Objective:Neisseria gonorrhoeae is a common bacterium responsible for sexually transmitted infections. The WHO recommends the use of 1 g ceftriaxone to treat gonococcal infections. However, ceftriaxone-resistant strains are emerging, and carbapenems may be the last remaining treatment option. Methods:We compared MICs for ceftriaxone, ertapenem, imipenem and meropenem in a collection of 81 clinical isolates and nine WHO reference isolates with various penA alleles. This previously characterized collection included nine ceftriaxone-resistant isolates. It was selected to include 42 different penA alleles (27 non-mosaic and 15 mosaic), 26 TEM penicillinase-producing isolates, five MDR and four XDR isolates. Results:The MICs of ceftriaxone, ertapenem, imipenem and meropenem ranged from <0.002 to 2 mg/L, <0.002 to 0.064 mg/L, 0.008 to 1 mg/L and 0.002 to 0.125 mg/L, respectively. In ceftriaxone-resistant isolates, the MIC50 of ertapenem, imipenem and meropenem were 0.012 mg/L (0.004-0.032 mg/L), 0.75 mg/L (0.125-1 mg/L) and 0.032 mg/L (0.016-0.064 mg/L), respectively. For all antibiotics, MICs were significantly higher in isolates with a mosaic penA allele (P-value <0.001). No significant difference in carbapenem MICs was found between isolates with and without a TEM beta-lactamase. Conclusions:Carbapenem MICs remain low in N. gonorrhoeae isolates but are higher in those with mosaic penA alleles than in those with non-mosaic penA alleles. MICs for ertapenem are lower than those for other carbapenems, supporting its use for the treatment of infections with ceftriaxone-resistant N. gonorrhoeae. However, the establishment of breakpoints for carbapenem resistance in N. gonorrhoeae is required.
Introduction:Inappropriate selection and dosing of antimicrobial prophylaxis (AP) for urological procedures remain common. We therefore evaluated the impact of a locally adapted AP guideline, embedded within standardized pre-procedure order sets and supported by antimicrobial stewardship interventions, on antimicrobial utilization in a high-resistance setting. Methods:A 1-year study of the three phases-pre-intervention, intervention and after intervention-was performed at a tertiary care hospital in Thailand. The intervention included development of local AP guidelines based on the institutional antibiogram, integration into one-page order sets, multifaceted education and feedback. Antimicrobial utilization was assessed using days of therapy (DOT) per 1000 patient-days. Interrupted time series (ITS) analysis was used to evaluate changes in antimicrobial use over time. Postoperative urinary tract infections (UTIs) and surgical site infections (SSIs) within 30 days were monitored. Results:A total of 657 urological procedures were included. Median total DOT per admission declined from 10 days (IQR 8-12) to 2 days (IQR 1-4) (P < 0.001). The proportion of patients receiving single-dose AP increased from 1.29% pre-intervention to 33.66% post-intervention (P < 0.001). ITS analysis demonstrated a significant immediate reduction in weekly total DOT per 1000 patient-days following intervention implementation (level change -3156.8; 95% CI -4604.7 to -1708.9), with no significant change in slope. The incidence of SSI and UTI remained below 1% across all periods. Conclusions:Implementation of locally tailored AP guidelines integrated into standardized order sets, supported by stewardship interventions, was associated with a substantial and sustained reduction in antimicrobial exposure for urological procedures. This approach is relevant to high-resistance, resource-limited settings.
