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Biomedical subjects

M J Snyder

Publications and source records attributed to M J Snyder.

At least 55 records · Page 3Linked to original sources

Pirbenicillin: comparison with carbenicillin and BL-P1654, alone and with gentamicin, against Pseudomonas aeruginosa.

Minimum inhibitory concentrations (MIC) of pirbenicillin against 135 clinical isolates of Pseudomonas aeruginosa were one-fourth of those required for carbenicillin but two times higher than those for BL-P1654. Increasing the inoculum size produced an adverse effect on the bactericidal activity for all three antibiotics. This was more apparent for pirbenicillin than for carbenicillin, but less than the effect on BL-P1654. When concentrations of antibiotics likely to be achieved clinically were used, gentamicin increased the inhibitory and bactericidal effects of all three semisynthetic penicillins for the majority of isolates. Strains highly resistant to the aminoglycoside antibiotic, however, were inhibited no more by the penicillin-gentamicin combinations than by the most effective of the antibiotics alone.

Carbenicillin↗

Diarrhea caused by Escherichia coli that produce only heat-stable enterotoxin.

To determine the role of Escherichia coli heat-stable enterotoxin (ST) as a virulence factor in human diarrhea, a strain that elaborates only ST (E. coli 214-4) was fed to free-living volunteers in doses of 10(6), 10(8), and 10(10) organisms. Short-lived (1 day) mild illness consisting of abdominal cramps with vomiting or diarrhea occurred in three of five individuals fed 10(8). Typical travelers' diarrhea (loose stools, abdominal cramps, and low-grade fever for 2 to 3 days) was seen in four of five volunteers given 10(10); two had brief cholera-like purging of rice-water stools. Despite fever, there was no evidence of mucosal invasion. E. coli 214-4 became the predominant coliform in stools; coproculture isolates were uniformly negative for heat-labile enterotoxin (LT), whereas most produced ST. Ten of 13 individuals developed rises in antibody to somatic E. coli antigen, and none had rises in LT antitoxin. E. coli that elaborate only ST can cause diarrheal disease in adults.

Adolescent↗

Comparative efficacy of chloramphenicol, ampicillin, and co-trimoxazole in the treatment of typhoid fever.

Two clinical trials were conducted to compare the efficacy of 3 antimicrobial agents often recommended for the treatment of typhoid fever. Chloramphenicol was more effective than parenteral ampicillin or oral co-trimoxazole (trimethaprim/sulphamethoxazole) in reducing the duration of fever. Oral chloramphenicol was more effective than parenteral chloramphenicol probably because oral doses resulted in higher blood concentrations of the drug. However, parenteral chloramphenicol was given during the initial period of acute illness, without loss of efficacy.

Administration, Oral↗

Attenuated, streptomycin-dependent Salmonella typhi oral vaccine: potential deleterious effects of lyophilization.

Four studies were done with streptomycin-dependent Salmonella typhi as an oral, attenuated vaccine. Studies 1 and 3 employed freshly harvested vaccine, whereas studies 2 and 4 involved lyophilized vaccine. Five to eight doses (3 x 10(10)-10(11) organisms/dose) were given; oral streptomycin (1.0 g) was administered concomitantly in studies 2 and 3, with only two of the doses of vaccine in study 1, and was not given in study 4. No adverse reactions were encountered in 179 vaccinated men, and 94% of the men excreted the vaccine. In challenge studies (which included the control groups) with 10(5) virulent S. typhi organisms (Quailes strain), the fresh vaccine was highly protective (66%-78% efficacy), while lyophilized vaccine gave no clinical protection. Fresh vaccine also interfered significantly with intestinal proliferation of virulent S. typhi; only 17% of the vaccinees excreted organisms as compared with 75% of the controls. Studies of protection in mice showed no difference between immunogen content of the fresh and the lyophilized vaccines. Field trials with streptomycin-dependent, oral typhoid vaccine must await development of a lyophilized product that will retain the protective properties of the vaccine.

Administration, Oral↗

Efficacy of a live oral typhoid vaccine in human volunteers.

A live oral attenuated vaccine, lacking the enzyme epimerase, has been given with complete safety to 173 men. Two preparations of the vaccine, one with and one without galactose in the initial culture media, led to somewhat differing results. Vaccine A, prepared with galactose, was more readily identified in the stool specimens of its recipients and was more likely to provoke an O antibody response than was vaccine B. Furthermore, the clinical protection from typhoid fever was significant in the vaccine A group, whereas not so with the vaccine B counterpart. The protection afforded by vaccine A exceeds that of any of our previous candidate strains. It is perhaps not presumptuous to imagine that such a vaccine would be equally effective in an area endemic for typhoid fever, where the vaccine might act as a booster effect in a previously exposed population. Remaining questions to be answered include the duration of the protection, and the efficacy of a lyophilized preparation.

Administration, Oral↗

Comparison of trimethoprim-sulfamethoxazole and amoxicillin in therapy of chloramphenicol-resistant and chloramphenicol-sensitive typhoid fever.

The efficacy of orally administered trimethoprim-sulfamethoxazole was compared with that of oral amoxicillin in therapy of typhoid fever due to both epidemic chloramphenicol-resistant and endemic chloramphenicol-sensitive Salmonella typhi. Both drug regimens were effective and of comparable value in treatment of chloramphenicol-resistant infections, as measured by duration of fever (124 hr and 115 hr, respectively) and duration of bacteremia (1.0 and 0.4 days, respectively). Trimethoprim-sulfamethoxazole therapy of infections due to chloramphenicol-sensitive S. typhi resulted in more rapid lysis of fever than did amoxicillin therapy. Trimethoprim and sulfamethoxazole were not synergistic in vitro against the chloramphenicol-resistant strain of S. typhi, and the role of sulfamethoxazole in treatment of such infections appears to be minimal. Oral administration of trimethoprim-sulfamethoxazole is effective therapy of chloramphenicol-resistant, and probably of ampicillin-amoxicillin-resistant, typhoid fever.

Adolescent↗

Studies of immunity in typhoid fever. Protection induced by killed oral antigens or by primary infection.

Adult male volunteers were orally vaccinated with two "killed" antityphoid preparations. The recommended doses of both vaccines resulted in serum antibody development in only a few of the subjects. When the dose of the monovalent preparation (Taboral) was doubled, serological responses occurred more frequently, with a rise in O agglutinins in nearly one-fifth of the subjects, in H agglutinins in approximately one-fourth, and in Vi antibodies in nearly half.When vaccinated volunteers were fed virulent typhoid organisms, disease occurred less frequently among those men vaccinated with Taboral at twice the recommended dose (38%) than among those not vaccinated (54%). This preparation did not confer protection at the recommended dose.Volunteers who had previously recovered from an induced typhoid infection received a further challenge with virulent organisms. These persons developed typhoid fever less frequently (23%) than individuals without prior typhoid exposure (30%).

Administration, Oral↗