Abstract
Among 64 Neisseria gonorrhoeae isolates, the MIC50 of tetracycline was 1 µg/mL while the MIC90 was 16 µg/mL. The MIC50 of doxycycline was 1 µg/mL while the MIC90 was 8 µg/mL. The essential agreement between doxycycline and tetracycline was 92.2% (95% confidence interval 82.7%–97.4%).
Over the past several decades, Neisseria gonorrhoeae has developed resistance to all antimicrobials used in its treatment.1 With rising rates of ceftriaxone resistance in some parts of the world,2–5 drug-resistant N. gonorrhoeae is now an urgent public health threat.6,7 Doxycycline postexposure prophylaxis (doxy-PEP) has become increasingly utilized8 as an effective strategy to prevent some bacterial sexually transmitted infections.9–11 One primary concern surrounding the use of doxy-PEP, however, is the potential to select for antimicrobial resistance.12 Recent reports have highlighted the dramatic increase in N. gonorrhoeae strains harboring genetic determinants of doxycycline resistance, which was temporally correlated with increased doxycycline use.13
Expansion of doxycycline resistance is concerning because it may further reduce the already uncertain effectiveness of doxy-PEP for preventing N. gonorrhoeae infection and may also crossselect for resistance to other antimicrobials.14 However, a key challenge for understanding and surveilling for doxycycline resistance is that doxycycline minimum inhibitory concentration (MIC) breakpoints have not been established. The Clinical and Laboratory Standards Institute (CLSI) recommends that isolates susceptible to tetracycline be considered susceptible to doxycycline. While historic reports demonstrated nonsignificant variability in MIC distribution between doxycycline and tetracycline,15 more recent data are not available. We thus aimed to compare MIC distribution among N. gonorrhoeae isolates for tetracycline and doxycycline.
METHODS
Antimicrobial Susceptibility Testing
We used N. gonorrhoeae isolates collected during prior studies,16 for laboratory validation and as a part of routine surveillance, which were stored at −80°C. Antimicrobial susceptibility testing using Agar dilution had been performed for ciprofloxacin, azithromycin, and ceftriaxone for all isolates using methods previously described.16 We conducted laboratory work in the United States for isolates stored in the United States, and in Australia for isolates stored in Australia.
We cultured N. gonorrhoeae isolates on gonococcal agar plates for 24 h in 5% CO2 at 35°C. We subcultured each isolate twice to ensure purity. We then prepared a standardized inoculum of 0.5 McFarland of each subculture, and incubated isolates on gonococcal agar supplemented with IsoVitaleX at 35°C in 5% CO2 with Etest strips (Etest, bioMérieux, France) for tetracycline and doxycycline. After 20–24 h we recorded the point of complete inhibition in accordance with European Committee on Antimicrobial Susceptibility Tests (EUCAST) gradient diffusion reading guidance. We evaluated each isolate in triplicate and used the modal MIC for analyses. For quality control, we used the American Type Culture Collection N. gonorrhoeae isolate 49226 (known tetracycline MIC range 0.25–1 µg/mL by Etest).
Comparison of MICs
Among all isolates, we compared the MIC at which 50% (MIC50) and 90% (MIC90) of isolates were inhibited by each antibiotic, and the modal MIC. We used tetracycline MIC breakpoints for the agar dilution method from both CLSI and EUCAST guidelines for all isolates.17,18 The CLSI defines tetracycline resistance in N. gonorrhoeae as an MIC ≥2 µg/mL, intermediate susceptibility as an MIC between 0.5–1 µg/mL, and susceptibility as an MIC ≤0.25 µg/mL.18 Tetracycline resistance is defined by EUCAST as an MIC >0.5 µg/mL with no intermediate category.17
We explored the essential and categorical agreement between tetracycline and doxycycline. Given the absence of established clinical MIC breakpoints or epidemiological cutoff values for doxycycline resistance, we used the tetracycline breakpoints established by the CLSI and EUCAST and evaluated the agreement for phenotypic classification between the 2 antibiotics. We defined essential agreement as the number of isolates within 1 doubling dilution divided by the total number of isolates tested. We defined categorical agreement as the number of isolates with the same susceptible/intermediate/resistant categorical assignment divided by the total number of isolates tested.
