Clinical Microbiology and Infection最新文献

Objectives: Guidelines recommend extragenital screening for sexually transmitted infections in men having sex with men but not for women who do not report extra-vaginal intercourses. However, it has been suggested that among female commercial sex workers, limiting sexually transmitted infection screening to vaginal samples would miss a sizeable number of infections. No study exists for non-sex worker women. Therefore, our objective was to assess the potential benefit of systematically testing three anatomical sites (oral, anal and vaginal) versus only vaginal testing in women attending free sexually transmitted infection screening centres in France.

Methods: A prospective longitudinal study was conducted in seven hospitals in France between April 2023 and September 2024 in which women were offered to be tested at the three sites instead of vaginal only.

Results: A total of 1498 women were included in the study, and 1483, 1492, and 1278 oral, vaginal and anal samples, respectively, were reported. With a three-site strategy, the detection rate increased from 151/1492 (10.1%) to 179/1295 (13.8%) (p<0.001) (127 (10.0%) to 152/1268 (12.0%); p<0.001 for all patients with three-site samples) for both infections (p<0.001). Similarly, rate increased from 137/1492 (9.2%) to (160/1293) 12.4% (p<0.001)(114 (9.0%) to 135/1268(10.7%), p<0.001 for all patients with three-site samples) for C. trachomatis and from 21/1492 (1.4%) to 30/1270 (2.4%) (p=0.008)( 20 (1.6%) to 28/1268 (2.2%), p=0.01 for all patients with three-site samples) for N. gonorrhoeae. Neither symptoms nor reported sex practices were reliable predictors of infection. Among the C. trachomatis or N. gonorrhoeae infections detected, 15 (10.0%) and 25 (17.0%) were exclusively anal or anal-oral infections, respectively, without vaginal involvement.

Conclusions: Multisite testing should be considered for women to ensure accurate diagnosis and treatment of C. trachomatis and N. gonorrhoeae.

Objectives: Severe infection risk associated with tumor necrosis factor-α inhibitors (TNFi) remains a concern. We aimed to assess the association between TNFi and bloodstream infections (BSI) in a population-based setting.

Methods: Nationwide, registry-based case-control study including all adults from 2010 to 2024 with a first-time microbiologically confirmed BSI (cases) compared to age and sex-matched controls from the general population. Users were defined as individuals with TNFi exposure within six months prior to the date of BSI. Adjusted odds ratios (aOR) with 95% confidence intervals (CIs) were estimated using conditional logistic regression. We further assessed risk variation by type of TNFi, pathogen, and underlying disease.

Results: We included 174,137 cases and 1,741,294 controls. Users had significantly increased odds of BSI compared to non-users (aOR: 1.41, 95% CI: 1.30-1.52), driven by increased odds among users of adalimumab and infliximab (aOR: 1.51, 95% CI: 1.33-1.72, and aOR: 2.01, 95% CI: 1.76-2.29). Use of certolizumab pegol and etanercept was associated with lower odds of BSI, and golimumab with higher odds compared to non-use, although not statistically significant. Species-specific analyses showed increased odds of BSI with Escherichia coli (aOR: 1.33, 95% CI: 1.16-1.53), Staphylococcus aureus (aOR: 1.69, 95% CI: 1.40-2.06), Streptococcus pneumoniae (aOR: 1.46, 95% CI: 1.05-2.04), and Enterococcus faecium (aOR: 1.62, 95% CI: 1.04-2.53). Highest odds were observed in individuals with inflammatory bowel disease (aOR: 2.27, 95% CI: 1.93-2.66), followed by individuals with rheumatoid arthritis. Compared to TNFi monotherapy, concomitant glucocorticoids increased the odds (aOR: 2.63, 95% CI: 2.06-3.36).

Conclusions: TNFi use is associated with increased odds of BSI and was observed across the most frequent species. Odds varied by TNFi type and underlying disease, with highest odds among patients with inflammatory bowel disease, emphasizing the need for individualized infection risk assessment.