Objectives:Unconfirmed penicillin allergy labels restrict antibiotic options and drive deviation from antimicrobial guidelines. To address this, we established an infection-embedded penicillin allergy de-labelling (PADL) service embedded within existing infection-liaison touchpoints (microbiology meetings, advice calls and infection reviews) to target patients with active infection needs. Methods:We performed a retrospective analysis of all 189 referrals to our PADL service (March 2022 to December 2025), nested within a baseline prevalence review of 218 375 admissions. Furthermore, to quantify the clinical cost of allergy labels, we surveyed infection experts, using 20 clinical vignettes, to determine prescribing variance had de-labelling not occurred. Results:Of patients, 82.5% (156/189) were classified as having acute, complex or recurrent infection; 45% (85/189) were directly de-labelled, while 41.8% (79/189) were excluded by low-risk criteria prompting specialist referral for full penicillin allergy testing. Critically, for patients on active therapy, de-labelling triggered an immediate regimen change in 84.1%, driving a 43% intravenous-to-oral switch rate, a mean reduction of 0.7 antibiotics per patient and significantly reducing antibiotic spectrum coverage (P = 0.0004). Expert review of vignettes revealed only minimal concordance on alternative regimens (Fleiss' kappa 0.28) had we not de-labelled, implying that persistent labels lead to non-standardized prescribing. Conclusions:Infection-embedded de-labelling is a high-yield intervention that can deliver immediate stewardship returns in patients with active infection needs. A caveat is that a significant proportion of excluded patients require specialist allergy referral, carrying resource implications and underscoring the need for careful planning with local allergy services at inception of 'low-risk' pathways.
Background and objectives:Antifungal resistance represents an increasing global threat, driven by the rising burden of fungal disease. Antifungal stewardship (AFS) is a critical component of broader antimicrobial resistance (AMR) efforts, but education in this area remains less established than antibacterial stewardship initiatives. The scope and characteristics of the current landscape of online AFS resources have not yet been systematically described. To identify and evaluate online educational resources focused on fungal disease management and AFS, and assess their accessibility, format, educational design and implementation focus. Methods:A structured search of internet search engines, distribution platforms and organizational websites was conducted to identify English-language web-based resources related to fungal disease management and stewardship. Resources were evaluated using predefined criteria including access model, format, length, educational design, interactivity and AFS content. An overall educational value score (1-10) was assigned. Results:Twenty-three educational resources were identified. Most were delivered as online unfacilitated courses (11, 48%) and were short (<4 h) (12, 52%). Most focused on guidelines and syndromic management (18, 78%) and targeted doctors and/or nurses/midwives (22, 96%). Limited interactivity was reported in nine (39%) courses. Five courses (22%) had either a substantial or comprehensive focus on AFS. Conclusions:Online AFS educational resources are available and support awareness and knowledge development. However, they remain relatively few in number. Greater emphasis on implementation-focused learning, behaviour change components and broader global representation may enhance their impact.
Objectives:Central nervous system (CNS) infections in children require rapid diagnostic evaluation and prompt empiric antimicrobial therapy. However, clinical presentation is often non-specific, leading to frequent use of broad-spectrum antibiotics while awaiting cerebrospinal fluid (CSF) results. We evaluated antibiotic treatment modifications during the diagnostic work-up and quantified changes in antibiotic spectrum coverage (ASC) before and after lumbar puncture (LP). Patients and methods:We conducted a retrospective single-centre study including children <18 years who underwent LP for suspected CNS infection between January 2016 and December 2024. CSF was analysed using the BioFire® FilmArray® Meningitis/Encephalitis (ME) Panel. Antibiotic treatment modifications after LP-related diagnostic information became available were assessed descriptively. Paired ASC scores before and after LP were compared using the Wilcoxon signed-rank test among treated children. Results:Among 1198 children undergoing LP, 730 (60.9%) received antibiotic therapy. Antibiotic use was highest in neonates (227/246; 92.3%) and infants aged 29 days to <6 months (118/140; 84.3%) and lowest in adolescents (106/329; 32.2%). Treatment was modified after LP-related diagnostic information became available in 412/1198 children (34.4%). Among treated children, 313 (42.9%) underwent de-escalation, 99 (13.6%) escalation and 318 (43.6%) had no change. Overall, mean ASC decreased from 8.5 before LP to 6.6 afterwards (ΔASC -1.9; P < 0.001). Conclusions:LP-related diagnostic information was associated with frequent antibiotic treatment modification and reduced antibiotic spectrum coverage. These findings support integrated CSF diagnostics, including multiplex polymerase chain reaction, as a component of antimicrobial stewardship in children with suspected CNS infection.
