Clinical meaning
STI treatment requires understanding of antimicrobial mechanisms, resistance patterns, and syndrome-based management. Gonorrhea resistance is the greatest current challenge: N. gonorrhoeae has developed resistance to sulfonamides (1940s), penicillin (1980s), tetracyclines (1980s), fluoroquinolones (2007 — CDC removed as recommended treatment), and azithromycin (2020s — CDC removed from dual therapy). Ceftriaxone remains the last reliable first-line agent, but decreased susceptibility has been reported globally. The CDC increased the recommended dose from 250 mg to 500 mg IM in 2021 to provide a higher margin above the MIC. Chlamydia: doxycycline's superiority over azithromycin is primarily driven by rectal chlamydia cure rates (doxycycline 97% vs. azithromycin 82%). Syphilis treatment relies entirely on penicillin: benzathine penicillin G's repository formulation provides sustained treponemicidal levels. The 2021 CDC guidelines also added doxy-PEP (doxycycline post-exposure prophylaxis 200 mg within 72 hours of condomless sex) as a strategy for STI prevention in MSM and transgender women, reducing chlamydia incidence by 88%, syphilis by 87%, but with less clear effect on gonorrhea.