zithromax and Syphilis

Syphilis is a very serious infection that causes acute cutaneous manifestations. Penicillin is the gold standard for treating syphilis. This meta-analysis was conducted based on self-published randomized controlled trials (RCTs) data to compare the efficacy of azithromycin with penicillin for treating syphilis. RCTs on azithromycin vs penicillin for the treatment of syphilis were retrieved from the Cochrane Library, MEDLINE, EBSCO, Embase, Ovid, and other databases, and the estimated risk ratio (RR) and 95% confidence interval (CI) were used to study the following outcome indicators: 3-month response rate, 6-month response rate, 12-month response rate, recurrence rate, serum fixation rate, and failure rate. This meta-analysis included seven RCTs involving 639 subjects (of whom 335 were treated with azithromycin and 304 were treated with penicillin). There was no significant difference in the 3-month response rate (RR = 0.97, 95% CI: 0.79-1.19), 6-month response rate (RR = 1.01, 95% CI: 0.85-1.20), 12-month response rate (RR = 1.02, 95% CI: 0.97-1.09), serum fixation rate (RR = 0.71, 95% CI: 0.24-2.12), and failure rate (RR = 0.62, 95% CI: 0.33-1.16). In summary, there is no evidence in the literature that azithromycin is less effective than penicillin for treating syphilis.

Topics: Anti-Bacterial Agents; Azithromycin; Humans; Penicillin G Benzathine; Randomized Controlled Trials as Topic; Syphilis

Syphilis is a chronic, multi-stage infectious disease that is usually transmitted sexually by contact with an active lesion of a partner or congenitally from an infected pregnant woman to her fetus. Although syphilis is still endemic in many developing countries, it has re-emerged in several developed countries. The resurgence of syphilis is a major concern to global public health, particularly since the lesions of early syphilis increase the risk of acquisition and transmission of infection with human immunodeficiency virus (HIV). Because there is no vaccine to prevent syphilis, control is mainly dependent on the identification and treatment of infected individuals and their contacts with penicillin G, the first-line drug for all stages of syphilis. The emergence of clinically significant azithromycin resistance in Treponema pallidum subsp. pallidum, the syphilis agent, has resulted in treatment failures, thus precluding the routine use of this second-line drug. Information is presented here on the diagnosis and recommended antibiotic treatment of syphilis and the challenge of macrolide-resistant T. pallidum.

Topics: Anti-Bacterial Agents; Azithromycin; Coinfection; Drug Resistance, Bacterial; Female; HIV Infections; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Male; Penicillin G; Pregnancy; Pregnancy Complications, Infectious; Syphilis; Syphilis, Congenital; Treponema pallidum

Syphilis is a complex systemic disease caused by a spirochete, Treponema pallidum. The World Health Organization estimates that at least 12 million people worldwide are currently infected with syphilis. In this review we compared two current standards of treatment for early syphilis, benzathine benzylpenicillin (penicillin G) and azithromycin.. To evaluate the efficacy and safety of azithromycin versus benzathine penicillin (penicillin G) for early syphilis.. We searched the following databases using the search terms detailed in Appendix 1: the Cochrane Sexually Transmitted Diseases Group Specialized Register (July 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) published in The Cochrane Library (Issue 7 2011), MEDLINE (1948 to July 2011), EMBASE (1980 to July 2011), PsycINFO (1806 to July 2011) and the Chinese Biological Medicine Literature Database (CBM) (1978 to 2011). The search was not limited by language.. Randomized controlled trials comparing azithromycin with benzathine penicillin G at any dose for the treatment of early syphilis.. Two review authors independently applied the inclusion criteria to potential studies, with any disagreements resolved by discussion. The risk of bias of each study was assessed by the same two review authors. We pooled data using an odds ratio (OR).. Three studies (generating four eligible study comparisons) were included. One study is ongoing. There was no statistically significant difference between azithromycin and benzathine penicillin treatment in the odds of cure (OR 1.04, 95% CI 0.69 to 1.56); nor any difference at three months (OR 0.97, 95% CI 0.62 to 1.50), six months (OR 1.09, 95% CI 0.76 to 1.54) or nine months (OR 1.45, 95% CI 0.46 to 6.42). Subgroup analysis by primary and latent syphilis and by dose of azithromycin (2 g and 4 g) did not explain the variation between the study results. The reporting of computed mild to tolerated adverse events, from two included trials, indicated no statistically significant difference between azithromycin and benzathine penicillin (OR 1.43, 95% CI 0.42 to 4.95), although with a high level of heterogeneity (P = 0.05, I(2) = 74%).. Differences in the odds of cure did not reach statistical significance when azithromycin was compared with benzathine penicillin for the treatment of early syphilis. No definitive conclusion can be made regarding the relative safety of benzathine penicillin G and azithromycin for early syphilis. Further studies on the utility of benzathine penicillin G for early syphilis are warranted.

Topics: Anti-Bacterial Agents; Azithromycin; Humans; Penicillin G Benzathine; Randomized Controlled Trials as Topic; Syphilis; Treponema pallidum

Genital ulcer disease by virtue of disruption of the mucosal surfaces may enhance HIV acquisition. Genital ulcer disease treatment with resolution of the ulcers may therefore contribute in reducing the sexual acquisition of HIV.. To determine the effects of treatment of genital ulcer disease on sexual acquisition of HIV.. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, LILACS, NLM Gateway, Web of Science, WHO International Clinical Trials Registry Platform, ClinicalTrials.gov, and reference lists of relevant publications for eligible studies published between 1980 and August 2011.. Randomized controlled trials of any treatment intervention aimed at curing genital ulcer disease compared with an alternative treatment, placebo, or no treatment. We included only trials whose unit of randomization was the individual with confirmed genital ulcer.. We independently selected studies and extracted data in duplicate; resolving discrepancies by discussion, consensus, and arbitration by third review author. We expressed study results as risk ratios (RR) with 95% confidence intervals (CI).. There were three randomized controlled trials that met our inclusion criteria recruited HIV-negative participants with chancroid (two trials with 143 participants) and primary syphilis (one trial with 30 participants). The syphilis study, carried out in the US between 1995 and 1997, randomized participants to receive a single 2.0 g oral dose of azithromycin (11 participants); two 2.0 g oral doses of azithromycin administered six to eight days apart (eight participants); or benzathine penicillin G administered as either 2.4 million units intramuscular injection once or twice seven days apart (11 participants). No participant in the trial seroconverted during 12 months of follow-up. The chancroid trials, conducted in Kenya by 1990, found no significant differences in HIV seroconversion rates during four to 12 weeks of follow-up between 400 and 200 mg single oral doses of fleroxacin (one trial, 45 participants; RR 3.00; 95% CI 0.29 to 30.69), or between 400 mg fleroxacin and 800 mg sulfamethoxazole plus 160 mg trimethoprim (one trial, 98 participants; RR 0.33; 95% CI 0.04 to 3.09). Adverse events reported were mild to moderate in severity, and included Jarisch-Herxheimer reactions and gastrointestinal symptoms. The differences between the treatment arms in the incidence of adverse events were not significant. The quality of this evidence on the effectiveness of genital ulcer disease treatment in reducing sexual acquisition of HIV, according to GRADE methodology, is of very low quality.. At present, there is insufficient evidence to determine whether curative treatment of genital ulcer disease would reduce the risk of HIV acquisition. The very low quality of the evidence implies that the true effect of genital ulcer disease treatment on sexual acquisition of HIV may be substantially different from the effect estimated from currently available data. However, genital ulcer diseases are public health problems in their own right and patients with these conditions should be treated appropriately; whether the treatment reduces the risk of HIV infection or not.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Azithromycin; Chancroid; Female; Fleroxacin; HIV Infections; HIV Seronegativity; Humans; Male; Penicillin G Benzathine; Randomized Controlled Trials as Topic; Sulfamethoxazole; Syphilis; Trimethoprim

Although the recommended treatment for syphilis is penicillin, azithromycin has been used as an alternative. We discuss azithromycin-related treatment failures and resistance in Treponema pallidum, and propose ways to meet the resulting clinical and public health challenges.. Azithromycin treatment failures in syphilis were first noted in San Francisco in 2002 and result from an A-->G mutation at position 2058 of the 23S rRNA gene of T. pallidum. This mutation confers resistance by precluding macrolide binding to the bacterial 50S ribosomal subunit, of which 23S rRNA is a structural component. Azithromycin resistance has also been identified in T. pallidum specimens from elsewhere in the United States, Ireland, and Canada, and the amount of resistant specimens has increased with time. Treatment with azithromycin or other macrolides appears to be a risk factor for presenting with a resistant T. pallidum strain.. Although T. pallidum remains sensitive to penicillin and certain other antibiotics, azithromycin resistance in T. pallidum has emerged and is increasing in the United States, Canada, and Ireland. This poses clinical and public health challenges, and indicates a need for further antibiotic drug development and surveillance for resistance in T. pallidum. If azithromycin is used to treat syphilis, clinicians and public health practitioners should remain vigilant for treatment failures.

Topics: Anti-Bacterial Agents; Azithromycin; Canada; Drug Resistance, Bacterial; Humans; Ireland; Syphilis; Treponema pallidum; United States

The World Health Organization estimates that at least 12 million people are infected with syphilis in the world. Southeast Asia accounts for 5.8 million; Africa accounts for 3.5 million. There has been controversy in using the two kinds of antibiotics for early syphilis. A systematic review comparing these antibiotics could affect treatment guidelines. The aim of this study was to evaluate the efficacy and safety of azithromycin vs. penicillin G benzathine for early syphilis and a meta-analysis to compare these two kinds of antibiotics for early syphilis. Four randomized controlled trials met the inclusion criteria; 476 patients were evaluated for their cure rate. Cure rates were 95.0% (227/239) for azithromycin and 84.0% (199/237) for penicillin G benzathine. After pooling the data, the difference in efficacy was computed. Cure rate (OR=1.37), 95% CI (1.05, 1.77) and the risk difference for cure rate between the two drugs were statistically significant. Although the gastrointestinal adverse effect of azithromycin is five times more than the adverse effect of penicillin G benzathine, the differences are not significant. Azithromycin achieved a higher cure rate than penicillin G benzathine in a long follow-up.

Topics: Anti-Bacterial Agents; Azithromycin; Early Diagnosis; Humans; Penicillin G Benzathine; Randomized Controlled Trials as Topic; Syphilis

Clinical management of patients with syphilis is controversial. This article summarizes recent research on syphilis treatment efficacy and outcomes and is based on a comprehensive systematic review of published literature, relevant abstracts, conference proceedings, technical reports, and guidelines. Penicillin remains the drug of choice for the treatment of syphilis. Although several studies have suggested that azithromycin may have clinical efficacy, macrolide resistance has been widely documented among strains of Treponema pallidum, and treatment failures have been reported. Ceftriaxone is effective for the treatment of syphilis when used in multiple-dose regimens. Lumbar puncture should be performed for human immunodeficiency virus-infected patients with syphilis of >1 year's duration and a serum nontreponemal test titer > or =1 : 32, as well for other patients for whom the clinical suspicion of neurosyphilis is high. Newer laboratory tests for syphilis are undergoing extensive evaluation and may prove to be useful for future clinical care. American and European approaches to syphilis treatment are similar, but they vary across several parameters.

