Clinical Efficacy of Cefixime for the Treatment of Early Syphilis.
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ABSTRACT:
SUBMITTER: Stafylis C
PROVIDER: S-EPMC8423500 | biostudies-literature | 2021 Sep
REPOSITORIES: biostudies-literature
Publications
Clinical Efficacy of Cefixime for the Treatment of Early Syphilis.
Stafylis Chrysovalantis C Keith Kori K Mehta Shivani S Tellalian David D Burian Pamela P Millner Carl C Klausner Jeffrey D JD
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20210901 5
Safe and efficacious alternative treatment options for syphilis are necessary. This randomized, 2-arm, noncomparative pilot study evaluated the efficacy of oral cefixime 400 mg in achieving a ≥4-fold rapid plasma reagin titer decrease by 3 or 6 months after treatment. The proportion of cefixime arm participants treated successfully was 87% (95% confidence interval, 69%-100%; 13/15). Clinical Trials Registration. NCT03752112. ...[more]
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Project description:BackgroundSyphilis rates have been increasing both in the USA and internationally with incidence higher among men-who-have-sex-with-men and people living with human immunodeficiency virus (HIV) infection. Currently, benzathine penicillin is the recommended treatment for syphilis in all patients. Global shortages and cost increases in benzathine penicillin call for alternative treatment options. This study evaluates the efficacy of oral cefixime for the treatment of early syphilis.MethodsWe are conducting a randomized, multisite, open-label, non-comparative clinical trial in Los Angeles and Oakland, CA. Eligible participants are ≥ 18 years old, with primary, secondary, or early latent syphilis (rapid plasma reagin [RPR] titer ≥ 1:8). Patients with HIV infection must have a viral load ≤ 200 copies/mL and CD4+ T cell count ≥ 350 cells/μL during the past 6 months. Participants are randomized to receive either 2.4 M IU benzathine penicillin G intramuscularly once or cefixime 400 mg orally twice a day for 10 days. Participants return at 3, 6, and 12 months post-treatment for follow-up RPR serological testing. The primary outcome is the proportion of participants who achieve ≥ 4-fold RPR titer decrease at 3 or 6 months post-treatment.DiscussionClinical trials evaluating the efficacy of alternative antibiotics to penicillin are urgently needed.Trial registrationClinicaltrials.gov NCT03660488 . Registered on 4 September 2018.
| S-EPMC7725115 | biostudies-literature
Project description:BackgroundSyphilis is a sexually and vertically transmitted infection caused by the bacteria Treponema pallidum for which there are few proven alternatives to penicillin for treatment. For pregnant women infected with syphilis, penicillin is the only WHO-recommended treatment that will treat the mother and cross the placenta to treat the unborn infant and prevent congenital syphilis. Recent shortages, national level stockouts as well as other barriers to penicillin use call for the urgent identification of alternative therapies to treat pregnant women infected with syphilis.MethodsThis prospective, randomized, non-comparative trial will enroll non-pregnant women aged 18 years and older with active syphilis, defined as a positive rapid treponemal and a positive non-treponemal RPR test with titer ≥1:16. Women will be a, domized in a 2:1 ratio to receive the oral third generation cephalosporin cefixime at a dose of 400 mg two times per day for 10 days (n = 140) or benzathine penicillin G 2.4 million units intramuscularly based on the stage of syphilis infection (n = 70). RPR titers will be collected at enrolment, and at three, six, and nine months following treatment. Participants experiencing a 4-fold (2 titer) decline by 6 months will be considered as having an adequate or curative treatment response.DiscussionDemonstration of efficacy of cefixime in the treatment of active syphilis in this Phase 2 trial among non-pregnant women will inform a proposed randomized controlled trial to evaluate cefixime as an alternative treatment for pregnant women with active syphilis to evaluate prevention of congenital syphilis.Trial registrationTrial identifier: www.Clinicaltrials.gov, NCT03752112. Registration Date: November 22, 2018.
