Journal of global antimicrobial resistance最新文献

Objectives: Ceftobiprole, a fifth-generation cephalosporin, is effective in treating complicated Staphylococcus aureus bacteremia, including methicillin-resistant Staphylococcus aureus (MRSA). This study compared ceftobiprole minimum inhibitory concentrations (MICs) determined by broth microdilution (BMD), agar dilution (AD), and Etest for MRSA isolates from a multicenter study in China.

Methods: The in vitro activity of ceftobiprole was evaluated against 60 MRSA isolates using AD and Etest, with BMD as reference.

Results: BMD showed 85% of MRSA isolates were susceptible to ceftobiprole (MIC₉₀ = 4 mg/L), with 95% having MICs within ±1 log₂ dilution of the EUCAST breakpoint (1-4 mg/L). Categorical agreement and essential agreement were suboptimal for both AD (85% and 85%) and Etest (81.7% and 80%). Eight of nine MRSA isolates classified as resistant by BMD were categorized susceptible by Etest, resulting in very major errors (VMEs), whereas only three isolates classified as susceptible by BMD were miscategorized as resistant by Etest. Using the error-rate-bound method, high VMEs were observed for Etest (22.2%) and agar dilution (25.0%), predominantly involving ST5 and ST239 MRSA lineages.

Conclusion: This study demonstrates frequent clustering of MRSA isolates within the EUCAST-defined area of technical uncertainty, defined for ceftobiprole as an MIC of 2 mg/L, corresponding to the susceptibility breakpoint and its adjacent zone where categorization is inherently unreliable. Methodological limitations of agar dilution and Etest further increase the risk of misclassification and potential failure to detect resistance. These findings underscore the need for optimized susceptibility testing strategies and refined interpretive guidance to support accurate clinical use of ceftobiprole.

Antimicrobial resistance (AMR) is a global health threat, emphasizing the need for antimicrobial stewardship (AMS) across sectors, including veterinary medicine. Inappropriate use of antimicrobials in livestock practices has contributed to the spread of AMR. A key challenge was the inadequate AMS integration within veterinary education, highlights the importance of bridging the awareness gap and enhancing preparedness among future veterinarians.

Objective: To identify the barriers and facilitators of implementing Antimicrobial Stewardship in veterinary education globally.

Methodology: Following PRISMA-ScR guidelines and Arksey and O'Malley's framework, this review analyzed studies published between 2015 and 2025 from databases PubMed (NCBI), Cochrane Library, Scopus (Elsevier, Embase (Elsevier) ProQuest, Web of Science (Clarivate) and CINAHL (Ebsco) to systematically explore.

Results: Twenty studies were included in this review, Barriers identified included inadequate AMS content integration within veterinary curricula, limited teaching hours dedicated to pharmacological training to the students. Other barriers including gaps between theoretical and clinical practice, lack of electronic record systems that would enable real time monitoring of antimicrobial use patterns in teaching hospitals, and weak policy enforcement in low- and middle-income countries. Facilitators included student and faculty engagement, educational interventions such as workshops, symposiums and online learnings. Institutional leadership and multidisciplinary collaboration were also found effective in AMS implementation. However, the integration of One Health and AMS programs remained limited and inconsistent in the veterinary education.

Conclusion: The findings emphasized need for AMS education reforms, as many curricula did not include components of responsible antimicrobial usage. Future efforts must involve veterinary stakeholder collaboration to improve curricula, infrastructure, capacity, faculty development, and promote interdisciplinary and one health education models.

Objective: To assess the efficacy and influencing factors of sulfamethoxazole-trimethoprim (SXT) in children with pertussis in regions with a high prevalence of macrolide-resistant Bordetella pertussis (MRBP).

Methods: A total of 317 PCR-confirmed pediatric pertussis cases treated with SXT were retrospectively analyzed. Patients were categorized into short-term (5-7 days, n=93) and long-term (10-14 days, n=65) treatment groups. Clinical outcomes, adverse events, and potential predictors of treatment response were analyzed.

Results: The median interval from symptom onset to SXT initiation was 12 days (IQR 9-15). Following SXT therapy, 243 patients (76.7%) achieved clinical remission, 68 (21.4%) showed partial improvement, and 6 (1.9%) experienced no relief, without clinical deterioration. Multivariate analysis identified nucleic acid negative conversion as a independent predictor of clinical remission (OR 5.14, 95% CI 2.66-9.88, p < 0.001). Compared to the short-course group, the long-course group demonstrated significantly higher rates of both clinical remission (83.1% vs. 66.7%, p=0.022) and nucleic acid clearance (87.7% vs. 71.0%, p=0.013). No serious adverse events were reported. Skin lesions were the most frequent adverse events (5.1%), with no significant difference between groups (3.2% vs. 7.7%, p = 0.373).

