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The antimicrobial susceptibilities of 16,441 gonococcal isolates from Seattle-King County were determined for ceftriaxone, cefoxitin, penicillin G, and tetracycline. From 1985 to 1989, ceftriaxone, in combination with doxycycline, was increasingly used for treatment of gonorrhea, and by 1989, it was used as therapy for > 80% of cases in Seattle-King County. MICs of ceftriaxone correlated significantly (P < 0.001) with those of the other beta-lactam antibodies included in this study. Geometric mean MICs of penicillin G for isolates that did not produce beta-lactamase increased from 1985 to 1991. The geometric mean MICs of cefoxitin, ceftriaxone, and tetracycline began to decline in 1987 but increased in 1990 and 1991. The percentage of strains with decreased susceptibility to ceftriaxone (MIC, 0.06 to 0.25 microgram/ml) rose from 0.3% in 1985 to 5.3% in 1987 but subsequently declined steadily to 2.6% in 1991, despite increased use of ceftriaxone as routine therapy for gonorrhea. Changes in patterns of antimicrobial susceptibility may be related not only to antimicrobial selection pressures but also to less well understood population shifts among Neisseria gonorrhoeae strains within a community.

Endocervical infections due to Chlamydia trachomatis remain difficult to diagnose due to the lack of an inexpensive, rapid, and accurate test. We evaluated an alternative strategy for diagnosis in which initial screening was performed with an enzyme immunoassay (Chlamydiazyme) followed by a direct fluorescent antibody (DFA) test on specimens in which the Chlamydiazyme optical density (OD) reading fell in an intermediate zone. Lowering the Chlamydiazme OD ratio (specimen to control) used to define a positive test from 1.0 (the ratio suggested by the manufacturer) to 0.3 raised the sensitivity of Chlamydiazyme from 73 to 83%. Confirmation of those specimens having OD ratios of 0.3 to 0.99 by DFA testing increased the specificity of Chlamydiazyme from 95 to 100%. This strategy necessitated performance of the DFA test on 5% of the specimens. Lowering the cutoff OD ratio below 0.3 increased the sensitivity even further but required DFA testing on greater than 25% of the specimens. Use of an adjusted positive cutoff value for defining positive enzyme immunoassays followed by DFA confirmation for intermediate-zone readings may be a feasible approach for some laboratories that lack cell culture facilities.

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 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.

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.

We evaluated a monoclonal fluorescent-antibody (FA) reagent (Neisseria gonorrhoeae Culture Confirmation Test; Syva Co., Palo Alto, Calif.) for confirmation of N. gonorrhoeae isolates obtained from clinics for sexually transmitted diseases in four cities. The FA test was performed in parallel with established confirmation procedures on all organisms growing on 773 primary culture plates of modified Thayer-Martin agar. All N. gonorrhoeae isolates reacted with the FA reagent and produced a bright, easily interpretable fluorescence. The FA test correctly identified 533 N. gonorrhoeae isolates from 474 patients and did not react with 90 N. meningitidis or with 213 non-Neisseria isolates. In one city (Baltimore), Gonochek II (Du Pont Co., Wilmington, Del.) failed to identify four N. gonorrhoeae isolates reactive with the FA reagent and confirmed as N. gonorrhoeae by Phadebact (Pharmacia Inc., Piscataway, N.J.) and acid production from sugars. The FA test was rapid and specific and could be performed directly from primary isolation plates. The test requires 1 h to perform and is applicable to mixed-flora cultures.

In a multicenter cooperative study, an enzyme immunoassay (EIA) using purified antigen of lymphadenopathy-associated virus was compared with radioimmune precipitation (RIP) for detection of antibody to human immunodeficiency virus (HIV) in 634 patients with acquired immunodeficiency syndrome or related conditions, 687 apparently healthy persons at risk for HIV infection, 93 controls with cancer or autoimmune diseases, and 10,038 blood or plasma donors. Excluding the donors, the EIA was reactive in 875 (61.9%) of 1,414 subjects; compared with RIP, the sensitivity and specificity of EIA both were 99.8%. There was one false-positive EIA among 148 intravenous drug abusers and two false-negative EIAs among 472 apparently healthy homosexual men; no other discordant results between EIA and RIP occurred in these subjects. The EIA was repeatably reactive in 20 donors (0.2%), among whom 13 (65%) were positive by RIP; none of 529 randomly selected EIA-negative donors was RIP positive. In addition to its utility as a screening test in low-risk populations, the EIA for antibody to lymphadenopathy-associated virus is useful as a diagnostic test in persons with clinical evidence of or at risk for HIV infection.

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.

In a double-blind comparative trial, 100 men with uncomplicated gonorrhea caused by beta-lactamase-negative Neisseria gonorrhoeae were treated with a single 0.25-g dose of ciprofloxacin administered orally or with 3.5 g of ampicillin plus 1.0 g of probenecid administered orally. Urethral infection was eradicated in all 49 men treated with ciprofloxacin and in 47 (92%) of 51 men treated with ampicillin-probenecid (P = 0.12). The geometric mean MICs for pretreatment isolates were 0.008 microgram of ciprofloxacin per ml, 0.09 microgram of penicillin G per ml, 0.52 microgram of tetracycline per ml, and 23.5 micrograms of spectinomycin per ml. Chlamydia trachomatis infection persisted in 10 of 11 men treated with ciprofloxacin and in 11 of 14 men treated with ampicillin-probenecid. A single 0.25-g dose of ciprofloxacin was effective for treatment of uncomplicated urethral gonorrhea in men, but it did not eradicate coinfection with C. trachomatis.

To assess the practical significance of reported increases in the prevalence of vancomycin-susceptible strains of Neisseria gonorrhoeae on isolation of this organism, antibiotic-free chocolate agar (CA), modified Thayer-Martin medium (MTM), and a vancomycin-free selective medium (VFSM) were compared in a sexually transmitted disease clinic. Among 326 cervical gonococcal infections detected in a comparison of CA with MTM, 92.0% were detected on CA, compared with 98.2% on MTM (P less than 0.001). Similarly, among 306 cervical infections detected in a comparison of MTM and VFSM, 95.8% of infections were detected with VFSM, compared with 98.4% for MTM (P = 0.10). For 1,632 urethral infections in men, all three media were equivalent, with none detecting fewer than 98% of the infections. Compared with a single inoculation, dual inoculation of MTM increased the diagnostic yield by 1.5% for 206 urethral infections and 2.4% for 83 cervical infections. In our clinic population, MTM is superior to CA or VFSM for the diagnosis of genital gonococcal infections, especially in women. The increased yield that accrued from inoculation of both MTM and either of the other media was not sufficiently high to warrant routine use of this practice in our clinic.

Uncomplicated gonorrhea in men was successfully treated with ceftriaxone in single intramuscular doses of 125 mg (15 patients), 250 mg (16 patients), or 500 mg (15 patients). All 45 pretreatment gonococcal isolates tested were inhibited by

Seven strains of Haemophilus ducreyi from diverse geographic origins were analyzed for their plasmid content. All strains were multiply resistant, but only resistance to ampicillin was transferred to Escherichia coli by transformation. The H. ducreyi plasmids encoding for ampicillin resistance were 7.4, 5.7, and 3.6 megadaltons and encoded for part or all of TnA, and ampicillin transposon. The relatedness of these plasmids was examined by restriction endonuclease digestion and DNA-DNA homology with isolated DNA fragments from TnA.

The safety and efficacy of ofloxacin, 400 mg orally, were compared with those of amoxicillin, 3.0 g, plus probenecid, 1.0 g orally, as single-dose therapy in 201 heterosexual patients (101 men and 100 women) with uncomplicated gonococcal infection. Treatment groups were comparable in age, duration of symptoms, number of sexual partners within the previous month, and number of previous episodes of sexually transmitted diseases. The cure rate for men treated with ofloxacin was 98% (47 of 48), and that for women was 100% (52 of 52). Cure rates for both men and women treated with amoxicillin-probenecid were 96% (51 of 53 men; 46 of 48 women). All 13 patients with positive rectal cultures and 7 of 8 patients with positive pharyngeal cultures treated with ofloxacin were cured. Neither regimen reliably eradicated coexistent infection with Chlamydia trachomatis. The MIC of ofloxacin for all but two of 198 pretreatment isolates was 0.3 microgram/ml or less. The MIC of amoxicillin for 90% of isolates tested was 1.0 microgram/ml. Single oral doses of ofloxacin and of amoxicillin plus probenecid were equally effective for treatment of urethral and cervical gonorrhea. Ofloxacin appears promising as treatment for rectal and pharyngeal infection, but studies with larger numbers of patients with rectal or pharyngeal infection or both are required for confirmation. Relative contraindications in children and possibly pregnant women plus the potential for single-step, high-level resistance may limit the usefulness of quinolone therapy for gonorrhea.

Amoxicillin (alpha-amino-p-hydroxybenzyl penicillin, BRL 2333) is a new semisynthetic penicillin which is structurally similar to ampicillin, but which is better absorbed and yields higher concentrations in serum and urine. The in vitro susceptibility of 145 strains of Enterobacteriaceae and 30 isolates of Pseudomonas aeruginosa was determined against various concentrations of amoxicillin and ampicillin in agar. In addition, inhibitory zones around discs containing 10 mug of amoxicillin were measured and compared with results of agar dilution studies. The drug also was evaluated in the treatment of 38 patients with bacteriuria, who received doses of either 750 mg or 1 g/day for 10 days. In vitro, amoxicillin was comparable in activity to ampicillin; most isolates of Escherichia coli and Proteus mirabilis were inhibited by 10 mug or less/ml, whereas the majority of strains of Enterobacter, Klebsiella, indole-positive Proteus species, and Pseudomonas grew in concentrations greater than 50 mug/ml. Clinically, amoxicillin was effective in eradicating bacteriuria due to susceptible organisms and was very well tolerated. For practical purposes, however, amoxicillin performed no better than a host of other drugs presently available for the treatment of acute, uncomplicated bacteriuria.