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Gonorrhea remains a major public health challenge, and current recommendations for gonorrhea treatment are threatened by evolving antimicrobial resistance and a diminished pipeline for new antibiotics. Evaluations of potential new treatments for gonorrhea currently make limited use of new understanding of the pharmacokinetic and pharmacodynamic contributors to effective therapy, the prevention of antimicrobial resistance, and newer designs for clinical trials. They are hampered by the requirement to utilize combination ceftriaxone/azithromycin therapy as the comparator regimen in noninferiority trials designed to seek an indication for gonorrhea therapy. Evolving gonococcal epidemiology and clinical trial design constraints hinder the enrollment of those populations at the greatest risk for gonorrhea (adolescents, women, and persons infected with antibiotic-resistant Neisseria gonorrhoeae). This article summarizes a recent meeting on the evaluation process for antimicrobials for urogenital gonorrhea treatment and encourages the consideration of new designs for the evaluation of gonorrhea therapy., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Potential legal liability for practicing expedited partner therapy is a common concern among providers, although it has been uncertain how these concerns translate into clinical practice. This study suggests that providers are more likely to practice expedited partner therapy in more favorable legal environments.

Background: Expedited partner therapy (EPT) has been shown to reduce the risk of persistent or recurrent gonorrhea and chlamydial infection in heterosexuals, and to increase the proportion of sex partners receiving treatment. The objective of this analysis was to evaluate the consistency of EPT's effect across sociodemographic and behavioral subgroups., Methods: Subset analyses from a randomized controlled trial compared EPT to standard partner referral (SPR) in sociodemographic and behaviorally defined subgroups. Outcomes included persistent or recurrent infection in study participants and participants' report that their partners received treatment., Results: Reinfection risk was lower among EPT recipients than nonrecipients in 21 of 22 subgroups, with relative risks (RRs) varying from 0.4 to 0.94. Compared to persons receiving SPR, persons receiving EPT were more likely to report that their partners were very likely to have been treated in 33 of 34 subgroups (RRs range, 1.03-1.36). Although EPT reduced the risk of persistent or recurrent infection somewhat more in men (RR, 0.56; 95% CI, 0.3-1.08) than in women (RR, 0.81; 95% CI, 0.61-1.07) and more in persons with gonorrhea (RR, 0.32; 95% CI, 0.13-0.78) than those with chlamydial infection (RR, 0.82; 95% CI, 0.63-1.07), the RR of partners being treated associated with EPT was similar in men (RR, 1.21; 95% CI, 1.05-1.39) and women (RR, 1.18; 95% CI, 1.10-1.27), and also in persons with gonorrhea (RR, 1.33; 95% CI, 0.80-2.23) and chlamydial infection (RR, 1.33; 95% CI, 1.07-1.66)., Conclusions: In this study, EPT is shown to be superior to SPR across a wide spectrum of sociodemographic and behaviorally defined subgroups.

Objective: To evaluate a partner notification program for gonorrhea and chlamydial infection that involves communitywide access to free patient-delivered partner therapy (PDPT) and use of case-report forms to triage patients to receive partner notification assistance., Methods: We evaluated program components in randomly selected cases and compared outcomes before and after program institution., Results: Following institution of the program, the percentage of cases who received PDPT from their diagnosing clinician increased from 5.6% to 16% (adjusted OR 3.2, 2.5-4.1). Among randomly selected cases, those referred to the health department via the case-report form were significantly more likely than nonreferred cases to have untreated sex partners (76% vs. 35%, OR 6.0, 95% CI 4.5-8.0), to accept PDPT from the health department (36% vs. 14%, 3.3, 95% CI 2.4-4.7), and to request that health department staff notify a partner for them (11% vs. 3%, OR 3.5, 95% CI 1.8-6.7). The percentage of cases classified as having all of their partners treated increased from 39% to 65% concurrent with institution of the program., Conclusions: A public health program that promotes routine use of PDPT and referral of selected patients for partner notification assistance appears to have improved partner notification outcomes.

Background: Many sex partners of persons with gonorrhea or chlamydial infections are not treated, which leads to frequent reinfections and further transmission., Methods: We randomly assigned women and heterosexual men with gonorrhea or chlamydial infection to have their partners receive expedited treatment or standard referral. Patients in the expedited-treatment group were offered medication to give to their sex partners, or if they preferred, study staff members contacted partners and provided them with medication without a clinical examination. Patients assigned to standard partner referral were advised to refer their partners for treatment and were offered assistance notifying partners. The primary outcome was persistent or recurrent gonorrhea or chlamydial infection in patients 3 to 19 weeks after treatment., Results: Persistent or recurrent gonorrhea or chlamydial infection occurred in 121 of 931 patients (13 percent) assigned to standard partner referral and 92 of 929 (10 percent) assigned to expedited treatment of sexual partners (relative risk, 0.76; 95 percent confidence interval, 0.59 to 0.98). Expedited treatment was more effective than standard referral of partners in reducing persistent or recurrent infection among patients with gonorrhea (3 percent vs. 11 percent, P=0.01) than in those with chlamydial infection (11 percent vs. 13 percent, P=0.17) (P=0.05 for the comparison of treatment effects) and remained independently associated with a reduced risk of persistent or recurrent infection after adjustment for other predictors of infection at follow-up (relative risk, 0.75; 95 percent confidence interval, 0.57 to 0.97). Patients assigned to expedited treatment of sexual partners were significantly more likely than those assigned to standard referral of partners to report that all of their partners were treated and significantly less likely to report having sex with an untreated partner., Conclusions: Expedited treatment of sex partners reduces the rates of persistent or recurrent gonorrhea or chlamydial infection., (Copyright 2005 Massachusetts Medical Society.)

