Advice
Key messages
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The content of this evidence review was up-to-date in November 2019. See summaries of product characteristics (SPCs), British national formulary (BNF), or the Medicines and Healthcare products Regulatory Agency (MHRA) or NICE websites for up-to-date information. |
Meropenem with vaborbactam (Vaborem, Menarini) is a combination of a broad-spectrum carbapenem antibiotic, which covers gram-positive, gram-negative and anaerobic bacteria, and a new beta-lactamase inhibitor, which protects against class A and class C (but not class B and class D) carbapenemases (enzymes that cause resistance to carbapenem antibiotics). It is given as a 3‑hour intravenous (IV) infusion every 8 hours and has a marketing authorisation for treating the following infections in adults:
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complicated urinary tract infection (cUTI), including pyelonephritis
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complicated intra-abdominal infection (cIAI)
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hospital-acquired pneumonia (HAP), including ventilator-associated pneumonia (VAP).
Meropenem with vaborbactam is also indicated for treating:
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adults with bacteraemia that occurs in association with, or is suspected to be associated with, any of the infections listed above
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infections due to aerobic gram-negative organisms in adults with limited treatment options (only after consulting a doctor with appropriate experience in managing infectious diseases).
Evidence is from 2 phase 3 randomised controlled trials (Tango I and Tango II). Tango I provides evidence for meropenem for treating adults with cUTI and acute pyelonephritis, but it cannot provide clinical evidence for the adequacy of the vaborbactam dosing regimen because the trial was not designed to assess efficacy against meropenem-resistant organisms (for the marketing authorisation, the dosage of vaborbactam was supported by pharmacokinetic and pharmacodynamic data). About 5% of people in Tango I had bacteraemia, providing some support for using meropenem with vaborbactam for this indication. Tango II provides limited support for using meropenem with vaborbactam to treat adults with infections due to aerobic gram-negative organisms and limited treatment options. The marketing authorisation for cIAI and HAP or VAP was granted based on experience with meropenem alone, and pharmacokinetic and pharmacodynamic data.
The safety profile of meropenem is well-established and the safety database for meropenem with vaborbactam, although relatively small, does not indicate any major concerns resulting from the addition of vaborbactam.
Likely place in therapy
The Vaborem European public assessment report (EPAR) states that there is an unmet need for well-tolerated antibacterial agents that are active against aerobic gram-negative organisms that express class A and class C carbapenemases. It reports that vaborbactam can protect meropenem from inactivation by these beta-lactamases in the absence of other types of carbapenem resistance, and concludes that, although meropenem with vaborbactam cannot wholly solve the problem of carbapenem resistance, it provides a potentially useful alternative for treating infections due to carbapenem-resistant enterobacteria.
Vaborbactam cannot protect meropenem against class B and class D beta-lactamases or restore susceptibility when resistance is wholly or partly due to impermeability or efflux mechanisms. According to the English surveillance programme for antimicrobial utilisation and resistance (ESPAUR) report 2018 to 2019, OXA‑48 carbapenemases (class D) were the most frequently identified carbapenem-resistant Enterobacterales, accounting for 52.0% of confirmed carbapenem-resistant Enterobacterales in 2018. In that year, the rates of NDM, IMP and VIM (class B) carbapenemases were 26.5%, 3.7% and 1.7% respectively. Klebsiella pneumoniae carbapenemase (KPC, class A) was the third most frequently identified carbapenem-resistant Enterobacterales (11.2%).
Specialists involved in producing this evidence summary expect that meropenem with vaborbactam will be used to treat 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. Local antibiotic resistance patterns need to be taken into account because meropenem with vaborbactam may not be appropriate in regions where class B or class D carbapenemase resistance is common. Therefore, using meropenem with vaborbactam in this way should be under the guidance of an appropriately experienced infection specialist (such as a clinical microbiologist or infectious diseases consultant), following the principles of good antimicrobial stewardship.
Local (or national) antimicrobial prescribing guidelines should be consulted when selecting treatment options for these indications.