JAC-Antimicrobial Resistance最新文献

Background: Cephalosporin susceptibility in methicillin-susceptible Staphylococcus aureus (MSSA) is typically inferred from oxacillin or cefoxitin results; however, the reliability of this surrogate approach remains uncertain. This study aimed to evaluate MSSA susceptibility to first- through fifth-generation cephalosporins and assess the predictive value of oxacillin minimum inhibitory concentrations (MICs) for identifying non-susceptibility.

Methods: A total of 514 MSSA bloodstream isolates were collected from two hospitals in Taiwan. MICs for oxacillin and various cephalosporins were determined using broth microdilution. Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the predictive performance of oxacillin MICs. Multilocus sequence typing (MLST) was performed on isolates exhibiting ceftaroline resistance or the susceptible-dose dependent (SDD) phenotype to examine their genetic diversity.

Results: Non-susceptibility rates ranged from 4.9% to 6.2% for cefazolin, cefuroxime, ceftriaxone, and cefepime. For ceftaroline, while resistance was uncommon (1.4%), a notable proportion of isolates (9.7%) exhibited the SDD phenotype. An oxacillin MIC ≥0.25 mg/L predicted non-susceptibility to first- through fourth-generation cephalosporins with high accuracy (area under the curve [AUC] 0.827-0.875; negative predictive value [NPV] ≥ 98.7%) but was less predictive for ceftaroline (AUC 0.614). Among 44 isolates with elevated ceftaroline MICs, MLST identified 36 distinct sequence types, including 25 novel ones, indicating substantial genetic diversity.

Conclusions: Cephalosporin non-susceptibility can occur among MSSA isolates. Although elevated oxacillin MICs were associated with higher MICs for several cephalosporins, this relationship was less predictive for ceftaroline. These findings highlight microbiological variability in MSSA cephalosporin susceptibility and may inform situations where direct MIC testing provides additional clarity.

Objectives: The spread of antimicrobial-resistant Neisseria gonorrhoeae has limited treatment options. To monitor trends in population structure, antimicrobial susceptibility rates and resistant determinants of gonococcus isolated from patients, we collected longitudinal isolates and performed AST and molecular analyses.

Methods: Of 985 gonococcus isolates obtained from clinical specimens submitted by health care institutions in the Kanto region of Japan between 2017 and 2023, one isolate per patient per year was eligible, and up to 50 isolates per year were randomly selected. A total of 349 isolates were analysed. MICs were determined by the agar dilution method. Multilocus sequence typing and N. gonorrhoeae sequence typing for antimicrobial resistance (NG-STAR) were performed using a high-throughput typing method based on multiplex PCR amplicon sequencing on the MiSeq (Illumina) platform.

Results: Over this study period, 29 sequence types (STs) were identified. Only one ceftriaxone non-susceptible strain-harbouring mosaic penA 60.001 and belonging to ST1903-was found in 2017. A ciprofloxacin-susceptible lineage belonging to ST9362, lacking quinolone resistance-determining region mutations, was sporadically predominant in 2018 and 2023. The susceptibility rate to azithromycin remained ≥86% throughout the study period. There was a clear association between lineage and carriage of antimicrobial resistance determinants.

Conclusions: Ceftriaxone remains a reliable first-line treatment option for gonorrhoea. Ongoing surveillance is essential to detect emerging fluoroquinolone-susceptible lineages that may inform future treatment strategies.

Background and objectives: Metallo-β-lactamase (MBL)-producing Enterobacterales infections are an urgent global healthcare problem with limited treatment options. To obtain greater understanding of international perspectives on optimal management of serious infections due to MBL-producing Enterobacterales, we used a modified Delphi process to elicit experts' opinion and establish consensus.

Methods: A Delphi panel comprising 10 expert physicians experienced in antimicrobial-resistant bacterial infection management were surveyed on epidemiology, disease, testing and management of MBL-producing Enterobacterales infections. Consensus statements were based on survey responses and reviewed by the panel for endorsement or revisions to achieve consensus during a virtual meeting.

Results: All panellists acknowledged MBL-producing Enterobacterales as a key source of antimicrobial resistance and infection in most countries. All agreed these infections have high morbidity and mortality, leading to the need for critical-level care, longer hospital stays and significant healthcare costs. The negative clinical and economic consequences of MBL-producing Enterobacterales are compounded by inappropriate use of multidrug antimicrobial regimens. Therefore, a specific MBL-targeting agent is considered desirable. When aztreonam-avibactam and cefiderocol are available, the preferred first-line treatment is aztreonam-avibactam, per in vitro data showing aztreonam-avibactam activity against >90% of New Delhi MBL-producing Enterobacterales. If aztreonam-avibactam or cefiderocol are unavailable, treatment options are limited to co-administration of antimicrobials. Regional differences made it difficult to achieve unanimous consensus across all survey questions due to differences in patient factors, local epidemiology and testing availability.

