Clinical Infectious Diseases最新文献

Background: Only 63% of patients initiating multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) treatment in 2020 were treated successfully. 24-Week all-oral bedaquiline, pretomanid, and linezolid (BPaL)-based regimens have demonstrated higher rates of treatment success and have been recommended by the World Health Organization. Operational research is urgently required to evaluate these regimens in non-trial settings.

Methods: This was a prospective cohort study of patients with microbiologically confirmed MDR/RR-TB and pre-extensively drug-resistant TB (pre-XDR-TB) initiated on BPaL-based regimens in Belarus and Uzbekistan (February 2022-June 2023). All clinical care and research procedures were delivered by treating physicians. After treatment completion, patients were followed up at 6 and 12 months, including collecting sputum to ascertain recurrence. The primary objective was to estimate the effectiveness (cured or treatment completed) and safety (the occurrence of serious adverse events) of BPaL-based regimens.

Results: A total of 677 patients initiated treatment with BPaL-based regimens during the study. We documented successful treatment outcomes in 95.3% (427/448) of patients with MDR/RR-TB treated with BPaL plus moxifloxacin and 90.4% (207/229) of patients with pre-XDR-TB treated with BPaL plus clofazimine. 10.2% (69/677) experienced serious adverse events including 24 deaths (3.5%), 11 of which occurred during treatment. 83.3% (20/24) of deaths were not related to TB or TB treatment. Of patients who were successfully treated and completed 12-month follow-up, 0.5% (2/383) had recurrence.

Conclusions: BPaL-based regimens for MDR/RR-TB and pre-XDR-TB are safe and highly effective in non-trial settings. These regimens should be considered for widespread implementation globally, and further research is needed to evaluate their performance in other key populations.

Background: Ensitrelvir, a severe acute respiratory syndrome coronavirus-2 main protease inhibitor, has demonstrated clinical and virologic efficacy in previous studies.

Methods: In this global phase 3 trial, nonhospitalized adults with mild-to-moderate coronavirus disease 2019 (COVID-19) and symptom onset within 5 days were randomized (1:1) to receive once-daily ensitrelvir (375 mg day 1, 125 mg days 2-5) or blinded matching placebo. The primary endpoint was the restricted mean time to sustained (≥2 days) resolution of 15 COVID-19 symptoms, recorded in participant daily diaries, through day 29 in participants starting treatment within 3 days after symptom onset. Virologic efficacy and safety were assessed.

Results: Of 2093 participants, 1888 started treatment within 3 days after symptom onset. Mean time to symptom resolution was 12.5 and 13.1 days with ensitrelvir and placebo, respectively (difference, -0.6 days; 95% confidence interval, -1.38 to 0.19; P = .14). On day 4, ensitrelvir reduced least-squares mean RNA by 0.72 log10 copies/mL more than placebo (95% confidence interval, 0.55-0.90). Among those with positive viral cultures at enrollment, 274/287 (95.5%) ensitrelvir-treated versus 210/280 (75.0%) placebo-treated participants had negative cultures on day 4. RNA rebound was similar (<1.5%) between groups. The proportion of participants with ≥1 adverse event was similar with ensitrelvir (61.5%) and placebo (60.6%). No treatment-related serious adverse events or deaths occurred. Three (0.3%) ensitrelvir-treated and 1 (0.1%) placebo-treated participants had COVID-19-related hospitalizations by day 29.

Conclusions: Despite the evidence of antiviral activity with ensitrelvir, this trial did not demonstrate a significant difference in time to sustained symptom resolution.

Background: Peripherally inserted central catheters (PICCs) have a 29% complication rate. This systematic review assessed 25 interventions to prevent PICC-associated infectious and noninfectious complications in participants of all ages.

Methods: We searched electronic databases (MEDLINE, Embase, Cochrane Library, WHO Global Index Medicus, CINAHL) and reference lists for randomized (RCTs) and nonrandomized studies published from January 1, 1980-May 8, 2024. We dually selected studies, assessed risk of bias, extracted data, and rated certainty of evidence (COE). We included both single interventions of interest and combinations of at least two (bundle/multimodal). If three or more RCTs existed, we conducted Bayesian random-effects meta-analyses.

Results: Seventy-four studies met our eligibility criteria (60 on individual interventions, 14 on bundle/multimodal), addressing 13 of 25 research questions. The majority were conducted in high-income countries; 36 focused on neonates. Evidence was very uncertain for 11 of the 13 research questions. Evidence with a stronger COE showed that ultrasound-guided catheter insertion reduced phlebitis/thrombophlebitis in adults compared to non-ultrasound-guided insertion (five RCTs; risk ratio [RR] 0.19, 95% credible interval 0.08-0.50); silicone catheters increased phlebitis/thrombophlebitis compared to nonsilicone (one RCT, RR 2.00, 95% confidence interval [95%CI] 1.26-3.17). Bundle interventions decreased local infections (one RCT, RR 0.47, 95%CI 0.31-0.72) and phlebitis/thrombophlebitis in adults (one RCT, RR 0.35, 95%CI 0.22-0.56) compared to routine care.

Conclusions: Ultrasound-guided catheter insertion and nonsilicone catheters effectively prevented PICC complications. The evidence for other comparisons was too uncertain to draw conclusions, highlighting the urgent need for additional studies on prevention and control interventions.