Journal article
Critical evaluation of ceftolozane-tazobactam for complicated urinary tract and intra-abdominal infections
Therapeutics and clinical risk management, v 12, pp 787-797
01 Jan 2016
PMID: 27279744
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The rise in resistant Gram-negative pathogens continues to challenge clinicians treating infections. These resistant infections have inspired the development of new antimicrobial agents, including ceftolozane-tazobactam, a novel beta-lactam/beta-lactamase inhibitor combination approved by the US Food and Drug Administration for the treatment of complicated urinary tract infections (cUTIs) and complicated intra-abdominal infections (cIAIs) in combination with metronidazole. Ceftolozane exhibits bactericidal activity by inhibiting penicillin-binding proteins (PBPs), with high affinity for PBP1b, PBP1c, and PBP3. The addition of tazobactam protects ceftolozane from hydrolysis by irreversibly binding to some beta-lactamase enzymes. Ceftolozane-tazobactam is active against a wide range of Gram-negative pathogens, including extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae and multidrug-resistant (MDR) Pseudomonas aeruginosa, several streptococcal species, and Bacteroides fragilis. When anaerobic coverage is needed, it should be used in combination with metronidazole. Ceftolozane demonstrates linear pharmacokinetics, low protein binding, and minimal accumulation with repeated dosing. The major pharmacokinetic/pharmacodynamic index for ceftolozane is the percentage of the dosing interval in which the plasma free drug concentration remains higher than the minimum inhibitory concentration (%T>MIC). Phase III clinical trials for the treatment of cUTIs and cIAIs have been completed, showing that it is an effective and safe alternative for the treatment of these infections. The approved dose for cUTIs and cIAIs is 1.5 g (1 g ceftolozane and 500 mg tazobactam) infused over 1 hour every 8 hours. A higher 3 g dose is currently in Phase III trials for the treatment of ventilated nosocomial pneumonia. Dosage adjustments are necessary for patients with moderate-to-severe renal impairment. Current data suggest that ceftolozane-tazobactam is a promising carbapenem-sparing alternative agent for the treatment of cUTIs and cIAIs, including those caused by ESBL-producing Enterobacteriaceae and MDR P. aeruginosa.
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Details
- Title
- Critical evaluation of ceftolozane-tazobactam for complicated urinary tract and intra-abdominal infections
- Creators
- Stephanie E. Giancola - St. Mary's Medical CenterMonica V. Mahoney - Beth Israel Deaconess Medical CenterTiffany E. Bias - Hahnemann University HospitalElizabeth B. Hirsch - Beth Israel Deaconess Medical Center
- Publication Details
- Therapeutics and clinical risk management, v 12, pp 787-797
- Publisher
- Dove Medical Press Ltd
- Number of pages
- 11
- Grant note
- Merck; Merck & Company Durata Therapeutics/Actavis Forest Pharmaceuticals/Actavis Actavis/Allergan
- Resource Type
- Journal article
- Language
- English
- Web of Science ID
- WOS:000376350100002
- Scopus ID
- 2-s2.0-84970003172
- Other Identifier
- 991019330631404721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Health Care Sciences & Services