The First Experience of Combined Use of Cefepime/Sulbactam and Aztreonam in ICU Patients with Nosocomial Infections Caused by Carbapenem-Resistant Gram-Negative Microorganisms Producing Class B and D Carbapenemases

Abstract

Background. The difficulties of antibacterial therapy of infections caused by carbapenemase-producing gram-negative bacteria are associated with limited options for adequate therapy since, in addition to resistance to carbapenems and other beta-lactams, these microorganisms are often characterized by associated resistance to other classes of antibiotics, including polymyxins. In vitro data support the idea of combined use of inhibitor-protected cephalosporins with aztreonam for the treatment of such infections. The aim of the study was to investigate the effectiveness of cefepime/sulbactam (FEP/SB) in combination with aztreonam (ATM) in infections caused by class B and D carbapenemase producers.Methods. A prospective observational study evaluated the effectiveness of the combination of FEP/SB + ATM in ICU patients with nosocomial infections complicated by sepsis or septic shock caused by carbapenem-resistant pathogens with documented production of class B or D carbapenemase. The ineffectiveness of previous treatment and the absence of other options for adequate therapy were used as inclusion criteria. Microbiological, clinical efficacy, and 30-day mortality were indicators of therapy evaluation.Results. The study included 25 patients with nosocomial infection (76% of them was VAP), with sepsis (60%) or septic shock (40%) and an average SOFA score of 6 points caused by Klebsiella pneumoniae (23 patients) or Pseudomonas aeruginosa (2) producing carbapenemases OXA-48 (56%), NDM (20%), NDM + OXA-48 (16%), and class B carbapenemase in two strains of P. aeruginosa. The average daily dose of FEP/SB and ATM was 6.6 g, the duration of therapy was 9.9 days. As a result of the treatment, eradication was achieved in 68% of patients, clinical efficacy was 72%, and the 30-day mortality rate was 28%.Conclusion. Our results show good clinical and bacteriological efficacy of the combination of FEP/SB and ATM in infections caused by extremely resistant K. pneumoniae, non-susceptible to carbapenems and producing class B or D carbapenemase.