Conclusions: The Delphi panel reached consensus on optimal management of MBL-producing Enterobacterales, confirming need for targeted MBL treatment, with monotherapy preferred where available.

Background: Carbapenem-resistant Enterobacterales (CRE) frequently cause serious, life-threatening infections with limited treatment options. The most common mechanism of carbapenem resistance is carbapenemase production. Colombia is considered endemic for KPC, while metallo-β-lactamases such as NDM and VIM are increasingly circulating. An emerging concern is the appearance of strains harbouring more than one carbapenemase. Here, we report a sentinel Enterobacter hormaechei isolate, highly resistant to β-lactams and co-harbouring three carbapenemases.

Methods: Enterobacter hormaechei was isolated from the wound of a 22-year-old male and molecularly characterized to decipher its resistance profile. Multiplex real-time PCR was used to screen for carbapenemases. Long-read WGS was performed using ONT MinION™, the genome was assembled de novo and resistome and plasmid types were analysed. Conjugation experiments were performed using E. coli J53-Az^R as a recipient.

Results: Multiplex PCR revealed the presence of bla _KPC, bla _VIM, and bla _NDM. Conjugation experiments yielded bla _KPC, and bla _KPC-bla _VIM-bla _NDM transconjugants, suggesting two distinct plasmids. WGS confirmed that bla _KPC-2 was encoded on a 58 Kb IncN plasmid, while bla _VIM-24 and bla _NDM-1 were carried by a 370 Kb multi-replicon plasmid (IncR-IncFII-IncC).

Conclusions: Although the emergence of triple-carbapenemase producers has been reported, it remains rare. However, sentinel isolates as the one described here (KPC-VIM-NDM) are extremely worrisome since dissemination of multiple carbapenemases could occur via conjugative plasmids in addition to horizontal gene transmission via mobile genetic elements. Considering that Colombia has long been considered a KPC-endemic country, the findings described here call for a thorough epidemiological surveillance to assess the real frequency of Enterobacterales carrying multiple carbapenemases.

Objectives: Invasive fusariosis is rising and poses challenges due to species complexity and antifungal resistance. In vitro susceptibilities of new antifungals against Fusarium isolates are seldomly evaluated in Asia. This study aimed to evaluate a two-step molecular identification algorithm and to perform in vitro antifungal susceptibility with correlation of species and susceptibility patterns.

Methods: Fusarium clinical isolates collected at three hospitals in Taiwan (2011-2023) were identified to species level using sequential ITS and TEF1α sequencing (step I), followed by RBP2 sequencing (step II) for inconclusive isolates. Minimum effective/inhibitory concentrations (MECs/MICs) of manogepix, olorofim, amphotericin B and voriconazole were determined by EUCAST method (E.Def 9.4).

Results: Of 103 isolates (37 blood and 66 cornea isolates) evaluated, the two-step algorithm achieved >90% to species level. Fusarium solani species complex (FSSC) was predominant, especially in blood isolates (86.5% versus 65.2% in cornea isolates; P = 0.02). The rest 28 isolates belonged to 12 species within six species complexes (SCs). Manogepix exhibited potent activity against all isolates (MEC ≤0.015 mg/L), while olorofim activities varied by SCs, with MIC ≤0.25 mg/L against Fusarium fujikuroi SC. FSSC displayed higher voriconazole and amphotericin B MICs compared with other SCs, with Neocosmospora keratoplastica displaying a highest amphotericin B modal MIC of 4 mg/L. Four major Neocosmospora species showed voriconazole MIC ≥16 mg/L.

Conclusions: Our findings indicated the two-step molecular algorithm accurately identifies Fusarium to species level. Further, we underscored the significance of considering both Fusarium SCs and species for predicting antifungal susceptibility, particularly to olorofim and amphotericin B.

The draft updated Global Action Plan (GAP) on antimicrobial resistance (AMR) for 2026-2035 acknowledges persistent gaps between political commitment and measurable implementation. This Viewpoint argues that progress can be facilitated by a simple, integrative indicator capable of capturing multisectoral action while remaining sensitive to national context. We propose the AMR footprint as a unifying concept to operationalize the updated GAP. Analogous to the carbon footprint, the AMR footprint consolidates and tracks selected AMR-specific and AMR-sensitive indicators across human health, animal and agrifood systems, and the environment, relative to national baselines over time. Anchoring monitoring, evaluation and accountability frameworks around an AMR footprint would shift the global response from aspirational targets towards continuous improvement, transparent benchmarking, and sustained financing. Without such an operational lens, the next decade of AMR action risks repeating the implementation failures of the past.

Background: Pseudomonas aeruginosa (PA) poses a significant clinical challenge due to its high antibiotic resistance. While microbial communities aid in spreading antibiotic resistance genes (ARGs), their role in the emergence of multidrug-resistant Pseudomonas aeruginosa (MDR-PA) is unclear. This study examines the impact of bacterial interactions on MDR-PA prevalence and underlying mechanisms.