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Ceftriaxone; Drug Resistance, Bacterial; Humans; Male; Neurosyphilis; Penicillins; Syphilis; Treatment Outcome; Treponema pallidum

Topics: Anti-Bacterial Agents; Azithromycin; Chancroid; Female; Gonorrhea; Humans; Pelvic Inflammatory Disease; Sexually Transmitted Diseases; Syphilis; Urethritis

Some syphilis patients remain in a serologically active state after the recommended therapy. We currently know too little about the characteristics of this serological response.. We conducted a cohort study using the clinical database from Zhongshan Hospital, Medical College of Xiamen. In total, 1,327 HIV-negative patients with primary, secondary, latent, and tertiary syphilis were enrolled. Bivariate and multivariate analyses were utilised to identify factors associated with a serological cure and serofast state in syphilis patients one year after therapy. Chi-square tests were used to determine the differences in the serological cure rate across different therapy time points.. One year after the recommended therapy, 870 patients achieved a serological cure, and 457 patients (34.4%) remained in the serofast state. The serological cure rate increased only within the first 6 months. The bivariate analysis indicated that male or younger patients had a higher likelihood of a serological cure than female or older patients. Having a baseline titre ≤ 1∶2 or ≥ 1∶64 was associated with an increased likelihood of a serological cure. The serological cure rate decreased for the different disease stages in the order of primary, secondary, latent, and tertiary syphilis. A distinction should be drawn between early and late syphilis. The multivariate analysis indicated that a serological cure was significantly associated with the disease phase, gender, age, and baseline rapid plasma reagin (RPR) titre.. The serofast state is common in clinical work. After one year of the recommended therapy, quite a few syphilis patients remained RPR positive. The primary endpoint of the study indicated that disease phase, gender, age and baseline RPR titre were crucial factors associated with a serological cure.

Topics: Adult; Azithromycin; Cohort Studies; Doxycycline; Female; HIV Infections; Humans; Immunoglobulin M; Male; Multivariate Analysis; Penicillin G; Reagins; Syphilis; Syphilis Serodiagnosis; Syphilis, Latent; Treponema pallidum; Young Adult

Serologic tests for syphilis results at the time of diagnosis are the basis for evaluating response to syphilis therapy. After treatment, however, serologic tests for syphilis titers may continue to increase for several weeks. We evaluated rapid plasma reagin (RPR) titer variation during the 14 days after therapy using data from a recent large, prospective randomized controlled trial.. Prospectively enrolled participants in North America and Madagascar with primary, secondary, or early latent syphilis were randomly assigned to penicillin, doxycycline (in the case of penicillin allergy), or azithromycin treatment. Blood for RPR analysis was drawn at days 0, 7, and 14 posttreatment. All RPR titers were determined simultaneously at a central laboratory.. Four hundred and seventy patients had data available for at least 2 of 3 RPR measurements. Overall, 20% of patients showed a titer increase of at least 1 dilution in the 14 days after therapy. The greatest proportion of titer increases following therapy was observed in patients with primary syphilis. Comparing outcome of therapy using the initial (day 0) RPR titer versus the maximal RPR titer (during 14 days) resulted in outcome reclassification in 2.98% of participants.. Despite the fact that about 20% of early syphilis patients had increases in RPR titers immediately after treatment, these changes rarely influenced assessment of therapeutic outcome. Only 3% of patients treated would have been reclassified.

Topics: Adult; Analysis of Variance; Anti-Bacterial Agents; Antibodies, Bacterial; Azithromycin; Doxycycline; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Immunologic Factors; Madagascar; Male; Middle Aged; North America; Penicillins; Prospective Studies; Reagins; Syphilis; Syphilis Serodiagnosis; Time Factors; Treatment Outcome; Treponema pallidum; Young Adult

Syphilis remains an important source of morbidity worldwide. Long-acting penicillin is the only therapy currently recommended for syphilis in much of the world. Because of hesitation to use penicillin for fear of anaphylaxis, there is a need for an effective, well-tolerated alternative to penicillin for syphilis therapy.. This multicenter, randomized clinical trial was conducted in clinics for the treatment of persons with sexually transmitted diseases. We compared serological cure rates for human immunodeficiency virus (HIV)-negative persons with early syphilis treated with azithromycin at a dosage of 2.0 g administered orally as a single dose with cure rates for those treated with benzathine penicillin G at a dosage of 2.4 million units administered intramuscularly.. A total of 517 participants were enrolled in the trial. In the intention-to-treat analysis, after 6 months of follow-up, serological cure was observed in 180 (77.6%) of 232 azithromycin recipients and 186 (78.5%) of 237 penicillin recipients (1-sided lower bound 95% confidence interval, 7.2%). Nonserious adverse events were more common among azithromycin recipients than they were among penicillin recipients (61.5% vs 46.3%), and such adverse events were accounted for, in large part, by self-limited gastrointestinal complaints.. In this trial, the efficacy of azithromycin at a dosage of 2.0 g administered orally was equivalent to that of benzathine penicillin G for the treatment of early syphilis in persons without HIV infection.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Azithromycin; Female; Humans; Male; Middle Aged; Penicillin G Benzathine; Syphilis; Treatment Outcome; Young Adult

Treponema pallidum resistance to azithromycin has been documented in the US, Canada, and Ireland. We found no evidence of resistance to azithromycin in specimens from 141 patients with syphilitic lesions in Madagascar suggesting resistance is geographically isolated and supporting use of azithromycin as alternative treatment for early syphilis in Madagascar.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Azithromycin; Bacterial Proteins; Drug Resistance, Bacterial; Female; Humans; Madagascar; Male; Microbial Sensitivity Tests; Middle Aged; Mutation; RNA, Ribosomal, 23S; Syphilis; Treponema pallidum; Young Adult

The goal of this study was to assess azithromycin and/or benzathine penicillin for treatment of syphilis.. In a population-based study, participants with serologic syphilis (TRUST with TPHA confirmation) were offered 2.4 MU benzathine penicillin intramuscularly. Intervention arm participants received 1 g presumptive oral azithromycin. We assessed cure rates with penicillin or azithromycin given alone and in combination. Cure assessed after 10 months was defined as seroreversion or a 4-fold decrease in titer. The rate ratio (RR) of cure and 95% confidence intervals (95% CIs) were estimated by log binomial regression.. Among 952 cases with syphilis, 18% received penicillin alone, 17% azithromycin only, and 65% dual treatment. The overall cure rate was 61%. Cure rates were lower in males compared with females (RR, 0.89; 95% CI, 0.80-0.99) and in subjects with initial titers > or =1:4 compared with < or =1:2 (RR, 0.77; 95% CI, 0.69-0.86). There was no significant differences in cure rates among HIV-positive and HIV-negative persons. With initial titers < or =1:2, there were no differences in cure rates by treatment regimen. However, with initial titers > or =1:4, significantly higher cure rates were observed with azithromycin alone (adjusted RR, 1.38; 95% CI, 0.97-1.96), and with dual treatment of azithromycin and benzathine penicillin (RR, 1.38; 95% CI, 1.03-1.87) compared with penicillin alone.. Azithromycin alone or in combination with penicillin achieved higher cure rates than penicillin alone in cases with a high initial TRUST titer. In low-titer infections, the 3 drug combinations were equally effective. HIV status did not affect cure rates.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Azithromycin; Drug Administration Schedule; Female; HIV Infections; Humans; Injections, Intramuscular; Male; Penicillin G Benzathine; Rural Health; Syphilis; Treatment Outcome; Uganda

Pilot studies suggest that a single, 2-g oral dose of azithromycin may be an alternative to a 2.4-MU intramuscular dose of penicillin G benzathine in the prevention and treatment of syphilis. We evaluated the efficacy of treatment with azithromycin in a developing country.. A total of 328 subjects, 25 with primary and 303 with high-titer (a titer of at least 1:8 on a rapid plasmin reagin [RPR] test) latent syphilis, were recruited through screening of high-risk populations in Mbeya, Tanzania, and randomly assigned to receive 2 g of azithromycin orally (163 subjects) or 2.4 million units of penicillin G benzathine intramuscularly (165 subjects). The primary outcome was treatment efficacy, with cure defined serologically (a decline in the RPR titer of at least two dilutions by nine months after treatment) and, in primary syphilis, by epithelialization of ulcers within one or two weeks.. The average age of participants was 27.0 years, 235 (71.6 percent) were female, and 171 (52.1 percent) were seropositive for human immunodeficiency virus. Cure rates were 97.7 percent (95 percent confidence interval, 94.0 to 99.4) in the azithromycin group and 95.0 percent (95 percent confidence interval, 90.6 to 97.8) in the penicillin G benzathine group (95 percent confidence interval for the difference, -1.7 to 7.1 percent), achieving prespecified criteria for equivalence. Cure rates were also similar three and six months after treatment in the two groups and in all subgroups. Cure rates at three months were 59.4 percent (95 percent confidence interval, 51.8 to 67.1) in the azithromycin group and 59.5 percent (95 percent confidence interval, 51.8 to 67.3) in the penicillin G benzathine group and at six months were 85.5 percent (95 percent confidence interval, 79.4 to 90.6) and 81.5 percent (95 percent confidence interval, 74.8 to 87.4), respectively.. Single-dose oral azithromycin is effective in treating syphilis and may be particularly useful in developing countries in which the use of penicillin G benzathine injections is problematic. However, recent reports of azithromycin-resistant Treponema pallidum in the United States indicate the importance of continued monitoring for resistance.

Topics: Administration, Oral; Adolescent; Adult; Anti-Bacterial Agents; Azithromycin; Developing Countries; Female; HIV Seropositivity; Humans; Injections, Intramuscular; Male; Penicillin G Benzathine; Proportional Hazards Models; Syphilis

Use of preexposure antibiotic prophylaxis for syphilis control has been limited by concerns about acceptability and adverse behavioral effects.. The goal was to determine whether persons at high risk for syphilis accept antibiotic prophylaxis and if so, whether they subsequently increase their risky behavior.. We gave a prospective cohort of persons either: 1) single doses of benzathine penicillin, azithromycin, and cefixime; or 2) a single dose of cefixime and 3 doses of azithromycin given biweekly.. Of 268 persons approached, 186 (69%) agreed to participate, 174 were treated, and 125 (72%) were located for follow up. Four weeks and 4 months after enrollment, participants reported reductions in the number of sex partners. At 4 months, 1% had acquired gonorrhea, 5% had acquired chlamydia, and none had acquired syphilis.. Antibiotic prophylaxis for syphilis was acceptable and not followed by increases in risky behavior. Larger trials of preexposure antibiotic prophylaxis of core group members to control syphilis outbreaks should be undertaken.

