Failure of Penicillin G Benzathine in the Treatment of Neurosyphilis

189

138

Syphilis is a multistage infectious disease that is usually transmitted through contact with active lesions of a sexual partner or from an infected pregnant woman to her fetus. Despite elimination efforts, syphilis remains endemic in many developing countries and has reemerged in several developed countries, including China, where a widespread epidemic recently occurred. In the absence of a vaccine, syphilis control is largely dependent upon identification of infected individuals and treatment of these individuals and their contacts with antibiotics. Although penicillin is still effective, clinically significant resistance to macrolides, a second-line alternative to penicillin, has emerged. Macrolide-resistant strains of Treponema pallidum are now prevalent in several developed countries. An understanding of the genetic basis of T. pallidum antibiotic resistance is essential to enable molecular surveillance. This review discusses the genetic basis of T. pallidum macrolide resistance and the potential of this spirochete to develop additional antibiotic resistance that could seriously compromise syphilis treatment and control.Spirochetes are motile, spiral-shaped bacteria that are divided into the families Spirochaetaceae, Brachyspiraceae, and Leptospiraceae (54). Treponema species, which are members of the family Spirochaetaceae, are fastidious anaerobic or microaerophilic host-associated spirochetes. While the majority of Treponema species are found in the flora of humans and animals, a few species are pathogenic for humans. Treponema pallidum subspp. pallidum, endemicum, and pertenue,

Section: Potential Mechanisms For Development Of Resistance To Tetracmentioning

confidence: 99%

Global Challenge of Antibiotic-Resistant Treponema pallidum

Stamm

2010

189

138

“…There are currently no accepted regimens for the use of oral penicillin in the treatment of latent or neurosyphilis (7). The various parenteral regimens advocated are time-consuming and uncomfortable for patients and, in certain cases, have been associated with treatment failure or have produced undetectable levels of penicillin in cerebrospinal fluid (CSF) (4,6,12). This study was designed to examine the penetration of oral doxycycline into the CSF of patients with latent or neurosyphilis.…”

mentioning

confidence: 99%

Penetration of oral doxycycline into the cerebrospinal fluid of patients with latent or neurosyphilis

Yim¹,

Flynn²,

Fitzgerald³

1985

119

Five patients with laboratory evidence of latent or neurosyphilis were treated orally with doxycycline (200 mg) twice a day for 21 days. After the seventh dose, the mean level of doxycycline in serum was 5.8 ,ug/ml, with a mean drug level in cerebrospinal fluid of 1.3 ,Lg/ml. The mean penetration into cerebrospinal fluid was 26%. These preliminary findings suggest that doxycycline, administered orally at a dose of 200 mg twice a day, reaches a sufficient concentration in cerebrospinal fluid to be worthy of further evaluation as an alternative regimen to penicillin therapy for latent or neurosyphilis.

“…The ability of clarithromycin to significantly reduce treponemal burden in lymph tissue was not inhibited by a suboptimal (8)(9)(10)(11)(12)(13)(14) 0.0 ± 0.0C 10.0 mg BID (8)(9)(10)(11)(12)(13)(14) 0.0 ± 0.0C (8)(9)(10)(11)(12)(13)(14) 0.0 ± 0.0C Clarithromycin 10 mg BID (8)(9)(10)(11)(12)(13)(14) penicillin dosage regimen of a single 250-U/kg dose (Table 3). Suboptimal doses of clarithromycin and penicillin did not appear to be antagonistic or synergistic in vivo.…”

Section: Clarithromycin Therapy Of T Pallidum Infections 865mentioning

confidence: 99%

“…There have been treatment failures with penicillin in human immunodeficiency virus-positive and AIDS patients (3,5,11,14,20,21), and some individuals have rapidly progressed to neurosyphilis despite normally adequate therapy (15,23). For penicillin-allergic patients, the choice of alternative therapy is limited to doxycycline or tetracycline, with erythromycin, ceftriaxone, or penicillin desensitization as alternatives in tetracycline-intolerant individuals (6).…”

mentioning

confidence: 99%

Clarithromycin therapy of experimental Treponema pallidum infections in hamsters

Alder

Jarvis

Mitten

et al. 1993

Clarithromycin was shown to be effective therapy for Treponena paUlidum infections in hamsters. Clarithromycin therapy was effective when initiated either 1 or 8 days after infection. The delay in initiation of therapy allowed an active infection to develop. The treponemal burden in lymph tissue of treated hamsters was eradicated, as determined by dark-field microscopy and by inoculation of lymph material into susceptible hamsters. Treatments with clarithromycin and the 14-hydroxy metabolite of clarithromycin were equally effective. Therapy with clarithromycin and penicillin was not antagonistic and did not appear to be synergistic when the two drugs were given concurrently. Pharmacokinetic evaluation of clarithromycin in hamsters showed that the doses which produced effective therapy yielded concentrations in serum similar to those routinely achieved in human sera. These findings demonstrate that clarithromycin is effective in treating active or incubating syphilis in the hamster model and could be useful in treating humans.