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Treatment of chancroid by clavulanic acid with amoxycillin in patients with beta-lactamase-positive Haemophilus ducreyi infection.

Multiresistant strains of Haemophilus ducreyi, the aetiological agent of chancroid, are prevalent in Nairobi, Kenya, where tetracyclines and sulphonamides are no longer very effective in the treatment of chancroid. The following regimens (given three times daily for seven days) were compared in a double-blind randomised trial--amoxycillin 500 mg, amoxycillin 500 mg and clavulanic acid 125 mg, and amoxycillin 500 mg and clavulanic acid 250 mg. 68 of 100 ulcers were culture-positive for H. ducreyi. All strains of H. ducreyi produced beta-lactamase. At day 7 none of the amoxycillin-treated patients had responded clinically or bacteriologically, whereas all but 2 of 56 patients treated with an amoxycillin/clavulanic-acid regimen had responded clinically and H. ducreyi had been eradicated from their ulcers. The combination of amoxycillin-clavulanic acid appears to be very effective for the treatment of chancroid. The results of this study accord with H. ducreyi as the primary pathogen of chancroid.

Amoxicillin↗

Chancroid epidemiology in New Orleans men.

Epidemiologic, clinical, and microbiologic data were collected from 299 men with nonsyphilitic genital ulcer disease. One hundred eighteen (39%) were culture-positive for Haemophilus ducreyi, 57 (19%) were culture-positive for herpes simplex virus, and 124 (41%) were culture-negative. Patients with chancroid were significantly more likely than those with genital herpes to have been frequent users of alcohol (44% vs. 23%, P = .006). They were also more likely recently to have used cocaine (25% vs. 9%, P = .013), had sex with a prostitute (17% vs. 5%, P = .035), traded drugs for sex (16% vs. 2%, P = .005), and had a sex partner who used drugs (38% vs. 13%, P = .001). Culture-negative patients were similar to chancroid patients with respect to most epidemiologic risk factors. Despite the epidemiologic similarities, the clinical features of culture-negative ulcers resembled those of culture-proven herpes ulcers more closely than they did those of culture-proven chancroid ulcers. These data establish a link between chancroid in the United States and the use of crack cocaine.

Adolescent↗

Treatment of chancroid with erythromycin.

Chancroid is a sexually transmitted disease that is not often recognized in the United States. It has traditionally been treated with sulfonamides and/or tetracyclines. Recently, 14 active-duty U. S. Army personnel who acquired chancroid in the Far East were seen at the Madigan Army Medical Center, Tacoma, Wash. All of the organisms were isolated from clinical material on solid media without the use of a blood-clot tube. Because of dissatisfaction with conventional treatment and the demonstration of in vitro sensitivity of the organism to erythromycin, seven of the last eight patients were treated with erythromycin. All patients treated with erythromycin had rapid and favorable responses and none suffered recurrences. The results of this study led to three conclusions: chancroid is a relatively common disease in the Far East, the causative organism can be isolated by most clinical microbiology laboratories with proper technique, and erythromycin is an effective drug in the treatment of chancroid.

Adult↗

Single dose azithromycin for the treatment of chancroid: a randomized comparison with erythromycin.

BACKGROUND AND OBJECTIVES: Chancroid is endemic in sub-Saharan Africa and enhances the sexual transmission of the human immunodeficiency virus Type 1 (HIV-1). Azithromycin is an orally absorbed macrolide antibiotic that is active against Haemophilus ducreyi, the causative agent of chancroid, and has pharmacokinetic properties that are suitable for single dosing. STUDY DESIGN: In a randomized single-blinded study of 127 men presenting to a referral STD clinic with culture proven chancroid, we compared the efficacy of azithromycin, administered as a single 1 g dose, with erythromycin 500 mg given 4 times daily for 7 days. RESULTS: Cure rates were 89% (73 of 82) in the azithromycin group and 91% (41 of 45) in the erythromycin group. A failure to respond to treatment was associated with HIV-1 seropositivity and a lack of circumcision. Both regimens were well tolerated. CONCLUSIONS: Azithromycin, given as a single 1 g oral dose, is an effective treatment for chancroid in men, and offers major prescribing advantages over erythromycin.

AIDS-Related Opportunistic Infections↗

A comparative study of therapeutic response of patients with clinical chancroid to ciprofloxacin, erythromycin, and cotrimoxazole.

