole-genome sequencing to avoid misclassification and unnecessary infection prevention and public health interventions.