The content of this evidence review was up-to-date in December 2019. See summaries of product characteristics (SPCs), British national formulary (BNF), the Medicines and Healthcare products Regulatory Agency (MHRA) or NICE websites for up-to-date information.
Ceftolozane with tazobactam (Zerbaxa, Merck Sharp & Dohme Limited) is a combination of a cephalosporin antibiotic, which predominantly covers Gram-negative bacteria, and a beta-lactamase inhibitor, which inhibits many (but not all) class A beta-lactamases (enzymes that cause resistance to beta-lactam antibiotics). It is given as a 1-hour intravenous (IV) infusion every 8 hours.
Ceftolozane with tazobactam received a marketing authorisation for treating complicated intra-abdominal infections, acute pyelonephritis and complicated urinary tract infections in adults in September 2015 (see complicated urinary tract infections: ceftolozane/tazobactam and complicated intra-abdominal infections: ceftolozane/tazobactam for more information). In August 2019, the indication for ceftolozane with tazobactam was extended to include treating hospital-acquired pneumonia (HAP), including ventilator-associated pneumonia (VAP) in adults (Zerbaxa: Procedural steps taken and scientific information after authorisation).
Evidence for using ceftolozane with tazobactam for treating HAP and VAP is from 1 phase 3 randomised controlled non-inferiority trial (ASPECT-NP). ASPECT-NP found that a high dose of ceftolozane with tazobactam was non-inferior to meropenem for treating seriously ill people with VAP or ventilated HAP (see the section on effectiveness for definition) caused by Gram-negative pathogens such as Pseudomonas aeruginosa (including multidrug-resistant strains) and Enterobacterales (formerly known as Enterobacteriaceae, including producers of extended-spectrum beta-lactamases [ESBL]). Rates of 28-day mortality and clinical cure were similar between the treatment groups, and findings in the intention-to-treat (ITT) population were supported by sensitivity and per-protocol analyses.
Ceftolozane with tazobactam was generally well tolerated. However, limited safety data are available for the high dose used in this study, which is recommended for HAP and VAP. Treatment-related adverse events were more common with ceftolozane with tazobactam than with meropenem (11% [38/361] compared with 8% [27/359] respectively; no statistical analysis). The most commonly reported treatment-related adverse events with ceftolozane with tazobactam were abnormal liver function tests, Clostridioides difficile (formerly known as Clostridium difficile) colitis and diarrhoea.
The manufacturer of ceftolozane with tazobactam (Merck Sharp & Dohme Limited) anticipates that it will be used in line with good antimicrobial stewardship, on the advice of a microbiologist, to treat critically ill ventilated adults with HAP and VAP, who are deteriorating or not responding to initial antibiotic therapy, and who have confirmed or highly suspected Pseudomonas aeruginosa.
Specialists involved in producing this evidence summary consider that ceftolozane with tazobactam provides a potentially useful alternative for treating some adults with HAP and VAP who have limited treatment options because they have infections suspected or proven to be caused by caused by Enterobacterales (excluding carbapenem-resistant bacteria) or multidrug-resistant Pseudomonas aeruginosa. Local antibiotic resistance patterns will need to be taken into account.