Ceftazidime with avibactam for treating severe drug-resistant gram-negative bacterial infections

NICE recommends further research to develop best practice in the health economic evaluation of antimicrobials in the UK, Europe and globally, as detailed in sections 5.2, 5.3 and 5.4.

Develop methods to model and quantify the additional elements of benefit of new antimicrobials, including, but not limited to, spectrum, transmission, enablement, diversity and insurance value.

Determine the relationship between a pathogen's in vitro susceptibility to an antimicrobial treatment and relevant outcomes in people with multi-drug-resistant bacterial infections. Data should include patient identification to allow linkage. It should reflect the site from which the sample was taken, state the probable site of infection, identify the pathogen, identify the mechanism of antimicrobial resistance, and record antimicrobial treatment. Relevant clinical outcomes may include, but are not limited to, mortality (including all-cause mortality and mortality attributable to the infection), clinical cure (signs and symptoms of infection resolved, and no further antimicrobial therapy needed) and microbiological eradication. Relevant safety outcomes include acute kidney injury, renal replacement therapy, colonisation with multi-drug-resistant pathogen after treatment, and Clostridioides difficile infection. Relevant resource-use outcomes include length of hospital stay by ward type and duration of treatment. Ideally, a range of different antimicrobial treatments would be included in a single study, to ensure consistent laboratory methods and clinical breakpoints.

Establish better methods to synthesise evidence from in vitro antimicrobial susceptibility studies. This could include:

• Establishing whether the different laboratory methods and clinical breakpoints used to assess antimicrobial susceptibility, which are set by different organisations (for example, European Committee on Antimicrobial Susceptibility Testing [EUCAST] and Clinical and Laboratory Standards Institute [CLSI]), are interchangeable.

• Establishing whether it is preferable to use clinical breakpoints at the same time as sample collection, or whether it is acceptable to apply newly published breakpoints to historical data.

• Developing a tool to assess the quality of in vitro antimicrobial susceptibility studies.

• Establishing if and how changes to laboratory methods used to assess susceptibility affect synthesising data from different antimicrobial susceptibility studies.

• Developing reporting guidelines (similar to those provided by PRISMA and CONSORT) to ensure studies of antimicrobial susceptibility are reported clearly and comprehensively.