Molteni Therapeutics srl, via Fiorentina 1, 53100 Siena, Italy.
Antimicrob Agents Chemother. 2010 Feb;54(2):637-42. doi: 10.1128/AAC.00603-09. Epub 2009 Dec 14.
Resistance to antimicrobial agents is emerging in a wide variety of nosocomial and community-acquired pathogens. The development of alternative therapies against nosocomial infections caused by clinically relevant pathogens represents a major public health concern. RLP068/Cl is a novel Zn(II) phthalocyanine proposed as a photosensitizer suitable for antimicrobial photodynamic therapy (APDT) for localized infections. Its ability, following activation by light, to induce resistance in three major human pathogens after 20 daily passages was studied. Simultaneously for the same strains, the ability of daily sequential subcultures in subinhibitory concentrations of RLP068/Cl to develop resistant mutants without illumination was evaluated. We demonstrate that 20 consecutive APDT treatments with RLP068/Cl did not result in any resistant mutants and that, in dark conditions, only Staphylococcus aureus strains had increased MICs of RLP068/Cl. However, even in this case, the susceptibility of the mutated bacteria to APDT was not affected by their MIC increase.
抗微生物药物的耐药性正在多种医院内和社区获得性病原体中出现。针对由临床相关病原体引起的医院感染的替代疗法的开发是一个主要的公共卫生关注点。RLP068/Cl 是一种新型的 Zn(II)酞菁，被提议作为一种适合局部感染的光动力抗菌治疗（APDT）的光敏剂。研究了其在经过 20 次每日传代后用光激活对三种主要人类病原体产生耐药性的能力。同时，对于相同的菌株，还评估了在亚抑菌浓度的 RLP068/Cl 下每日连续传代在没有光照的情况下产生耐药突变体的能力。我们证明，20 次连续的 RLP068/Cl APDT 治疗没有产生任何耐药突变体，并且在暗条件下，只有金黄色葡萄球菌菌株的 RLP068/Cl MIC 增加。然而，即使在这种情况下，突变细菌对 APDT 的敏感性也不会受到其 MIC 增加的影响。