Given that we used Etests to determine the MIC, which permit interpretation between doubling dilutions, we report Etest MICs rounded to the nearest upper doubling dilution19 and calculated essential agreement after rounding the log2 transformed modal MIC values. The Supplemental Table, https://links.lww.com/OLQ/B345 shows the raw Etest MIC values. For comparison purposes, we used the modal MICs if the difference between technical repeats was less than 2-fold. If the difference between technical repeats was greater than 2-fold, we assumed an error had occurred and repeated the culture.
Ethical Considerations
The isolates tested in the United States were collected during a prior study16 or for laboratory validation with consent for future use. The secondary use of those isolates was approved by the Mass General Brigham Institutional Review Board. Bacterial isolates provided by the Victorian Infectious Disease Reference Laboratory, Australia, were shared under a collaborative agreement.
RESULTS
We cultured 64 N. gonorrhoeae isolates collected between 2011 and 2024 (Table 1). Of those 64 isolates, 9 (14.1%) were susceptible to ciprofloxacin, 32 (50.0%) were susceptible to penicillin, 59 (92.3%) were susceptible to ceftriaxone, and 56 (87.5%) were susceptible to azithromycin using CLSI breakpoints.18,20
TABLE 1.
Characteristics of 64 Neisseria gonorrhoeae Isolates Evaluated for Tetracycline and Doxycycline Minimum Inhibitory Concentrations
| Study ID | Year | Anatomic Site | Ciprofloxacin | Penicillin | Spectinomycin | Cefixime | Ceftriaxone | Azithromycin | Tetracycline* | Doxycycline* |
|---|---|---|---|---|---|---|---|---|---|---|
| FQ005† | 2014 | Pharynx | ≤0.015 | 1.00 | S | 0.032 | 0.016 | 0.25 | 0.064 | 0.064 |
| FQ027† | 2014 | Urethra | 8.00 | 1.00 | S | 0.064 | 0.032 | 0.25 | 1.00 | 1.00 |
| FQ043† | 2013 | Urethra | 8.00 | 1.00 | S | 0.064 | 0.032 | 0.25 | 1.00 | 1.00 |
| FQ056† | 2013 | Urethra | 8.00 | 1.00 | S | 0.064 | 0.032 | 0.25 | 1.00 | 1.00 |
| FQ059† | 2013 | Urethra | 16.00 | 1.00 | S | ≤0.015 | ≤0.008 | 1.00 | 0.50 | 1.00 |
| FQ049† | 2013 | Urethra | >16 | 4.00 | S | 0.064 | 0.032 | 0.25 | 1.00 | 1.00 |
| FQ093† | 2014 | Urethra | >16 | 2.00 | S | 0.064 | 0.032 | 2.00 | 2.00 | 2.00 |
| FQ091† | 2014 | Urethra | 8.00 | 2.00 | S | 0.125 | 0.032 | 8.00 | 2.00 | 1.00 |
| FQ009† | 2014 | Urethra | >16 | 16.00 | S | 0.125 | 0.25 | 0.50 | 2.00 | 2.00 |
| FQ071† | 2014 | Urethra | 8.00 | 2.00 | S | 0.25 | 0.125 | 0.50 | 1.00 | 1.00 |
| FQ041† | 2011 | Urethra | 16.00 | 4.00 | S | 0.25 | 0.125 | 2.00 | 1.00 | 1.00 |
| FQ045† | 2011 | Urethra | 16.00 | 2.00 | S | 0.25 | 0.125 | 0.50 | 1.00 | 1.00 |
