The treatment of choice for Stenotrophomonas maltophilia is trimethoprim-sulfamethoxazole (SXT). Fluoroquinolones (FQs) have in vitro activity against S. maltophilia; however, there is limited published information on their effectiveness. The purpose of this study is to compare the effectiveness of FQs and SXT for the treatment of S. maltophilia. A retrospective review of 98 patients with S. maltophilia infections who received SXT or FQ monotherapy was conducted. Patients >18 years old with a positive culture for S. maltophilia and clinical signs of infection who received treatment for >48 h were included. Microbiological cure and clinical response were evaluated at the end of therapy (EOT). In-hospital mortality and isolation of nonsusceptible isolates were also evaluated. Thirty-five patients received SXT, and 63 patients received FQ; 48 patients received levofloxacin, and 15 patients received ciprofloxacin. The most common infection was pulmonary. The overall microbiological cure rate at EOT was 63%. Thirteen of 20 patients (65%) who received SXT and 23 of 37 patients (62%) who received FQ had microbiological cure at EOT (P ‫؍‬ 0.832). The overall clinical success rate was 55%, 52% for those who received FQ and 61% for those who received SXT (P ‫؍‬ 0.451). In-hospital mortality was 24%, with similar rates in the two groups (25% for FQ versus 22% for SXT; P ‫؍‬ 0.546). Development of resistance on repeat culture was 30% for FQ and 20% for SXT (P ‫؍‬ 0.426). Fluoroquinolone and SXT monotherapies may be equally effective for the treatment of S. maltophilia infections. Resistance was documented in subsequent isolates of S. maltophilia in both groups.

Background Effective therapies to combat COVID-19 are urgently needed. Hydroxychloroquine (HCQ) has in vitro antiviral activity against SARS-CoV-2, but the clinical benefit of HCQ in treating COVID-19 is unclear. Randomized controlled trials are needed to determine the safety and efficacy of HCQ for the treatment of hospitalized patients with COVID-19. Methods We conducted a multicenter, double-blind, randomized clinical trial of HCQ among patients hospitalized with laboratory confirmed COVID-19. Subjects were randomized in a 1:1 ratio to HCQ or placebo for five days and followed for 30 days. The primary efficacy outcome was a severe disease progression composite endpoint (death, ICU admission, mechanical ventilation, ECMO, and/or vasopressor use) at day 14. Results A total of 128 patients were included in the intention-to-treat analysis. Baseline demographic, clinical, and laboratory characteristics were similar between HCQ (N=67) and placebo (N=61) arms. At day 14, 11 (16.4%) subjects assigned to HCQ and 6 (9.8%) subjects assigned to placebo met the severe disease progression endpoint, but this did not achieve statistical significance (P=.350). There were no significant differences in COVID-19 clinical scores, number of oxygen-free days, SARS-CoV-2 clearance, or adverse events between HCQ and placebo. HCQ was associated with a slight increase in mean corrected QT interval, an increased D-dimer, and a trend towards an increased length of stay. Conclusions In hospitalized patients with COVID-19, our data suggest that HCQ does not prevent severe outcomes or improve clinical scores. However, our conclusions are limited by a relatively small sample size, and larger randomized controlled trials or pooled analyses are needed.

Polymyxin B is used as a last treatment resort for multidrug-resistant Gram-negative bacterial infections. The objectives of this study were to examine the population pharmacokinetics of polymyxin B and investigate factor(s) influencing pharmacokinetic variability. Four serial blood samples each were collected from 35 adult patients at steady state. The concentrations of individual polymyxin B components were analyzed using a validated liquid chromatography / tandem mass spectrometry assay and combined to derive total concentrations. A maximum likelihood expectation maximization approach was used to fit the data. Various demographic variables were investigated as potential covariates for clearance and volume of distribution (V ) using linear regression analysis. A one-compartment model fit to the data satisfactorily (r = 0.96). The best-fit mean ± SD for clearance and V were 2.5 ± 1.1 L/h and 34.3 ± 16.4 L, respectively. Creatinine clearance was found to be a statistically significant covariate of clearance, but the magnitude was deemed clinically insignificant.

Polymyxin B remains the last-line treatment option for multidrug-resistant Gram-negative bacterial infections. Current U.S. Food and Drug Administration-approved prescribing information recommends that polymyxin B dosing should be adjusted according to the patient's renal function, despite studies that have shown poor correlation between creatinine and polymyxin B clearance. The objective of the present study was to determine whether steady-state polymyxin B exposures in patients with normal renal function were different from those in patients with renal insufficiency. Nineteen adult patients who received intravenous polymyxin B (1.5 to 2.5 mg/kg [actual body weight] daily) were included. To measure polymyxin B concentrations, serial blood samples were obtained from each patient after receiving polymyxin B for at least 48 h. The primary outcome was polymyxin B exposure at steady state, as reflected by the area under the concentration-time curve (AUC) over 24 h. Five patients had normal renal function (estimated creatinine clearance [CL CR ] Ն 80 ml/min) at baseline, whereas 14 had renal insufficiency (CL CR Ͻ 80 ml/min). The mean AUC of polymyxin B Ϯ the standard deviation in the normal renal function cohort was 63.5 Ϯ 16.6 mg·h/liter compared to 56.0 Ϯ 17.5 mg·h/liter in the renal insufficiency cohort (P ϭ 0.42). Adjusting the AUC for the daily dose (in mg/kg of actual body weight) did not result in a significant difference (28.6 Ϯ 7.0 mg·h/liter versus 29.7 Ϯ 11.2 mg·h/liter, P ϭ 0.80). Polymyxin B exposures in patients with normal and impaired renal function after receiving standard dosing of polymyxin B were comparable. Polymyxin B dosing adjustment in patients with renal insufficiency should be reexamined.KEYWORDS polymyxins, dosing adjustment, drug exposure P arenteral polymyxins (polymyxin B and polymyxin E [colistin]) have become one of the most important antibiotics for therapy of extensively drug-resistant Gramnegative bacterial infections over the past decade, including infections caused by carbapenem-resistant nonfermenters and carbapenem-resistant Enterobacteriaceae. The similarities and differences between polymyxin B and colistin have been reviewed elsewhere (1). Polymyxin B has been increasingly used due to the active drug form used, more straight-forward dosing, more favorable pharmacokinetics, and potentially lower incidence of nephrotoxicity than colistin (2, 3). Current U.S. Food and Drug Administration-approved prescribing information recommends polymyxin B dosing adjustment in patients with renal insufficiency (package inserts from Bedford Laboratories,