For the treatment of drug-resistant Pseudomonas aeruginosa, ceftolozane/tazobactam regimens are superior to alternative therapies, according to a study published in Clinical Infectious Diseases.

The United States Centers for Disease Control and Prevention (CDC) considers multidrug-resistant Pseudomonas aeruginosa a major public health threat. A multidrug-resistant infection is defined as a pathogen that is resistant to ³1 agent in ³3 different antimicrobial classes. Although rates of multidrug-resistant P aeruginosa infection are fairly stable, they have remained elevated. These high rates and cross-resistance between beta-lactams has led to the use of polymyxins and aminoglycosides for the management of this infection. However, these agents have high rates of nephrotoxicity, suboptimal pharmacokinetic profiles, a narrow therapeutic window, and inferior efficacy to first-line options.

In 2014, the novel cephalosporin/beta-lactamase inhibitor combination ceftolozane/tazobactam was approved in the United States by the Food and Drug Administration. However, previous studies have demonstrated the efficacy of this combination only in patients with intra-abdominal infections and complicated urinary tract infections, but not in those with P aeruginosa infections. Therefore, this retrospective, multicenter, observational cohort study compared ceftolozane/tazobactam with alternative therapy for the treatment of drug-resistant P aeruginosa infection.

In total, 200 patients (100 patients in each treatment group) with drug-resistant P aeruginosa infection were included in this study. The patients in the first treatment group received ceftolozane/tazobactam and patients in the second group received either polymyxin or aminoglycoside-based regimens. The independent effects of ceftolozane/tazobactam on acute kidney injury, clinical cure, and in-hospital mortality were assessed using multivariate logistic regression and controlling for factors associated with treatment. All patients included in the study were critically ill: 42% had severe sepsis or septic shock, 63% were undergoing mechanical ventilation, and 69% were receiving care in the intensive care unit. Ventilator-associated pneumonia (52%) was the most common type of infection and a small percentage of patients (7%) had bacteremia.


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Results suggested that for the treatment of drug-resistant P aeruginosa infections, ceftolozane/tazobactam regimens are superior to alternative therapy. Clinical cure was demonstrated in 81% of those treated with ceftolozane/tazobactam compared with 61% of those who received a polymyxin or aminoglycoside-based regimen (P =.002; odds ratio [OR], 2.72; 95% CI, 1.43-5.17]. After adjustment for differences between the groups, the ceftolozane/tazobactam regimen showed an independent protective association against acute kidney injury (adjusted OR, 0.08) and with clinical cure (adjusted OR, 2.63). In addition, there were no differences regarding in-hospital mortality between patients in the ceftolozane/tazobactam and those who received alternative treatment (20% vs 25%, respectively; adjusted OR, 0.62; 95% CI, 0.30-1.28). Further, when compared with the ceftolozane/tazobactam group, combination therapy was more commonly used in the polymyxin/aminoglycoside group (15% vs 72%, P <.001).

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Overall, the study authors concluded that, “These data are consistent with results from other novel beta-lactam therapies, and ceftolozane/tazobactam should be given preferential use over polymyxins or aminoglycosides for the management of drug-resistant P aeruginosa infections.”

Reference

Pogue JM, Kaye KS, Veve MP, et al. Ceftolozane/tazobactam vs polymyxin or aminoglycoside-based regimens for the treatment of drug-resistant Pseudomonas aeruginosa [published online September 23, 2019]. Clin Infect Dis. doi:10.1093/cid/ciz816