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

Expert Opin Drug Metab Toxicol. 2016 Aug;12(8):959-66. doi: 10.1080/17425255.2016.1201065. Epub 2016 Jul 7.

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; CXA-201; Pseudomonas aeruginosa; beta-lactamase inhibitors; ceftolozane-tazobactam; cephalosporins; urinary tract infections; uropathogens.

Publication types

  • Comparative Study
  • Review

MeSH terms

  • Anti-Infective Agents, Urinary / administration & dosage
  • Anti-Infective Agents, Urinary / pharmacology
  • Anti-Infective Agents, Urinary / therapeutic use*
  • Cephalosporins / administration & dosage
  • Cephalosporins / pharmacology
  • Cephalosporins / therapeutic use*
  • Drug Administration Schedule
  • Drug Resistance, Multiple, Bacterial
  • Humans
  • Penicillanic Acid / administration & dosage
  • Penicillanic Acid / analogs & derivatives*
  • Penicillanic Acid / pharmacology
  • Penicillanic Acid / therapeutic use
  • Tazobactam
  • Urinary Tract Infections / drug therapy*
  • Urinary Tract Infections / microbiology

Substances

  • Anti-Infective Agents, Urinary
  • Cephalosporins
  • ceftolozane, tazobactam drug combination
  • Penicillanic Acid
  • Tazobactam