| FQ048† | 2012 | Urethra | 16.00 | 4.00 | S | 0.25 | 0.125 | 0.50 | 1.00 | 1.00 |
| FQ050† | 2011 | Urethra | 16.00 | - | S | 0.25 | 0.064 | 0.25 | 1.00 | 1.00 |
| FQ053† | 2011 | Urethra | 16.00 | 2.00 | S | 0.25 | 0.125 | 0.50 | 2.00 | 2.00 |
| FQ069† | 2014 | Urethra | >16 | 1.00 | S | 0.25 | 0.064 | 0.125 | 0.50 | 0.50 |
| FQ030† | 2014 | Urethra | 1.00 | 8.00 | S | ≤0.015 | ≤0.008 | 0.25 | 8.00 | 8.00 |
| FQ038† | 2014 | Urethra | 1.00 | 0.50 | S | ≤0.015 | ≤0.008 | 0.50 | 0.50 | 0.50 |
| FQ047† | 2013 | Urethra | 1.00 | 16.00 | S | ≤0.015 | ≤0.008 | 0.125 | 16.00 | 8.00 |
| FQ023† | 2014 | Urethra | 16.00 | >16.00 | S | ≤0.015 | 0.016 | 0.25 | 64.00 | 8.00 |
| FQ059† | 2013 | Urethra | 16.00 | 1.00 | S | ≤0.015 | ≤0.008 | 1.00 | 0.50 | 1.00 |
| CCC009‡ | 2015 | Urethral | 32.00 | >64.00 | 16.00 | 2.00 | 1.00 | 0.50 | 2.00 | 1.00 |
| DDD004‡ | 2017 | Urethral | 32.00 | 4.00 | 16.00 | 2.00 | 1.00 | 0.50 | 2.00 | 2.00 |
| DDD044‡ | 2018 | Urethral | 8.00 | 0.50 | 16.00 | 1.00 | 0.50 | 0.125 | 2.00 | 2.00 |
| EEE004‡ | 2018 | Urethral | 8.00 | 2.00 | 16.00 | 2.00 | 0.50 | 0.25 | 1.00 | 1.00 |
| FFF040‡ | 2014 | Urethral | 16.00 | 2.00 | 16.00 | 2.00 | 0.50 | 0.125 | 0.50 | 0.50 |
| CCC018‡ | 2016 | Urethral | 16.00 | 8.00 | 16.00 | 0.25 | 0.25 | 0.50 | 2.00 | 1.00 |
| DDD022‡ | 2017 | Urethral | 16.00 | 1.00 | 16.00 | 1.00 | 0.25 | 0.25 | 1.00 | 1.00 |
| CCC007‡ | 2014 | Urethral | 16.00 | 4.00 | 16.00 | 0.25 | 0.25 | 0.50 | 1.00 | 1.00 |
| FFF010‡ | 2014 | Urethral | 16.00 | 8.00 | 16.00 | 0.25 | 0.25 | 0.25 | 2.00 | 2.00 |
| CCC006‡ | 2015 | Urethral | 32.00 | 2.00 | 16.00 | 0.25 | 0.125 | 0.25 | 1.00 | 1.00 |
| DDD014‡ | 2017 | Urethral | 32.00 | 1.00 | 32.00 | 0.50 | 0.125 | 0.25 | 1.00 | 0.50 |
| DDD021‡ | 2017 | Urethral | 16.00 | 0.50 | 32.00 | 0.50 | 0.125 | 0.25 | 0.50 | 0.50 |
| DDD035‡ | 2018 | Urethral | 16.00 | 1.00 | 16.00 | 0.50 | 0.125 | 0.125 | 1.00 | 0.50 |
| DDD050‡ | 2018 | Urethral | 16.00 | 1.00 | 16.00 | 0.50 | 0.125 | 0.125 | 1.00 | 0.50 |
| CCC001‡ | 2015 | Cervical | 16.00 | 4.00 | 16.00 | 0.25 | 0.125 | 0.25 | 1.00 | 1.00 |
| AM001§ | 2024 | ≤0.03 | 0.50 | ≤0.008 | ≤0.064 | 8.00 | 4.00 | |||
| AM002§ | 2024 | ≤0.03 | 2.00 | ≤0.008 | ≤0.064 | 16.00 | 8.00 | |||
| AM003§ | 2024 | 4.00 | 2.00 | ≤0.016 | ≤0.064 | 16.00 | 8.00 | |||
| AM004§ | 2024 | 4.00 | 0.50 | ≤0.008 | ≤0.064 | 16.00 | 8.00 | |||
| AM006§ | 2024 | ≤0.03 | 2.00 | ≤ 0.008 | ≤0.064 | 0.032 | 0.25 | |||
| AM007§ | 2024 | 4.00 | 0.50 | ≤0.008 | 1.00 | 0.50 | 1.00 | |||
| AM008§ | 2024 | 4.00 | 0.50 | ≤0.008 | 1.00 | 0.50 | 1.00 | |||
| AM009§ | 2024 | 1.00 | 0.25 | 0.032 | 0.25 | 16.00 | 8.00 | |||
