Table 3 provides an overview of the cross-effects of aPDT reported across the included studies. The subsequent section highlights a representative subset that best illustrates the key concepts. The variability observed among studies underscores the challenges of standardizing outcomes for a single photosensitizer, given the strong influence of species- and strain-specific factors as well as the characteristics of the light source employed. Moreover, test results are shaped by physicochemical parameters that differ according to the pathology under investigation. Dose dependence is also critical, since three interrelated factors must be taken into account in aPDT: the availability of oxygen, the local concentration of the photosensitizer around the targeted microorganism(s), and the intensity of the applied light.
Table 3. Overview of studies examining cross-tolerance between aPDT and other antimicrobials.
aPDT Conditions | Targeted microorganism(s) | Observation(s) | Reference |
GlamTMPn, Incandescent lamps, 400-8-700 nm, 10 cycles | Actinobacillus actinomycetemcomitans, Peptostreptococcus micros & Prevotella intermedia | No change in antibiotic susceptibility to AMK, AMP, ATM, CAZ, CIP, CST, CTX, CFZ, GEN, IPM, PIP, SAM, STR, SXT, & TET | |
BOHTMPn, Incandescent lamps, 400-8-700 nm, 10 cycles | A. actinomycetemcomitans, Peptostreptococcus micros & P. intermedia | No change in antibiotic susceptibility to AMK, AMP, ATM, CAZ, CIP, CST, CTX, CFZ, GEN, IPM, PIP, SAM, STR, SXT, & TET | |
PPArg2, Halogen lamp with polarization filter, 624 nm | S. aureus | No changes in antibiotic susceptibility to OXA, ERY, LIN, GEN, CIP, SXT, VAN, TET, RIF, FA, PEN, AMP, MUP, NFU, OFX, TMP, TEC, CHL, DA, NET, TOB, AMK, KAN, LZD, TEL, and QUD | |
PPIX, Halogen lamp with polarization filter, 624 nm | S. aureus | No changes in antibiotic susceptibility to OXA, ERY, LIN, GEN, CIP, SXT, VAN, TET, RIF, FA, PEN, AMP, MUP, NFU, OFX, TMP, TEC, CHL, DA, NET, TOB, AMK, KAN, LZD, TEL, and QUD | |
MB, Xenon short arc lamp, 630 nm, 3 cycles | S. aureus | No changes in antibiotic susceptibility to VAN, MUP, and LIN | |
TNP, Xenon short arc lamp, 630 nm, 3 cycles | S. aureus | No changes in antibiotic susceptibility to VAN, MUP, and LIN | |
MB, Diode laser, 670 nm | E. coli & S. aureus | No change in antibiotic susceptibility to OXA | |
MB & TNP, LED, 635 nm, 10 cycles | S. aureus & P. aeruginosa | No change in antibiotic susceptibility to PIP/TZO, CAZ, MEM, and TOB | |
MB, Diode laser, 630 nm, 3 cycles | S. aureus | Increased resistance to ERY, AMC, and AMK, increased sensitivity to OXA and PIP | |
TBO, Diode laser, 630 nm, 3 cycles | S. aureus | Increased resistance to ERY, AMC, and AMK, increased sensitivity to OXA and PIP | |
Tetra-Py+-Me, LED, 380-700 nm, 10 cycles | S. aureus | No change in susceptibility to MET | |
TBO, LED, 630 nm | A. baumannii | Increased antibiotic susceptibility to LVX, CST, RIF for both strains, and for MIN, TET, TGC, and TZP for one of them, inhibition of the efflux pump system, and increased cell wall permeability | |
MB, Diode laser, 660 nm | K. pneumoniae, E. coli, P. aeruginosa, | In vivo resensitization to CHL, SXT, SUL, TET, AMC, AZT, FOX, unchanged sensitivity to NAL, STR, AMP for K. pneumoniae in boid snake. Loss of resistance genes sul1, dfrA12, and tetA, SUL, SXT, and TET- resistance genes, respectively | |
5-ALA, LED, 633nm, 2 cycles | Prototheca wickerhamii | No change in antibiotic susceptibility to CHL, AMP, CFZ, CIP, MIN, AMK | |
RB, LED, 515 nm, 5 cycles | S. aureus | Resensitization to GEN and DOX, no change for VAN, CHL, and RIF, increased mutation frequency of the rpoB gene that confers resistance to rifampicin | |
ICG, N.C., NIR light, 8 or 10 cycles | S. aureus | In vitro, decreased cell wall thickness and increased susceptibility to OXA, CEF, ERY, TET, and unchanged susceptibility to VAN, RIF, and PMB. In vitro, mecA, mecI, and mecR1 gene deletions; mecA expression is unchanged, decreased, or absent depending on the strain; and reduced PBP2a protein levels. Unchanged OXA susceptibility in murine skin infection and pneumonia models | |
