Ceftolozane/Tazobactam for Pseudomonas aeruginosa Infections: Going Beyond the Package Insert

Shmuel Shoham, MD; Patricia J. Simner, PhD; Kathryn E. Dzintars, PharmD

Disclosures

February 09, 2016

In This Article

Antimicrobial Susceptibility Testing; Now and in the Future

Ceftolozane/tazobactam received FDA approval before the availability of FDA-cleared commercial antimicrobial testing devices. Antimicrobial susceptibility testing (AST) methods available for ceftolozane/tazobactam, based on the FDA and CLSI interpretative criteria, include the reference-standard broth dilution, Etest, and Kirby-Bauer disks. Currently, Etest strips and Kirby-Bauer disks are available for research use only. These research use-only devices were made available through a microbiology volunteer program, in which healthcare institutions were encouraged to evaluate the activity of ceftolozane/tazobactam against pathogens encountered in their institutions. However, these results were not to be used to determine whether ceftolozane/tazobactam was a therapeutic option for patient management.

The manufacturer of ceftolozane/tazobactam (Merck & Co., Inc.) provides reference-standard broth dilution AST services through a reference laboratory, Laboratory Specialists, Inc., for organisms isolated from FDA-approved indications (complicated UTIs and intra-abdominal infections). Laboratory-grade powder for AST by individual laboratories is difficult to procure and is unavailable without a material transfer agreement between Merck and the testing laboratory.

TREK Diagnostic Systems is currently in the process of validating FDA-cleared lyophilized 96-well broth microbroth dilution panels for clinical use. An advantage of these panels is the ability to customize them to include other antimicrobials of interest. However, a significant disadvantage is the commitment to purchasing a large number of panels (500), making it financially unfeasible for most clinical laboratories.

Requests for AST of ceftolozane/tazobactam are becoming commonplace in clinical microbiology laboratories as more and more MDR gram-negative bacilli are encountered in the hospital setting. Most of these requests are made for organisms isolated from blood or respiratory specimens, which are not FDA-approved sources. The lack of availability of FDA-cleared AST methods makes it challenging for laboratories to provide accurate results to guide use of ceftolozane/tazobactam for clinical care. Although clinical isolates from indicated sources can be sent to Merck's reference laboratory for testing, no AST method for clinical care is available for off-label indications, where the demand for testing is highest.

In the future, as new antimicrobial agents receive FDA approval, commercially available FDA-cleared testing devices need to be made available in parallel. This is especially critical when we are faced with difficult-to-treat organisms and a lack of available treatment options to be able to determine activity for patient management.

It is anticipated that ceftolozane/tazobactam Kirby-Bauer disks will receive FDA clearance shortly. At that point, individual laboratories will be able to validate the disks and test ceftolozane/tazobactam clinically to yield actionable results for patient management. Clinicians will still need to decide whether they should use the drug for an off-label indication, but they will have a better sense as to whether the organism causing the infection is susceptible.

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