Ceftolozan / Tazobactam (5) – Zerbaxa®

• Clinical trials
  • Clinical data were presented from a retrospective observational study (Gallagher et al., 2018) which investigated serious infections caused by multidrug-resistant P. aeruginosa in 20 hospitals in the USA.

• The application for exemption from the requirement to submit evidence pursuant to Section 35a(1), third sentence, points 2 and 3 of the German Social Code, Book V (SGB V), on the grounds of reserve status pursuant to Section 35a(1c) of SGB V, is granted, as the information provided by the pharmaceutical manufacturer is sufficient to justify the classification of the active ingredient ceftolozan/tazobactam as a reserve antibiotic in accordance with Chapter 5, Section 15a of the VerfO.
• Ceftolozan/Tazobactam has marketing authorisation for the treatment of the following infections in adults: complicated intra-abdominal infections (cIAI); acute pyelonephritis; complicated urinary tract infections; hospital-acquired pneumonia (HAP), including ventilator-associated pneumonia (VAP).
• There is no pathogen-specific marketing authorisation for patients with limited treatment options and, accordingly, criterion 1.1 of the Robert Koch Institute’s list of indicators does not apply.
• In vitro data have been submitted for this purpose, demonstrating sufficient pathogen susceptibility to ceftolozan-tazobactam in imipenem- and meropenem-resistant P. aeruginosa.
• Given the sufficient total number of isolates, the data are considered to be sufficiently meaningful.
• Carbapenem-resistant P. aeruginosa is listed on the Robert Koch Institute’s list of pathogens.
• Criterion 1.2.1 (relevant in vitro data) on the RKI’s list of indicators is therefore met.
• Carbapenem-resistant P. aeruginosa are considered relevant pathogens, particularly in the therapeutic indication for hospital-acquired pneumonia caused by multidrug-resistant pathogens.
• Despite uncertainties regarding the transferability of the data from the American study to the healthcare situation in Germany, sufficient clinical efficacy against carbapenem-resistant P. aeruginosa (Criterion 1.2.2) is inferred as a therapeutic indication for nosocomial pneumonia.
• In accordance with the RKI’s list of indicators, there must be no, or only limited, clinically equivalent treatment options available for the authorised indications in relation to relevant multidrug-resistant pathogens.
• The recommendations of the S3 guideline ‘Epidemiology, Diagnosis and Treatment of Adult Patients with Nosocomial Pneumonia’ form the basis for this assessment.
• Where carbapenem resistance is present, the remaining treatment options for pneumonia caused by P. aeruginosa are considered to be very limited.
• Criterion 2.1 of the RKI’s list of indicators is therefore also met.
• The factual requirement that the use of the antibiotic is subject to strict indications is, according to the current assessment, not sufficiently met by the indication “The official guidelines for the appropriate use of antibiotics must be observed” in the summary of product characteristics (SmPC).
• The classification of ceftolozane/tazobactam in the Reserve Group of the WHO AwaRe classification currently has no direct implications in terms of restricting the prescription of the medicinal product in Germany.
• However, the Federal Joint Committee (G-BA) reserves the right to lay down further requirements for a quality-assured application in its resolution pursuant to Section 35a(3) of Book V of the Social Code (SGB V) in order to fulfil the criterion of strict indication.
• Morbidity – Clinical efficacy in nosocomial pneumonia caused by carbapenem-resistant P. aeruginosa
  • Of the 205 patients included, 121 (59 %) had pneumonia.
  • 96.8 % of the multidrug-resistant P. aeruginosa isolates were resistant to carbapenems.
  • The ‘clinical success’ rate for ceftolozane/tazobactam was 66.1% in patients with pneumonia.
• Overall assessment
  • The application was therefore approved.

Courtesy translation only, please refer to the German original.