RB, LED, 515 nm, 15 cycles | S. aureus | No change in antibiotic susceptibility to FA, GEN, LZD, MUP, SXT, & VAN | |
NMB, LED, 632 nm, 15 cycles | S. aureus | No change in antibiotic susceptibility to FA, GEN, LZD, MUP, SXT, & VAN | |
Cur, LED, 450 nm, 10 cycles | Streptococcus pyogenes | No change in antibiotic susceptibility to AMX, AZM, CIP, and STR | |
PDZ, LED, 660 nm, 5 cycles | Candida albicans | No changes in the MIC50 of FLU | |
HMME, N.C., 400-780 nm | E. coli | Decreased MIC for CAZ and CST | |
TMPyP, Diode laser, 445 nm | E. faecalis | Increased expression of vanA, the VAN-resistance gene | |
MB, Diode laser, 635nm, 15 cycles | A. baumannii | No change in antibiotic susceptibility to GEN, STR, NAL, and CHL | |
MB, LED, 650 nm | S. aureus | Resensitization to CHL and TET | |
[Ru(II)]1 or [Ru(II)]2, LED, 450-470 nm, 8 cycles | S. aureus | Unchanged antibiotic susceptibility to OXA, AMX, GEN, NET, KAN, TOB, AMK, LVX, ERY, LIN, LZD, FA, FOS, RIF, MUP | |
[Ru(II)]1 or [Ru(II)]2, LED, 450-470 nm, 8 cycles | P. aeruginosa | Unchanged antibiotic susceptibility to TIC, PIP, ATM, IPM, MEM, CAZ, FEP, GEN, AMK, TOB, LVX, CIP, CST, NET | |
TBO, N.C., 635 nm | S. aureus | Decrease in efflux pump encoding gene expression | |
5-ALA, LED, 635 nm | Mycobacterium abscessus | Increased cell wall permeability, reduced antifungal resistance gene expression (whiB7 and erm), efflux pump genes (MAB_1409c and MAB_3142c), resensitization to AZM, MXF, CIP, MEME, and LZD. Unchanged sensitivity to CLR, AMK, and MIN | |
PSRu-L2, LED, white light | K. pneumoniae | Resensitization to IPM | |
PSRu-L3, LED, white light | K. pneumoniae | Resensitization to IPM | |
MB + KI, LED, 633 nm | C. albicans | Reduced antibiotic susceptibility to AmB, FLU, and 5-FC depending on the strain or PS. Unchanged MIC50 for ITR | |
ZnPPc4+, Halogen lamp, 380-700, 10 cycles | E. coli | No change in antibiotic susceptibility to GEN, CAZ, AMS, CTX, TMS | |
aBL, LED, 415 nm, 10 cycles | E. coli | Increased tolerance to aBL and temperature, but without changes in antibiotic susceptibility to AMP, CIP, CAZ, CXM, GEN, MEM, PIP, TGC, TMP | |
Abbreviations: AmB: amphotericin B; 5-ALA: 5-aminolevulinic acid; AMC: amoxicillin-clavulanate; AMK: amikacin; AMP: ampicillin; AMS: ampicillin/sulbactam; AMX: amoxicillin; ATM: aztreonam; AZM: azithromycin; AZT: aztreonam; CAZ: ceftazidime; CFZ: cefazolin; CHL: chloramphenicol, CIP: ciproflaxin; CLR: clarithromycin; CST: colistin; CTX: cefotaxime; CXM: Cefuroxime; Cur: curcumin; DA: clindamycin; DOX: doxycycline; ERY: erythromycin; FA: fusidic acid; FLU: fluconazole; FOS: fosfomycin; FOX: cefoxitin; GEN: gentamicin; HY: hypericin, 4,5,7,4′,5′,7′-hexahydroxy-2,2′-dimethylnaphthodianthrone; ICG: indocyanine green, Periogreen®; IPM: imipenem; ITR: itraconazole; KAN; kanamycin; KI: potassium iodide; LED: light-emitting diode; LIN : lincomycin; LVX: levofloxacin; LZD: linezolid; MB: methylene blue; MEM: meropenem; MIN: minocycline; MUP: mupirocin; MXF: moxifloxacin; NAL: nalidixic acid; NET: netilmicin; NFU: nitrofurantoin; NMB: new methylene blue; OFX: ofloxacin; OXA: oxacillin; PDZ: Photodithazine®; PEN: penicillin G; PIP: piperacillin; Pl–cp6: poly-lysine-conjugated chlorin; PMB: polymyxin B; PPArg2 : protoporphyrin diarginate; PPIX : protoporphyrin IX; QUD: quinupristin + dalfopristin; RB: rose bengal; RIF: rifampicin; SAM: ampicillin + sulbactam; STR: streptomycin; SUL: sulfonamides; SXT: sulfamethoxazole + trimethoprim; TBO: toluidine blue; TEC: teicoplanin; TEL: telithromycin; TET: tetracycline; TGC: tigecycline; TIC: ticarcillin; TLRs: toll-like receptors; TMP: trimethoprim; TMPyP: 5,10,15,20-tetrakis (1methyl-4-pyridinium) porphyrin tetra(p-toluenesulfonate); TMS: trimethoprim-sulfamethoxazole; TOB: tobramycin; TZO: tazobactam; TZP: piperacillin/tazobactam; VAN: vancomycin; ZnPc: zinc phthalocyanine; ZnPPc4+: zinc(II) 2,9,16,23-tetrakis[4-(N-methylpyridyloxy)]phthalocyanine iodide; 5-FC: flucytosine; [Ru(II)]1: [Ru(Phen)3]2+ (PF6-)2; [Ru(II)]2: [Ru(Phen)2(Phen-T-Fluorenyl)]2+ (Cl-)2. | |||