European Journal of Clinical Microbiology & Infectious Diseases最新文献

Purpose: Antimicrobial-resistant (AMR) related deaths were predicted to have the greatest impact in Türkiye, Greece, Italy, and Portugal by 2050. Outpatient misuse and overuse of antibiotics are major contributors. We aimed to identify the underlying causes of inappropriate antibiotic use in outpatient settings and to develop context-specific, expert-driven solutions.

Methods: A two-round e-Delphi process was used among experts, including primary care physicians, infectious disease specialists, ENT doctors, emergency medicine physicians, public health professionals, pharmacists, and policymakers working in outpatient settings. A 7-point Likert scale assessed 47 potential causes and 25 proposed solutions. Consensus was defined using interquartile range, median, and percent agreement. Expert agreement was assessed using Kendall's W.

Results: 109 experts from 52 cities in Greece, Italy, Portugal, and Türkiye participated, with a response rate of 88% (109/124) in both rounds. Consensus was reached on 6 (12.76%) causes and 21 solutions (84%). Patient-related factors, such as low health literacy, limited awareness of AMR, and expectations of rapid recovery, emerged as major contributors. System-level shortcomings, including weak regulatory enforcement and underfunded stewardship efforts, were also identified. High-priority solutions included stricter regulation of non-prescription antibiotic sales, updated national prescribing guidelines, and integration of clinical decision-support tools.

Conclusion: Addressing AMR in high-risk countries requires both systemic reform and individual behaviour change. While common challenges exist, national differences require tailored strategies, such as healthcare accessibility, appointment length, and physician-patient communication. Sharing best practices is critical, but context-sensitive strategies are essential to effectively address this global health threat.

Bloodstream infections (BSIs) are serious conditions caused by the presence of microorganisms in the blood. Although blood culture remains the diagnostic gold standard, it is time-consuming. Neutrophil activation plays a central role in the early immune response to infection and can be quantified using the Neutrophil-Reactive Intensity (NEUT-RI) parameter, derived from hematological analyzer using the fluorescence flow cytometry technology. The purpose of this study is to evaluate NEUT-RI as an early marker of BSI and compare its diagnostic performance with standard infection biomarkers. We conducted a retrospective study involving 120 inpatients with documented BSI. Each inpatient underwent blood testing for PCT (Procalcitonin), serum CRP (C-Reactive Protein), WBCs (White Blood Cells), neutrophil absolute count within 12 h prior to blood culture sampling. NEUT-RI values were retrieved from the complete blood count. A control group of 52 inpatients with negative blood cultures was also analyzed. Median NEUT-RI was significantly higher in BSI patients than in controls (53.43 FI vs 48.65 FI; p < 0.001). ROC (Receiver Operating Characteristic) curve analysis showed an AUC (Area Under the Curve) of 0.785 for NEUT-RI, with 72.5% sensitivity and 76.9% specificity at a cut-off of 50.7 FI. Only Procalcitonin (AUC 0.882) outperformed NEUT-RI (p = 0.01). Our findings suggest that NEUT-RI increases in the early stages of bacteremia and may serve as a useful early indicator of bloodstream infection. NEUT-RI could be integrated into multi-parametric diagnostic algorithms to improve early detection of BSIs. Further studies are warranted to validate these preliminary results.

Background: Respiratory syncytial virus (RSV) peaks in fall-winter and is well known in children. In adults, however, severe outcomes especially compared to influenza are less well-defined. With RSV vaccines newly available in 2024, this study evaluated RSV burden versus influenza.

Methods: Multicenter retrospective cohort study including adults ≥ 50 years with RT-PCR-confirmed influenza (A/B) or RSV during two pre-COVID-19 fall-winter seasons (2016-2018). Outcomes were hospital admission, length of stay, short-term favorable outcome (within 5 days), intensive care unit (ICU) admission, superinfection, and 90-day mortality.

