ro13-9904 and Chancroid

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Azithromycin; Ceftriaxone; Cephalosporins; Chancroid; Ciprofloxacin; Erythromycin; HIV Infections; Humans

Chancroid, an ulcerous disease of the genitalia caused by Haemophilus ducreyi, occurs rarely but regularly in Germany. Exact diagnosis is based on the clinical features and a direct smear, and in particular on cultivation of the organism, showing its unique macromorphological characteristics. The sensitivity of cultivation has increased due to the development of selective media for primary isolation. Resistance problems during the last decade meant that a change to new therapeutic strategies was unavoidable. The work presented here includes a case report and a review of the recent literature, it illustrates modern methods of diagnosis and treatment of Haemophilus ducreyi infections 100 years after the first description of the organism.

Topics: Administration, Topical; Bacteriological Techniques; Balanitis; Ceftriaxone; Chancroid; Drug Therapy, Combination; Haemophilus ducreyi; Humans; Injections, Intramuscular; Male; Microbial Sensitivity Tests; Middle Aged; Tetracycline

Since the treatment of chancroid was reviewed in 1982, the results of subsequent treatment trials have offered the clinician additional therapeutic choices as well as shorter courses of therapy. Erythromycin (500 mg four times a day for seven days) provides consistently effective treatment for cases acquired throughout the world, although erythromycin-resistant strains have been isolated in Singapore. Sulfamethoxazole and trimethoprim (800 mg/160 mg orally twice a day for seven days), ceftriaxone (250 mg intramuscularly one time), and amoxicillin/clavulanic acid (500 mg/125 mg orally three times a day for seven days) are also efficacious. There is, however, significant geographic variability in the susceptibility of Haemophilus ducreyi to sulfamethoxazole and trimethoprim, suggesting this combination may become increasingly less effective, and a lack of in-depth experience in the treatment of chancroid with ceftriaxone and amoxicillin/clavulanic acid.

Topics: Amoxicillin; Anti-Bacterial Agents; Ceftriaxone; Chancroid; Clavulanic Acid; Clavulanic Acids; Clinical Trials as Topic; Drug Combinations; Erythromycin; Haemophilus ducreyi; Humans; Penicillin Resistance; Rifampin; Sulfonamides; Trimethoprim

A review is given of the selection and rational of optimal treatment regimens for patients with sexually transmitted pathogens, e.g. in cases of gonorrhea, chlamydial infections, chancroid, syphilis, pelvic inflammatory diseases and ophthalmia neonatorum. The scientific basis for the selection of a beta-lactam agent is discussed, including dose, MIC, the critical serum level and maintenance interval, and the duration of therapy. Except in the case of penicillinase-producing Neiserria gonorrhoeae, penicillin remained until recently the most effective agent available against many sexually transmitted diseases. However, ceftriaxone, a new third-generation cephalosporin, has been shown to have a long half-life (8 h) and excellent in vitro efficacy against Neiserria gonorrhoeae (including penicillinase-producing strains) and Haemophilis ducreyi. In view of its exceptional clinical efficacy against both gonorrhea and chancroid, clinical studies of its efficacy against other sexually transmitted diseases appear warranted.

Topics: Anti-Bacterial Agents; Cefotaxime; Ceftriaxone; Cephalosporins; Chancroid; Chlamydia Infections; Female; Gonorrhea; Humans; Infant, Newborn; Male; Ophthalmia Neonatorum; Pelvic Inflammatory Disease; Penicillins; Sexually Transmitted Diseases; Syphilis; Time Factors; Urethritis

