Background We evaluated the association between mortality and colistin resistance in Acinetobacter baumannii infections and the interaction with antibiotic therapy. Methods This is a secondary analysis of a randomized controlled trial of patients with carbapenem-resistant gram-negative bacterial infections treated with colistin or colistin-meropenem combination. We evaluated patients with infection caused by carbapenem-resistant A. baumannii (CRAB) identified as colistin susceptible (CoS) at the time of treatment and compared patients in which the isolate was confirmed as CoS with those whose isolates were retrospectively identified as colistin resistant (CoR) when tested by broth microdilution (BMD). The primary outcome was 28-day mortality. Results Data were available for 266 patients (214 CoS and 52 CoR isolates). Patients with CoR isolates had higher baseline functional capacity and lower rates of mechanical ventilation than patients with CoS isolates. All-cause 28-day mortality was 42.3% (22/52) among patients with CoR strains and 52.8% (113/214) among patients with CoS isolates (P = .174). After adjusting for variables associated with mortality, the mortality rate was lower among patients with CoR isolates (odds ratio [OR], 0.285 [95% confidence interval {CI}, .118–.686]). This difference was associated with treatment arm: Mortality rates among patients with CoR isolates were higher in those randomized to colistin-meropenem combination therapy compared to colistin monotherapy (OR, 3.065 [95% CI, 1.021–9.202]). Conclusions Colistin resistance determined by BMD was associated with lower mortality among patients with severe CRAB infections. Among patients with CoR isolates, colistin monotherapy was associated with a better outcome compared to colistin-meropenem combination therapy. Clinical Trials Registration NCT01732250

patients treated with colistin monotherapy, synergism was not protective against 14-day clinical failure (aOR 0.52, 95% CI 0.26e1.04) or 14-day mortality (aOR1.09, 95% CI 0.60e1.96). Discussion: In vitro synergism between colistin and meropenem via checkerboard method did not translate into clinical benefit.

Invasive pulmonary aspergillosis (IPA) has dire consequences in hemato-oncological patients. We report our experience with performing routine baseline chest computed tomography for early diagnosis of IPA. We found high rates of proven or probable IPA diagnosed on admission among patients with newly diagnosed acute myeloid leukemia.

In vivo fitness of carbapenem-resistant Acinetobacter baumannii (CRAB) strains in murine infection is associated with treatment failure in human infections

<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.