trimethoprim--sulfamethoxazole-drug-combination and Gonorrhea

The reasons for combining trimethoprim (TMP) with sulfonamides (SUL) are still mainly theoretical but are supported by results from experimental infections and treatment of specific pathogens in humans, such as Branhamella catarrhalis, Neisseria gonorrhoeae, Brucella, Nocardia asteroides and perhaps Bordetella pertussis and Chlamydia trachomatis. Addition of SUL to TMP confers a therapeutic advantage also in patients with complicated urinary tract infection but probably not in young women with acute cystitis. Conditions that may enable TMP-SUL synergy in vivo can be expected to occur only in occasional cases of infection due to staphylococci, streptococci, Haemophilus or enteric bacteria. This fact together with ethical problems and availability of alternative therapies make further evaluations of the clinical significance of the SUL component of TMP-SUL very difficult. Although the use of TMP alone has shown promise in exacerbations of chronic bronchitis the role of the SUL component in TMP-SUL treatment of infections outside the urinary tract remains to be defined in comparative clinical trials.

Topics: Aged; Anti-Bacterial Agents; Brucellosis; Clinical Trials as Topic; Drug Combinations; Drug Synergism; Female; Gonorrhea; Humans; Kinetics; Lymphogranuloma Venereum; Male; Microbial Sensitivity Tests; Nocardia Infections; Sulfamethoxazole; Tissue Distribution; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

Gonorrhea continues to maintain its position as the most common reportable infectious disease in the United States. Penicillin is still the antibiotic of choice for the treatment of uncomplicated gonococcal urethritis in most of the United States, but the increasing incidence of penicillinase-producing Neisseria gonorrhoeae (PPNG) in many areas of the world necessitates a reconsideration of standard therapy. In addition to penicillin resistance, the gonococcus is also developing resistance to spectinomycin and tetracycline, which further complicates the choice of therapy.

Topics: Amoxicillin; Ampicillin; Bacteriological Techniques; Cephalosporins; Culture Media; Drug Combinations; Erythromycin; Female; Follow-Up Studies; Gonorrhea; Humans; Male; Neisseria gonorrhoeae; Penicillin G; Penicillin Resistance; Penicillinase; Spectinomycin; Sulfamethoxazole; Tetracyclines; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Urethritis

The reasons for combining trimethoprim (TMP) with sulfonamides (SUL) are still mainly theoretical but are supported by results from experimental infections and treatment of specific pathogens in humans, such as Branhamella catarrhalis, Neisseria gonorrhoeae, Brucella, Nocardia asteroides and perhaps Bordetella pertussis and Chlamydia trachomatis. Addition of SUL to TMP confers a therapeutic advantage also in patients with complicated urinary tract infection but probably not in young women with acute cystitis. Conditions that may enable TMP-SUL synergy in vivo can be expected to occur only in occasional cases of infection due to staphylococci, streptococci, Haemophilus or enteric bacteria. This fact together with ethical problems and availability of alternative therapies make further evaluations of the clinical significance of the SUL component of TMP-SUL very difficult. Although the use of TMP alone has shown promise in exacerbations of chronic bronchitis the role of the SUL component in TMP-SUL treatment of infections outside the urinary tract remains to be defined in comparative clinical trials.

Topics: Aged; Anti-Bacterial Agents; Brucellosis; Clinical Trials as Topic; Drug Combinations; Drug Synergism; Female; Gonorrhea; Humans; Kinetics; Lymphogranuloma Venereum; Male; Microbial Sensitivity Tests; Nocardia Infections; Sulfamethoxazole; Tissue Distribution; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

We evaluated the effect of treatment of gonorrhea on simultaneous Chlamydia trachomatis infection by randomly assigning 293 heterosexual men and 246 heterosexual women with gonorrhea to receive one of the following treatment regimens: (1) 4.8 million units of aqueous procaine penicillin plus 1 g of probenecid, (2) nine tablets of trimethoprim-sulfamethoxazole daily for three days, or (3) 500 mg of tetracycline four times a day for five days. Among the men, gonococcal infection was cured in 99 per cent given penicillin plus probenecid, 96 per cent given trimethoprim-sulfamethoxazole, and 98 per cent given tetracycline. Among the women, only 90 per cent given tetracycline were cured, in contrast to 97 per cent given penicillin plus probenecid and 99 per cent given trimethoprim-sulfamethoxazole. Chlamydial infection, present in 15 per cent of the men and 26 per cent of the women, was cured in 30 of 32 patients given trimethoprim-sulfamethoxazole and 27 of 29 given tetracycline, but in only 10 of 23 given penicillin plus probenecid. Among chlamydia-positive patients, postgonococcal urethritis in men and cervicitis in women occurred more often in patients given penicillin plus probenecid. Salpingitis developed in 6 of 20 women given penicillin plus probenecid, but in only 1 of 26 given trimethoprim-sulfamethoxazole and in none of 24 given tetracycline. We conclude that the use of penicillin plus probenecid alone for gonorrhea in heterosexual patients carries an unacceptably high risk of postgonococcal chlamydial morbidity. Trimethoprim-sulfamethoxazole and tetracycline were highly effective against both pathogens and were well tolerated in men, but both drugs caused frequent side effects in women. The failure of tetracycline to cure gonorrhea in 10 per cent of women argues against its use alone; treatment with penicillin followed by tetracycline has been recommended for further trial.