Topics: Adolescent; Adult; Antibiotic Prophylaxis; Azithromycin; Cefixime; Cohort Studies; Drug Administration Schedule; Female; Humans; Louisiana; Male; Middle Aged; Patient Satisfaction; Penicillin G Benzathine; Prospective Studies; Risk-Taking; Sexual Behavior; Syphilis; Treatment Outcome

Penicillin is the only medication currently recommended for treatment of early syphilis in non-penicillin-allergic patients. Preliminary data suggest that azithromycin may be effective for syphilis therapy.. This was a randomized, comparative pilot study of intramuscular injections of benzathine penicillin G and two oral azithromycin regimens for treatment of syphilis.. We randomly assigned patients with early syphilis to treatment with either intramuscular injections of 2.4 million units of benzathine penicillin G or azithromycin administered orally, either as a single 2.0-g dose or as two 2.0-g doses given 1 week apart. Serological response to therapy was evaluated at 3, 6, 9, and 12 months following therapy. Participants whose rapid plasma reagin (RPR) test became nonreactive or whose RPR titer decreased > or =2 dilutions were classified as responding to therapy. When serological tests did not show a response to therapy, the treatment was classified as a failure if RPR titers increased > or =2 dilutions. Nonresponders were those whose serologic titers remained within +/-1 dilution of the initial RPR titer.. Cumulative response rates were as follows: benzathine penicillin G, 86% (12 of 14); azithromycin, 2.0-g single dose, 94% (16 of 17); and azithromycin, two 2.0-g doses given 1 week apart, 83% (24 of 29). Therapy failed for one patient treated with benzathine penicillin and one patient treated with the two-dose azithromycin regimen, whereas in six patients the clinical manifestations of infection resolved but there was no serological response.. Oral therapy with 2.0 g of azithromycin as a single dose or as two doses 1 week apart is a promising alternative to therapy with benzathine penicillin G for syphilis and should be studied further.

Topics: Administration, Oral; Adolescent; Adult; Anti-Bacterial Agents; Azithromycin; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Injections, Intramuscular; Male; Middle Aged; Penicillin G Benzathine; Penicillins; Pilot Projects; Reagins; Syphilis; Treponema pallidum

An open, noncomparative study was performed to establish the efficacy of azithromycin in the treatment of early syphilis. Sixteen patients were treated with oral azithromycin: 1g the first day and then 500 mg for the following 8 days. Two patients were excluded from the study, leaving 14 patients for the evaluation of the efficacy. Venereal Disease Research Laboratory (VDRL) negativity was observed in 3 out of 6 patients treated for primary syphilis after 3 months and in all patients after 6 months. Two of 8 patients treated for manifest or early latent secondary syphilis had VDRL negativity after 3 months and 4 patients after 6 months. This study demonstrates that azithromycin is effective in the treatment of early syphilis. Two patients experienced gastrointestinal side effects which did not require treatment interruption.

Topics: Administration, Oral; Adult; Anti-Bacterial Agents; Azithromycin; Female; Humans; Male; Middle Aged; Pilot Projects; Syphilis

Preventive therapy is an important element of syphilis control efforts. No currently recommended, single-dose alternatives to penicillin G benzathine are available for treatment of incubating syphilis.. To evaluate the use of a single 1.0-g dose of azithromycin for treatment of persons recently exposed to sexual partners with infectious syphilis.. Single-center, open-label, randomized pilot study to compare azithromycin with penicillin G benzathine therapy. Participants were evaluated serologically for 3 months.. Sexually transmitted disease clinic in Birmingham, Alabama.. 96 participants who in the preceding 30 days had been exposed to partners with infectious syphilis through sexual intercourse.. Syphilis prevention, as indicated by nonreactive serologic tests (rapid plasma reagin and fluorescent treponemal antibody-absorbed), throughout the 3-month follow-up.. Among 96 participants enrolled, none of 40 evaluable persons in the azithromycin group and none of 23 evaluable persons in the penicillin group developed evidence of syphilis. Significantly more penicillin-treated participants (21 of 44 [48%]) than azithromycin-treated participants (12 of 52 [23%]) became nonevaluable during follow-up (P = 0.01).. A single 1.0-g dose of azithromycin seems to be efficacious for prevention of syphilis in persons exposed to infected sexual partners.

Topics: Administration, Oral; Adolescent; Adult; Anti-Bacterial Agents; Azithromycin; Disease Transmission, Infectious; Follow-Up Studies; Humans; Middle Aged; Penicillin G Benzathine; Penicillins; Pilot Projects; Syphilis; Treatment Outcome

Azithromycin has in vitro activity against Treponema pallidum and is effective against experimental syphilis in rabbits. We undertook an open, noncomparative pilot study of oral azithromycin (500 mg once daily for 10 days) to treat 16 patients with primary or secondary syphilis who were seronegative for human immunodeficiency virus. Cure was documented for 11 of 13 patients observed > or = 3 months; three patients were lost to follow-up. The serological response of one patient with secondary syphilis was indeterminate, and one patient with primary syphilis had either relapse or reinfection. Four patients had mild gastrointestinal side effects, and another patient had an episode of nausea and vomiting; all side effects occurred in the first 3 days and resolved spontaneously as treatment continued. Azithromycin shows promise as an alternative agent for treatment of early syphilis; controlled trials and assessment of other dosage regimens are indicated.

Topics: Administration, Oral; Adult; Azithromycin; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Male; Pilot Projects; Syphilis; Treatment Outcome

The results of the use of azithromycin (sumamed) in the treatment of 100 patients with fresh syphilis were analyzed. The antibiotic was used in accordance with two treatment schemes: 500 mg daily for 10 days and 500 mg every two days. The total course dose was 5 g in both the cases. The results of the treatment with azithromycin were compared with those of the treatment with erythromycin (30 g) and penicillin (300,000 U every 3 hours for 16-28 days depending on the disease stage). The results were estimated by the rate of the elimination of Treponema pallidum and syphilids as well as by the time course of the seroreactions. The analysis provided a conclusion that the therapeutic efficacy of sumamed in the treatment of patients with fresh manifest syphilis was high: by comparison with penicillin and erythromycin it more rapidly eliminated the clinical signs of syphilis and in the majority of the cases induced negativation of the cutaneous serological reactions within the first 4 months of the treatment.

Topics: Adolescent; Adult; Azithromycin; Erythromycin; Female; Humans; Male; Middle Aged; Penicillins; Syphilis; Time Factors

Topics: Azithromycin; Chlamydia Infections; Chronic Disease; Female; Female Urogenital Diseases; Humans; Male; Male Urogenital Diseases; Syphilis

These days sexually transmitted infections (STIs) are important public health problems not only due to their high prevalence, but also because they require early diagnosis and treatment to avoid complications. In recent years, there has been an exponential increase in cases of infections caused by Chlamydia trachomatis and gonococcus in the population under 25years of age. In addition, an increase in the incidence of syphilis and hepatitisC (HCV) has also been detected, especially in men who have sex with other men (MSM). Genital herpes continues to be the second most frequent STI in the world, behind condyloma acuminata, and the first cause of genital ulcer among Spain in the sexually active population. A decrease in reported HIV cases was observed during 2020, but almost half of these new cases had a late diagnosis (<350CD4cell/μL). Current guidelines recommend offering STI annual screening to populations at risk or more often depending on the risk. STIs can appear in the form of syndromes, such as secretory syndrome (urethritis, proctitis, and cervicitis) or ulcerated syndrome (ulcers). The STIs that can cause secretory syndrome are mainly caused by Neisseria gonorrhoeae and C.trachomatis, which co-infect up to 40% of cases, and also cause urethritis, cervicitis or proctitis depending on where they are located. Gonococcus has an incubation period of 2-7days and Chlamydia 2-6weeks, and they are diagnosed using PCR and/or culture (the last one only valid for gonococcus) of samples collected according to sexual activities. Empirical treatment to cover both germs will be accomplished with ceftriaxone, 1g single intramuscular dose plus doxycycline 100mg every 12h orally for 7days, or azithromycin 1g single dose orally (we will use azithromycin only if we suspect a poor compliance with treatment, difficulty in going to the control or in pregnancy). Likewise, whenever we diagnose an STI firstly, we must offer advice and health education in order to promote the adoption of safe sexual behaviours and the correct use of barrier methods. Secondly, we must also screen for other STIs (HIV, syphilis, hepatitisB, and hepatitisA andC depending on the risk), offer HBV and HAV vaccination if it is appropriate, and finally study and treat all sexual partners from the previous 3months.

Topics: Azithromycin; Female; HIV Infections; Homosexuality, Male; Humans; Male; Neisseria gonorrhoeae; Pregnancy; Primary Health Care; Sexual and Gender Minorities; Sexually Transmitted Diseases; Syphilis; Urethritis; Uterine Cervicitis

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.

Topics: Amoxicillin; Animals; Anti-Bacterial Agents; Azithromycin; Ceftriaxone; Drug Resistance, Bacterial; Globus Pallidus; Humans; Infant, Newborn; Linezolid; Macrolides; Syphilis; Treponema; Treponema pallidum

Azithromycin is an antibiotic used to treat syphilis, especially in the context of penicillin allergy. Although resistance to azithromycin has been widely reported to be associated with one- and/or two-point mutations on the 23S rRNA gene, it has yet to be described in Indonesia. Specimens were collected from 220 patients diagnosed with secondary syphilis. A multiplex nested polymerase chain reaction (PCR) testing system using the 23S rRNA target gene of Treponema pallidum was designed using three primer pairs. The first step involved the use of PCR primer pairs to detect T. pallidum. In the second step, two PCR primer pairs were constructed to identify azithromycin-resistant T. pallidum based on A2058G and A2059G point mutations. T. pallidum detected in samples from Jakarta or Bandung were not resistant to azithromycin. However, azithromycin-resistant T. pallidum were found in samples from Makassar, Medan, and Bali. Specimens from heterosexual males and patients with HIV accounted for the majority of azithromycin resistance noted in the study. This study demonstrated that the azithromycin-resistant T. pallidum detected in Indonesia appear to be a novel variant of resistance, containing both the A2058G and A2059G mutations found in Medan and Makassar.

