The bactericidal activity and postantibiotic effect of trospectomycin

Yagi, Betty H.; Schaadt, Ronda D.; Zurenko, Gary E.

doi:10.1016/0732-8893(92)90083-6

Cited by 8 publications

(8 citation statements)

References 8 publications

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“…The AmSPCs exhibited good antibacterial activity (MICs from 1.6 to 6.3 g/ml; Table 1) as well as bactericidal activity against N. gonorrhoeae in the broth dilution assay (MBC values from 1ϫ to 2ϫ the MIC value; Table 2). Unlike the AGs, such as GEN, SPC was previously designated a bacteriostatic antibiotic (34) and later specified as having a bactericidal mechanism against certain bacterial species, including N. gonorrhoeae (35,36). Thus, the AmSPCs behave similarly to AGs, such as GEN and SPC, against N. gonorrhoeae.…”

Section: Discussionmentioning

confidence: 99%

Aminomethyl Spectinomycins as Therapeutics for Drug-Resistant Gonorrhea and Chlamydia Coinfections

Butler

Waidyarachchi

Connolly

et al. 2018

Antimicrob Agents Chemother

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Bacterial sexually transmitted infections are widespread and common, with (gonorrhea) and (chlamydia) being the two most frequent causes. If left untreated, both infections can cause pelvic inflammatory disease, infertility, ectopic pregnancy, and other sequelae. The recommended treatment for gonorrhea is ceftriaxone plus azithromycin (to empirically treat chlamydial coinfections). Antibiotic resistance to all existing therapies has developed in gonorrheal infections. The need for new antibiotics is great, but the pipeline for new drugs is alarmingly small. The aminomethyl spectinomycins, a new class of semisynthetic analogs of the antibiotic spectinomycin, were developed on the basis of a computational analysis of the spectinomycin binding site of the bacterial 30S ribosome and structure-guided synthesis. The compounds display particular potency against common respiratory tract pathogens as well as the sexually transmitted pathogens that cause gonorrhea and chlamydia. Here, we demonstrate the potencies of several compounds of this class against both bacterial species; the compounds displayed increased potencies against compared to that of spectinomycin and, significantly, demonstrated activity against that is not observed with spectinomycin. Efficacies of the compounds were compared to those of spectinomycin and gentamicin in a murine model of infection caused by ceftriaxone/azithromycin-resistant; the aminomethyl spectinomycins significantly reduced the colonization load and were as potent as the comparator compounds. In summary, data produced by this study support aminomethyl spectinomycins as a promising replacement for spectinomycin and antibiotics such as ceftriaxone for treating drug-resistant gonorrhea, with the added benefit of treating chlamydial coinfections.

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Section: Discussionmentioning

confidence: 99%

Aminomethyl Spectinomycins as Therapeutics for Drug-Resistant Gonorrhea and Chlamydia Coinfections

Butler

Waidyarachchi

Connolly

et al. 2018

Antimicrob Agents Chemother

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“…Whether these properties are likewise unique with regard to B. fragilis needs further study. Long PAEs of 5–7 h have similarly been demonstrated for trospectomycin against B. fragilis [11].…”

Section: Discussionmentioning

confidence: 99%

Postantibiotic effects with Bacteroides fragilis determined by viable counts and CO2 generation

Valdimarsdóttir

Erlendsdóttir

Guðmundsson

1997

Clinical Microbiology and Infection

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OBJECTIVE: To study the postantibiotic effect (PAE) for Bacteroides fragilis after exposure to common anaerobic antimicrobials with two different methods, by viable counting and by measuring CO2 generation in a BACTEC(R) blood culture system. METHODS: Four strains of B. fragilis were exposed for 1, 2 and 4 h to cefoxitin, chloramphenicol, clindamycin, imipenem or metronidazole at concentrations from 1 to 16 x MIC. The drugs were removed by dilution into BACTEC 7A(R) vials and growth determined with viability counts and CO2 production. RESULTS: The durations of the PAEs determined by the two methods correlated well (r=0.913, p<0.005). PAEs of up to 4-5 h were induced by imipenem and metronidazole with achievable concentrations and exposure durations. Chloramphenicol induced short or no PAEs, but cefoxitin and clindamycin induced PAEs up to 2 h with high AUC values. The imipenem PAEs and the short cefoxitin and clindamycin PAEs were dependent on AUC. CONCLUSIONS: Significant PAEs against B. fragilis were induced by imipenem and metronidazole. Determining PAE by measuring CO2 production is an accurate and less time-consuming alternative to the conventional method of viable counts.

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“…Trospectomycin is a 6Ј propyl analog of spectinomycin with unique pharmacokinetics and broad spectrum of activity. It is highly effective against anaerobes, gram-positive and gram-negative aerobes, [6][7][8] penicillin-sensitive and -resistant N. gonorrhoeae, 11 and C. trachomatis. 6,12 A single 250 mg intramuscular injection of trospectomycin has been shown to be as effective as a single dose of ceftriaxone in the treatment of uncomplicated gonococcal infection.…”

Section: Discussionmentioning

confidence: 99%

“…5 Trospectomycin sulfate is a novel broadspectrum aminocyclitol antibiotic with activity against a majority of aerobes, anaerobes, N. gonorrhoeae, and C. trachomatis. [6][7][8] This study was undertaken to evaluate the safety and clinical efficacy of trospectomycin as a single-agent therapy in the treatment of acute PID. Monotherapy has many advantages.…”

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confidence: 99%

Trospectomycin in acute pelvic inflammatory disease: a preliminary report

Chatwani

Dandalou

Harmanli

et al. 1997

Infect. Dis. Obstet. Gynecol.

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Objective: The purpose of this study was to compare the clinical efficacy and safety of intravenous trospectomycin to that of cefoxitin plus doxycycline in the treatment of women hospitalized with acute pelvic inflammatory disease (PID).Methods: Thirty-nine patients admitted with a clinical diagnosis of an acute PID were enrolled in this prospective, single-blind study. Patients were treated with either intravenous trospectomycin, 500 mg every 8 h, or intravenous cefoxitin, 2 g every 6 h, plus oral or intravenous doxycycline, 100 mg every 12 h, in a 2:1 ratio. The patients were followed for clinical response and side effects. Both groups of patients were discharged on oral doxycycline for 10 days. Appropriate cultures were obtained before starting inpatient treatment, on completion of inpatient treatment, and at 2 followup visits.Results: The overall success rate for trospectomycin was 95.6% and for cefoxitin/doxycycline was 91.6%. This difference was not statistically significant (P = 0.63). Trospectomycin was found to be effective against Chlamydia trachomatis.Conclusions: Single-agent therapy with trospectomycin may be as effective as cefoxitin plus doxycycline in the treatment of women hospitalized with acute PID.

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The bactericidal activity and postantibiotic effect of trospectomycin

Cited by 8 publications

References 8 publications

Aminomethyl Spectinomycins as Therapeutics for Drug-Resistant Gonorrhea and Chlamydia Coinfections

Aminomethyl Spectinomycins as Therapeutics for Drug-Resistant Gonorrhea and Chlamydia Coinfections

Postantibiotic effects with Bacteroides fragilis determined by viable counts and CO2 generation

Trospectomycin in acute pelvic inflammatory disease: a preliminary report

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