In this short series, Pranita Tamma, MD, MHS, associate professor of pediatrics in the Division of Pediatric Infectious Diseases at The Johns Hopkins University School of Medicine, has a discussion about ceftolozane-tazobactam vs ceftazidime-avibactam for gram-negative resistant Pseudomonas aeruginosa infections and the latest data supporting these decisions.
In one retrospective observational study, which compared ceftolozane-tazobactam and ceftazidime-avibactam and was funded by the National Institutes of Health, the findings showed similar 30-day mortality rates but higher resistance emergence in the ceftolozane-tazobactam group (38% vs 25%). Tamma was the senior investigator in this trial.
Below is a response from a question about infection source and combination therapy.
Contagion: Were there any notable differences in patient outcomes based on infection source or use of combination therapy in either group?
Pranita Tamma, MD, MHS: We also examined other variables that might differ between the groups, including the source of infection and the use of combination therapy. As expected, since these patients were infected with Pseudomonas, the vast majority had pneumonia, followed by bacteremia. We did not find any notable differences between the groups—either at baseline or in exploratory analyses of mortality by infection source.
Similarly, only a minority of patients received combination therapy, which we defined as adding a second agent such as an aminoglycoside, fluoroquinolone, or polymyxin. Fewer than 15% of the cohort received such therapy. In general, there are limited effective options for combination therapy: the only aminoglycoside with breakpoints for Pseudomonas in pneumonia and bloodstream infections is tobramycin; polymyxins are never reported as “susceptible” due to concerns about efficacy; and by definition, DTR Pseudomonas are resistant to fluoroquinolones. This leaves very few opportunities for a viable second agent.
We did not observe any trend suggesting better outcomes with combination therapy. This aligns with prior observational studies in drug-resistant Pseudomonas as well as clinical trials in pan-susceptible Pseudomonas, all of which have failed to show a benefit from adding a second agent. So, not surprisingly, we did not see an advantage with combination therapy. Unfortunately, it would have been encouraging if we had found such a benefit, but we did not.
The conversation was edited for grammar and clarity.