BACKGROUND AND OBJECTIVES: Cotrimoxazole has traditionally been used as first drug for treatment of chancroid in India. With reports of increasing resistance to the drug, this study was conducted to compare treatment response of clinical chancroid between ciprofloxacin, 500 mg twice daily for 3 days, erythromycin, 500 mg four times daily for 7 days, and double-strength cotrimoxazole (trimethoprim 160 mg + sulfamethoxazole 800 mg), twice daily for 7 days. STUDY DESIGN: Forty-six patients with a clinical diagnosis of chancroid were randomly divided into 3 groups. Sixteen patients received ciprofloxacin, whereas 15 each received erythromycin and cotrimoxazole. Patients were seen on day 7, 14, and if needed day 21. Clinical response was noted in terms of cure, improvement, or failure. RESULTS: Excellent response was observed to both ciprofloxacin and erythromycin therapy with cure rates of 93.7% and 93.3%, respectively. Improvement was observed in 6.7% cases in both groups. There were no failures with either ciprofloxacin or erythromycin. Poor response to cotrimoxazole therapy was observed with 53.3% cure rates and a high failure rate of 46.7%. CONCLUSION: Ciprofloxacin and erythromycin are equally effective in chancroid. Ciprofloxacin is better in terms of dosage schedule, duration of treatment, and low cost. Cotrimoxazole should be discontinued as drug of choice because of high failure rates.

Adult↗

In vitro stimulation of peripheral blood mononuclear cells (PBMC) from HIV- and HIV+ chancroid patients by Haemophilus ducreyi antigens.

The cellular immune responses to fractionated Haemophilus ducreyi antigens, coated on latex beads, were assessed in patients with chancroid and in controls, using an in vitro lymphocyte proliferation assay. Several fractions of H. ducreyi antigen revealed stimulating activity. However, only the molecular size ranges 91-78 kD, 59-29 kD, and 25-21 kD induced proliferation that may be specifically related to H. ducreyi infection. Lymphocytes from four HIV- patients, successfully treated for chancroid, were not stimulated by H. ducreyi antigen. In general, lymphocytes from HIV+ chancroid patients were less responsive to H. ducreyi antigen compared with those from HIV- chancroid patients. However, two HIV-infected patients showed exceptionally strong responses to high molecular weight fractions. To our knowledge this is the first report demonstrating that H. ducreyi contains specific T cell-stimulating antigens. Based on this work, further identification and purification of the T cell antigens is feasible.

Antigens, Bacterial↗

Sulphaphenazole, streptomycin and sulphaphenazole combination, trimethoprim, and erythromycin in the treatment of chancroid.

One hundred and thirty six patients with chancroid were treated with four different treatment regimens; (A) Sulphaphenazole 1 g 12 hourly by mouth x 10 days (B) Inj streptomycin 1 g intramuscularly daily with sulphaphenazole 1 g 12 hourly orally x 10 days; (C) trimethoprim 200 mg 12 hourly by mouth x 7-10 days, and (D) erythromycin 500 mg 6 hourly orally x 7-10 days. Cure rates of 9% with sulphaphenazole alone, 48% with streptomycin and sulphaphenazole combination, 93% with trimethoprim and 100% with erythromycin were obtained. Sulphaphenazole alone or in combination with streptomycin were thus inferior in the treatment of chancroid. There is need for modification of treatment regimens recommended for chancroid in the textbooks of dermatology and venereology. Trimethoprim can be recommended as first line of treatment for chancroid in developing countries like India where resistance to trimethoprim is uncommon and erythromycin is suggested as a second line of therapy because by that time syphilis can be easily ruled out.

Administration, Oral↗

Cultural diagnosis of chancroid.

Culture of Haemophilus ducreyi remains the definitive way to diagnose chancroid. Since its discovery in 1889, cultural isolation of this fastidious organism has been a challenge for clinicians and microbiologists. A recent chancroid epidemic in our locale prompted a review of available culture techniques. Despite the development of various selective solid media in the last 20 years, cultural diagnosis of chancroid remains problematic. Many pitfalls may complicate this procedure, such as concomitant syphilis, syphilis, or herpes progenitalis simulating chancroid, strain differences in nutritional requirements, improper handling and delayed inoculation of clinical specimens, use of suboptimal growth conditions, and vancomycin hydrochloride-sensitive organisms. Highest cultural yield will be obtained by using enriched gonococcal agar base and enriched Müeller-Hinton agar in a biplate fashion. As most isolates are sensitive to vancomycin, incorporation of this antibiotic should be routine. However, screening for vancomycin-sensitive organisms is indicated when negative cultures are repeatedly obtained from clinically typical cases originating from the same community. Development of immunodiagnostic and DNA probe tests is underway.

Bacteriological Techniques↗

Isolation of anaerobes from clinical chancroid associated with fluctuant bubo in men.