| S-EPMC7288542 | biostudies-literature
Project description:ImportanceSyphilis rates have been increasing in the US for the past decade. The incidence of the Jarisch-Herxheimer reaction (JHR) after penicillin treatment for early syphilis is reported to range from 8% to 56%.ObjectivesTo prospectively assess the incidence of JHR signs and symptoms among adults with early syphilis treated with benzathine penicillin G and to document factors associated with JHR and benzathine penicillin G treatment response outcomes.Design, setting, and participantsThe main study was designed as a phase 4 randomized clinical trial to compare the treatment efficacy of 1 vs 3 doses of benzathine penicillin G in adults with early syphilis, measured as serologic response at 6 months. A total of 249 adults with or without HIV were screened and enrolled between October 31, 2018, and March 3, 2020. Participants were screened and enrolled at 10 US study sites in the Sexually Transmitted Infections Clinical Trials Group. Statistical analysis for this secondary analysis took place between March 2023 and August 2024.InterventionParticipants received a first dose of benzathine penicillin G, 2.4 million units intramuscularly, at the enrollment visit. The JHR assessment window was day 1 to day 7 after the first dose of benzathine penicillin G.Main outcomes and measuresPrimary outcomes in this study were the incidence of symptoms consistent with JHR within 7 days after benzathine penicillin G treatment. Unelicited and elicited symptoms were assessed by participant self-report using a standardized checklist during contact made by a study clinician. Factors associated with JHR were collected at baseline, and serologic treatment response was assessed at 6 months. Posttreatment incident JHR symptoms were captured as safety outcomes for this trial. Analysis was performed on an intention-to-treat basis.ResultsOf 249 participants, the median age was 32 years (IQR, 27-41 years), 242 (97.2%) were men, and 153 (61.4%) were living with HIV. One or more JHR symptoms occurred in 59 participants (23.7%) treated for early syphilis, with a median symptom onset at 4.9 hours (IQR, 3.0-9.2 hours) and a median duration of 12.8 hours (IQR, 5.0-24.0 hours). Symptom onset was within 12 hours of treatment for 49 of 57 participants (86.0%). Among 59 symptomatic participants, myalgias (30 [50.8%]), chills (27 [45.8%]), weakness (23 [39.0%]), and feverishness (21 [35.6%]) were most common. In adjusted models, JHR was associated with secondary syphilis (adjusted odds ratio [AOR], 2.91 [95% CI, 1.51-5.61]) and the absence of HIV (AOR for living with HIV, 0.49 [95% CI, 0.26-0.94]). The proportion of participants with a serologic treatment response to benzathine penicillin G at 6 months was higher among participants with JHR (84.7% [50 of 59] vs 68.9% [131 of 190] without JHR).Conclusions and relevanceIn this prespecified secondary analysis of a randomized clinical trial of early syphilis treatment wtih benzathine penicillin G in adults, approximately 1 in 4 participants experienced short-lived JHR symptoms, which were associated with secondary syphilis stage, lack of HIV, and successful treatment outcomes at 6 months. These messages could be used in patient counseling.Trial registrationClinicalTrials.gov Identifier: NCT03637660.