Topics: Adolescent; Clinical Trials as Topic; Drug Administration Schedule; Drug Combinations; Female; Gonorrhea; Humans; Lymphogranuloma Venereum; Male; Pelvic Inflammatory Disease; Penicillin G Procaine; Probenecid; Random Allocation; Sex Factors; Sulfamethoxazole; Tetracycline; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Urethritis; Uterine Cervicitis

Each of 201 men with symptoms and signs of acute urethritis was randomly assigned to one of two treatment regimens: ampicillin (2g) plus probenecid (1g), or sulphamethoxazole-trimethoprim (SMX-TMP) (sulphamethoxazole 1600 mg plus trimethoprim 320 mg) four tablets twice daily for two days. Before treatment Neisseria gonorrhoeae was isolated from 162 patients, while coexistent Chlamydia trachomatis was recovered from 42 (26%) men. After treatment N gonorrhoeae persisted in 11 (14.3%) of the 77 patients treated with ampicillin and probenecid and in three (3.5%) of the 85 treated with SMX-TMP (p less than 0.05), while C trachomatis persisted in four (16%) of the 25 men treated with SMX-TMP and in all 17 patients treated with ampicillin and probenecid. SMX-TMP was thus more effective than ampicillin in treating acute gonorrhoea in men and in eradicating concurrent C trachomatis infection.

Topics: Acute Disease; Ampicillin; Anti-Infective Agents, Urinary; Chlamydia Infections; Chlamydia trachomatis; Clinical Trials as Topic; Drug Combinations; Drug Therapy, Combination; Gonorrhea; Humans; Male; Probenecid; Random Allocation; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Urethritis

The World Health Organization has proposed the syndromic approach for management of sexually transmissible diseases (STD) in countries where diagnostic laboratory tests are not consistently available. The purpose of this study was to evaluate the effectiveness of this approach for treatment of ureteral discharge in Senegal. Twenty seven men presenting ureteral discharge underwent two-week treatment using a combination of cotrimoxazole plus tetracycline for suspected gonococcal and a chlamydial infections. Ureteral samples were collected before and after treatment to detect Neisseria gonorrhoeae by culture and Chlamydia trachomatis by direct immunofluorescence and ELISA. Results demonstrated successful treatment of all patients presenting gonococcal and chlamydial infections i.e. 84.6% of cases. Neither germ was detected in 15.4% of cases. Before treatment, Neisseria gonorrhoeae, Chlamydia trachomatis or both were found respectively in 53.9%, 5.1% and 25.6% of samples respectively. Based on these findings we conclude that the syndromic approach was effective in 84.6% of cases but treatment was in adequation with STD biologically documented only with 25.6% of cases.

Topics: Anti-Bacterial Agents; Chlamydia Infections; Chlamydia trachomatis; Drug Therapy, Combination; Gonorrhea; Humans; Male; Neisseria gonorrhoeae; Senegal; Syndrome; Tetracycline; Trimethoprim, Sulfamethoxazole Drug Combination; Urethral Diseases

Topics: Adult; Anti-Infective Agents; Ciprofloxacin; Gonorrhea; HIV Infections; Homosexuality, Male; Humans; Male; Rectal Diseases; Recurrence; Trimethoprim, Sulfamethoxazole Drug Combination

