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Efficacy of ciprofloxacin alone and in combination with azlocillin in experimental endocarditis due to pseudomonas aeruginosa

Wirksamkeit von Ciprofloxacin allein und in Kombination mit Azlocillin bei der experimentellen Pseudomonas aeruginosa-Endokarditis

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Summary

The efficacy of ciprofloxacin alone and in combination with azlocillin was compared with that of azlocillin plus tobramycin in a rat model of aortic valve endocarditis due toPseudomonas aeruginosa. MICs against the infecting strain of ciprofloxacin, azlocillin and tobramycin were 0.125, 8, and 0.5 mg/l, respectively. Antimicrobials were administered 24 h after bacterial challenge and for six days. Mean peak/trough serum levels for ciprofloxacin (50 mg/kg i.v. q 12 h), azlocillin (500 mg/kg i.v. q 12 h) and tobramycin (6.5 mg/kg i.v. q 12 h) were: 10.5/0.2, 386/<16, and 6.2/<0.6 mg/l, respectively. Ciprofloxacin alone was more effective than the combination azlocillin-tobramycin in increasing survival (p<0.05), sterilizing blood (p<0.05) and valves (p<0.001), and in reducing bacterial titers in vegetations (p<0.001). Ciprofloxacin-azlocillin combination was not more effective than ciprofloxacin alone. Drug resistance was not encountered in post-treatment isolates with any therapy regimen.

Zusammenfassung

Mit einem Rattenmodell für die Aortenklappenendokarditis, verursacht durchPseudomonas aeruginosa, wurde eine Vergleichsstudie zur Wirksamkeit von Ciprofloxacin allein oder in Kombination mit Azlocillin und der Kombination Azlocillin plus Tobramycin durchgeführt. Die MHK-Werte von Ciprofloxacin, Azlocillin und Tobramycin für den für die Infektion verwendeten Stamm waren 0,125, 8 und 0,5 mg/l. Die Antibiotikatherapie wurde 24 Stunden nach Setzen der Infektion begonnen und sechs Tage lang durchgeführt. Bei einer Dosierung von 50 mg Ciprofloxacin pro kg Körpergewicht alle 12 h i.v. wurden Spitzenspiegel von 10,5 mg/l und Talspiegel von 0,2 mg/l erreicht, mit Azlocillin in einer Dosierung von 500 mg pro kg Körpergewicht alle 12 h i.v. 386 mg/l bzw. 16 mg/l; Tobramycin erreichte nach Gabe von 6,5 mg pro kg alle 12 h i.v. Spitzenspiegel von 6,2 mg/l und Talspiegel von 0,6 mg/l. Bezüglich Überlebensrate, und Erregerelimination aus dem Blut war Ciprofloxacin allein der Kombination Azlocillin-Tobramycin auf dem Signifikanzniveau p<0,05 und bezüglich Sterilisierung der Klappen oder Reduktion der Bakterienzahlen in den Vegetationen auf dem Signifikanzniveau p<0,001 überlegen. Die Kombination Ciprofloxacin-Azlocillin war nicht wirksamer als Ciprofloxacin allein. Mit keinem der Therapieregime war bei den nach Therapie gezüchteten Isolaten eine Resistenzentwicklung nachzuweisen.

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Authors and Affiliations

  1. Laboratoire de Bactériologie et Unité, INSERM 295, Hôtel Dieu, 51, rue Lecat, F-76031, Rouen Cedex

    Cl. Thauvin M.D., F. Lecomte M.D., I. Le Boete M.D., G. Grise M.D. &  J. F. Lemeland

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  1. Cl. Thauvin M.D.
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  2. F. Lecomte M.D.
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  3. I. Le Boete M.D.
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Thauvin, C., Lecomte, F., Le Boete, I. et al. Efficacy of ciprofloxacin alone and in combination with azlocillin in experimental endocarditis due to pseudomonas aeruginosa. Infection 17, 31–34 (1989). https://doi.org/10.1007/BF01643497

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