Clinical Microbiology and Infection最新文献

Objectives: In sub-Saharan African children aged under 5 years, nontyphoidal Salmonella (NTS) frequently cause fatal bloodstream infections. Antimicrobial resistance and absence of antibiotic treatment efficacy data challenge effective treatment. In this prospective observational study, we provide treatment efficacy data of susceptibility-matched antibiotic regimens from the treatment of NTS bloodstream infections in children in Kisantu district hospital (Democratic Republic of Congo).

Methods: Children (>28 days to <5 years) admitted with severe febrile illness were enrolled after blood culture sampling. Clinical and microbiological data of children with NTS bloodstream infection were collected in-hospital and at 1-month after discharge.

Results: NTS bloodstream infection was diagnosed in 12.7% (239/1867) of enrolled children. Extensive drug-resistance (concurrent ampicillin, cotrimoxazole, chloramphenicol, third-generation cephalosporin and fluoroquinolone nonsusceptibility) occurred in 60% (144/236), i.e. 69% (71/103) in O5-antigen positive Typhimurium, 85% (72/85) in O5-antigen negative Typhimurium but only 2% (1/48) in Enteritidis serovars. Only 64% (146/228) of children received susceptibility-matched antibiotics and overall in-hospital case fatality was 25.1% (60/239). Compared with susceptibility-mismatched antibiotic treatment, susceptibility-matched third-generation cephalosporin treatment on hospital day 0-1 had better 14-day in-hospital survival (hazard ratio at death [HR_death]: 0.37 [0.16-0.88]). Similarly, susceptibility-matched third-generation cephalosporin, ciprofloxacin or azithromycin treatment on hospital day 2-6 had better 28-day in-hospital survival (HR_death: 0.21 [0.06-0.68], 0.15 [0.02-1.10] and 0.26 [0.08-0.84], respectively). After ≥5 days of susceptibility-matched antibiotics, NTS persisted in control blood cultures in 15% (13/88).

Conclusions: NTS bloodstream infections were often extensively drug resistant, leading to susceptibility-mismatched antibiotic treatment. When NTS were susceptible, third-generation cephalosporin, ciprofloxacin and azithromycin treatment appeared to be effective.

Objectives: Traditionally, the detection of intestinal parasites, including Cryptosporidium, has relied on microscopic examination of bulk stool samples. However, obtaining bulk stool samples requires waiting time, collection can be messy, and children may not readily produce a sample, particularly if severely dehydrated. This study aimed to evaluate the diagnostic performance of rectal swab samples in comparison with bulk stool samples for the point-of-care diagnosis of cryptosporidiosis using light-emitting diode auramine-phenol (LED-AP) fluorescence microscopy.

Methods: A cross-sectional study was conducted among diarrhoeic children aged 1-59 months attending six health centres in Dire Dawa and Shinile, Eastern Ethiopia. Both rectal swabs and bulk stool samples were collected, stained with auramine-phenol and examined for Cryptosporidium spp. oocysts using LED-AP fluorescence microscopy, blinded to the results obtained from the corresponding sample. The diagnostic performance of rectal swabs was evaluated against bulk stool results by estimating sensitivity, specificity, positive and negative predictive values, and the kappa coefficient. McNemar's test was used to assess whether discordant results between rectal swabs and bulk stools were statistically significant.

Results: Stool and rectal swab samples were obtained from 485 children with median age of 16 months (interquartile range: 12-28). Most children (71.5%, 347/485) were below 2 years of age. Cryptosporidium was detected in 19.4% (94/485) of stool and 17.1% (83/485) of rectal swab samples by LED-AP fluorescence microscopy, with 96.9% (95% CI 95.0-98.3%) overall concordance. Compared with bulk stools, rectal swabs showed 86.2% (95% CI 83.1-89.2%) sensitivity, 99.5% (95% CI 98.5-100.0%) specificity, and excellent agreement (κ = 0.90, 95% CI 0.81-0.99). Oocyst numbers were consistently higher in bulk stool samples than in rectal swabs.

