Therapy For Gonorrhea Research Articles

Ceftriaxone for Treatment of Uncomplicated Gonorrhea

We retrospectively analyzed the efficacy of ceftriaxone in a single dose of 125 mg given intramuscularly for treatment of uncomplicated gonorrhea. Neisseria gonorrhoeae was eradicated from 152 (99%) of 154 patients who returned for test-of-cure, including all 83 heterosexual men and women and 69 (97%) of 71 homosexual men. Cure was achieved for 109 (99%) of 110 urethral or cervical infections, 52 (98%) of 53 rectal infections, and 15 of 15 pharyngeal infections. All infected sites were cured in 58 additional patients treated with ceftriaxone (125 mg) plus tetracycline (500 mg four times daily for seven days). These results confirm those of earlier clinical trials showing that 125 mg of ceftriaxone is effective therapy for uncomplicated gonorrhea in a geographic area with a high prevalence of gonococci with chromosomally mediated antibiotic resistance.

Norfloxacin in the therapy of uncomplicated gonorrhea

In an open study, 70 patients with uncomplicated anogenital Neisseria gonorrhoeae infection were evaluated to determine the efficacy and safety of a single oral dose of norfloxacin (800 mg). Norfloxacin cured all 31 male urethral and 25 endocervical infections. All 63 isolates of N. gonorrhoeae tested were inhibited by 0.05 microgram of norfloxacin per ml.

Treatment of Uncomplicated Infections due to Neisseria gonorrhoeae

GONORRHEA remains the most frequently reported infectious disease in the United States. Antimicrobial resistance in the gonococcus continues to evolve, and coinfection withChlamydia trachomatisis a serious problem. Therefore, the periodic review of current therapies for gonorrhea to ensure effective treatment must be a major objective of the National Gonorrhea Control Program in the United States. In the past five years, the number of potentially useful antimicrobial agents for the treatment of gonococcal infections has proliferated: these include second- and third-generation cephalosporins, regimens combining the β-lactamase inhibitors clavulanic acid and sulbactam with penicillin and amoxicillin, and the quinolones. This article reviews (1) recent trends in gonococcal antimicrobial resistance and in vitro susceptibility to established and experimental regimens; (2) coinfection due toC trachomatisandNeisseria gonorrhoeaewithin the past five years; (3) therapy for incubating syphilis and gonorrhea; (4) prophylaxis of sexual partners exposed to resistant organisms; and (5)

Oral Acyclovir for Treatment and Suppression of Genital Herpes Simplex Virus Infection

ACYCLOVIR is the only antiviral agent shown to be effective for the treatment of genital herpes simplex virus (HSV) infection. Effective therapy for this disease, however, has a different meaning from that for other sexually transmitted diseases. When we speak of effective therapy for gonorrhea, we mean that therapy cures the disease. The presence of gonorrhea in a patient is an indication for treatment. A clinician cannot ethically choose not to treat a patient with gonorrhea. Likewise, the patient with gonorrhea cannot refuse treatment. Public health regulations usually require that patients with gonorrhea be treated, not only to prevent further damage in the patient but to prevent transmission of disease. In contrast, the presence of genital herpes infection is not necessarily an indication for acyclovir treatment. Public health regulations do not require either the clinician to prescribe or the patient with genital herpes to accept therapy. We must evaluate the

Gonococcal infections.

Gonorrhea may be the most extensively studied infection of the past 20 years. The gonorrhea epidemic in the United States began in the early 1960s and peaked in 1975. Ironically, since 1976 the declining overall incidence has been offset by the advent of plasmid-mediated beta-lactamase production by Neisseria gonorrhoeae and by a growing problem with outbreaks due to strains with chromosomally mediated penicillin and tetracycline resistance. This new antimicrobial resistance, coupled with the frequency of concurrent chlamydial infection in developed countries and concurrent syphilis in some developing countries, has created a need for new approaches to gonorrhea therapy. With the introduction of certain new antimicrobial agents, highly effective forms of therapy are again available. New approaches to rapid diagnosis are also becoming available, but require critical appraisal. Unfortunately, in most of the world's population, gonorrhea remains epidemic, diagnosis of gonorrhea in women is extremely difficult, and highly effective antimicrobial agents are no longer affordable. Thus, vaccine development remains an extremely important goal. Although no candidate gonococcal vaccine currently holds high promise, the increasing understanding of the biology of the gonococcus and the pathogenesis of gonorrhea will serve to focus future research on vaccine development.