Conclusions: SXT effectively alleviates clinical symptoms of pertussis in children in high MRBP prevalence regions. Nucleic acid negative conversion predicts clinical remission. An extended SXT course (10-14 days) demonstrates superior efficacy to a shorter course (5-7 days). No serious adverse events were observed; skin lesions were the most common side effect.

Background: Older populations (≥ 60 years) are frequent users of healthcare services, often vulnerable to infections and antimicrobial resistance (AMR). Urinary tract infection (UTI) is often diagnosed in this cohort based on non-specific or atypical symptoms, yet empirical therapy seldom considers the potential influence of residential setting on resistance patterns. This study therefore aimed to quantify and compare the in-vitro AMR profiles of urinary pathogens from these two settings and assessed temporal resistance trends to inform antimicrobial-stewardship (AMS) priorities.

Methodology: A retrospective analysis was conducted using anonymised microbiology data from Ampath Laboratories in Gauteng. Urine cultures collected from older adults (≥60 years) between 2015 and 2023 were included. The five most common uropathogens were analysed. Resistance differences between LTCF and community samples were assessed using univariate and multivariable logistic regression models adjusting for age, sex, inpatient status, and sampling year. Temporal trends were evaluated using Kendall's tau-b.

Results: A total of 50,704 urine cultures were analysed, of which 18.81% were from LTCFs. Escherichia coli and Proteus mirabilis showed consistently higher resistance in LTCF isolates. In E. coli, LTCF residence was associated with increased resistance to ciprofloxacin (adjusted OR 1.26; 95% CI 1.18-1.34), nitrofurantoin (1.55; 1.38-1.75), ceftriaxone (1.24; 1.14-1.34), amoxicillin/clavulanic acid (1.11; 1.05-1.19) and co-trimoxazole (1.10; 1.03-1.18). P. mirabilis showed similar patterns, with higher resistance to ciprofloxacin (2.16), gentamicin (1.64), fosfomycin (1.72) and co-trimoxazole (1.49). Trend analysis showed increasing fosfomycin resistance from E. coli isolates in both LTCFs (3.74% to 6.18%) and community settings (2.75% to 3.74%) and rising ceftriaxone resistance in community isolates (13.32% to 17.60%).

Conclusion: LTCF residence was independently associated with higher AMR in several common urinary pathogens. These findings suggest that empirical UTI regimens commonly used in community-dwelling older adults may be inadequate for LTCF residents. Setting-specific antibiograms, improved diagnostic stewardship, and strengthened AMS interventions are needed to support appropriate prescribing. Further studies incorporating patient-level clinical factors are warranted to refine empirical treatment recommendations for older adults across care settings.

Background: Extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-EC) and Klebsiella pneumoniae (ESBL-KP) represent major clinical threats globally. Genomic epidemiological data remain scarce in low- and middle-income countries, limiting comprehensive understanding of antimicrobial-resistant pathogen diversity and clonal distribution. The present study investigated the genomic epidemiology of ESBL-EC and ESBL-KP isolates in Mwanza, Tanzania.

Methods: This cross-sectional hospital-based study employed whole-genome sequencing to characterize ESBL-EC (n=39) and ESBL-KP (n=49) isolated from patients with bloodstream, urinary tract, and wound infections at a zonal referral hospital between June 2019-June 2020 and March-August 2023.

Results: Thirteen sequence types (STs) were identified among ESBL-EC, predominantly ST131 (30.7%) and ST648 (28.2%). ESBL-KP comprised 15 STs, with ST2390 (24.5%) and ST17 (18.4%) most common. The bla_CTX-M-15 gene was detected in 87.2% of ESBL-EC and 95.9% of ESBL-KP. IncFII was the dominant plasmid replicon in ESBL-EC (63.9%) and ESBL-KP (83.7%), while repB was detected exclusively in ESBL-KP (28.6%), particularly among ST2390. ESBL-EC showed significantly higher resistance to ciprofloxacin (p<0.01), whereas ESBL-KP demonstrated higher resistance to gentamicin and piperacillin-tazobactam (both p<0.01). The cgMLST-based Neighbor-Joining phylogenetic analysis revealed substantial genetic diversity and identified clonal clusters involving the high-risk clone ESBL-EC ST131. Clusters of ESBL-EC ST131 and ST648 were observed across medical and neonatology wards, while ESBL-KP ST2390 clusters were mainly confined to neonatology wards.