Topics: Anti-Bacterial Agents; Azithromycin; Drug Resistance, Bacterial; Genes, rRNA; Humans; Indonesia; Macrolides; Male; Multiplex Polymerase Chain Reaction; RNA, Ribosomal, 23S; Syphilis; Treponema pallidum

In South Africa, male urethritis syndrome (MUS) is the most common sexually transmitted infection (STI) syndrome in men. We determined the distribution of STI etiologies and the susceptibility profiles of Neisseria gonorrhoeae isolates from men presenting with MUS to 3 sentinel surveillance health care facilities. Secondary objectives were to determine the seroprevalence of coinfections (HIV, syphilis, herpes simplex virus 2).. Consecutive, consenting men with symptomatic urethral discharge were enrolled between January 1, 2019, and December 31, 2020. Genital discharge swab and blood specimens were collected and transported to a central STI reference laboratory in Johannesburg, South Africa.. Among 769 men enrolled, N. gonorrhoeae was the commonest cause of MUS (674 [87.8%]; 95% confidence interval [CI], 85.2%-89.9%), followed by Chlamydia trachomatis (161 [21.0%]; 95% CI, 18.2%-24.0%). Of 542 cultivable N. gonorrhoeae isolates, all were susceptible to ceftriaxone (modal minimum inhibitory concentration, 0.004 mg/L) and azithromycin (modal minimum inhibitory concentration, 0.128 mg/L). Seroprevalence rates of HIV, syphilis, and HSV-2 were 21.4% (95% CI, 18.5%-24.5%), 2.3%, and 50.1%, respectively. Condom use at last sexual encounter was reported by only 7%, less than 50% had been medically circumcised, and only 66.7% (58 of 87) who self-reported an HIV-positive status were adherent on antiretroviral drugs.. Neisseria gonorrhoeae and C. trachomatis were the predominant causes of MUS. Currently recommended dual ceftriaxone and azithromycin therapy are appropriate for MUS syndromic management; however, surveillance must be maintained to timeously detect emerging and increasing gonococcal resistance. Clinic-based interventions must be intensified in men seeing sexual health care to reduce the community transmission and burden of STI and HIV.

Topics: Azithromycin; Ceftriaxone; Chlamydia trachomatis; Gonorrhea; Herpesvirus 2, Human; HIV Infections; Humans; Male; Neisseria gonorrhoeae; Seroepidemiologic Studies; Sexually Transmitted Diseases; South Africa; Syphilis; Urethritis

British Columbia (BC) implemented the syphilis reverse screening algorithm and Treponema pallidum PCR testing in 2014. We summarize the performance characteristics of the algorithm, together with PCR direct detection, and report on syphilis cases identified from 2015 to 2020. Prior to 2015, samples for syphilis diagnosis were first screened by rapid plasma reagin (RPR). As of 2015, sera were screened by the Siemens Advia Centaur syphilis assay (enzyme immunoassay [EIA]). Positive and equivocal samples were reflex tested by a T. pallidum passive particle agglutination assay (TPPA) and RPR. We used T. pallidum DNA PCR on clinical samples and restriction fragment length polymorphism analysis to identify azithromycin resistance mutations. Case/epidemiological data were obtained from the BC surveillance system. Of 1,631,519 samples screened by the EIA, 72,492 (4.4%) were positive and 187 (<0.1%) were equivocal. Of EIA-positive/equivocal samples, 10.6% were false positive, and false positivity was higher at lower EIA indices. The reverse algorithm detected 4,693 late latent syphilis cases that likely would have been missed by RPR screening. PCR had a very high sensitivity of 100% versus 52.9% and 52.4% for dark-field (DF) and immunofluorescence (IF) microscopy, respectively. The azithromycin resistance mutation A2058G was identified in 96% of PCR-positive samples, and A2059G was identified in 4%. Annually, there were 944 to 1,467 syphilis cases, with 62% in men who reported male sexual partners. The reverse algorithm had a low false-positive rate and very few equivocal screening results but did identify previously undiagnosed late latent syphilis cases. PCR was more sensitive than both DF and IF microscopy for direct diagnosis and enabled monitoring for azithromycin resistance.

Topics: Algorithms; Azithromycin; British Columbia; Humans; Male; Polymerase Chain Reaction; Syphilis; Treponema pallidum

Neisseria meningitidis is a Gram-negative bacterium frequently associated with invasive diseases with high mortality. Although its natural reservoir is the human nasopharynx, in recent years there have been increasing reports of isolation of this agent in the anorectal mucosa, mainly in men who have sex with men (MSM). We present the case of an HIV-positive MSM who consulted for urethritis and primary syphilis, in which N. meningitidis was isolated in an anorectal specimen. He was treated empirically with ceftriaxone and azithromycin, and a post-treatment control culture was negative. Despite the increase in anogenital infections and colonization by N. meningitidis, its role is unknown as a genital pathogen and in the transmission of other infections and the need for specific therapeutic regimens.

Topics: Azithromycin; Ceftriaxone; Homosexuality, Male; Humans; Male; Neisseria meningitidis; Sexual and Gender Minorities; Syphilis

Since the beginning of the 21st century, Reunion Island has experienced a syphilis epidemic. Infected patients are mostly heterosexual, with a high proportion of women, suggesting that congenital syphilis is present on the island. To determine whether azithromycin can be used for mass treatment of syphilis on Reunion Island, we assessed the prevalence of macrolide resistance in Treponema pallidum (TP).. This monocentric cross-sectional study was conducted at the Reunion Island University Hospital. Samples were collected from lesions suggestive of primary or secondary syphilis. Samples positive for TP by multiplex polymerase chain reaction (PCR) were sent to the French National Reference Centre (NRC) for further analysis. Nested PCR-tpp47 was performed on these samples for detection of TP-DNA; 23s rRNA was amplified by PCR in confirmed positive samples. The Restriction Fragment Length Polymorphism (RFLP) technique was performed on samples with amplified 23s rRNA for detection of the A2058G mutation.. A total of 129 samples were collected from 119 patients. Of these, 18 tested positive for TP using multiplex PCR and were sent to the NRC. Fifteen (83.3%) of the 18 samples were confirmed positive by nested PCR-tpp47, and 23s rRNA was amplified in only 7 (38.9%) samples. Azithromycin resistance was detected in all TP strains with amplified 23s rRNA.. Amplification of 23s rRNA was successful in only 7 TP strains, all of which displayed resistance to macrolides. Keeping in mind the small sample size of our study, this suggests that azithromycin should not be used for mass treatment of syphilis in Reunion Island.

Topics: Anti-Bacterial Agents; Azithromycin; Cross-Sectional Studies; Drug Resistance, Bacterial; Female; Humans; Macrolides; Reunion; Syphilis; Treponema pallidum

Topics: Anti-Bacterial Agents; Antiviral Agents; Azithromycin; Chancroid; Humans; Intellectual Disability; Male; Medication Adherence; Mupirocin; Syphilis; Valacyclovir; Young Adult

Syphilis is a sexually transmitted infection caused by Treponema pallidum subspecies pallidum and may lead to severe complications. Recent years have seen striking increases in syphilis in many countries. Previous analyses have suggested one lineage of syphilis, SS14, may have expanded recently, indicating emergence of a single pandemic azithromycin-resistant cluster. Here we use direct sequencing of T. pallidum combined with phylogenomic analyses to show that both SS14- and Nichols-lineages are simultaneously circulating in clinically relevant populations in multiple countries. We correlate the appearance of genotypic macrolide resistance with multiple independently evolved SS14 sub-lineages and show that genotypically resistant and sensitive sub-lineages are spreading contemporaneously. These findings inform our understanding of the current syphilis epidemic by demonstrating how macrolide resistance evolves in Treponema subspecies and provide a warning on broader issues of antimicrobial resistance.

Topics: Anti-Bacterial Agents; Azithromycin; Drug Resistance, Bacterial; Genome, Bacterial; Genomics; Genotype; Humans; Macrolides; Molecular Epidemiology; Pandemics; Phylogeny; Sequence Analysis, DNA; Species Specificity; Syphilis; Treponema pallidum

Topics: Anti-Bacterial Agents; Azithromycin; HIV; Humans; Penicillin G Benzathine; Syphilis

The patient's history and the clinical appearance of the ulcer led to the diagnosis of this re-emerging condition.

Topics: Administration, Oral; Adult; Azithromycin; Humans; Male; Penis; Sexual and Gender Minorities; Syphilis; Treatment Outcome; Ulcer

To identify predictors of treatment success in syphilitic uveitis (SU).. Retrospective multicentric analysis of patients treated for SU.. A total of 95 eyes (66 patients, mean [standard deviation] aged 49 [12.5] years, 31 [47%] of whom were human immunodeficiency virus [HIV]+) were analyzed.. Activity of SU was assessed at 1 week and 1 month after treatment onset, and at last follow-up. Improvement was defined by a ≥2-step decrease of both anterior chamber and vitreous haze inflammation levels, and by the size reduction in chorioretinal lesions.. Recovery was defined as the resolution of inflammation in all anatomic structures at 1 month.. Panuveitis and posterior uveitis were the most frequent findings. Inflammatory parameters were higher in HIV+ patients. Recovery was reported in 65% and 85% of eyes at 1 month and at last follow-up, respectively. In multivariate analysis, after adjusting for initial best-corrected visual acuity and the antimicrobial treatment regimen, clinical improvement at 1 week (corrected risk ratios [cRR], 3.5 [2.3-3.8]; P = 0.001) was predictive of recovery at 1 month, whereas the use of periocular dexamethasone injections (cRR, 0.05 [0.02-0.6]; P = 0.01) and methylprednisolone pulses negatively affected the outcomes of eyes.. Early improvement is the strongest predictor of ophthalmological recovery in SU.

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Doxycycline; Eye Infections, Bacterial; Female; Fluorescent Treponemal Antibody-Absorption Test; Follow-Up Studies; HIV Seropositivity; Humans; Male; Middle Aged; Penicillin G Benzathine; Polymerase Chain Reaction; Prognosis; Retrospective Studies; Sulfadiazine; Syphilis; Syphilis Serodiagnosis; Uveitis; Visual Acuity

Effectiveness of single-dose azithromycin (2 g) in the treatment of early syphilis among HIV-infected patients has rarely been evaluated in the era of combination ART.. Consecutive HIV-infected patients with early syphilis, who received 2 g single-dose azithromycin or 2.4 MU benzathine penicillin G, between 2007 and 2014, were prospectively observed. Genotypic resistance to macrolides was determined in Treponema pallidum isolates identified from clinical specimens using PCR assays. Rapid plasma reagin (RPR) titres were determined at baseline and every 3 months after treatment. Primary outcome was a decline of RPR titre by ≥4-fold at 12 months after treatment.. During the study period, 162 HIV-infected patients with early syphilis received benzathine penicillin G and 237 patients received azithromycin. At 12 months follow-up, the serological response rate for penicillin and azithromycin groups was 61.1% and 56.5% (P = 0.41), respectively; respective response rate was 61.1% and 65.9% (P = 0.49) if we only included patients infected with T. pallidum not harbouring macrolide resistance in the azithromycin group. In multivariate analysis, RPR titres ≥1:32 (OR 2.56; 95% CI 1.55-4.21) and prior syphilis (OR 0.54; 95% CI 0.35-0.81) were predictors of serological response. Most common adverse effects of azithromycin included diarrhoea (52.7%), nausea (22.4%), abdominal pain (18.6%), bloating (17.7%) and lassitude/somnolence (27.4%).. In the setting of a low prevalence of macrolide-resistant T. pallidum, 2 g single-dose azithromycin achieved a similar serological response to benzathine penicillin G in HIV-infected patients with early syphilis. Major adverse effects of azithromycin were gastrointestinal symptoms and lassitude/somnolence.

