Does Quinine Potentiate Antimicrobial Blue Light Therapy in Patients With Cutaneous Mold Infection?

Quinine hydrochloride (Q-HCL) was found to significantly increase the efficacy of antimicrobial blue light (aBL) therapy in patients with cutaneous mold infections. In addition, Q-HCL in combination with aBL was also more effective than standard treatment with voriconazole. These findings were published in The Journal of Infectious Diseases.

A team of investigators cultured clinically relevant mold species, including Aspergillus flavus, Fusarium oxysporum, and A fumigatus, derived from infected soldiers in Iraq and Afghanistan with a cutaneous mold infection to assess the in vitro effects of aBL (405 nm wavelength) with or without Q-HCL on mold conidia. A fumigatus was used as a representative species in transmission electron microscopy (TEM) to analyze the effect of aBL with or without Q-HCL on conidia cell structures.

The investigators infected dermabrasion wounds of 6-week-old female BALB/c mice with A fumigatus to assess the in vivo effects of aBL with or without Q-HCL. They separated mice into 5 treatment groups: aBL alone, aBL + Q-HCL, Q-HCL alone, a phosphate-buffered saline (PBS) vehicle control, or standard treatment with voriconazole. With exception to the standard treatment group which contained 10 mice, there were 12 mice in each treatment group. Mice were exposed to aBL (range, 0-576 J/cm²) for 0 to 80 minutes. The investigators also treated mice with 2 applications of 0.3 mg/cm² of Q-HCL at 0 and 30 minutes. Dermabrasion wounds of all mice in each treatment group were visualized via real-time bioluminescence imaging.

The investigators monitored the mice for 3 days after infection to measure recurrence of fungal burden within the wounds, followed by treatment with a single exposure of 576-J/cm² aBL or aBL plus Q-HCL (1 mg/mL), as well as voriconazole 20 mg/mL once daily.

Of note, when F oxysporum was irradiated with 540 J/cm² of aBL, the colony forming units (CFU) were decreased by 0.95 log₁₀. The investigators found that the addition of 1mg/mL of Q-HCL significantly potentiated the effects of aBL, leading to a 6.52 log₁₀ decrease in CFU (P =.0003). Similar effects were seen for A flavus (P =.00002) and A fumigatus (P =.01), with A fumigatus requiring 720 J/cm² of aBL to confer significant decrease in CFU with aBL alone. In addition, treatment with Q-HCL alone had no effect on conidia viability.

The investigators noted damage to conidia via TEM. Treatment with Q-HCL alone caused vacuole formation, and aBL alone caused destruction of the cytoplasmic material and organelles without damage to the cell wall. Treatment with Q-HCL in combination with aBL led to damage of both cytoplasmic material and organelles, as well as significant damage to the cell wall.

Of the mice, treatment with 144-J/cm² aBL alone for 20 minutes was found to decrease relative luminescence units (RLU) by 1.29 log₁₀, reflecting a greater than 90% decrease in A fumigatus viability. Treatment with the same aBL exposure in combination with Q-HCL 0.3 mg/cm² was associated with a RLU decrese of 2.08 log₁₀ (P =.008), reflecting a greater than 99% reduction in mold viability. In addition, maximum aBL exposure in the Q-HCL and voriconazole treatment groups resulted in an RLU decrease of 0.56 and 0.91 log₁₀, respectively (P <.03).

Three days following treatment, the bioluminescence signals among patients in both the aBL alone and aBL+Q-HCL treatment groups were initially decreased compared with the PBS control, but were similar to the PBS control at 72 hours. The investigators found that bioluminescence signals were significantly increased among patients in the voriconazole group increased compared with the PBS control group at 24 hours post-treatment (P <.0001), and they remained significantly increased at 48 and 72 hours post-treatment (P <.005 and P =.036, respectively).

In light of the post-treatment bioluminescence signal results for aBL, aBL+Q-HCL and voriconazole, the investigators suggested that “frequent treatment with aBL and Q-HCL [may] decrease [the risk for recurrent cutaneous mold infection].” In addition, “more frequent treatment with voriconazole…[may] mitigate disease progression,” the investigators concluded.

Reference

Leanse LG, dos Anjos C, Wang Y, Murray CK, Hooper DC, Dai T. Effective treatment of cutaneous mold infections by antimicrobial blue light that is potentiated by quinine. J Infect Dis. 2021;224(6):1024-1028. doi:10.1093/infdis/jiab058

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