Favipiravir is an oral broad-spectrum inhibitor of viral RNA-dependent RNA polymerase that is approved for treatment of influenza in Japan. We conducted a prospective, randomized, open-label, multicenter trial of favipiravir for the treatment of COVID-19 at 25 hospitals across Japan. Eligible patients were adolescents and adults admitted with COVID-19 who were asymptomatic or mildly ill and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Patients were randomly assigned at a 1:1 ratio to early or late favipiravir therapy (the same regimen starting on day 6 instead of day 1). The primary endpoint was viral clearance by day 6. The secondary endpoint was change in viral load by day 6. Exploratory endpoints included time to defervescence and resolution of symptoms. Eighty-nine patients were enrolled, of whom 69 were virologically evaluable. Viral clearance occurred within 6 days in 66.7% and 56.1% of the early and late treatment groups (adjusted hazard ratio [aHR], 1.42; 95% confidence interval [95% CI], 0.76–2.62). Of 30 patients who had a fever (≥37.5°C) on day 1, time to defervescence was 2.1 days and 3.2 days in the early and late treatment groups (aHR, 1.88; 95%CI, 0.81–4.35). During therapy, 84.1% developed transient hyperuricemia. Favipiravir did not significantly improve viral clearance as measured by RT-PCR by day 6 but was associated with numerical reduction in time to defervescence. Neither disease progression nor death occurred to any of the patients in either treatment group during the 28-day participation (Japan Registry of Clinical Trials jRCTs041190120).

ObjectivesThrombocytopenia (TP) is a common adverse effect of linezolid (LZD). However, risk factors for LZD-associated TP have been reported in Western patients with relatively heavy body weight. The aim of this study was to determine the risk factors for LZD-associated TP in Asian population.Materials and methodsA retrospective cohort study was conducted among 101 consecutive patients who received LZD therapy (1,200 mg/day) between July 2003 and December 2013 at a tertiary referral hospital in Tokyo, Japan. The patients with obvious other causes for TP were excluded. The information of target infectious disease, patients’ age, gender, body weight, body mass index, baseline serum creatinine (SCr), baseline platelet count, and treatment duration was collected retrospectively. TP was defined as ≥50 % decrease in platelet count from baseline. Bi- and multi-variate analyses were performed.ResultsA total of 101 patients were included (mean age [SD] 64 [18]; male gender [%], 57 [56]). Median duration [range] of LZD therapy was 14 days [1–67]. LZD-associated TP was identified in 42 patients (42 %). For TP, adjusted odds ratio (OR) [95 % CI] of daily per kg dose (DPKD) and SCr was 1.14 [1.05–1.26] and 1.51 [1.01–2.50], respectively.ConclusionsHigher DPKD and elevated SCr are significantly associated with LZD-associated TP. These findings suggest that daily dose of LZD should be adjusted using body weight, as typically done in pediatrics, in adults as well. Renal function also should be considered for dose adjustment.

An association between visit-to-visit variability (VVV) of blood pressure (BP) and renal damage was recently reported in a cross-sectional study. We aimed to clarify the longitudinal effect of VVV of BP on deterioration of renal function in patients with non-diabetic chronic kidney disease (CKD). We retrospectively studied 56 patients with non-diabetic CKD (stage 3 or 4) who visited our nephrology clinic between September 1994 and May 2011. VVV of BP was defined as the standard deviation and coefficient of variation (CV) of office BP measured at 12 consecutive visits. Main outcomes were the annual decline in the estimated glomerular filtration rate (eGFR) and the composite renal end point defined as a doubling of serum creatinine or the need for dialysis. The median observation period was 83 months. Standard deviation and CV of office systolic BP (SBP) were significantly associated with the slope of the eGFR after adjustments for confounders. The adjusted risk for composite renal end points more than doubled for each increment of 1-standard deviation of the standard deviation of office SBP (hazard ratio (HR) 2.20, P=0.001), and for each increment of 1-standard deviation of the CV of office SBP (HR 2.12, P=0.002). The present study demonstrated that the visit-to-visit variability of BP is an independent determinant of deterioration of renal function in patients with non-diabetic CKD.

Raoultella planticola (formerly Klebsiella planticola) is a Gram-negative bacterium that has been rarely reported in association with human infection. Here we describe a case of cholangitis complicated with septic shock caused by R. planticola in an immunocompromised patient with advanced cancer who underwent endoscopic retrograde cholangiopancreatography to extract common bile duct stones. The infection was cleared by piperacillin-tazobactam treatment.