Clinical Microbiology and Infection最新文献

Objectives: The objectives of this study are to analyse the effect and safety of procalcitonin (PCT)-guided antibiotic therapy in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD).

Methods: We conducted a multicentre, open-label, randomized controlled trial amongst patients hospitalized for AECOPD in six hospitals in China. Enrolled patients were randomly assigned to either the PCT-guided group or the Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy-guided group. The co-primary endpoints were antibiotic prescription rate for AECOPD within 30 days after randomization (to demonstrate superiority) and treatment success rate at day 30 after randomization (to demonstrate non-inferiority). For primary outcomes, χ² test, corrected χ² test, or Fisher's exact test was used to evaluate the differences between the intervention and control groups. 95% CIs were calculated for all the outcomes. Secondary outcomes, including days of antibiotic use during hospitalization, length of hospital stay, and change in modified Medical Research Council dyspnoea scale and COPD Assessment Test score, were compared using the Student's t-test, with corresponding differences and 95% CIs calculated. Intention-to-treat (ITT) population were those who were randomly assigned, and per-protocol population were those who strictly adhered to the treatment plan.

Results: A total of 455 patients were randomly assigned, with 229 in the PCT-guided group and 226 in the GOLD-guided group. The rate of antibiotic prescription for AECOPD by day 30 was significantly lower in the PCT-guided group than that in the GOLD-guided group (38% [88/229] vs. 59% [134/226]; difference -21%; 95% CI: -30% to -12%; p < 0.0001) in the ITT analysis. There was no significant difference in the clinical treatment success rate by day 30 between the 2 groups (97% [223/229] vs. 94% [212/229]; difference 4%, 95% CI: 0-7%; p 0.06). Compared with the GOLD strategy, PCT-guided antibiotic therapy was significantly associated with lower antibiotic prescription rate during hospitalization (37% vs. 59%, difference -22%, 95% CI: -31 to -13; p < 0.0001), and fewer days of antibiotic use during hospitalization (2.63 ± 4.66 vs. 4.86 ± 4.83, difference -2.23 days, 95% CI: -1.35 to -3.11; p < 0.0001). There were no significant differences between the two groups in length of hospital stay, subsequent exacerbation rate, hospital readmission rate, intensive care unit admission, and 30-day mortality in the ITT analysis. The results in the per-protocol analysis were consistent with that in the ITT analysis.

Discussion: Compared with the GOLD strategy, PCT-guided antibiotic therapy significantly reduced the rate of antibiotic prescription for patients with AECOPD, without negatively affecting the treatment success rate.

Objectives: The objectives of this study are to investigate the presence of Clostridioides difficile in faeces of patients with recurrent C. difficile infection (rCDI) before and after faecal microbiota transplantation (FMT) and to identify risk factors for faecal C. difficile and C. difficile infection (CDI) recurrence.

Methods: n = 83 faecal sample triads (pre-FMT [∼1 day], post-FMT [∼3 weeks], and a corresponding FMT donor sample), and n = 22 long-term (∼1-3 years) follow-up faecal samples were collected from FMT-treated patients. The presence of C. difficile in faeces was assessed by enrichment broth culture and PCR (tcdB gene) and associated with patient characteristics, FMT outcome, duration of pre-FMT vancomycin, FMT donor, post-FMT antibiotic use, and faecal microbiota composition (shotgun metagenomics).

Results: The FMT cure rate for rCDI was 92.8% (77/83), with six early CDI recurrences (<2 months post-FMT). Toxigenic C. difficile was cultured in 27.7% (23/83) of all patients post-FMT, 23.4% (18/77) of patients cured 2 months post-FMT, and 13.6% (3/22) at long-term follow-up. Early CDI recurrence (n = 6) was associated with positive C. difficile culture post-FMT (21.7% [5/23] vs. 1.7% [1/60], p 0.01), post-FMT antibiotics (30.0% [3/10] vs. 4.6% [3/65], p 0.03), and a short course of pre-FMT vancomycin (median 6.0 days, IQR [5-12] vs. 18 days, IQR [10.8-29], p < 0.05). Additionally, positive C. difficile culture directly pre-FMT was associated with a short course of pre-FMT vancomycin (median 9 days IQR [5-18] vs. 17 days, IQR [10-29.2], p 0.04). Gut microbiota analyses did not reveal signatures associated with C. difficile culture result, despite statistically non-significant trends in relative abundances of the Enterobacteriaceae family, and Dorea, Roseburia, and Clostridiales species.

