What Is the Role of Ceftolozane/Tazobactam?

Michael J. Postelnick, BSPharm

Disclosures

July 20, 2015

Question

What is the role of ceftolozane/tazobactam in the treatment of serious infections?

Response from Michael J. Postelnick, BSPharm
Senior Infectious Diseases Pharmacist, Clinical Coordinator, Department of Pharmacy, Northwestern Memorial Hospital, Chicago, Illinois

Ceftolozane/tazobactam (Zerbaxa®) is a new cephalosporin combined with a familiar beta-lactamase inhibitor that has recently been marketed for the treatment of complicated intra-abdominal infections and complicated urinary tract infections.[1]

Ceftolozane demonstrates activity against common gram-negative pathogens, similar to ceftazidime (Fortaz®, Tazicef®) and ceftriaxone (Rocephin®), and like these older agents it is inactivated by extended-spectrum beta-lactamases (ESBLs). The addition of tazobactam extends activity to most ESBL producers as well as anaerobic organisms[2] (although metronidazole [multiple brand names] was added in trials for the treatment of intra-abdominal infections due to the potential for anaerobic organism resistance).

Ceftolozane differs from other cephalosporins by its enhanced activity against Pseudomonas aeruginosa, including those strains which are resistant to ceftazidime, carbapenems, and piperacillin/tazobactam. Against gram-positive pathogens, ceftolozane/tazobactam demonstrates activity against most streptococci but demonstrates little to no activity against staphylococci or enterococci.[2] A phase 3 trial is currently underway to examine its efficacy in nosocomial pneumonia.

Ceftolozane/tazobactam shares similar pharmacodynamic characteristics with other beta-lactam antibiotics. Activity is best described by optimizing the amount of time the antibiotic concentration remains above the minimum inhibitory concentration of the infecting organism.[2] It achieves concentrations likely to be effective against susceptible pathogens in abdominal fluid, urine, and pulmonary epithelial lining fluid.[3]

While ceftolozane/tazobactam alone has demonstrated noninferiority to levofloxacin (Levaquin®) in complicated urinary tract infections,[1] and the combination of ceftolozane/tazobactam plus metronidazole has demonstrated noninferiority to meropenem (Merrem®) in complicated intra-abdominal infections,[4] the best application of this new agent is probably much more limited. Due to its excellent activity against P aeruginosa, it is better positioned to be a go-to agent for the treatment of serious infections where this difficult-to-treat pathogen is highly suspected or documented as the cause. Although not active against carbapenem-resistant Enterobacteriaceae (CRE), ceftolozane/tazobactam may also offer an alternative in the rare situation where carbapenem resistance is not due to carbapenemases or metallo-beta-lactamases.[2]

While this new combination is a welcome addition to the antibiotic armamentarium, targeting utilization in the above described manner has the potential to preserve the activity of this agent against difficult-to-treat pathogens where alternative therapy may not be available.

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