Successful prophylaxis of experimental streptococcal endocarditis with single doses of sublethal concentrations of penicillin

Penicillin prophylaxis against experimental endocarditis due to a strain of Streptococcus intermedtus isolated from a patient with endocarditis was studied in rats. The minimum bactericidal concentration of penicillin for this strain was more than 64 mg/l and was higher than the peak penicillin serum level obtained in rats 30 min after the iv injection of 60 mg/kg, and in man after an oral dose of 2 g of phenoxymethyl penicillin. Moreover timed kill curves performed in the presence of 64 mg/l of penicillin showed no decrease in the number of colony-forming units during the first 6 h of incubation and only a 95% decrease after 24 h. In addition, no bactericidal activity could be detected in the serum 30 min after penicillin injection, that is at the time of bacterial challenge. Using the minimum bacterial inoculum needed to produce endocarditis in 90% of control animals (ID90), penicillin successfully prevented endocarditis due to this strain. We conclude that penicillin may prevent streptococcal endocarditis by other mechanisms than bacterial killin

Successful Prophylaxis Against Experimental Streptococcal Endocarditis with Bacteriostatic Antibiotics

Because bacteriostatic concentrations of vancomycin are effective in prophylaxis against endocarditis due to Streptococcus sanguis in rats, the efficacy of three other bacteriostatic antibiotics was investigated against three different streptococcal species that cause subacute endocarditis in humans: Streptococcus intermedius, S. sanguis, and Streptococcus mitior. Rats were challenged by intravenous injection of 2 × 105 colony-forming units of streptococci 24 hr after intracardiac insertion of a transaortic catheter and 30 min after intravenous injection of various doses of clindamycin, erythromycin, and doxycycline. Significant protection was achieved with all three antibiotics, but only clindamycin was fully effective against all three species at doses that simulated serum levels achievable in humans after oral administration. Endocarditis was prevented by antibiotic concentrations in serum far below minimal bactericidal concentrations for these streptococci. Furthermore, serum at the time of bacterial challenge was not bactericidal. Therefore, single doses of nonbactericidal antibiotics prevented endocarditis in rats by mechanisms other than bacterial killin

Relevance of animal models to the prophylaxis of infective endocarditis

Intravascular or cardiac endothelial lesions may become colonized during bacteraemic episodes and lead to the development of bacterial endocarditis (BE). It has therefore long been recommended that patients with known cardiac lesions receive prophylactic antibiotics before undergoing procedures that might release bacteria into the blood stream. Because clinical trials of antibiotic prophylaxis of endocarditis cannot be conducted in humans for ethical as well as for statistical reasons (Durack, 1985), the questions of which antibiotic, what dosage, and for how long are a matter of controversy. Unfortunately, these questions can only be studied in animals, with all the limitations that this type of approach brings with it. However, animal experimental studies have helped in understanding the conditions and, to some extent, the mode of action of antibiotics in preventing the development of endocardial infection, thus allowing some rationale for devising prophylactic recommendations for the various patients at risk of developing B

Comparison of Single Doses of Amoxicillin or of Amoxicillin-Gentamicin for the Prevention of Endocarditis Caused by Streptococcus faecalis and by Viridans Streptococci

Recent recommendations for the prophylaxis of endocarditis in humans have advocated single doses or short courses of antibiotic combinations (β-lactam plus aminoglycoside) for susceptible patients in whom enterococcal bacteremia might develop or for patients at especially high risk of developing endocarditis (e.g., patients with prosthetic cardiac valves). We tested the prophylactic efficacy (in rats with catheter-induced aortic vegetations) of single doses of amoxicillin plus gentamicin against challenge with various streptococcal strains (two strains of Streptococcus faecalis, one of Streptococcus bovis, and three of viridans streptococci); we then compared this efficacy with that of single doses of amoxicillin alone. Successful prophylaxis against all six strains was achieved with single doses of both amoxicillin alone and amoxicillin plus gentamicin. This protection, however, was limited, for both regimens, to the lowest bacterial-inoculum size producing endocarditis in 90% of control rats and was not extended to higher inocula by using the combination of antibiotics. We concluded that a single dose of amoxicillin alone was protective against enterococcal and nonenterococcal endocarditis in the rat, but that its efficacy was limited and could not be improved by the simultaneous administration of gentamici