| AM010§ | 2024 | 4.00 | 0.50 | 0.032 | 2.00 | 0.50 | 1.00 | |||
| AM011§ | 2024 | 8.00 | >2.00 | 0.032 | 0.125 | 32.00 | 8.00 | |||
| AM012§ | 2024 | 4.00 | 0.50 | ≤0.008 | 0.25 | 0.50 | 0.50 | |||
| AM013§ | 2024 | ≤0.03 | 2.00 | ≤0.008 | ≤0.064 | 16.00 | 8.00 | |||
| AM014§ | 2024 | 2.00 | >2.00 | 0.032 | 0.25 | 16.00 | 8.00 | |||
| AM015§ | 2024 | 4.00 | 0.50 | ≤0.008 | 0.25 | 0.50 | 1.00 | |||
| AM016§ | 2024 | 2.00 | 0.25 | ≤0.008 | 0.125 | 0.125 | 0.25 | |||
| AM017§ | 2024 | ≤0.032 | 0.25 | ≤0.008 | ≤0.064 | 0.25 | 0.50 | |||
| AM018§ | 2024 | 4.00 | 0.50 | ≤0.008 | 1.00 | 0.50 | 1.00 | |||
| AM019§ | 2024 | 4.00 | 0.50 | 0.064 | 1.00 | 0.25 | 1.00 | |||
| AM020§ | 2024 | 2.00 | >2.00 | 0.032 | 0.125 | 16.00 | 8.00 | |||
| AM021§ | 2024 | 8.00 | 0.50 | 0.016 | 1.00 | 0.50 | 1.00 | |||
| AM022§ | 2024 | 4.00 | 0.50 | ≤0.008 | 1.00 | 0.50 | 1.00 | |||
| AM023§ | 2024 | ≤0.032 | >2.00 | ≤0.008 | ≤0.064 | 8.00 | 8.00 | |||
| AM024§ | 2024 | 8.00 | 1.00 | 0.016 | 0.25 | 0.25 | 0.50 | |||
| AM025§ | 2024 | 4.00 | 0.50 | 0.016 | 1.00 | 0.25 | 0.50 | |||
| AM026§ | 2024 | 4.00 | >2.00 | 0.032 | 0.25 | 16.00 | 16.00 | |||
| AM027§ | 2024 | 8.00 | 0.50 | ≤0.008 | 0.50 | 0.50 | 1.00 | |||
| AM028§ | 2024 | 4.00 | 0.50 | ≤0.008 | 0.25 | 0.25 | 1.00 | |||
| AM029§ | 2024 | ≤0.032 | 0.25 | ≤0.008 | 0.25 | 0.50 | 1.00 |
MICs for doxycycline and tetracycline were measured using Etests as a part of this study. The values reported represent the modal MIC across 3 replicates.
Isolates collected in the United States for laboratory validation, Clinical Laboratory Improvement Amendment studies. MICs measured using Agar dilution.
Isolates collected during a prior study. MICs measured using Agar dilution.16
Isolates collected as part of routine surveillance in Australia. MICs measured using Agar dilution.
By CLSI breakpoints, 24 (37.5%) isolates were tetracycline resistant, 33 (52.6%) were intermediate, and 7 (10.9%) were susceptible. By EUCAST breakpoints, 41 (64.1%) isolates were tetracycline resistant, and 23 (35.9%) were susceptible. The MIC50 of tetracycline was 1 µg/mL while the MIC90 was 16 µg/mL, with a modal MIC of 1 µg/mL (range 0.019–64). The MIC MIC50 of doxycycline was 1 µg/mL, while the MIC90 was 8 µg/mL with a modal MIC of 1 µg/mL (range 0.125–16) (Fig. 1). Among isolates susceptible to tetracycline, the doxycycline MIC50 was 0.5 µg/mL, and the MIC90 was 1 µg/mL. Among isolates with intermediate susceptibility to tetracycline, the doxycycline MIC50 and MIC90 were 1 µg/mL. Among isolates with tetracycline resistance, the doxycycline MIC50 was 1 µg/mL, and the MIC90 was 8 µg/mL.
Figure 1.
Distribution of tetracycline and doxycycline MICs among 64 Neisseria gonorrhoeae isolates. Resistance breakpoints are shown using CLSI cutoffs.
The essential agreement between tetracycline and doxycycline MICs was 92.2% (95% confidence interval [CI] 82.7%–97.4%). Using CLSI breakpoints, 5 isolates were classified as tetracycline susceptible but intermediate susceptible to doxycycline, while 3 isolates were classified as tetracycline resistant but intermediate susceptible to doxycycline, leading to a categorical agreement of 87.5% (95% CI 76.9%–94.5%). Using the EUCAST breakpoints, 12 isolates were classified as tetracycline susceptible but resistant to doxycycline, while 3 were classified as tetracycline resistant but susceptible to doxycycline, resulting in a categorical agreement of 76.6% (95% CI 64.3%–86.3%).
DISCUSSION
We evaluated the concordance between tetracycline and doxycycline phenotypic susceptibility profiles of N. gonorrhoeae. The 2 antibiotics appeared to have similar efficacy with a high essential agreement, although doxycycline had a lower MIC90, potentially indicating higher potency than tetracycline. Phenotypic discordance between tetracycline and doxycycline MICs has implications for resistance surveillance and public health policy, particularly as doxycycline use continues to increase globally.
We found that the MIC90 of doxycycline was lower than the MIC90 of tetracycline. That finding is consistent with prior work demonstrating that doxycycline was more potent than tetracycline against N. gonorrhoeae15 and against Streptococcus pneumoniae.21 The difference may reflect variation in how resistance mechanisms affect each drug. For example, the plasmid-mediated ribosomal protection protein encoded by the tetM gene may have a greater impact on tetracycline than doxycycline,21 while chromosomally mediated mutations also appear to have a differential impact on doxycycline and tetracycline resistance.22,23 As tetracycline resistance rates continue to rise globally,24 reliance on tetracycline-based measures may increasingly overestimate doxycycline resistance in N. gonorrhoeae.
However, we also found a nontrivial proportion of N. gonorrhoeae isolates susceptible to tetracycline that may have harbored intermediate susceptibility or resistance to doxycycline, particularly using the EUCAST breakpoints. The difference in categorical agreement using the CLSI and EUCAST breakpoints likely arose because approximately half of the isolates harbored intermediate susceptibility to tetracycline – a category not included in the EUCAST breakpoints. That difference also underscores the need to harmonize such thresholds across regulatory agencies to avoid conflicting interpretations.
The impact of subtle differences in resistance classification between tetracycline and doxycycline is not clear. Doxy-PEP may be efficacious for preventing gonorrhea among some populations,10,25 with efficacy likely impacted by the baseline prevalence of doxycycline resistance in the population.26 Overestimating the prevalence of doxycycline resistance may lead to inappropriate deferral of doxy-PEP as a strategy in some settings. Clinical treatment failures using doxycycline for cases of gonorrhea have been reported among N. gonorrhoeae strains with an MIC ≥1 µg/mL,27 which does not align with tetracycline breakpoints. Thus, while the 2 antibiotics have overall similar efficacy, the differences observed warrant further consideration of doxycycline-specific susceptibility testing in research and surveillance programs.
LIMITATIONS
This study had several limitations. Primarily, the sample size was small, limiting the precision of our findings. Further, as there is no defined MIC breakpoint for doxycycline resistance, direct comparisons are limited. Etests are not the reference method for MIC testing in N. gonorrhoeae; however, prior work has demonstrated a strong concordance between Etests and agar dilution methods.28 Further, while all isolates analyzed were collected more recently than prior studies, approximately half of the isolates evaluated were collected before widespread use of doxycycline for treating Chlamydia trachomatis infection and as doxy-PEP. Microbial evolution consequent to such widespread use could impact differences in phenotypic profiles. Finally, we were unable to characterize the genomic resistance determinants within our sample. However, given the outstanding questions pertaining to doxycycline susceptibility in N. gonorrhoeae, we feel those limitations do not negate the importance of our findings.