We collected specimens from women who tested positive for Neisseria gonorrhoeae using the Gen-Probe APTIMA Combo 2 (AC2), and we performed confirmatory tests using a nucleic acid amplification test (NAAT) that targets alternate gonococcal nucleic acid sequences. Among 59,664 specimens, 280 (0.47%) had positive results using AC2; 265 of these specimens were tested using the confirmatory NAAT, of which 258 yielded positive results (positive predictive value, 97.4%; 95% confidence interval, 95.1%-98.8%). Routine confirmatory testing of specimens with positive AC2 gonorrhea test results is not indicated.

Background: Rescreening patients after treatment of Chlamydia trachomatis or Neisseria gonorrhoeae infection has had high yield but low rates of participation., Goal: The goal of this study was to determine if rescreening for gonorrhea and chlamydial infection in a largely urban sexually transmitted disease population would be more successful if individuals were given the option of submitting a specimen for testing through the mail., Study Design: We conducted a randomized clinical trial involving 122 patients of whom 62 were assigned to clinic rescreening and 60 were given the option of either mailing a specimen for testing or going to a clinic for rescreening., Results: Twenty-seven patients (45%) given the option of either rescreening in the clinic or through the mail and 20 (32%) assigned to clinic rescreening were rescreened within 28 days of enrollment in the study (odds ratio, 1.7; 95% confidence interval, 0.8-3.8). Of the 60 patients randomized to the clinic rescreening or mailing option, 11 of 18 (61%) who opted to mail in a specimen and 16 of 42 (38%) who chose clinic rescreening were rescreened within 28 days of enrollment (P = 0.10)., Conclusions: Although not statistically significant, this study indicates that mailed rescreening could be a successful method to increase rescreening rates.

Unlabelled: A study of heterosexuals with gonorrhea and/or chlamydial infection in King County, Washington, found that 5.2% of study participants had both local and geographically distant sex partners in the 60 days before diagnosis. Individuals who served as spatial bridges were of higher socioeconomic status and older than other patients., Background: Sexual mixing between distant geographic areas (spatial bridging) is important in the spread of antimicrobial resistance and new sexually transmitted disease pathogens., Goal: The goal was to define the extent of sexual mixing between persons with gonorrhea or chlamydial infection in King County, Washington, and persons outside the Seattle area, and to identify characteristics of persons and partnerships associated with spatial bridging., Methods: Patients contacted for purposes of partner notification were interviewed regarding demographics, sexual behavior, and the characteristics of their sex partners., Results: Of 2912 participants, 150 (5.2%) were spatial bridgers. Bridgers were of higher socioeconomic status than nonbridgers and more often reported concurrent partnerships. Over a 39-month period, bridgers and potential bridgers linked King County with 35 states and 13 foreign countries., Conclusion: Spatial bridging could represent an important channel of transmission between geographic areas. These results highlight the need for linkage of prevention efforts across geographic boundaries.

Background: Key strategies advocated for lowering personal risk of sexual exposure to STD/HIV include having fewer partners and avoiding risky partners. However, few studies have systematically examined how well people can actually discern their sex partners' risk behaviours., Methods: We conducted face to face interviews with 151 heterosexual patients with gonorrhoea or chlamydial infection and 189 of their sex partners. Interviews examined the patients' perceptions of their sex partners' sociodemographic characteristics and risk behaviours. Patients' perceptions of partners were then sociometrically compared for agreement with partner self reports, using the kappa statistic for discrete variables and concordance correlation for continuous variables., Results: Agreement was highest for perceived partner age, race/ethnicity, and duration of sexual partnership; and lowest for knowledge of partner's work in commercial sex, number of other sex partners, and for perceived quality of communication within the partnership. Index patients commonly underestimated or overestimated partners' risk characteristics. Reported condom use was infrequent and inconsistent within partnerships., Conclusion: Among people with gonorrhoea or chlamydial infection, patients' perceptions of partners' risk behaviours often disagreed with the partners' self reports. Formative research should guide development and evaluation of interventions to enhance sexual health communication within partnerships and within social networks, as a potential harm reduction strategy to foster healthier partnerships.

Objective: To define utility of age and cervical findings in predicting infection with Chlamydia trachomatis and Neisseria gonorrhoeae among women universally tested for both infections, and to assess the independent contribution of Gram stain (GS) smear of endocervical secretions., Methods: Visits by women to Seattle sexually transmitted diseases clinics from 1995 through 1999 were retrospectively reviewed. All women had endocervical GS and cultures for C trachomatis and N gonorrhoeae performed. Predictive values of age, cervical signs, and inflammation on GS (more than 30 polymorphonuclear leukocytes per 1000x field) were calculated., Results: Among 6230 women, prevalence of C trachomatis and N gonorrhoeae was 6.9% and 2.1%, respectively; 520 women (8.3%) had either organism detected. Age, cervical signs (mucopus, induced bleeding), and inflammation on endocervical GS were independently associated with infection. However, the positive predictive value (PPV) of any cervical finding for infection was less than 19% in women 25 years and older. Inflammation on endocervical GS was the sole indicator of infection in 79 of 520 (15%) infections, but was insensitive in the absence of mucopurulent cervicitis (sensitivity, 26%; PPV, 21%)., Conclusion: Cervical signs suggesting chlamydial or gonococcal infection have higher positive predictive value (PPV) in younger women. The PPV of inflammation on endocervical GS is too low to recommend its use to direct empiric treatment in the absence of mucopurulent cervicitis, especially in women 25 years and older. Further, its low sensitivity in detecting infection in women without mucopurulent cervicitis does not justify routine use. Signs suggesting mucopurulent cervicitis should be interpreted in the context of age, and empiric treatment may not be indicated in women aged 25 years and older.

Background: Public health partner notification (PN) services currently affect only a small minority of patients with gonorrhea or chlamydial infection and new approaches to PN are needed., Objectives: To expand PN for gonorrhea and chlamydial infection to private sector patients and to assess the feasibility of treating sex partners through commercial pharmacies., Methods: Selected patients were offered PN assistance and were randomly offered medication to deliver to their partners., Results: Providers permitted the health department to contact 3613 (91%) of 3972 potentially eligible patients, and 1693 (67%) of 2531 successfully contacted patients consented to interview. Of these, 1095 (65%) reported at least one untreated partner. Most patients (90%) wished to notify partners themselves. Patients were more likely to have partners who had not yet been treated and to request PN assistance if they had more than one sex partner in the preceding 60 days or a partner they did not anticipate having sex with in the future. These two factors characterized 49% of all patients interviewed, 70% of those with a partner that was untreated 7 or more days after index patient treatment, and 83% of those accepting PN assistance. Among 458 randomly selected patients with untreated partners at time of study interview, 346 (76%) agreed to deliver treatment to a partner. Of these, most (266) chose to obtain medication for a partner at a pharmacy, of whom 223 (84%) successfully did so., Conclusion: A substantial minority of private sector patients have untreated partners more than 7 days after their own treatment; some need help with PN, but most will agree to deliver medication to partners themselves.

Objectives: This study sought to define, among sexually transmitted disease (STD) clinic attendees, (1) patterns of sex partner selection, (2) relative risks for gonococcal or chlamydial infection associated with each mixing pattern, and (3) selected links and potential and actual bridge populations., Methods: Mixing matrices were computed based on characteristics of the study participants and their partners. Risk of infection was determined in study participants with various types of partners, and odds ratios were used to estimate relative risk of infection for discordant vs concordant partnerships., Results: Partnerships discordant in terms of race/ethnicity, age, education, and number of partners were associated with significant risk for gonorrhea and chlamydial infection. In low-prevalence subpopulations, within-subpopulation mixing was associated with chlamydial infection, and direct links with high-prevalence subpopulations were associated with gonorrhea., Conclusions: Mixing patterns influence the risk of specific infections, and they should be included in risk assessments for individuals and in the design of screening, health education, and partner notification strategies for populations.

Background and Objectives: Azithromycin is a new, long-acting azalide antibiotic that is active against Neisseria gonorrhoeae. A single oral dose of 1.0 g is effective against uncomplicated genital infection with Chlamydia trachomatis., Goal of This Study: To compare the efficacy and tolerance of single-dose treatment of uncomplicated gonorrhea with azithromycin, 2.0 g orally, and ceftriaxone, 250 mg intramuscularly., Study Design: Seven hundred twenty-four men and women with presumptive, uncomplicated gonorrhea were treated with azithromycin 2.0 g orally or ceftriaxone 250 mg intramuscularly in a 2:1 ratio in a multicenter, open, randomized control trial in 10 public sexually transmitted disease clinics in the United States. Patients were followed up in 5 to 9 days and, for a subset of patients, 12 to 18 days after treatment. The main outcome measures were the isolation of N. gonorrhoeae and C. trachomatis and patient-reported side effects., Results: Among infected patients who returned for follow-up, N. gonorrhoeae was eradicated from all anatomic sites in 370 of 374 (98.9%; 95% confidence interval [95%CI] 97.9%-100%) treated with azithromycin and 171 of 175 (97.7%; 95%CI 95.5%-99.9%) given ceftriaxone. Treatment with either drug was effective in all 73 patients infected with beta-lactamase-producing N. gonorrhoeae. Chlamydial infection was eradicated in all 17 patients given azithromycin who returned and were recultured at follow-up and in two of seven patients given ceftriaxone (P < 0.001). Gastrointestinal side effects occurred in 35.3% (95%CI 30.7%-39.8%) of patients given azithromycin; of those with symptoms, these were moderate in 10.1% and severe in 2.9%., Conclusions: Azithromycin 2.0 g and ceftriaxone 250 mg are equally effective in the treatment of uncomplicated gonorrhea. Azithromycin was associated with a relatively high frequency of gastrointestinal side effects and is expensive, but it has the advantages of oral administration and efficacy against concomitant chlamydial infection.

Background: Single-dose cefixime 400 mg orally is effective in the treatment of uncomplicated gonorrhea. However, lower doses of cefixime have not been studied, and the minimum effective single-dose regimen may risk selecting resistant strains of Neisseria gonorrhoeae. Therefore, we studied the efficacy of a lower dose of cefixime., Objective: To assess the efficacy of 200 mg cefixime in the treatment of uncomplicated gonorrhea., Methods: One hundred twenty-five patients (106 men, 19 women) with presumptive gonorrhea were treated with single doses of cefixime 200 mg orally in an open non-comparative study. Follow-up visits were scheduled for four to seven days after treatment., Results: Genital and rectal gonorrhea were eradicated in 93 (95%, CI95 90.5-99.2%) of 98 patients who were culture-positive at enrollment and returned for follow-up. Treatment was effective in 78 (95%) of 82 men with urethral infection and 15 (94%) of 16 women with anogenital infection. Two of three pharyngeal infections also were eradicated. Persistent infection was not associated with resistance to cefixime, penicillin, or tetracycline., Conclusions: Cefixime 200 mg in a single dose has substantial efficacy in the treatment of uncomplicated gonorrhea, enhancing confidence that use of 400 mg cefixime for gonorrhea has a low risk of selecting gonococci with clinically significant antibiotic resistance. However, the 200 mg dose should not be used for routine treatment.

Background and Objectives: Cefotaxime is a third-generation cephalosporin that has in vitro activity against Neisseria gonorrhoeae, including beta-lactamase-producing strains. A single 1-g intramuscular dose is effective and is recommended by the Centers for Disease Control and Prevention as an alternative treatment for uncomplicated gonorrhea., Goal of This Study: This study was conducted to evaluate the efficacy and safety of a lower 500-mg dose of cefotaxime in the treatment of uncomplicated gonococcal infections., Study Design: In a randomized multicenter study, patients who had uncomplicated gonorrhea were treated with 500 mg of cefotaxime or 250 mg of ceftriaxone. Both antibiotics were given intramuscularly. Efficacy and safety were assessed four to seven days following treatment., Results: Six hundred thirteen patients were enrolled. Bacteriologic eradication rates for anogenital infection were 97.7% of the patients (213/218) in the cefotaxime group and 99.1% of the patients (221/223) in the ceftriaxone group (P = 0.243). Adverse events occurred in 4.2% and 7.5% of patients in the two groups, respectively., Conclusion: Cefotaxime 500 mg appears to be a safe and cost-effective alternative to ceftriaxone 250 mg for the treatment of uncomplicated gonorrhea.

In a multicenter, randomized, open, comparative trial, patients with uncomplicated gonorrhea were treated with 400 mg of oral fleroxacin or 250 mg of intramuscular ceftriaxone. A total of 458 men and 447 women were enrolled. Of these, 312 men (68%) and 245 women (55%) were evaluable for efficacy. The treatment groups were demographically similar. Among evaluable men, fleroxacin eradicated 154 of 155 (99%; 95% confidence interval [CI]: 98.1-100%) urethral and 2 of 2 pharyngeal infections, while ceftriaxone eradicated 156 of 156 (95% CI: 99.4-100%) urethral and 5 of 5 pharyngeal infections. Among evaluable women, fleroxacin eradicated 127 of 128 (99%; 95% CI: 97.7-100%) cervical, 20 of 20 anorectal, 16 of 16 urethral, and 7 of 7 pharyngeal infections, while ceftriaxone eradicated 108 of 108 (95% CI: 99.1-100%) cervical, 24 of 24 anorectal, 25 of 25 urethral, and 9 of 9 pharyngeal infections. Adverse events were reported by 68 (16%) of 426 subjects in the fleroxacin group and 20 (5%) of 380 in the ceftriaxone group (p < 0.0001). The most common adverse events reported by the patients who received fleroxacin were nausea (5%), headache (3%), and vaginitis (3%). One patient had severe vomiting, 19 participants had adverse reactions classified as moderate, and 48 patients had mild adverse reactions. Fleroxacin was highly effective in the treatment of uncomplicated gonorrhea and represents an oral alternative to ceftriaxone. Adverse events were more common with fleroxacin than with ceftriaxone.

Gonorrhea is among the most common sexually transmitted diseases. Treatment for uncomplicated gonorrhea should be efficacious in > or = 95% of cases. Because patients with gonococcal infections often have other sexually transmitted diseases concurrently, individuals enrolled in clinical trials of therapy for gonorrhea should also be evaluated for infection with Chlamydia trachomatis and for syphilis. Testing for other pathogens should be considered in light of the clinical presentation. The presence of gonococcal infection is defined by a positive culture of a specimen obtained from an appropriate mucosal site. Patients enrolled in clinical trials should be otherwise-healthy adults who agree to return for follow-up assessment. These patients should be stratified by gender and anatomic site of infection. The preferred study design is a prospective, randomized, double-blind, active-control comparison. In some circumstances, however, historical controls may suffice. The study drug must have an efficacy rate of > or = 95% in genital and rectal infections. Microbiological eradication, demonstrated by negative cultures of samples from all potentially infected mucosal sites at follow-up, is the sole determinant of efficacy.

Background: Because of the widespread existence of Neisseria gonorrhoeae resistant to penicillin or tetracycline, ceftriaxone is now recommended for the treatment of gonorrhea. There is, however, a need for effective antibiotics that can be administered orally as an alternative to ceftriaxone, which requires intramuscular administration. Cefixime is an orally absorbed cephalosporin that is active against resistant gonococci and has pharmacokinetic activity suitable for single-dose administration., Methods and Results: In a randomized, unblinded multicenter study of 209 men and 124 women with uncomplicated gonorrhea, we compared three single-dose treatment regimens: 400 mg or 800 mg of cefixime, administered orally, and 250 mg of ceftriaxone administered intramuscularly. The overall cure rates were 96 percent for the 400-mg dose of cefixime (89 of 93 patients) (95 percent confidence interval, 93.5 percent to 97.8 percent); 98 percent for the 800-mg dose of cefixime (86 of 88 patients) (95 percent confidence interval, 94.6 percent to 100 percent); and 98 percent for ceftriaxone (92 of 94 patients) (95 percent confidence interval, 94.9 to 100 percent). The cure rates were similar in men and women, and pharyngeal infection was eradicated in 20 of 22 patients (91 percent). Thirty-nine percent of 303 pretreatment gonococcal isolates had one or more types of antimicrobial resistance; the efficacy of all three regimens was independent of the resistance pattern. Chlamydia trachomatis infection persisted in at least half the patients infected in each treatment group. All three regimens were well tolerated., Conclusions: In the treatment of uncomplicated gonorrhea, a single dose of cefixime (400 or 800 mg) given orally appears to be as effective as the currently recommended regimen of ceftriaxone (250 mg given intramuscularly).

Background: Despite a declining incidence during the AIDS era, gonorrhea remains the most frequently reported communicable disease in the United States., Methods: During 1986 and 1987 we supplemented gonorrhea case reporting with laboratory surveillance in King County, Washington. Incidence rates were correlated with demographic variables., Results: Overall incidence of gonorrhea was similar for men and women, but highest for 16- to 21-year-old females and urban Seattle residents. Incidence rates by ethnicity were Blacks, 3033; Native Americans, 843; Hispanics, 617; Asians, 190; and Whites, 121. Census tracts representing the lowest socioeconomic status (SES) quartile accounted for 58% of reported gonorrhea. Black female teenagers residing in the lowest SES urban areas had highest incidence rates: aged 14 to 15, 3.4%; 16 to 17, 10.4%; 18, 17.0%; and 19, 15.4%. Rates in female teenagers were even higher after adjustment for estimated proportion of those who were sexually experienced., Conclusions: Gonorrhea incidence is associated with age, gender, ethnicity, SES, and residence. Identification of populations at highest risk for gonorrhea can direct interventions against all sexually transmitted diseases. Clearly, interventions to alter high-risk behaviors must be initiated in early adolescence.

Trends in sexually transmitted diseases (STDs) in homosexually active men were analyzed in King County, Washington, from 1980 to 1990. New-problem visits to the public STD clinic declined from 4142 in 1980 to 509 in 1988 (-88%), then rose to 937 (+84%) in 1989, and 527 in the first half of 1990. Cases of gonorrhea in homosexually active men treated at the STD clinic plus private sector cases of rectal gonorrhea in men fell from 955 in 1982 to 33 in 1988 (-97%), then rose to 102 in 1989 (+209%). Similar trends were observed for several other STDs. Of 109 Neisseria gonorrhoeae isolates from homosexual or bisexual men in 1988 to 1989, 46 (42%) belonged to 3 auxotype/serovar classes; one of these was a penicillinase-producing strain (PPNG), the first appearance of PPNG in substantial numbers in homosexually active men in King County. The remaining 58% of isolates were distributed among 20 strains. These data imply substantial reductions in the frequency of high-risk sexual behavior in homosexually active men in King County over most of the 1980s, followed by an increased frequency of unsafe behavior after 1988. Maintenance of sexual safety may require increased educational effort and societal support as time passes.

In a randomized, double-blind, dose-ranging study, single oral doses of rosoxacin were used to treat 126 patients with uncomplicated genital or anorectal gonorrhea. Neisseria gonorrhoeae was eradicated from 5 (28%) of 18 men treated with 100 mg, compared with 101 (94%) of 108 men and women treated with 200 mg, 300 mg, or 400 mg (P less than 0.001). Susceptibility to rosoxacin was determined for 6 pretreatment gonococcal isolates from these patients and for 194 stored clinical isolates; 296 (98.7%) of these 300 isolates, including 10 strains of penicillinase-producing N. gonorrhaeae, required a minimal inhibitory concentration of less than or equal to 0.062 microgram/ml. Urethral or cervical infection with Chlamydia trachomatis coexisted with gonococcal infection in 14 (22%) of 63 patients and persisted in 7 of 10 patients treated with rosoxacin. Postgonococcal urethritis developed in 11 (34%) of 32 men who were monitored for 12 to 30 days. Sixty-four subjects (51%) developed transient dizziness, drowsiness, altered visual perceptions, or other symptoms suggestive of central nervous system dysfunction after treatment with rosoxacin, but these symptoms were not clearly dose related. Rosoxacin in doses of greater than or equal to 200 mg appears to be effective for single-dose treatment of uncomplicated gonorrhea, but further studies of its possible central nervous system toxicity are indicated.

