Extending ceftolozane-tazobactam infusions may prevent emerging resistance
A small study of patients infected with carbapenem-resistant Pseudomonas aeruginosa demonstrated the potential emergence of resistance to ceftolozane-tazobactam during treatment, researchers reported in Clinical Infectious Diseases.
Results of the study suggested that extending treatment through an infusion lasting more than 3 hours may protect against emerging resistance, but the researchers acknowledged that larger studies are needed to assess this association.
“We are excited to have new beta-lactam agents available that can combat some highly resistant pathogens that cause infections in particularly vulnerable populations. However, it has been concerning to see resistance gradually emerge [with] these agents as they are being used with increasing frequency in clinical practice,” Pranita D. Tamma, MD, MHS, associate professor of pediatrics at Johns Hopkins University School of Medicine, told Healio. “We wanted to explore whether there were any modifiable risk factors that we could potentially act on as an infectious diseases community to slow the emergence of resistance to these antibiotics. For this work, we focused on the antibiotic ceftolozane-tazobactam.”
Tamma and colleagues assessed 28 patients infected with carbapenem-resistant P. aeruginosa isolates susceptible to ceftolozane-tazobactam (TOL-TAZ) and treated with 72 hours or more of TOL-TAZ between January 2018 and December 2019. Isolates were available before and after treatment exposure.
According to the study, the researchers used whole-genome sequencing of paired isolates to identify resistance that emerged during TOL-TAZ exposure. In all, 14 patients (50%) had P. aeruginosa isolates that developed high-level TOL-TAZ resistance.
“We were surprised to find that half of the carbapenem-resistant Pseudomonas clinical isolates in the study developed resistance to ceftolozane-tazobactam after ceftolozane-tazobactam exposure,” Tamma said.
The researchers also found that among these cases, patients were more likely to have inadequate source control (29% vs. 0%, P = .04) and were less likely to receive TOL-TAZ as an extended 3-hour infusion (0% vs. 29%; P = .04). Additionally, the study demonstrated that 86% of index isolates susceptible to ceftazidime-avibactam (CAZ-AVI) had P. aeruginosa isolates with high-level resistance to CAZ-AVI after TOL-TAZ exposure.
“Our findings suggest that the emergence of TOL-TAZ resistance during therapy may not be a rare event and extending the infusion of TOL-TAZ may be protective against the development of resistance,” Tamma said. “Larger, interventional studies are needed to validate our findings. In the meantime, appropriate source control and limiting durations of therapy to evidence-based durations remain modifiable risk factors that can limit the emergence of resistance to all antibiotics including ceftolozane-tazobactam.”