Azithromycin Treatment Failures in Syphilis Infections
JWissmille
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Brief Report: Azithromycin Treatment Failures in Syphilis Infections - San
Francisco, California, 2002-2003
MMWR 53(9):197-198, 2004. © 2004 Centers for Disease Control and Prevention
(CDC)
Posted 03/29/2004
The San Francisco Department of Public Health (SFDPH) is investigating several
clinical failures in syphilis patients treated with the macrolide antibiotic
azithromycin. This report describes the use of azithromycin for syphilis
treatment, recent treatment failures in San Francisco, and CDC recommendations
for syphilis treatment. Clinicians should exercise caution in using
azithromycin for treating incubating syphilis or syphilis infection until the
risk and mechanism of failure are better understood.
Syphilis has been increasing in the United States since 2000 and is of
particular concern in San Francisco, which, in 2002, had one of the highest
rates of primary and secondary syphilis in the United States. To facilitate
treatment of early syphilis patients and their sexual contacts, certain
disease-control programs have administered azithromycin as a single oral
regimen. Several small studies have documented the efficacy of a single oral
dose of azithromycin in the treatment of incubating and early syphilis
infection in patients who were not infected with the human immunodeficiency
virus (HIV).[1] In addition, the oral dose is more convenient to administer
than intramuscular benzathine penicillin, CDC's recommended treatment for
sexually transmitted diseases.[2]
In April 2003, SFDPH became aware of an azithromycin failure in the treatment
of primary syphilis in one patient and subsequently collected case information
on this and seven other apparent treatment failures occurring during September
2002-July 2003. The median patient age was 34 years (range: 23-39 years); seven
patients were non-Hispanic whites, and one was Asian-American; all were male
and self-reported as homosexual. Five patients were positive for HIV, and the
median number of sex partners during the 90 days preceding diagnosis was three
(range: two to 100 partners; one nonrespondent among the eight patients who
provided such information).
Treatment failure was well documented in three patients with ulcers (two penile
and one oral). After treatment of each patient with 2 grams of azithromycin,
one penile ulcer was still positive by dark-field microscopy after 5 days, one
penile ulcer persisted and was dark-field positive during the next 5 weeks, and
the oral ulcer worsened during the next 18 days. Five other patients who were
asymptomatic, seronegative contacts to early syphilis patients received 1 gram
of azithromycin but seroconverted subsequently or had early syphilis. One
patient returned to the clinic 11 days after treatment with a penile ulcer.
Four patients either returned with symptoms (i.e., rash in two cases and penile
ulcer in one) or seroconverted (rapid plasma reagin: 1:128) 6-12 weeks after
treatment. Investigation by SFDPH indicated that two patients had direct sexual
contact with each other, but no other common partners were found. All patients
were treated subsequently with penicillin or doxycycline and responded
clinically and serologically.
SFDPH continues to conduct surveillance for azithromycin treatment failure.
Because resistance to the macrolide antibiotic erythromycin has been reported
in Treponema pallidum,[3] investigators at the University of Washington are
collaborating with SFDPH and other sites to identify the molecular mechanism
that confers azithromycin resistance. The likelihood of azithromycin treatment
failure in treating syphilis is unknown. CDC recommends penicillin as the
preferred therapy for syphilis. However, a 2-gram dose of azithromycin may be
considered for penicillin-allergic patients, but only with close follow-up
because treatment efficacy is not well documented and has not been studied in
persons with HIV infection.[2]
Reported by: JD Klausner, MD, J Engelman, MD, STD Prevention and Control Svcs,
San Francisco Dept of Public Health, San Francisco, California. SA Lukehart,
PhD, Univ of Washington, Seattle, Washington. SM Berman, MD, Div of STD
Prevention, National Center for HIV, STD, and TB Prevention; SJ Mitchell, MD,
EIS Officer, CDC.
References
Hook EW III, Martin DH, Stephens J, Smith BS, Smith K. A randomized,
comparative pilot study of azithromycin versus benzathine penicillin G for
treatment of early syphilis. Sex Transm Dis 2002;29:486-90.
CDC. Sexually transmitted diseases treatment guidelines 2002. MMWR 2002;51(No.
RR-6).
Stapleton JT, Stamm LV, Bassford PJ. Potential for development of antibiotic
resistance in pathogenic treponemes. Rev Infect Dis 1985;7(suppl 2):S314-S317.
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