STD control in less developed countries: the time is now.

This discussion of sexually transmitted diseases (STDs) in less developed countries covers incidence/prevalence, antimicrobial resistance, sequelae, future trends, and new opportunities for STD control -- technological changes, health service changes, and social and political changes. For most countries, current, population-based information on STD is lacking, yet STDs appear to be common problems in nearly all countries. The prevalence of gonococcal infection in non-STD clinic populations has been as high as 5-20%, and incidence estimates made in a few settings have ranged from 3-10% per annum. These observations may overrepresent the STD problem, yet they have been identified in countries in Asia, Africa, and the Americas. The prevalence of reactive serological tests for syphilis among antenatal clinic attendees has been as high as 10-15% in some countries of Africa and the Western Pacific. Chancroid infection is extremely common in many of the developing countries of Asia, Africa, and the Americas. Penicillinase-producing "N. gonorrhoeae" (PPNG) infections are a dramatic example of the emergence and worldwide dissemination of resistant gonococci since 1976. At this time PPNG isolates constitute over 10% of all gonococcal infections in nearly all southeast Asian and Africa settings where this problem has been explored. PPNG cause more than 50% of gonococcal infections in some settings. As a result of increasing PPNG prevalence, penicillin, previously the standard therapy for gonorrhea, has been replaced by alternative agents in many settings. A variety of antimicrobial agents are effective for PPNG infections, but these are too expensive or unavailable in many developing countries. Sequelae of STD produce enormous direct and indirect costs. Acute pelvic inflammatory disease (PID) caused by gonorrhea, chlamydia, and other STD agents is common throughout the world. In developing countries ectopic pregnancy is a common surgical emergency. Improved diagnostic tests, new approaches to treatment of STD, and development of vaccines provide opportunities for better STD control, as have changes in health care delivery. The promotion of the primary health care concept, a shift in emphasis of the international family planning programs, as well as a focus on support systems of health programs all are crucial to STD efforts, and their improvement enhances STD control possibilities. Also, greater discussion of the STD health problems has led to more serious consideration of these diseases and their control.

"One-minute treatment" with thiamphenicol in 50,000 cases of gonorrhea: a 22-year study.

The results obtained with single-dose (2.5 g of thiamphenicol) therapy of gonorrhea in 50,000 patients are reported. Male patients included recent cases of acute or subacute urethritis and uncomplicated cases; all female patients had uncomplicated gonorrhea. Asymptomatic gonorrhea in both men and women was included in the therapy trial in all cases when "epidemiological" treatment was necessary. Tolerance of thiamphenicol was excellent; we observed only 62 cases of gastralgia or nausea and 12 cases of generalized pruritus reaction. No hematologic side effect was reported. The prescribed dose does not conceal incubating syphilis since 211 cases of recent syphilis were observed. Failures are reported year by year from 1961 to 1982 and, on the average, failure rates for men and women were 3.42% and 3.24%, respectively.

Clinical trial of thiamphenicol therapy for uncomplicated gonorrhea.

The need for a safe drug that is easy to administer and not too expensive prompted a study of treatment of uncomplicated gonorrhea with a single oral dose of 2.5 g of thiamphenicol. Of 169 patients treated, 161 were cured. Of the 92 patients with acute infections, all of the 13 men and 74 (93.7%) of the 79 women were cured. Seventy-seven cases were defined as reinfection; all of the 22 men in this group were cured, as were 52 (94.5%) of the 55 women. Only minor adverse effects were noted. It is concluded that thiamphenicol is a safe and effective antibiotic for therapy of uncomplicated gonorrhea.