The efficacy of cefonicid (1.0 g given in a single intramuscular dose) was assessed in 50 women with uncomplicated infections due to beta-lactamase-negative strains of Neisseria gonorrhoeae. Forty-three (96%) of 45 cervical infections but only 23 (82%) of 28 anorectal infections were eradicated; overall, 44 (90%) of 49 women were cured of anogenital gonorrhea. Cefonicid failed to eradicate six (55%) of 11 pharyngeal gonococcal infections and 17 (85%) of 20 endocervical infections with Chlamydia trachomatis. Cefonicid had good activity against N. gonorrhoeae in vitro; 41 (98%) of 42 isolates were inhibited by less than or equal to 1.0 micrograms/ml. However, because of its poor efficacy against anorectal and pharyngeal gonococcal infections, single-dose cefonicid is not suitable for the treatment of gonorrhea in women or homosexually active men.

Patients with uncomplicated gonorrhea due to beta-lactamase-negative Neisseria gonorrhoeae were treated with cefotaxime (1.0 g given im in a single dose) or with aqueous procaine penicillin G (APPG; 4.8 x 10(6) units given im) plus probenecid (1.0 g given orally). Genital or rectal gonococcal infection was cured in 51 (93%) of 55 patients given cefotaxime and in 23 (96%) of 24 patients given APPG plus probenecid. Gonococcal isolates from homosexual men were less susceptible to cefotaxime (geometric mean MIC, 0.021 microgram/ml) than were strains isolated from heterosexual men (geometric mean MIC, 0.012 microgram/ml; P less than 0.05). Genital infection with Chlamydia trachomatis persisted in four of eight patients given cefotaxime and was first detected after treatment in three others. Of 23 men with gonococcal urethritis who were treated with cefotaxime and followed for 11--30 days, ten (43%) developed postgonococcal urethritis; five of these were associated with chlamydial infection. Administration of cefotaxime or APPG caused equal pain, but cefotaxime was better tolerated because of the need for only one injection. Cefotaxime and APPG plus probenecid are comparable for treatment of uncomplicated genital and rectal infection with beta-lactamase-negative N. gonorrhoeae.

Sexually active young adults with an acute arthralgia or arthritis, with or without associated skin lesions, often have disseminated gonococcal infection (DGI). In recent years, an increasing proportion of patients seen with such complaints at the University of Washington Hospitals, Seattle, have had systemic meningococcal infection rather than DGI. Among 151 patients with acute arthritis studied prospectively from 1970 to 1972, blood or synovial fluid cultures yielded Neisseria gonorrhoeae in 30 patients and Neisseria meningitidis in two. Among 62 patients meeting the same criteria who were studied prospectively from 1980 to 1983, blood or synovial fluid cultures yielded gonococci in nine and meningococci in five. Separate analysis of blood culture results from two University of Washington Hospitals also revealed a decline in the number of cases of gonococcemia from 1970 through 1984 and a shift in the relative numbers of patients with bacteremia due to N gonorrhoeae and N meningitidis. The observed decline in gonococcemia coincides with a decline in the proportion of gonorrhea in Seattle caused by gonococcal strains that have been associated with DGI.

Of the currently recommended regimens for treatment of uncomplicated gonorrhea, only aqueous penicillin G procaine is effective against infections at all sites. However, procaine penicillin is not effective against penicillinase-producing Neisseria gonorrhoeae and suffers from poor patient acceptability owing to the 10-mL volume of injection and allergic and toxic procaine reactions. Ceftriaxone is a new extended-spectrum cephalosporin with a long serum half-life and is many times more active than penicillin G against both beta-lactamase-positive or -negative strains of N gonorrhoeae. Ceftriaxone was compared as a single, 125-mg, 0.5-mL injection with a single 2-g injection of spectinomycin in difficult to treat pharyngeal gonorrhea in men and women and anorectal gonorrhea of men. Ceftriaxone cured 30/32 (94%) pharyngeal and 52/52 anorectal infections, compared with 6/14 (43%) and 9/9, respectively, for spectinomycin. Both regimens were well tolerated. Ceftriaxone may prove to be a drug of choice for uncomplicated gonorrhea, particularly where homosexual men are treated and/or penicillinase-producing N gonorrhoeae is prevalent.

The efficacy of intramuscular sulbactam for uncomplicated gonorrhea was assessed in 20 men infected with beta-lactamase-negative Neisseria gonorrhoeae. Ten subjects received 2.0 g of sulbactam given in a single intramuscular dose with 1.0 g of probenecid orally; 4 of 10 urethral infections persisted, as did one rectal infection. Ten subjects were treated with 0.5 g of intramuscular sulbactam given twice, 4 h apart; 3 of 10 urethral infections and 2 of 2 rectal infections persisted. The geometric mean MIC of sulbactam for 20 pretreatment isolates of N. gonorrhoeae was 1.37 microgram/ml (range, 0.25 to 8.0 micrograms/ml). Serum levels of sulbactam, determined for nine subjects in the two treatment groups, fell below the MIC of some gonococci after less than 6 h with both regimens. In the regimens studied, sulbactam alone is not suitable as therapy for uncomplicated gonorrhea. determined for nine subjects in the two treatment groups, fell below the MIC of some gonococci after less than 6 h with both regimens. In the regimens studied, sulbactam alone is not suitable as therapy for uncomplicated gonorrhea.