To recommend a cost-effective approach for the management of acute male urethritis in the developing world, based on the findings of a theoretical study.. A model was developed to assess the cost-effectiveness of three urethritis management strategies in a theoretical cohort of 1000 men with urethral syndrome. (1) All patients were treated with cefixime and doxycycline for gonococcal urethritis (GU) and nongonococcal urethritis (NGU), respectively, as recommended by WHO. (2) All patients were treated with doxycycline for NGU; treatment with cefixime was based on the result of direct microscopy of a urethral smear. (3) All patients were treated with cotrimoxazole or kanamycin for GU and doxycycline for NGU. Cefixime was kept for patients not responding to the first GU treatment. Strategy costs included consultations, laboratory diagnosis (where applicable) and drugs. The outcome was the rate of patients cured of urethritis. Cost-effectiveness was measured in terms of cost per cured urethritis.. Strategy costs in our model depended largely on drug costs. The first strategy was confirmed as the most effective but also the most expensive approach. Cefixime should cost no more than US$ 1.5 for the strategy to be the most cost-effective. The second strategy saved money and drugs but proved a valuable alternative only when laboratory performance was optimal. The third strategy with cotrimoxazole was the least expensive but a low follow-up visit rate, poor treatment compliance or lower drug efficacy limited effectiveness. Maximizing compliance by replacing cotrimoxazole with single-dose kanamycin had the single greatest impact on the effectiveness of the third strategy.. Our model suggested that a cost-effective approach would be to treat gonorrhoea with a single-dose antibiotic selected from locally available products that cost no more than US$ 1.5.

Topics: Acute Disease; Anti-Bacterial Agents; Anti-Infective Agents; Cefixime; Cost-Benefit Analysis; Decision Trees; Developing Countries; Doxycycline; Drug Costs; Drug Therapy, Combination; Follow-Up Studies; Gonorrhea; Humans; Kanamycin; Male; Sensitivity and Specificity; Syndrome; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Urethritis

The relative frequency of pharyngeal gonococcal infection may be increased in certain prenatal populations. Therapy of penicillin-sensitive strains of Neisseria gonorrhoeae is associated with acceptable cure rates using aqueous procaine penicillin with probenecid. Infection of the oropharynx of pregnant women with penicillinase-producing strains is more problematic. The antibiotics normally used for the therapy of uncomplicated penicillinase-producing N gonorrhoeae infections, spectinomycin or cefoxitin, are not effective in the therapy of pharyngeal infection. Reported is the first case of penicillinase-producing N gonorrhoeae oropharyngeal infection during pregnancy. The patient was successfully treated with trimethoprim/sulfamethoxazole, and no maternal or neonatal morbidity was noted.

Topics: Adult; Anti-Bacterial Agents; Drug Combinations; Female; Gonorrhea; Humans; Infant, Newborn; Neisseria gonorrhoeae; Penicillinase; Pharyngitis; Pregnancy; Pregnancy Complications, Infectious; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adolescent; Adult; Doxycycline; Drug Combinations; Drug Therapy, Combination; Follow-Up Studies; Gonorrhea; Humans; Levamisole; Male; Recurrence; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents, Urinary; Drug Combinations; Gonorrhea; Humans; Military Medicine; Oropharynx; Pharyngeal Diseases; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Between 1976 and 1984 204 infections by penicillinase-producing Neisseria gonorrhoeae (PPNG) were seen in the Whitechapel Clinic. In 1984 PPNG were isolated from 4.7% of all patients attending with gonorrhoea. Three infections were homosexually acquired; 140 infections (68%) were acquired in the U.K. Strains that were tested were fully sensitive to spectinomycin (190), cefuroxime (177), kanamycin (170), amoxycillin combined with clavulanic acid (24) and rosoxacin (18). Of 135 strains 61% were resistant to co-trimoxazole, 69% of 169 to tetracycline (MIC greater than or equal to I mg/l) and 32% of 75 to streptomycin. Of 109 strains subjected to plasmid typing, 72(66%) were Asian strains. Of these, 55 (50% of the total) were without and 17 (16% of the total) possessed the 24.5 Mdal transfer plasmid; 27 (25%) were African strains without and 10 (9%) with the transfer plasmid. Of the Asian strains 10 were acquired in Africa. All four plasmid-containing strains are now endemic in the U.K. On the basis of the sensitivity tests, spectinomycin, cefuroxime and kanamycin should be effective in treatment, but not co-trimoxazole and tetracycline.

Topics: Drug Combinations; Drug Resistance, Microbial; Female; Gonorrhea; Humans; Male; Microbial Sensitivity Tests; Neisseria gonorrhoeae; Penicillinase; Plasmids; Streptomycin; Sulfamethoxazole; Tetracycline; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Drug Combinations; Drug Evaluation; Drug Synergism; Female; Gonorrhea; Humans; Middle Aged; Sulfamethoxazole; Tablets; Time Factors; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Drug Combinations; Gentamicins; Gonorrhea; Humans; Male; Sulfamethoxazole; Sulfanilamides; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Urethritis