More aggressive dosing of piperacillin-tazobactam is one of several recommendations for improving antibiotic use in neutropenic fever highlighted in an Australian study.

In a review of antimicrobial use in neutropenic fever, researchers at the National Centre for Infections in Cancer, Peter MacCallum Cancer Centre, Melbourne, identified three key areas for improvement: piperacillin-tazobactam dosing, paediatric prescribing and private hospital prescribing.

The study, published in the Journal of Antimicrobial Chemotherapy [link here], interrogated 2,887 prescriptions for neutropenia fever in adult and paediatric patients receiving chemotherapy across 254 health facilities between August 2013 and May 2022.

Patients included those receiving chemotherapy for solid tumours and for haematological malignancy or allogeneic HSCT.

The data was extracted from the Hospital National Antimicrobial Prescribing Survey (Hospital NAPS) database.

The study found prescribing was mostly appropriate (87.4%).

Piperacillin-tazobactam was the predominant antimicrobial prescribed (58%), which reflects compliance with the 2011 Australian consensus guidelines [link here].

However incorrect piperacillin-tazobactam dose or frequency was also observed, particularly in private and non-principal referral hospitals.

The IV antibiotic was frequently prescribed 8-hourly whereas Therapeutic Guidelines have recommended 6-hourly since 2014.

“Despite the prevalence of piperacillin-tazobactam underdosing, many 8-hourly prescriptions were still assessed as appropriate suggesting that this issue is under-recognised among auditing clinicians and prescribers,” the study said.

It also found vancomycin was the least appropriately used antibiotic – either for incorrect dose or frequency (42.3%) or “spectrum too broad” (36.5%) which suggests that MRSA or other resistant Gram-positive coverage was not required.

“The lowest appropriateness was observed among the private hospital and paediatric cohorts, suggesting that these prescribers would benefit from targeted AMS intervention.”

“Pleasingly, however, this study observed an overall decrease in both gentamicin and vancomycin use from 2013 to 2021, which may reflect steadily increasing adherence to Australian consensus guidelines recommendations as well as effective AMS interventions.”

The study noted that use of cefepime was low (8.7%) despite being recommended as a suitable alternative to piperacillin-tazobactam. In particular, there is evidence that cefepime may better preserve the gastrointestinal microbiota than piperacillin-tazobactam.

“Given the growing renewed interest in this area, the role of cefepime in NF should be addressed in the pending update to the Australian consensus guidelines as well as future international guidelines,” it said.

Meropenem had the highest rates of guideline non-compliance “…suggesting that available guidelines are not addressing current needs.”

The investigators noted there was no guidance on the role of meropenem in patients with persistent or recurrent neutropenic fever, “…a frequently encountered reason for meropenem use in clinical practice.”

The study also found that 20.3% of prescriptions were for patients with at least one antibiotic allergy label, usually to unspecified penicillins.

“Antibiotic allergy testing successfully removes a high proportion of allergy labels resulting in improved antimicrobial appropriateness, decreased broad-spectrum antimicrobial use and reduced hospital medication expenditure,” it said.

Investment in antibiotic allergy services was therefore likely to be of great benefit, they said.

The study was led by Melbourne pharmacist Nikhil Singh, from the National Centre for Infections in Cancer.