Ceftriaxone A Review of its Antibacterial Activity, Pharmacological Properties and Therapeutic Use

Ceftriaxone is a new 'third generation' semisynthetic cephalosporin with a long half-life which has resulted in a recommended once daily administration schedule. It is administered intravenously or intramuscularly and has a broad spectrum of activity against Gram-positive and Gram-negative aerobic, and some anaerobic, bacteria. The activity of ceftriaxone is generally greater than that of the 'first' and 'second generation' cephalosporins against Gram-negative bacteria, but less than that of the earlier generations of cephalosporins against many Gram-positive bacteria. Although ceftriaxone has some activity against Pseudomonas aeruginosa, on the basis of present evidence it cannot be recommended as sole antibiotic therapy in pseudomonal infections. Ceftriaxone has been effective in treating infections due to other 'difficult' organisms such as multidrug-resistant Enterobacteriaceae. Ceftriaxone was effective in complicated and uncomplicated urinary tract infections, lower respiratory tract infections, skin, soft tissue, bone and joint infections, bacteraemia/septicaemia, and paediatric meningitis due to susceptible organisms. In most of these types of infections once-daily administration appears efficacious. Results were also encouraging in a few patients with ear, nose and throat, intra-abdominal, obstetric and gynaecological infections, and adult meningitis, but conclusions are not yet possible as to the efficacy of the drug in these indications due to limited experience. A single intramuscular dose of ceftriaxone has been compared with standard therapy for gonorrhoea due to non-penicillinase-producing and penicillinase-producing strains of Neisseria gonorrhoeae and shown to be highly effective. In a few small trials the comparative efficacy of ceftriaxone and other antibacterials has been assessed in other types of infections and in perioperative prophylaxis in patients undergoing surgery. Few significant differences in response rates were found between therapeutic groups in these comparative studies, but larger well-designed studies are needed to more clearly assess the comparative efficacy of ceftriaxone and other antimicrobials, especially the aminoglycosides and other 'third generation' cephalosporins, and to confirm the apparent lack of serious side effects with ceftriaxone. If more widespread use confirms the safety and efficacy of ceftriaxone, it will offer an important alternative, particularly for the treatment of serious infections due to multidrug-resistant Gram-negative bacteria and in situations where the long half-life of the drug could result in worthwhile convenience and cost benefits.

Repeated exposition to subinhibitory concentrations of antibiotic in vitro readily decreases susceptibility of Neisseria gonorrhoeae to rifampicin, but not to new cephalosporins and penicillin G.

Repeated subcultivation of Neisseria gonorrhoeae in the presence of subinhibitory concentrations of antibiotic has turned out as a reliable model to predict the low potential for development of resistance with respect to the beta-lactam antibiotic penicillin. Before large-scale introduction of the new cephalosporins we exposed 5 N. gonorrhoeae strains of different susceptibility to penicillin repeatedly to subinhibitory concentrations of cefotiam, ceftizoxime, rifampicin and penicillin G incorporated into chocolate agar. each time the most resistant representatives of a strain were propagated, on the whole 25 times. While resistance to rifampicin increased readily (all strains became relatively resistant, MIC = 4 micrograms/ml), the same was not true of the cephalosporins. Although their susceptibility decreased, too, no strain acquired partial or even total resistance (final MIC less than or equal to 0.128 with cefotiam and ceftizoxime). The cephalosporins thus rather parallelled penicillin G which hardly induced any increase of resistance. Thus, a quick loss of clinical efficacy need not be feared after large-scale introduction of the new cephalosporins into the therapy of gonorrhea.

A preliminary evaluation of the Gonozyme test.

Gonozyme is a solid-phase enzyme immunoassay that detects antigens of Neisseria gonorrhoeae in clinical specimens. The test was 100% sensitive and 96.8% specific when applied to 71 urethral specimens from men with symptomatic urethritis, and 89.5% specific for 19 urethral specimens from men examined after eradication of gonorrhea by antibiotics. For cervical specimens obtained before therapy from 368 women with gonorrhea, the Gonozyme test had a sensitivity of 88.5% and a specificity of 94.3%. The test was 100% specific when used for testing of 37 cervical specimens obtained after therapy of gonorrhea. The predictive values of a positive Gonozyme test were 90.5% for cervical specimens from women attending a sexually transmitted disease clinic and 97% for urethral specimens from men with urethritis. The predictive values of negative Gonozyme tests in these same circumstances were 100% for urethral specimens and 93.6% for cervical specimens.

1200 mg Rifampicin (Rimactan<sup>®</sup>) als Einzeldosisbehandlung der unkomplizierten Gonorrhoe der Frau

40 women were treated for uncomplicated genital gonorrhoea, verified by culture, with a single oral dose of 1,200 mg rifampicin (Rimactan). The ages ranged between 15 and 51 years. In 33 patients that could be evaluated, the gonorrhoea was cured. In 8 of 18 patients the preexistent vaginal discharge improved. 4 women experienced six different side effects which were probably related to rifampicin. The 1,200-mg rifampicin oral one-dose treatment is a reliable, efficient, and well-tolerated therapy of uncomplicated gonorrhoea in women.

