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

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


February 09, 2016

In This Article

Clinical Trials and FDA Approval

Using these preclinical data, large-scale clinical trials were performed to assess the effectiveness of ceftolozane/tazobactam for treating complicated UTI and intraabdominal infections. Ceftolozane/tazobactam was compared with levofloxacin in a multicenter, international UTI trial.[7] The cure rate in that study with ceftolozane/tazobactam 1.5 g given intravenously every 8 hours for 7 days was 77%, which compared favorably with 69% for levofloxacin 750 mg given intravenously daily for 7 days.

Of note, the apparent superiority of ceftolozane/tazobactam over levofloxacin in that study was probably related to a higher proportion of levofloxacin-resistant organisms in the levofloxacin arm than ceftolozane/tazobactam-resistant organisms in the ceftolozane/tazobactam arm (28% vs 3%). When this discrepancy was corrected for, the efficacy of the two drugs was similar.

The combination of ceftolozane/tazobactam and metronidazole was compared with meropenem for treatment of complicated intra-abdominal infection.[8] Outcomes with ceftolozane/tazobactam 1.5 g plus metronidazole 500 mg every 8 hours for 4-14 days were similar to those of meropenem 1 g every 8 hours (83% vs 87.3%, respectively).

On the basis of these results, ceftolozane/tazobactam gained approval from the FDA in December 2014 for treatment of adults with complicated UTI or intraabdominal infection. The approval was facilitated by the drug's designation as a Qualified Infectious Disease Product, giving its application an expedited review. Clinicians need to work together to determine the best use of this drug (Figure).

Figure. Roles of the prescriber, antimicrobial stewardship pharmacist, and clinical microbiologist for using ceftolozane/tazobactam.

Returning to our original questions:

  • Should we use this drug for our patient if she develops an invasive lower respiratory tract infection? Yes.

  • Will the drug work against the P aeruginosa strain with which she is colonized? Probably.

As indicated above, more than 95% of P aeruginosa isolates tested from 32 US centers were susceptible to ceftolozane/tazobactam at an MIC of ≤ 4 µg/mL. We will need to perform susceptibility testing on the patient's specific isolate, but this is easier said than done.


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