ro13-9904 and Rectal-Diseases

Antibiotic-resistant Neisseria gonorrhoeae has prompted the development of new therapies. Zoliflodacin is a new antibiotic that inhibits DNA biosynthesis. In this multicenter, phase 2 trial, zoliflodacin was evaluated for the treatment of uncomplicated gonorrhea.. We randomly assigned eligible men and women who had signs or symptoms of uncomplicated urogenital gonorrhea or untreated urogenital gonorrhea or who had had sexual contact in the preceding 14 days with a person who had gonorrhea to receive a single oral dose of zoliflodacin (2 g or 3 g) or a single 500-mg intramuscular dose of ceftriaxone in a ratio of approximately 70:70:40. A test of cure occurred within 6±2 days after treatment, followed by a safety visit 31±2 days after treatment. The primary efficacy outcome measure was the proportion of urogenital microbiologic cure in the microbiologic intention-to-treat (micro-ITT) population.. From November 2014 through December 2015, a total of 179 participants (167 men and 12 women) were enrolled. Among the 141 participants in the micro-ITT population who could be evaluated, microbiologic cure at urogenital sites was documented in 55 of 57 (96%) who received 2 g of zoliflodacin, 54 of 56 (96%) who received 3 g of zoliflodacin, and 28 of 28 (100%) who received ceftriaxone. All rectal infections were cured in all 5 participants who received 2 g of zoliflodacin and all 7 who received 3 g, and in all 3 participants in the group that received ceftriaxone. Pharyngeal infections were cured in 4 of 8 participants (50%), 9 of 11 participants (82%), and 4 of 4 participants (100%) in the groups that received 2 g of zoliflodacin, 3 g of zoliflodacin, and ceftriaxone, respectively. A total of 84 adverse events were reported: 24 in the group that received 2 g of zoliflodacin, 37 in the group that received 3 g of zoliflodacin, and 23 in the group that received ceftriaxone. According to investigators, a total of 21 adverse events were thought to be related to zoliflodacin, and most such events were gastrointestinal.. The majority of uncomplicated urogenital and rectal gonococcal infections were successfully treated with oral zoliflodacin, but this agent was less efficacious in the treatment of pharyngeal infections. (Funded by the National Institutes of Health and Entasis Therapeutics; ClinicalTrials.gov number, NCT02257918 .).

Topics: Administration, Oral; Adolescent; Adult; Anti-Bacterial Agents; Barbiturates; Ceftriaxone; Female; Female Urogenital Diseases; Gonorrhea; Humans; Injections, Intramuscular; Intention to Treat Analysis; Isoxazoles; Male; Male Urogenital Diseases; Microbial Sensitivity Tests; Middle Aged; Morpholines; Neisseria gonorrhoeae; Oxazolidinones; Pharyngeal Diseases; Rectal Diseases; Sexual Partners; Spiro Compounds; Treatment Outcome; Young Adult

Cefotaxime is a third-generation cephalosporin with excellent in vitro antimicrobial activity against Neisseria gonorrhoeae, including beta-lactamase-producing strains. A single 1-g intramuscular dose is suitable for the treatment of uncomplicated gonorrhea. We conducted an open, randomized study to evaluate the efficacy, safety, and cost impact of a lower dose (500 mg) of cefotaxime versus 250 mg ceftriaxone, an often recommended treatment for uncomplicated gonorrhea. Of the 222 patients enrolled, the cases of 151 were fully assessable. Bacteriologic elimination rates were 99% in the cefotaxime group and 100% in the ceftriaxone group. Clinical response rates were 78% and 83% in the two groups, respectively. Adverse clinical events occurred in 4% and 9% of patients in the two groups, respectively. The average wholesale price of 500 mg cefotaxime is 31% lower than that of 250 mg ceftriaxone. A 500-mg dose of cefotaxime appears to be a safe and cost-effective alternative to 250 mg ceftriaxone for the treatment of uncomplicated gonorrhea.

Topics: Adolescent; Adult; Cefotaxime; Ceftriaxone; Costs and Cost Analysis; Drug Resistance, Microbial; Female; Gonorrhea; Humans; Injections, Intramuscular; Male; Neisseria gonorrhoeae; Rectal Diseases; Urethral Diseases; Uterine Cervicitis

Topics: Anti-Bacterial Agents; Ceftriaxone; Chancre; Colonoscopy; Doxycycline; Humans; Lymphadenopathy; Magnetic Resonance Imaging; Male; Middle Aged; Rectal Diseases; Retreatment; Ulcer