We conducted a randomized, unblinded, prospective study designed to determine the efficacy of single-dose azithromycin for the treatment of chancroid. Men and women 16 years of age and older who had darkfield-negative genital ulcers that were clinically suspected to be caused by Haemophilus ducreyi and who attended urban sexually transmitted disease clinics or presented to hospital emergency departments were enrolled in the study. Patients were randomized to receive 250 mg of ceftriaxone im or 1 g of azithromycin orally, both given as a single dose. They were followed for up to 23 days after treatment. For 65 patients, cultures were positive for H. ducreyi; there were 68 patients whose cultures were negative for both H. ducreyi and herpes simplex virus and who had no evidence of syphilis. All 133 patients returned for at least one follow-up visit. At the time of the last follow-up visit, all 32 patients whose cultures were positive for H. ducreyi and who were treated with azithromycin were clinically cured. In all 33 culture-positive cases in which ceftriaxone was used, there was either clinical improvement or cure at the time of the patient's last follow-up visit. In addition, azithromycin and ceftriaxone were equally effective in healing ulcers for which cultures were negative. We conclude that a single 1-g oral dose of azithromycin is as effective as a 250-mg im dose of ceftriaxone for the treatment of chancroid.

Topics: Administration, Oral; Adolescent; Adult; Anti-Bacterial Agents; Azithromycin; Ceftriaxone; Cephalosporins; Chancroid; Female; Genital Diseases, Female; Genital Diseases, Male; Humans; Injections, Intramuscular; Male; Prospective Studies; Treatment Outcome; Ulcer

The antimicrobial susceptibility of Haemophilus ducreyi varies according to the geographic region. Increased resistance to trimethoprim and/or sulfamethoxazole led the Centers for Disease Control to recommend 250 mg ceftriaxone as a single intramuscular dose for chancroid. Intravenous or muscular routes of administration result in equivalent bioavailability. To avoid side effects such as syringe abscess and lidocaine intolerance, we prefer intravenous ceftriaxone therapy. The efficacy of this regimen is reported in 3 cases of chancroid. The intravenous administration of 1 g of ceftriaxone in chancroid seems to be as effective as administration by the intramuscular route, but it may lower the risk of syringe abscess, lidocaine intolerance and the emergence of resistant strains.

Topics: Adult; Azure Stains; Ceftriaxone; Chancroid; Drug Resistance, Microbial; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Tomography, X-Ray Computed

Men with genital ulcers that were culture positive for Haemophilus ducreyi were treated with intramuscular ceftriaxone and randomized to three different dose regimens. All but 1 of 50 men treated with 1 g of intramuscular ceftriaxone were cured. Similarly, 0.5 and 0.25 g cured 43 of 44 men and 37 of 38 men, respectively. A single dose of 250 mg of intramuscular ceftriaxone is an effective treatment for chancroid.

Topics: Adult; Ceftriaxone; Chancroid; Drug Administration Schedule; Humans; Injections, Intramuscular; Male; Random Allocation

Since the treatment of chancroid was reviewed in 1982, the results of subsequent treatment trials have offered the clinician additional therapeutic choices as well as shorter courses of therapy. Erythromycin (500 mg four times a day for seven days) provides consistently effective treatment for cases acquired throughout the world, although erythromycin-resistant strains have been isolated in Singapore. Sulfamethoxazole and trimethoprim (800 mg/160 mg orally twice a day for seven days), ceftriaxone (250 mg intramuscularly one time), and amoxicillin/clavulanic acid (500 mg/125 mg orally three times a day for seven days) are also efficacious. There is, however, significant geographic variability in the susceptibility of Haemophilus ducreyi to sulfamethoxazole and trimethoprim, suggesting this combination may become increasingly less effective, and a lack of in-depth experience in the treatment of chancroid with ceftriaxone and amoxicillin/clavulanic acid.

