Infection最新文献

Background: Multidrug-resistant Gram-negative bacteria (GNB), including carbapenem-resistant Enterobacterales and Pseudomonas aeruginosa, pose a growing global health threat with limited treatment options. Imipenem-relebactam (IMI/REL) is a promising therapy, but emerging resistance patterns remain poorly defined worldwide.

Objectives: This meta-analysis aimed to provide a comprehensive assessment of global IMI/REL resistance among Enterobacterales and non-fermenting GNB, highlighting species-specific, geographic, and temporal patterns.

Methods: Studies were searched in Scopus, PubMed, and EMBASE (until October 23 2024), and all statistical analyses were conducted using R (ver. 4.2.1).

Results: A total of 149,396 Enterobacterales and non-fermenting GNB were included. Overall, IMI/REL resistance was low at 8.8% (95% CI 7.3-10.5), with Enterobacterales showing the lowest resistance (2.9%) and Pseudomonas the highest (30.7%). Resistance was higher in carbapenemase-producing Enterobacterales and non-fermenting species, and varied by infection source and geography. Temporal analysis indicated a rising trend in resistance over recent years, while data were mostly derived from the Americas, limiting global generalizability.

Conclusion: IMI/REL remains largely effective against Enterobacterales, including ESBL and MDR strains, but resistance is increasing in high-risk subgroups and non-fermenting bacteria. These findings underscore the need for local susceptibility testing, cautious empiric therapy, and robust antimicrobial stewardship to preserve the efficacy of IMI/REL.

Purpose: Burkholderia cepacia complex (BCC) showed increased resistance to recommended therapeutic agents, including levofloxacin, ceftazidime, meropenem and trimethoprim/sulfamethoxazole (TMP/SMX). BCC genospecies have different antibiogram patterns, so genospecies dynamics may affect overall susceptibility rates. This study analyzed the clinical epidemiology of BCC bloodstream infections (BSIs), assessed in vitro susceptibility of novel antibiotics, and explored prognostic factors for outcomes of BCC BSIs METHODS: We performed molecular identification to species level and antimicrobial susceptibility test to 12 antibiotics by the CLSI broth microdilution method. The 14-day mortality was used to evaluate the outcomes of BCC BSIs. Multivariate logistic regression was used for outcome analysis RESULTS: From January 2021 to December 2023, the study included 122 BCC isolates and 100 adult patients with evaluable clinical outcome. Among 122 isolates, we identified 97 isolates of B. cenocepacia, 14 of B. contaminans and 11 of non-cenocepacia and non-contaminans Burkholderia by recA or hisA analysis. Cefiderocol and ceftazidime/avibactam both showed potent activity across different genospecies. Aztreonam/avibactam and ceftolozane/tazobactam showed similar and even lower activity compared to ceftazidime and meropenem. Source control was associated with better survival (adjust odds ratio, 0.02; 95% CI 0.003-0.12). Neither regimens of antibiotic therapy nor genospecies was associated with 14-day survival CONCLUSIONS: The study highlighted the survival benefit of source control, instead of therapeutic regimens. Further, in vitro potency of cefiderocol and ceftazidime/avibactam may have a potential role to improve outcomes among patients with BCC BSIs.

During World War II, Polish physicians Eugeniusz Łazowski and Stanisław Matulewicz fabricated a typhus epidemic, which they reported in detail only after the war. They injected inactivated Proteus bacteria to patients suffering from mild, flu-like ailments in order to trigger a positive Weil-Felix reaction in their serum, the standard diagnostic tool for typhus at that time. These falsely labelled typhus patients would then be protected from seizure by German occupiers, who were much concerned about transmission of this highly deadly disease. According to Łazowski and Matulewicz, this action saved many Poles from forced labour and other atrocities. We here show that this false epidemic was possible with the simple means available at that time, and that it is plausible from a medical and a historical perspective. How the two doctors combined medical textbook knowledge, social responsibility, epidemiological know-how and ingenuity under war conditions is outstanding. They should serve as role models for humanity and resistance under oppressive systems for present and future generations of physicians.

Purpose: This study aimed to describe the molecular epidemiology and antimicrobial susceptibility profiles of invasive (iGAS) and non-invasive (non-iGAS) Group A Streptococcus (GAS) isolates collected from Greek children, including all the Greek fatal pediatric GAS infections, in 2023.

Methods: GAS isolates were prospectively collected from children (0-16 years) with iGAS and non-iGAS infections from January to December 2023. Antimicrobial susceptibility was examined with the disk diffusion method and the MIC of resistant isolates was determined. Emm typing was performed in all isolates. Whole genome analysis was performed on emm1 GAS isolates collected from fatal cases.

Results: GAS isolates from 510 children, with median (IQR) age: 67.8 (46.1-96.0) months, were analyzed in the study. There were 30 (5.9%) iGAS cases, of which nine were fatal. All isolates were penicillin-susceptible, while the resistance rates to tetracycline, erythromycin, and clindamycin were 16.9%, 11.6% and 5.1%, respectively. The M, cMLSB and iMLSB phenotypes were found in 33/510 (6.5%), 22/510 (4.3%) and 4/510 (0.8%) isolates, respectively. Thirty-two emm types were detected, with the most prevalent being emm12 (41.0%), emm1 (26.9%) and emm89 (7.5%). Among the different emm types, emm1 was marginally associated with iGAS. The emm12 type was associated with resistance to clindamycin (p = 0.039). GAS isolates from the nine deceased children p-value were identified as emm1 (7/9), of which 6/7 belonged to M1_UK lineage, and emm12 (2/9).