Pelvic Inflammatory Disease: Considerations Related to Therapy

Since the early 1970s, the Centers for Disease Control (CDC) and the U.S. Public Health Service have recommended regimens of therapy for gonorrhea and its recognized complications, including pelvic inflammatory disease (PID). This paper summarizes the current situation with regard to PID and provides background information essential to the reassessment and possible revision of the current (1979) CDC recommendations [1]. Pelvic inflammatory disease is the most important complication of gonorrhea in terms of morbidity, personal suffering, and economic loss [2]. According to Curran [3], more than 850,000 episodes occur each year, resulting in more than 200,000 hospitalizations, more than 100,000 surgical procedures, and about 2,500,000 visits to the offices of private physicians. The direct and indirect costs of PID and PID-associated ectopic pregnancy in 1979 are estimated to have been $1.25 billion. The postsalpingitic state is associated with an increased risk of recurrence of PID. Also, each episode increases the risk of other consequences, such as infertility, ectopic pregnancy, pelvic adhesions, chronic pelvic pain, dyspareunia, and tuboovarian abscess [2, 4-7]. Many of these conditions ultimately lead to major pelvic surgery [2, 7-9]. The treatment of pelvic inflammatory disease, more than that of many other sexually transmitted

Treatment of gonococcal urethritis in men with a rifampicin-erythromycin combination.

A group of men with uncomplicated gonococcal urethritis were treated with a single oral dose of rifampicin (900 mg) and erythromycin stearate (1 g). Neisseria gonorrhoeae was isolated from four of 108 men at the first follow-up examination, and from none of 68 who attended a second follow-up examination. It is concluded that this rifampicin-erythromycin combination may be useful for the therapy of gonorrhea. It may be of particular value in the treatment of infections due to penicillin-resistant N. gonorrhoeae, since in vitro studies showed that both rifampicin and erythromycin were active against 20 strains of beta-lactamase-producing N. gonorrhoeae. The effect of this rifampicin-erythromycin combination against associated infections with Chlamydia trachomatis was disappointing. This organism was isolated from five of nine patients who had yielded isolates of C. trachomatis before treatment.

Effect of Menstrual Cycle and Method of Contraception on Recovery of Neisseria gonorrhoeae

We examined the records of 5,287 women who were names as sexual contacts of men who had gonococcal urethritis in the National Gonorrhea Therapy Monitoring Study. Neisseria gonorrhoeae was recovered from endocervical cultures from 3,247 (61.4%) of the women. Participants who were seen during the first five days of the menstrual cycle were slightly more likely to have a positive culture (64.9%) than women who were seen on days 6 through 10 (61.3%), days 11 through 15 (60.0%), days 16 through 20 (59.8%), days 21 through 25 (60.4%), or after day 25 (61.2%). Similar data were obtained for 1,489 untreated women who presented because a recent screening culture contained N gonorrhoeae. Neisseria gonorrhoeae was isolated from pretreatment cultures from 231 (79.7%) of 290 such women who were examined during the first five days of their menstrual cycle and from 884 (73.7%) of 1,199 women who were examined later in the cycle. Method of contraception had no statistically significant influence on the recovery of N gonorrhoeae.

Sulfamethoxazole-trimethoprim synergism for Neisseria gonorrhoeae.

Sulfamethoxazole and trimethoprim are synergistic against many bacteria in sulfamethoxazole/trimethoprim concentrations of 20:1, but single-dose therapy of gonorrhea with the combination is disappointing. We used agar dilution techniques to determine minimal inhibitory concentrations of sulfamethoxazole and trimethoprim for 168 gonococci isolated from men with acute urethritis in Atlanta, Ga. The geometric mean minimal inhibitory concentrations were 5.6 microgram of sulfamethoxazole per ml and 24.3 microgram of trimethoprim per ml, a ratio of 1:4. The concentration of sulfamethoxazole inhibiting 50% of gonococcal strains dropped only from 4.7 microgram/ml to 2.9 microgram/ml with the addition of a 1/20 dilution of trimethoprim. We studied synergism with various ratios of sulfamethoxazole to trimethoprim against 20 random strains. A ratio of 1:1 was always synergistic and was the most synergistic ratio for 15 strains, whereas the 19:1 ratio was never the most syngergistic. The 19:1 ratio failed to show synergism against seven strains, but showed antagonism at this ratio with five of these seven. The sulfamethoxazole/trimethoprim ratio of 19:1 usually achieved in serum after oral administration is minimally syngergistic and is sometimes antagonistic for gonococci.