Topics: Amoxicillin; Anti-Bacterial Agents; Ceftriaxone; Chancroid; Clavulanic Acid; Clavulanic Acids; Clinical Trials as Topic; Drug Combinations; Erythromycin; Haemophilus ducreyi; Humans; Penicillin Resistance; Rifampin; Sulfonamides; Trimethoprim

Topics: Anti-Bacterial Agents; Azithromycin; Breast Feeding; Ceftriaxone; Chancroid; Ciprofloxacin; Contraindications; Erythromycin; Female; Genital Diseases, Female; Genital Diseases, Male; Haemophilus ducreyi; Humans; Male; Pregnancy; Pregnancy Complications, Infectious; Ulcer

We report the sensitivity and specificity of physical examination findings for diagnosing primary syphilis, chancroid, and genital herpes. The physical features of genital ulcers in 446 men were measured in accordance with a quantitative scale. Two hundred-twenty of these men had an established, single microbiological diagnosis. Forty-five (20%) had primary syphilis, 118 (54%) had chancroid, and 57 (26%) had genital herpes. There was considerable overlap in the clinical presentation of these three diseases. The classic clinical sign complex attributed to primary syphilis (painless, indurated, clean-based ulcers) was only 31% sensitive but 98% specific. The classic presentation of a chancroid ulcer (a deep, undermined, purulent ulcer) was only 34% sensitive but 94% specific. The classic description of genital herpes ulcers (multiple, shallow, tender ulcers) was only 35% sensitive but 94% specific. Inguinal lymph node findings did not contribute significantly to clinical diagnostic accuracy. These data indicate that the clinical diagnosis of genital ulcer disease can be made with reasonable certainty only for a minority of patients. Rapid, sensitive, and specific diagnostic tests for syphilis, chancroid, and genital herpes are needed.

Topics: Adolescent; Adult; Aged; Ceftriaxone; Cephalosporins; Chancre; Chancroid; Genitalia, Male; Herpes Genitalis; Humans; Male; Middle Aged; Penicillin G; Penicillins; Predictive Value of Tests; Sensitivity and Specificity; Sexually Transmitted Diseases; Syphilis; Ulcer

Haemophilus ducreyi was isolated from 59 (52%) of 113 men with a clinical diagnosis of chancroid. The following MIC50 (MIC90) values for H. ducreyi were obtained: erythromycin 0.14 (0.5) micrograms/ml, trimethoprim 0.25 (8.0) micrograms/ml, ceftriaxone 0.009 (0.14) micrograms/ml, and ciprofloxacin 0.007 (0.04) micrograms/ml. These data indicate that all isolates appear to be fully susceptible to erythromycin and the other antimicrobial agents tested, although ciprofloxacin was the most effective antibiotic.

Topics: Anti-Bacterial Agents; Ceftriaxone; Chancroid; Ciprofloxacin; Erythromycin; Haemophilus ducreyi; Humans; Male; Microbial Sensitivity Tests; Trimethoprim

We determined the in vitro susceptibilities of 54 isolates of Haemophilus ducreyi from Thailand (29 isolates) and San Francisco (25 isolates) to penicillin G, tetracycline, amoxicillin-clavulanic acid, ceftriaxone, cefixime, erythromycin, azithromycin, ciprofloxacin, ofloxacin, and trimethoprim-sulfamethoxazole. Isolates were susceptible to < or = 0.25 microgram of ceftriaxone per ml, < or less 0.5 microgram of cefixime per ml, < or = 0.125 microgram of ciprofloxacin per ml, and < or = 0.06 microgram of ofloxacin per ml. Erythromycin was active against all isolates (MIC for 90% of isolates tested, 0.25 microgram/ml), as was azithromycin (MIC, < or = micrograms/ml). In contrast, all but one isolate were resistant to > or = 8.0 micrograms of tetracycline per ml, 11.1% of the isolates were resistant to and 40.9% of the isolates were resistant to trimethoprim-sulfamethoxazole (MIC, > or = 4/76 microgram/ml.)

Topics: Anti-Bacterial Agents; Ceftriaxone; Chancroid; Erythromycin; Haemophilus ducreyi; Humans; Microbial Sensitivity Tests; Thailand; United States

Ceftriaxone in a dose of 250 mg given intramuscularly is currently recommended for the treatment of chancroid. Among 133 men in Nairobi, Kenya, with culture-proven chancroid, who were treated with ceftriaxone, treatment failed in 35%. Poor outcome was associated with human immunodeficiency virus type 1 seropositivity. Thus, treatment recommendations for chancroid should be reevaluated.

