부산대학교 도서관

Background: MG treatment failures are increasing. Lefamulin (Nabriva Therapeutics) is a novel pleuromutilin with FDA-approval for treating bacterial pneumonia. Minimum inhibitory concentrations for MG are low, suggesting it may be effective for MG treatment failures. Methods: Patients attending Melbourne Sexual Health Centre (MSHC) with macrolide-resistant MG having failed ≥1 prior regimen were enrolled in a compassionate access program in-person (C. Bradshaw). Initially, patients were treated with oral lefamulin (600mg twice daily for 7 days). Subsequently, patients were pretreated with oral doxycycline (100mg twice daily for 7 days) followed by lefamulin for 7 days (doxycycline-lefamulin). Informed by these data, symptomatic US patients with MG treatment failure were referred, enrolled remotely (April 2022-February 2023), and randomized 1:1 to lefamulin or doxycycline-lefamulin (ClinicalTrials.gov NCT05111002). In-person (MSHC) and remote (US; mailed specimens) tests of cure occurred 21-28 and 42-47 days after completing lefamulin. Symptom and side effect data were elicited at both sites. MG was detected by ResistancePlus (SpeeDx, Pty; first 4 MSHC patients) and Aptima (Hologic, Inc; all others). Results: MSHC enrolled 12 patients (5 male/7 female); two people were treated twice. Treatment regimens were lefamulin (6 episodes, 1 withdrawal), doxycycline-lefamulin (6 episodes), and doxycycline followed by lefamulin+doxycycline combined (2 episodes) (Table). Twelve US patients enrolled (10 male/2 female). Five received lefamulin; 6 received doxycycline-lefamulin; 1 withdrew. Most MSHC patients (73%) had previously failed ≥3prior regimens (moxifloxacin, minocycline, sitafloxacin, pristinamycin); most US patients (82%) had previously failed moxifloxacin plus ≥1 other antibiotic (primarily doxycycline, azithromycin). Microbiologic cure was observed in 0/5 (0%) MSHC and 3/5 (60%) US patients after lefamulin and in 3/6 (50%) MSHC and 3/6 (50%) US patients after doxycyclinelefamulin. Doxycycline followed by lefamulin+doxycycline failed in 2/2. Overall, ≥50% reported mild-moderate nausea and/or diarrhea; two reported moderate-severe nausea; one withdrew due to side-effects. Conclusion: Lefamulin monotherapy failed in heavily pre-treated macrolide-resistant MG infections in Australia, but cured 3 of 5 less treatmentexperienced US patients. Sequential doxycyclinelefamulin cured half of infections in both cohorts, including those who had previously failed ≥3 prior regimens. Gastrointestinal side-effects were common. More data are needed to understand the role of lefamulin in managing resistant MG. [ABSTRACT FROM AUTHOR]