Al-Jabri Maha Y, Dousa Khalid M, Wilson Brigid M, Bonomo Robert A
Division of Infectious Diseases and HIV Medicine, Department of Medicine, University Hospitals-Cleveland Medical Center, Cleveland, OH, USA.
Department of Medicine, Case Western Reserve University, Cleveland, OH, USA.
JAC Antimicrob Resist. 2024 Sep 13;6(5):dlae142. doi: 10.1093/jacamr/dlae142. eCollection 2024 Oct.
The complex (MAC) are non-tuberculous mycobacteria responsible for chronic and debilitating conditions. Guideline-recommended therapy for MAC is a combination of clarithromycin/azithromycin, ethambutol and a rifamycin. However, culture conversion rates with this regimen are 67%. Alternative treatment options are needed. Recent findings of β-lactam combinations in the treatment of other mycobacterial diseases have been promising. The proposed mechanism is an additive inhibition of multiple enzymes in the peptidoglycan synthesis pathway by the β-lactam combinations. Given the similarity in cell wall structures of MAC and , we hypothesize that using dual β-lactams will result in interruption of peptidoglycan synthesis in MAC and reduction of MIC. In this study, we sought to determine the MIC of meropenem in combination with ceftaroline, cefdinir and cefuroxime in MAC.
A total of 31 clinical MAC isolates were used for susceptibility testing using broth microdilution method. MICs were tested for meropenem, ceftaroline, cefdinir and cefuroxime, alone, as well as combinations of meropenem plus ceftaroline, cefdinir, or cefuroxime.
MAC susceptibility to meropenem was significantly enhanced with the addition of ceftaroline, cefdinir, and cefuroxime. This effect was most significant with addition of ceftaroline and cefdinir, with a change of meropenem MIC/MIC from 16/32 to 0.125/0.5 and 0.125/4 mg/L, respectively ( value ≤0.0001, Wilcoxon signed-rank test).
This study demonstrates that the susceptibility of MAC to meropenem is restored with the addition of ceftaroline and cefdinir. These findings underscore the potential effectiveness of combining β-lactams as an alternative therapeutic strategy for MAC infections.
鸟分枝杆菌复合体（MAC）是非结核分枝杆菌，可导致慢性衰弱性疾病。指南推荐的MAC治疗方案是克拉霉素/阿奇霉素、乙胺丁醇和利福霉素联合使用。然而，该方案的培养转阴率为67%。需要其他治疗选择。β-内酰胺类联合用药治疗其他分枝杆菌疾病的最新研究结果很有前景。推测的机制是β-内酰胺类联合用药对肽聚糖合成途径中的多种酶具有累加抑制作用。鉴于MAC和[此处原文缺失相关信息]的细胞壁结构相似，我们假设使用双重β-内酰胺类药物将导致MAC中肽聚糖合成中断并降低最低抑菌浓度（MIC）。在本研究中，我们试图确定美罗培南与头孢托罗、头孢地尼和头孢呋辛联合使用时对MAC的MIC。
使用肉汤微量稀释法对31株临床MAC分离株进行药敏试验。测试了美罗培南、头孢托罗、头孢地尼和头孢呋辛单独使用时以及美罗培南加头孢托罗、头孢地尼或头孢呋辛联合使用时的MIC。
添加头孢托罗、头孢地尼和头孢呋辛后，MAC对美罗培南的敏感性显著增强。添加头孢托罗和头孢地尼时这种效果最为显著，美罗培南的MIC分别从16/32变为0.125/0.5和0.125/4mg/L（P值≤0.0001，Wilcoxon符号秩检验）。
本研究表明，添加头孢托罗和头孢地尼可恢复MAC对美罗培南的敏感性。这些发现强调了联合使用β-内酰胺类药物作为MAC感染替代治疗策略的潜在有效性。
