The effect of gentamicin against 130 clinical isolates of Pseudomonas aeruginosa was compared with that of two investigational aminoglycoside antibiotics, tobramycin and amikacin. Minimal inhibitory concentration data indicated that, on a weight basis, tobramycin was two to four times as active as gentamicin against most isolates. However, 14 of 18 organisms highly resistant to gentamicin (≥80 μg/ml) were also highly resistant to tobramycin. Amikacin was the least active aminoglycoside on a weight basis, but none of the isolates were highly resistant to this antibiotic. When therapeutically achievable concentrations were used, adding carbenicillin to gentamicin or to tobramycin enhanced inhibitory activity against those isolates susceptible (≤5 μg/ml) or moderately resistant (10 to 40 μg/ml) to the aminoglycoside. Such synergy was seldom demonstrated for isolates highly resistant to gentamicin or tobramycin. The combination of carbenicillin and amikacin enhanced inhibition against all but two of the isolates. Both tobramycin and amikacin offer in vitro advantages over gentamicin against P. aeruginosa .

Alum-precipitated and soluble, purified M protein vaccines were prepared from type 3 and type 12 group A Streptococcus. Adult volunteers were assigned to one of three groups: group I received placebo by both parenteral and intranasal routes; group 2 received vaccine parenterally (either type 3 or type 12) and placebo intranasally; and group 3 received placebo parenterally and vaccine intranasally (either type 3 or type 12). Subjects were inoculated three times at montly intervals. Thirty to 50 days after the last dose, all subjects were challenged with homologous streptococci applied to the oropharynx. Six subjects (30%) vaccinated subcutaneously had definite illness, three (15%) had probable illness, and 11 (55%) had no illness. In the group vaccinated intranasally, four (14%) had definite illness, two (7%) had probable illness, and 22 (79%) had no illness. Fifteen controls (42%) had definite illness, and 21 (58%) had no illness. The rate of colonization was significantly lower in recipients of intranasal vaccine. Average clinical scores and vaccine side effects were also decreased in subjects vaccinated intranasally. Induced serum antibody as measured by passive hemagglutination was not a reliable predictor of resistance to streptococcal pharyngitis. Penicillin was administered to all subjects five days after challenge. No sequelae of streptococcal infection or other complications occurred. Thus, local immunization with M protein apparently may reduce both colonization and clinical illness after challenge with homologous streptococci.

Treatment with either pentamidine isethionate or trimethoprim-sulfamethoxazole significantly reduces the mortality of Pneumocystis carinii pneumonia. It is not known whether a combination might act in an additive, synergistic, or antagonistic manner. We studied the interaction of these two agents in the steroid-conditioned rat model of pneumocystosis. Of animals receiving pentamidine alone, 48% died and 45% had P. carinii cysts at autopsy. Trimethoprimsulfamethoxazole alone resulted in 21% mortality, and cysts were found in 28%. Both agents in full doses resulted in 45% deaths and cysts in 37%. Animals treated with half-dosages of pentamidine plus trimethroprim-sulfamethoxazole had mortality of 35%, and 21% had cysts. Trimethoprim alone, in two dosages, was ineffective in eradicating P. carinii cysts. The data suggest that combination therapy is no more effective than trimethoprim-sulfamethoxazole alone in the treatment of P. carinii pneumonia.

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