Background:The global health threat of antimicrobial resistance involves the human, animal and environmental sectors. Data from Cameroon are scarce. Objectives:This study aimed to define extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-Ec) rates and associated risk factors across the three sectors in Douala, Cameroon, and to define molecular characteristics of isolates. Methods:From June 2022 to May 2023, we collected blood cultures from hospitalized patients, rectal swabs from healthy pregnant women, caeca from broiler chickens and environmental wastewater. Samples were screened for ESBL-Ec using CHROMAgar™ ESBL and cefotaxime-supplemented Tryptone Bile X-glucuronide agar. Antimicrobial susceptibility testing was performed by disk diffusion following EUCAST guidelines. Whole-genome sequencing was carried out using Illumina technology. Results:Of 628 samples, 374 yielded ESBL-Ec. Prevalence was 54.6% (131/240) in pregnant women, 70.4% (169/240) in chickens and 93.1% (67/72) in wastewater. The proportion of ESBL-Ec among E. coli-positive-blood cultures was 9.2% (7/76). Multi-family household living was independently associated with ESBL-Ec carriage among pregnant women (adjusted odds ratio = 1.7, 95% CI 1.0-3.1, P = 0.03). High co-resistance (>70%) was observed for tetracycline, ciprofloxacin and trimethoprim/sulfamethoxazole. Sequencing of 32 isolates revealed 45 distinct resistance genes, including blaCTX-M-15 (n = 13, 40.6%), blaCTX-M-55 (n = 11, 34.4%) and last-resort antibiotic resistance genes mcr-1 and bla OXA-181. High-risk sequence types included ST131 (pregnant women) and ST10 (chickens). Notably, ST48 was shared between pregnant women and chickens, and ST155 between pregnant women and wastewater. Conclusion:Cross-sectoral ESBL-Ec in Douala exhibits high genomic diversity and alarming resistance. The occurrence of last-resort genes requires immediate One Health surveillance and coordinated interventions.
Background:Antimicrobial resistance (AMR) is a major global health concern. Japan's National Action Plan on AMR, initiated in 2016, aims to reduce antimicrobial consumption. Although overall antimicrobial consumption has declined, detailed data on the clinical appropriateness of outpatient antibiotic prescriptions remain limited. We evaluated longitudinal changes in the quality and patterns of outpatient antibiotic prescribing in Japan between 2016 and 2022. Methods:This multicentre cross-sectional chart review was conducted in Aichi Prefecture and included acute-care hospitals with antimicrobial stewardship teams. Outpatient visits with antibiotic prescriptions in 2016, 2019 and 2022 were identified, and 1000 visits per year were randomly sampled. Electronic medical records were reviewed to extract patient and prescription characteristics and to assess the appropriateness of antibiotic selection based on the recorded diagnoses. Results:Among 1 177 552 outpatient visits with antibiotic prescriptions, 2987 randomly sampled visits from 34 hospitals were analysed. Treatment prescriptions decreased (from 58.8%-46.1%), whereas medical prophylaxis increased (from 16.8%-33.4%), largely driven by trimethoprim-sulfamethoxazole use. The use of third-generation cephalosporins and macrolides declined, whereas trimethoprim-sulfamethoxazole became the most frequently prescribed antibiotic by 2022. Among the evaluable treatment prescriptions (n = 1083), the proportion of inappropriate prescriptions decreased from 59.2%-47.4% (P = 0.02). This improvement was mainly observed for third-generation cephalosporins, whereas macrolide and fluoroquinolone prescribing remained largely inappropriate. Conclusions:The quality of outpatient antibiotic prescribing improved during the National Action Plan period; however, persistent drug class-specific gaps indicate the need for targeted antimicrobial stewardship interventions in the post-pandemic period.
