From the Journals

Ceftolozane-tazobactam found effective in critically ill patients with Pseudomonas aeruginosa infections



Ceftolozane-tazobactam (C/T) was found effective for treating pneumonia, intra-abdominal, and urinary tract infections caused by Pseudomonas aeruginosa, according to the results of a retrospective, observational study conducted in critically ill patients.

The multicenter, observational study assessed 95 patients who received C/T for P. aeruginosa serious infections, according to a report published online in the International Journal of Antimicrobial Agents.

C/T is a novel beta-lactam/ beta-lactamase inhibitor combination active against gram-negative bacteria including P. aeruginosa, “This paper presents the largest real-life experience published on C/T therapy for treating serious P. aeruginosa infections according to researchers Barbara Balandin, MD, of the Hospital Universitario Puerta de Hierro, Majadahonda, Spain, and colleagues.

The main infections treated were nosocomial pneumonia (56.2%), intra-abdominal infection (10.5%), tracheobronchitis (8.4%), and urinary tract infection (6.3%). Most infections were complicated with sepsis (49.5%) or septic shock (45.3%), and bacteremia (10.5%).

A total of 46 episodes were treated with high-dose C/T (3 g every 8 hours), and 38 episodes were treated with standard dosage (1.5 g every 8 hours). Almost half (44.2%) of the patients were treated with C/T monotherapy, and the remaining group received combination therapy with other antibiotics, according to the researchers.

The primary outcome of the study was to assess the efficacy and toxicity of C/T therapy. The secondary outcome was to evaluate the risk factors for all-cause 30-day mortality from the first day of therapy.

Favorable results

Most of the infections (93.7%) were severe and included the presence of sepsis (49.5%) or septic shock (45.3%). Bacteremia was observed in 15 (15.7%) patients. Bacteremia was secondary to nosocomial pneumonia in eight cases, catheter infection in five, urinary tract infection in one, and soft tissue infection in one. According to their susceptibility profiles, 46 (48.4%) of the strains were classified as extensively drug-resistant (XDR) P. aeruginosa and 35 (36.5%) were multidrug-resistant (MDR) P. aeruginosa.

Sixty-eight (71.6%) patients presented a favorable clinical response, which was defined as a resolution of presenting symptoms and signs of the infection by the end of therapy. An unfavorable clinical response was considered as persistence or worsening of the presenting symptoms and signs or death occurring during treatment with no other cause identified. Death associated with infection was defined as persistence of signs and symptoms of P. aeruginosa infection during C/T therapy with no other cause identified.

Microbiological eradication was documented in 42.1% (40/95) of the episodes. However, the global ICU mortality was still high, at 36.5%, with mortality mainly related to the severity of the infection.

Mortality was found to be significantly correlated with the Charlson Comorbidity Index (5.7 vs. 4.3; P = .04) and the need for life-supporting therapies such as vasopressors (66.6% vs. 46.9%; P = .03) and renal replacement therapy (46.6% vs. 18.1%; P = .002). In addition, mortality was significantly associated with a higher sequential organ failure assessment (SOFA) score during C/T therapy (SOFA1, SOFA 3, and SOFA 7; P < .001).

No significant differences in outcomes were correlated with demographic features, type and severity of infection, and dose of C/T. Also, there were no differences seen in outcomes between patients treated with C/T monotherapy and combined therapy (30.9% vs. 30.1%; P = .55).

“The lack of a positive effect from combined therapy suggests that C/T monotherapy may be sufficient for treating P. aeruginosa isolates that are susceptible to that agent,” the researchers suggested. “This study shows that C/T appears to be a suitable, effective, and safe drug for treating severe infections due to P. aeruginosa, highlighting nosocomial pneumonia caused by MDR/XDR P. aeruginosa in ICU patients with multiple comorbidities, such as immunosuppression, and needing life-sustaining therapies,” they concluded.

The authors reported that they had no outside funding source and had no conflicts of interest.

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