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.

Efficacy of anidulafungin in the treatment of experimental Candida parapsilosis catheter infection using an antifungal-lock technique.

OBJECTIVES: The effectiveness of anidulafungin versus liposomal amphotericin B (LAmB) for treating experimental Candida parapsilosis catheter-related infection by an antifungal-lock technique was assessed. METHODS: Two clinical strains of C. parapsilosis (CP12 and CP54) were studied. In vitro studies were used to determine the biofilm MICs (MBIC50 and MBIC90) by XTT reduction assay and LIVE/DEAD biofilm viability for anidulafungin and LAmB on 96-well microtitre polystyrene plates and silicone discs. An intravenous catheter was implanted in New Zealand white rabbits. Infection was induced by locking the catheter for 48 h with the inoculum. The 48 h antifungal-lock treatment groups included control, 3.3 mg/mL anidulafungin and 5.5 mg/mL LAmB. RESULTS: Anidulafungin showed better in vitro activity than LAmB against C. parapsilosis growing in biofilm on silicone discs. MBIC90 of LAmB: CP12, >1024 mg/L; CP54, >1024 mg/L. MBIC90 of anidulafungin: CP12, 1 mg/L; CP54, 1 mg/L (P ≤ 0.05). Moreover, only anidulafungin (1 mg/L) showed >90% non-viable cells in the LIVE/DEAD biofilm viability assay on silicone discs. No differences were observed between the in vitro susceptibility of anidulafungin or LAmB when 96-well plates were used. Anidulafungin achieved significant reductions relative to LAmB in log10 cfu recovered from the catheter tips for both strains (P ≤ 0.05). Only anidulafungin achieved negative catheter tip cultures (CP12 63%, CP54 73%, P ≤ 0.05). CONCLUSIONS: Silicone discs may be a more reliable substrate for the study of in vitro biofilm susceptibility of C. parapsilosis. Anidulafungin-lock therapy showed the highest activity for experimental catheter-related infection with C. parapsilosis.