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Effects of cefetamet (Ro 15-8074) on Treponema pallidum and experimental syphilis
1Department of Medical Microbiology and Immunology, School of Medicine, University of Minnesota, Duluth 55812.
Abstract:
Cefetamet pivoxil (Ro 15-8075) is a newly developed, expanded-spectrum cephalosporin that is orally active. In vitro, the active form, cefetamet (Ro 15-8074), at a concentration of 0.05 micrograms/ml killed and lysed Treponema pallidum. Rabbit serum did not diminish its effectiveness. The antibiotic rapidly entered the circulation following intramuscular injection into rabbits, attaining its highest levels of 24 to 37 micrograms/ml within 10 to 30 min. Animals were infected intradermally with T. pallidum and then treated with different doses of cefetamet. Accelerated healing was detected following treatment with 15 and 30 mg/kg of body weight. The antibiotic was also effective in killing organisms that had disseminated to distant tissues. In three separate sets of experiments, rabbits were infected with treponemes and then treated with cefetamet intramuscularly at 1, 15, or 30 mg/kg as follows: (i) after lesions had just become clinically apparent, (ii) after lesions were enlarged and well developed, or (iii) prior to the appearance of clinical lesions. Antibiotic effectiveness was determined by sacrificing the animals 1 week after antibiotic treatment and examining splenic tissue for residual, disseminated treponemes. Cefetamet was treponemicidal in all three situations. Maximum effects occurred when the antibiotic was injected before lesions had become clinically apparent (incubation period). These results suggest that cefetamet pivoxil might be useful for treating syphilitic infections.
Insights
Cefetamet pivoxil demonstrates potent activity against Treponema pallidum, effectively clearing infections in rabbits. This expanded-spectrum cephalosporin shows promise as a treatment for syphilis.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Syphilis remains a significant global health concern.
- Novel therapeutic agents are needed to combat Treponema pallidum infections.
Purpose of the Study:
- To evaluate the efficacy of cefetamet pivoxil, an orally active expanded-spectrum cephalosporin, against Treponema pallidum.
Main Methods:
- In vitro susceptibility testing of cefetamet against T. pallidum.
- Pharmacokinetic analysis of cefetamet in rabbits following intramuscular administration.
- In vivo efficacy studies in rabbits infected with T. pallidum and treated with varying doses of cefetamet.
Main Results:
- Cefetamet (active form) demonstrated potent in vitro bactericidal and lytic activity against T. pallidum.
- Rapid absorption and high serum concentrations of cefetamet were observed in rabbits post-injection.
- Cefetamet treatment accelerated lesion healing and eradicated disseminated T. pallidum in rabbits, with maximum efficacy when administered during the incubation period.
Conclusions:
- Cefetamet pivoxil exhibits significant treponemicidal activity in vitro and in vivo.
- The drug is well-absorbed and effective in treating experimental syphilis in rabbits.
- Cefetamet pivoxil represents a potential therapeutic option for human syphilis infections.