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Drug-Related Side Effects and Adverse Reactions; Female; Gastrointestinal Diseases; Genotype; HIV Infections; Humans; Macrolides; Male; Middle Aged; Penicillin G Benzathine; Polymerase Chain Reaction; Prospective Studies; Reagins; Syphilis; Treatment Outcome; Treponema pallidum; Young Adult

This study aimed to assess the presence of macrolide-resistant Treponema pallidum subtypes in Havana, Cuba. Samples from 41 syphilis patients were tested for T. pallidum 23S rRNA gene mutations. Twenty-five patients (61%) harbored T. pallidum with the A2058G mutation, which was present in all 8 subtypes that were identified. The A2059G mutation was not detected.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Azithromycin; Cuba; Drug Resistance, Bacterial; Female; Genotype; Humans; Macrolides; Male; Middle Aged; Point Mutation; Syphilis; Treponema pallidum; Young Adult

Azithromycin is used as an alternative medicine in patients with syphilis who are intolerant to penicillin. Nevertheless, the report of treatment failure of azithromycin for patients with syphilis has raised concerns in China in the past years. In this study, 178 patients with early syphilis, who were treated in sexually transmitted infections clinics in four cities in Guangxi Zhuang Autonomous Region were enrolled to investigate the regional prevalence of Treponema pallidum strain resistant to azithromycin. Nested PCR was performed to amplify the 23S ribosomal RNA (23SrRNA) gene. The point mutation of A2058G in 23SrRNA, which confers Treponema pallidum resistance to azithromycin, was measured by endonuclease digestion of PCR amplification products using MboII. A2058G point mutation was detected in 91.0% (162/178; 95% CI, 86.8%, 95.2%) of the specimens, but no difference in prevalence of azithromycin resistance was found between the patients who had taken antibiotics before enrollment and the patients who had not (91.8% vs. 89.4%), nor between the patients with and without past sexually transmitted infections (87.1% vs. 93.1%). We concluded that azithromycin may not be suitable for syphilis as a treatment option in Guangxi Zhuang Autonomous Region because of the extremely high prevalence of resistance in the general syphilis population.

Topics: Adult; Anti-Bacterial Agents; Azithromycin; China; Drug Resistance, Bacterial; Female; Humans; Male; Middle Aged; Point Mutation; Polymerase Chain Reaction; Syphilis; Treponema pallidum

High rates of 23S rDNA mutations implicated in macrolide resistance have been identified in Treponema pallidum samples from syphilis patients in many countries. Nonetheless, some clinicians have been reluctant to abandon azithromycin as a treatment for syphilis, citing the lack of a causal association between these mutations and clinical evidence of drug resistance. Although azithromycin resistance has been demonstrated in vivo for the historical Street 14 strain, no recent T. pallidum isolates have been tested. We used the well-established rabbit model of syphilis to determine the in vivo efficacy of azithromycin against 23S rDNA mutant strains collected in 2004 to 2005 from patients with syphilis in Seattle, Wash.. Groups of 9 rabbits were each infected with a strain containing 23S rDNA mutation A2058G (strains UW074B, UW189B, UW391B) or A2059G (strains UW228B, UW254B, and UW330B), or with 1 wild type strain (Chicago, Bal 3, and Mexico A). After documentation of infection, 3 animals per strain were treated with azithromycin, 3 were treated with benzathine penicillin G, and 3 served as untreated control groups. Treatment efficacy was documented by darkfield microscopic evidence of T. pallidum, serological response, and rabbit infectivity test.. Azithromycin uniformly failed to cure rabbits infected with strains harboring either 23S rDNA mutation, although benzathine penicillin G was effective. Infections caused by wild type strains were successfully treated by either azithromycin or benzathine penicillin G.. A macrolide resistant phenotype was demonstrated for all strains harboring a 23S rDNA mutation, demonstrating that either A2058G or A2059G mutation confers in vivo drug resistance.

Topics: Animals; Anti-Bacterial Agents; Azithromycin; Disease Models, Animal; DNA, Bacterial; DNA, Ribosomal; Drug Resistance, Bacterial; Humans; Macrolides; Mutation; Penicillin G Benzathine; Rabbits; Syphilis; Treponema pallidum

The abrupt onslaught of the syphilis pandemic that started in the late fifteenth century established this devastating infectious disease as one of the most feared in human history

Topics: Anti-Bacterial Agents; Azithromycin; DNA, Bacterial; Drug Resistance, Bacterial; Evolution, Molecular; Genetic Variation; Genome, Bacterial; Genotype; Global Health; Humans; Molecular Epidemiology; Pandemics; Phylogeny; Sequence Analysis, DNA; Syphilis; Treponema pallidum

The preferred drugs for the treatment of syphilis, benzathine and procaine penicillin, have not been available in Shanghai for many years, and currently, the incidence of syphilis is increasing. Alternative antibiotics for patients with syphilis during the benzathine and procaine penicillin shortage include macrolides. The failure of macrolide treatment in syphilis patients has been reported in Shanghai, but the reason for this treatment failure remains unclear. We used polymerase chain reaction technology to detect a 23S rRNA A2058G mutation in Treponema pallidum in 109 specimens from syphilis patients. The use of azithromycin/erythromycin in the syphilis patients and the physicians' prescription habits were also assessed based on two questionnaires regarding the use of macrolides. A total of 104 specimens (95.4%) were positive for the A2058G mutation in both copies of the 23S rRNA gene, indicating macrolide resistance. A questionnaire provided to 122 dermatologists showed that during the penicillin shortage, they prescribed erythromycin and azithromycin for 8.24±13.95% and 3.21±6.37% of their patients, respectively, and in the case of penicillin allergy, erythromycin and azithromycin were prescribed 15.24±22.89% and 7.23±16.60% of the time, respectively. A second questionnaire provided to the syphilis patients showed that 150 (33.7%), 106 (23.8%) and 34 (7.6%) individuals had used azithromycin, erythromycin or both, respectively, although the majority did not use the drugs for syphilis treatment. Our findings suggest that macrolide resistance in Treponema pallidum is widespread in Shanghai. More than half of the syphilis patients had a history of macrolide use for other treatment purposes, which may have led to the high prevalence of macrolide resistance. Physicians in China are advised to not use azithromycin for early syphilis.

Topics: Adult; Azithromycin; China; Drug Resistance, Bacterial; Erythromycin; Ethylenediamines; Female; Humans; Incidence; Macrolides; Male; Mutation; Penicillin G Procaine; RNA, Ribosomal, 23S; Surveys and Questionnaires; Syphilis; Treatment Failure; Treponema pallidum

Treponema pallidum ssp. pallidum (TPA) causes over 10 million new cases of syphilis worldwide whereas T. pallidum ssp. pertenue (TPE), the causative agent of yaws, affects about 2.5 million people. Although penicillin remains the drug of choice in the treatment of syphilis, in penicillin-allergic patients, macrolides have been used in this indication since the 1950s. Failures of macrolides in syphilis treatment have been well documented in the literature and since 2000, there has been a dramatic increase in a number of clinical samples with macrolide-resistant TPA. Scarce data regarding the genetics of macrolide-resistant mutations in TPA suggest that although macrolide-resistance mutations have emerged independently several times, the increase in the proportion of TPA strains resistant to macrolides is mainly due to the spread of resistant strains, especially in developed countries. The emergence of macrolide resistance in TPA appears to require a two-step process including either A2058G or A2059G mutation in one copy of the 23S rRNA gene and a subsequent gene conversion unification of both rRNA genes. Given the enormous genetic similarity that was recently revealed between TPA and TPE strains, there is a low but reasonable risk of emergence and spread of macrolide-resistant yaws strains following azithromycin treatment.

Topics: Anti-Bacterial Agents; Azithromycin; Drug Resistance, Bacterial; Humans; Macrolides; Mutation; Operon; RNA, Ribosomal, 23S; Syphilis; Treatment Failure; Treponema pallidum; Yaws

Azithromycin has shown high efficacy in randomized trials when used for treating infectious syphilis in Africa. However, its use in clinical practice has been limited by the development of antimicrobial drug resistance. Resistance has not previously been reported from Australasia. The aim of this study was to determine the prevalence of and risk factors for azithromycin-resistant syphilis-causing strains in Sydney, Australia. We evaluated 409 samples that were PCR positive for Treponema pallidum DNA collected between 2004 and 2011 for the presence of the A2058G mutation, which confers resistance to macrolide antibiotics such as azithromycin. Overall, 84% of samples harbored the mutation. The prevalence of the mutation increased during the study period (P trend, 0.003). We also collected clinical and demographic data on 220 patients from whom these samples had been collected to determine factors associated with the A2058G mutation; 97% were from men who have sex with men. Reporting sex in countries other than Australia was associated with less macrolide resistance (adjusted odds ratio, 0.25; 95% confidence interval, 0.09 to 0.66; P = 0.005), with other study factors showing no association (age, HIV status, recent macrolide use, stage of syphilis, or history of prior syphilis). Azithromycin cannot be recommended as an alternative treatment for syphilis in Sydney.

