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Dispersin B therapy of Staphylococcus aureus experimental port-related bloodstream infection

Abstract number: 1733_1282

Serrera A., del Pozo J.L., Martinez A., Alonso M., Gonzalez R., Leiva J., Vergara M., Lasa I.

Objectives:S. aureus is a common cause of port-related bloodstream infections (PRBI). Treatment of these infections typically consists of surgical removal of the port and prolonged therapy with adequate antimicrobials. Dispersin B (Dsp-B) is an enzyme produced by Actinobacillus actinomycetemcomitans that cleaves beta 1–6 N-Acetylglucosamine polymers in S. aureus biofilm. We analysed the activity of Dsp-B (administered as a lock solution inside the port with teicoplanin) in a sheep model of PRBI.

Methods: Experimental PRBI was established in 24 female sheeps. Three days after initialing the infection, animals were randomised into three equal groups and antimicrobial therapy was initiated as follows: (i) no treatment, (ii) iv teicoplanin (loading dose of 6 mg/k/12 h × 3 doses and then 4 mg/k/24 h) plus teicoplanin locks (10 mg/mL) and (iii) iv teicoplanin plus Dsp-B-teicoplanin locks (40 mg/mL and 10 mg/mL respectively). This treatment was administered every day for ten days. Blood cultures were extracted (venipuncture and port) every day. Three days after completion of therapy, sheeps were sacrificed and ports were aseptically removed and cultured (swabbing of the internal port lumen, septum sonication and catheter tip sonication).

Results: All the animals in no treatment group died due to septic complications and all blood and port cultures were positive for S. aureus. In group ii, 75% of the animals got sterile blood cultures during treatment (mean: 7, range: 3–10 days), but all the port cultures were positive after removal. In group iii 100% of the animals got sterile blood cultures during treatment (mean: 3, range: 3–8 days), and catheter cultures were completely negative in 50% of the animals.

Conclusion: Our results indicate that a combination lock of Dsp-B with teicoplanin besides systemic antibiotherapy is active in a sheep model of PRBI. Application of this therapy in the human setting could eliminate the need for port removal in related infections.

This work was supported by a grant from Proy. Inst. Carlos III ref. 03/1102

Session Details

Date: 31/03/2007
Time: 00:00-00:00
Session name: European Society of Clinical Microbiology and Infectious Diseases
Subject:
Location: ICC, Munich, Germany
Presentation type:
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