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

Antibiotic Resistant Strain Clinical Trial

— GMC-9  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03963297
• Other study ID #: GMC-9
• Status: Completed
• Start date: March 1, 2019
• Est. completion date: December 30, 2022

Study information

• Verified date: April 2023
• Source: Groupe Hospitalier Paris Saint Joseph
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Description:

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 747
• Est. completion date: December 30, 2022
• Est. primary completion date: March 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Antibiotic Resistant Strain
• Disease Susceptibility
• Pseudomonas Infections

Locations

Country	Name	City	State
France	Groupe Hospitalier Paris Saint Joseph	Paris	Ile-de-France

Sponsors (1)

Lead Sponsor	Collaborator
Groupe Hospitalier Paris Saint Joseph

Country where clinical trial is conducted

France, 

References & Publications (5)

Castanheira M, Duncan LR, Mendes RE, Sader HS, Shortridge D. Activity of Ceftolozane-Tazobactam against Pseudomonas aeruginosa and Enterobacteriaceae Isolates Collected from Respiratory Tract Specimens of Hospitalized Patients in the United States during — View Citation

Chen M, Zhang M, Huang P, Lin Q, Sun C, Zeng H, Deng Y. Novel beta-lactam/beta-lactamase inhibitors versus alternative antibiotics for the treatment of complicated intra-abdominal infection and complicated urinary tract infection: a meta-analysis of rando — View Citation

Monogue ML, Nicolau DP. Antibacterial activity of ceftolozane/tazobactam alone and in combination with other antimicrobial agents against MDR Pseudomonas aeruginosa. J Antimicrob Chemother. 2018 Apr 1;73(4):942-952. doi: 10.1093/jac/dkx483. — View Citation

Munita JM, Aitken SL, Miller WR, Perez F, Rosa R, Shimose LA, Lichtenberger PN, Abbo LM, Jain R, Nigo M, Wanger A, Araos R, Tran TT, Adachi J, Rakita R, Shelburne S, Bonomo RA, Arias CA. Multicenter Evaluation of Ceftolozane/Tazobactam for Serious Infecti — View Citation

Walkty A, Adam H, Baxter M, Lagace-Wiens P, Karlowsky JA, Hoban DJ, Zhanel GG. In vitro activity of ceftolozane/tazobactam versus antimicrobial non-susceptible Pseudomonas aeruginosa clinical isolates including MDR and XDR isolates obtained from across Ca — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Value of the minimum inhibitory concentration (MIC)	Value of the minimum inhibitory concentration (MIC) obtained for ceftolozane/tazobactam for each strain	1 year
Secondary	Patient History	Clinical profil of patients (yes/no) correlated with resistance or susceptibility of strains to ceftolozane/tazobactam	1 year
Secondary	Number of strains producing ESBL and/or carbapenemase (yes or no)	biochemical tests (ESBL NDP test and/or Carba NP test)	1 year
Secondary	Molecular profil of enterobacteriaceae (produced genes : yes or no)	Molecular test (PCR + sequencing: blaCTX-M, blaTEM, blaSHV)	1 year
Secondary	Molecular profil of pseudomonas aeruginosa (produced genes : yes or no)	Molecular test (PCR + sequencing : blaGES, blaVEB and blaPER)	1 year