Clinical Microbiology and Infection最新文献

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.

Objectives: Bacillus cereus sensu lato (s.l.) or B. cereus group increasingly causes severe infections in preterm neonates. However, species-level identification and virulence characterization remain limited. This study aimed to identify B. cereus group species responsible for invasive infections in preterm neonates and to correlate genomic virulence profiles with clinical outcomes.

Methods: We conducted a retrospective, multicentre study across 13 French hospitals (2010-21), including 40 B. cereus group isolates from blood or cerebrospinal fluid of preterm neonates with invasive infections. Clinical data were extracted from patient records. Whole-genome sequencing (Illumina and Oxford Nanopore) with hybrid assemblies enabled species identification using digital DNA-DNA hybridisation and average nucleotide identity. Virulence genes were screened against a curated database of 65 virulence genes, and associations with clinical outcomes were analysed.

Results: Forty isolates were analyzed, 42.5% (17/40) of patients developed septic shock, and 37.5% (15/40), died, usually following rapid clinical deterioration. WGS identified seven species, predominantly Bacillus paranthracis (47.5%, 19/40) and B. cereus sensu stricto (20%, 8/40). Virulence gene content varied by species. The presence of hblCDAB (60%, 9/15), nprB (46.5%, 7/15), asbABCDEF (80%, 12/15), and essC-cereus/esxA (66.7%, 10/15) genes correlated with mortality (p=0.00015, 0.002, 0.0027, and 0.02, respectively). B. cereus sensu stricto carried more virulence determinants and was associated with higher mortality than B. paranthracis and other species, at day 7 (p=0.05) and at day 28 (p=0.0065). The cesH gene (60%, 15/25) is significantly associated with survival (p=0.007), particularly with B. paranthacis, the predominant species in our cohort.

Conclusions: Invasive B. cereus group infections in preterm neonates are associated with high mortality, particularly in cases due to B. cereus sensu stricto. WGS enables precise species identification and virulence profiling, which are essential insights for diagnostic refinement, outbreak control, and risk stratification in neonatal intensive care settings.