Efficacy, pharmacokinetic and pharmacodynamic profile of ceftolozane + tazobactam in the treatment of complicated urinary tract infections

ABSTRACT

Introduction: Urinary tract infections (UTIs) are the second most common nosocomially acquired infections, responsible for approximately 21% of healthcare-associated pyelonephritis and 10.5% of urosepsis. Worldwide trends of increasing resistance resulted in the urgent need for novel antimicrobials that would be active against bacterial resistance mechanisms as an alternative to carbapenems, which are considered last resort antibiotics.

Areas covered: The current review is based on a Medline search of published English language literature and contains summary information regarding the evaluation of pharmacologic properties, efficacy, safety and activity of ceftolozane+tazobactam against common bacterial resistance mechanisms.

Expert opinion: In vivo and vitro studies demonstrated high activity of ceftolozane+tazobactam in the combination of 2:1 against a variety of uropathogens, including ESBL-producers. Phase II and Phase III studies performed in patients with complicated UTIs showed good tolerability and safety of ceftolozane+tazobactam when prescribed intravenously 1.5 g every 8 h for 7 days and at least non-inferiority to a high dose (750 mg) of levofloxacin. The pharmacokinetics of ceftolozane+tazobactam makes it a worthy alternative to carbapenems in cases of complicated UTIs, also caused by multidrug resistant uropathogens.

KEYWORDS:

• Antimicrobial agents
• beta-lactamase inhibitors
• cephalosporins
• ceftolozane-tazobactam
• CXA-201
• Pseudomonas aeruginosa
• urinary tract infections
• uropathogens

Declaration of interest

FME Wagenlehner was the consultant and principal investigator in the clinical Phase III ASPECT-cUTI study in complicated urinary tract infections including pyelonephritis. JF Alidjanov has received a 1-year Clinical/Lab Scholarship grant from European Urological Scholarship Programme for his Research Project on urinary tract infections. Authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Notes

1. GR – grade of recommendations.

2. LE – level of evidence.