Antimicrobial susceptibility of Treponema pallidum subspecies pallidum : an in-vitro study
Tantalo, Lauren C (Department of Medicine, University of Washington)
Lieberman, Nicole A P (Department of Laboratory Medicine and Pathology, University of Washington)
Pérez-Mañá, Clara (Universitat Autònoma de Barcelona. Departament de Farmacologia, de Terapèutica i de Toxicologia)
Suñer, Clara (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Vall Mayans, Marti (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Ubals, Maria (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
González-Beiras, Camila (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Rodríguez-Gascón, Alicia (Universidad del País Vasco)
Canut-Blasco, Andrés (Hospital Universitario Araba (Osakidetza, País Basc))
González-Candelas, Fernando (Universitat de València)
Mueller, John (Innoviva Specialty Therapeutics (Waltham, Estats Units d'Amèrica))
Tapia, Kenneth (Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington)
Greninger, Alexander L (University of Washington)
Giacani, Lorenzo (University of Washington. Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington)
Mitjà, Oriol (University of Papua New Guinea)
Universitat Autònoma de Barcelona

Data:	2023
Resum:	The increasing incidence of syphilis and the limitations of first-line treatment with penicillin, particularly in neurosyphilis, neonatal syphilis, and pregnancy, highlight the need to expand the therapeutic repertoire for effective management of this disease. We assessed the in-vitro efficacy of 18 antibiotics from several classes on Treponema pallidum subspecies pallidum (T pallidum), the syphilis bacteria. Using the in-vitro culture system for T pallidum, we exposed the pathogen to a concentration range of each tested antibiotic. After a 7-day incubation, the treponemal burden was evaluated by quantitative PCR targeting the T pallidum tp0574 gene. The primary outcome was the minimum inhibitory concentration (MIC) at which the quantitative PCR values were not significantly higher than the inoculum wells. We also investigated the susceptibility of macrolide-resistant strains to high concentrations of azithromycin, and the possibility of developing resistance to linezolid, a proposed candidate for syphilis treatment. Amoxicillin, ceftriaxone, several oral cephalosporins, tedizolid, and dalbavancin exhibited anti-treponemal activity at concentrations achievable in human plasma following regular dosing regimens. The experiments revealed a MIC for amoxicillin at 0·02 mg/L, ceftriaxone at 0·0025 mg/L, cephalexin at 0·25 mg/L, cefetamet and cefixime at 0·0313 mg/L, cefuroxime at 0·0156 mg/L, tedizolid at 0·0625 mg/L, spectinomycin at 0·1 mg/L, and dalbavancin at 0·125 mg/L. The MIC for zoliflodacin and balofloxacin was 2 mg/L. Ertapenem, isoniazid, pyrazinamide, and metronidazole had either a poor or no effect. Azithromycin concentrations up to 2 mg/L (64 times the MIC) were ineffective against strains carrying mutations associated to macrolide resistance. Exposure to subtherapeutic doses of linezolid for 10 weeks did not induce phenotypic or genotypic resistance. Cephalosporins and oxazolidinones are potential candidates for expanding the current therapeutic repertoire for syphilis. Our findings warrant testing efficacy in animal models and, if successful, clinical assessment of efficacy. European Research Council.
Ajuts:	European Commission 850450
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	The Lancet microbe, Vol. 4 (december 2023) , p. e994-e1004, ISSN 2666-5247

DOI: 10.1016/S2666-5247(23)00219-7
PMID: 37827185

11 p, 1.0 MB

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