Increasing Antimicrobial Resistance to First-Line Therapies in Chronic Endometritis: A 2020–2024 Cross-Sectional Study

Objectives: In the context of the global rise in antimicrobial resistance (AMR), this study aimed to investigate temporal trends in AMR among pathogens isolated from endometrial cultures of patients diagnosed with chronic endometritis (CE). Methods: This cross-sectional study included 244 women consecutively diagnosed with CE at the Gynecology Unit of the University of Bari, Italy, between January 2020 and June 2024. Exclusion criteria were (i) previous CE diagnosis or treatment; (ii) antimicrobial use in the month prior to hysteroscopy and biopsy; (iii) use of oral or vaginal prebiotics/probiotics or contraceptives in the three months prior; (iv) known immunosuppression; and (v) hypersensitivity to quinolones or macrolides. CE was diagnosed using hysteroscopy combined with endometrial histology and microbial culture. Specifically, in cases with hysteroscopic signs suggestive of CE, endometrial biopsies were obtained using a Novak curette and processed for histological and immunohistochemical analyses, as well as for microbial identification and antimicrobial susceptibility testing in accordance with EUCAST guidelines. The primary outcomes were the prevalence of CE-associated pathogens and their AMR profiles. Results: The median age at CE diagnosis was 33 years (range 26–44). The most frequently isolated pathogens were Enterococcus faecalis (26.2%), Escherichia coli (19.3%), and Ureaplasma urealyticum (16.4%). High AMR rates were observed, with increasing trends over time. Ampicillin resistance reached 98.5% (63/64), penicillin resistance 30.8% (16/52), and extended-spectrum beta-lactamase (ESBL) positivity 34.7% (25/72), all with statistically significant trends (p < 0.001). Resistance to commonly used first-line antimicrobials, such as tetracyclines, quinolones, and nitroimidazoles, was also substantial. Conclusions: This study highlights a significant increase in AMRs among microorganisms responsible for CE between 2020 and 2024. As a result, empirical first-line antimicrobial therapies commonly used to treat patients with CE may be increasingly ineffective in a growing number of cases. This underscores the need for improved and targeted diagnostic and therapeutic strategies to effectively manage CE and prevent treatment failures. Strengthening surveillance systems, implementing antimicrobial stewardship programs, and enhancing patient education may help counter the growing threat of AMR.