1956. Teicoplanin-based antimicrobial therapy in Staphylococcus aureus bone and joint infection (BJI): tolerance, efficacy and experience with subcutaneous (SC) administration
Session: Poster Abstract Session: Antimicrobial Pharmacokinetics and Pharmacodynamics
Saturday, October 29, 2016
Room: Poster Hall

Background: Staphylococci represent the first etiologic agents of BJIs, leading to a wild use of glycopeptides, especially in case of methicillin-resistance or betalactam intolerance. In this setting, teicoplanin may represent an interesting alternative to vancomycin because of its acceptable bone diffusion and possible – but poorly evaluated – SC administration.

Methods: Retrospective cohort study evaluating tolerance and pharmacokinetics of intravenous or SC teicoplanin in S. aureus BJI. Each SC dose was diluted in 50 mL of 0.9% NaCl and delivered by a 30- to 60-min gravity infusion using a butterfly disposable needle. Outcome of BJI was also assessed using multivariate logistic regression analysis.

Results: 65 BJIs (orthopedic device-related infections, 69%; methicillin-resistance, 17%) were treated by teicoplanin at the initial dose of 5.7 mg/kg/day (IQR, 4.7-6.5) after a loading dose of 5 injections 12h apart. The first trough teicoplanin level (Cmin) reached the therapeutic target (15 mg/L) in 26% of patients, only. An overdose (Cmin >25 mg/L) was observed in 16% patients, 50% of which had chronic renal failure (p=0.049). Seven adverse events occurred in 6 patients (10%); no predictive factor could be highlighted. After a 91-week follow-up (IQR, 51-183), 27 treatment failures were observed (42%), associated with diabetes (OR 5.1; p=0.057), systemic inflammatory disease (OR 5.6; p=0.043), and the presence of abscess (OR 4.1; p<10-3). A normal CRP-value at 1 month was protective (OR, 0.2; p=0.029). SC administration (14 patients) showed no difference regarding pharmacokinetics and tolerance compared to the intravenous route (Figure 1). No necrosis at the SC injection site was observed among 1456 SC injections in total.

Conclusion: Teicoplanin constitutes a well-tolerated therapeutic alternative in S. aureus BJI. The loading dose might necessitate an increase up to 9-12 mg/kg in order to quickly reach the therapeutic target, but the tolerance of such higher doses remains to be evaluated, especially if using the SC route. The SC administration may facilitate teicoplanin use in outpatients, without enhancing the risk of adverse events.

Figure 1. Comparison of median teicoplanin trough concentrations in intravenously- and subcutaneously-treated patients during the first two weeks of treatment.

Tristan Ferry, MD, PhD1,2, Olivier Peeters, MD1, André Boibieux, MD1, Evelyne Braun, MD1, Anissa Bouaziz, MD3, Judith Karsenty, MD4, Frederic Laurent, DPharm, PhD2,5, Sébastien Lustig, MD, PhD6, Emmanuel Forestier, MD7, Florence Ader, MD, PhD1,2, Christian Chidiac, MD, PhD1,2, Florent Valour, MD, PhD1,2 and Lyon BJI study group, (1)ID Department, Regional Reference Center for Bji, Hospices Civils de Lyon, Lyon, France, (2)INSERM U1111 - International Center for Research in Infectiology - Claude Bernard Lyon 1 University, Lyon, France, (3)ID Department, Centre Hospitalier de Vienne, Vienne, France, (4)ID Department, Centre Hospitalier de Chalon sur Saone, Chalon sur Saone, France, (5)Laboratory of Bacteriology, Regional Reference Center for Bji, Hospices Civils de Lyon, Lyon, France, (6)Orthopaedic Surgery, Regional Reference Center for Bji, Hospices Civils de Lyon, Lyon, France, (7)ID Department, Centre Hospitalier Métropole Savoie, Chambéry, France

Disclosures:

T. Ferry, None

O. Peeters, None

A. Boibieux, None

E. Braun, None

A. Bouaziz, None

J. Karsenty, None

F. Laurent, None

S. Lustig, None

E. Forestier, None

F. Ader, None

C. Chidiac, None

F. Valour, None

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