Discussion: Although eradication of C. difficile is not required for clinical cure of rCDI by FMT, it is associated with reduced prevalence of early CDI recurrence, as are the full completion of pre-FMT vancomycin (at least 10 days) and avoiding post-FMT antibiotics.

Objectives: The effect of the COVID-19 booster vaccination and the long-term consequences concerning preventing post-COVID-19 condition (PCC) remains unclear. We aimed to investigate the association of COVID-19 booster vaccination dose and vaccination timing before infection with the risk of PCC during the Omicron variant-dominant wave.

Methods: This population-based study included patients confirmed with COVID-19 (extracted from the Health Center Real-time Information-sharing System) aged 20-69 years, who were infected between 1 July and 31 August 2022. We used a self-report questionnaire to evaluate PCC and extracted information on vaccination from the municipal vaccine registry system. We calculated multiple propensity scores for COVID-19 vaccination status (unvaccinated, 1-2 doses and ≥3 doses) to control for baseline population differences. We then used a logistic regression model with inverse probability weighting to analyse the associations between the number of vaccine doses and the risk of PCC. Additionally, we conducted stratified analysis by gender and subgroup analysis for respiratory and neurological symptoms. Multivariable logistic regression was used to analyse the association between vaccination timing and PCC risk, adjusting for vaccination doses.

Results: Of the 7936 participants with COVID-19 (mean age 42.9 years, 4553 women), 940 (11.8%) had at least 1 PCC. Compared with people unvaccinated, those vaccinated ≥3 times before the infection had a lower probability of PCC with the OR of 0.69 (95% CI: 0.53-0.90), although we detected no association with one or two doses. This association was present in women (≥3 doses vs. unvaccinated OR: 0.70, 95% CI: 0.51-0.95) but not in men. Those vaccinated ≥3 times had fewer neurological symptoms compared with those unvaccinated (OR: 0.61, 95% CI: 0.45-0.83); however, no significant association was found for respiratory symptoms.

Discussion: This study suggests that booster vaccination could lower the risk of PCC.

Scope: The emergence of post-COVID-19 condition (PCC) after SARS-CoV-2 infection underscores the critical need for preparedness in addressing future post-acute infection syndromes (PAIS), particularly those linked to epidemic outbreaks. The lack of standardized clinical and epidemiological data during the COVID-19 pandemic has significantly hindered timely diagnosis and effective treatment of PCC, highlighting the necessity of pre-emptively standardizing data collection in clinical studies to better define and manage future PAIS. In response, the Cohort Coordination Board, a consortium of European-funded COVID-19 research projects, has reviewed data from PCC studies conducted by its members. This paper leverages the Cohort Coordination Board's expertise to propose a standardized catalogue of variables, informed by the lessons learned during the pandemic, intended for immediate use in the design of future observational studies and clinical trials for emerging infections of epidemic potential.

Recommendations: The early implementation of standardized data collection, facilitated by the PAIS data catalogue, is essential for accelerating the identification and management of PAIS in future epidemics. This approach will enable more precise syndrome definitions, expedite diagnostic processes, and optimize treatment strategies, while also supporting long-term follow-up of affected individuals. The availability of harmonized data collection protocols will enhance preparedness across European and international cohort studies, and trials enabling a prompt and coordinated response, as well as more efficient resource allocation, in the event of emerging infections and associated PAIS.

