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Antimicrobial Resistance in Extragenital Neisseria gonorrhoeae Infections, US Military Centers, 2022–2024
Author affiliation: William Beaumont Army Medical Center, El Paso, Texas, USA (J.L. Dombach); Tripler Army Medical Center, Honolulu, Hawaii, USA (J.L. Dombach, J.L. MacArthur, C. Mekonnen, N.K. Copeland, E. Kamau); United States Military Academy, West Point, New York, USA (J.L. MacArthur); University of Hawai’i at Mānoa, Honolulu (T.H.A. La, M.H. Norris); University of Hawai’i at Manoa, Manoa, Hawaii, USA (V. Nxedhlana); Armed Forces Health Surveillance Center, Silver Spring, Maryland, USA (H.J. Smith); Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA (H.J. Smith, N.K. Copeland)
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Abstract
We analyzed antimicrobial resistance markers in 189 Neisseria gonorrhoeae patient encounters from 2 US military medical centers. Co-occurring resistance-associated markers were common; we detected plasmid-mediated β-lactamase in extragenital sites. Our findings highlight the importance of anatomic site–specific surveillance and, potentially, molecular antimicrobial resistance detection to guide screening and treatment strategies.
Neisseria gonorrhoeae infection remains a major global public health concern because of increasing antimicrobial resistance (AMR), including reduced susceptibility to extended-spectrum cephalosporins (1,2). Extragenital infections, particularly in the pharynx and rectum, are often asymptomatic and can contribute to persistence and transmission of resistant organisms (3–5).
We analyzed samples from 189 N. gonorrhoeae–positive clinical encounters collected during 2022–2024 at Tripler Army Medical Center (TAMC; Honolulu, Hawaii, USA) and Madigan Army Medical Center (MAMC; Tacoma, Washington, USA). The human research protection offices from both institutions, under the umbrella of the Defense Health Agency, reviewed the study and determined it to be research not involving human subjects. Investigators adhered to US policies for the protection of human subjects as prescribed in 45 Code of Federal Regulation 46.
We analyzed data from specimens that included urine and swabs from oropharyngeal, rectal, and urogenital sites (Table). We deidentified data and analyzed it at the encounter level; we were unable to exclude repeat encounters from the same patient. We performed targeted next-generation sequencing using the Urinary Pathogen ID/AMR Panel (Illumina, https://www.illumina.com). We identified AMR markers using predefined sequence-matching rules specific to each gene or mutation (e.g., exact match for point mutations such as rpsJ V57M and curated allele grouping for penA variants). Because short-read data and panel design did not support reliable allele-level or phylogenetic resolution, we analyzed penA variants as a single category. This study did not include phylogenetic reconstruction, multilocus sequence typing, or transmission network analysis; therefore, our findings describe marker prevalence and co-occurrence patterns rather than clonal relationships.
Figure
Figure. Prevalence of AMR markers in study of AMR patterns in extragenital Neisseria gonorrhoeaeinfections, US military medical centers, 2022–2024. Heatmap shows percent of encounters in which each genotypic marker…
Across all encounters, resistance-associated markers frequently co-occurred. The most prevalent markers were macB (77.2%) and rpsJ V57M (75.7%), and we detected penA variants in 63.0% of isolates (Figure). We observed co-occurrence of these markers in 60.3% of encounters, which suggested common resistance-associated marker combinations within the cohort. Findings from TAMC demonstrated higher prevalence of rpsJ V57M (84.2% vs. 65.9%; p = 0.004) and penA variants (70.3% vs. 54.5%; p = 0.034) than for those from MAMC.
Markers associated with fluoroquinolone resistance were also present (gyrA S91F, 35.4%). We frequently detected structural efflux pump genes (macB, farA, mtrE); however, because those genes are part of the core genome, their presence alone does not predict phenotypic resistance. Regulatory mutations (e.g., mtrR variants) and combined genetic contexts are more directly associated with resistance expression.
We observed anatomic site–specific differences. The plasmid-mediated β-lactamase gene blaTEM-1 was more prevalent in extragenital specimens; we detected blaTEM-1 in 10/17 (58.8%) of rectal swab samples and 10/24 (41.7%) of oropharyngeal swab samples, compared with 22/125 (17.6%) of urine specimens (Figure). Compared with oropharyngeal swab samples, rectal specimens had increased odds of blaTEM-1 detection (odds ratio [OR] 6.3; p = 0.004), whereas urine specimens had lower odds (OR 0.29; p = 0.012). In adjusted analyses controlling for age, sex, and institution, rectal specimens showed increased odds and wide 95% CIs (adjusted OR 2.57 [95% CI 0.94–7.00]).
Chromosomal resistance-associated markers such as rpsJ V57M were more common in urine specimens (80.0%) than in oropharyngeal specimens (50.0%; OR 3.90; p = 0.014). Conversely, we detected farA more frequently in urine (66.4%) than in extragenital (oropharyngeal and rectal) sites (<12.5%) (Figure). Those findings suggest that different anatomic niches may harbor distinct resistance-associated profiles.
Among 189 encounters, 24.9% occurred in persons with documented use of HIV pre-exposure prophylaxis. blaTEM-1 was more common among users (36.2% vs. 21.8%; p = 0.056), whereas farA was less frequent (21.3% vs. 62.7%; OR 0.16, p<0.001). Associations were attenuated after adjustment.
Antimicrobial drug treatment varied across encounters. Doxycycline exposure was common; however, doxycycline is not recommended for treating uncomplicated gonorrhea and was likely prescribed for concurrent or presumptive chlamydial infection or syndromic management (6). A high (78.3%) percentage of isolates exposed to doxycycline contained rpsJ V57M, consistent with tetracycline-associated resistance markers (7).
Our study targeted sequencing and short-read data, which limited resolution of gene variants (e.g., blaTEM subtypes) and precluded plasmid reconstruction or phylogenetic analyses. The absence of phenotypic susceptibility testing limited our ability to interpret clinical resistance. Retrospective data and incomplete sampling across anatomic sites might affect prevalence estimates. Finally, lack of temporal and patient-level linkage data limited inferences regarding transmission dynamics.
In summary, we identified frequent co-occurrence of resistance-associated markers in N. gonorrhoeae from US military medical centers and found enrichment of blaTEM-1 in extragenital sites. Our findings support the value of anatomic site–specific surveillance, especially for extragenital infections in sexually transmitted infections, and molecular AMR marker detection (1,4,8,9).
Dr. Dombach is currently a DVM student at Purdue University after serving as the laboratory services officer for the United States Military Hospital–Kuwait. Current research interests are focused on One Health initiatives and combatting antimicrobial resistance.
Acknowledgments
This work was supported by funding from Global Emerging Infections Surveillance.
The views expressed in this study are those of the authors and do not necessarily reflect the official policy or position of the Defense Health Agency, Department of Defense, nor the US Government. This work was prepared as part of official duties. Title 17, U.S.C., Section 105 provides that copyright protection under this title is not available for any work of the US Government. Title 17, U.S.C., Section 101 defines a US Government work as a work prepared by a military service member or employee of the US Government as part of that person’s official duties.
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Suggested citation for this article: Dombach JL, MacArthur JL, Mekonnen C, La THA, Nxedhlana V, Norris MH, et al. Antimicrobial resistance in extragenital Neisseria gonorrhoeae infections, US military centers, 2022–2024. Emerg Infect Dis. 2026 Aug [date cited]. https://doi.org/10.3201/eid3208.260337
Original Publication Date: July 16, 2026
1Current affiliation: Cepheid, Sunnyvale, California, USA.
Table of Contents – Volume 32, Number 8—August 2026