Methods: This retrospective cohort study analysed 2965 PA-positive culture patients from the Medical Information Mart for Intensive Care IV (MIMIC-IV version 3.1) database, stratified by bacterial co-detection with PA. Propensity score matching (PSM) and logistic regression were used. Metagenomic sequencing was performed on deep endotracheal secretions from 19 PA ventilator-associated pneumonia (VAP) patients, constructing an ARGs dissemination network within the lower respiratory tract (LRT) microbiota. Comparative analysis of LRT microbiota and ARGs profiles was conducted between PA-VAP survivors and non-survivors.

Results: Patients with bacterial co-detection with PA had a significantly higher MDR-PA prevalence and mortality than those with PA-only detection. Logistic regression identified bacterial co-detection as an independent risk factor for MDR-PA (adjusted OR 2.14; 95% CI 1.64-2.83, P < 0.001) and subsequent mortality (adjusted OR 1.67; 95% CI 1.30-2.14, P < 0.001). Metagenomic analysis of 19 PA-VAP cases suggested that horizontal gene transfer (HGT) may facilitate inter-species dissemination of ARGs (e.g. eptB, smeE, ANT(4')-Ia) between PA and other co-colonizing LRT microbiota. Distinct ARG profiles were observed between PA-VAP survivors and non-survivors.

Conclusion: Our findings indicate that bacterial co-detection with PA elevates the risk of MDR-PA and worsens clinical outcomes, potentially driven by HGT-mediated ARG exchange within the host microbiota.

Background: Antibiotic use is the main driver of antimicrobial resistance and adverse events. The aim of our study was to investigate the magnitude of prescribing antibacterials to outpatients with an acute upper respiratory infection (AURI) in Finland.

Materials and methods: For the period 2017-2021, we linked data on antibacterial prescriptions (ATC group J01) from the Finnish Social Insurance Institution with disease data from Primary Care Outpatient Treatment Register and excluded diagnoses for which antibacterial treatment is indicated. We calculated the percentage of visits associated with at least one antibacterial prescription and performed univariate and multivariate logistic regression to assess the effect of year, demographic factors, AURI and selected underlying conditions.

Results: Overall, 9% of all outpatient AURI diagnoses, most of which are of viral origin, were prescribed antibacterials in the public healthcare sector. This proportion decreased from 11% in 2017 to 6% in 2021 and increased with age. Women were slightly more likely to obtain a prescription than men (adjusted probability 1.09; 95%CI 1.08-1.11). Chronic pulmonary disease was associated with increased prescribing for AURIs in the multivariate analysis (adjusted probability 1.93; 95%CI 1.84-2.03), and acute tonsillitis had the highest likelihood of antibacterial prescribing compared with other AURIs (adjusted probability 14.70; 95%CI 13.41-16.12).

Conclusions: Our research indicates that despite previous antimicrobial stewardship efforts, prescribing antibacterials for non-bacterial infections is still common in Finland. Nonetheless, the percentage of inappropriate prescribing decreased over time. Prescribing habits seem to be influenced by patient demographics and underlying chronic illnesses.

Background: Oral fosfomycin is commonly prescribed as a single 3 g dose to empirically treat uncomplicated cystitis. This study investigated the mechanisms and frequency of fosfomycin resistance among clinical isolates of Escherichia coli from Canada.

Methods: In total, 5012 clinical isolates of E. coli collected by the CANWARD surveillance programme from 2007 to 2022 were tested for susceptibility to fosfomycin using the CLSI reference agar dilution method. MICs were interpreted by 2024 CLSI M100 breakpoints. The 19 fosfomycin-resistant (MIC ≥256 mg/L) and 45 fosfomycin-intermediate (MIC 128 mg/L) isolates identified, and 69 fosfomycin-susceptible (MIC ≤1-64 mg/L) control isolates underwent WGS.

Results: In total, 98.7% (4948/5012) of all E. coli isolates tested were fosfomycin-susceptible; 0.4% were fosfomycin-resistant and 0.9% were fosfomycin-intermediate. ST131 accounted for 42.1%, 40.0% and 20.3%, respectively, of fosfomycin-resistant, fosfomycin-intermediate and fosfomycin-susceptible isolates. Six (31.6%) fosfomycin-resistant isolates and one (2.2%) fosfomycin-intermediate isolate carried a fosA gene. All fosA genes were plasmid mediated and all but one fosA-carrying plasmid harboured multiple other antimicrobial resistance genes. A nonsense mutation in, or complete deletion of, one or more genes in the fosfomycin transport systems GlpT and UhpT were observed in 63.2% (37/57) of fosA-negative fosfomycin-resistant and fosfomycin-intermediate isolates but were not detected in any of the 69 fosfomycin-susceptible isolates tested.

Conclusions: In Canada, the occurrence of mobile fosfomycin resistance determinants (fosA genes) in clinical isolates of E. coli is low (∼0.14% of all isolates). Our results highlight the importance of the functional transporter systems GlpT and UhpT for the in vitro activity of fosfomycin.