Simulated human serum profiles of one daily dose of ceftriaxone plus netilmicin in treatment of experimental streptococcal endocarditis.

Abstract

We performed experiments in rats aimed at determining whether a combination of ceftriaxone (CRO) and netilmicin (NET), by using once-daily administration in rats, which simulated profiles of drug in human serum, was more effective than either agent alone in the treatment of endocarditis caused by viridans group streptococci. A programmable infusion pump system enabled the production of profiles of CRO in serum that simulate those found in humans after the intravenous administration of 2 g. The subcutaneous administration of 18 mg of NET per kg of body weight produced levels in the sera of rats comparable to those after the intravenous administration of a dose of 5 mg of NET per kg in humans. Rats with catheter-induced aortic vegetations were infected intravenously with two test strains, a CRO-susceptible Streptococcus sanguis strain (MICs of CRO and NET, 0.064 and 8 mg/liter, respectively) and a relatively CRO-resistant Streptococcus mitis strain (MICs of CRO and NET, 2 and 8 mg/liter, respectively). Against both strains, the combination of CRO and NET was synergistic in vitro as determined by time-kill curves. Treatment of rats was started 48 h postinfection and lasted for 3 days. CRO alone was effective against the susceptible strain (P < 0.001 compared with control animals) but was not effective against the resistant organism. A significantly enhanced antibacterial activity of the CRO-NET combination in reducing the valvular bacterial counts was observed with both test strains (P < 0.001). The synergistic effect was obtained with a single daily injection of NET which provided detectable levels in serum for only 8 h, suggesting that in vivo synergism in the treatment of infections caused by viridans group streptococci can be obtained without 24 h of aminoglycoside coverage. These experimental data might provide a rationale for clinical trials of a once-a-day dosing regimen in the treatment of streptococcal but nonenterococcal endocarditis.

• Authors: M Blatter, U Fluckiger, J Entenza, M P Glauser, P Francioli
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 37 Issue 9 Pg. 1971-6 (Sep 1993) ISSN: 0066-4804 [Print] United States
• PMID: 8239615 (Publication Type: Journal Article)

Chemical References

• Netilmicin
• Ceftriaxone

Topics

• Animals
• Ceftriaxone (administration & dosage, blood, therapeutic use)
• Endocarditis, Bacterial (blood, drug therapy, microbiology)
• Female
• Humans
• Infusion Pumps
• Microbial Sensitivity Tests
• Netilmicin (administration & dosage, blood, therapeutic use)
• Rats
• Rats, Wistar
• Serum Bactericidal Test
• Streptococcal Infections (blood, drug therapy, microbiology)
• Streptococcus (drug effects)
• Streptococcus sanguis (drug effects)