| S-EPMC11826359 | biostudies-literature
Project description:ImportanceThe incidence of syphilis in the United States is increasing; it is estimated that more than 55,000 new infections will occur in 2014. Treatment regimens are controversial, especially in specific populations, and assessing treatment response based on serology remains a challenge.ObjectiveTo review evidence regarding penicillin and nonpenicillin regimens, implications of the "serofast state," and treatment of specific populations including those with neurosyphilis or human immunodeficiency virus (HIV) infection and pregnant women.Evidence reviewWe searched MEDLINE for English-language human treatment studies dating from January 1965 until July 2014. The American Heart Association classification system was used to rate quality of evidence.FindingsWe included 102 articles in our review, consisting of randomized trials, meta-analyses, and cohort studies. Case reports and small series were excluded unless they were the only studies providing evidence for a specific treatment strategy. We included 11 randomized trials. Evidence regarding penicillin and nonpenicillin regimens was reviewed from studies involving 11,102 patients. Data on the treatment of early syphilis support the use of a single intramuscular injection of 2.4 million U of benzathine penicillin G, with studies reporting 90% to 100% treatment success rates. The value of multiple-dose treatment of early syphilis is uncertain, especially in HIV-infected individuals. Less evidence is available regarding therapy for late and late latent syphilis. Following treatment, nontreponemal serologic titers should decline in a stable pattern, but a significant proportion of patients may remain seropositive (the "serofast state"). Serologic response to treatment should be evident by 6 months in early syphilis but is generally slower (12-24 months) for latent syphilis. Evidence defining treatment for HIV-infected persons and for pregnant women is limited, but available data support penicillin as first-line therapy.Conclusions and relevanceThe mainstay of syphilis treatment is parenteral penicillin G despite the relatively modest clinical trial data that support its use.
| S-EPMC6690208 | biostudies-literature
Project description:ObjectiveThis study aims to analyze the efficacy of anti-syphilis treatment and the impact of syphilis events on HIV virology and immunology in HIV/syphilis co-infected patients on long-term antiretroviral therapy (ART) and to investigate the incidence and factors of syphilis recurrence/re-infection/serofast state. The insights derived from this investigation can potentially guide strategies for preventing and managing syphilis and AIDS.MethodsA retrospective case-control study was conducted at the AIDS clinic of Peking Union Medical College Hospital from January 2003 to December 2022. The study involved 86 HIV/syphilis co-infected patients and 86 HIV mono-infected patients matched based on age, baseline CD4 + T cell counts, and viral load. We examined the clinical characteristics of HIV/syphilis co-infected patients, evaluated the efficacy of anti-syphilis treatment, and analyzed the dynamic changes in HIV virology and immunology. The Generalized Estimating Equations (GEE) model investigated the factors associated with HIV/syphilis co-infection and syphilis recurrence/reinfection/serofast state.ResultsSyphilis serofast state was observed in 11.6% (10/86) of HIV/syphilis co-infected patients after treatment, and 33.7% (29/86) had syphilis recurrence or re-infection. The overall effectiveness of syphilis treatment stood at 76.8% (63/82). Notably, the effectiveness of syphilis treatment displayed a significant correlation with baseline syphilis titers exceeding 1:128 (p = 0.003). Over the 10-year follow-up period on ART, the HLA-DR + CD8+/CD8 + % levels in the HIV/syphilis co-infected group were markedly higher than those in the HIV mono-infected group (p < 0.05). However, no significant differences were observed between the two groups regarding HIV viral load, CD4+ T cell counts, CD8+ T cell counts, CD4/CD8 ratio, and CD38 + CD8+/CD8 + % (p > 0.05). GEE analysis model revealed that elevated HLA-DR + CD8+/CD8 + % levels were associated with HIV/syphilis co-infection (OR = 1.026, 95% CI = 1.007-1.046; p = 0.007) and syphilis recurrence/reinfection/serofast state (OR = 1.036, 95% CI = 1.008-1.065; p = 0.012).ConclusionWhile HIV/syphilis co-infected patients typically receive adequate treatment, the incidence of syphilis recurrence and reinfection remain notably elevated. A heightened HLA-DR + CD8+/CD8+ % is a notable risk factor for HIV/syphilis co-infection and syphilis recurrence/reinfection/serofast state. Therefore, it is advisable to reinforce health education efforts and ensure regular follow-ups for people living with HIV undergoing ART to monitor syphilis infection or increased risk of syphilis infection.