Topics: Adult; Ceftriaxone; Chancroid; Follow-Up Studies; HIV Seropositivity; HIV-1; Humans; Kenya; Male; Treatment Outcome

A recent (and continuing) epidemic of chancroid in Houston has included morphologic variation in the disease, including so-called dwarf, classic, giant, transient, follicular, phagedenic, and pseudogranuloma inguinale types. Most cases were clearly acquired by unprotected sexual encounters with local prostitutes. The strain of Haemophilus ducreyi responsible for this outbreak was relatively easily cultured on routine media; unexpected sensitivity of this strain to vancomycin rendered the recommended "selective" growth medium much less optimal for isolation. Therapeutic success uniformly followed the use of intramuscular ceftriaxone sodium; one case responded to oral ciprofloxacin hydrochloride.

Topics: Administration, Oral; Adult; Black People; Ceftriaxone; Chancroid; Disease Outbreaks; Drug Administration Schedule; Drug Therapy, Combination; Erythromycin; Haemophilus ducreyi; Humans; Injections, Intramuscular; Male; Middle Aged; Retrospective Studies; Texas

From June to November 1987 an outbreak of chancroid occurred in Winnipeg, the first in more than 10 years; 14 people (9 men, 5 women) were involved. Nine of the cases were confirmed through culture. A control strategy was implemented in November 1987 that included presumptive treatment of genital ulcer disease with single-dose antimicrobial therapy, intensive tracing of contacts and treatment of asymptomatic sexual contacts. The origin of the outbreak was not determined, and an epidemiologic link between all the patients could not be demonstrated. The isolates were found to contain the same plasmid; this suggested that a single clone of Haemophilus ducreyi was responsible for the outbreak.

Topics: Adult; Aged; Canada; Ceftriaxone; Chancroid; Disease Outbreaks; Female; Haemophilus ducreyi; Humans; Male; Manitoba; Middle Aged; Plasmids; Sex Work; Trimethoprim, Sulfamethoxazole Drug Combination

The treatment of non-complicated or complicated (by a bubo) chancroid with 1 single i.m. injection of 250 mg ceftriaxone gave excellent results. Treatment is simple and economical. This is particularly profitable in countries where chancroid is endemic.

Topics: Adolescent; Adult; Ceftriaxone; Chancroid; Humans; Male

A single dose of ceftriaxone (250 mg) administered intramuscularly was compared with trimethoprim-sulfamethoxazole (TMP-SMZ; 160/800 mg) administered orally twice daily for seven days or with a single dose of TMP-SMZ (640/3,200 mg) administered orally for the treatment of chancroid in men in Thailand. Haemophilus ducreyi was isolated from 79 (48%) of 164 men with a clinical diagnosis of chancroid. For men with ulcers that were culture positive for H. ducreyi, rates of cure were 100% in 25 men treated with ceftriaxone, 87% in 23 men given TMP-SMZ for seven days, and 55% in 31 men given TMP-SMZ in a single dose. For men with ulcers that were culture negative for H. ducreyi, rates of cure were 100% in 29 men treated with ceftriaxone, 66% in 32 men given TMP-SMZ for seven days, and 63% in 24 men given TMP-SMZ in a single dose. The MIC50 of the three antibiotics for 94 isolates of H. ducreyi were as follows: 0.004 micrograms/ml for ceftriaxone, 16 micrograms/ml for trimethoprim, and greater than 512 micrograms/ml for sulfamethoxazole. Our study indicates that ceftriaxone in a single dose of 250 mg is effective, but that TMP-SMZ, even when given in a standard seven-day regimen, is not effective treatment for chancroid in Thailand.

Topics: Administration, Oral; Adult; Ceftriaxone; Chancroid; Drug Combinations; Drug Resistance, Microbial; Haemophilus ducreyi; Humans; Injections, Intramuscular; Male; Sulfamethoxazole; Thailand; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination