In the manuscript (ID Pathogens-608522), authors assessed ciprofloxacin susceptibility in 510 urethral Neisseria gonorrhoeae isolates and identified correlates associated with ciprofloxacin-resistant. This paper is interesting because it raises an important issue today, such as the use of antibiotics that we already have as a therapeutic alternative in those infections caused by resistant bacteria. However, the manuscript requires some modifications before being published. Comments:

(1) Treatment for gonococcal infection is being seriously threatened by the emergence of antimicrobial resistance. Bearing this in mind, governments all over the world have created programs to collect data in order to study the ways in which this species is developing resistances and presenting itself at a community level. Three of the most established programs are the Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP) in the United Kingdom (https://www.gov.uk/government/ publications/gonococcal-resistance-to-antimicrobialssurveillance-programme-grasp-report), the Gonococcal Isolate Surveillance Project (GISP) in the United States (https://www.cdc.gov/std/gisp/), and the European Gonococcal Antimicrobial Surveillance Programme (EuroGASP) (http://ecdc.europa.eu/en/healthtopics/gonorrhoea/ response-plan/pages/strengthening-antimicrobialsurveillance.aspx). The detection of ciprofloxacin-resistant strains increased in GRASP since 2012 (25 to 37.3% in 2014) and in GISP since 2009 (12 to 21% in 2014). On the other hand, Euro-GASP reports show a decrease in ciprofloxacin resistance from 63% in 2009 to 50% in 2014. Isolates were collected from 2014 to 2016. It has been 3 years, and resistance to ciprofloxacin has been able to vary. Authors should add this fact to the limitations of the study.

(2) Conclusions: authors conclude that: “Given the lower proportion of ciprofloxacin resistance in younger individuals, a targeted treatment approach may be more beneficial for patients under 35 years of age”. This is not entirely correct, because 57.6% (95/165) were confirmed as ciprofloxacin resistant in patients under 35 years of age. Please, clarify this conclusion.

(3) Table 3: to analyze the Odds Ratio in this study, authors should have made two age groups: < 35 years old and > 35 years old. Please, explain why you have not done it that way.

(4) According to the World Health Organization (WHO) guidelines, first-line antimicrobial therapy should be highly effective, widely available and affordable, lack toxicity, single dose, and (rapidly) cure at least >95% of infected patients. Currently, treatment guidelines according to different health organizations worldwide (Centers for Disease Control and Prevention, European Union and World Health Organization) are ceftriaxone + azithromycin (or cefixime). Authors should comment about these guidelines.

(5) Page 6, line 203 : Correct the reference number: “(MIC) of ciprofloxacin as previously described.14 Additionally..”

(6) Reference 20 does not follow the standard.

Comments for the editor:

The manuscript will improve if the authors take into account all the suggestions and make the appropriate amendments.