Clinical Infectious Diseases最新文献

Background: Higher than standard doses of rifampicin could improve the treatment outcome of drug-susceptible tuberculosis without compromising the safety of patients.

Methods: We performed a systematic review of prospective clinical studies including adults with pulmonary and extrapulmonary TB receiving rifampicin doses above 10mg/kg/day. We extracted the data on overall adverse events (AE), hepatic AE, sputum culture conversion (SCC) at week 8, recurrence, mortality, and pharmacokinetics. We performed a Bayesian network meta-analysis (NMA) using a random-effects model.

Results: In 19 studies, 2033 out of 3654 participants received rifampicin doses higher than 10mg/kg/day. The NMA showed an increased risk of overall and hepatic AE for the 40mg/kg/day dose (RR 4.8, 95% CrI 1.1; 25, and 15.00, 95% CrI 1.1; 58.0, respectively), but no other doses, including 50mg/kg/day showed such an increase. Increasing doses improved sputum culture conversion at week 8 (RR 1.3, 95% CrI 1.1; 1.7 for SCC with 35mg/kg/day).

Conclusion: Optimal doses of rifampicin may be between 25 and 35mg/kg/day, but should be tailored at the individual or, at least, at the population level.

Background: While invasive fusariosis and lomentosporiosis are known to be associated with fungemia, overall data on mold-related fungemia are limited, hampering early management. This study aimed to describe the epidemiology of mold-positive blood cultures.

Methods: Epidemiological and clinical data on mold-positive blood cultures from 2012 to 2022 were obtained from the RESSIF database. Pseudofungemia was excluded using modified Duthie and Denning criteria. Univariable and multivariable Firth logistical regression was used to study factors associated with 90-day mortality.

Results: Fusarium spp accounted for 67.5% of the 80 events, involving predominantly Fusarium fujikuroi spp complex (FFSC), Neocosmospora spp, and Fusarium oxysporum spp complex (FOSC). Lomentospora prolificans was the second most frequent (10%), followed by Trichoderma spp, Aspergillus spp, and Mucorales (5% each).Most patients had a history of hematological malignancy (HM) (70%). Forty-three percent had undergone allogeneic hematopoietic stem cell transplantation. Cutaneous and pulmonary lesions were common (43% each). Median time to blood culture positivity was 72 hours.HM and neutropenia were commonly reported in patients with FFSC, Neocosmospora spp, and L. prolificans fungemia. Pulmonary lesions were frequent in cases of L. prolificans fungemia. Patients with gastrointestinal conditions were frequently diagnosed with FOSC molds. HM (75%), particularly acute myeloblastic leukemia, was frequent in patients with Aspergillus spp fungemia. All patients with Trichoderma spp fungemia were exposed to corticosteroids.Day 90 mortality was 53%. Independent predictive factors of day 90 mortality included L. prolificans (odds ratio [OR], 33.3), Aspergillus spp fungemia (OR, 14.2), and corticosteroid exposure (OR, 7.85).

Conclusions: Underlying conditions and clinical presentation vary between genera and could be considered to guide early management.

Background: Chronic hepatitis C virus (HCV) infection affects >1% of the U.S. population, higher among U.S. Veterans. Direct-acting antiviral (DAA) medications are effective for viral cure, termed sustained virologic response (SVR), but repeat viremia after SVR is recognized. Prior work has been limited by use of electronic medical record data. We aim to better understand repeat viremia in the DAA era through detailed chart review.

Methods: We identified 1,129 individuals from Veteran's Health Administration (VHA) who achieved SVR using DAA therapy but subsequently had detectable serum HCV nucleic acid. A random subset of 110 were chart reviewed and assigned one of four categories using laboratory, diagnosis, and chart review data: definite reinfection (25.5%), probable reinfection (25.5%), false positive (11.8%), and presumed late relapse (37.3%). We conducted between-group analysis of variance to identify demographic, behavioral, and laboratory features specific to each.

Results: In our medical record cohort (n=1,129), substance use and unstable housing were common and median time to repeat viremia was 1.9 years. In our chart review cohort (n=110), younger age (18-34) and substance use were more frequent in definite or probable reinfection. Presumed relapse had comparatively more comorbid hepatocellular carcinoma (HCC) (20%, p<0.05) and more than half occurred prior to 1 year. The unique category of false positive has not previously been reported.

Conclusions: This study deepens understanding of HCV reinfection and relapse and highlights important features including the HCV and opioid syndemic, contribution of laboratory error, possibility of a viral reservoir in HCC, and clinical engagement implications for those with ongoing risk.

Background: There is growing interest in using high-dose rifampin for tuberculosis treatment. Recent studies suggest that triple-dose rifampin (TDR; ≥30 mg/kg/day) may be unsafe. We updated a systematic review to investigate the safety and efficacy of TDR.

Methods: We searched Embase, MEDLINE, Cochrane Central Registry of Controlled Trials, Cochrane Database for Systematic Reviews and clinicaltrials.gov for randomized-controlled trials from January 1, 1965 to February 10, 2024 comparing standard-dose rifampin (SDR) to TDR and/or double-dose rifampin (DDR) in human tuberculosis treatment. The primary outcome was pooled incidence rate ratio (IRR) of severe adverse events (SevAE) between participants receiving TDR and SDR. Pooled relative risk (RR) of death was a key secondary outcome. Meta-analysis was performed by the inverse variance method. Heterogeneity was assessed by I2 and bias assessed by Cochrane Risk of Bias 2. The protocol was prospectively registered (osf.io/kfn5a).

Results: Of the 11315 articles identified, 17 met inclusion criteria, enrolling 2313 SDR participants (17 studies), 2238 receiving DDR (12 studies), and 1199 receiving TDR (11 studies). Six studies had a high risk of bias. There was an increase in pooled SevAE among participants receiving TDR compared to SDR (IRR 1.48, 95% CI 1.12-1.96, I2 23%), driven by an increase in hepatic events (IRR 1.96, 95% CI 1.21-3.18). Death did not differ between participants receiving TDR and SDR (RR 1.19, 95% CI 0.71-1.99). One limitation is that only two included studies were blinded.

Conclusions: Regimens using TDR were associated with an increase in SevAE, raising concerns regarding safety of TDR in humans.