Clinical Guidelines, Stewardship Practices for Managing DTR Pseudomonas Infections

EP: 1.Looking at Mortality Rates Comparing Treatments for Gram-Negative Resistant Pseudomonas aeruginosa Infections

EP: 2.Determining Resistance Patterns in Difficult-to-Treat Resistant Pseudomonas Infections

EP: 3.Statistical Weighting Helps Reduce Bias in Observational Studies

EP: 4.Practical Strategies to Minimize Antimicrobial Resistance in Patients With Critical Illness

EP: 5.Are There Benefits to Combination Therapy for Drug-Resistant Pseudomonas Infections?

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EP: 6.Clinical Guidelines, Stewardship Practices for Managing DTR Pseudomonas Infections

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 the findings and how it should influence management of this particular infection.

Contagion: how might the findings of this study influence future clinical guidelines or stewardship practices for managing DTR Pseudomonas infections?

Pranita Tamma, MD, MHS: I think all 3 observational studies were valuable and I’m glad they were conducted. They addressed an important question involving a serious infection—one where the stakes are high, the number of active drugs is limited, and resistance to the available agents is a real and growing problem. Unfortunately, we are likely to lose these drugs for a substantial portion of DTR Pseudomonas cases in the years ahead.

The good news, in my view, is that none of the 3 studies showed a difference in mortality, which remains the most objective outcome. Based on these results, I don’t think we can say ceftolozane–tazobactam or ceftazidime–avibactam is definitively better or worse for treating DTR Pseudomonas. My approach would be to test both agents, choose the one that is active against the infection, and monitor the patient very closely.

That said, resistance is a major concern. Across studies, at least 20%—and likely more—of patients treated for DTR Pseudomonas with either of these drugs subsequently developed resistance, meaning that when the infection recurs, the same drug is no longer effective. Due to the structural similarities between these agents, there is also considerable cross-resistance. For example, if a patient develops resistance to ceftolozane–tazobactam, resistance to ceftazidime–avibactam is also often expected.

From my perspective, the 3 studies do not change my view that neither drug is inherently superior. However, from an antibiotic stewardship standpoint, I would prioritize ceftolozane–tazobactam when both drugs test active. The reason is that ceftazidime–avibactam offers broader utility beyond DTR Pseudomonas: it can sometimes be combined with aztreonam to treat metallo-β-lactamase–producing organisms, and it retains activity against certain carbapenem-resistant Enterobacterales such as KPC and OXA-48–like producers. By using ceftolozane–tazobactam first, we may preserve ceftazidime–avibactam as an option for those other difficult-to-treat pathogens.

The conversation was edited for grammar and clarity.