Risk factors for failure of outpatient parenteral antibiotic therapy (OPAT) in infective endocarditis.

OBJECTIVES: To identify risk factors for failure of outpatient antibiotic therapy (OPAT) in infective endocarditis (IE). PATIENTS AND METHODS: We identified IE cases managed at a single centre over 12 years from a prospectively maintained database. 'OPAT failure' was defined as unplanned readmission or antibiotic switch due to adverse drug reaction or antibiotic resistance. We analysed patient and disease-related risk factors for OPAT failure by univariate and multivariate logistic regression. We also retrospectively collected follow-up data on adverse disease outcome (defined as IE-related death or relapse) and performed Kaplan-Meier survival analysis up to 36 months following OPAT. RESULTS: We identified 80 episodes of OPAT in IE. Failure occurred in 25/80 episodes (31.3%). On multivariate analysis, cardiac or renal failure [pooled OR 7.39 (95% CI 1.84-29.66), P=0.005] and teicoplanin therapy [OR 8.69 (95% CI 2.01-37.47), P=0.004] were independently associated with increased OPAT failure. OPAT failure with teicoplanin occurred despite therapeutic plasma levels. OPAT failure predicted adverse disease outcome up to 36 months (P=0.016 log-rank test). CONCLUSIONS: These data caution against selecting patients with endocarditis for OPAT in the presence of cardiac or renal failure and suggest teicoplanin therapy may be associated with suboptimal OPAT outcomes. Alternative regimens to teicoplanin in the OPAT setting should be further investigated.

Development of teicoplanin dosage guidelines for patients treated within an outpatient parenteral antibiotic therapy (OPAT) programme.

OBJECTIVES: The long elimination half-life of teicoplanin facilitates outpatient parenteral antibiotic therapy (OPAT) with thrice-weekly dosing. This study aimed to develop teicoplanin dosage guidelines for OPAT use from routine clinical data. METHODS: Patients received 15-25 mg/kg/day for 3 days, then 15-25 mg/kg thrice weekly. Trough concentrations were measured weekly and doses adjusted to maintain 20-30 or 10-20 mg/L according to clinical condition. Concentration-time data were analysed using the pharmacokinetic package NONMEM and the final model was used to develop new dosage guidelines. RESULTS: Data from 94 and 36 patients were used for model development and validation, respectively. Patient ages ranged from 15 to 94 years, weights from 43 to 146 kg and estimated CL(CR) from 9 to 195 mL/min. Teicoplanin concentrations (n = 670) ranged from 6.7 to 66.9 mg/L and a one-compartment model adequately described the data. The typical estimate of CL was 0.542 L/h and changed by 10.6% for every 10 mL/min difference from a CL(CR) of 66 mL/min. V was 1.62 L/kg. Dosage guidelines based on body weight and CL(CR) can be expected to lead to a significant improvement in the proportion of concentrations in the range 20-30 mg/L. Alternative doses aimed at lower target concentrations have also been developed. CONCLUSIONS: New dosage guidelines have been developed to support thrice-weekly administration of teicoplanin in an OPAT setting.