Antimicrobial Photodynamic Therapy For Oral Candida Infection In Adult AIDs Patients:A Pilot Clinical Trial

Background and Objectives:This study aimed to explore the clinical application of antimicrobial photodynamic therapy（a PDT）with methylene blue（MB）plus potassium iodide（KI）for the treatment of oral infection caused by C.albicans in adult acquired immune deficiency syndrome（AIDS）patients.Methods:A total of 21 adult AIDS patients with C.albicans oral candidiasis were divided into two groups according to MB concentration（400 or600μM）and received two consecutive a PDT treatments with the same light-emitting diode（LED）light source（continuous-wave 633 nm,37.29 J/cm²）,same pre-incubation time（5 min）,same KI concentration（300 m M）.Immediately after the a PDT treatments,C.albicans yeast isolates were recovered from the oral cavities of the patients to measure the colony-forming units per m L（CFU/m L）.The number of C.albicans colonies were compared before and after a PDT.Patients were assessed for the clinical recovery of oral lesions and improvement of symptoms.Results:The Log₁₀CFU/m L of C.albicans decreased significantly before and after the second a PDT（P=0.048,0.016,respectively）but not after the first a PDT（P=0.424）.There was no significant difference between the two MB concentrations after the second a PDT（P=0.593）.Both a PDT protocols decreased the oral lesions and clinical symptoms with no significant difference after 2-time a PDT（P=0.263）.Conclusions:Two-time-a PDT with MB（400 or 600μM）plus KI could reduce the number of fungal colonies and improve the clinical symptoms of oral candidiasis in adult AIDS patients.Objectives: 1.Tried to find whether the biofilm formation,relative CAT1 and HWP1 gene expression of the Candida albicans isolates surviving after a PDT would change;2.Tried to find the associations between the fungicidal effect of MB+KI-a PDT and the biofilm formation,25 S r DNA genotype of Candida albicans isolates.Methods: 1.A total of 21 adult AIDS patients with C.albicans oral candidiasis were divided into two groups according to MB concentration（400 or600 μM）and received two consecutive a PDT treatments with same KI concentration（300 m M）.Immediately after the a PDT treatments,C.albicans yeast isolates were recovered to analyze the biofilm formation ability with both crystal violet staining method and XTT reduction method,to analyze the relative gene expressions of CAT1,HWP1 in C.albicans isolates,and to analyze the 25 S r DNA genotype.The biofilm forming ability of C.albicans（expressed as CV-OD and XTT-OD）,the relative gene expressions of CAT1,HWP1 in C.albicans were compared before and after a PDT.2.Analyze the associations between the fungicidal effect of MB+KI-a PDT and the biofilm formation,25 S r DNA genotype of Candida albicans isolates.Results:1.The percentage of patients that had decreased biofilm formation of C.albicans isolates surviving after 2-time-a PDT were respectively 45.45%,60.00% on CV-OD and 54.55%,80.00% on XTT-OD in group a and b,while the percentages had no significance between two groups.2.Comparison of C.albican biofilm formation abilities between isolates recovered before and after a PDT treatment in two groups showed that the total biomass of the biofilm（CV-OD）and the biofilm viability（XTT-OD）hadn’t reduced significantly after 2-time-a PDT.3.The real-time q PCR results showed that after 2-time-MB+KI-a PDT,the relative expression of CAT1、HWP1 gene had increased after1-time-a PDT and2-time-a PDT in Group a and b（P=0.035、0.044,respectively.）4.25 S r DNA genotype results showed that the distribution of genotypes A,B and C were not significantly different in the two groups（P>0.05）,genotype D or E were not seen in our results.5.Either biofilm formation ability or the 25 S r DNA genotype was correlated with the 2-time-a PDT fungicidal effect in the two groups（All P>0.05）.Conclusions:1.Two-time-a PDT with MB 400 or 600μM plus KI 300 mM could not reduce the biofilm formation of Candida albicans isolates surviving after a PDT.However,relative gene expression of CAT1,HWP1 before and after a PDT had been different,they could be higher than before.Relative gene expression of CAT1 can discriminately increase in different MB concentrations.2.Clinical MB+KI-a PDT fungicidal effect may not affected by the biofilm formation ability in vitro or 25 S r DNA genotype of Candida albicansObjectives: Tried to find that whether the methylene blue（MB）plus potassium iodide（KI）a PDT applications would increase the antifungal susceptibility testing profile of the Candida albicans isolates surviving after a PDT.Methods: A total of 21 adult AIDS patients with C.albicans oral candidiasis were divided into two groups according to MB concentration（400 or600 μM）and received two consecutive a PDT treatments with same KI concentration（300 m M）.Immediately after the a PDT treatments,C.albicans yeast isolates were recovered to analyze the antifungal susceptibility testing profile of Amphotericin B（Amp B）,Itraconazole（ITR）,Flucytosine（5-FC）and Fluconazole（FLU）.Compared MIC（Minimum Inhibitory Concentration）before and after a PDTResults:1.Part of patients had increased antifungal susceptibility testing profile of the four antifungals for the C.albicans isolates surviving after 2-time-a PDT,the percentages were from 9.09% to 27.27% in two groups.Of the four antifungals,Fluconazole had the highest percentage（27.27%）.2.The total percentage of patients that had increased antifungal susceptibility testing profile of the C.albicans isolates surviving after2-time-a PDT in two groups were respectively 18.18%、2.5%,the percentage in Group a turned to be higher than Group b（P=0.036）.3.In group a,there were one fluconazole-resistant strain（R）and one susceptible dose-dependent strain（S-DD）.After 2-time-a PDT treatment,the oral Candida albicans strains changed from S-DD to susceptible（S）.There was no change in susceptibility of fluconazole-resistant strain before and after a PDT.4.Comparison of C.albican MIC between isolates recovered before and after a PDT treatment in two groups showed that the total MIC of antifungal susceptibility testing hadn’t increased significantly after 2-time-a PDT（All P>0.05）.Conclusions: Two-time-a PDT with MB 400 or 600μM plus KI 300 m M could partially increase the antifungal susceptibility testing profile of the Candida albicans isolates surviving after a PDT,which might be enhanced after the a PDT parameters had been optimized.