In Vitro Resistance Selection Studies of RLP068/Cl, a New Zn(II) Phthalocyanine Suitable for Antimicrobial Photodynamic Therapy
In Vitro Resistance Selection Studies of RLP068/Cl, a New Zn(II) Phthalocyanine Suitable for Antimicrobial Photodynamic Therapy
复制标题
DOI：
10.1128/aac.00603-09
复制
发表时间：
2010-02-01
影响因子：
4.9
通讯作者：
Roncucci, Gabrio
中科院分区：
文献类型：
--
作者：
Giuliani, Francesco;Martinelli, Manuele;Roncucci, Gabrio
对抗菌药物的耐药性出现在各种各样的医院和社区获得性病原体中。针对由临床相关病原体引起的医院感染的替代疗法的发展代表了主要的公共卫生问题。RLP 068/Cl是一种新型的锌酞菁类光敏剂，适用于局部感染的抗菌光动力疗法（APDT）。研究了其在经光活化后在20天传代后诱导三种主要人类病原体抗性的能力。同时，对于相同的菌株，评价了在亚抑制浓度的RLP 068/Cl中每日连续传代培养在没有光照的情况下产生抗性突变体的能力。我们证明，20个连续的APDT处理与RLP 068/Cl没有导致任何耐药突变体，在黑暗条件下，只有金黄色葡萄球菌菌株有增加的MIC的RLP 068/Cl。然而，即使在这种情况下，突变细菌对APDT的敏感性也不受其MIC增加的影响。
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.