Conclusion: This study highlights clonal clusters, the first report of ESBL-KP ST2390, and the predominance of the virulent high-risk clone ESBL-EC ST131 in Mwanza, Tanzania. Underscoring the critical need for reinforced infection control strategies and genomic surveillance.

Objectives: This study reports complete chromosome and pESI-like megaplasmid sequences of multidrug-resistant Salmonella enterica serovar Infantis (S. Infantis) isolates obtained from retail chicken meat in South Korea in 2023 and characterizes their antimicrobial resistance gene repertoire and the structural diversity of their pESI-like plasmids.

Methods: Twenty-one multidrug-resistant S. Infantis isolates were subjected to whole-genome sequencing using Illumina NextSeq and Oxford Nanopore MinION platforms. Hybrid assemblies were generated using Trycycler v0.5.0 and corrected using Polypolish v1.2.3. AMR genes were identified, and plasmid structures were reconstructed and visualized using Proksee.

Results: All isolates belonged to sequence type ST32 and carried pESI-like megaplasmid encoding multiple AMR genes. Conserved resistance genes included aac(3)-IVa, aph(4)-Ia, bla_CTX-M-65, and tet(A), while ant(3'')-Ia, aph(3')-Ia, dfrA14, floR, and sul1 were variably present. Comparative plasmid analysis revealed six plasmid structural variants (Types A-F), primarily distinguished by deletions within AMR regions. Type A retained all resistance loci, whereas Types B-F exhibited partial loss of regions harboring aph(3')-Ia, dfrA14, floR, or sul1. Comparative plasmid mapping showed that the Korean pESI-like plasmids exhibited high overall structural similarity to internationally reported pESI-like plasmids, including those from the UK and USA.

Conclusions: These complete genome sequences expand the current knowledge of pESI-like plasmid diversity in S. Infantis and highlight their role in the dissemination of multidrug resistance in the poultry sector. Continued genomic surveillance is warranted to monitor the emergence and spread of high-risk S. Infantis clones across the food chain.

Objectives: This study aimed to investigate the prevalence of diarrheagenic Escherichia coli (DEC) among outpatients in Beijing, and to analyze the antimicrobial susceptibility profiles and antimicrobial resistance gene characteristics of the isolated strains.

Methods: From 2021 to 2024, DEC strains were collected from outpatient specimens. After isolation and identification, the minimum inhibitory concentration (MIC) method was used to assess their susceptibility to 16 antibiotics. Whole-genome sequencing was conducted for further analysis.

Results: Among the 1,209 DEC strains, the highest resistance rates were observed for ampicillin (63.28%) and tetracycline(45.57%). In contrast, significantly lower rates were found for tigecycline (0.41%), amikacin (0.66%), meropenem (3.97%), ertapenem (6.70%), ceftazidime (7.20%), and ciprofloxacin (9.26%). The 0-5 age group demonstrated higher resistance rates to most antibiotics compared with other age groups. Multilocus sequence typing revealed significant genetic diversity among all strains, with the predominant sequence types identified as ST10(5.96%), ST1491(5.21%), ST4(4.22%), and ST48(3.47%). Among 111 fluoroquinolone-resistant strains, chromosomal mutations in gyrA and parC genes were predominant (56.76%). Among 612 cephalosporin-resistant isolates, the bla_CTX-M gene was the most prevalent resistance gene (30.72%).

Conclusions: DEC infections and the spread of resistance genes pose a significant health threat, especially in children. Consequently, there is an urgent need to enhance the surveillance and research of resistance genes and to promote the rational use of antibiotics.

Research background: mecA-positive MRSA is generally assumed to be broadly non-susceptible to β-lactams. Reports of penicillin-susceptible MRSA (PS-MRSA) challenge this view. We describe CDSYY2023, a cefoxitin-resistant yet penicillin-susceptible MRSA carrying three mecA substitutions (S225R, K239E, E246G) and a novel sequence type, ST9332.

Methods: The strain was recovered from the sputum of a hospitalized older adult with dementia and identified as S. aureus by MALDI-TOF MS (Autobio MS1000). Susceptibility testing followed CLSI procedures on VITEK 2 with parallel Mueller-Hinton edge tests (cefoxitin, penicillin). Key readouts were verified by Etest and independently confirmed at a referral laboratory. Whole-genome sequencing (Illumina HiSeq 2500) was assembled de novo with SOAPdenovo2. Functional annotation used COG/GO/KEGG; resistance and virulence genes were queried against CARD and VFDB. MLST was assigned and registered via PUBMLST.

