Combinations with Antimicrobial Chemotherapy

Abstract

The combination of antimicrobial chemotherapy with photodynamic therapy is one among many alternative antimicrobial combination treatments that were triggered by the rising incidence of drug resistance. The most common approaches include combinations by simple co-administration of the antibacterial chemotherapy drug and the photosensitizer, combinations using covalently linked photosensitizers and antibiotics, and combinations using nanoconjugate systems that incorporate the antibacterial drug and photosensitizer. As researchers pursued the purpose of enhancing the efficacy using these antibacterial combination approaches, selective bacterial cell targeting has emerged as an additional purpose offering the possibility of enhanced drug dosing while eliminating excessive systemic distribution and therefore the potential emergence or improvement of resistance. Typical clinical applications include infections of the skin and mucosal membranes, bacterial infections that colonize surfaces including those that form biofilms, infection with the highly resistant Burkholderia cepacia complex, bacterial infections of the urinary tract, nontuberculous mycobacterial keratitis, and conventional antibiotic endodontic treatment. Although it was the predominant approach initially, co-administration has all but given way to nanoparticle mediated approaches. Some of the antibiotics that have been reported in the combination approach include vancomycin, erythromycin, amoxicillin, streptomycin, ampicillin, amikacin, and gentamycin. Some of the commonly used photodynamic therapy photosensitizers include chlorin-e6, zinc(ii)phthalocyanine, meso-tetrakis(4-aminophenyl)porphyrin, meso-tetrakis(1-methylpyridinium-4-yl)porphyrin tetra-iodide (Figure 11.4(c)), and meso-tetrakis(3-hydroxyphenyl)chlorin. Several nanoconjugates have been designed and investigated as potential antibiotic drug and photosensitizer carrier systems as well as for bacterial cell targeting, including liposomes, core–shell mesoporous silica–carbon quantum dots, and copper sulfide.