Other specific DSP article suggested by Editorial Board
Carbapenemase-producing Klebsiella oxytoca complex in France (2017–2023): molecular epidemiology integrated with virulence and biofilm phenotypes
Authors:Rezzoug, I
Abstract
Objectives: This study analysed a large French collection of carbapenemase-producing Klebsiella oxytoca complex (KoC) isolates (2017–2023) to map species and carbapenemase distributions and identify emerging lineages. We further investigated virulence traits to understand the epidemiological success of the dominant ST-2 lineage.
Methods: We conducted a retrospective study of all KoC isolates received at the French National Reference Center for Antimicrobial Resistance from 2017 to 2023. Whole-genome sequencing was performed to assess species assignment, phylogeny, and sequence types. Virulence analyses included biofilm formation assays (on abiotic surfaces and eukaryotic cells) and Galleria mellonella infection models.
Results: K. oxytoca sensu stricto remained the most prevalent species among the KoC. OXA-48-like enzymes were the most common carbapenemases, and two major lineages predominated: ST-141 and, far ahead, ST-2. The success of ST-2 appears linked to its low virulence combined with a strong capacity for long-term persistence.
Conclusion: Our findings confirm that K. oxytoca comprises a complex of distinct species whose taxonomy warrants continued revision. ST-2 circulates widely in France and, despite its limited virulence, shows remarkable persistence, making it an epidemiological important lineage.
Other specific DSP article suggested by Editorial Board
Distinct effects of GES variants on ceftazidime-avibactam and imipenem-relebactam resistance in carbapenem-resistant Pseudomonas aeruginosa: a ten-year retrospective study
Authors: Wang, L.
Abstract
Ceftazidime-avibactam (CZA) and imipenem-relebactam (IMR) are β-lactam/β-lactamase inhibitor combinations active against carbapenem-resistant Pseudomonas aeruginosa (CRPA), yet resistance to these agents is increasingly reported. In this study, 916 CRPA isolates collected from 2016 to 2025 were screened for blaGES by PCR, and fifty isolates were identified as blaGES-positive. Five subtypes were detected, including GES-1 (68%), GES-5 (24%), GES-7 (2%), GES-15 (4%), and a novel variant, GES-69 (2%). Antimicrobial susceptibility testing by broth microdilution revealed distinct resistance patterns. Isolates carrying blaGES-1, blaGES-7, blaGES-15, and blaGES-69 showed elevated CZA MICs, whereas blaGES-5 was associated with increased IMR MICs. Cloning experiments and structural modelling suggested that substitutions at position 170, Ω-loop conformational changes, and alterations in residues such as E104 may affect substrate binding and inhibitor interactions. Whole-genome sequencing showed that blaGES variants were located on the chromosome within class 1 integrons embedded in Tn6584-like transposons. Analysis of publicly available genomes further indicated that blaGES-positive isolates were mainly associated with the high-risk clone ST235, were distributed across multiple Gram-negative species with P. aeruginosa as the predominant host and exhibited an expanding cross-species distribution. In summary, these findings demonstrate that subtype-specific variation in GES enzymes is likely to shape the activity of β-lactam/β-lactamase inhibitor combinations within a conserved ST235 background.
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Clinical outcomes of carbapenem therapy in OXA-48–producing Enterobacterales infections: a French multicentre cohort, systematic review, and meta-analysis
Authors:Dortet, L.,
Abstract
OXA-48–producing Enterobacterales (OXA-48-PE) represent a growing global health threat. Most of OXA-48–PE remain categorized susceptible to carbapenems, which might encourage their use despite uncertain clinical efficacy. This study evaluated clinical outcomes of infections caused by OXA-48-PE treated with carbapenem compared with alternative active therapies. The analyses were performed at three levels: a descriptive analysis of the French cohort, a comparative descriptive analysis of all published studies, and a meta-analysis restricted to studies providing direct comparisons between carbapenem-based and alternative active regimens. Between September 2021 and March 2023, 59 patients with monomicrobial OXA-48-PE infections were included in a French multicenter retrospective cohort. In parallel, a systematic review was conducted to identify clinical studies published through 31 December 2024, reporting outcomes of OXA-48-PE infections. In the French cohort, the overall 30-day mortality was 49.1%. Clinical failure occurred in 57.1% of patients receiving meropenem monotherapy, including patients infected with isolates exhibiting meropenem MICs within the susceptible range. Across 12 clinical studies (817 patients), carbapenem therapy was associated with high and variable crude mortality (52%), whereas newer agents active against OXA-48-PE, particularly ceftazidime-avibactam, were associated with lower and more consistent crude mortality (30.7%). In the primary meta-analysis of 6 human comparative studies, carbapenem therapy was associated with an increased risk of clinical failure compared with alternative active regimens (OR = 2.02; 95% CI = 1.05–3.88). Despite apparent in vitro susceptibility, carbapenem therapy was consistently associated with unfavourable clinical outcomes in OXA-48–PE infections, supporting the prioritization of alternative active agents whenever available.