Background and objectives:Effective therapies for the treatment of uncomplicated urinary tract infections (uUTIs) are increasingly limited due to rising multidrug resistance, necessitating the development of novel antimicrobials. Gepotidacin is a first-in-class triazaacenaphthylene antibiotic that inhibits bacterial DNA gyrase and topoisomerase IV through a distinct binding site, a unique mechanism of action, and with well-balanced inhibition for most pathogens. Gepotidacin was recently approved by the FDA and MHRA for the treatment of uUTIs and by the FDA for uncomplicated urogenital gonorrhoea. This study investigated the development of resistance to gepotidacin among isolates from two Phase 3 uUTI clinical trials (EAGLE-2 [NCT04020341]/EAGLE-3 [NCT04187144]). Methods:Post-baseline isolates exhibiting a reproducible ≥4-fold increase in minimum inhibitory concentration (MIC) and non-distinct multi-locus sequence typing/pulsed-field gel electrophoresis results underwent single nucleotide polymorphism/insertion-deletion analysis. Results:Across both studies, initial MIC testing showed 58/1045 (5.6%) patients with pathogen(s) demonstrating an apparent ≥4-fold increase in post-baseline gepotidacin MIC. Analyses identified only one patient with multiple Escherichia coli isolate pairs displaying potential development of resistance to gepotidacin. While the post-baseline isolates did not meet the putative direct descendancy criteria, we have conservatively considered this a case of possible development of resistance due to the rarity of the gepotidacin target-specific mutation (ParC D79G) in the on-therapy and test-of-cure E. coli isolates. Conclusions:Collectively, results from the Phase 3 trials indicate a low incidence of resistance development to gepotidacin, with only one potential case among gepotidacin-treated patients (1/1045; 0.096%). Further research is warranted to elucidate the mechanisms underlying elevated post-baseline gepotidacin MICs.
Background:There is an absence of practical educational resources for both healthcare professionals and patients, which are crucial to support safe and consistent delivery of Outpatient Parenteral Antimicrobial Therapy (OPAT) across health systems. Objectives:To identify and appraise high-quality, free-to-access educational resources available in the English language across grey literature to support OPAT service delivery for healthcare professionals and/or patients. Methods:This review searched three grey-literature databases, conducted a targeted web search, reviewed six organizational websites and consulted international experts in OPAT service delivery to identify free-to-access educational resources published in the English language to address the educational needs of healthcare professionals and patients. Study investigators identified a final list of resources based on applied inclusion and exclusion criteria and categorized as peer-reviewed accredited, non-accredited or expert-opinion-based materials. Results:A total of 36 potential resources were identified, of which nine were selected for review. Resources were grouped into four categories; webinars and conference archives, expert-led service overviews, patient-facing information and online courses for healthcare professionals. Only two patient-directed OPAT educational materials were identified and these were based on expert opinion rather than formally accredited materials. Most resources were developed within high-income healthcare systems but offer adaptable principles that can support OPAT practice development in low- and middle-income country settings. Conclusions:The lack of readily available resources aimed at general OPAT information represents a missed opportunity in patient care and education. Addressing these educational gaps is essential to support safe, effective and sustainable OPAT service delivery and improve patient outcomes.
Background:Scalable measures that capture post-diagnostic antibiotic decisions are lacking. We developed and validated the guidance ratio (GR), a registry-based measure of post-diagnostic antibiotic decision-making. Methods:We conducted a retrospective multi-centre validation study of the GR and discontinuation ratio (DR), two registry-based indicators of post-diagnostic antibiotic decision-making in paediatric febrile urinary tract infection. Prescribing outcomes were classified using rule-based algorithms and compared with manually classified outcomes from medical record review. Indicator performance was evaluated against medical record data used as the reference standard. Results:Among 909 episodes, the GR identified guided treatment with a sensitivity of 0.78 and specificity of 1.00. Although registry-based estimates underestimated absolute values, they closely tracked temporal prescribing patterns. Calibration substantially improved agreement with manually classified outcomes. Conclusions:The GR captured clinically meaningful prescribing patterns and may support scalable monitoring of post-diagnostic antibiotic decision-making in stewardship programmes.