Topics: Adult; Aged; Anti-Bacterial Agents; Australia; Azithromycin; DNA, Ribosomal; Drug Resistance, Bacterial; Female; Humans; Male; Middle Aged; Point Mutation; Prevalence; Retrospective Studies; Risk Factors; Syphilis; Treponema pallidum; Young Adult

The Jarisch-Herxheimer reaction, a febrile inflammatory reaction that often occurs after the first dose of chemotherapy in spirochetal diseases, may result in deleterious effects to patients with neurosyphilis and to pregnant women. A single 2-g oral dose of azithromycin is an alternative treatment to benzathine penicillin G for early syphilis in areas with low macrolide resistance. With its potential anti-inflammatory activity, the impact of azithromycin on the incidence of the Jarisch-Herxheimer reaction in HIV-positive patients with early syphilis has rarely been investigated.. In HIV-positive patients with early syphilis, the Jarisch-Herxheimer reaction was prospectively investigated using the same data collection form in 119 patients who received benzathine penicillin G between 2007 and 2009 and 198 who received azithromycin between 2012 and 2013, when shortage of benzathine penicillin G occurred in Taiwan. Between 2012 and 2013, polymerase chain reaction (PCR) assay was performed to detect Treponema pallidum DNA in clinical specimens, and PCR restriction fragment length polymorphism of the 23S ribosomal RNA was performed to detect point mutations (2058G or A2059G) that are associated with macrolide resistance.. The overall incidence of the Jarisch-Herxheimer reaction was significantly lower in patients receiving azithromycin than those receiving benzathine penicillin G (14.1% vs. 56.3%, p<0.001). The risk increased with higher rapid plasma reagin (RPR) titres (adjusted odds ratio [AOR] per 1-log2 increase, 1.21; confidence interval [CI], 1.04-1.41), but decreased with prior penicillin therapy for syphilis (AOR, 0.37; 95% CI, 0.19-0.71) and azithromycin treatment (AOR, 0.15; 95% CI, 0.08-0.29). During the study period, 310 specimens were obtained from 198 patients with syphilis for PCR assays, from whom T. pallidum was identified in 76 patients, one of whom (1.3%) was found to be infected with T. pallidum harbouring the macrolide resistance mutation (A2058G). In subgroup analyses confined to the 75 patients infected with T. pallidum lacking resistance mutation, a statistically significantly lower risk for the Jarisch-Herxheimer reaction following azithromycin treatment was noted.. Treatment with azithromycin was associated with a lower risk for the Jarisch-Herxheimer reaction than that with benzathine penicillin G in HIV-positive patients with early syphilis. Previous benzathine penicillin G therapy for syphilis decreased the risk, whereas higher RPR titres increased the risk, for the reaction.

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Cohort Studies; DNA, Bacterial; DNA, Ribosomal; Drug-Related Side Effects and Adverse Reactions; Female; Fever; HIV Infections; Humans; Incidence; Male; Microbial Sensitivity Tests; Penicillin G Benzathine; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Prospective Studies; RNA, Ribosomal, 23S; Syphilis; Taiwan; Treponema pallidum

We herein describe a case of secondary syphilis in a patient with HIV infection that presented with an unusually diffuse polyostotic osteitis with skull involvement. Syphilis has to be added to the differential diagnosis of extensive inflammatory bone pain in patients at risk, especially if pain worsens at night.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Azithromycin; beta-Lactams; Doxycycline; Humans; Male; Osteitis; Radiography; Skull; Stevens-Johnson Syndrome; Syphilis; Treatment Outcome

Treatment with effective antibiotics is one important strategy for syphilis control in China. This study aimed to evaluate the prevalence of azithromycin resistance to T. pallidum in China. A cross-sectional study was conducted among 391 patients with early syphilis recruited from STD clinics in eight cities during October 2008 and October 2011. The swabs were obtained from the moist lesions of the participating patients. A touchdown/nested PCR of the 23S ribosomal RNA (rRNA) gene was performed on DNA samples extracted from these specimens. The presence or absence of the A2058G point mutation, conferring resistance to azithromycin, was determined by restriction enzyme digestion analysis of the PCR amplicon by MboII. Two hundred and eleven patients with primary or secondary syphilis were found to have T. pallidum DNA in their moist lesions by PCR assays. The A2058G mutation was present in 91.9% (194/211, 95% CI, 87.2-95.1%) of these patients, with no significant differences noted between patients from the eastern part (93.8%), southern part (88.6%) and northern part (95.2%) of China (χ(2) = 2.303, p 0.316). Compared with patients who had not taken macrolides in previous years before study entry, the patients who had taken the antibiotics had a significantly higher prevalence of azithromycin resistance (97.0% vs. 62.5%), with an odds ratio of 19.65 (95% CI, 5.77-66.93). It can be concluded that prevalence of azithromycin resistance is substantial in China and consequently that the macrolides should not be used as a treatment option for early or incubating syphilis in China.

Topics: Adult; Anti-Bacterial Agents; Azithromycin; China; Cross-Sectional Studies; Drug Resistance, Bacterial; Humans; Male; Prevalence; Syphilis; Treponema pallidum

This study aimed to reassess rates of syphilis azithromycin resistance in Dublin. Of the 104 samples, 36 (34.6%) were positive for Treponema pallidum DNA by polymerase chain reaction. Thirty samples were analyzed for A2058G mutation, 29 samples sequenced. Of the 29 samples, 27 (93.1%) had the mutation. Azithromycin cannot be recommended for the treatment of syphilis in Dublin.

Topics: Adult; Anti-Bacterial Agents; Azithromycin; DNA, Bacterial; Drug Resistance, Bacterial; Female; Humans; Ireland; Male; Middle Aged; Mutation; RNA, Ribosomal, 23S; Syphilis; Treponema pallidum; Young Adult

The 23S rRNA A2058G point mutation in Treponema pallidum is associated with macrolide antibiotic treatment failure. Its prevalence and potential association with a molecular subtype within the United States are unknown.. During 2007 to 2009, 11 clinics across the United States sent samples from genital ulcers to the Centers for Disease Control and Prevention. Molecular techniques were used to identify T. pallidum DNA sequences, the A2058G mutation, and subtype of T. pallidum. Accompanying epidemiologic information was abstracted from medical records.. A total of 141 samples with T. pallidum were collected from individuals whose median age was 33 years (range, 13-68 years): 118 were male (69% reported as men having sex with men [MSM]). The A2058G mutation was carried in 75 samples (53%) with T. pallidum, with samples from MSM (versus women and other men) more likely carrying the A2058G mutation (65/82 samples versus 8/57 samples; prevalence ratio, 5.7; 95% confidence interval, 2.9-10.8). Of 98 strain-typed samples, 61 (62%) were the 14d9 subtype of T. pallidum, which was also associated with samples with T. pallidum from MSM (prevalence ratio, 3.5; 95% confidence interval, 1.9-6.5). However, among T. pallidum from MSM, the A2058G mutation was not associated with the 14d9 subtype.. The A2058G mutation and 14d9 subtype of T. pallidum were present throughout the United States. Both were more commonly found in T. pallidum from MSM compared with women or other men but were not associated with each other. Treating syphilis with azithromycin should be done cautiously and only when treatment with penicillin or doxycycline is not feasible.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Azithromycin; DNA, Bacterial; Drug Resistance, Bacterial; Female; Humans; Male; Middle Aged; Molecular Typing; Penicillin G Benzathine; Point Mutation; Prevalence; RNA, Ribosomal, 23S; Syphilis; Treponema pallidum; United States; Young Adult

Topics: Anti-Bacterial Agents; Azithromycin; Female; Humans; Male; Penicillin G Benzathine; Syphilis; Treponema pallidum

Although azithromycin promised to be a safe and effective single-dose oral treatment of early syphilis, azithromycin treatment failure has been documented and is associated with mutations in the 23S rDNA of corresponding Treponema pallidum strains. The prevalence of strains harboring these mutations varies throughout the United States and the world. We examined T. pallidum strains circulating in Seattle, Washington, from 2001 to 2010 to determine the prevalence of 2 mutations associated with macrolide resistance and to determine whether these mutations were associated with certain T. pallidum strain types.. Subjects were enrolled in a separate ongoing study of cerebrospinal fluid abnormalities in patients with syphilis. T. pallidum DNA purified from blood and T. pallidum strains isolated from blood or cerebrospinal fluid were analyzed for two 23S rDNA mutations and for the molecular targets used in an enhanced molecular stain typing system.. Nine molecular strain types of T. pallidum were identified in Seattle from 2001 to 2010. Both macrolide resistance mutations were identified in Seattle strains, and the prevalence of resistant T. pallidum exceeded 80% in 2005 and increased through 2010. Resistance mutations were associated with discrete molecular strain types of T. pallidum.. Macrolide-resistant T. pallidum strains are highly prevalent in Seattle, and each mutation is associated with discrete strain types. Macrolides should not be considered for treatment of syphilis in regions where prevalence of the mutations is high. Combining the resistance mutations with molecular strain typing permits a finer analysis of the epidemiology of syphilis in a community.

Topics: Azithromycin; Bacterial Typing Techniques; Drug Resistance, Bacterial; Female; Humans; Macrolides; Male; Molecular Epidemiology; Molecular Typing; Point Mutation; Prevalence; Syphilis; Treponema pallidum; Washington

There are several important unanswered key questions in the management of adult syphilis. A systematic literature review was conducted and tables of evidence were constructed to answer these important questions. A single dose of 2.4 million units of benzathine penicillin G remains the drug of choice for managing early syphilis. Enhanced antibiotic therapy has not been shown to improve treatment outcomes, regardless of human immunodeficiency virus (HIV) status. Although additional data on the efficacy of azithromycin in treating early syphilis have emerged, reported increases in the prevalence of a mutation associated with azithromycin resistance precludes a recommendation for its routine use. Cerebrospinal fluid (CSF) examination should be performed in all persons with serologic evidence of syphilis infection and neurologic symptoms. In those persons with early syphilis who do not achieve a ≥ 4-fold serologic decline in their rapid plasma reagin (RPR) titers 6-12 months after adequate therapy and those with late latent infection who do not achieve a similar decline within 12-24 months, CSF examination should be considered. Among HIV-infected persons, CSF examination among all those with asymptomatic late latent syphilis is not recommended owing to lack of evidence that demonstrates clinical benefit. HIV-infected persons with syphilis of any stages whose RPR titers are ≥ 1:32 and/or whose CD4 cell counts are <350 cells/mm(3) may be at increased risk for asymptomatic neurosyphilis. If CSF pleocytosis is evident at initial CSF examination, these examinations should be repeated every 6 months until the cell count is normal. Several important questions regarding the management of syphilis remain unanswered and should be a priority for future research.

Topics: Adult; Anti-Bacterial Agents; Azithromycin; CD4 Lymphocyte Count; Cerebrospinal Fluid; Drug Resistance, Bacterial; HIV Infections; Humans; Leukocytosis; Penicillin G Benzathine; Practice Guidelines as Topic; Serologic Tests; Syphilis; Treatment Outcome

Resurgence of syphilis in Canada and worldwide requires laboratories to update their methods for molecular epidemiology investigation and surveillance. This study utilizes polymerase chain reaction diagnostic tests for syphilis, identifies macrolide resistance, and uses a molecular typing system to characterize Treponema pallidum clinical strains causing syphilis in Alberta and Northwest Territories, Canada.. In total 449 specimens including genital swabs, whole blood, sera, and cerebrospinal fluid were obtained from 374 patients with suspect syphilis in Alberta and Northwest Territories. Molecular subtyping was based on genetic characterization of treponemal repeat genes, arp and tpr. Detection of macrolide resistance was accomplished by identification of the 23S rRNA gene mutation associated with the resistance pattern.. Forty-nine specimens obtained from 43 patients were found to be positive for T. pallidum DNA using bmp, tpp47 and polA polymerase chain reaction assays. Four molecular subtypes were identified, with one type, 14d, accounting for 70% of all cases and 83% of typeable strains. Seven patients (16%) were found to be infected by macrolide-resistant strains, of which 6 were men who have sex with men and 1 whose infection was acquired in China.. A single molecular type of T. pallidum, characterized as 14d, caused the majority of the syphilis cases identified in this study. A more discriminatory typing method would be required to determine if these strains are clonal. Treatment of infectious syphilis with macrolide antibiotics should be restricted to patient populations where resistance is rare and clinical and serological follow up of patients is possible.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Alberta; Anti-Bacterial Agents; Azithromycin; Bacterial Typing Techniques; Child; Child, Preschool; DNA, Bacterial; Drug Resistance, Bacterial; Female; Humans; Infant; Infant, Newborn; Macrolides; Male; Microbial Sensitivity Tests; Middle Aged; Molecular Epidemiology; Molecular Typing; Northwest Territories; Polymerase Chain Reaction; Syphilis; Treponema pallidum; Young Adult

We describe the molecular epidemiology of syphilis in San Francisco (SF) using Treponema pallidum specimens obtained from patients examined at the SF municipal sexually transmitted diseases clinic during 2004-2007. Of 69 specimens, 52 (75%) were subtype 14d9. Single subtype predominance might reflect a closely linked sexual network in SF.