To guide interpretation of gonorrhea tests of cure using nucleic acid amplification testing, this study examined the persistence of Neisseria gonorrhoeae DNA following treatment for pharyngeal and rectal gonorrhea.. Men who had sex with men diagnosed with pharyngeal or rectal gonorrhea underwent swabbing from the pharynx or rectum 7 and 14 days following treatment. Repeat testing for N. gonorrhoeae was undertaken using real-time polymerase chain reaction (PCR) assays targeting the opa gene and porA pseudogene.. One hundred pharyngeal and 100 rectal gonorrhea infections in 190 men were included. For pharyngeal gonorrhea, positivity of N. gonorrhoeae DNA on both PCR assays was present at days 7 or 14 in 13% (95% confidence interval [CI], 6.4%-19.6%) and 8% (95% CI, 2.7%-13.3%), respectively. For rectal gonorrhea, DNA positivity was present in 6% (95% CI, 1.4%-10.7%) and 8% (95% CI, 2.7%-13.3%), respectively. Among 200 baseline pharyngeal and rectal isolates, there were 10 with ceftriaxone minimum inhibitory concentration (MIC) ≥0.06 mg/L and azithromycin MIC ≥0.5 mg/L, of which 3 (30%) had DNA detected at day 14; among the 190 isolates with lower ceftriaxone and azithromycin MICs, only 13 (7%) had persistent DNA (odds ratio, 5.8 [95% CI, 1.3-25.4]; P = .019). One man initially infected with N. gonorrhoeae multiantigen sequence type 2400 had type 4244 infection at day 14, indicating reinfection.. Pharyngeal and rectal gonorrhea DNA persisted in 8% of men 14 days after treatment. Persistence was associated with elevated ceftriaxone and azithromycin MICs. Persistence can also reflect reinfection.

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Bacterial Load; Bacterial Outer Membrane Proteins; Ceftriaxone; DNA; Gonorrhea; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Neisseria gonorrhoeae; Nucleic Acid Amplification Techniques; Pharyngeal Diseases; Pharynx; Porins; Real-Time Polymerase Chain Reaction; Rectal Diseases; Rectum; Young Adult

Because of the decreasing susceptibility of Neisseria gonorrhoeae to cephalosporin therapy, the Centers for Disease Control and Prevention recommends test of cure (TOC) 1 week after gonorrhea (GC) treatment if therapies other than ceftriaxone are used. In addition, the Centers for Disease Control and Prevention asks clinicians, particularly those caring for men who have sex with men (MSM) on the west coast, to consider retesting all MSM at 1 week. However, it is unclear if this is acceptable to providers and patients or if nucleic acid amplification tests (NAATs) are useful for TOC at 7 days.. Between January and July 2012, MSM with GC were advised to return 1 week after treatment for TOC using NAAT. A multivariate logistic regression model was used to determine demographic and behavioral differences between MSM who returned for follow-up and MSM who did not.. Of 737 men with GC, 194 (26.3%) returned between 3 and 21 days of treatment. Individuals who returned were more likely to have no GC history (P = 0.0001) and to report no initial symptoms (P = 0.02) when compared with individuals who did not return for TOC. Of those who returned, 0% of urethral samples, 7.4% of rectal samples, and 5.3% of pharyngeal samples were NAAT positive at TOC.. Although TOC may be an important strategy in reducing complications and the spread of GC, low return rates may make implementation challenging. If implemented, extra efforts should be considered to enhance return rates among individuals with a history of GC. If TOCs are recommended at 1 week and NAATs are used, the interpretation of positive results, particularly those from extragenital sites, may be difficult.

Topics: Adolescent; Adult; Azithromycin; Ceftriaxone; Drug Resistance, Bacterial; Follow-Up Studies; Gonorrhea; Homosexuality, Male; Humans; Logistic Models; Los Angeles; Male; Mass Screening; Middle Aged; Neisseria gonorrhoeae; Nucleic Acid Amplification Techniques; Patient Compliance; Patient Satisfaction; Pharyngeal Diseases; Rectal Diseases; Sentinel Surveillance; Sexual Behavior; Time Factors

Topics: Aged; Anal Canal; Anti-Bacterial Agents; Anti-Infective Agents; Anus Diseases; Ceftriaxone; Female; Humans; Intestinal Perforation; Intestine, Small; Metronidazole; Rectal Diseases; Rectum; Rupture, Spontaneous; Time Factors

Topics: Adult; Anti-Bacterial Agents; Ceftriaxone; Diagnosis, Differential; Drug Eruptions; Gonorrhea; HIV Seropositivity; HIV-1; Humans; Male; Neisseria gonorrhoeae; Penicillin G Procaine; Rectal Diseases; Rectum; Syphilis Serodiagnosis; Syphilis, Cutaneous; Viral Load