Aim Indications for medicines are poorly recorded in prescriptions at our hospitals. Indications are ‘optional’ on paper prescriptions but can be mandated in electronic prescriptions. As part of an initiative to improve indication documentation for antimicrobial medicines, a prospective controlled study of compulsory indications for antibacterial medicines was undertaken. Our aim was to assess the effect of making indications compulsory in an electronic prescribing and administration (ePA) system. Methods Compulsory indications on prescriptions were implemented in our tertiary hospital ePA system for eight antibacterial medicines. The proportion of ‘credible indications’ following the intervention for these medicines was compared with 23 antibacterial medicines with pre-existing (positive control) and 71 without (negative control) compulsory indications. Documented indications for all antibacterial medicines four weeks before and after implementation of compulsory indications were extracted from the ePA system and manually classified as ‘credible indication’, ‘other text’, ‘rubbish text’, or ‘blank’. Results The proportion of ‘credible indications’ for the intervention group had an absolute increase of 64.8%, from 12.5% (270/2166) to 77.3% (1684/2179). In the intervention group ‘rubbish text’ increased by 1.3% (from 0.05% to 1.3%), ‘other text’ increased from 5.4% to 15.3%, and ‘blank’ decreased from 82.1% to 6.1%. For antibacterials with no compulsory indication ‘credible indications’ increased from 22.0% (793/3611) to 46.0% (1667/3621), and in those with pre-existing compulsory indications from 80.3% (191/238) to 83.2% (183/220). Conclusion Implementation of compulsory indications for antibacterial medicines in the ePA system increased ‘credible indications’ substantially with a small increase in ‘rubbish text’.

Aim Oral flucloxacillin may be co-administered with probenecid to increase flucloxacillin concentrations and increase attainment of pharmacokinetic-pharmacodynamic (PK-PD) targets. The aims of this study were to describe outcomes of patients treated with oral flucloxacillin plus probenecid as follow-on therapy from initial intravenous treatment, and to identify optimal dosing regimens when treating infections caused by susceptible Gram-positive organisms. Methods We performed a prospective observational study of adults treated with oral flucloxacillin 1000 mg and probenecid 500 mg 8-hourly (with food) for proven or probable staphylococcal infections. We developed a population pharmacokinetic model of free flucloxacillin concentrations within Monolix, in order to estimate probability of PK-PD target attainment (fT>MIC), and used Monte Carlo simulation to explore optimal dosing regimens. Results The 45 patients (73% male) had a median (range) age of 49 years (20 – 74), weight of 90 kg (59 – 167), fat free mass (Janmahasatian) of 65 kg (38 – 89) and eGFR (CKD-EPI) of 89 mL/min/1.73m2 (41 – 124). The most common infections were osteomyelitis (n=18, 40%) and septic arthritis (n=12, 27%). Forty patients (89%) were cured 30 days after completion of therapy. 10 (22%) experienced nausea which did not require treatment alternation. Free flucloxacillin clearance depended on allometrically-scaled fat free mass, and increased by 1% for each unit increase in eGFR. Conclusion Oral flucloxacillin and probenecid was well-tolerated and efficacious. Patients with higher fat free mass and eGFR may require four times daily dosing and/or therapeutic drug monitoring to ensure PK-PD target attainment.