Microbial flora especially anaerobes were studied in 67 patients with genital ulcers due to chancroid (diagnosed clinically) and 53 controls with genital ulcers due to other causes. The aerobic flora was similar in patients of chancroid with or without associated bubo and in controls. Anaerobes were however, isolated with higher frequency from chancroid ulcers associated with fluctuant bubo compared to those without bubo (P less than 0.01) and with non-fluctuant bubo (P less than 0.05). Anaerobic bacteria like Bacteroides melaninogenicus, B. fragilis and anaerobic cocci may play a role in the perpetuation of genital ulcers and development of bubo in chancroid.

Adolescent↗

Chancroid detected by polymerase chain reaction--Jackson, Mississippi, 1994-1995.

Chancroid is a sexually transmitted disease (STD) caused by infection with Haemophilus ducreyi and is characterized by genital ulceration. Chancroid is underreported in the United States (1), reflecting, in part, difficulties in diagnosis because of clinical similarities between chancroid and other ulcerative STDs. In addition, laboratory confirmation by culture is 53%-84% sensitive and often is unavailable in clinical settings (2). In September 1994, clinicians at the District V STD clinic of the Mississippi State Department of Health (MSDH) in Jackson reported examining patients with genital ulcers characteristic of chancroid but lacked capacity to confirm the diagnosis. To determine the cause of the ulcers, MSDH, in conjunction with CDC, conducted an investigation of all patients with genital ulcers examined at the Jackson STD clinic during October 20, 1994-February 1, 1995. This report summarizes the findings of the investigation.

Adolescent↗

Localization of Haemophilus ducreyi in naturally acquired chancroidal ulcers.

Haemophilus ducreyi causes the sexually transmitted genital ulcer disease chancroid. In human inoculation experiments, bacteria colocalize with neutrophils and macrophages but remain extracellular. The organism also colocalizes with collagen and fibrin but not with keratinocytes, fibroblasts, laminin, or fibronectin. These relationships are established by 48 h postinoculation and persist through the pustular stage of disease. To extend these observations to the ulcerative stage of disease, and to compare results in the human model with those of natural disease, we obtained biopsies from patients with naturally acquired chancroid. All ulcers were culture positive for H. ducreyi and histologically very similar to pustules from the human model. Staining with H. ducreyi-specific monoclonal antibodies demonstrated H. ducreyi within 5 biopsies. The organism was chiefly found within the granulocytic infiltrate of the ulcer. Dual staining for H. ducreyi and eukaryotic tissue components showed that H. ducreyi colocalized with neutrophils and fibrin at the ulcerative stage of disease. No bacteria were associated with keratinocytes, fibroblasts, or collagen. Overall, these findings are consistent with results from the human model. This is the first reported study to localize bacteria specifically identified as H. ducreyi within naturally acquired chancroid.

Chancroid↗

Epidemiology of chancroid and Haemophilus ducreyi in Nairobi, Kenya.

Of 300 men in Nairobi, Kenya, with culture-proven chancroid, 57% had acquired infection from prostitutes. The majority of infections were acquired in the city of Nairobi. All 10 female source contacts examined had genital ulcers. 13 of 29 female secondary contacts were culture-positive for Haemophilus ducreyi and 10 of these infected women had clinical chancroid. Of 122 prostitutes from the middle and lower social strata, 12 had genital ulcers, 5 of which were culture-positive for H ducreyi, and a further 5 had symptomless genital carriage of H ducreyi. Prostitutes are a major reservoir of H ducreyi in Nairobi. No evidence of transmission of H ducreyi by women without clinical chancroid was detected.

Chancroid↗

Chancroid: clinical variants and other findings from an epidemic in Dallas County, 1986-1987.

Dallas, Texas, recently joined the ranks of cities in the United States that have been plagued by outbreaks of chancroid. This article describes an epidemic of chancroid in Dallas County and presents cases that illustrate the spectrum of clinical illness that this venereal disease can produce. Also reviewed are the current diagnostic and therapeutic methods of managing patients with chancroid.

Adult↗

Chancroid, primary syphilis, genital herpes, and lymphogranuloma venereum in Antananarivo, Madagascar.

Ulcer material from consecutive patients attending clinics in Antananarivo, Madagascar, was tested using multiplex polymerase chain reaction (M-PCR) to detect Treponema pallidum, Haemophilus ducreyi, and herpes simplex virus. Sera were tested for syphilis and for IgG and IgM antibodies to Chlamydia trachomatis by microimmunofluorescence testing (MIF). By M-PCR, 33% of 196 patients had chancroid, 29% had syphilitic ulcers, and 10% had genital herpes; 32% of the ulcer specimens were M-PCR negative. Compared with M-PCR, syphilis serology was 72% sensitive and 83% specific. The sensitivity of clinical diagnosis of syphilis, chancroid, and genital herpes was 93%, 53%, and 0% and specificity was 20%, 52%, and 99%, respectively. Less schooling was associated with increased prevalence of syphilitic ulcers (P=.001). Sixteen patients (8%) were clinically diagnosed with lymphogranuloma venereum (LGV); 1 plausible case of LGV was found by MIF. In Madagascar, primary care of genital ulcers should include syndromic treatment for syphilis and chancroid.