Strains of Neisseria gonorrhoeae requiring arginine, hypoxanthine, and uracil (Arg-Hyx-Ura-) are highly susceptible to penicillin G, and have been associated with asymptomatic urethral infection and disseminated gonococcal infection (DGI). The authors recovered Arg-Hyx-Ura- strains from 48% of 282 heterosexual men and women, versus only 9% of 69 homosexual or bisexual men (P less than 0.0001). In a separate population of consecutive men with urethral gonococcal infections, urethral discharge was absent in 0 of 96 homosexual men, versus 18 of 261 heterosexual men (P less than 0.025). Homosexual men accounted for none of 41 cases of DGI in men in 1970--1973, compared with 35% of men with uncomplicated gonorrhea in 1978. These findings suggest that asymptomatic urethral gonococcal infection and DGI are uncommon in homosexual men, perhaps because infection with Arg-Hyx-Ura- strains is relatively uncommon. Screening cultures of urethral specimens for N. gonorrhoeae had a low yield among homosexual men in the population studied. Strains of N. gonorrhoeae recovered from homosexual men were significantly more resistant to penicillin than were isolates from heterosexual subjects; this was true even for non-Arg-Hyx-Ura-strains. This difference may help to explain the lesser efficacy of ampicillin in treatment of rectal gonococcal infection in homosexual men.

Single 500-mg intramuscular doses of imipenem-cilastatin cured 116 (95%) of 122 men and 9 of 9 women with uncomplicated gonorrhea due to beta-lactamase-negative Neisseria gonorrhoeae. Most co-existing Chlamydia trachomatis infections persisted. Imipenem-cilastatin is effective for uncomplicated gonorrhea in men but has no advantages over other available regimens.

Beta-lactamase-negative Neisseria gonorrhoeae infections were treated with single-dose cefoperazone (0.5 or 1.0 g) or spectinomycin (2.0 g). Anogenital infections were cured in 36 (83%) of 43 volunteers given 0.5 g of cefoperazone, 61 of 61 volunteers given 1.0 g of cefoperazone, and 99 of 100 volunteers given spectinomycin. The cefoperazone geometric mean MIC for 242 isolates was 0.028 microgram/ml. Cefoperazone (1.0 g) and spectinomycin (2.0 g) are comparable for the therapy of anogenital gonorrhea in men.

In King County, Washington, penicillinase-producing Neisseria gonorrhoeae infections increased from 0.8% of reported cases of gonorrhea in 1986 to 6.8% of cases in the third quarter of 1987, then stabilized at 2.7% to 3.6% of cases. Of 268 penicillinase-producing N gonorrhoeae isolates tested, 159 (59%) belonged to a single clone, as evidenced by auxotyping, protein-I serotyping, plasmid analysis, and antimicrobial susceptibility testing. As this strain spread, the predominance of cases shifted from whites to blacks and from men to equal numbers of men and women. The proportion of cases associated with illicit drug use rose steadily from 19% in the first quarter of 1987 to 82% in the fourth quarter. Sixty percent of cases occurred in prostitutes or recent sexual contacts of prostitutes. These results suggest that core gonorrhea transmitters in King County are predominantly black illicit drug users, prostitutes, and their sexual partners. These are priority target populations for behavioral intervention and other measures to control the spread of all sexually transmitted diseases, including human immunodeficiency virus infection.

A technique to detect Neisseria gonorrhoeae directly in clinical specimens was developed using a modified DNA-hybridization method. It uses the gonococcal cryptic plasmid as the radiolabeled probe, can detect as few as 100 colony-forming units of N gonorrhoeae or as little as 0.1 pg of purified gonococcal plasmid DNA, and is highly specific. This technique for differentiating between gonococcal and nongonococcal urethritis was evaluated in men with symptomatic urethritis in Seattle. Sixty-three (89%) of 71 who had cultures positive for N gonorrhoeae were also positive by DNA hybridization, and all 42 whose cultures were negative were also negative by DNA hybridization. Five of six isolates from patients who were positive by culture but negative by hybridization lacked the gonococcal cryptic plasmid and belonged to a unique auxo-type which requires proline, citrulline, and uracil for growth.

Auxotyping and serogrouping by coagglutination were used to characterize penicillinase-producing Neisseria gonorrhoeae and penicillinase-negative isolates from the state of Washington, Shreveport (Louisiana), and the Far East. Fifty-four of 75 penicillinase-producing isolates (72 per cent) from Washington required proline for growth and were serogroup W-l (Pro-1), the predominant type of penicillinase-producing strains in the Philippines; none of 86 penicillinase-negative isolates from Washington was Pro-1 (P less than 0.0001). All 38 penicillinase-producing isolates from Shreveport required proline and were serogroup W-11 (Pro-11); five of 26 penicillinase-negative isolates (19 per cent) from Shreveport were also Pro-11 (P less than 0.0001) but had antigenic specificities within serogroup W-ll that distinguished them from the penicillinase-producing isolates. We conclude that the Washington and Shreveport outbreaks resulted from the spread of imported strains rather than transmission of penicillinase-encoding plasmids to indigenous gonococci. The Shreveport outbreak involved a single strain of penicillinase-producing N, gonorrhoeae and probably originated from a common source, whereas several types were involved in the multiple-source Washington outbreak, indicating repeated introduction of new strains.

