The new england journal of medicine n engl j med 351;2 www.nejm.or decades, syphilis infection has been treated with penicillin , and Treponema pallidum has not developed resistance to penicillin. In many countries, the recommended treatment for early syphilis is a single dose of penicillin G benzathine, which maintains bactericidal levels for weeks, killing the slowly metabolizing treponemes. Azithromycin, which has a long tissue half-life and can be administered orally, was found to be effective in the treatment of syphilis in a rabbit model 1 and in small studies in humans. 2-6 Because of its convenience and efficacy, azithromycin is increasingly being used for the treatment of syphilis by clinicians and in disease-control activities in Canada and the United States, although it is not currently recommended by the Centers for Disease Control and Prevention. 7 We discuss one patient with clinical failure of azithromycin therapy for syphilis, among several cases that have been recognized. 8 We identified a mutation in the 23S ribosomal RNA (rRNA) genes in a specimen of T. pallidum obtained from this patient, and we confirmed functional azithromycin resistance in vivo in a strain of T. pallidum that contain this mutation. Testing of T. pallidum samples obtained at four geographically diverse sites revealed a high frequency of this mutation in clinical specimens. samples Swab samples were collected from primary or moist secondary syphilis lesions in patients at

Diagnosis and treatment of syphilis are challenging because of its variable clinical presentation and course and the lack of definitive tests of cure after treatment. This review of the most recent literature on the epidemiology, clinical manifestations, current diagnosis, and treatment of syphilis is focused toward clinicians who treat patients with this disease. Syphilis coinfection with human immunodeficiency virus is emphasized because it is increasingly common in the United States and affects the initial presentation, disease course, diagnosis, and treatment of syphilis. Of particular consequence is the effect of human immunodeficiency virus on the clinical diagnosis, prevalence, and course of neurosyphilis, one of the most serious consequences of syphilis infection. linicians from large metropolitan areas frequently face the challenge of diagnosing syphilis and treating patients with syphilis. In doing so, they are often faced with questions regarding interpretation of clinical findings and laboratory results and selection of appropriate therapy. Interpretation of the data available to answer these questions is often challenging given the paucity of large well-designed studies and the substantial variability that characterizes the clinical presentation of syphilis. Such a challenge is particularly found in the treatment of patients coinfected with syphilis and human immunodeficiency virus (HIV). To guide clinicians in this difficult task, we discuss the most recent literature on the epidemiology, clinical manifestations, diagnosis, and treatment of syphilis and the corresponding effects of HIV coinfection.

Azithromycin-resistant T. pallidum is widespread in San Francisco. We recommend against using azithromycin for the management of syphilis in communities where macrolide-resistant T. pallidum is present and recommend active surveillance for resistance in sites where azithromycin is used.

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Enzyme immunoassays for the detection of chlamydial antigens are commonly used to diagnose Chlamydia trachomatis infection. As is true for ail nonculture methods, the specificities of these tests are a concern. A confirmatory blocking assay (Abbott Laboratories, North Chicago, Ill.) was evaluated at four sexually transmitted disease test sites. This assay is designed to confirm true-positive Chlamydiazyme (CZ) specimens and to identify false-positive CZ reactions caused by cross-reacting bacteria. Cervical specimens were collected from 2,891 women. Chlamydia prevalence by tissue culture (TC) was 9.2% (266 of 2,891 specimens). Compared with TC, the sensitivity and specificity of CZ were 78.9% (210 of 266 specimens) and 98.2% (2,577 of 2,625 specimens), respectively. There were 48 CZ false-positive reactions. The direct fluorescent-antibody test (DFA) was positive for 31 of 48 false-positive reactions, indicating culture misses. Thus, when the standard was both TC and DFA, CZ sensitivity was 81.1% and CZ specificity was 99.3%. Of the 17 CZ-positive patients who were negative by both TC and DFA, 3 were negative on repeat CZ and Il of 14 were identified as false positive by the confirmatory assay. The confirmatory test was positive for CZ-positive women who were positive by TC or DFA. Use of the confirmatory test, which increased the specificity to 99.9%, would increase confidence in positive CZ results and make the test more useful for screening populations with a low prevalence of C. trachomatis infection.