Background and objectives:Antimicrobial resistance is a pressing public health concern in Croatia, where antibiotic consumption exceeds the European average. Assessing the impact of education on antimicrobial resistance literacy among future prescribers is a priority, yet parallel evidence from both medicine and dentistry remains limited. Here we evaluated the effect of curriculum-based education on antimicrobial resistance literacy among Croatian medical and dental students across all study years. Methods:We used a cross-sectional survey to assess dental and medical students' attitudes towards antibiotics and antimicrobial resistance. Domains included perceptions, knowledge, confidence to prescribe and educational interest. Descriptive statistics were used coupled with statistical testing for comparison across study years. Results:A total of 692 responses were collected. Antimicrobial resistance was selected as one of the top global priorities by both medical and dental students. While AMR was broadly recognized as a global challenge, significant knowledge gains across study years were more pronounced in dental than in medical students, particularly from year 1 to subsequent years. Over 58% of final-year medical students reported feeling patient-imposed pressure to prescribe antibiotics. For fifth- and sixth-year students, a marked difference in patient communication was observed as >60% of medical students reported discussing antimicrobial resistance with patients very often, compared with only 10% of dental students. Conclusions:We showed a positive effect of education throughout the study years in both medicine and dentistry, with more evident effects in the latter. High reported pressures to prescribe coupled with a gap in communication practices were observed.
Background:Antimicrobial stewardship (AMS) in Ethiopia requires practical and scalable educational resources that can support healthcare workers in resource-limited settings. Online resources may help strengthen stewardship knowledge and implementation, but their value depends on accessibility, contextual relevance and practical utility. Objectives:To identify and appraise online AMS educational resources relevant to Ethiopia and to assess their potential contribution to AMS education and implementation. Methods:We conducted a targeted education resource review of six publicly accessible online AMS resources. Targeted searches combined antimicrobial stewardship (AMS) and antimicrobial resistance (AMR) education terms with Ethiopia, low- and middle-income country settings, toolkit, training, online course, massive open online course (MOOC), OpenWHO, FutureLearn, CDC, BSAC and WHO. Resources were evaluated for accessibility, educational design, contextual appropriateness, implementation utility and complementarity. Results:The Ethiopian national practical guide had the strongest implementation relevance because of its close alignment with local stewardship priorities and facility-level needs. WHO- and course-based resources added structured learning and broader programmatic support. Across resources, common limitations included dependence on internet connectivity, limited offline usability and insufficient locally contextualized case-based learning. Conclusions:The included resources offer complementary value for AMS education in Ethiopia, but no single resource is sufficient on its own. A blended, context-adapted approach that integrates national guidance with selected online educational resources is likely to provide the greatest educational and system-level benefit.
Objectives:This study evaluated the antimicrobial activity of ceftaroline and comparator antimicrobials against clinical isolates of Gram-positive bacteria (GPB) from paediatric patients globally and in Africa/Middle East (AfME), Asia-Pacific (APAC), Europe and Latin America (LATAM) as part of the Antimicrobial Testing Leadership and Surveillance programme between 2018 and 2023. Methods:Susceptibility and minimum inhibitory concentrations of all organisms were determined using broth microdilution methodology for ceftaroline and comparators from Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints. Results:Overall and across regions, Staphylococcus aureus (CLSI/EUCAST, ≥99.0%) and methicillin-resistant S. aureus (CLSI, ≥95.6%) demonstrated high susceptibility to ceftaroline. High susceptibility to daptomycin, linezolid, teicoplanin, tigecycline (from the FDA), trimethoprim/sulfamethoxazole and vancomycin was demonstrated against these isolates for both breakpoints. Globally and across regions, for Streptococcus pneumoniae (CLSI/EUCAST, 93.3%-100%) and penicillin-intermediate S. pneumoniae (CLSI/EUCAST, 100%), high susceptibility to ceftaroline was observed. For penicillin-resistant S. pneumoniae, higher susceptibility to ceftaroline following the CLSI (96.5%-100%) than EUCAST (74.4%-88.7%) was observed except in LATAM. High susceptibility to linezolid, levofloxacin, tigecycline and vancomycin was demonstrated against these isolates across regions from both breakpoints, whereas, for ceftriaxone, higher susceptibility following the CLSI than EUCAST was observed. For β-haemolytic streptococci, high susceptibility to ceftaroline was observed (CLSI, 100%). High susceptibility to linezolid, penicillin and vancomycin was demonstrated against these isolates from both breakpoints. Conclusions:Ceftaroline demonstrated potent activity against key GPB. This study significantly contributes to the limited current information on paediatric antimicrobial resistance patterns across AfME, APAC, Europe and LATAM.