Conclusions: Rectal swabs demonstrated high diagnostic accuracy and excellent agreement with bulk stools, supporting their use as a reliable and practical alternative when rapid results are needed or stool collection is challenging.

Background: Treatment-emergent resistance is increasingly reported in carbapenem-resistant Enterobacterales during therapy with newly developed antibiotics. However, standardized definitions and studies evaluating the impact of treatment-emergent resistance on patient 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 carbapenem-resistant Enterobacterales 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 studies, and in vitro studies focusing on ceftazidime-avibactam, meropenem-vaborbactam, imipenem-relebactam, cefiderocol, aztreonam-avibactam, 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 ceftazidime-avibactam, with Klebsiella pneumoniae carbapenemase (KPC) variants carrying Ω-loop mutations (e.g. KPC-31) as the most common reported mechanism worldwide. Resistance during or after meropenem-vaborbactam or imipenem-relebactam therapy is uncommon and only reported in selected cases from Europe where the drugs have been used more broadly. Cefiderocol resistance is mainly reported from Europe and United States in New-Delhi metallo-β-lactamase (NDM)-producing Enterobacterales and commonly linked to iron transporter defects, penicillin-binding protein 3 (PBP3) substitutions, or increased bla_NDM copy number. For aztreonam-avibactam, resistance during or after treatment has been reported in selected strains of NDM-producing Escherichia coli isolates with PBP3 and CMY mutations from Singapore and United States.

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: Information on influenza vaccine effectiveness in tropical regions with year-round influenza transmission remains scarce. We evaluated real-world influenza vaccine effectiveness in a tropical setting following the resurgence of influenza activity post-COVID-19, assessing the impact of repeated vaccination on vaccine effectiveness and waning.

Methods: Population-based retrospective cohort study, including all adult Singaporeans (1 May 2022-30 April 2024). Person-time was divided into vaccinated (<365 days prior), and unvaccinated/vaccinated ≥365 days prior, using the National Immunisation Registry. Cox regression, with overlap weights applied, was utilized to evaluate the hazard ratio (HR) of influenza hospitalisation between vaccinated/unvaccinated groups. Vaccine effectiveness was calculated as 1 HR. Relative waning of vaccine effectiveness in older adults (≥65 years) was separately evaluated via logistic regression, using weeks 2 to 9 post-vaccination as reference, and stratified by prior doses (1/2/≥3 doses) in the past 2 years.

Results: In total, 3 445 961 adult Singaporeans (≥18 years) were included, comprising 6 245 014 vaccinated/unvaccinated observations >1 376 225 223 person-days. Overall vaccine effectiveness against influenza hospitalisation was 37% (95% CI, 32-42%) amongst older adults (≥65 years). However, relative vaccine effectiveness waned to 43% of baseline (95% CI, 34-54%) by 18 to 25 weeks post-vaccination. Receipt of two or more vaccine doses in the preceding two years was associated with lower odds of vaccine failure (adjusted odds ratio = 0.81 (95% CI, 0.71-0.91%)); no significant waning was observed in those who cumulatively received three or more vaccine doses in the past two years.

Conclusion: Vaccine effectiveness against influenza hospitalisation was estimated at 37% in a tropical setting with year-round influenza transmission, although protection waned by ≥ 50% 6 months postvaccination. No significant waning was observed in those who received three or more vaccine doses in the past two years; increased revaccination frequency may mitigate waning in tropical settings.

Background: The emergence of multidrug-resistant Gram-negative bacteria poses a significant threat to global health. This has prompted the development of novel antimicrobials and combinations with β-lactamase inhibitors.

Objectives: This review aims to shed light on the resistance mechanisms associated with new drugs against Enterobacterales.

Sources: We searched PubMed relevant English literature in up to 30 June 2025, as well as including articles known to the authors. We analysed Enterobacterales resistance mechanisms for diazabicyclooctanes, bicyclic boronates, cefepime/enmetazobactam, cefiderocol, and eravacycline.

