High-dose rifampicin in tuberculosis: Experiences from a Dutch tuberculosis centre.

BACKGROUND: Recent evidence suggests that higher rifampicin doses may improve tuberculosis (TB) treatment outcome. METHODS: In this observational cohort study we evaluated all TB patients who were treated with high-dose rifampicin (> 10 mg/kg daily) in our reference centre, from January 2008 to May 2018. Indications, achieved plasma rifampicin exposures, safety and tolerability were evaluated. RESULTS: Eighty-eight patients were included. The main indications were low plasma concentrations (64.7%) and severe illness (29.5%), including central nervous system TB. Adjusted rifampicin dosages ranged from 900 mg to a maximum of 2400 mg (corresponding to 32 mg/kg) per day. Patients with severe illness received high-dose rifampicin immediately, the others had a higher dosage guided by therapeutic drug monitoring. Four patients developed hepatotoxicity, of which two were proven due to isoniazid. Re-introduction of high-dose rifampicin was successful in all four. Eighty-seven patients tolerated high-dose rifampicin well throughout treatment. Only one patient required a dose reduction due to gastro-intestinal disturbance. CONCLUSION: High-dose rifampicin, used in specific groups of patients in our clinical setting, is safe and well-tolerated for the whole treatment duration. Measurement of drug exposures could be used as a tool/guide to increase rifampicin dosage if a reduced medication absorption or a poor treatment outcome is suspected. We suggest to administer high-dose rifampicin to patients with severe manifestations of TB or low rifampicin exposure to improve treatment outcome.

The short-term and long-term effectiveness of a multidisciplinary hand hygiene improvement program.

BACKGROUND: Although hand hygiene (HH) compliance has been an important issue for years, the compliance rate is still a problem in health care today. METHODS: This was an observational, prospective, before-and-after study. We measured HH knowledge and HH compliance before (baseline), directly after (poststrategy), and 6 months after the performance of HH team strategies (follow-up). The study was composed of employed nurses and physicians working in the department of internal medicine of a university hospital. We performed a multifaceted improvement program including HH education, feedback, reminders, social influence activities including the use of role models, and improvement of HH facilities. RESULTS: Ninety-two nurses and physicians were included. Compared with baseline, there was a significant improvement in the overall mean HH knowledge score at poststrategy (from 7.4 to 8.4) and follow-up (from 7.4 to 8.3). The overall HH compliance was 27% at baseline, 83% at poststrategy, and 75% at follow-up. At baseline, the compliance rate was 17% in nurses and 43% in physicians and significantly improved to 63% in nurses and 91% in physicians at follow-up. CONCLUSION: Our multifaceted HH improvement program resulted in a sustained improvement of HH knowledge and compliance in nurses as well as physicians.