Background:Vancomycin, as a first-line treatment for methicillin-resistant staphylococcus aureus infections, is notably nephrotoxic. Research on vancomycin nephrotoxicity in patients with moderate chronic kidney disease (CKD) is still lacking. This study aims to investigate the incidence of vancomycin-associated acute kidney injury (VA-AKI) in patients with moderate CKD and to identify associated risk factors in this specific population. Methods:This was a multicentre, retrospective, cohort study from China. Patients with estimated glomerular filtration rate (eGFR) ˂90 mL/(min·1.73 m2) who received vancomycin from January 2009 to December 2024 were included. For patients with moderate CKD and eGFR ˂60 mL/(min·1.73 m2), multivariate logistic regression analysis was used to identify the independent risk factors for VA-AKI and the prognosis of VA-AKI patients. Results:A total of 3844 patients were included, and 1194 patients had moderate CKD. The incidence of VA-AKI in patients with moderate CKD was 19.1% (228/1194). The risk of VA-AKI increased significantly with the progression of CKD stages (P = 0.003). Cardiac insufficiency (OR 1.816, 95% CI 1.320-2.500, P < 0.001), ICU admission (OR 2.018, 95% CI 1.449-2.810, P < 0.001), and duration of vancomycin therapy (OR 1.482, 95% CI 1.071-2.051, P = 0.018) were significantly and independently associated with VA-AKI in patients with moderate CKD. Conclusions:The incidence of VA-AKI in patients with moderate CKD is slightly higher than that in mixed populations (general, unselected hospitalized cohorts). This study indicates that the risk of VA-AKI increases with the severity of CKD staging. Heart failure, ICU admission, and duration of vancomycin therapy may result in a higher risk of VA-AKI occurrence.
Background:Outpatient parenteral antimicrobial therapy (OPAT) enables patients to receive intravenous antimicrobials outside hospital settings. Elastomeric infusion devices facilitate continuous antibiotic delivery; however, limited stability data and constrained aseptic unit capacity have led some services to adopt nurse-led 'fresh-fill' preparation in uncontrolled environments, which may increase microbial contamination risk. Objectives:To evaluate whether preparation of B. Braun Easypump® II elastomeric devices using Chemfort™ closed system transfer devices (CSTDs) in uncontrolled environments reduces microbial contamination compared with preparation using needles and syringes. Methods:Forty-six elastomeric devices were prepared with tryptic soy broth by eight operators across three uncontrolled rooms using either Chemfort™ CSTDs (n = 23) or needles and syringes (n = 23). Aseptic non-touch technique was followed. Devices were incubated at 32°C for 7 days before microbiological testing. Environmental monitoring included settle plates and finger dabs. Fisher's exact test was used to analyse contamination rates. Results:No contamination occurred in devices prepared using CSTDs (0/23), whereas 5/23 (22%) prepared using needles were contaminated. This difference was statistically significant (P = 0.0491). Preparation times were shorter and more consistent using CSTDs (median 26 min; range 20-40) compared with needles and syringes (median 34 min; range 22-64). Conclusions:Preparation using Chemfort™ CSTDs was associated with reduced microbial contamination and shorter preparation times compared with needle-based methods. CSTDs may provide a useful risk-reduction strategy for nurse-prepared elastomeric infusions in OPAT services, although further evaluation in larger studies is required.
