Successful Treatment of Multi-Drug Resistant Pseudomonas aeruginosa Bacteremia with the Recommended Renally Adjusted Ceftolozane/Tazobactam Regimen

Infect Dis Ther. 2016 Mar;5(1):73-9. doi: 10.1007/s40121-016-0104-3. Epub 2016 Mar 2.

Abstract

Introduction: Ceftolozane/tazobactam (C/T) is a novel antibiotic approved for complicated intra-abdominal and urinary tract infections caused by Gram-positive and Gram-negative organisms, including some MDR strains. Little is known about the use of this agent for treatment of bacteremia and even less so about the appropriateness of the renally defined regimens. We describe a case of a 66-year-old man with a history of chronic kidney disease (baseline Cr = 3-4 mg/dl) and recurrent nephrolithiasis with bilateral stents who had positive concurrent urine and blood cultures for MDR Pseudomonas aeruginosa (PSA), susceptible only to amikacin and colistin. Due to the MDR phenotype and his underlying kidney disease, the 375 mg (250 mg/125 mg) dose of C/T was given as monotherapy every 8 h for his bloodstream infection.

Methods: Once steady state was anticipated, blood was obtained at the end of infusion (1 h), and at 3, 5 and 8 h for drug concentration determination using a validated high-performance liquid chromatography method at the Center for Anti-Infective Research and Development, Hartford Hospital, Hartford.

Results: The minimum inhibitory concentration (MIC) for the PSA was 2/4 for C/T, indicating susceptibility. Concentration of ceftolozane of 21.87 µg/ml at 8 h indicated that serum concentrations were maintained above the MIC throughout the dosing interval. The patient was given 25 days of C/T and experienced a successful clinical outcome. Blood cultures obtained at 1 and 3 weeks after completion of treatment remained sterile. No adverse events were attributed to C/T.

Conclusion: In this patient, the renally adjusted dose of C/T was safe and provided sufficiently high drug concentrations that exceeded the MIC of the infecting organism over the course of therapy. More data are required to determine the clinical utility of C/T in the setting of MDR PSA bacteremia.

Keywords: Bacteremia; Ceftolozane/tazobactam; Multi-drug resistant; Pseudomonas aeruginosa.