Background Gram-negative bacteremia is a major cause of morbidity and mortality in hospitalized patients. Data to guide the duration of antibiotic therapy are limited. Methods This was a randomized, multicenter, open-label, noninferiority trial. Inpatients with gram-negative bacteremia, who were afebrile and hemodynamically stable for at least 48 hours, were randomized to receive 7 days (intervention) or 14 days (control) of covering antibiotic therapy. Patients with uncontrolled focus of infection were excluded. The primary outcome at 90 days was a composite of all-cause mortality; relapse, suppurative, or distant complications; and readmission or extended hospitalization (>14 days). The noninferiority margin was set at 10%. Results We included 604 patients (306 intervention, 298 control) between January 2013 and August 2017 in 3 centers in Israel and Italy. The source of the infection was urinary in 411 of 604 patients (68%); causative pathogens were mainly Enterobacteriaceae (543/604 [90%]). A 7-day difference in the median duration of covering antibiotics was achieved. The primary outcome occurred in 140 of 306 patients (45.8%) in the 7-day group vs 144 of 298 (48.3%) in the 14-day group (risk difference, –2.6% [95% confidence interval, –10.5% to 5.3%]). No significant differences were observed in all other outcomes and adverse events, except for a shorter time to return to baseline functional status in the short-course therapy arm. Conclusions In patients hospitalized with gram-negative bacteremia achieving clinical stability before day 7, an antibiotic course of 7 days was noninferior to 14 days. Reducing antibiotic treatment for uncomplicated gram-negative bacteremia to 7 days is an important antibiotic stewardship intervention. Clinical Trials Registration NCT01737320.

IntroductionLeptospirosis has recently come to international attention as a globally important re-emerging infectious disease. Our case is unusual given the season, location and setting in which leptospirosis occurred. According to the New York City Board of Health, there were only two other cases of leptospirosis in New York City in the year that our patient was diagnosed.Case presentationA 49-year-old healthy Chinese man presented to our hospital with sepsis and multiorgan failure. The patient did not respond to antibiotics and his multiorgan failure worsened. His workup did not show any significant findings except for a positive nasopharyngeal swab result for influenza A. Later the patient developed hemoptysis with evidence of bilateral infiltrates on radiography. His status mildly improved after he was started on steroids. Eventually, a microagglutination test confirmed the presence of antibodies against Leptospira icterohaemorrhagiae. The patient subsequently recovered after a course of intravenous antibiotics.ConclusionThe case of fulminant leptospirosis presented here should serve to alert health care providers and the general public to the clinical importance of this severe, sometimes fatal, disease. Leptospirosis should be considered early in the diagnosis of any patient with acute, non-specific febrile illness with multiorgan system involvement or high fever in a returning traveler. In addition, not only should it be considered in tropical and rural areas between late summer to early fall, but also in any location or time if the risk factors are present.

Objective To identify risk factors for functional decline after hospitalization for Gram-negative bacteremia. Patients and methods A prospective cohort study based on a randomized controlled trial conducted between January 1, 2013 and August 31, 2017 in Israel and Italy. Hospitalized patients with Gram-negative bacteremia who survived until day 90 and were not bedridden at baseline were included. The primary end point was functional decline at 90 days. Results Five hundred and nine patients were included. The median age of the cohort was 71 years (interquartile range [IQR], 60–80 years), 46.4% (236/509) were male and 352 of 509 (69%) patients were independent at baseline. Functional decline at 90 days occurred in 24.4% of patients (124/509). In multivariable analysis; older age (odds ratio [OR], 1.03; for an one-year increment, 95% confidence interval [CI] 1.01–1.05), functional dependence in instrumental activities of daily living at baseline (OR, 4.64; 95% CI 2.5–8.6), low Norton score (OR, 0.87; 95% CI 0.79–0.96) and underlying comorbidities: cancer (OR, 2.01; 95% CI 1.14–3.55) and chronic pulmonary disease (OR, 2.23 95% CI 1.12–4.42) and longer length of hospital stay (OR 1.09; for one-day increment, 95% CI 1.04–1.15) were associated with functional decline. Appropriate empirical antibiotic treatment was associated with lower rates of functional decline within 90 days (OR, 0.4; 95% CI 0.21–0.78). Conclusions Patients surviving bloodstream infections have poor long term trajectories after clinical recovery and hospital discharge. This has vast implications for patients, their family members and health policy makers.

<b><i>Introduction:</i></b> Reports regarding the external validity of randomized controlled trials (RCTs) are scarce. We aimed to assess the population external validity of an investigator-initiated RCT on the duration of antibiotics for the treatment of Gram-negative bacteremia by comparing patients included in the RCT to patients that were not included in the trial. <b><i>Methods:</i></b> Hospitalized patients with Gram-negative bacteremia were recruited into an RCT and randomized to receive 7 or 14 days of covering antibiotic therapy in Israel and Italy from 2013 to 2017. In a concomitant observational study, RCT participants were compared with patients who fulfilled the inclusion criteria but were not included in the trial due to participation in other trials, discharge before approached by researchers, refusal to participate, or unwillingness of the treating physician to allow participants’ recruitment. <b><i>Results:</i></b> Six hundred and four RCT patients were compared with 613 nonincluded patients. Almost 50% of nonincluded patients (288/613) were dependent on others for activities of daily living at baseline compared to 37.7% of RCT participants (228/604). Dementia was nearly 2-fold more frequent in nonincluded patients than those included (5.9% [36/613] versus 3.6% [22/604], <i>p</i> = 0.07). Patients who were not included in the RCT were more likely to acquire their infection in the hospital (53.3% [327/613] versus 29.1% [176/604], <i>p</i> &#x3c; 0.001). The primary composite outcome of mortality, clinical failure, readmissions, or extended hospitalization at 90 days occurred in 353 of 613 nonincluded patients (57.6%) compared to 299 of 604 RCT participants (49.6%), <i>p</i> = 0.005. However, on multivariate analysis noninclusion in the RCT was not an independent risk factor for clinical failure and mortality. <b><i>Conclusions:</i></b> RCTs, even with broad eligibility criteria, do not represent the whole spectrum of patients and leave out a population with more severe illness for whom the evidence is lacking.