Antimicrobial-resistant Gram-negative bacilli (AMR GNB) are associated with poor patient outcomes, are increasing in prevalence and are recognized by national and international public health authorities as a major threat to human health. The most common resistance elements vary by organism, but resistant Enterobacterales, Pseudomonas and Acinetobacter species have reservoirs in the human colon, natural environment and healthcare settings. Persistence of these organisms on inanimate surfaces contributes to the risk of bacterial transmission in healthcare settings. Standard infection prevention practices including hand hygiene, low-level disinfection and use of isolation precautions are effective in interrupting transmission of AMR GNB. However, the optimal use of isolation precautions is an area of active reconsideration and research. High-risk equipment, such as duodenoscopes, can be difficult to disinfect and has been associated with hospital transmission. The immunocompromised and critical care populations are at higher risk of infection and may benefit from additional infection control interventions. Innovative approaches to reduce healthcare transmission have included screening surveillance with the use of isolation or decolonization protocols, but these approaches require further study. Antimicrobial stewardship remains a key strategy to reduce the pressure to select for AMR GNB in healthcare settings and the general environment. Low-resource settings can implement existing World Health Organization infection prevention tools to reduce transmission of AMR GNB infections. Although implementation of existing infection prevention and antimicrobial stewardship strategies can limit transmission of AMR GNB infections, development of new approaches is needed to curb increasing prevalence of AMR GNB.
Background:Carbapenem-resistant Gram-negative (CRGN) pathogens-including Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii-are a major global health threat. Newer β-lactam agents including novel β-lactam/β-lactamase inhibitor combinations and other recently introduced β-lactam agents have expanded treatment options. However, although current guidelines focus on their use as targeted therapy, their role in empirical treatment of suspected bacterial sepsis remains unclear. Methods:In this review we evaluate epidemiological studies, randomized trials, comparative observational studies, international guidelines, microbiological surveillance data on CRGN infections and clinical factors supporting consideration of empirical use of newer β-lactam agents in patients with sepsis at risk for CRGN infection. Results:Carbapenem resistance epidemiology varies substantially across regions and strongly affects the likelihood of CRGN infection. Key risk factors include prior CRGN colonization or infection, recent broad-spectrum antibiotic exposure, prolonged hospitalization and healthcare contact in high-prevalence settings. In sepsis, delayed effective antimicrobial therapy-particularly in septic shock or severe immunosuppression-is associated with poorer outcomes. However, indiscriminate empirical use of newer β-lactam agents may promote resistance and compromise stewardship efforts. Direct evidence supporting empirical use of these agents remains limited and is based largely on observational data and extrapolation from targeted-therapy studies. Empirical use of newer agents may be appropriate for carefully selected patients with a high probability of CRGN infection and clinical scenarios where delayed active therapy could have serious consequences. Conclusion:A risk-stratified, stewardship-integrated approach incorporating local epidemiology, patient-level risk factors, illness severity and rapid diagnostics may optimize timely effective therapy while preserving the long-term utility of these agents.
Background:In Sub-Saharan Africa, over-the-counter antibiotic dispensing and limited resources drive high antimicrobial resistance (AMR), yet data on community-acquired urinary tract infections (UTIs) remain scarce. This review synthesizes available AMR evidence in this population. Methods:We searched MEDLINE, Embase and Global Health (January 2000-April 2026) for studies evaluating AMR in acute community-acquired UTIs across Sub-Saharan Africa. Random-effects meta-analyses evaluated resistance of Escherichia coli and Klebsiella spp. against five commonly prescribed antibiotics. Results:From 3099 screened articles, 42 studies (19 countries) were analysed. Pooled AMR prevalence was high for E. coli and Klebsiella spp., respectively: trimethoprim-sulfamethoxazole [62.2% (95% CI: 51.9%-72.5%) versus 66.4% (95% CI: 46.7%-86.2%)]; amoxicillin-clavulanic acid [48.9% (95% CI: 39.8%-58.0%) versus 47.5% (95% CI: 31.0%-63.2%)]; ceftriaxone [40.8% (95% CI: 19.4%-62.2%) versus 44.6% (95% CI: 28.6%-60.7%)]; ciprofloxacin [32.8% (95% CI: 25.1%-40.4%) versus 35.8% (95% CI: 20.3%-51.4%)] and nitrofurantoin [18.2% (95% CI: 9.2%-27.2%) versus 28.3% (95% CI: 12.1%-44.5%)]. All estimates showed very high heterogeneity (I 2 > 96%), unresolved by subgroup analysis. E. coli resistance to amoxicillin-clavulanic acid increased significantly over time (P = 0.028). Resistance did not differ significantly by pathogen or geographic region. Conclusions:Community-acquired UTIs in Sub-Saharan Africa exhibit high rates of AMR. Addressing this burden requires targeted community antimicrobial stewardship, rapid diagnostic tools to guide empiric therapy and standardized laboratory reporting to enable accurate global surveillance.
