Efficacy of Ceftolozane/Tazobactam in Comparison with Piperacillin/Tazobactam in Severe Pseudomonas aeruginosa Pneumonia Swine Model
Abstract
Introduction: Ceftolozane/Tazobactam (C/T) is a promising treatment option against nosocomial pneumonia caused by Pseudomonas aeruginosa. Objectives: We assessed the efficacy and the clinically relevant outcomes of C/T versus piperacillin/tazobactam (TZP) in a P. aeruginosa pneumonia model. Methods: Severe pneumonia by P.aeruginosa (C/T and TZP MIC 4 and 64 mg/L, respectively) was induced in 21 pigs (32.1±1.7Kg). After 24h, animals were randomized to receive: saline(control), 50 mg/kg of C/T q8h, and 200 mg/kg of TZP q8h. Animals were mechanically ventilated for 76h. Every 24h, tracheal secretions were cultured, clinical parameters and pulmonary mechanics were assessed. Upon autopsy, lungs were harvested to quantify P.aeruginosa concentration. The primary outcome were bacterial burden in tracheal secretions and lung tissue. The secondary outcomes were pulmonary, clinical parameters, respiratory mechanics, and the emergence of resistance. Results: Figure 1 summarize the main outcomes. Of note, exposure to TZP caused an increase in MIC in 5 out of 7 animals, while no resistance or increase was detected in C/T treated animals. Conclusions: In a swine model of P.aeruginosa pneumonia, resistant to TZP, ceftolozane/tazobactam decreased tracheal respiratory bacterial burden, with similar tissue concentrations and no evidence of the emergence of antibiotic resistance in comparison with TZP.
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