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BackgroundNeisseria gonorrhoeae (commonly known as gonorrhea) has developed resistance to all first-line therapy in Southeast Asia. East Africa has historically had absent or rudimentary gonorrhea surveillance programs and, while the existence of antimicrobial-resistant gonorrhea is recognized, the extent of its resistance is largely unknown. In 2016, the World Health Organization’s Enhanced Gonococcal Antimicrobial Surveillance Program (EGASP) was initiated in Uganda to monitor resistance trends. ObjectiveThis study characterizes gonorrhea and antibiotic resistance in a large surveillance program of men with urethral discharge syndrome from Kampala, Uganda. MethodsMen attending sentinel clinics with urethritis provided demographic information, behavior data, and a urethral swab in line with the World Health Organization’s EGASP protocols for culture, identification, and antibiotic-sensitivity testing using 2 methods—disk diffusion (Kirby-Bauer test) and Etest (BioMérieux Inc). A subset of samples underwent detailed antimicrobial resistance testing. ResultsOf 639 samples collected from September 2016 to February 2018, 400 (62.6%) were culture-positive though 414 (64.8%) had microscopic evidence of gonorrhea. The mean age of the men from whom the samples were collected was 26.9 (SD 9.6) years and 7.2% (46/639) reported having HIV. There was high-level resistance to ciprofloxacin, tetracycline, and penicillin (greater than 90%) by Kirby-Bauer disk diffusion and 2.1% (4/188) had reduced azithromycin sensitivity by Etest. Of the early isolates that underwent detailed characterization, 60.3% (70/116) were culture-positive, 94% (66/69) isolates were either ciprofloxacin-resistant or ciprofloxacin-intermediate by Etest, 96% (65/68) were azithromycin-sensitive, and 96% (66/69) were gentamicin-sensitive. Resistance profiles were comparable between methods except for ceftriaxone (disk diffusion: 68/69, 99%; Etest: 67/69, 97%) and for gentamicin (disk diffusion: 2/8, 25%; Etest: 66/69, 96%) sensitivity. ConclusionsThis is the first report from a systematic gonorrhea surveillance program in Uganda. Findings demonstrated resistance or increased minimum inhibitory concentration to all key antigonococcal antibiotics. There was evidence of poor antibiotic stewardship, near-universal resistance to several antibiotics, and emerging resistance to others. Individuals in the population sampled were at exceptionally high risk of STI and HIV infection requiring intervention. Ongoing surveillance efforts to develop interventions to curtail antimicrobial-resistant gonorrhea are needed.