CONCLUSIONS
Among N. gonorrhoeae isolates, tetracycline and doxycycline had overall similar MIC distributions. As doxycycline use continues to increase, how and in what contexts surveillance programs should monitor for elevated doxycycline MICs specifically will be an important subject for future research.
Supplementary Material
Footnotes
Conflict of Interest and Sources of Funding: This work was supported in part by the National Institute of Allergy and Infectious Diseases (K23AI182453 to L.T.A.B.) and the Australian Research Council Industrial Transformation Research Hub Grant (IH190100021).
Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal’s Web site (http://www.stdjournal.com).
REFERENCES
- 1.Unemo M, Shafer WM. Antimicrobial resistance in Neisseria gonorrhoeae in the 21st century: past, evolution, and future. Clin Microbiol Rev 2014;27:587–613. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Ouk V, Pham CD, Wi T, et al. ; EGASP Cambodia working group. The enhanced gonococcal surveillance programme, Cambodia. Lancet Infect Dis 2023;23:e332–e333. [DOI] [PubMed] [Google Scholar]
- 3.Lan PT, Nguyen TT P, Anh VT, et al. The World Health Organization (WHO) enhanced gonococcal antimicrobial surveillance programme (EGASP) reports continuously high levels of ceftriaxone resistance across Viet Nam, 2024. Lancet Reg Health West Pac 2025;63:101709. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Adamson PC, Hieu VN, Nhung PH, et al. Ceftriaxone resistance in Neisseria gonorrhoeae associated with the penA-60.001 allele in Hanoi, Viet Nam. Lancet Infect Dis 2024;24:e351–e352. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Laumen JGE, Hieu VN, Nhung PH, et al. High prevalence of ceftriaxone-resistant Neisseria gonorrhoeae in Hanoi, Vietnam, 2023-2024. J Infect Dis 2025;232:e73–e77. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Centers for Disease Control and Prevention. Antibiotic Resistance Threats in the United States, 2019. Report; 2019. Available at: https://www.cdc.gov/antimicrobial-resistance/data-research/threats/index.html. Accessed March 9, 2026. [Google Scholar]
- 7.United Nations News. Antimicrobial resistance a “global health emergency,” UN, ahead of awareness week. November 12, 2018. Available at: https://news.un.org/en/story/2018/11/1025511 Accessed March 9, 2026.
- 8.Allan-Blitz LT, Traeger M, Gitin S, et al. Facilitators and barriers to the rollout of doxycycline postexposure prophylaxis for sexually transmitted infections in a Boston community health center. Sex Transm Dis 2025;52:585–590. [DOI] [PubMed] [Google Scholar]
- 9.Molina JM, Charreau I, Chidiac C, et al. ; ANRS IPERGAY Study Group. Post-exposure prophylaxis with doxycycline to prevent sexually transmitted infections in men who have sex with men: an open-label randomised substudy of the ANRS IPERGAY trial. Lancet Infect Dis 2018;18:308–317. [DOI] [PubMed] [Google Scholar]
- 10.Luetkemeyer AF, Donnell D, Dombrowski JC, et al. ; DoxyPEP Study Team. Postexposure doxycycline to prevent bacterial sexually transmitted infections. N Engl J Med 2023;388:1296–1306. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Molina JM, Bercot B, Assoumou L, et al. ; ANRS 174 DOXYVAC Study Group. Doxycycline prophylaxis and meningococcal group B vaccine to prevent bacterial sexually transmitted infections in France (ANRS 174 DOXYVAC): a multicentre, open-label, randomised trial with a 2 x 2 factorial design. Lancet Infect Dis 2024;24:1093–1104. [DOI] [PubMed] [Google Scholar]
- 12.Chu VT, Glascock A, Donnell D, et al. Impact of doxycycline post-exposure prophylaxis for sexually transmitted infections on the gut microbiome and antimicrobial resistome. Nat Med 2025;31:207–217. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Helekal D, Mortimer TD, Grad YH. Expansion of tetM-carrying Neisseria gonorrhoeae in the United States, 2018-2024. N Engl J Med 2025;393:198–200. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Mortimer TD, Grad YH. A genomic perspective on the near-term impact of doxycycline post-exposure prophylaxis on Neisseria gonorrhoeae antimicrobial resistance. Clin Infect Dis 2023;77:788–791. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Whittington WL, Roberts MC, Hale J, et al. Susceptibilities of Neisseria gonorrhoeae to the glycylcyclines. Antimicrob Agents Chemother 1995;39:1864–1865. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Bristow CC, Mortimer TD, Morris S, et al. Whole-genome sequencing to predict antimicrobial susceptibility profiles in Neisseria gonorrhoeae. J Infect Dis 2023;227:917–925. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.European Committee on Amtimicrobial Susceptibility Tests. Clinical breakpoints and dosing of antibiotics. Available at: https://www.eucast.org/clinical_breakpoints Accessed October 16, 2025.
