Walter W. Karney

A trial of minocycline given after exposure to prevent gonorrhea.

In a prospective evaluation of antibiotic prophylaxis against gonorrhea, 1080 men were given 200 mg of oral minocycline or placebo after sexual intercourse with prostitutes in a Far Eastern port. Later, at sea, gonococcal infection was detected in 57 of 565 men given placebo and 24 of 515 men given minocycline (P less than 0.001). Minocycline prophylaxis completely prevented infection by gonococci susceptible to 0.75 microgram or less of tetracycline per milliliter, reduced the risk of infection or prolonged the incubation period in men exposed to gonococci susceptible to 1.0 to 2.0 micrograms per milliliter, but did not prevent infection or prolong incubation in men exposed to gonococci resistant to 2.0 micrograms. Minocycline did not increase the proportion of asymptomatic infections. Minocycline prophylaxis would probably have limited effectiveness as a public-health measure because of the tendency to select resistant gonococci.

Evaluation of Cefazolin, a New Cephalosporin Antibiotic

Cefazolin sodium was tested in vitro against 308 isolates of Enterobacteriaceae, Pseudomonas aeruginosa, Neisseria meningitidis, Haemophilus influenzae, Staphylococcus aureus, and enterococcus. Broth and agar dilution and disk diffusion techniques were used with at least two sizes of inocula of organisms. Cefazolin was also studied in the treatment of 85 hospitalized patients with a variety of serious infections. In concentations of 5 μg or less/ml, cefazolin inhibited and killed more than 90% of isolates of Enterobacteriaceae with the exception of indole-positive Proteus and Enterobacter species. No isolate of P. aeruginosa and only a few of Enterobacter and enterococci were killed by 25 μg of cefazolin/ml, a concentration readily attainable in serum with a 500-mg dose given intramuscularly. Penicillin-susceptible as well as penicillin-resistant isolates of S. aureus were killed by 1 μg or less of cefazolin per ml; however, 25 μg/ml was required to kill 100% of the strains when the inoculum size was increased 100-fold. Cefazolin treatment appeared effective in 82 of 85 patients, including four with endocarditis. Pain was minimal after intramuscular injection, and thrombophlebitis was not observed in those treated intravenously. No patient developed a positive Coombs test, and no evidence of renal toxicity was apparent in clinical studies.

Comparison of five aminocyclitol antibiotics in vitro against Enterobacteriaceae and Pseudomonas.

The in vitro susceptibility of 163 strains of Enterobacteriaceae and 23 isolates of Pseudomonas aeruginosa to various concentrations of gentamicin, kanamycin, spectinomycin, tobramycin, and BB-K8, a new semisynthetic aminoglycoside antibiotic, was determined. Studies were performed in Mueller-Hinton agar and broth, and two different sizes of bacterial inocula were used. On a weight basis, gentamicin and tobramycin demonstrated comparable activity in vitro and were the most active of the five drugs tested against Escherichia coli, Klebsiella, Enterobacter, and Proteus species. All of these organisms were inhibited by gentamicin or tobramycin at concentrations of 5.0 μg or less/ml in agar with both inocula of bacterial cells. In addition, tobramycin was the most active drug against isolates of P. aeruginosa and gentamicin was the most active against Salmonella and Shigella species. Although kanamycin and BB-K8 demonstrated a high degree of activity against most Enterobacteriaceae, they were not the most active agents tested for any genus. Spectinomycin was the least active compound, and many isolates grew in concentrations higher than those readily attainable in serum.

Comparative Therapeutic and Pharmacological Evaluation of Amoxicillin and Ampicillin Plus Probenecid for the Treatment of Gonorrhea

Single doses of 3.5 g of ampicillin with 1.0 g of probenecid or of 3.0 g of amoxicillin alone were administered orally to 58 males and 56 females with uncomplicated gonococcal infection. The failure rate for genital or anal infection, or both, was 1.7% for ampicillin plus probenecid and 4.2% for amoxicillin alone. However, patients with oropharyngeal infection responded poorly. Seventy-five isolates of Neisseria gonorrhoeae recovered from patients in this study were all inhibited by 1.0 μg or less of ampicillin or amoxicillin per ml; penicillin G, ampicillin, and amoxicillin had similar activity in vitro against these isolates. Serum concentrations of amoxicillin in 10 volunteers remained above the minimal inhibitory concentration for most strains of N. gonorrhoeae for periods up to 10 h after a 3.0-g oral dose. After 2.0 g of ampicillin was given with probenecid, the serum levels during the 5- to 12-h period approached those achieved with 3.5 g of ampicillin plus probenecid, and actually exceeded levels attained during the same interval with 3.0 g of amoxicillin administered alone.