| S-EPMC10823526 | biostudies-literature
Project description:To minimize the clinical burden associated with multiple sclerosis (MS), early control of focal and diffuse CNS disease activity is a treatment priority. A post hoc analysis was conducted to evaluate the onset of efficacy of fingolimod treatment in patients with relapsing MS. Data from patients who received fingolimod 0.5 mg or placebo during either of two 24-month, double-blind, randomized, parallel-group clinical trials (FREEDOMS and FREEDOMS II) were pooled for analysis. Efficacy outcomes were: time to first confirmed relapse; annualized relapse rate (ARR); proportions of patients free from T1 gadolinium-enhancing lesions or new/newly enlarged T2 lesions; percentage brain volume loss (BVL); and change in Multiple Sclerosis Functional Composite (MSFC) z-score from baseline to 6 months. An early benefit was seen with fingolimod (N = 783) vs. placebo (N = 773) for ARR at both 3 and 6 months (3 months, 0.32 vs. 0.52, p = 0.0015; 6 months, 0.21 vs. 0.45, p < 0.0001). Time to first relapse was also delayed with fingolimod vs. placebo from day 48 onwards. At 6 months, more patients in the fingolimod group than in the placebo group were free from new MRI activity (65.3 vs. 40.5%, p < 0.0001) and had less BVL (37.1% reduction vs. placebo, p < 0.001). MSFC z-score favored fingolimod over placebo at 6 months, with improvements noted in 9-Hole Peg Test and Paced Auditory Serial Addition Test scores. Improvements in outcomes related to relapses, MRI, disability, cognition, and BVL occurred within 6 months of treatment initiation with fingolimod.
| S-EPMC4751181 | biostudies-literature
Project description:In this article, we present a historical revision of syphilis treatment since the end of the XV century up until the current days. For centuries, it was understood that syphilis had been brought to Spain by Columbus after coming back from America. It became an epidemic soon after. Later on, it was spread all over Europe. The chronologic and geographic origin of this illness have been debated in recent years, however, there has been no agreement about it as yet. Mercury was the main used therapy for four and a half centuries, until the discovery of penicillin in 1943. This discovery changed the therapeutic approach to syphilis since then. Other remedies were used during this period. Guaiacum was one of them, but it was dismissed in the mid-sixteenth century. Iodides were also used, especially in the tertiary symptoms of the disease. The discovery of arsphenamine (Salvarsan) at the beginning of the XX century, used by itself at its onset and associated to mercury or bismuth later on, was a significant therapeutic contribution. Bismuth was in itself a great therapeutic asset. It displaced the use of mercury in an important way until 1943, when the appearance of penicillin became the treatment of choice.
| S-EPMC6254479 | biostudies-other
Project description:A 36-year old man with known HIV infection presented to an outpatient genitourinary service with jaundice, rash and sore throat. Investigations revealed marked biochemical abnormalities, including alkaline phosphatase and alanine transaminase >10 times the upper limit of normal. Liver ultrasound was normal, but stricturing and beading of the intrahepatic biliary tree was seen on magnetic resonance cholangiopancreatography (MRCP), similar to changes associated with sclerosing cholangitis. Serological syphilis antibodies were detected with a positive immunoglobulin M (IgM) and rapid plasma reagin of 1:128, in keeping with early infection. Liver biopsy showed large bile duct obstruction with portal oedema, bilirubinostasis and neutrophil polymorph infiltration around proliferating ductules; specific stains for spirochaetes were negative. Symptoms and biochemical markers improved rapidly after treatment for secondary syphilis with oral steroids and intramuscular benzathine penicillin. A repeat MRCP 18 months post syphilis treatment showed resolution. This case illustrates syphilis presenting as acute sclerosing cholangitis.