Results: Of 386 patients, 288 (74.6%) had influenza (A: 190, B: 98), 98 (25.4%) had RSV. RSV patients exhibited more frequently chronic respiratory diseases (41.8% vs. 24.3%, p = 0.001) and prior hospitalized respiratory infections (39.8% vs. 25.7%, p = 0.01) than influenza patients. Admission rates trended higher for RSV (88.8%, n = 87) than influenza (80.2%, n = 231; p = 0.06). Among admissions (n = 318), RSV stays were significantly longer (median 12 days [IQR 8-18] vs. 9 days [IQR 4-15], p = 0.006), with lower short-term favorable outcomes than influenza B (13.8% vs. 41.4%, aOR 5.1 [1.53-16.86], p < 0.01), but not influenza A (p = 0.34). ICU admissions were higher in younger age groups (50-64 years: aOR 13.4 [2.7-67.2], p = 0.002; 65-74 years: aOR = 4.17 [1.18-14.7], p = 0.03), regardless of viral etiology. Superinfection (10.2% vs. 12.5%, p = 0.57) and 90-day mortality (6.9% vs. 12.9%, p = 0.18) were similar.

Conclusion: RSV imposes a burden comparable to influenza in admission and mortality, with slower recovery than influenza B. These pre-COVID-19 data provide a critical baseline to support targeted RSV vaccination for adults with comorbidities and aged ≥ 50 years, informing future recommendations.

Purpose: This review aims to provide an overview of current knowledge on the involvement of QS in phage infection. The role of QS in bacterial defence against phages is emphasized, without overlooking the fact that QS can sometimes also promote phage infection. We also review the implications of QS in phage therapy and current perspectives.

Methods: For the bibliographic review, PubMed and Google Scholar were used to search for publications on "quorum-sensing" and "phage infection".

Results: The relationships between bacteria and phages are extremely complicated and involve several mechanisms. Quorum sensing (QS) is a communication system involved in controlling bacterial fitness, both at population and individual levels. Phages (viruses that infect bacteria) play a major role in the natural regulation of bacterial populations. In order to protect themselves, bacteria have developed several defence mechanisms involving different levels of protection, such as prevention of phage entry and phage assembly, degradation of phage nucleic acids, and entrance in a dormant state (persistence). QS has recently been shown to affect some of these phage defence mechanisms. In this review, the main influence of QS in phage infection is discussed. Finally, some innovative treatment approaches, including using engineered phages harbouring T7aiiA QQ enzyme and QS inhibitors such as SsoPox-W2631 and penicillinic acid, are also considered. However, it is important to note that the use of QS-interfering molecules may also reduce the efficacy of phage therapy.

Conclusion: QS is an important mechanism that affects several bacterial metabolisms, particularly in phage defence. Despite the complex interaction between QS and phages, modifying QS has been found to enhance phage therapy.

Mobile colistin resistance (mcr) genes, initially described in livestock and humans, remain less frequently reported in companion animals. We conducted a global genomic survey of 14,643 bacterial genomes retrieved from the NCBI National Database of Antibiotic Resistant Organisms and identified 105 (0.7%) mcr-positive Enterobacterales from dogs (79.0%) and cats (21.0%). Escherichia coli (73.3%) and the Enterobacter cloacae complex (20.9%) predominated, with the mcr-1 and mcr-9 variants being the most frequent. Most genomes originated from Asia, Europe, and North America, reflecting the uneven geographic distribution of sequenced mcr-positive strains. Genomic analysis revealed a genetic plurality and co-occurrence of mcr genes with CTX-M-type extended-spectrum β-lactamases (46.6%), carbapenemases (5.7%), and 16S rRNA methyltransferases (8.6%), particularly in international high-risk clones. These findings underscore the diversity and epidemiological relevance of mcr-positive bacteria in pets, reinforcing the need for closer monitoring through One Health-based surveillance.

Purpose: Effective antiretroviral therapy has significantly reduced mortality rates among people living with HIV (PWH) and has altered the distribution of causes of death. We aimed to investigate trends in causes of death among PWH over time.

