Abstract
Several in vitro and in vivo studies as well as clinical trials have demonstrated that once-daily aminoglycoside regimens are as effective as or more effective than multiple daily dosings. However, the most favorable aminoglycoside dosing regimen for treating enterococcal endocarditis remains controversial. The same total dose of netilmicin was administered as once-daily (24-micrograms/ml peaks) and thrice-daily (8 micrograms/ml) regimens in a pharmacodynamic in vitro model simulating exposure of Enterococcus faecalis to human serum kinetics. Netilmicin was administered in combination with continuous infusions of amoxicillin, vancomycin, or penicillin against a bacterial biofilm adhering to glass beads. No significant differences in bacterial killing were found after 24 or 48 h between the once- and thrice-daily regimens. Additional experiments considering animal kinetics (half-life of netilmicin, 20 min) instead of human kinetics (half-life, 2.5 h) in the pharmacodynamic model also revealed similar results. The addition of netilmicin synergistically increased the activity of vancomycin (P < 0.05). In contrast, amoxicillin alone was as effective as the combination with netilmicin. Thus, it could not be established in this model that once-daily dosing of aminoglycosides is contraindicated for treating infections caused by E. faecalis.
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Selected References
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- Anwar H., Strap J. L., Costerton J. W. Establishment of aging biofilms: possible mechanism of bacterial resistance to antimicrobial therapy. Antimicrob Agents Chemother. 1992 Jul;36(7):1347–1351. doi: 10.1128/aac.36.7.1347. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Blaser J. Efficacy of once- and thrice-daily dosing of aminoglycosides in in-vitro models of infection. J Antimicrob Chemother. 1991 May;27 (Suppl 100):21–28. doi: 10.1093/jac/27.suppl_c.21. [DOI] [PubMed] [Google Scholar]
- Blaser J., Stone B. B., Groner M. C., Zinner S. H. Impact of netilmicin regimens on the activities of ceftazidime-netilmicin combinations against Pseudomonas aeruginosa in an in vitro pharmacokinetic model. Antimicrob Agents Chemother. 1985 Jul;28(1):64–68. doi: 10.1128/aac.28.1.64. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Craig W. A., Redington J., Ebert S. C. Pharmacodynamics of amikacin in vitro and in mouse thigh and lung infections. J Antimicrob Chemother. 1991 May;27 (Suppl 100):29–40. doi: 10.1093/jac/27.suppl_c.29. [DOI] [PubMed] [Google Scholar]
- Fantin B., Carbon C. Importance of the aminoglycoside dosing regimen in the penicillin-netilmicin combination for treatment of Enterococcus faecalis-induced experimental endocarditis. Antimicrob Agents Chemother. 1990 Dec;34(12):2387–2391. doi: 10.1128/aac.34.12.2387. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gavaldà J., Cardona P. J., Almirante B., Capdevila J. A., Laguarda M., Pou L., Crespo E., Pigrau C., Pahissa A. Treatment of experimental endocarditis due to Enterococcus faecalis using once-daily dosing regimen of gentamicin plus simulated profiles of ampicillin in human serum. Antimicrob Agents Chemother. 1996 Jan;40(1):173–178. doi: 10.1128/aac.40.1.173. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gavaldà J., Pahissa A., Almirante B., Laguarda M., Crespo E., Pou L., Fernández F. Effect of gentamicin dosing interval on therapy of viridans streptococcal experimental endocarditis with gentamicin plus penicillin. Antimicrob Agents Chemother. 1995 Sep;39(9):2098–2103. doi: 10.1128/aac.39.9.2098. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mghir A. S., Cremieux A. C., Jambou R., Muffat-Joly M., Pocidalo J. J., Carbon C. Dextranase enhances antibiotic efficacy in experimental viridans streptococcal endocarditis. Antimicrob Agents Chemother. 1994 May;38(5):953–958. doi: 10.1128/aac.38.5.953. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Saleh-Mghir A., Cremieux A. C., Vallois J. M., Muffat-Joly M., Devine C., Carbon C. Optimal aminoglycoside dosing regimen for penicillin-tobramycin synergism in experimental Streptococcus adjacens endocarditis. Antimicrob Agents Chemother. 1992 Nov;36(11):2403–2407. doi: 10.1128/aac.36.11.2403. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Vergères P., Blaser J. Amikacin, ceftazidime, and flucloxacillin against suspended and adherent Pseudomonas aeruginosa and Staphylococcus epidermidis in an in vitro model of infection. J Infect Dis. 1992 Feb;165(2):281–289. doi: 10.1093/infdis/165.2.281. [DOI] [PubMed] [Google Scholar]
- Vree T. B., Hekster Y. A., Baars A. M., Van der Kleijn E. Rapid determination of amoxycillin (clamoxyl) and ampicillin (penbritin) in body fluids of many by means of high-performance liquid chromatography. J Chromatogr. 1978 May 1;145(3):496–501. doi: 10.1016/s0378-4347(00)81384-5. [DOI] [PubMed] [Google Scholar]