Effect of montelukast in preventing dengue with warning signs among patients with dengue: A multicenter, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Montelukast has shown potential as a candidate treatment for dengue. This study aimed to evaluate the efficacy and safety of montelukast in preventing dengue with warning signs. METHODS: This multicenter, randomized, double-blind, placebo-controlled trial enrolled adult participants with NS1 antigenemia in Thailand. The participants were randomly assigned to receive either oral montelukast (10 mg) or a placebo for 10 days or until all symptoms resolved. RESULTS: Between January 2021 and June 2023, 358 participants were enrolled and randomly assigned (1:1) to receive either montelukast or placebo. The incidence rate of warning signs in the montelukast group and the placebo group were 9.5% and 7.8% per day, respectively. There was no difference between the two groups (HR 1.36; 95%CI 0.94-1.96, P = 0.105). No statistically significant differences were observed in the incidence rate of severe dengue, hemoconcentration, thrombocytopenia, admission, or recovery from dengue. Neither dengue shock, nor mortality occurred. The montelukast group exhibited a decreased incidence rate of transaminase elevations (0.7% vs 1.4% per day, HR: 0.48, 95%CI 0.25-0.90, P = 0.023). CONCLUSION: Oral montelukast does not reduce the incidence of warning signs among patients with dengue. Nevertheless, the observed decrease in transaminase elevations warrants further investigation to evaluate the potential effect of montelukast. CLINICAL TRIALS REGISTRATION: Clinicaltrials.gov, NCT04673422, registered on 9 December 2020.

Towards optimizing carbapenem selection in stewardship strategies: a prospective propensity score-matched study of ertapenem versus class 2 carbapenems for empirical treatment of third-generation cephalosporin-resistant Enterobacterales bacteraemia.

BACKGROUND: Third-generation cephalosporin-resistant Enterobacterales (3GCRE) are increasing in prevalence, leading to greater carbapenem consumption. Selecting ertapenem has been proposed as a strategy to reduce carbapenem resistance development. However, there are limited data for the efficacy of empirical ertapenem for 3GCRE bacteraemia. OBJECTIVES: To compare the efficacy of empirical ertapenem and class 2 carbapenems for the treatment of 3GCRE bacteraemia. METHODS: A prospective non-inferiority observational cohort study was performed from May 2019 to December 2021. Adult patients with monomicrobial 3GCRE bacteraemia receiving carbapenems within 24 h were included at two hospitals in Thailand. Propensity scores were used to control for confounding, and sensitivity analyses were performed in several subgroups. The primary outcome was 30 day mortality. This study is registered with clinicaltrials.gov (NCT03925402). RESULTS: Empirical carbapenems were prescribed in 427/1032 (41%) patients with 3GCRE bacteraemia, of whom 221 received ertapenem and 206 received class 2 carbapenems. One-to-one propensity score matching resulted in 94 pairs. Escherichia coli was identified in 151 (80%) of cases. All patients had underlying comorbidities. Septic shock and respiratory failure were the presenting syndromes in 46 (24%) and 33 (18%) patients, respectively. The overall 30 day mortality rate was 26/188 (13.8%). Ertapenem was non-inferior to class 2 carbapenems in 30 day mortality (12.8% versus 14.9%; mean difference -0.02; 95% CI: -0.12 to 0.08). Sensitivity analyses were consistent regardless of aetiological pathogens, septic shock, source of infection, nosocomial acquisition, lactate levels or albumin levels. CONCLUSIONS: Ertapenem may be of comparable efficacy to class 2 carbapenems in the empirical treatment of 3GCRE bacteraemia.