Comparative Studies of Fluoroquinolones in the Treatment of Urinary Tract Infections

The results of comparative trials of fluoroquinolones for the treatment of uncomplicated and complicated urinary tract infections (UTI) were reviewed. Severalrandomized, comparative trials showedthat in uncomplicatedUTI norfloxacin, ciprofloxacin, and ofloxacin wereat least as effectiveas trimethoprim-sulfamethoxazole (TMP-SMZ) and amoxicillinand usually more effectivethan nalidixicacid, pipemidic acid, and nitrofurantoin. Comparativetrials of single-dose regimens have, however, beenlimited. A few randomized, comparative trials have shown that in complicated UTI norfloxacin, ciprofloxacin, and ofloxacin wereat least as effectiveas amoxicillinand TMP-SMZand usually more effective than pipemidic acid. Moreover, preliminary results indicate that fluoroquinolones might be effective for the oral treatment of complicated UTI that are difficult to treat, especially those due to Pseudomonas aeruginosa. Comparative trials are neededto establish the value of fluoroquinolones for chronic bacterial prostatitis. There are no conclusivedata on fluoroquinolone treatment of UTI in patients with renal failure. Emergence of resistantpathogensduring therapywith fluoroquinolones has beeninfrequentbut might be more frequent in complicated UTI caused by P. aeruginos

Prophylaxis of pyelonephritis by aminoglycosides accumulated in the kidney

When given prophylactically, gentamicin accumulates and persists in the rat kidney and affords protection against obstructive acute Escherichia coli pyelonephritis. Similar protection is observed after administration of amikacin, netilmicin and tobramycin, which accumulate to various degrees in the renal parenchyma. In those animals developing pyelonephritis despite aminoglycoside prophylaxis, renal infection and inflammation are reduced during the acute phase of the disease. This results in almost complete protection against renal scarring later on. Administrée à titre prophylactique, la Gentamicine s'accurnule dans le rein du rat et le protège contre l'apparition de pyélonéphrite aiguë à E. coli. Un effet protecteur identique est observé aprés administration d'Amikacine, de Nétilmicine, et de Tobramycine, qui s'accumulent à des degrés divers dans le parenchyme rénal. Chez l'animal, lorsqu'apparait une pyélonéphrite, malgré le traitement prophylactique par les aminoglycosides, l'infection et l'inflammation rénales sont diminuées durant la phase aiguë de la maladie. Ceci réduit le risque de lésion et de formation ultérieure de tissu cicatricie

The value of experimental models in the prophylaxis of bacterial endocarditis

Infective endocarditis (IE) is still a serious medical problem. It not only carries significant mortality during the actual period of endocardial infection, but causes morbidity that may persist beyond the duratio

Comparative Studies of Fluoroquinolones in the Treatment of Urinary Tract Infections

The results of comparative trials of fluoroquinolones for the treatment of uncomplicated and complicated urinary tract infections (UTI) were reviewed. Severalrandomized, comparative trials showedthat in uncomplicatedUTI norfloxacin, ciprofloxacin, and ofloxacin wereat least as effectiveas trimethoprim-sulfamethoxazole (TMP-SMZ) and amoxicillinand usually more effectivethan nalidixicacid, pipemidic acid, and nitrofurantoin. Comparativetrials of single-dose regimens have, however, beenlimited. A few randomized, comparative trials have shown that in complicated UTI norfloxacin, ciprofloxacin, and ofloxacin wereat least as effectiveas amoxicillinand TMP-SMZand usually more effective than pipemidic acid. Moreover, preliminary results indicate that fluoroquinolones might be effective for the oral treatment of complicated UTI that are difficult to treat, especially those due to Pseudomonas aeruginosa. Comparative trials are neededto establish the value of fluoroquinolones for chronic bacterial prostatitis. There are no conclusivedata on fluoroquinolone treatment of UTI in patients with renal failure. Emergence of resistantpathogensduring therapywith fluoroquinolones has beeninfrequentbut might be more frequent in complicated UTI caused by P. aeruginosa