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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).
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| Measure | Description | Time Frame |
|---|---|---|
| Value of the minimum inhibitory concentration (MIC) | Value of the minimum inhibitory concentration (MIC) obtained for ceftolozane/tazobactam for each strain | 1 year |
| Measure | Description | Time Frame |
|---|---|---|
| Patient History | Clinical profil of patients (yes/no) correlated with resistance or susceptibility of strains to ceftolozane/tazobactam | 1 year |
| Number of strains producing ESBL and/or carbapenemase (yes or no) |
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Inclusion Criteria:
Exclusion Criteria:
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Hospitalized patient with community-acquired or nosocomial Gram-negative bacillus infection of enterobacteriaceae or P. aeruginosa type (bacteremia, low respiratory infection, intra-abdominal infection)
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| Name | Affiliation | Role |
|---|---|---|
| Alban Le Monnier, Professor | Fondation Hôpital Saint-Joseph | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Groupe Hospitalier Paris Saint Joseph | Paris | Île-de-France Region | 75014 | France |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29263073 | Result | 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 2013 to 2015. Antimicrob Agents Chemother. 2018 Feb 23;62(3):e02125-17. doi: 10.1128/AAC.02125-17. Print 2018 Mar. | |
| 29244121 |
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For hospitalized patients who may have a community or nosocomial Gram-negative bacillus infection of the enterobacterial type or P. aeruginosa type, diagnostic specimens are taken by the clinical department and sent to the local microbiology laboratory for investigation, in accordance with standard management. Depending on the location, the samples may be AMLs (Bronchial-Alveolar Washing), PDPs (Protected Distal Sampling), blood culture, ascites, operating room samples or other puncture.
biochemical tests (ESBL NDP test and/or Carba NP test)
| 1 year |
| Molecular profil of enterobacteriaceae (produced genes : yes or no) | Molecular test (PCR + sequencing: blaCTX-M, blaTEM, blaSHV) | 1 year |
| Molecular profil of pseudomonas aeruginosa (produced genes : yes or no) | Molecular test (PCR + sequencing : blaGES, blaVEB and blaPER) | 1 year |
| 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 Canada as part of the CANWARD study, 2008-16. J Antimicrob Chemother. 2018 Mar 1;73(3):703-708. doi: 10.1093/jac/dkx468. |
| 29272436 | Result | 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. |
| 28329350 | Result | 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 Infections Caused by Carbapenem-Resistant Pseudomonas aeruginosa. Clin Infect Dis. 2017 Jul 1;65(1):158-161. doi: 10.1093/cid/cix014. |
| 29343141 | Result | 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 randomized controlled trials. Expert Rev Anti Infect Ther. 2018 Feb;16(2):111-120. doi: 10.1080/14787210.2018.1429912. Epub 2018 Jan 24. |