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Background: Whether the antiinflammatory and immunomodulatory effects of glucocorticoids may decrease mortality among patients with severe community-acquired pneumonia is unclear., Methods: In this phase 3, multicenter, double-blind, randomized, controlled trial, we assigned adults who had been admitted to the intensive care unit (ICU) for severe community-acquired pneumonia to receive intravenous hydrocortisone (200 mg daily for either 4 or 7 days as determined by clinical improvement, followed by tapering for a total of 8 or 14 days) or to receive placebo. All the patients received standard therapy, including antibiotics and supportive care. The primary outcome was death at 28 days., Results: A total of 800 patients had undergone randomization when the trial was stopped after the second planned interim analysis. Data from 795 patients were analyzed. By day 28, death had occurred in 25 of 400 patients (6.2%; 95% confidence interval [CI], 3.9 to 8.6) in the hydrocortisone group and in 47 of 395 patients (11.9%; 95% CI, 8.7 to 15.1) in the placebo group (absolute difference, -5.6 percentage points; 95% CI, -9.6 to -1.7; P = 0.006). Among the patients who were not undergoing mechanical ventilation at baseline, endotracheal intubation was performed in 40 of 222 (18.0%) in the hydrocortisone group and in 65 of 220 (29.5%) in the placebo group (hazard ratio, 0.59; 95% CI, 0.40 to 0.86). Among the patients who were not receiving vasopressors at baseline, such therapy was initiated by day 28 in 55 of 359 (15.3%) of the hydrocortisone group and in 86 of 344 (25.0%) in the placebo group (hazard ratio, 0.59; 95% CI, 0.43 to 0.82). The frequencies of hospital-acquired infections and gastrointestinal bleeding were similar in the two groups; patients in the hydrocortisone group received higher daily doses of insulin during the first week of treatment., Conclusions: Among patients with severe community-acquired pneumonia being treated in the ICU, those who received hydrocortisone had a lower risk of death by day 28 than those who received placebo. (Funded by the French Ministry of Health; CAPE COD ClinicalTrials.gov number, NCT02517489.)., (Copyright © 2023 Massachusetts Medical Society.)

Background: The management of prosthetic joint infection usually consists of a combination of surgery and antimicrobial therapy. The appropriate duration of antimicrobial therapy for this indication remains unclear., Methods: We performed an open-label, randomized, controlled, noninferiority trial to compare 6 weeks with 12 weeks of antibiotic therapy in patients with microbiologically confirmed prosthetic joint infection that had been managed with an appropriate surgical procedure. The primary outcome was persistent infection (defined as the persistence or recurrence of infection with the initial causative bacteria, with an antibiotic susceptibility pattern that was phenotypically indistinguishable from that at enrollment) within 2 years after the completion of antibiotic therapy. Noninferiority of 6 weeks of therapy to 12 weeks of therapy would be shown if the upper boundary of the 95% confidence interval for the absolute between-group difference (the value in the 6-week group minus the value in the 12-week group) in the percentage of patients with persistent infection within 2 years was not greater than 10 percentage points., Results: A total of 410 patients from 28 French centers were randomly assigned to receive antibiotic therapy for 6 weeks (205 patients) or for 12 weeks (205 patients). Six patients who withdrew consent were not included in the analysis. In the main analysis, 20 patients who died during follow-up were excluded, and missing outcomes for 6 patients who were lost to follow-up were considered to be persistent infection. Persistent infection occurred in 35 of 193 patients (18.1%) in the 6-week group and in 18 of 191 patients (9.4%) in the 12-week group (risk difference, 8.7 percentage points; 95% confidence interval, 1.8 to 15.6); thus, noninferiority was not shown. Noninferiority was also not shown in the per-protocol and sensitivity analyses. We found no evidence of between-group differences in the percentage of patients with treatment failure due to a new infection, probable treatment failure, or serious adverse events., Conclusions: Among patients with microbiologically confirmed prosthetic joint infections that were managed with standard surgical procedures, antibiotic therapy for 6 weeks was not shown to be noninferior to antibiotic therapy for 12 weeks and resulted in a higher percentage of patients with unfavorable outcomes. (Funded by Programme Hospitalier de Recherche Clinique, French Ministry of Health; DATIPO ClinicalTrials.gov number, NCT01816009.)., (Copyright © 2021 Massachusetts Medical Society.)