Objectives:OXA-244-producing Escherichia coli emerge in Europe and are difficult to detect. We evaluated the performance of different carbapenemase-producing Enterobacterale (CPE) screening and confirmation protocols used across five clinical microbiology laboratories in the Netherlands for the detection of OXA-244-producing E. coli isolates. Methods:Twelve E. coli isolates (CPE n = 9, non-CPE-ESBL n = 3) containing bla OXA-244 (n = 5), bla OXA-48(n = 1), bla OXA-181 (n = 1), bla KPC-2 (n = 1) and bla NDM-5 (n = 1) were distributed to five laboratories. Laboratories performed identification, susceptibility tests and subsequent additional tests for resistance mechanisms in accordance with their local CPE screening and confirmation protocol which all adhered to the current Dutch guideline for CPE detection. Results:All laboratories correctly detected no carbapenemase in three E. coli isolates without carbapenemase genes and correctly determined the E. coli isolates with bla KPC-2 and bla NDM-5 as CPE. Detection rates of carbapenemase among the five E. coli isolates with bla OXA-244 ranged from 0/5 (0%) to 4/5 (80%) isolates. One E. coli isolate with bla OXA-244, a meropenem MIC ≤0.125 mg/L and an imipenem MIC ≤0.25 mg/L was not detected by any laboratory. Discussion:Differences in CPE screening and confirmation protocols across five laboratories contributed to inconsistent detection of OXA-244-producing E. coli. Laboratories that used a gradient strip test confirmed meropenem minimum inhibitory concentration (MIC) >0.25 mg/L CPE screening breakpoint detected fewer or no OXA-244-producing E. coli strains than laboratories that implemented additional measures in their CPE screening protocols. A key recommendation is that laboratories evaluate whether the performance of their CPE screening protocol remains adequate, considering the current epidemiology of emerging difficult-to-detect OXA-244-producing E. coli.
Objectives:We aimed to determine the effects of a 12-month antimicrobial stewardship (AMS) programme in two provincial-level general hospitals in Viet Nam, a lower-middle-income country. Methods:We performed controlled interrupted time-series analyses to evaluate the intervention effects on antibiotic use in days of therapy (DOT) per 1000 patient-days, antibiotic non-susceptibility percentage and patient outcomes. In each hospital, four wards received the intervention, and four wards acted as controls. Pre-intervention periods began in January 2019 and continued to May 2020 (Hospital 1) and July 2020 (Hospital 2). Results:Regarding antibiotic use, the intervention was associated with an immediate absolute reduction of 95.9 DOT/1000 patient-days (95%CI 10.9-180.8) in Hospital 1, while Hospital 2 showed no overall change but declining slopes in selected antibiotics including aminoglycosides and penicillin/beta-lactamase inhibitors. Escherichia coli showed decreasing non-susceptibility to aminoglycosides and third-generation cephalosporins in both hospitals. Carbapenem non-susceptibility increased for both E. coli and Klebsiella spp. in Hospital 2 but decreased for Klebsiella spp. in Hospital 1. Non-susceptibility of P. aeruginosa increased to carbapenems (Hospital 1), aminoglycosides, ciprofloxacin and ceftazidime (Hospital 2). Acinetobacter spp. showed increased non-susceptibility to aminoglycosides and piperacillin-tazobactam in Hospital 1 but decreased to carbapenems, ciprofloxacin and piperacillin-tazobactam in Hospital 2. No evidence of changes in mortality or hospitalization costs were observed in both hospitals. Conclusions:The impact of AMS varied between the two hospitals, highlighting the context-specific nature of implementation. Sustained monitoring of antibiotic use and resistance is needed to support locally tailored interventions that respond to evolving resistance epidemiology.
