Abstract
Prosthetic heart valve sewing rings were impregnated with gentamicin crobefat (EMD 46217), a poorly soluble gentamicin salt, gentamicin sulfate, and clindamycin palmitate to prevent early prosthetic endocarditis. MICs and MBCs of gentamicin and/or clindamycin were tested against several pathogens of early prosthetic endocarditis. The combination of gentamicin and clindamycin was found to be effective against most relevant bacterial pathogens. With an in vitro pharmacokinetic model, the antibacterial activity of gentamicin and clindamycin was tested against Staphylococcus aureus and Escherichia coli. High gentamicin levels over the first 24 h were required for a strong reduction of bacterial counts of both strains. Equal amounts of gentamicin and clindamycin sustained the antibacterial effect and prevented regrowth. The most effective release curves of gentamicin and clindamycin found with an in vitro model were used for monitoring release profiles of these antibiotics from impregnated sewing rings by investigating combinations of gentamicin sulfate, gentamicin crobefat, and clindamycin palmitate. Sewing rings impregnated with 4 mg of gentamicin sulfate, 14 mg of gentamicin crobefat, and 20 mg of clindamycin palmitate gave an initial gentamicin burst and afterwards yielded a lower sustained release of gentamicin and clindamycin palmitate. These in vitro release kinetics were confirmed in vivo by pharmacokinetic analysis after intramuscular implantation of impregnated sewing ring segments. Gentamicin and active clindamycin palmitate metabolites were obtained at the implantation site for at least 2 weeks in concentrations of 3 and 5 micrograms per g of muscle, respectively. The investigated method of impregnation holds promise for revision implants after prosthetic valve endocarditis. It may also serve as a prophylactic tool for routine use against this disease.
Full Text
The Full Text of this article is available as a PDF (285.8 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Adam D., Nawrath I. Zur Kombination von Clindamycin mit beta-Laktam-Antibiotika und Aminoglykosiden. Arzneimittelforschung. 1981;31(8):1295–1298. [PubMed] [Google Scholar]
- Anderson J. M., Niven H., Pelagalli J., Olanoff L. S., Jones R. D. The role of the fibrous capsule in the function of implanted drug-polymer sustained release systems. J Biomed Mater Res. 1981 Nov;15(6):889–902. doi: 10.1002/jbm.820150613. [DOI] [PubMed] [Google Scholar]
- Fass R. J., Rotilie C. A., Prior R. B. Interaction of clindamycin and gentamicin in vitro. Antimicrob Agents Chemother. 1974 Nov;6(5):582–587. doi: 10.1128/aac.6.5.582. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Grasso S., Meinardi G., de Carneri I., Tamassia V. New in vitro model to study the effect of antibiotic concentration and rate of elimination on antibacterial activity. Antimicrob Agents Chemother. 1978 Apr;13(4):570–576. doi: 10.1128/aac.13.4.570. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Guidelines for reporting morbidity and mortality after cardiac valvular operations. Ann Thorac Surg. 1988 Sep;46(3):257–259. doi: 10.1016/s0003-4975(10)65920-6. [DOI] [PubMed] [Google Scholar]
- Karck M., Siclari F., Wahlig H., Sperling U., Schmid C., Haverich A. Pretreatment of prosthetic valve sewing-ring with the antibiotic/fibrin sealant compound as a prophylactic tool against prosthetic valve endocarditis. Eur J Cardiothorac Surg. 1990;4(3):142–146. doi: 10.1016/1010-7940(90)90185-3. [DOI] [PubMed] [Google Scholar]
- Klemm K. Gentamycin-PMMA-Kugeln in der Behandlung abszedierender Knochen- und Weichteilinfektionen. Zentralbl Chir. 1979;104(14):934–942. [PubMed] [Google Scholar]
- Lau J. K., Robles A., Cherian A., Ross D. N. Surgical treatment of prosthetic endocarditis. Aortic root replacement using a homograft. J Thorac Cardiovasc Surg. 1984 May;87(5):712–716. [PubMed] [Google Scholar]
- Raychaudhury T., Cameron E. W., Walbaum P. R. Surgical management of prosthetic valve endocarditis. J Thorac Cardiovasc Surg. 1983 Jul;86(1):112–114. [PubMed] [Google Scholar]
- Wahlig H., Dingeldein E., Bergmann R., Reuss K. The release of gentamicin from polymethylmethacrylate beads. An experimental and pharmacokinetic study. J Bone Joint Surg Br. 1978 May;60-B(2):270–275. doi: 10.1302/0301-620X.60B2.659478. [DOI] [PubMed] [Google Scholar]
- Wilson W. R., Danielson G. K., Giuliani E. R., Geraci J. E. Prosthetic valve endocarditis. Mayo Clin Proc. 1982 Mar;57(3):155–161. [PubMed] [Google Scholar]