Metronidazole prescribing practices in Australian hospitals: Measuring guideline compliance and appropriateness to support antimicrobial stewardship.

BACKGROUND: Metronidazole is a commonly prescribed antimicrobial in Australian hospitals. Inappropriate use may increase risks to patient care, such as toxicities and antimicrobial resistance. To date, there is limited information on the quality of metronidazole prescriptions to inform antimicrobial stewardship and quality improvement initiatives. This study aims to describe the quality of metronidazole prescribing practices in Australian hospitals. METHODS: Retrospective data analysis of the Hospital National Antimicrobial Prescribing Survey (Hospital NAPS). Data were collected by auditors at each participating hospital using a standardised auditing tool. All data from 2013 to 2021 were de-identified and analysed descriptively. Variables included were antimicrobial prescribed, indication, guideline compliance and appropriateness. RESULTS: Metronidazole was the fifth most prescribed antimicrobial in the Hospital NAPS dataset (2013-2021), accounting for 5.7 % (n = 14,197) of all antimicrobial prescriptions (n = 250,863). The proportion of metronidazole prescriptions declined by 2 % from 2013 to 2021 (p < 0.001). The most common indications were surgical prophylaxis (15.3 %), diverticulitis (9.4 %), aspiration pneumonia (7.3 %). Over half (53.5 %) of metronidazole prescriptions were deemed compliant with prescribing guidelines and 67.8 % were deemed appropriate. These rates were comparatively lower than the overall results of all antimicrobials. The primary documented reason for inappropriateness was that the spectrum was too broad (34.2 %). Surgical prophylaxis had the lowest rates of guideline compliance (53.8 %) and appropriateness (54.3 %). CONCLUSIONS: Metronidazole remains widely used in Australian hospitals with suboptimal rates of guideline compliance and appropriateness. A noted area for improvement that we identified was using metronidazole when its spectrum was too broad, possibly when anaerobic therapy is unnecessary. With increasing international adoption of the Hospital NAPS programme, future comparative studies will be critical to identify global trends of antimicrobial prescribing quality. Antimicrobial stewardship (AMS) programmes have proven to be effective in improving prescribing quality and should be considered to specifically target improvements in metronidazole prescribing.

Rapid and profound rewiring of brain lipid signaling networks by acute diacylglycerol lipase inhibition.

Diacylglycerol lipases (DAGLα and DAGLß) convert diacylglycerol to the endocannabinoid 2-arachidonoylglycerol. Our understanding of DAGL function has been hindered by a lack of chemical probes that can perturb these enzymes in vivo. Here, we report a set of centrally active DAGL inhibitors and a structurally related control probe and their use, in combination with chemical proteomics and lipidomics, to determine the impact of acute DAGL blockade on brain lipid networks in mice. Within 2 h, DAGL inhibition produced a striking reorganization of bioactive lipids, including elevations in DAGs and reductions in endocannabinoids and eicosanoids. We also found that DAGLα is a short half-life protein, and the inactivation of DAGLs disrupts cannabinoid receptor-dependent synaptic plasticity and impairs neuroinflammatory responses, including lipopolysaccharide-induced anapyrexia. These findings illuminate the highly interconnected and dynamic nature of lipid signaling pathways in the brain and the central role that DAGL enzymes play in regulating this network.