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Beyond Koplik spots: aphthous-like ulcers as a novel enanthem in adolescent and adult measles
Authors:Fenn B
Abstract
Objectives: Measles is re-emerging in adolescents and adults, yet its oral phenotype beyond Koplik spots is poorly characterised. We describe the oral mucosal manifestations of confirmed measles in this group, focusing on aphthous-like ulcers, a less characterised enanthem of measles.
Methods: In a prospective observational cohort at a tertiary centre in Kerala, India (June 2024 to June 2026), patients aged 12 years or older with acute fever and generalised rash were enrolled consecutively; those with measles confirmed by IgM ELISA and/or nasopharyngeal RT-PCR are reported. The oral cavity was examined systematically; ulcer-base swabs were obtained where feasible and one ulcer was biopsied.
Results: Of 307 patients with fever and rash, 31 had confirmed measles (median age 26 years; 30 of 31 vaccinated, 22 of them with a single infant dose). Any oral mucosal finding occurred in 21 of 31 (67.7%). Aphthous-like ulcers occurred in 11 of 31 (35.5%), spanned illness days 3 to 8, and outlasted Koplik spots (13 of 31, 41.9%), which were associated with earlier presentation (median day 4 versus 6, p=0.001). Ulcer-base swabs, obtained in three patients, were measles RT-PCR-positive in all three and negative for herpes simplex virus 1/2, enteroviruses, cytomegalovirus, Epstein–Barr virus and varicella-zoster virus; biopsy showed non-specific aphthous morphology.
Conclusions: Aphthous-like oral ulcers are a frequent enanthem of measles that outlasts the Koplik window and warrants active recognition and prompt measles testing.
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Oral antibiotics prescribing patterns and associated diarrhea risk: Public health implications.
Authors: Naumovska Z, et al
Abstract
Background: Inappropriate antibiotic use contributes to antimicrobial resistance and adverse drug reactions (ADR), including antibiotic-associated diarrhea (AAD), underscoring the importance of WHO AWaRe recommendations for rational prescribing. Clinical evidence supports the use of specific probiotic strains to reduce AAD risk, with strain-specific recommendations that should be adapted to regional contexts.
Objectives: To assess oral antibiotic consumption in the Republic of North Macedonia (2011-2022), evaluate prescribing patterns according to the WHO AWaRe classification, identify antibiotics associated with a higher burden of AAD, and determine the availability of evidence-supported probiotics for AAD prevention. Design: Observational pharmaco-epidemiological study integrating antibiotic utilization data, pharmacovigilance signals, and evidence synthesis from systematic reviews and market analysis.
Methods: Reimbursed oral antibiotic data (ATC J01) were obtained from the National Health Insurance Fund. Gastrointestinal ADR reports were extracted from EudraVigilance and FAERS. Diarrhea risk was estimated using SmPC frequency categories and normalized pharmacovigilance indicators. Systematic reviews and meta-analyses were used to identify probiotic strains with evidence for AAD prevention, and online pharmacy surveys assessed market availability.
Results: Penicillins and cephalosporins predominated in antibiotic use. Amoxicillin/clavulanic acid, cefixime, and clindamycin ranked highest for diarrhea risk based on combined utilization and pharmacovigilance indicators. Saccharomyces boulardii and Lactobacillus rhamnosus GG showed the strongest evidence for AAD prevention. Considerable variability was observed in probiotic product composition and reporting across the market.
Conclusion: Findings highlight antibiotics with higher AAD-related public health burden and support antimicrobial stewardship strategies, including evidence-based probiotic co-administration.