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Drug Resistance, Bacterial; Female; Humans; Male; Middle Aged; Molecular Epidemiology; San Francisco; Syphilis; Treponema pallidum

Azithromycin has been used to treat primary and secondary syphilis and as prophylaxis for sexual partners. We evaluated syphilis treatment failure in patients who received azithromycin therapy.. Patients who did not respond to azithromycin therapy were referred to Shanghai Skin Disease and sexually transmitted disease hospital. Treatment failure was defined as follows: (1) persistent ulcers or cutaneous or mucosal lesions 1 month after therapy; or (2) detection of spirochetes in dark-field microscopy examination of a lesion at least 1 week after treatment; or (3) failure of rapid plasma reagin titers to decrease 4-fold at 3 months after treatment.. A total of 132 patients with primary and secondary syphilis who failed azithromycin therapy were referred to our hospital between January 2001 and October 2008. Of 132 patients, 42 (31.8%) had primary syphilis and 90 (68.2%) had secondary syphilis. Twenty-six patients with primary syphilis developed multiple lesions or secondary syphilis, or persistent ulcers despite using azithromycin. The skin or mucosal lesions did not resolve in 37 patients with secondary syphilis after azithromycin treatment. Ten patients had a positive dark-field examination for Treponema pallidum (T. pallidum) after treatment. The serum rapid plasma reagin titers studied in all cases had failed to decrease 4-fold at 3 months after therapy. The doses of azithromycin used for treatment ranged from 4 to 30 g.. The failure of azithromycin to cure a substantial number of patients with primary and secondary syphilis in Shanghai suggests that azithromycin has limited therapeutic value in this setting.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Azithromycin; China; Drug Resistance, Bacterial; Female; Humans; Male; Middle Aged; Mutation; Polymerase Chain Reaction; RNA, Ribosomal, 23S; Sequence Analysis, DNA; Syphilis; Treatment Failure; Treponema pallidum; Young Adult

To investigate the contribution of a real-time PCR assay for the detection of Treponema pallidum in various biological specimens with the secondary objective of comparing its value according to HIV status.. Prospective cohort of incident syphilis cases from three Swiss hospitals (Geneva and Bern University Hospitals, Outpatient Clinic for Dermatology of Triemli, Zurich) diagnosed between January 2006 and September 2008. A case-control study was nested into the cohort. Biological specimens (blood, lesion swab or urine) were taken at diagnosis (as clinical information) and analysed by real-time PCR using the T pallidum 47 kDa gene.. 126 specimens were collected from 74 patients with primary (n = 26), secondary (n = 40) and latent (n = 8) syphilis. Among primary syphilis, sensitivity was 80% in lesion swabs, 28% in whole blood, 55% in serum and 29% in urine, whereas among secondary syphilis, it was 20%, 36%, 47% and 44%, respectively. Among secondary syphilis, plasma and cerebrospinal fluid were also tested and provided a sensitivity of 100% and 50%, respectively. The global sensitivity of T pallidum by PCR (irrespective of the compartment tested) was 65% during primary, 53% during secondary and null during latent syphilis. No difference regarding serology or PCR results was observed among HIV-infected patients. Specificity was 100%.. Syphilis PCR provides better sensitivity in lesion swabs from primary syphilis and displays only moderate sensitivity in blood from primary and secondary syphilis. HIV status did not modify the internal validity of PCR for the diagnosis of primary or secondary syphilis.

Topics: Adult; Anti-Bacterial Agents; Azithromycin; DNA, Bacterial; Drug Resistance, Bacterial; Epidemiologic Methods; Female; HIV Seropositivity; Humans; Male; Polymerase Chain Reaction; Pregnancy; Sequence Analysis, RNA; Syphilis; Syphilis Serodiagnosis; Treponema pallidum; Unsafe Sex

Although detection of Treponema pallidum DNA in whole-blood specimens of syphilis patients has been reported, it is uncertain at what stage of the disease such specimens are most suitable for the molecular diagnosis of syphilis. Also, few studies have directly compared the different gene targets for routine laboratory diagnostic usage in PCR assays. We examined 87 specimens from 68 patients attending two urban sexually transmitted disease clinics in Alberta, Canada. PCR was used to amplify the T. pallidum tpp47, bmp, and polA genes as well as a specific region of the 23S rRNA gene linked to macrolide antibiotic susceptibility. In primary syphilis cases, PCR was positive exclusively (75% sensitivity rate) in ulcerative swabs but not in blood specimens, while in secondary syphilis cases, 50% of the blood specimens were positive by PCR. Four out of 14 (28.6%) of our PCR-positive syphilis cases were found to be caused by an azithromycin-resistant strain(s). Our results confirmed that swabs from primary ulcers are the specimens of choice for laboratory diagnostic purposes. However, further research is required to determine what specimen(s) would be most appropriate for molecular investigation of syphilis in secondary and latent syphilis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Alberta; Anti-Bacterial Agents; Azithromycin; Blood; Child; Child, Preschool; DNA, Bacterial; Drug Resistance, Bacterial; Female; Humans; Infant; Infant, Newborn; Male; Middle Aged; Polymerase Chain Reaction; Sensitivity and Specificity; Syphilis; Treponema pallidum; Ulcer; Young Adult

Topics: Anti-Bacterial Agents; Azithromycin; Bacterial Proteins; Drug Resistance, Bacterial; Humans; Madagascar; Mutation; Syphilis; Treponema pallidum

We report on a patient from a London clinic, (a Jamaican heterosexual man known to have herpes) who has donovanosis and syphilis in a single genital ulcer. The case highlights the importance of careful clinical examination of genital ulcers.

Topics: Azithromycin; Doxycycline; Granuloma Inguinale; Herpes Simplex; Humans; Male; Middle Aged; Penile Diseases; Syphilis

To evaluate the efficacy of azithromycin in preventing congenital syphilis.. Five pregnant women with syphilis who were allergic to penicillin were given azithromycin, 1 g daily orally or intravenously, in different hospitals. The duration of the therapy ranged from 1 day to 10 days. A second course of therapy was provided at 28 weeks gestation. The babies were given a physical examination and blood test for serum rapid plasma reagin test (RPR), treponema pallidum hemagglutination test (TPHA), and fluorescent treponemal antibody adsorption test (FTA-ABS-19-sIgM) within three months after birth.. Five infants born to these mothers developed skin rashes. Four of the infants had hepatomegaly and one showed osteochondritis. The tests RPR, TPHA, and FTA-ABS-19-sIgM were positive. The RPR titers varied from 1:64 to 1:256 and the babies were diagnosed with congenital syphilis. They were successfully treated with penicillin.. Successful therapy for syphilis during pregnancy demands maternal care as well as prevention or cure of congenital infection. The failure of azithromycin in preventing congenital syphilis in our report suggests that azithromycin should not be recommended as an alternative in treating syphilitic pregnant women or fetal syphilis.

Topics: Administration, Oral; Adult; Anti-Bacterial Agents; Azithromycin; China; Drug Administration Schedule; Female; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Infusions, Intravenous; Male; Pregnancy; Pregnancy Complications, Infectious; Prenatal Care; Syphilis; Syphilis Serodiagnosis; Syphilis, Congenital

There are recent reports of a sustained increase in the incidence of syphilis around the world, including in the Australian cities of Sydney and Melbourne.

Topics: Australia; Azithromycin; Disease Outbreaks; Family Practice; Female; Global Health; Humans; Incidence; Male; Mass Screening; Queensland; Risk Factors; Syphilis

The incidence of syphilis has been increasing in the United States since reaching a nadir in 2000. Several clinical trials have demonstrated that treatment with oral azithromycin may be useful for syphilis control. After reports of azithromycin treatment failures in San Francisco, we investigated the clinical and epidemiologic characteristics of patients with syphilis due to azithromycin-resistant Treponema pallidum infection.. We reviewed city-wide case reports and conducted molecular screening for patients seen at the San Francisco metropolitan STD clinic (San Francisco City Clinic) to identify patients who did not respond to azithromycin treatment for syphilis or who were infected with azithromycin-resistant T. pallidum. We conducted an epidemiologic investigation and retrospective case-control study to identify risk factors for acquiring syphilis due to azithromycin-resistant T. pallidum.. From January 2000 through December 2004, molecular screening of 124 samples identified 46 azithromycin-resistant T. pallidum isolates and 72 wild-type T. pallidum isolates. Six instances of treatment failure were identified through record review. In total, we identified 52 case patients (one of whom had 2 episodes) and 72 control patients. All case patients were male and either gay or bisexual, and 31% (16 of 52) were infected with human immunodeficiency virus. Investigation of patient-partner links and a retrospective case-control study did not reveal a sexual network or demographic differences between cases and controls. However, 7 case patients had recently used azithromycin, compared with 1 control patient. Surveillance data demonstrated that azithromycin-resistant T. pallidum prevalence increased from 0% in 2000 to 56% in 2004 among syphilis cases observed at the San Francisco City Clinic.. 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.