Results: The draft genome is ∼2,750,950 bp (GC 32.94%), with no plasmids, encoding 2,521 CDSs, 55 tRNAs, and 19 rRNAs. MLST designated ST9332. Phenotypically, VITEK 2 and MH edge tests agreed on cefoxitin resistance (17 mm), while penicillin remained susceptible (25 mm; Etest MIC 0.032 µg/mL), contrary to expectations for a mecA-positive background. Genomics revealed the triple mecA substitutions noted above and no definitive evidence of blaZ. The resistome/virulome included multiple efflux and regulatory elements.

Conclusions: CDSYY2023 is a PS-MRSA with triple-substituted mecA on a novel MLST background (ST9332). Its penicillin-susceptible/cefoxitin-resistant profile likely reflects a specific mecA sequence/regulatory context, highlighting the limits of relying solely on cefoxitin-based screening to infer β-lactam behavior.

Objectives: This study investigates the transmission risk of extended-spectrum ß-lactamase (ESBL) producers, carbapenemase producers, polymyxin-resistant, and fosfomycin-resistant Enterobacterales from healthy and sick dogs and cats in Tanta governate, Nile Delta region, Egypt.

Methods: A total of 206 different samples were collected from healthy and sick pet animals. Samples were screened for different resistance mechanisms using mSuperCarba, SuperPolymyxin, ChromID ESBL, and SuperFOS selective plates. Antimicrobial susceptibility testing was performed using disk diffusion and broth microdilution techniques. Phenotypic confirmation of resistance traits was done using various rapid diagnostic tests. PCR screening was performed for ESBLs, carbapenemases, mcr, and fosA genes. Molecular typing and clonality evaluation were also performed.

Results: The isolates (Escherichia coli, n=17 and Enterobacter cloacae, n=1), showing acquired multidrug resistance (MDR) phenotype, were identified in 13 animals, accounting for 25% of the total cases. Production of ESBLs was the most prevalent resistance mechanism, the corresponding producers predominantly carrying the bla_CTX-M-15 gene (92.3%), while the bla_SHV-12 gene was identified in a single isolate. The bla_NDM-5 carbapenemase gene was identified in three E. coli isolates, those latter sharing the same sequence type (ST361). A single colistin-resistant E. coli was isolated and carried both mcr-1 and bla_CTX-M-15, while a fosfomycin-resistant E. coli isolate co-produced fosA5 and SHV-12. Notably, 69.2% of resistant bacteria were isolated from sick pets, compared to 30.7% in healthy ones. E. coli isolates showed various sequence types, with ESBL-producing strains belonging to seven different STs and NDM-5 enzyme producers belonging to ST361.

Conclusion: This study highlights significant antimicrobial resistance in companion animals and the potential risk for zoonotic transmission.

Objective: Infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) have a poor prognosis, particularly in immunocompromised patients. While carbapenemase production is the primary resistance mechanism in CRKP, other mechanisms may contribute synergistically to carbapenem resistance. Here, we describe a case in which extended-spectrum β-lactamase (ESBL)-producing K. pneumoniae, initially susceptible to carbapenems, acquired carbapenem resistance without carbapenemase production following ceftolozane-tazobactam exposure.

Methods: Whole-genome sequencing was performed on ESBL-producing K. pneumoniae strains detected during the clinical course to investigate the relationship between the genetic characteristics and antimicrobial susceptibility, particularly to ceftolozane-tazobactam and carbapenems. Changes in the transcription levels of the beta-lactamase genes were also analyzed using reverse transcription quantitative PCR (RT-qPCR).

Results: Active surveillance stool culture before cord blood transplantation (CBT) identified colonization with an ESBL-producing K. pneumoniae strain. Febrile neutropenia occurred on day 7 after CBT and was treated empirically with ceftolozane-tazobactam. Fatal bacteremia developed on day 30 after CBT due to a carbapenemase-negative isolate resistant to both ceftolozane-tazobactam and carbapenems. Whole-genome sequencing analysis revealed that K. pneumoniae ST307 strains harboring bla_CTX-M-15, bla_SHV-28, and bla_TEM-1B acquired a nonsense mutation in ompK36 following ceftolozane-tazobactam exposure. RT-qPCR analysis documented a significant increase in bla_SHV-28 transcription after ceftolozane-tazobactam exposure.

Conclusions: This case demonstrates that K. pneumoniae without carbapenemase production can acquire carbapenem resistance through a combined resistance mechanisms following exposure to non-carbapenem antibiotics. Antimicrobial stewardship must be implemented comprehensively, not focused solely on specific antibiotics.