## 4 _C. trachomatis_ Sensitivity Surveillance Efforts  
Surveillance of _C. trachomatis_ susceptibility across different countries should be seen as a pivotal step even though clinically relevant resistance is debated [56; 67], as it provides important insights into potential shifts in antimicrobial efficacy. There is a variability in local antibiotic use, strain diversity, and diagnostic practices that actually necessitates country-specific monitoring to detect emerging resistance patterns that might not yet manifest as widespread clinical failure but could signal future challenges--particularly in high-burden regions and regions with a high number of antibiotic prescriptions. In our review, only surveillance studies with more than 20 specimens were included to ensure robust sample sizes, enabling meaningful comparisons across diverse populations and healthcare systems. In what is considered one of the earliest examples of larger surveillance efforts of _C. trachomatis_ antimicrobial sensitivity in the literature, researchers from Israel evaluated the in vitro efficacy of clarithromycin, azithromycin, roxithromycin, erythromycinromycin, doxycycline, and tetracycline against 50 _C. trachomatis_ clinical isolates using a cycloheximide-treated Mc-Coy cell tissue culture system to determine MICs and minimal bactericidal concentrations (MBCs) [68]. All isolates showed MICs of \(\leq\)0.015 \(\upmu\)g/mL for clarithromycin, \(\leq\)0.125 \(\upmu\)g/mL for roxithromycin and azithromycin, and \(\leq\)0.25 \(\upmu\)g/mL for erythromycinom and doxycycline, while 44% required 0.5 \(\upmu\)g/mL of tetracycline for inhibition [68]. MBCs reached up to 4 \(\upmu\)g/mL for doxycycline (8% of isolates) and tetracycline (4%), but azithromycin, a CDC-recommended treatment, demonstrated significantly superior in vitro activity compared to erythromycinomcin and doxycycline. Another laudable and very broad surveillance effort on _C. trachomatis_ sensitivity was conducted in Japan [69]. In this study, urethral discharge specimens were collected from patients with urethritis in 51 hospitals and clinics in 2009 and 38 in 2012. MIC was determined for 19 isolates in 2009 and 39 in 2012. In both years, the MICs (MIC\({}_{90}\)) for several antibiotics were as follows: ciprofloxacin (2 \(\upmu\)g/mL in 2009; 1 \(\upmu\)g/mL in 2012), levofloxacin (0.5 \(\upmu\)g/mL), tousfloxacin (0.125 \(\upmu\)g/mL), sitafloxacin (0.063 \(\upmu\)g/mL), doxycycline (0.125 \(\upmu\)g/mL), minocycline (0.125 \(\upmu\)g/mL), erythromycinomcin (0.016 \(\upmu\)g/mL), clarithromycin (0.063 \(\upmu\)g/mL), and azithromycin (0.063 \(\upmu\)g/mL) [69]. In this study, there were no resistant strains against macrolide and/or tetracycline agents in Japan. This was followed more recently by the second broad nationwide surveillance of the antimicrobial susceptibility of _C. trachomatis_ in Japan from 26 hospitals and clinics in 2016 and 2017 [70], which (once again) did not identify any strains resistant to aforementioned antimicrobial agents. MIC values were comparable with the previous research endeavor [70]. Solithromycin was introduced into this study and showed the lowest MIC (0.016 \(\upmu\)g/mL) in comparison to other antimicrobials tested; however, azithromycin's MIC was slightly higher than in the first surveillance, though possibly within acceptable error margins, warranting the need for ongoing monitoring. As part of a national surveillance effort in Croatia--a country with Europe's highest azithromycin consumption and elevated antibiotic prescription rates--[PERSON] et al. [71] initially evaluated the in vitro susceptibility of 24 urogenital _Chlammydia trachomatis_strains to azithromycin and doxycycline, the recommended first-line treatments.