Three hundred seventy-six patients with uncomplicated infection due to beta-lactamase-negative Neisseria gonorrhoeae were treated with 1.0 g of cefotaxime intramuscularly or with 4.8 x 10(6) units of aqueous procaine penicillin G (APPG) intramuscularly plus 1.0 g of probenecid, administered orally. Cefotaxime eradicated 157 (98.1%) of 160 urethral or endocervical gonococcal infections, 22 (96%) of 23 rectal infections, and 8 (73%) of 11 pharyngeal infections. In comparison, APPG-probenecid eradicated 125 (98.4%) of 127 urethral or endocervical gonococcal infections, 17 (94%) of 18 rectal infections, and 4 (100%) of 4 pharyngeal infections. Of 304 domestic beta-lactamase-negative gonococcal isolates, 294 (96.7%) were inhibited by less than or equal to 0.03 microgram/ml of cefotaxime. In a separate study, cefotaxime eradicated 31 of 31 urethral infections due to beta-lactamase-positive strains of N. gonorrhoeae acquired by U.S. Navy personnel in the Philippines. Treatment with cefotaxime was tolerated better than treatment with APPG, primarily because only one injection is required for cefotaxime. The efficacy of cefotaxime was comparable to that of APPG-probenecid in the treatment of uncomplicated genital or rectal infection due to beta-lactamase-negative N. gonorrhoeae, and cefotaxime appears to be highly effective for the treatment of urethral infection due to beta-lactamase-positive N. gonorrhoeae. Further studies are needed for assessment of the efficacy of cefotaxime for treatment of pharyngeal gonococcal infection.

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.

Gonorrhea remains the most commonly reported sexually transmitted infection, with a total of 2-2.5 million cases occurring annually in the United States. The annual incidence of gonococcal and nongonococcal pelvic inflammatory disease (PID) is 600,000-1,000,000 cases, 10-15% of which result in infertility due to bilateral tubal occulusion. PID results from ascending infection with sexually transmitted pathogens or components of the normal vaginal flora, or both. Uncomplicated gonorrhea usually is best treated with a single dose of ampicillin or procaine penicillin G (given with probenecid) or spectinomycin, in each case followed by a 7 day course of tetracycline or doxycycline to eradicate coexisting chlamydial infection. PID, both gonococcal and non-gonococcal, ideally should be treated in the hospital with parenteral antibiotics. Regimens utilizing various combinations of doxycycline, cefoxitin, clindamycin, aminoglyocosides, or metronidazole are recommended. The sexual partners of patients with gonorrhea or with PID (non-gonococcal as well as gonococcal) should be routinely examined and treated.

We conducted a two-center dose ranging study to evaluate the efficacy, tolerance, and toxicity of cefpimizole, a new cephalosporin, in the treatment of uncomplicated gonorrhea in 96 males. Twelve patients at each center were treated intramuscularly with single doses of 1.0, 0.5, 0.25, and 0.125 g of cefpimizole. All urethral infections were cured at the highest dose, but lower doses produced progressively decreasing cure rates of 90% (0.5 g), 83% (0.25 g), and 71% (0.125 g). Treatment failures of rectal and pharyngeal infections occurred at the highest dose level. Geometric mean MICs for cefpimizole for successfully and unsuccessfully treated volunteers were 0.088 and 0.282 micrograms/ml, respectively. A prominent adverse effect was clinically significant pain at the injection site, which occurred in 57 (59%) of 96 patients. Results of the study demonstrate that cefpimizole offers no advantage over currently available antibiotics in the treatment of uncomplicated gonorrhea in men.

Single-dose ceftriaxone, 125 mg or 250 mg intramuscularly (IM), was compared with spectinomycin, 2 g IM, for treatment of men with uncomplicated urethral or anorectal infections due to penicillinase-negative Neisseria gonorrhoeae. Cure rates were 100% for 31 and 28 men treated with 125 mg and 250 mg ceftriaxone, respectively, and 97% for 58 men given spectinomycin. Among patients followed up for greater than or equal to 14 days, post-gonococcal urethritis occurred in 25% of 44 men treated with ceftriaxone and 19% of 47 given spectinomycin (p = NS). The geometric mean minimum inhibitory concentration of ceftriaxone for 79 pre-treatment isolates of N gonorrhoeae was 0.0058 microgram/ml, and all strains were inhibited by less than or equal to 0.063 micrograms/ml. Neither drug caused perceptible toxicity, but patient acceptance was greater for ceftriaxone than for spectinomycin. Ceftriaxone in a single dose of 125 mg is effective against uncomplicated urethral or anorectal gonorrhoea in men and may become a regimen of choice for this infection.