Institute of Immunology & Microbiology, Costerton Biofilm Center, University of Copenhagen, Copenhagen, Denmark.
Department of Clinical Microbiology, Rigshospitalet, Copenhagen, Denmark.
APMIS. 2024 Dec;132(12):1086-1095. doi: 10.1111/apm.13413. Epub 2024 Apr 15.
Azithromycin (AZM) is efficient for treatment of chronic Pseudomonas aeruginosa biofilm lung infections, despite of resistance in conventional susceptibility testing. It has been shown that planktonic P. aeruginosa are more susceptible to AZM when tested in RPMI 1640 medium. The aim of the study was to test the susceptibility to AZM of P. aeruginosa biofilms in LB vs RPMI 1640 media. We investigated the effect of AZM on planktonic and biofilms of (WT) P. aeruginosa (PAO1), the hypermutable (ΔmutS) and the antibiotic-resistant phenotype(ΔnfxB) mutants. The effect of AZM on young and mature biofilms was investigated in the modified Calgary Biofilm Device by estimation of the minimal biofilm inhibitory concentration (MBIC). The AZM MBIC in LB/RPMI1640 on young biofilms treated for 24 h was 16/4 μg/mL for PAO1, 32/8 μg/mL for ΔmutS, and 256/16 μg/mL for ΔnfxB, while in mature biofilms was 256/2 μg/mL for PAO1 and ΔmutS and 16/1 μg/mL for ΔnfxB. The effect of AZM was improved when the treatment was prolonged to 72 h, supporting the intracellular accumulation of AZM. An increased susceptibility of P. aeruginosa biofilms to AZM was observed in RPMI 1640 than in LB medium. Our results might improve susceptibility testing and dosing of AZM for treatment of biofilm infections.
阿奇霉素（AZM）在治疗慢性铜绿假单胞菌生物膜肺部感染方面非常有效，尽管在常规药敏试验中存在耐药性。已经表明，在 RPMI 1640 培养基中测试时，浮游态铜绿假单胞菌对 AZM 更敏感。本研究旨在测试 LB 与 RPMI 1640 培养基中铜绿假单胞菌生物膜对 AZM 的敏感性。我们研究了 AZM 对（WT）铜绿假单胞菌（PAO1）浮游态和生物膜、高突变（ΔmutS）和抗生素耐药表型（ΔnfxB）突变体的影响。通过估计最小生物膜抑制浓度（MBIC），在改良的卡尔加里生物膜装置中研究了 AZM 对年轻和成熟生物膜的影响。在 LB/RPMI1640 中处理 24 小时的年轻生物膜中，PAO1 的 AZM MBIC 为 16/4 μg/mL，ΔmutS 为 32/8 μg/mL，ΔnfxB 为 256/16 μg/mL，而在成熟生物膜中，PAO1 和 ΔmutS 为 256/2 μg/mL，ΔnfxB 为 16/1 μg/mL。当治疗延长至 72 小时时，AZM 的效果得到改善，支持 AZM 的细胞内积累。在 RPMI 1640 培养基中观察到铜绿假单胞菌生物膜对 AZM 的敏感性增加，而在 LB 培养基中则没有。我们的结果可能会改善生物膜感染治疗中 AZM 的药敏试验和剂量。
