## 4 _C. trachomatis_ Sensitivity Surveillance Efforts
Conducted using a McCoy cell culture system, they tested 14 cervical, 9 urethral, and 1 prostatic secretion isolate, finding all strains susceptible, with MICs of 0.064-0.125 \(\upmu\)g/mL for azithromycin and 0.016-0.064 \(\upmu\)g/mL for doxycycline and MCCs of 0.064-2.0 \(\upmu\)g/mL and 0.032-1.0 \(\upmu\)g/mL, respectively [71]. Despite reported clinical treatment failures linked to resistance elsewhere, no resistance was detected, underscoring the importance of ongoing surveillance to monitor potential shifts in antimicrobial susceptibility amid high antibiotic use. This was broadened several years later by [PERSON] et al. [72], with a total of 40 tested _C. trachomatis_ strains from Croatia showing susceptibility to the antibiotics evaluated (MIC < 4 \(\upmu\)g/mL), with no evidence of homotypic or heterotypic resistance patterns. The MCCs were either equivalent to or 1-5 dilutions greater than the MICs. In vitro testing demonstrated statistically significant variations in the efficacy of the antimicrobial agents in laboratory conditions [72]. A notable correlation was observed between MCCs for two pairs of antibiotics: azithromycin with levofloxacin and doxycycline with levofloxacin. When comparing median values across different clinical sample types, no significant differences emerged. And although not statistically significant, a trend toward higher MICs for azithromycin was observed, suggesting the need for further investigation [72]. In two surveillance studies from Tanzania, researchers investigated potential resistance development in ocular _C. trachomatis_ infections following three annual mass drug administrations (MDA). In an earlier study from [PERSON], [PERSON] et al. [73] assessed _C. trachomatis_ susceptibility to azithromycin and tetracycline before and two months after mass antibiotic treatment. All chlamdial isolates had MCCs of azithromycin \(\leq\) 2.0 \(\upmu\)g/mL, well below the mean conjunctival tissue concentration of 24.5 (\(\pm\)9.7) \(\upmu\)g/g measured in four patients 24 h after a 1 g dose, indicating sufficient drug levels [73]. Pre-treatment MCCs for tetracycline were \(\leq\)0.5 \(\upmu\)g/mL, dropping to \(\leq\)0.06 \(\upmu\)g/mL post treatment. Hence, mass antibiotic treatment did not induce clinically or programmatically significant changes in _C. trachomatis_ susceptibility to either azithromycin or tetracycline in this community. In a study by [PERSON] et al. [74] in 32 endemic communities, one year post MDA, there were 107 children infected; after another MDA, 90 were re-evaluated at two months, with 30 still infected. Paired isolates from 15 children before and after MDA showed no significant resistance, with average MICs of 0.26 \(\upmu\)g/mL and 0.20 \(\upmu\)g/mL for azithromycin, respectively, and all MICs \(\leq\) 0.50 \(\upmu\)g/mL [74]. Of note, infectious loads were similar between consistently infected children and those whose infections cleared, indicating that persistent infections were not due to azithromycin resistance or higher pre-treatment bacterial loads. In a surveillance study from Italy, [PERSON] et al. [75] evaluated the in vitro antimicrobial susceptibility of 20 _C. trachomatis_ strains--representing common genovars D, E, F, and G--in HeLa (endocervical) and Caco-2 (colorectal) cell lines to mimic urogenital and rectal infection sites. Susceptibility to azithromycin, erythromycin, doxycycline, and levofloxacin was tested, also exploring correlations between MIC values and bacterial load. Results showed that macrolides (azithromycin and erythromycin) had higher MIC and MBC values (by 2-fold dilutions) in Caco-2 cells compared to HeLa cells, while doxycycline and levofloxacin exhibited no notable differences between cell lines; additionally, azithromycin MICs in Caco-2 cells rose significantly with higher _C. trachomatis_ elementary body loads [75]. Their findings suggest that elevated azithromycin MICs in colorectal cells, combined with load-dependent increases, may contribute to treatment failures for rectal _C. trachomatis_ infections.