Efficacy of 250 mg Trospectomycin Sulfate IM vs. 250 mg Ceftriaxone IM for Treatment of Uncomplicated Gonorrhea

Rompalo, Anne; Colletta, Lorraine; Caine, Virginia A.; Linnemeier, Paula; Neumann, Theresa; Hook, Edward W.; Jones, Robert B.

doi:10.1097/00007435-199407000-00006

Cited by 6 publications

(2 citation statements)

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“…Activity against Chlamydia species is notable given its close phylogeny to Chlamydia pneumoniae , a respiratory pathogen that commonly causes pneumonia. The dual activity of amSPCs against both N. gonorrhoeae and C. trachomatis is consistent with published data for trospectomycin, a 5'-spectinomycin derivative that is efficacious in humans for treatment of both gonorrhea and chlamydia infections (15, 27, 28). …”

Section: Resultssupporting

confidence: 88%

“…Activity against Chlamydia species is notable, given its close phylogeny to Chlamydia pneumoniae, a respiratory pathogen that commonly causes pneumonia. The dual activity of amSPCs against both N. gonorrhoeae and C. trachomatis is consistent with published data for trospectomycin, a 5′-spectinomycin derivative that is efficacious in humans for treatment of both gonorrhea and chlamydia infections (15,27,28). N-Benzyl aminomethyl spectinomycins have a unique spectrum of activity The spectrum of antibacterial activity of our N-benzyl-substituted amSPCs appeared to differ from that reported for the N-alkyl aminomethyl spectinomycins (19).…”

Section: Common Bacterial Respiratory Pathogens Are Susceptible To Am...supporting

confidence: 83%

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Aminomethyl spectinomycins as therapeutics for drug-resistant respiratory tract and sexually transmitted bacterial infections

et al. 2015

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The antibiotic spectinomycin is a potent inhibitor of bacterial protein synthesis with a unique mechanism of action and an excellent safety index, but it lacks antibacterial activity against most clinically important pathogens. A novel series of N-benzyl substituted 3'-(R)- 3'-aminomethyl-3'-hydroxy spectinomycins was developed based on a computational analysis of the aminomethyl spectinomycin binding site and structure guided synthesis. These compounds had ribosomal inhibition values comparable to spectinomycin but showed increased potency against common respiratory tract pathogens Streptococcus pneumoniae, Haemophilus influenzae, Legionella pneumophila, and Moraxella catarrhalis as well as the sexually transmitted bacteria Neisseria gonorrhoeae and Chlamydia trachomatis. Non-ribosome binding 3'-(S) isomers of the leads demonstrated weak inhibitory activity in in vitro protein translation assays and poor antibacterial activity, indicating that the antibacterial activity of the series remains on target. In addition to improved antibacterial potency, compounds also demonstrated no mammalian cytotoxicity, improved microsomal stability, and favorable pharmacokinetic properties in rats. The lead compound from the series, compound 1, exhibited excellent chemical stability, which was superior to spectinomycin and had no significant interaction with a panel of human receptors and drug metabolism enzymes suggesting low potential for adverse reactions or drug-drug interactions in vivo. Compound 1 was active in vitro against a panel of penicillin, macrolide, and cephalosporin resistant S. pneumoniae clinical isolates and cured mice of fatal pneumococcal pneumonia and sepsis at a dose of 5 mg/kg. Together, these studies indicate N-benzyl aminomethyl spectinomycins possess suitable properties for further development as novel antibacterial agents to treat drug resistant respiratory tract and sexually transmitted bacterial infections.

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Section: Resultssupporting

confidence: 88%