Adult↗

Epidemiologic, clinical, laboratory, and therapeutic features of an urban outbreak of chancroid in North America.

An epidemic of 135 cases of chancroid occurred in Winnipeg, Manitoba, Canada, from July 1975 to September 1977. Probable contributing factors for development of chancroid lesions included male sex, lack of circumcision, and genital trauma. A previous history of venereal disease, sexual contact with a person from a bar or hotel in the core city area, unemployment, alcoholism, American Indian or Métis (mixed American Indian and Caucasian) race, and unstable domestic relationships were often accessory findings for infected patients. The tracing and treatment of lesion-free contacts of patients with chancroid may have contributed to the restriction of the outbreak to the core city area. Nineteen isolations of Hemophilus ducreyi were made, most by the use of a new selective medium. Treatment with a short course of penicillin antibiotics was ineffective for 10 of 16 patients, whereas an adequate course of sulfonamide or tetracycline antibiotics, combined when necessary with drainage of fluctuant inguinal abscesses, was effective therapy for most patients.

Adolescent↗

Short-course and single-dose antimicrobial therapy for chancroid in Kenya: studies with rifampin alone and in combination with trimethoprim.

Tetracyclines and sulfonamides are no longer effective for the treatment of chancroid in many parts of the world. Rifampin and trimethoprim both possess in vitro activity against Haemophilus ducreyi, the causative agent of chancroid. In a randomized, controlled study, 22 patients with H. ducreyi-positive genital ulcers received 600 mg of rifampin once daily for three days, and 32 patients received 600 mg of rifampin plus 160 mg of trimethoprim once daily for three days. Both regimens rapidly eradicated H. ducreyi from ulcers, with subsequent healing of ulcers and buboes. Two relapses of ulcers and one therapeutic failure were observed in the rifampin-trimethoprim group, whereas no relapses or failures were noted in the rifampin group. In addition, all of 16 H. ducreyi-negative ulcers responded rapidly to treatment with either regimen. In an uncontrolled, open study, 22 H. ducreyi-positive ulcers were treated with a single dose of rifampin (600 mg) plus trimethoprim (160 mg). Ulcers and buboes resolved by day 14 in all but one patient. Thus, these short-course and single-dose regimens are effective against chancroid.

Adolescent↗

Antimicrobial therapy of chancroid: effectiveness of erythromycin.

The emergence of Haemophilus ducreyi resistant to multiple antibiotics has limited the effectiveness of sulfonamides and tetracycline for the therapy of chancroid. A randomized, double-blind study compared 10-day courses of erythromycin base (500 mg) and rosaramicin (250 mg) each given four times daily for the treatment of men with chancroid in Nairobi, Kenya. Of 99 evaluable patients, 84 were positive for H ducreyi. H ducreyi-positive genital ulcers in men treated with either drug resolved with mean +/- SD healing times of 10.8 +/- 5.1 days for erythromycin and 10.7 +/- 5.5 for rosaramicin. There were no clinical or bacteriologic failures with either agent. Fifteen men with H ducreyi-negative genital ulcers for whom no other etiology could be determined also responded rapidly to treatment with either agent. Both erythromycin and rosaramicin are highly effective in the treatment of chancroid.

Adolescent↗

An outbreak of chancroid in Orange County, California: descriptive epidemiology and disease-control measures.

From May 1981 through February 1983, greater than 1,700 patients were examined for genital ulcers at the Orange County Special Diseases Clinic in Santa Ana, California. Of these patients, 923 had either confirmed chancroid or genital ulcers of unknown etiology. Haemophilus ducreyi was recovered from lesions or inguinal buboes of 271 patients. In the previous year, no cases of chancroid were reported in this community. Men accounted for 266 (98%) of the confirmed cases; 95% of the men were Hispanic, and at least 53% had had sexual contact with a prostitute. All five culture-positive women were prostitutes. Antimicrobial sensitivity testing showed resistance to both sulfamethoxazole and tetracycline but susceptibility to erythromycin and to the combination trimethoprim-sulfamethoxazole. Treatment of patients with chancroid, their sex partners, and temporarily incarcerated prostitutes contributed to the successful control of this outbreak.

California↗