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.

The MacDonald's [2 + 2] condensation of unsubstituted dipyrromethane and 3- or 4-hydroxyalkoxybenzoaldehydes afforded 5,15-meso-hydroxyalkoxyphenylporphyrins. The hydroxyl groups on the side chains were then transformed to tertiary amines via synthesis of the mesylate and substitution with the appropriate amines or aminoalcohols. Methylation of such products afforded a series of cationic porphyrins which have been tested in vitro as photodynamic agents against microorganisms, showing high antimicrobial activity.