A study found no significant difference in outcomes between ceftazidime, carbapenems, and piperacillin-tazobactam as monotherapy for treating P aeruginosa, offering insight that may help antibiotic stewardship programs.
Treatment of Pseudomonas aeruginosa with carbapenems has led to greater drug resistance, but a recent study may offer alternatives, finding no significant difference in outcomes between ceftazidime, carbapenems, and piperacillin-tazobactam as monotherapy for treating the bacterium.
The multination retrospective study, published in the journal Clinical Infectious Diseases, involved 767 patients at 25 health centers in 9 countries in Europe, Australia, and Israel between 2009 and 2015.
“Our biggest takeaway message is that carbapenems are not necessary to treat susceptible pseudomonas bacteremia and may even be harmful ecologically (with the higher resistance reported),” corresponding author Dafna Yahav, MD, senior physician in the Infectious Diseases Unit, Rabin Medical Center, Beilinson Hospital in Petah-Tikva, Israel, told Contagion®. “In addition, the message that there is no difference between ceftazidime and piperacillin/tazobactam is also important and people can now choose between them according to their local susceptibility profile and antimicrobial stewardship purposes (for example, if you have a lot of Clostridioides difficile in your hospital—you may prefer pip/taz rather than ceftazidime). Ideally, the next step would be a randomized controlled trial, but this will probably not happen without funding.”
The comparison considered the 3 antibiotics most commonly used to treat P aeruginosa.
The primary outcome of 30-day mortality was observed in 17.4% of the patients in the ceftazidime group, 20% of the carbapenem group, and 16% of the piperacillin-tazobactam group. There were 213, 210, and 344 patients in each group, respectively. Factors associated with mortality included bedridden patients, solid metastatic tumor and higher comorbidity index, previous hospitalization within 90 days, nosocomial acquisition of infection, and sequential organ failure assessment scores. The study also noted that using the maximum dose of beta-lactams did not decrease mortality.
Isolation of P aeruginosa with new resistance to antipseudomonal drugs was observed in 17.5% of the carbapenems group, compared with 12.4% of the ceftazidime group and 8.4% of the piperacillin-tazobactam group.
The study also noted that the use of carbapenems has been associated with higher rates of C diff.
The study included patients over age 18 with a median age of 68 who were hospitalized with P aeruginosa bacteremia and treated with definitive monotherapy. It found no significant differences in mortality, clinical failure, microbiological failure, or adverse events.
Previous studies have found similar results, but this is the largest study to date comparing beta-lactam monotherapies.
The emergence of drug resistance is an ongoing and continually evolving challenge for providers. It has become a major health crisis, underscoring the importance of antibiotic stewardship programs and the need to maintain antibiotic breakpoints.
Another recent study found 2 clinical isolates of P aeruginosa that were resistant to all beta-lactam antibiotics, including novel combinations. The bacteria carried 2 Guiana extended-spectrum beta-lactamase enzymes that were linked to infections in Mexico and also found among Enterobacteriaceae in the region, suggesting the drug-resistant pathogen may be widespread and could spread across species.