Methods: We investigated all reported deaths in the Turkish Clinical Microbiology and Infectious Diseases Society HIV Cohort. Causes of death were categorized and analyzed across four time periods: 1997-2006, 2007-2014, 2015-2019, and 2020-2023. Factors associated with HIV/AIDS-related causes of death were compared to other causes of death.

Results: A total of 9,334 PWH were followed, of which 414 deaths (4.4%) occurred, including 44 (11.6%) among individuals assigned female at birth. The most common causes of death were AIDS-related illnesses (57.7%), non-AIDS-related cancers (11.1%), and cardiovascular diseases (9.9%). Among causes of death, the rate of AIDS-related diseases has declined over the years (p<0.001). Rates of non-AIDS-related cancers (p=0.013) and non-AIDS-related infections (p=0.008) have increased, and deaths due to comorbid conditions such as cardiovascular diseases have remained stable (p=0.193). In multivariate analysis, AIDS-related deaths were significantly associated with an increased risk in individuals who had an AIDS-defining illness at baseline. The rate of AIDS-related deaths declined in later periods compared to 1997-2006. AIDS-related deaths decreased with older age at HIV diagnosis. The rate of AIDS-related deaths was less frequent among men who have sex with men, smokers, and ex-smokers, individuals on antiretroviral therapy, those with higher CD4 counts, and individuals with comorbid diseases.

Conclusions: Among all deaths, AIDS-related deaths have declined. In contrast, the proportion of deaths attributed to non-AIDS-related cancers has increased, and the mortality rate from cardiovascular disease has remained unchanged over the years. Therefore, it is crucial to implement interventions that address comorbid conditions, particularly by enhancing the management of cardiovascular disease and cancer.

Purpose: This study aimed to investigate differences in virulence factors between exoU and exoS lineages of Pseudomonas aeruginosa from microbial keratitis (MK).

Method: Initially, the whole genome sequence (WGS) data of 20 exoU and 19 exoS P. aeruginosa keratitis isolates from India and Australia retrieved from NCBI genome database was assessed for the presence of different virulence genes using the Virulence Factors Database (VFDB). To confirm the VFDB results, a separate set of keratitis isolates consisting of 148 P. aeruginosa (36 from India and 112 from Australia) were screened by PCR for the presence of exoU, exoS, and the virulence genes found to be significantly different in the VFDB analysis. Flagellar length was measured by transmission electron microscopy (TEM) and phospholipase D (PLD) activity was determined by Amplex Red Phospholipase D Assay Kit.

Results: From 327 virulence-associated genes, the VFDB analysis identified significant differences in four virulence factor genes pilA, pldA, algP, and flaG between the exoU and exoS groups (all p < 0.05).When combining PCR and VFDB data from 187 keratitis isolates, pldA (83.6% vs. 31.8%, p < 0.01) and flaG (80% vs. 55.3%, p < 0.01) showed significantly higher prevalence in the exoU than the exoS. Similar trends were observed among Australian isolates while within the Indian isolates, only pldA (77.3% vs. 35.3%, p < 0.01) differed significantly. No association was found between flagellar length and flaG, but PLD activity correlated with the presence of the pldA.

Conclusion: The pldA and flaG genes might be relevant virulence factors for the exoU group, potentially associated with the severity of MK.

Objectives: The present study aimed to investigate the effects of Ureaplasma urealyticum (U. urealyticum, UU) infection on sperm DNA, semen parameters and sperm quality in male patients for interpreting the proposed mechanisms of male infertility.

Methods: The morphology of sperm was observed under the standard bright-field microscope at 1000× magnification after the hematoxylin-eosin (HE) staining. All the experiments of semen biochemical parameters of seminal plasma zinc, fructose, citric acid, neutral α-glucosidase, elastase, and sperm acrosin activity were performed on the SK6000 Fully Automated Biochemical Analyzer. The values of DNA fragmentation index (DFI) and high DNA stainability (HDS) in semen were tested by using the sperm chromatin structure assay (SCSA).

