Clinical Microbiology and Infection最新文献

Objectives: Patients' perspectives on outcomes of clinical trials is critical to the design of meaningful trials. As they are the primary recipients of treatment, it is important to focus on outcomes that are of value to the patients. We planned a study involving patients in defining and prioritizing endpoints for intervention trials for bloodstream infections (BSI).

Methods: A survey was conducted at Rambam Health Care Campus, targeting hospitalized patients over 18 years old. Participants were asked to score the importance of various outcomes on a scale of 1 to 10, 10 being most important. We calculated the mean and median and dispersion measures per outcome.

Results: 732 randomly selected patients were approached; 378 were not available due to technical reasons. Of the remaining 354 approached to take the survey, 300 consented and participated in the study. The median age was 51.9 years, with 55.3% female. Death was scored as the most important outcome, while the length of hospital stay was the least important.

Conclusions: Eliciting patient views on outcome importance was challenging but revealed key insights. Patients prioritized death, functional decline, and the development of secondary infections. Non-clinical outcomes, such as microbiological failure, were less clearly understood. Future studies should focus on clinical outcomes and include larger, more diverse patient populations to enhance the relevance of BSI trials.

Background: Maintaining access to a broad range of old and new antibiotics is increasingly difficult due to supply, market and demand issues. Next to immediate negative consequences for individual patients and healthcare systems, antibiotic unavailability can accelerate resistance development due to unmotivated use of suboptimal broad-spectrum antibiotics.

Objectives: While academics and policymakers agree that lack of access to antibiotics is a major public challenge, there are widely different situations of lack of access which are not always clearly identified. Therefore, this paper aims to clarify potential confusion by delving into four different types of lack of access, their specific causes, consequences and potential solutions.

Sources: The paper builds on a narrative review of academic and policy literature about lack of access to antibiotics and potential solutions to address it.

Content: We discuss causes as well as economic and clinical consequences of four different types of antibiotic unavailability: short-term shortages, long-term shortages, deregistrations and lack of registration. The discussion is supported by examples from Norway, Romania and Ethiopia, three countries characterized by clearly different market sizes and ability to pay. Common causes for all types of lack access include unattractive markets, dependence on few suppliers and insufficient communication, whereas other causes are specific to one type (e.g., insufficient inventories cause short-term shortages or regulatory complexity hinders registration). Longer lack of access entails more serious clinical consequences and higher risk of resistance development, but may not correspondingly increase costs in the long-term if alternatives are identified.

Implications: It is essential to understand the type of unavailability at hand because no single solution can address all types. For instance, stockpiling addresses short-term shortages, but not long-term ones or deregistrations. However, supply chain transparency and pooled procurement are remedies that support other solutions and can cope with several types of lack of access.

Background: The diagnosis of Pneumocystis jirovecii pneumonia (PCP) can be challenging because of diagnostic tests that are imperfect and/or invasive. The Fungitell serum (1→3)-β-D-glucan (BDG) assay is a non-invasive blood test studied for PCP; however, the manufacturer-recommended cut-off of 80pg/mL is not well validated for this disease.

Objectives: We conducted a systematic review and meta-analysis to determine the diagnostic test accuracy of the Fungitell BDG assay for the diagnosis of PCP.

Methods: Data Sources A search strategy of MEDLINE and Embase from a previous meta-analysis on BDG was updated to January 31, 2024. Test Fungitell BDG assay. Reference Standard One or more of: lung biopsy, bronchoalveolar lavage, induced sputum, or nasopharyngeal swab specimens tested for PCP by histopathology, microscopy using immunofluorescence or staining, or polymerase chain reaction. Assessment of Risk of Bias The QUADAS-2 tool. Methods of Data Synthesis Diagnostic test accuracy data of the Fungitell serum BDG assay across all reported cut-offs were pooled by meta-analysis. We then evaluated a categorical approach using <80pg/mL as a rule-out threshold and ≥400pg/mL as a rule-in threshold.

Results: 26 articles were included comprising 5111 patients and 1150 PCP cases. At the conventional cut-off of 80pg/mL, the overall pooled sensitivity and specificity were 83.5% (95% Confidence Interval [95%CI]=72.8-90.6) and 75.5% (95%CI=66.0-83.0), respectively. At a pre-test probability of <20% and a BDG <80pg/mL, the post-test probability would be <5% (negative predictive value >95%). At 400pg/mL, sensitivity was reduced to 63.5% (95%CI=45.8-78.1) with specificity increased to 93.6% (95%CI=88.6-96.5). At a pre-test probability of 47.5%, a BDG >400pg/mL would have a post-test probability of >90%.