Serum and subcutaneous chamber fluid dynamics of penicillins after single large parenteral doses.

Serum and subcutaneous chamber fluid (CF) dynamics of penicillin G, ampicillin, and amoxicillin were studied in rabbits after single large parenteral doses comparable to doses used in treating gonorrhea and endocarditis. The effects of parenteral probenecid and of injection of an antibiotic directly into a subcutaneous chamber ("intrachamber" injection) also were studied. Peak serum antibiotic concentrations exceeded peak CF concentrations and occurred sooner. Antimicrobial activity persisted longer in CF than in serum. Percent penetration [100 x (CF peak/serum peak)] of CF was least after intramuscular ampicillin and amoxicillin, was greatest after intrachamber ampicillin and intramuscular aqueous procaine penicillin G, and was related to duration of antibiotic concentration gradients from serum to CF. Intramuscular aqueous crystalline penicillin G resulted in higher serum and CF penicillin G concentrations than intramuscular aqueous procaine penicillin G, which prolonged the duration of penicillin G in serum and CF. Amoxicillin diffused into CF more readily than ampicillin. Probenecid resulted in higher early serum and CF antibiotic concentrations, but had little or no effect on duration of antibiotic activity. Intrachamber ampicillin resulted in more prolonged serum and CF ampicillin activity than intramuscular ampicillin, but much lower peak serum concentrations. The data suggest a possible means by which probenecid improves the efficacy of gonorrhea therapy with aqueous procaine penicillin G. Intrachamber administration of penicillins could be useful in treating experimental infections requiring prolonged therapy.

Pharmacokinetic determinants of penicillin cure of gonococcal urethritis.

In a 1964 study of the pharmacokinetic determinants of penicillin cure of gonococcal urethritis, 45 male prisoner volunteers were experimentally infected with strains of Neisseria gonorrhoeae having known in vitro penicillin susceptibility. After developing urethritis, subjects received intramuscular penicillin G and had serum samples obtained serially to determine penicillin concentration. Using a multiple regression technique, we studied patient-associated parameters and parameters of the serum penicillin curves to determine the best predictors of treatment results. Cure was best predicted by the time the serum penicillin concentration remained above three to four times the penicillin minimum inhibitory concentration of the infecting strain (probability of correct classification, >0.80). Those cured had serum penicillin concentrations which remained in this range for means of 7 to 10 h. Our findings confirm principles of antimicrobial therapy derived from animal models and may have application in studying therapy of gonorrhea and other infectious diseases.

The National Gonorrhea Therapy Monitoring Study

REYNOLDS, GLADYS H. PhD; ZAIDI, AKBAR A. MS; THORNSBERRY, CLYDE PHD; GUINAN, MARY MD; BIDDLE, JAMES; WIESNER, PAUL J. MD, AND THE COOPERATIVE STUDY GROUP Author Information

Therapy of Gonorrhea

Eighty-nine men with gonococcal urethritis were randomly treated with trimethoprim-sulfamethoxazole, four tablets (trimethoprim, 320 mg, and sulfamethoxazole, 1,600 mg) twice daily for two days, or ampicillin, 3.5 g, plus probenecid, 1 g, in a single dose. Forty-one (95.3%) of 43 patients who received trimethoprim-sulfamethoxazole and 41 (97.6%) of 42 given ampicillin were cured. Neither drug caused major side effects. All isolates of Neisseria gonorrhoeae were susceptible in vitro to trimethoprim-sulfame-thoxazole, and all but one were inhibited by ampicillin. The ampicillin-resistant strain (minimum inhibitory concentration, 4 μg/ml) produced penicillinase and was recovered from a patient who responded to treatment with trimethoprim-sulfamethoxazole. There was no significant correlation between the minimum inhibitory concentrations of trimethoprim-sulfame-thoxazole and ampicillin. It is concluded that trimethoprim-sulfamethoxazole is as efficacious and safe as ampicillin in the therapy of gonococcal urethritis. (<i>JAMA</i>240:2267-2270, 1978)