Results: The seminal plasma elastase level increased (p = 0.0006) and sperm morphology abnormality increased in UU-positive group (p < 0.0001). There was no significant difference in each of other semen parameters including semen volume, leukocyte concentration, seminal plasma zinc, fructose, citric acid, neutral α-glucosidase, and sperm acrosin activity (p > 0.05 for each). The values of DFI in the UU-positive group were higher than those in the UU-negative group (p < 0.01), but there was no significant difference in HDS between UU-positive group and UU-negative group (p > 0.05).

Conclusions: UU infection in male genital tract can not only significantly increase the seminal plasma elastase levels and sperm morphological abnormalities, but also markedly elevate sperm DNA fragmentation levels and decrease sperm DNA integrity. It may represent an important pathway contributing to male infertility.

Purpose: Due to rising antibiotic resistance rates, treating infections becomes more complex. To tackle this, old and new antibiotics will need to be used more frequently for additional indications outside the scope of their original registrations. We aimed to introduce a mixed methods approach to identify off-label indications for antimicrobials in specific settings, and applied this to an antimicrobial not commonly used in the Netherlands, ceftaroline.

Methods: We developed the Exploratory Positioning of Antimicrobials in New Settings (EXPANS) approach, which includes a systematic literature review, an observational study and an expert meeting. We applied our approach to ceftaroline to explore off-label indications and its potential use in outpatient parenteral antimicrobial therapy (OPAT).

Results: In both the literature and Dutch hospitals, ceftaroline was mainly prescribed as second-line treatment following treatment failure or side effects, often for endocarditis and bone and joint infections. Combination therapy with daptomycin was common, and ceftaroline was used in OPAT. In Dutch hospitals, only 48 patients were prescribed ceftaroline in the last five years. Experts experienced a lack of evidence, reimbursement issues, and the risk of leukopenia as key barriers to its use. Dutch experts noted potential for off-label use of ceftaroline in endocarditis and as prophylaxis for prosthetic joint revision surgery.

Conclusion: The components used in our EXPANS approach were complementary, gathering original data on clinical experiences with specific antimicrobials and identifying barriers to their use in practice. We recommend this systematic approach to explore untapped potential of existing antimicrobial agents and optimize their use.

We investigated the genetic and biochemical determinants that reduce the activity of several β-lactam/β-lactamase inhibitor combinations against Serratia marcescens clinical isolates after carbapenem exposure. We analyzed paired clinical S. marcescens isolates recovered before and after treatment of a prolonged infection with ertapenem. We tested the susceptibility of the isolates to ceftazidime/avibactam, aztreonam/avibactam, imipenem/relebactam and meropenem/vaborbactam. Mechanisms of resistance were investigated using whole-genome sequencing and RNA expression analysis. The bla_FOX-14 gene was cloned into Escherichia coli, to assess the phenotype in wild-type and low-permeability backgrounds. FOX-14 was purified to determine steady-state kinetics and avibactam IC₅₀. The baseline isolate was susceptible to ceftazidime/avibactam, aztreonam/avibactam, imipenem/relebactam and meropenem/vaborbactam, whereas the post-therapy isolate displayed high-level resistance. The post-therapy isolate harboured a premature stop in ompF, loss of an additional putative porin, and overexpressed of bla_FOX-14 due to triplication of the bla_FOX-14 surrounding region. Cloning of bla_FOX-14 conferred an extended-spectrum AmpC phenotype in E. coli, which was further accentuated under reduced permeability. Complementation of the post-therapy resistant clinical isolate with functional OmpF restored susceptibility to new β-lactam/β-lactamase inhibitor combinations. Purified FOX-14 displayed marked cephalosporinase activity against ceftazidime and cefepime, with low K_m values, while negligible turnover for aztreonam and ertapenem and a low avibactam IC₅₀. In S. marcescens, in vivo resistance in clinical isolates emerged from FOX-14 overproduction combined with reduced outer-membrane permeability, predominantly due to OmpF disruption. These findings elucidate resistance to newer β-lactam/β-lactamase inhibitor combinations and warrant close monitoring of antimicrobial activity during carbapenem-based therapy for S. marcescens infections.