Conclusion: A predominance of emm12 and emm1 was detected in non-iGAS isolates and of emm1 in iGAS isolates, and specifically M1_UK in fatal isolates. A decline in GAS macrolide resistance, compared to previous studies in our area, was detected.

Purpose: To evaluate adherence patterns, effectiveness, and sexually transmitted infection (STI) incidence among pre-exposure prophylaxis (PrEP) users in Germany and identify strategies to optimize HIV and STI prevention through individualized care and alternative PrEP modalities.

Methods: A single-site, pseudonymized prospective cohort study was conducted in Hamburg, Germany from December 2019 to September 2024. Clinical and laboratory data were linked with structured behavioral surveys from PrEP users at the University Medical Center Hamburg-Eppendorf.

Results: Of 980 consented individuals, 589 initiated PrEP (median age 32 years, 97.1% male, and 81.8% were born in Germany). The mean follow-up was 102.3 weeks (IQR: 38.6-151.4), totaling 1189.5 person-years. Daily users averaged 315 days of PrEP coverage per year (IQR: 293.0-361.9 days), whereas on-demand users averaged 219 days (IQR: 138.4-311.6 days), highlighting substantial variability in usage patterns. The overall dropout rate was 46.9%. No cases of HIV occurred during active PrEP use. STI incidence remained high 52.4 /100 PY (95% CI: 47.8-57.4, n = 421) for daily PrEP users, 38.9/100 PY (95% CI: 30.1-49.5, n = 79) for event-driven users, predominantly due to Chlamydia trachomatis (21.1/100 PY) and Neisseria gonorrhoeae (18.8/100 PY). Interest in long-acting PrEP was high (70%), especially among illicit substance users (OR 5.54). Renal function remained stable during follow-up.

Conclusion: PrEP demonstrated high effectiveness despite heterogeneous risk burden and generally stable renal function. This supports flexible, person-centered models with simplified, risk-stratified monitoring and long-acting options. To extend impact beyond MSM, services should add multilingual access and women- and migrant-inclusive outreach.

The misdiagnosis of acute febrile illness (AFI) aetiology is associated with antibiotic overuse and improper patient management. To develop novel strategies, a more comprehensive understanding of the pathophysiological mechanisms underlying the early response to different causes of fever is essential.Here we examined the host response to AFI, through the retrospective investigation of serum samples from febrile patients with bacterial infection (n = 52) or malaria (n = 73). The systemic levels of CXCL10, IFNγ, IL-2, IL-4, IL-6, IL-8, procalcitonin (PCT), TRAIL, ICAM-1, VCAM-1, osteopontin, TNFα, MMP-2 and MMP-9 were measured by multiplex immunoassays, while the relative abundance of 37 different surface markers of circulating extracellular vesicles (EVs) was determined using the MACSplex kit (Miltenyi Biotec).Markers of endothelial activation (CD29⁺, CD62P⁺, CD9⁺ EVs) and immune cell migration (MMP-2 and MMP-9) appeared elevated in bacterial AFI (q-value < 0.05). Mediators associated with antigen recognition (CD8⁺, CD81⁺, HLA-DR/DP/DQ⁺ EVs) and cytokine storm (IFNγ, CXCL10, TNFα) were instead prominent in malaria infection (q-value < 0.005). Interestingly, HLA-DR/DP/DQ⁺ EVs distinguished between bacterial and malaria AFI with area under the ROC curve (AUC) of 0.87, not significantly different from platelets' AUC (0.92), which was the best individual discriminator.Our results showed different biological processes as associated with bacterial and malaria AFI, paving the way for the identification of novel potential markers for a timely and reliable AFI diagnosis. The study also provides novel insights on the potential role of EVs as mediators of pro-inflammatory signalling during acute fever, which should be investigated more comprehensively in vitro.

Chronic infections are a persistent global health problem and are frequently sustained by polymicrobial communities rather than by a single pathogen. This review brings together current evidence for the infectome concept, defined as the dynamic set of pathogenic or pathobiont taxa in the host, their shared functional capacities, and the interactions that connect them. We analyze how community-level processes promote persistence, cause diagnostic failure, and drive therapeutic resistance, with emphasis on multispecies biofilms, quorum sensing, horizontal gene transfer, metabolic cooperation, and immune modulation. We also highlight advances in multi-omics and computational integration that now permit high-resolution infectome profiling and reveal taxa and interspecies networks that are not captured by routine culture. Clinical examples such as periodontitis, bacterial vaginosis, chronic rhinosinusitis, device-associated infections, and recurrent urinary tract infections show the translational value of this shift. On the therapeutic side, we discuss infectome-informed options including antivirulence agents, biofilm-disrupting enzymes, bacteriophages and lysins, community-wide susceptibility-guided regimens, and microbiome-restoration strategies. Finally, we identify the main requirements for the field: standardized sampling and analytic workflows, reproducible infectome signatures linked to clinical outcomes, and trial designs able to capture ecological dynamics and meet regulatory expectations for community-targeted interventions. Adopting an infectome perspective can enable precision infectiology and reshape the management of chronic and recurrent infections.