Multicenter Evaluation of the Susceptibility of Enterobacteriaceae and Pseudomonas Aeruginosa to Ceftolozane/Tazobactam Combination

Multicenter Evaluation of the Susceptibility of Enterobacteriaceae and Pseudomonas Aeruginosa to Ceftolozane/Tazobactam Combination

Ceftolozane/tazobactam is a new antibiotic with broad spectrum activity. This molecule is currently one of the most active beta lactams against Pseudomonas aeruginosa and its spectrum of activity also includes enterobacteriaceae producing a broad spectrum beta-lactamase (EBLSE). Ceftolozane/tazobactam is currently marketed for the treatment of complicated intra-abdominal infections and complicated urinary tract infections. These intra-abdominal and urinary infections are mainly caused by enterobacteriaceae (Escherichia coli, Klebsiella pneumoniae) and more rarely by P. aeruginosa. Concerning enterobacteriaceae, French epidemiology reports a prevalence of BLSE of between 10 and 15% in E. coli and 10%-30% in K. pneumoniae.

Currently, the probabilistic treatment of these multi-resistant bacteria involves the use of carbapenems. Unfortunately, the increasing and unreasonable use of carbapenems invariably leads to the spread of even more resistant strains, BHRe (Emerging Highly Resistant Bacteria) including enterobacteriaceae producing carbapenemases. Thus, it is strongly recommended by health authorities to limit the use of carbapenems ("carbapenem savings") by promoting the use of therapeutic alternatives. Ceftolozane/tazobactam is one of those therapeutic alternatives for which an evaluation must be carried out. Currently, in addition to complicated intra-abdominal infections and complicated urinary tract infections, ceftolozane/tazobactam combination is used in clinical practice in gram-negative infections such as upper and lower respiratory infections and bacteremia. In any case, the choice of probabilistic antibiotic therapy must take into account local and regional epidemiological data. However, published data on the in vitro activity of ceftolozane/tazobactam remain limited, particularly in France (only one French epidemiological study on Gram-negative non-fermenting bacillus strains isolated in patients with cystic fibrosis). This study does not take into account in particular multi-resistant enterobacteriaceae producing BLSE for which ceftolozane/tazobactam remains effective (particularly in E. coli and K. pneumoniae).

Inclusion Criteria:

• Patient whose age is ≥ 18 years old
• Hospitalized patient with community-acquired or nosocomial Gram-negative bacillus infection of enterobacteriaceae or P. aeruginosa type (bacteremia, low respiratory infection, intra-abdominal infection)
• French-speaking patient

Exclusion Criteria:

• Patient under tutorship or curatorship
• Patient deprived of liberty
• Patient under the protection of justice
• Refusal to participate in the study
• Patients judged by the investigator as being unable to express their non-opposition to the study
• Urinary localization of the infection to avoid strains responsible for simple colonization. Indeed, the collection of microbiological data (as carried out in this study) makes it difficult to distinguish between real infection and simple colonization. In addition, the impact of early implementation of appropriate therapy on the evolution of infectious disease (mortality, morbidity, etc.) has been clearly demonstrated for serious infections such as bacteremia and respiratory infections, while this impact remains more limited or even insignificant for urinary infections. Hence the desire to exclude isolated strains of urine samples.