Background: Moderate therapeutic hypothermia is currently recommended to improve neurologic outcomes in adults with persistent coma after resuscitated out-of-hospital cardiac arrest. However, the effectiveness of moderate therapeutic hypothermia in patients with nonshockable rhythms (asystole or pulseless electrical activity) is debated., Methods: We performed an open-label, randomized, controlled trial comparing moderate therapeutic hypothermia (33°C during the first 24 hours) with targeted normothermia (37°C) in patients with coma who had been admitted to the intensive care unit (ICU) after resuscitation from cardiac arrest with nonshockable rhythm. The primary outcome was survival with a favorable neurologic outcome, assessed on day 90 after randomization with the use of the Cerebral Performance Category (CPC) scale (which ranges from 1 to 5, with higher scores indicating greater disability). We defined a favorable neurologic outcome as a CPC score of 1 or 2. Outcome assessment was blinded. Mortality and safety were also assessed., Results: From January 2014 through January 2018, a total of 584 patients from 25 ICUs underwent randomization, and 581 were included in the analysis (3 patients withdrew consent). On day 90, a total of 29 of 284 patients (10.2%) in the hypothermia group were alive with a CPC score of 1 or 2, as compared with 17 of 297 (5.7%) in the normothermia group (difference, 4.5 percentage points; 95% confidence interval [CI], 0.1 to 8.9; P = 0.04). Mortality at 90 days did not differ significantly between the hypothermia group and the normothermia group (81.3% and 83.2%, respectively; difference, -1.9 percentage points; 95% CI, -8.0 to 4.3). The incidence of prespecified adverse events did not differ significantly between groups., Conclusions: Among patients with coma who had been resuscitated from cardiac arrest with nonshockable rhythm, moderate therapeutic hypothermia at 33°C for 24 hours led to a higher percentage of patients who survived with a favorable neurologic outcome at day 90 than was observed with targeted normothermia. (Funded by the French Ministry of Health and others; HYPERION ClinicalTrials.gov number, NCT01994772.)., (Copyright © 2019 Massachusetts Medical Society.)

Background: Patients who are treated with targeted temperature management after out-of-hospital cardiac arrest with shockable rhythm are at increased risk for ventilator-associated pneumonia. The benefit of preventive short-term antibiotic therapy has not been shown., Methods: We conducted a multicenter, double-blind, randomized, placebo-controlled trial involving adult patients (>18 years of age) in intensive care units (ICUs) who were being mechanically ventilated after out-of-hospital cardiac arrest related to initial shockable rhythm and treated with targeted temperature management at 32 to 34°C. Patients with ongoing antibiotic therapy, chronic colonization with multidrug-resistant bacteria, or moribund status were excluded. Either intravenous amoxicillin-clavulanate (at doses of 1 g and 200 mg, respectively) or placebo was administered three times a day for 2 days, starting less than 6 hours after the cardiac arrest. The primary outcome was early ventilator-associated pneumonia (during the first 7 days of hospitalization). An independent adjudication committee determined diagnoses of ventilator-associated pneumonia., Results: A total of 198 patients underwent randomization, and 194 were included in the analysis. After adjudication, 60 cases of ventilator-associated pneumonia were confirmed, including 51 of early ventilator-associated pneumonia. The incidence of early ventilator-associated pneumonia was lower with antibiotic prophylaxis than with placebo (19 patients [19%] vs. 32 [34%]; hazard ratio, 0.53; 95% confidence interval, 0.31 to 0.92; P = 0.03). No significant differences between the antibiotic group and the control group were observed with respect to the incidence of late ventilator-associated pneumonia (4% and 5%, respectively), the number of ventilator-free days (21 days and 19 days), ICU length of stay (5 days and 8 days if patients were discharged and 7 days and 7 days if patients had died), and mortality at day 28 (41% and 37%). At day 7, no increase in resistant bacteria was identified. Serious adverse events did not differ significantly between the two groups., Conclusions: A 2-day course of antibiotic therapy with amoxicillin-clavulanate in patients receiving a 32-to-34°C targeted temperature management strategy after out-of-hospital cardiac arrest with initial shockable rhythm resulted in a lower incidence of early ventilator-associated pneumonia than placebo. No significant between-group differences were observed for other key clinical variables, such as ventilator-free days and mortality at day 28. (Funded by the French Ministry of Health; ANTHARTIC ClinicalTrials.gov number, NCT02186951.)., (Copyright © 2019 Massachusetts Medical Society.)

Background: Head-lice infestation is prevalent worldwide, especially in children 3 to 11 years old. Topical insecticides (i.e., pyrethroids and malathion) used as a lotion, applied twice at an interval of 7 to 11 days, are typically used for treatment. Resistance of lice to insecticides, particularly pyrethroids, results in treatment failure. The efficacy of alternative agents is controversial., Methods: We conducted a multicenter, cluster-randomized, double-blind, double-dummy, controlled trial comparing oral ivermectin (at a dose of 400 microg per kilogram of body weight) with 0.5% malathion lotion, each given on days 1 and 8, for patients with live lice not eradicated by topical insecticide used 2 to 6 weeks before enrollment. The cluster was defined as the household. Infestation was confirmed and monitored by means of fine-toothed combing. Patients were at least 2 years of age and weighed at least 15 kg; all were treated at the study sites. The primary end point was the absence of head lice on day 15., Results: A total of 812 patients from 376 households were randomly assigned to receive either ivermectin or malathion. In the intention-to-treat population, 95.2% of patients receiving ivermectin were lice-free on day 15, as compared with 85.0% of those receiving malathion (absolute difference, 10.2 percentage points; 95% confidence interval [CI], 4.6 to 15.7; P<0.001). In the per-protocol population, 97.1% of patients in the ivermectin group were lice-free on day 15, as compared with 89.8% of those in the malathion group (absolute difference, 7.3 percentage points; 95% CI, 2.8 to 11.8; P=0.002). There were no significant differences in the frequencies of adverse events between the two treatment groups., Conclusions: For difficult-to-treat head-lice infestation, oral ivermectin, given twice at a 7-day interval, had superior efficacy as compared with topical 0.5% malathion lotion, a finding that suggests that it could be an alternative treatment. (ClinicalTrials.gov number, NCT00819520.), (2010 Massachusetts Medical Society)