Advice
Advisory statement on likely place in therapy
Imipenem with cilastatin and relebactam may be an option for treating infections due to gram-negative aerobic organisms in adults with limited treatment options, particularly when other antimicrobials have failed. Take account of local antimicrobial resistance and seek specialist microbiological advice. Follow recommendations on new antimicrobials in the NICE guideline on antimicrobial stewardship.
Rationale
The European public assessment report for imipenem with cilastatin and relebactam states that there is still a high unmet clinical need for additional antimicrobials addressing carbapenem resistance in gram-negative organisms.
Evidence from 2 phase 3 randomised controlled trials in around 600 people treated in a non-UK hospital setting suggests that the efficacy of imipenem and cilastatin with relebactam was similar (no planned statistical analysis) to colistin plus imipenem for treating imipenem non-susceptible pathogens, and non-inferior to piperacillin with tazobactam for treating susceptible pathogens. Imipenem and cilastatin with relebactam has not been compared with other treatments.
The infections treated in the studies were hospital‑acquired pneumonia (including ventilator-associated pneumonia), complicated intra-abdominal infection and complicated urinary tract infection (UTI) in adults. There is no evidence for treating other infections with limited treatment options.
In both studies, participants had no response to previous antimicrobial treatment before receiving imipenem and cilastatin with relebactam. Therefore, it may be an option for people with limited treatment options who have serious infections suspected or proven to be caused by multi-drug resistant aerobic gram-negative bacteria according to its licensed indications. The daily cost of imipenem and cilastatin with relebactam is £614.20 at the usual dose (1 vial [500 mg/500 mg/250 mg] every 6 hours).
Imipenem with cilastatin has been combined with relebactam to overcome carbapenem resistance. Local antimicrobial resistance patterns and trends need to be considered because imipenem with cilastatin and relebactam may not be appropriate in areas where class B enzymes and class D carbapenemase resistance is common.
The NICE guideline on antimicrobial stewardship makes recommendations on the effective use of new antimicrobials. Imipenem and cilastatin with relebactam should be reserved for those people most likely to benefit from their use, following specialist microbiological advice to help monitor use and limit antimicrobial resistance.