Objectives: The COVID-19 pandemic was associated with a global decrease in antimicrobial consumption (AMC) in 2020. However, the persistence of this downwards trend is not known at a global level. This study examined the global and longer-term trends in AMC after the emergence of COVID-19.

Methods: The change rate of AMC was compared (a) 2020 over 2019, (b) 2021 over 2020, and (c) 2022 over 2021 using monthly sales volume data of antimicrobials in 69 countries obtained from the IQVIA MIDAS information service. Changepoints were detected using time-series data of global monthly antimicrobial sales from November 2016 to December 2023. We defined antimicrobials as oral and parenteral drugs classified as J1 by the Anatomical Therapeutic Chemical code. Antimicrobial sales were reported in standard units, as defined by IQVIA. We assessed the data using standard units per 1000 population per day, with populations based on World Population Prospects data issued by the United Nations. In addition, interrupted time-series analysis was used to examine the impact of movement restrictions in G7 countries.

Results: In the IQVIA MIDAS data, 68 of the 69 countries had more than one changepoint between 2016 and 2023. Of these 68 countries, 61 experienced a decrease in AMC after the COVID-19 pandemic started. However, 53 of these 61 countries showed a reverse increasing trend in AMC in 2022. Interrupted time-series analysis revealed that movement restrictions had a negative impact on AMC in all G7 countries.

Discussion: The global decrease in AMC in 2020 might not have been because of COVID-19 itself but to non-pharmaceutical interventions such as movement restrictions. Human mobility could possibly be one of the key determinants of antimicrobial use at the population level.

Objectives: Disseminated histoplasmosis (DH) is a lethal fungal disease in patients living with HIV in endemic regions of the world. Diagnosis relies mainly on microscopy, culture, and antigen detection. Our goal was to evaluate the diagnostic and prognostic role of our RT-quantitative PCR (RT-qPCR) in blood specimens allowing to quantify the whole nucleic acids (WNA) load.

Methods: We tested RT-qPCR assays on serial blood (n = 325) of 105 DH patients at baseline (day 0 or day 1, D0/1) and during antifungal therapy (day 3, D3; day 4 or day 5, D4/5; day 7, D7; and day 14, D14) collected from a phase II trial comparing three different regimens of liposomal amphotericin B for DH treatment in HIV patients from Brazil.

Results: The RT-qPCR was positive at D0/D1 in 64.2% (63/98) of the patients, but positivity increased to 89% (47/53) in patients with proven infection. Urine antigen was positive in 94.2% (97/103) of DH patients. RT-qPCR positive at or after D7 was significantly associated with higher initial WNA load (Cq = 31 [27-34]) when compared with RT-qPCR negative at D7 (Cq = 38 [33-40]) (p 0.001). The WNA load was equivalent in all treatment arms, and an equivalent decrease in the % of RT-qPCR-positive patients was observed in the three arms. Flat of negative WNA slope (increase of WNA load) was associated with an increased relative risk of death at D7 (relative risk, 8.6; p 0.046) and W12 (relative risk, 3.3; p 0.008). This association was not observed when analysing antigen slopes (p > 0.5).

Discussion: We found in this study an association between the progression of flat Histoplasma WNA load during treatment and early death at D7 and D14. This diagnostic tool should be evaluated specifically in a prospective trial to assess its usefulness in identifying patients with poorer prognosis and adapt their treatment accordingly.

Background: Bacteraemia and sepsis have traditionally required continued intravenous (IV) antibiotics.

Objectives: This study aims to evaluate if early transition to oral antibiotics is non-inferior to continued IV antibiotic therapy in treating patients with bacteraemia and sepsis.

Data sources: Data sources include MEDLINE, Embase, Web of Science, the Cochrane Library, and Wanfang databases from inception to 13 July 2024, along with clinical trial registries and Google.com.

Study eligibility criteria: Study eligibility criteria include randomized controlled trials (RCTs) and cohort studies.

Participants: Participants include patients with bacteraemia and sepsis.

