The Effect of Amoxicillin Pre-Exposure on Treatment Outcomes and Antimicrobial Susceptibility in Patients with Urogenital Chlamydia trachomatis Infection

Abstract

Purpose We investigated the influence of amoxicillin pre-exposure on treatment outcomes, Chlamydia trachomatis (CT) culture, the presence of drug-resistant genes, minimum inhibitory concentrations (MICs), and fractional inhibitory concentrations (FICs) in CT clinical strains. Additionally, we explored the effect of different antimicrobial combinations on CT. Patients and Methods Clinical data of 62 patients with CT infection were recorded. Of these, 33 had pre-exposure to amoxicillin and 29 did not. Among patients with pre-exposure, 17 received azithromycin and 16 received minocycline. Among the patients without pre-exposure, 15 received azithromycin and 14 received minocycline. All patients underwent microbiological cure follow-ups one month after completing the treatment. 23S rRNA gene mutations, acquisition of tet (M) and tet (C) were detected using reverse transcription PCR (RT-PCR) and PCR, respectively. The MICs and FICs of azithromycin, minocycline, and moxifloxacin, alone or in combination, were determined using the microdilution and checkerboard methods, respectively. Results More cases of treatment failure occurred in pre-exposed patients, in both treatment groups ( P <0.05). No 23S rRNA gene mutations or tet (M) and tet (C) acquisitions were found. More inclusion bodies were cultured from patients without amoxicillin pre-exposure than from those with pre-exposure ( P <0.0001). The MICs of all antibiotics were higher in pre-exposed patients than in those without pre-exposure ( P <0.01). The FICs of azithromycin plus moxifloxacin were lower than those of the other antibiotic combinations ( P <0.0001). The synergy rate of azithromycin plus moxifloxacin was significantly higher than those of azithromycin plus minocycline and minocycline plus moxifloxacin ( P <0.001). The FICs of all antibiotic combinations were comparable between isolates from the two patient groups (all P >0.05). Conclusion Pre-exposure to amoxicillin in CT patients may inhibit CT growth and decrease sensitivity of CT strains to antibiotics. Azithromycin plus moxifloxacin may be a promising treatment regimen for genital CT infections with treatment failure.

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“…The discovery of novel “green” OOP-based formulations as anti-chlamydial agents is highly relevant in light of the fact that, in recent years, the problem of antimicrobial resistance has also acquired growing importance in C. trachomatis , as suggested by significant treatment failure rates following first-line antimicrobials like doxycycline or azithromycin [ 26 ]. In particular, treatment failure ranged from 5% to 23% depending upon the population examined, and further evidence showed higher treatment failure rates (up to 14%) during azithromycin treatment than with doxycycline [ 9 , 27 , 28 ]. These observations are not surprising since in vitro studies have reported that azithromycin resistance could be raised through mutations in C. trachomatis 23S rRNA genes [ 10 , 29 ].…”

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