- 18.Performance standards for antimicrobial susceptibility testing, 24th informational supplement, CLSI document M100-S24. CLSI; 2014. [Google Scholar]
- 19.Pitt-Kendall R, Minshull J, Vivekanand S, et al. A testing time for gradient strips: an evaluation of ETEST for the antimicrobial susceptibility testing of Neisseria gonorrhoeae. J Med Microbiol 2025;74:002088. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Clinical & Laboratory Standards Institute (CLSI). January 2026. Performance standards for antimicrobial susceptibility testing, M100, 36th ed.: Clinical and Laboratory Standards Institute, Wayne: PA. [Google Scholar]
- 21.Dallas SD, McGee L, Limbago B, et al. Development of doxycycline MIC and disk diffusion interpretive breakpoints and revision of tetracycline breakpoints for Streptococcus pneumoniae. J Clin Microbiol 2013;51:1798–1802. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Hu M, Nandi S, Davies C, et al. High-level chromosomally mediated tetracycline resistance in Neisseria gonorrhoeae results from a point mutation in the rpsJ gene encoding ribosomal protein S10 in combination with the mtrR and penB resistance determinants. Antimicrob Agents Chemother 2005;49:4327–4334. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Robinson LR, McDevitt CJ, Regan MR, et al. Revisiting the potential impact of doxycycline post-exposure prophylaxis on the selection of doxycycline resistance in Neisseria commensals. Sci Rep 2025;15:12400. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Do K, Unemo M, Kenyon C, et al. Tetracycline-resistant Neisseria gonorrhoeae global estimates-impacts on doxycycline post-exposure prophylaxis implementation and monitoring: a systematic review. JAC Antimicrob Resist 2025;7:dlaf120. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Molina J, Bercot B, Assoumou L, Michele AG, Rubenstein E, Pialoux G, Katlama C, Sugers L, Bebear C, Dupin N, Viard JP, Pavie J, Duvivier C, Ghosn J, Costagliola D. ANRS 174 DOXYVAC: AN OPEN-LABEL RANDOMIZED TRIAL TO PREVENT STIs IN MSM ON PrEP. Presented at the Conference on Retroviruses and Opportunistic Infections. February 19-22 2023, Seattle, Washington. Abstract Available at: https://www.croiconference.org/abstract/anrs-174-doxyvac-an-open-label-randomized-trial-to-prevent-stis-in-msm-on-prep/ Accessed April 19, 2024. 2023. [Google Scholar]
- 26.Stewart J, Oware K, Donnell D, et al. ; dPEP Kenya Study Team. Doxycycline prophylaxis to prevent sexually transmitted infections in women. N Engl J Med 2023;389:2331–2340. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Wiesner PJ, Holmes KK, Sparling PF, et al. Single doses of methacycline and doxycycline for gonorrhea: a cooperative study of the frequency and cause of treatment failure. J Infect Dis 1973;127:461–466. [DOI] [PubMed] [Google Scholar]
- 28.Van Dyck E, Smet H, Piot P. Comparison of E test with agar dilution for antimicrobial susceptibility testing of Neisseria gonorrhoeae. J Clin Microbiol 1994;32:1586–1588. [DOI] [PMC free article] [PubMed] [Google Scholar]