Comparative capacity of orally administered amoxicillin and parenterally administered penicillin-streptomycin to protect rabbits against experimentally induced streptococcal endocarditis

Abstract

A single-intramuscular-dose immunization regimen with a penicillin G-streptomycin combination was compared with three oral-dose amoxicillin regimens for the capacity to prevent Streptococcus sanguis infections of experimentally induced valvular heart lesions in rabbits. Challenge doses of 104, 106, and 108 CFU of a strain of S. sanguis equally susceptible to penicillin and amoxicillin were used in this study. Measured by recovery of test organisms from endocardial lesions, the lowest concentration of these inocula was infective for 60% of the recipients; the two higher-concentration inocula were infective for all recipients. The penicillin G-streptomycin combination provided complete protection against infection with inocula of all sizes. A single-oral-dose amoxicillin regimen (50 mg/kg of body weight) prevented endocarditis when rabbits were challenged with 104 CFU, but protection diminished with increasing inoculum concentrations. Similar results were achieved when five oral doses of amoxicillin (8.5 mg/kg of body weight) added at 8-h intervals were included in the single-oral-dose regimen. In contrast, when rabbits received two oral doses of amoxillin (50 mg/kg of body weight) with a 10-h interval between doses, prophylaxis was fully effective with even the highest inoculum concentration.Patients with valvular heart disease or intracardiac prostheses are presumed to be at risk for infective endocarditis (IE) after dental work. Experimental studies on the prevention of streptococcal endocarditis suggested that application of bactericidal antibiotics would reduce this risk and that a penicillin G-streptomycin combination was the most effective regimen (5, 10). This led the American Heart Association to suggest that patients at high risk should be given penicillin plus an aminoglycoside intramuscularly for prophylaxis of IE caused by viridans streptococci (1). In Europe, however, orally administered amoxicillin has been used for coverage because of the following reasons. Compliance with the American Heart Association regimens has been reported to be low (7), essentially all strains of viridans streptococci are susceptible to amoxicillin, and this antibiotic is well absorbed and well tolerated when administered orally (12,13 ,ug/ml, streptomycin was tested at concentrations of 10 and 55 p.g/ml, amoxicillin was tested at concentrations of 1 and 21 ,ug/ml, and the penicillin G-streptomycin combination was tested at concentrations of 0.5 and 5 ,ug/ml, respectively. A bacterial inoculum of 106 CFU of S. sanguis (1 ml of a 1:200 dilution of an overnight culture) was added to tubes containing 1 ml of Mueller-Hinton broth with or without antibiotic as a growth control. All tubes were incubated in 10% CO2 at 909

Tolerance and efficacy of parenterally administered penicillin-streptomycin and orally administered amoxicillin or penicillin V for prophylaxis of experimentally induced streptococcal endocarditis

“…In previous studies the addition of probenecid to oral amoxicillin (8.5 mg/kg) led to peak levels of 5.4 ± 1.7 ,ug/ml of serum. These levels were similar to those achieved in humans after an oral dose of 0.5 g of amoxicillin, decreasing at similar rates (13).…”

“…The MICs and MBCs, respectively, were 0.04 and >128 ,ug/ml for amoxicillin, penicillin V, and penicillin G; both were 32 ,ug/ml for streptomycin. Thus, the MICs of amoxicillin and penicillin were comparable to that obtained with the highly susceptible strain of S. sanguis (strain HPE93) used in previous prophylactic experiments (MIC, 0.4 ,ug/ml) (13,14), but S. sanguis HPE77 was highly tolerant to both antibiotics and thus a wide disparity in their respective MBCs was found (MBCs, >128 and 0.08 ,ug/ml for HPE77 and HPE93, respectively). a p value for analysis of overall equality of proportions of infected to noninfected rabbits among orally treated prophylactic groups (AMOX-1, AMOX-2, AMOX-6, PCN-1, and PCN-2).…”

“…These peak levels were similar to those achieved in humans after an intramuscular dose of crystalline penicillin G (1,000,000 U) plus procaine penicillin G (600,000 U) and streptomycin (1 g). Although levels of streptomycin decreased faster in rabbits, all levels of penicillin G in serum were roughly similar to those achieved in humans (13).…”

“…Oral amoxicillin achieves higher and more sustained levels of antibiotic in serum than does penicillin V (16). However, we have found no differences between these two drugs for prophylaxis of IE in rabbits with experimentally induced valvular heart lesions challenged with a highly susceptible strain of Streptococcus sanguis biotype 11 (13,14) when both antibiotics were administratered at dosages comparable to scheduled regimens recommended by the American Heart Association (17) and the Working Party of the British Society for Antimicrobial Chemotherapy (19). Further work evaluating protection against less susceptible strains is needed to elucidate the relative merits of each anitibiotic and define the most cost-efficient regimen.…”

“…The MICs and MBCs of amoxicillin, penicillin V, penicillin G, and streptomycin were measured by a standard twofold tube dilution method (13) On the basis of the results obtained in previous studies with intramuscularly administered procaine penicillin G plus streptomycin and orally administered amoxicillin (13) and penicillin V (19) for prophylaxis of streptococcal endocarditis in fasting rabbits, 1 h before challenge subgroups of 15 animals received one of the following regimens.…”