Interventions: Interventions include early transition to oral antibiotics vs. continued IV antibiotics. Early oral switch was defined as 5-9 days for uncomplicated Staphylococcus aureus bacteraemia, <4 weeks for complicated S. aureus bacteraemia, 3-7 days for uncomplicated Streptococcus bacteraemia, and 3-5 days for uncomplicated Enterobacterales bacteraemia.

Assessment of risk of bias: Assessment of risk of bias includes Cochrane risk of bias tool and Newcastle-Ottawa Scale.

Methods of data synthesis: Random-effect models were used to pool the data. The primary outcome was treatment failure. The non-inferiority margin for treatment failure was 10%. The Grading of Recommendations Assessment, Development, and Evaluation approach was used to rate the certainty of the evidence.

Results: In total, 38 studies (6 RCTs, 10 adjusted cohorts, and 22 unadjusted cohorts) involving 11 566 patients were included. A primary analysis of 6 RCTs and 10 adjusted cohorts comprised 7102 patients. High-certainty evidence from six RCTs showed that early transition to oral antibiotics was non-inferior to continued IV therapy for treatment failure (n = 529; OR 0.89; 95% CI: 0.54-1.48). Low-certainty evidence from five adjusted cohorts also found no significant difference in treatment failure between the two groups (n = 929; OR 0.60; 95% CI: 0.29-1.72). Moderate-certainty evidence showed that oral switch therapy significantly reduced hospital stay (n = 2041; mean difference: -5.19 days; 95% CI: -8.16 to -2.22).

Conclusions: Early transition to oral antibiotics was non-inferior to continued IV antibiotic treatment for bacteraemia and sepsis.

Objectives: The objective of this study is to assess the frequency of the novel sodium bicarbonate (NaHCO₃)-responsive phenotype, wherein clinical methicillin-resistant Staphylococcus aureus (MRSA) isolates are rendered susceptible to standard-of-care β-lactams in the presence of NaHCO₃, in a collection of 103 clinical U.S. MRSA skin and soft-tissue infection (SSTI) isolates and 22 clinical European SSTI isolates. This study determined the correlation between specific phenotypic and genotypic metrics and the NaHCO₃-responsive phenotype among U.S. SSTI isolates.

Methods: Antimicrobial susceptibility testing was performed to determine susceptibility phenotypes. Targeted and whole-genome sequencing with a genome-wide sequence analysis were conducted to identify specific and novel genotypes of interest that may be associated with the NaHCO₃-responsive phenotype. Gene expression analysis and targeted gene deletion were performed to assess the role of a specific novel genetic locus in the NaHCO₃-responsive phenotype.

Results: The NaHCO₃-responsive phenotype was identified in 78/103 U.S. isolates and 4/22 UK isolates to cefazolin (CFZ), and in 17/103 U.S. isolates and 1/22 UK isolates to oxacillin. In U.S. isolates, a significant association was identified between NaHCO₃-responsiveness to CFZ and: (a) susceptibility to amoxicillin-clavulanate; (b) a specific mecA genotype; (c) clonal complex type 8; and (d) spa type t008. Genome-wide sequence analysis identified single nucleotide polymorphisms (SNPs) in an AraC family regulator (SAUSA300_RS00540) to be exclusively found in NaHCO₃-non-responsive SSTI strains. In vitro HCO₃ exposures of NaHCO₃-responsive strains, but not -non-responsive strains, caused >2-fold upregulated expression of this gene. Deletion of this gene rendered NaHCO₃-responsive strain MRSA 11/11 no longer NaHCO₃-responsive to CFZ; we have termed this gene the staphylococcal AraC bicarbonate-response regulator.

Discussion: NaHCO₃-responsiveness is highly associated with clonal complex type 8/spa type t008, a commonly circulating genetic background in North America. The AraC bicarbonate-response regulator, staphylococcal AraC bicarbonate-response regulator, appears to be associated with the mechanism of NaHCO₃-responsiveness, but more work is needed to verify.