Clinical Microbiology and Infection最新文献

Background: Bacteriophage (phage) therapy is a promising alternative antimicrobial approach that has the potential to transform the way we treat bacterial infections. The antibiotic resistance crisis is driving renewed interest in phage therapy. There are currently no licensed phage therapy medicinal products and phage therapy is used in small but growing patient numbers on an unlicensed basis.

Objectives: This article provides guidelines on the assessment of patient suitability for unlicensed phage therapy for clinicians in the United Kingdom.

Sources: This article builds on Health Improvement Scotland's recommendation for the consideration of phage therapy in difficult-to-treat infections and the experience of the author group, who have collectively assessed the suitability of 30 patients for phage therapy.

Content: In the United Kingdom, unlicenced medicines, including phages, may be considered to meet special clinical needs. The use of unlicenced medicines is governed by national legislation and local National Health Service trust policies. Phages can be used in any National Health Service trust and decisions about suitability should be made through existing local clinical management pathways. This article sets out guidelines to support local clinical teams in the assessment of patient suitability for phage therapy. Clinical and microbiological considerations are presented, including allergy and pregnancy.

Implications: The assessment of patient suitability for phage therapy is within the scope of local clinical teams. Local assessment through existing clinical management pathways will develop confidence and competence in phage therapy among clinical teams nationally and ensure timely patient care.

Objectives: The pathogen of community-acquired pneumonia (CAP) in children is typically uncertain during initial treatment, leading to systematic empiric antibiotic use. This study investigates if having rapid multiplex PCR results in the emergency department (ED) improves empiric treatment.

Methods: OPTIPAC, a French multicentre study (2016-2018), enrolled patients consulting for CAP at the paediatric ED in 11 centres. Patients were randomized to either receive a multiplex PCR test plus usual care or usual care alone and followed for 15 days. The primary outcome was the appropriateness of initial antimicrobial management, determined by a blinded committee.

Results: Of the 499 randomized patients, 248 were tested with the multiplex PCR. Appropriateness of the antibiotic treatment was higher in the PCR group (168/245, 68.6% vs. 120/249, 48.2%; Relative risk 1.42 [1.22-1.66]; p < 0.0001), chiefly by reducing unnecessary antibiotics in viral pneumonia (RR 3.29 [2.20-4.90]). No adverse events were identified.

Discussion: The multiplex PCR assay result at the ED improves paediatric CAP's antimicrobial stewardship, by both reducing antibiotic prescriptions and enhancing treatment appropriateness.

Objectives: The value of C-reactive protein point-of-care testing (CRP POCT) to guide antibiotic prescriptions in adults has previously been emphasized. The aim of this study was to assess the impact of CRP POCT on antibiotic prescriptions by general practitioners (GPs) for suspected lower respiratory tract infections in children ≥3 years old and in adults.

Methods: This was an open-label randomized trial (NCT03540706) conducted in 26 GPs in France between October 2019 and March 2023. Of the 404 participating patients, 207 (51.2%) were randomized to the CRP POCT group and 197 (48.8%) to the control group (i.e. no CRP POCT). During consultations, GPs measured CRP levels in patients randomized to the CRP POCT group. The primary endpoint was the proportion of patients in each group who were prescribed antibiotics by their GP during the consultation. Z-tests were used for comparisons.

Results: The overall proportion of patients treated with antibiotics was similar in the CRP POCT (n = 89/207, 43% CI: 36.2, 50.0) and in the control group (n = 94/197, 47.7% CI: 40.6, 54.9), difference: -4.7 CI: -14.4, 5.0; p 0.3. Overall, 75% of the GPs followed CRP-based antibiotic prescription recommendations in the CRP POCT group.

Discussion: CRP POCT did not reduce antibiotic prescriptions in this trial.

Objectives: To evaluate posaconazole (POS) gastro-resistant tablets for preventing invasive fungal disease (IFD) in haematopoietic stem cell transplantation (HSCT) patients and analyse POS plasma concentrations.

Methods: A single-arm trial was designed with a historical cohort as a control. Patients aged 13 years and older undergoing HSCT at the HSCT Center of Blood Diseases Hospital, Chinese Academy of Medical Sciences between December 2020 and May 2022 were enrolled, prospectively taking POS gastro-resistant tablets orally from day 1 to day 90 post-transplant and monitoring plasma concentrations. We also identified a retrospective cohort treated with alternative antifungal prophylaxis between January 2018 and December 2020, matched using propensity score methods. The primary outcome was the cumulative incidence of IFD at day 90 post-transplant.

Results: The prospective study involved 144 patients receiving POS gastro-resistant tablets for IFD prevention, contrasting with 287 patients receiving non-POS tablets. By day 90 post-transplant, the POS tablet group exhibited a significantly lower cumulative incidence of IFD (2.81%; 95% CI, 0.09-5.50% vs. 7.69%; 95% CI, 4.60-10.78%; p 0.044). Adverse events were comparable between the groups with liver changes in 33/144 (22.92%) vs. 84/287 (29.27%) (p 0.162), and renal injuries in 15/144 (10.41%) vs. 37/287 (12.89%) (p 0.457). Mean POS plasma concentrations on days 4, 8, 15, and 22 post-administration were 930.97 ng/mL, 1143.97 ng/mL, 1569.8 ng/mL, and 1652.57 ng/mL, respectively.

Discussion: Patients administered POS gastro-resistant tablets for antifungal prophylaxis experienced a lower cumulative incidence of IFD. POS plasma concentrations in HSCT patients stabilized by day 15 of medication.

Background: Plasma collected from recovered patients with COVID-19 (COVID-19 convalescent plasma [CCP]) was the first antibody-based therapy employed to fight the COVID-19 pandemic. While the therapeutic effect of early administration of CCP in COVID-19 outpatients has been recognized, conflicting data exist regarding the efficacy of CCP administration in hospitalized patients.

Objectives: To examine the effect of CCP compared to placebo or standard treatment, and to evaluate whether time from onset of symptoms to treatment initiation influenced the effect.

Data sources: Electronic databases were searched for studies published from January 2020 to January 2024.

Study eligibility criteria: Randomized clinical trials (RCTs) investigating the effect of CCP on COVID-19 mortality in hospitalized patients with COVID-19.

Participants: Hospitalized patients with COVID-19.

Interventions: CCP versus no CCP.

Assessment of risk of bias: Cochrane risk of bias tool for RCTs.

Methods of data synthesis: The random-effects model was used to calculate the pooled risk ratio (RR) with 95% CI for the pooled effect estimates of CCP treatment. The Grading of Recommendations Assessment, Development and Evaluation was used to evaluate the certainty of evidence.

Results: Twenty-seven RCTs were included, representing 18,877 hospitalized patients with COVID-19. When transfused within 7 days from symptom onset, CCP significantly reduced the risk of death compared to standard therapy or placebo (RR, 0.76; 95% CI, 0.61-0.95), while later CCP administration was not associated with a mortality benefit (RR, 0.98; 95% CI, 0.90-1.06). The certainty of the evidence was graded as moderate. Meta-regression analysis demonstrated increasing mortality effects for longer interval to transfusion or worse initial clinical severity.

Conclusions: In-hospital transfusion of CCP within 7 days from symptom onset conferred a mortality benefit.