Topics: Anti-Bacterial Agents; Azithromycin; Case-Control Studies; Contact Tracing; Drug Resistance, Bacterial; Humans; Male; Risk Factors; San Francisco; Syphilis; Treatment Failure

Topics: Administration, Oral; Anti-Bacterial Agents; Azithromycin; Drug Resistance, Bacterial; Female; Humans; Pregnancy; Pregnancy Complications, Infectious; Syphilis; Syphilis, Congenital; Treponema pallidum

Topics: Anti-Bacterial Agents; Azithromycin; Drug Resistance, Bacterial; Humans; Penicillin G Benzathine; Syphilis; Treatment Failure; Treponema pallidum

Topics: Anti-Bacterial Agents; Azithromycin; Brazil; Developing Countries; Drug Costs; Drug Resistance, Bacterial; Humans; Penicillin G Benzathine; Syphilis; Treponema pallidum

Topics: Anti-Bacterial Agents; Azithromycin; HIV Infections; Humans; Male; Secondary Prevention; Syphilis; Treponema pallidum

In 2000, syphilis mass treatment using oral azithromycin was delivered to at-risk British Columbians during a sex trade-related outbreak. The initiative included education, counselling and referral. This cross-sectional, observational study examines knowledge, attitudes and self-reported behaviour after one year among mass treatment participants compared with eligible non-participants. Participants self-reported positive changes: reduction in sexual partners overall (P=0.001) and for sex workers (P<0.01), decrease in unprotected oral sex (P=0.03), knowledge of asymptomatic syphilis (P=0.02), positive attitudes to mass treatment (P=0.02) and to the street nurses (P=0.01). Increased awareness was associated with increased condom use for vaginal sex overall (P=0.02) and for sex workers (P=0.03) and increased condom use for oral sex (P=0.05). There was no difference in syphilis incidence. Syphilis outbreak interventions that include education, support and referral can result in long-term positive behaviour changes.

Topics: Adolescent; Adult; Azithromycin; Cross-Sectional Studies; Female; Follow-Up Studies; Health Education; Health Knowledge, Attitudes, Practice; Humans; Male; Middle Aged; Risk-Taking; Sexual Behavior; Syphilis

Topics: Anti-Bacterial Agents; Azithromycin; Drug Resistance, Bacterial; Global Health; Homosexuality, Male; Humans; Incidence; Macrolides; Male; Penicillin G Benzathine; Syphilis; Treponema pallidum

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Ceftriaxone; Controlled Clinical Trials as Topic; Doxycycline; Female; Follow-Up Studies; Humans; Male; Neurosyphilis; Penicillin G; Penicillin G Benzathine; Penicillin G Procaine; Penicillins; Practice Guidelines as Topic; Pregnancy; Probenecid; Prospective Studies; Syphilis; Syphilis Serodiagnosis; Time Factors; Uricosuric Agents

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.

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Drug Resistance, Bacterial; Humans; Male; San Francisco; Syphilis; Treatment Failure; Treponema pallidum

Topics: Anti-Bacterial Agents; Azithromycin; Humans; Mass Screening; Syphilis; Syphilis Serodiagnosis; Syphilis, Congenital; Treponema pallidum

Topics: Adult; Animals; Anti-Bacterial Agents; Azithromycin; Drug Resistance, Bacterial; Genes, Bacterial; Genes, rRNA; HIV Infections; Humans; Ireland; Macrolides; Male; Mutation; Penicillin G Benzathine; Rabbits; Syphilis; Treatment Failure; Treponema pallidum; United States

From mid 1997 to end of 1999, there was a sexually-transmitted infectious syphilis outbreak mainly in heterosexual people in British Columbia, Canada, that was concentrated in Vancouver. The rate across the province increased from less than 0.5 to 3.4 per 100000, and the rate in Vancouver reached 12.9 per 100000. We aimed to eliminate the syphillis outbreak by treating people at risk of infection. In 2000, a targeted mass treatment programme provided azithromycin (1.8 g orally) to 4384 at-risk residents in this city. After the programme, syphilis frequency fell significantly for 6 months (p=0.016), but rose again in 2001. Results from curve fitting analyses showed that the number of cases in 2001 (177) was higher than expected (0.0001

Topics: Adolescent; Adult; Anti-Bacterial Agents; Azithromycin; British Columbia; Disease Outbreaks; Female; Humans; Male; Preventive Health Services; Syphilis; Urban Population

After a precipitous increase in the incidence of infectious syphilis in the United States during the late 1980s and early 1990s, the rate of new cases has declined so dramatically that a program initiated by the Centers for Disease Control and Prevention (CDC) to achieve elimination appears to stand a good chance of succeeding. In the fall of 2000, the CDC convened an advisory group to examine the recent medical literature regarding syphilis treatment. Published literature in peer-reviewed journals and abstracts from relevant scientific meetings that have appeared since the last STD Treatment Guidelines meeting in 1997 were reviewed. Where applicable, unpublished data from studies in progress were also discussed. Expert opinion was sought. Through all these efforts, it appears that the azalide azithromycin and the third-generation cephalosporin ceftriaxone should find more definitive roles in the treatment of syphilis. None will eclipse the continued primacy of penicillin for this purpose.

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Ceftriaxone; Databases, Factual; Ethylenediamines; HIV Infections; Humans; Incidence; Neurosyphilis; Outcome Assessment, Health Care; Penicillins; Syphilis; United States

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Directly Observed Therapy; Female; Humans; Ill-Housed Persons; Mental Disorders; Syphilis

This study describes the epidemiology and ethnography of an outbreak of infectious syphilis in Vancouver, British Columbia. Between 1996 and 1999, British Columbias's rate of infectious syphilis rose from 0.5 to 3.4 per 100,000, with a dense concentration of cases among sex trade workers, their clients, and street-involved people in the downtown eastside area of Vancouver. Sexual networks were imported cases with secondary spread (dyads and triads), large densely connected dendritic networks of sex trade workers and clients, or occasional starburst networks among gay men. Only 232 of 429 partners were documented as having been treated (54% of those named, or 0.9 per case). The geographical and demographic concentration of this outbreak led to consideration of a programme of focused mass treatment with single dose azithromycin.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Azithromycin; British Columbia; Contact Tracing; Disease Outbreaks; Female; Homosexuality; Humans; Indians, North American; Male; Sex Work; Syphilis

We present a case of a 39-year-old woman with a vulval lesion, which macroscopically looked consistent with a fungating squamous cell carcinoma of the vulva. However, further investigations demonstrated a less common cause for this presentation.

Topics: Adult; Azithromycin; Carcinoma, Squamous Cell; Diagnosis, Differential; Female; Granuloma Inguinale; Humans; Penicillin G Benzathine; Syphilis; Vulvar Diseases

Topics: Adult; Anti-Bacterial Agents; Azithromycin; British Columbia; Disease Outbreaks; Female; Humans; Male; Middle Aged; Syphilis

Topics: Adult; Anti-Bacterial Agents; Anti-Infective Agents; Antitrichomonal Agents; Azithromycin; Chlamydia Infections; Chlamydia trachomatis; Condylomata Acuminata; Doxycycline; Epididymitis; Female; Humans; Infectious Disease Transmission, Vertical; Male; Metronidazole; Papillomaviridae; Papillomavirus Infections; Pelvic Inflammatory Disease; Penicillins; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Complications, Parasitic; Scabies; Sexually Transmitted Diseases; Sexually Transmitted Diseases, Bacterial; Sexually Transmitted Diseases, Viral; Syphilis; Tumor Virus Infections; Urethritis

The syphilis epidemic, that fueled the HIV epidemic in the late 1980s, has subsided. Syphilis is now at the lowest levels ever recorded. This reduction has led to optimism that the disease may be eliminated in the next ten years. Elimination is defined as one case per million people. The United States has the highest syphilis rates in the industrialized world. The syphilis cases are concentrated in fewer than 40 counties, mostly in the South, offering a unique opportunity to eliminate syphilis from the United States. Federal and private organizations are funding programs that seek to reduce the risk of HIV transmission while eliminating syphilis. The syphilis elimination strategies include developing a national task force, involving the community, funding demonstration projects, enhancing surveillance systems, deploying technical assistance, and targeting prevention and research programs.

Topics: Anti-Bacterial Agents; Azithromycin; Female; HIV Infections; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; National Health Programs; Population Surveillance; Pregnancy; Pregnancy Complications, Infectious; Prevalence; Syphilis; United States

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Granuloma Inguinale; Humans; Penicillin G Benzathine; Syphilis

The efficacy of oral azithromycin (500 mg daily for 10 days or 500 mg on alternate days for 11 days) in 100 patients with seropositive syphilis was studied. Clinical manifestations regressed more rapidly in azithromycin-treated patients compared with patients who received erythromycin or penicillin, and there was also a more rapid reduction in serum antibody levels. In 90.3% of patients, the complete resolution of classic serological tests was observed within 4 months of completion of the azithromycin treatment. The immobilization (TPI) test and absorbed fluorescent treponema antibody tests became negative 12 months after treatment in 40% of patients. After 4 years of follow-up, no symptoms of neurosyphilis or syphilitic changes of visceral organs were observed.

Topics: Administration, Oral; Adolescent; Adult; Anti-Bacterial Agents; Azithromycin; Drug Administration Schedule; Erythromycin; Female; Follow-Up Studies; Humans; Male; Middle Aged; Penicillins; Remission Induction; Syphilis; Time Factors; Treatment Outcome

Topics: Adolescent; Adult; Anti-Bacterial Agents; Azithromycin; Drug Evaluation; Drug Tolerance; Female; Humans; Male; Middle Aged; Penicillin G Benzathine; Penicillins; Recurrence; Remission Induction; Syphilis; Time Factors

Topics: Adult; Azithromycin; Female; Granuloma Inguinale; Humans; Male; Syphilis; Urethritis

Azithromycin was shown to be as effective as standard benzathine penicillin and erythromycin in the therapy of active syphilis in the rabbit model. Following production of primary chancres by intradermal inoculation of 10(6) Treponema pallidum, groups of six rabbits were treated with benzathine penicillin (200,000 units im weekly for two weeks), erythromycin base (30 mg/kg/day orally four times daily for 15 days) or azithromycin (30 mg/kg/day given orally once or twice daily for 15 days); one group was untreated. Daily darkfield (DF) microscopic examinations of chancre aspirates were conducted to identify motile organisms. Although all treated animals became DF negative prior to completion of therapy, the median time to DF negativity was longer in animals given azithromycin once daily, compared with animals receiving benzathine penicillin (P less than 0.01); no difference was seen in comparison with animals receiving erythromycin. Untreated animals remained DF positive for greater than 15 days. The mean maximum lesion diameters for all treated animals were similar and were significantly smaller than in untreated rabbits; fewer lesions ulcerated in treated than in untreated animals. Subsequent dose-ranging studies indicated that administration of lower doses of azithromycin (15 mg/kg/day given orally either once or twice daily, or 7.5 mg/kg/day given once daily) was as effective as benzathine penicillin for therapy of active syphilis in this model, though the median time to darkfield negativity was significantly longer in the azithromycin-treated animals (P less than 0.01). Persistent infection was demonstrable in lymph nodes of untreated animals, but no evidence of virulent T. pallidum was found three months following transfer of tissue from any animal treated with penicillin, erythromycin, or azithromycin.

Topics: Animals; Azithromycin; Erythromycin; Male; Penicillin G Benzathine; Rabbits; Syphilis; Treponema pallidum