title: In vitro resistance selection studies of RLP068/Cl, a new Zn(II) phthalocyanine suitable for antimicrobial photodynamic therapy.
abstract: 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.
authors.affiliation: Molteni Therapeutics srl, via Fiorentina 1, 53100 Siena, Italy. f.giuliani@moltenitherapeutics.it
authors.forename: Francesco
authors.initials: F
authors.lastname: Giuliani
authors.forename: Manuele
authors.initials: M
authors.lastname: Martinelli
authors.forename: Annalisa
authors.initials: A
authors.lastname: Cocchi
authors.forename: Debora
authors.initials: D
authors.lastname: Arbia
authors.forename: Lia
authors.initials: L
authors.lastname: Fantetti
authors.forename: Gabrio
authors.initials: G
authors.lastname: Roncucci
mesh_terms: D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial / Q000528:radiation effects; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology*; D054833:Isoindoles; D008027:Light; D008826:Microbial Sensitivity Tests; D009942:Organometallic Compounds / Q000737:chemistry / Q000494:pharmacology*; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000528:radiation effects
chemical_list: D000890:Anti-Infective Agents; D007211:Indoles; D054833:Isoindoles; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; C477806:RLP068; C013647:phthalocyanine