| S-EPMC5369580 | biostudies-other
Project description:OBJECTIVE:To assess the efficacy of gatifloxacin versus cefixime in the treatment of uncomplicated culture positive enteric fever. DESIGN:A randomized, open-label, active control trial with two parallel arms. SETTING:Emergency Room and Outpatient Clinics in Patan Hospital, Lagankhel, Lalitpur, Nepal. PARTICIPANTS:Patients with clinically diagnosed uncomplicated enteric fever meeting the inclusion criteria. INTERVENTIONS:Patients were allocated to receive one of two drugs, Gatifloxacin or Cefixime. The dosages used were Gatifloxacin 10 mg/kg, given once daily for 7 days, or Cefixime 20 mg/kg/day given in two divided doses for 7 days. OUTCOME MEASURES:The primary outcome measure was fever clearance time. The secondary outcome measure was overall treatment failure (acute treatment failure and relapse). RESULTS:Randomization was carried out in 390 patients before enrollment was suspended on the advice of the independent data safety monitoring board due to significant differences in both primary and secondary outcome measures in the two arms and the attainment of a priori defined endpoints. Median (95% confidence interval) fever clearance times were 92 hours (84-114 hours) for gatifloxacin recipients and 138 hours (105-164 hours) for cefixime-treated patients (Hazard Ratio[95%CI] = 2.171 [1.545-3.051], p<0.0001). 19 out of 70 (27%) patients who completed the 7 day trial had acute clinical failure in the cefixime group as compared to 1 out of 88 patients (1%) in gatifloxacin group(Odds Ratio [95%CI] = 0.031 [0.004 - 0.237], p<0.001). Overall treatment failure patients (relapsed patients plus acute treatment failure patients plus death) numbered 29. They were determined to be (95% confidence interval) 37.6 % (27.14%-50.2%) in the cefixime group and 3.5% (2.2%-11.5%) in the gatifloxacin group (HR[95%CI] = 0.084 [0.025-0.280], p<0.0001). There was one death in the cefixime group. CONCLUSIONS:Based on this study, gatifloxacin is a better treatment for uncomplicated enteric fever as compared to cefixime. TRIAL REGISTRATION:Current Controlled Trials ISRCTN75784880.
| S-EPMC1891439 | biostudies-literature
Project description:BackgroundParenteral penicillin is the first-line regimen for treating syphilis, but unsuitable for some patients due to penicillin allergy and lacking health resources. Unfortunately, the efficacy of penicillin alternatives remains poorly understood. This study aimed to assess the efficacy of ceftriaxone and doxycycline/tetracycline in treating early syphilis relative to that of penicillin, and thereby to determine which antibiotic is a better replacement for penicillin.MethodBy searching literature from PubMed, Cochrane Central Register of Controlled Trials, Embase, the Web of Science, and ClinicalTrials.gov and systematically screening relevant studies, eligible randomized controlled trials (RCTs) and observational studies on treatments with penicillin, doxycycline/tetracycline, and ceftriaxone for early syphilis were identified and combined in this systematic review. Estimated risk ratios (RRs) and 95% confidence intervals (CIs) were utilized to compare their serological response and treatment failure rates. At 12-month follow up, serological response rates were compared by a direct meta-analysis and network meta-analysis (NMA), while treatment failure rates were compared with a direct meta-analysis.ResultThree RCTs and seven cohort studies were included in this research. The results of NMA demonstrated that no significant differences existed in serological response rate at 12-month follow-up between any two of the three treatments (doxycycline/tetracycline vs. penicillin RR = 1.01, 95%CI 0.89-1.14; ceftriaxone vs. penicillin RR = 1.00, 95%CI 0.89-1.13; ceftriaxone vs. doxycycline/tetracycline RR = 0.99, 95%CI 0.96-1.03), which was consistent with the outcomes of the direct meta-analysis. In addition, the direct meta-analysis indicated that, at 12-month follow-up, penicillin and ceftriaxone treatment groups had similar treatment failure rates (RR = 0.92, 95%CI 0.12-6.93), while treatment failure rate was significantly lower among penicillin recipients than among doxycycline/tetracycline recipients (RR = 0.58, 95%CI 0.38-0.89).ConclusionCeftriaxone is as effective as penicillin in treating early syphilis with regard to serological response and treatment failure rate. Compared with doxycycline/tetracycline, ceftriaxone appears to be a better choice as the substitution of penicillin.
| S-EPMC5489196 | biostudies-literature