Content: The review summarises the main mechanisms of resistance to recently introduced ß-lactamase inhibitor families, including diazabicyclooctanes and bicyclic boronates, as well as other novel combinations or antimicrobials, such as cefiderocol and eravacycline.

Implications: Understanding how microorganisms develop resistance to new antimicrobials or combinations with inhibitors is essential for redesigning treatment strategies and for the design of future antibiotics.

Objectives: Sputum-based diagnostic methods for pulmonary tuberculosis (TB), including culture and nucleic acid amplification tests, provide high sensitivity and specificity. However, these methods rely on the patients' ability to produce sputum. In cases where sputum cannot be obtained, invasive procedures such as bronchoscopy may become necessary. Our objective was to evaluate the diagnostic accuracy of face mask sampling (FMS) as a noninvasive alternative.

Methods: Adults with microbiologically confirmed pulmonary TB who had received fewer than 3 days of anti-TB therapy were recruited in Chişinău, Moldova. FMS was conducted and samples were analysed on-site using Xpert MTB/RIF Ultra. Diagnostic performance was compared with conventional methods including sputum Xpert MTB/RIF Ultra and culture, which was considered a combined reference standard.

Results: Between April 2024 and February 2025, a total of 117 adults were enrolled. Of these, 88.0% (103/117) tested positive by sputum culture and/or Xpert MTB/RIF Ultra. Among participants testing positive by this combined reference standard, 59.2% (61/103) tested positive by FMS. Compared against sputum culture and sputum Xpert MTB/RIF Ultra, the sensitivity of FMS was 64.4% (95% CI: 54.4-74.4%) and 58.3% (95% CI: 48.1-68.0%), respectively. Among 90 participants with a positive sputum culture, FMS was positive in 6.0% (5/90) that were negative by sputum Xpert MTB/RIF Ultra.

Conclusions: These findings highlight the potential additive yield and complementary role of FMS. Where resources allow, FMS may serve as a valuable diagnostic tool used in parallel to conventional diagnostics to enhance the rapid detection of pulmonary TB in adults.

Background: The spread of multidrug-resistant gram-negative bacteria, particularly those with carbapenem-resistant or difficult-to-treat resistance phenotypes, is a major public health threat. New agents offer potent therapeutic options but carry the challenge of preserving their effectiveness against resistance.

Objectives: This narrative review summarizes antimicrobial and non-antimicrobial strategies to prevent or mitigate resistance development to novel agents.

Sources: We searched PubMed-MEDLINE for English-language articles published in the last 5 years.

Content: Among antimicrobial strategies, we reviewed the role of optimising pharmacokinetic/pharmacodynamic targets for novel β-lactam/β-lactamase inhibitor combinations and the impact of combination vs. monotherapy regimens. Achieving aggressive joint pharmacokinetic/pharmacodynamic targets may help prevent resistance, supported by approaches such as continuous infusion of time-dependent agents and therapeutic drug monitoring. Current evidence does not demonstrate a routine benefit of combination therapy over monotherapy for novel drugs; however, available studies are limited in size and quality, and resistance emergence has rarely been a primary endpoint. Non-antimicrobial strategies reviewed include faecal microbiota transplantation, phage therapy, and active or passive immunisation. These approaches may reduce the burden of multidrug-resistant gram-negative bacteria, particularly in high-risk populations such as immunocompromised patients, those undergoing invasive procedures, or patients with foreign bodies. By lowering pathogen load and transmission, these interventions could enhance the effectiveness of current drugs and limit further resistance development.

Implications: Prevention of resistance to novel β-lactam/β-lactamase inhibitor combinations currently relies on optimized dosing and infusion strategies. The benefit of combination regimens remains uncertain and warrants further investigation, ideally with resistance emergence as a defined endpoint and addressed with appropriate analysis. Non-antimicrobial interventions show promise as adjunctive tools in high-risk settings and merit integration into broader resistance prevention frameworks.