Real-Life Use of Ceftolozane/Tazobactam for the Treatment of Bloodstream Infection Due to Pseudomonas aeruginosa in Neutropenic Hematologic Patients: a Matched Control Study (ZENITH Study).

We sought to assess the characteristics and outcomes of neutropenic hematologic patients with Pseudomonas aeruginosa (PA) bloodstream infection (BSI) treated with ceftolozane-tazobactam (C/T). We conducted a multicenter, international, matched-cohort study of PA BSI episodes in neutropenic hematologic patients who received C/T. Controls were patients with PA BSI treated with other antibiotics. Risk factors for overall 7-day and 30-day case fatality rates were analyzed. We compared 44 cases with 88 controls. Overall, 91% of episodes were caused by multidrug-resistant (MDR) strains. An endogenous source was the most frequent BSI origin (35.6%), followed by pneumonia (25.8%). There were no significant differences in patient characteristics between groups. C/T was given empirically in 11 patients and as definitive therapy in 41 patients. Treatment with C/T was associated with less need for mechanical ventilation (13.6% versus 33.3%; P = 0.021) and reduced 7-day (6.8% versus 34.1%; P = 0.001) and 30-day (22.7% versus 48.9%; P = 0.005) mortality. In the multivariate analysis, pneumonia, profound neutropenia, and persistent BSI were independent risk factors for 30-day mortality, whereas lower mortality was found among patients treated with C/T (adjusted OR [aOR] of 0.19; confidence interval [CI] 95% of 0.07 to 0.55; P = 0.002). Therapy with C/T was associated with less need for mechanical ventilation and reduced 7-day and 30-day case fatality rates compared to alternative agents in neutropenic hematologic patients with PA BSI. IMPORTANCE Ceftolozane-tazobactam (C/T) has been shown to be a safe and effective alternative for the treatment of difficult to treat infections due to Pseudomonas aeruginosa (PA) in the general nonimmunocompromised population. However, the experience of this agent in immunosuppressed neutropenic patients is very limited. Our study is unique because it is focused on extremely immunosuppressed hematological patients with neutropenia and bloodstream infection (BSI) due to PA (mainly multidrug resistant [MDR]), a scenario which is often associated with very high mortality rates. In our study, we found that the use of C/T for the treatment of MDR PA BSI in hematological neutropenic patients was significantly associated with improved outcomes, and, in addition, it was found to be an independent risk factor associated with increased survival. To date, this is the largest series involving neutropenic hematologic patients with PA BSI treated with C/T.

Vancomycin MIC Does Not Predict 90-Day Mortality, Readmission, or Recurrence in a Prospective Cohort of Adults with Staphylococcus aureus Bacteremia.

Staphylococcus aureus bacteremia (SAB) is a tremendous health burden. Previous studies examining the association of vancomycin MIC and outcomes in patients with SAB have been inconclusive. This study evaluated the association between vancomycin MICs and 30- or 90-day mortality in individuals with SAB. This was a prospective cohort study of adults presenting from 2008 to 2013 with a first episode of SAB. Subjects were identified by an infection surveillance system. The main predictor was vancomycin MIC by MicroScan. The primary outcomes were death at 30 and 90 days, and secondary outcomes included recurrence, readmission, or a composite of death, recurrence, and readmission at 30 and 90 days. Covariates included methicillin susceptibility, demographics, illness severity, comorbidities, infectious source, and antibiotic use. Cox proportional-hazards models with propensity score adjustment were used to estimate 30- and 90-day outcomes. Of 429 unique first episodes of SAB, 11 were excluded, leaving 418 individuals for analysis. Eighty-three (19.9%) participants had a vancomycin MIC of 2 µg/ml. In the propensity-adjusted Cox model, a vancomycin MIC of 2 µg/ml compared to <2 µg/ml was not associated with a greater hazard of mortality or composite outcome of mortality, readmission, and recurrence at either 30 days (hazard ratios [HRs] of 0.86 [95% confidence interval {CI}, 0.41, 1.80] [P = 0.70] and 0.94 [95% CI, 0.55, 1.58] [P = 0.80], respectively) or 90 days (HRs of 0.91 [95% CI, 0.49, 1.69] [P = 0.77] and 0.69 [95% CI, 0.46, 1.04] [P = 0.08], respectively) after SAB diagnosis. In a prospective cohort of patients with SAB, vancomycin MIC was not associated with 30- or 90-day mortality or a composite of mortality, disease recurrence, or hospital readmission.