Discussion: A categorical approach using <80pg/mL to rule-out and >400pg/mL to rule-in PCP may allow for a more nuanced interpretation based on pre-test probability. More accurate estimates of pre-test probability and further external validation is required.

Objectives: Pseudomonas aeruginosa (PA) is a common causative pathogen of pneumonia acquired in the ICU. The aim of this study was to determine the incidence of PA ICU pneumonia (PAIP) and to quantify its independent association with PA colonisation at different body sites.

Methods: Adult patients on mechanical ventilation at ICU admission were prospectively enrolled across 30 European ICUs. PA colonisation in the perianal area and in the lower respiratory tract were assessed within 72 hours after ICU admission and twice weekly until ICU discharge. PAIP development was evaluated daily. Competing risk models with colonisation as a time-varying exposure and ICU death and discharge as competing events were fitted and adjusted for confounders to investigate the association between PA carriage and PAIP.

Results: 1971 subjects were enrolled. The colonisation prevalence with P. aeruginosa in the first 72 hours of ICU admission was 10.4% (179 perianal, 51 respiratory), while the acquisition incidence during the ICU stay was 7.0% (158 perianal, 47 respiratory). Of the 43 (1.8%) patients who developed PAIP, 11 (25.6%) were PA colonised on admission and 9 (20.9%) acquired colonisation prior to PAIP onset. Both perianal (adjusted sub distribution hazard ratio [aSHR] 4.4, 95%CI 1.7-11.6) and respiratory colonisation (aSHR 4.6, 95%CI 1.9-11.1) were independently associated with PAIP development.

Conclusions: PAIP incidence was higher in PA colonised vs non-colonised patients. Both colonisation of the rectum and of the respiratory tract were associated with development of PAIP. The increased risk of P. aeruginosa colonisation for subsequent infection provides an opportunity for targeted preventive interventions.

Objectives: Extrapulmonary tuberculosis (EPTB) presents with nonspecific symptoms which can pose a significant diagnostic challenge. Various factors, including age, sex, and HIV status, have been associated with an increased risk of developing EPTB. However, the influence of the lineage of the infecting Mycobacterium tuberculosis complex (Mtbc) strain remains controversial.

Methods: Between 2008 and 2023, comprehensive clinical data from 1035 cases, along with whole genome sequencing (WGS) data of the respective Mtbc strains have been collected. To examine the association between Mtbc lineage and EPTB, we calculated crude and adjusted odds ratios (OR) using logistic regression and performed propensity score matching with a subset of the cohort.

Results: Of the 1035 patients, 272 had exclusively extrapulmonary disease and 138 had both pulmonary and extrapulmonary disease. Patients infected with a lineage 1 strain had the highest odds of developing EPTB in the univariate analysis (OR: 3.30, 95% CI: 1.97-5.49). However, Mtbc lineage was not a significant predictor in the multivariable model, while the odds of developing extrapulmonary disease were higher among patients born in the South-East Asian region (adjusted OR: 6.00, 95% CI: 3.41-10.69) and the Eastern Mediterranean Region (adjusted OR: 5.95, 95% CI: 3.61-9.96) compared to those born in the European region. Further, female sex and age were significant positive predictors for EPTB.

Conclusions: Our results demonstrate that host factors, such as geographic origin, age and sex are stronger predictors for EPTB than infection with a Mtbc strain of a particular lineage. Further investigation of this host-pathogen interaction is needed.

Background: Carbapenem-resistant Gram-negative bacteria represent a challenging healthcare threat, accounting for metallo-β-lactamases (MBL) production increase across the world. MBL-producing Enterobacterales and P. aeruginosa represent the main target for ultimate antibiotics combinations due to the difficulty to include carbapenems within the antimicrobial treatment.

Objectives: To provide a comprehensive review of the current knowledge about the aztreonam/avibactam (ATM-AVI) combination, which has emerged as a promising option for treating MBL-producing bacteria. Sources Relevant in vitro and in vivo studies on ATM-AVI effectiveness.

Content: The review summarizes ATM-AVI characteristics and targets, examining how avibactam restores aztreonam effectiveness against MBLs while protecting it from other β-lactamases. Key in vitro and in vivo studies on ATM-AVI efficacy are presented.

Implications: This review provides insights into the potential clinical management implications of ATM-AVI for treating carbapenem-resistant Gram-negative infections, particularly those caused by MBL-producing organisms.