Bosman Mark A, Craig Jennifer P, Swift Simon, Dean Simon J, Marasini Sanjay
Department of Ophthalmology, The University of Auckland, Auckland 1142, New Zealand.
Department of Molecular Medicine and Pathology, The University of Auckland, Auckland 1142, New Zealand.
Antibiotics (Basel). 2025 Apr 1;14(4):361. doi: 10.3390/antibiotics14040361.
Fungal corneal infections are challenging to treat due to delayed diagnostic procedures, bacterial co-infections, and limited antifungal efficacy. This study investigates the therapeutic potential of ultraviolet C (UVC) light alone and combined with antifungal drugs. A subsurface infection model was developed in semi-solid agar droplets, with cells or spores inoculated into 0.75% yeast peptone dextrose (YPD) agar in a 96-well microplate (5 µL per well). Two treatment groups were tested: (1) UVC exposure (265 nm, 1.93 mW/cm) for durations of 0 s, 5 s, 10 s, 15 s, 30 s, 60 s, or 120 s, and (2) UVC combined with antifungal drugs (Amphotericin B and Natamycin) at their minimum inhibitory concentrations (MICs), determined in YPD broth. After treatment, agar droplets were homogenized, diluted, and plated for microbial enumeration. The most effective UVC doses were further tested in an ex vivo porcine keratitis model, where the corneal epithelium was debrided, infected with , and exposed to UVC. Corneas were then homogenized and plated to evaluate treatment efficacy. UVC exposure of ≥15 s inhibited and ≥10 s inhibited (all < 0.05). The broth MICs were 0.1875 µg/mL for Amphotericin B against , 6.25 µg/mL against , and 0.78125 µg/mL for Natamycin against , 7.8125 µg/mL against . The broth MIC did not eradicate fungi in the subsurface model. Combined treatments enhanced inhibition (all < 0.05), with 30 s UVC + amphotericin B for ( = 0.0218) and 30 s UVC + natamycin for ( = 0.0017). Ex vivo, 15 s and 30 s UVC inhibited growth ( = 0.0476), but no differences were seen between groups (all > 0.05). UVC demonstrated strong antifungal efficacy, with supplementary benefits from combining UVC with low doses of antifungal drugs.
由于诊断程序延迟、细菌合并感染以及抗真菌疗效有限，真菌性角膜感染的治疗具有挑战性。本研究调查了单独使用紫外线C（UVC）光以及将其与抗真菌药物联合使用的治疗潜力。在半固体琼脂滴中建立了一种皮下感染模型，将细胞或孢子接种到96孔微孔板中的0.75%酵母蛋白胨葡萄糖（YPD）琼脂中（每孔5微升）。测试了两个治疗组：（1）UVC照射（265纳米，1.93毫瓦/平方厘米），持续时间为0秒、5秒、10秒、15秒、30秒、60秒或120秒，以及（2）UVC与抗真菌药物（两性霉素B和那他霉素）以其在YPD肉汤中确定的最低抑菌浓度（MIC）联合使用。治疗后，将琼脂滴匀浆、稀释并接种以进行微生物计数。在体外猪角膜炎模型中进一步测试了最有效的UVC剂量，在该模型中，角膜上皮被清创、感染并暴露于UVC。然后将角膜匀浆并接种以评估治疗效果。暴露于UVC≥15秒可抑制[具体真菌名称1]，≥10秒可抑制[具体真菌名称2]（所有P<0.05）。两性霉素B对[具体真菌名称1]的肉汤MIC为0.1875微克/毫升，对[具体真菌名称2]为6.25微克/毫升，那他霉素对[具体真菌名称1]的肉汤MIC为0.78125微克/毫升，对[具体真菌名称2]为7.8125微克/毫升。肉汤MIC在皮下模型中未能根除真菌。联合治疗增强了抑制作用（所有P<0.05），30秒UVC+两性霉素B对[具体真菌名称1]（P=0.0218），30秒UVC+那他霉素对[具体真菌名称2]（P=0.0017）。在体外，15秒和30秒UVC抑制了生长（P=0.0476），但各组之间未见差异（所有P>0.05）。UVC显示出强大的抗真菌功效，将UVC与低剂量抗真菌药物联合使用具有额外益处。
