Ceftolozane/tazobactam versus colistin in the treatment of ventilator-associated pneumonia due to extensively drug-resistant Pseudomonas aeruginosa

Abstract

Resistant strains of Pseudomonas aeruginosa are common pathogens in the intensive care unit (ICU), limiting available therapeutic options. We aimed to compare ceftolozane/tazobactam (C/T) with colistimethate sodium (CMS) in the treatment of ventilator-associated pneumonia (VAP) due to extensively drug-resistant (XDR) Pseudomonas aeruginosa. A retrospective, observational study was performed at a tertiary care ICU. Clinical and microbiological success rate, 28-day all-cause mortality, and adverse events were compared in patients who received C/T with those treated with systemic CMS. A total of 51 patients were included (18 in the C/T and 33 in the CMS group). Clinical success rates in the C/T and CMS groups were 13 (72.2%) and 10 (30.3%), respectively. On multivariate regression analysis, treatment with C/T was independently associated with clinical success (odds ratio 4.47, 95% CI 1.17–17.08). There was no difference in 28-day all-cause mortality (27.8% and 33.3% in the C/T and CMS group, p = 0.76). Acute kidney injury was more common in patients who received CMS (48.5% vs 11.1%, p = 0.01). In our study, ceftolozane/tazobactam was more efficacious in the treatment of XDR Pseudomonas aeruginosa VAP and showed a better safety profile compared to CMS.

New antibiotics for Gram-negative pneumonia

“…In this study, after adjusting for differences between groups, patients treated with ceftolozane-tazobactam had a better clinical cure (adjusted OR (aOR) 2.63, 95% CI 1.31–5.30) and lower acute kidney injury (aOR 0.08, 95% CI 0.03–0.22) [ 39 ]. Concordant results were also reported in two similar case control studies, in which compared to “old antibiotics”, ceftolozane-tazobactam was more effective in the treatment of MDR/XDR P. aeruginosa VAP [ 40 ] and HAP [ 16 ], while reporting a better safety profile in terms of acute kidney injury.…”

IgM-enriched immunoglobulin improves colistin efficacy in a pneumonia model by Pseudomonas aeruginosa

“…Although 77% of patients had ventilator-associated pneumonia, only 21% were caused by P. aeruginosa . In this context, in the experimental P. aeruginosa pneumonia model, we found that the administration of IgM-IG combined with colistin was useful in reducing the bacterial lung concentration, which points to the possible efficacy of antibiotics combined with IgM-IG to diminish the mortality of multidrug-resistant P. aeruginosa pneumonia in human beings, which may be as high as 33.3% in patients with ventilator-associated pneumonia treated with colistimethate sodium ( Mogyoródi et al, 2022 ). To extrapolate these results to pneumonia by other multidrug-resistant GNB deserves further research with experimental pneumonia models by other pathogens.…”

Recent advances in therapeutic targets identification and development of treatment strategies towards Pseudomonas aeruginosa infections

“…Some antibiotics efficiency towards P. aeruginosa infections could be improved by context-specific actions. Indeed, in ventilator-associated pneumonia, combination of cephalosporin and beta-lactamase inhibitor ceftolozane/tazobactam (C/T) exhibited both efficacy and safety in treating extensively drug-resistant P. aeruginosa [ 58 ]. However, antibiotic resistance against such a combination has been reported when administered at suboptimal steady-state concentrations of 20 mg/L in the susceptible P. aeruginosa ST175 isolate [ 59 ].…”