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Although the authors acknowledged the potential for the emergence of azithromycin-resistant Treponema pallidum, ongoing monitoring for such resistance, as they suggested, requires molecular-sequencing techniques,2 which are unavailable in most developing countries. More important, the inability of azithromycin to cross the placenta3 limits its use in the prevention of congenital disease. Treatment of seropositive mothers with oral azithromycin, after routine antenatal screening, could result in declining maternal titers on the rapid plasma reagin test without affecting the potential for fetal infection.
Since the prevention of congenital syphilis remains a major objective of control programs and is a current focus for global elimination activities,4 we believe that azithromycin has only a limited role in the management of syphilis in resource-constrained settings.
Ronald C. Ballard, Ph.D.
Stuart M. Berman, M.D., Sc.M.
Kevin A. Fenton, M.D., Ph.D., M.F.P.H.
Centers for Disease Control and Prevention
Atlanta, GA 30333
rballard{at}cdc.gov
References
Ricardo F. Savaris, M.D.
Alberto M. Abeche, M.D.
Universidade Federal do Rio Grande do Sul
90035-003 Porto Alegre, Brazil
rsavaris{at}hcpa.ufrgs.br
References
In San Francisco, where an estimated 56 percent of circulating strains of T. pallidum were resistant to azithromycin in 2004,2 we conducted a randomized, controlled trial of azithromycin (1 g given orally as a single dose) as compared with penicillin G benzathine (2.4 million units intramuscularly) in sexual contacts of persons with infectious syphilis; our aim was to compare the efficacy of the two drugs for the treatment of incubating syphilis. A data safety monitoring board (DSMB) supervised the study.
After two treatment failures in the 12 patients receiving azithromycin as compared with none in 13 patients receiving penicillin, the DSMB terminated the study (P=0.18, by Fisher's exact test). Although it was a small study sample (n=25), our data suggest that azithromycin was inferior to penicillin in the presence of high community levels of azithromycin-resistant T. pallidum. Although we have feasible methods to monitor macrolide resistance in T. pallidum, routine surveillance is not currently supported by federal agencies.
Jeffrey D. Klausner, M.D., M.P.H.
Robert P. Kohn, M.P.H.
Charlotte K. Kent, M.P.H.
San Francisco Department of Public Health
San Francisco, CA 94103
jeff.klausner{at}sfdph.org
Dr. Klausner reports having received honoraria from King Pharmaceuticals and a research grant from Pfizer.
References
Resistance is clearly a concern in view of the high proportion of strains of T. pallidum found among men who have sex with men in the United States and Ireland that contain mutations that may confer resistance to macrolides. The clinical significance of this mutation has not been definitively established, although the small study by Klausner et al.2 provides some support for such a link. The results of our trial suggest that azithromycin resistance is not currently a clinically significant problem among heterosexual patients in Tanzania. We recognize that most laboratories in Africa do not have the facilities to identify mutations in local strains of T. pallidum. In view of the considerable advantages that would be conferred by a single-dose oral treatment for syphilis, however, we believe further studies are warranted to study the geographic distribution and clinical significance of strains bearing this mutation.
We do not agree with Savaris and Abeche that azithromycin is too expensive to be used for the treatment of syphilis in developing countries. Generic supplies of the drug, made in India, have been available for some years at a cost of approximately $1.20 for a 2-g dose.3 Azithromycin came off patent in the United States in November 2005. Although penicillin G benzathine is an inexpensive drug, the cost of administering it has to include the cost of the needle and syringe.
Despite the issues raised by the correspondents, we consider that single-dose azithromycin may have a place in the treatment of early syphilis and in the management of genital-ulcer disease at the primary health care level in developing countries.
Gabriele Riedner, M.D., Ph.D.
London School of Hygiene and Tropical Medicine
London WC1E 7HT, United Kingdom
riednerg{at}emro.who.int
Heiner Grosskurth, M.D., Ph.D.
Uganda Virus Research Institute
Entebbe, Uganda
Richard Hayes, D.Sc.
London School of Hygiene and Tropical Medicine
London WC1E 7HT, United Kingdom
References
Fortunately, T. pallidum remains fully susceptible to penicillin G benzathine worldwide, and the forthcoming 2006 Sexually Transmitted Disease Guidelines from the Centers for Disease Control and Prevention will correctly recommend that "penicillin G, administered parenterally, is the preferred drug for treatment of all stages of syphilis" and that the recommended regimen for adults with primary, secondary, or early latent syphilis is "benzathine penicillin G 2.4 million units IM [intramuscular] in a single intramuscular dose."
King K. Holmes, M.D., Ph.D.
University of Washington
Seattle, WA 98195
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