Objective: Combination antibiotic therapy may improve treatment success for bacterial infections, but bacterial strain-to-strain variability in synergy and its clinical impact remains unclear. This study evaluated whether positive in vitro interactions (synergy or additivity) between vancomycin or daptomycin and a β-lactam in methicillin-resistant Staphylococcus aureus(MRSA) bloodstream infections are associated with improved clinical outcomes in the CAMERA2 trial.

Methods: In this post-hoc analysis of the multicentre randomised CAMERA2 trial, adults with MRSA bacteraemia were randomised to standard care (vancomycin or daptomycin) or combination therapy with an anti-staphylococcal β-lactam. Of 174 combination-therapy patients, 24 were excluded for unavailable isolates or missing outcome data, leaving 150 for analysis. Synergy testing was performed centrally, post hoc, using a microdilution checkerboard assay, stratifying patients into positive-interaction (synergy/additivity) and negative-interaction (antagonism/indifference) groups. Clinical outcomes - including primary composite end point of 90-day mortality - were compared between groups, using statistical tests and multivariate regression adjusting for confounders.

Results: Among 150 patients, 103 were in the positive interaction group and 47 in the negative interaction group. Patient characteristics were similar. The primary composite endpoint of 90-day mortality [34% (16/47) vs 32% (33/103), p = 0.81] did not differ significantly between groups. Persistent bacteraemia rate at day 2 was higher [32.0% (33/103) vs 19.1% (9/47), p = 0.10] in the positive interaction group. However, 14-day all-cause mortality was significantly lower in the positive interaction group [2.9% (3/103) vs 12.8% (6/47), p = 0.03).

Conclusions: Positive interactions between vancomycin or daptomycin and a β-lactam were associated with lower 14-day mortality in MRSA bacteraemia. However, these findings should be interpreted with caution and considered hypothesis-generating. Combination therapy may be beneficial when positive interactions are present, not universally effective. Synergy testing may help optimise combination therapy, warranting confirmation in a randomised trial.

Background: Treatment-emergent resistance is increasingly reported in carbapenem-resistant Enterobacterales (CRE) during therapy with newly developed antibioticss. However, standardized definitions and studies evaluating the impact of treatment-emergent resistance on patients outcome are lacking.

Objectives: To review current evidence on the epidemiology, risk factors, and clinical impact of resistance emerging during or after exposure to novel antibiotics against CRE and to explore strategies to mitigate this phenomenon.

Sources: We searched PubMed/MEDLINE for studies published in the last 15 years, including clinical reports, observational and in vitro studies focusing on ceftazidime-avibactam (CAZ/AVI), meropenem-vaborbactam (MVB), imipenem-relebactam (IMI/REL), cefiderocol (FDC), aztreonam-avibactam (ATM/AVI), eravacycline, and plazomicin.

Content: Literature on resistance development during treatment with novel antibiotics is sparse and mainly represented by case reports or retrospective cohort studies. In most cases, data including antibiotic dosages, duration or cross-resistance to other antibiotics are not reported. Treatment-emergent resistance is best described for CAZ/AVI, with KPC variants carrying Ω-loop mutations (e.g. KPC-31) as the most common reported mechanism worldwide. Resistance during or following MVB or IMI/REL therapy is uncommon and only reported in selected cases from Europe where the drugs have been used more broadly. FDC resistance is mainly reported from Europe and US in NDM-producing Enterobacterales and commonly linked to iron transporter defects, PBP3 substitutions, or increased bla_NDM copy number. For ATM/AVI, resistance during or after treatment have been reported in selected strains of NDM-producing E. coli isolates with PBP3 and CMY mutations from Singapore and US.

Implications: Treatment-emergent resistance is a consequence of antibiotic exposure, but its impact is likely underestimated. Preventive strategies include optimization of pharmacokinetic/pharmacodynamic targets, therapeutic drug monitoring, timely and complete source control, and stewardship-driven rational use of novel agents.