Efficacy and safety of combined lactoferrin and luliconazole therapy compared with luliconazole alone in fungal skin infections: a prospective, randomized and active-controlled study
DOI:
https://doi.org/10.18203/2319-2003.ijbcp20261111Keywords:
Superficial fungal infection, Lactoferrin, Luliconazole, Biofilm inhibitionAbstract
Background: Fungal skin infections are a prevalent global health concern, affecting millions and often impairing quality of life. Standard antifungal therapies, including azoles, are increasingly limited by rising resistance and biofilm-mediated tolerance. Lactoferrin, an iron-chelating glycoprotein with antimicrobial and antifungal synergy, may enhance therapeutic outcomes. Sequential application of lactoferrin with luliconazole, a potent topical azole, offers a potential strategy to improve biofilm inhibition and accelerate clinical and mycological cure.
Methods: This prospective, randomized, open-label, single-center clinical trial included 60 adults with KOH-confirmed cutaneous candidiasis or dermatophytosis. Participants were randomized 1:1 to receive either sequential lactoferrin with luliconazole (Group A) or luliconazole alone (Group B) for 14 days. Outcomes included biofilm inhibition, mycological and clinical cure, and lesion size reduction. Assessments were performed at baseline, Day 7, and Day 14. Safety was evaluated through adverse event monitoring.
Results: Sixty patients were randomized and analyzed. Baseline demographic characteristics were comparable between groups. Biofilm inhibition was significantly greater in Group A at Day 7 (45.45% vs 19.64%) and Day 14 (90.90% vs 58.92%; p<0.001). Mycological cure reached 96.66% in both groups by Day 14, while clinical cure was higher in Group A (80% vs 40%; p<0.05). Lesion size reduction was greater in Group A (80.56% vs 65.44%; p=0.004). Adverse events were mild and fewer in Group A.
Conclusions: These findings indicate that lactoferrin, when used alongside standard antifungal treatment, showed beneficial effect on biofilm inhibition, supporting its use as a promising adjunctive therapy in superficial fungal infections.
References
Wang H, Sun F, Wang C, Ye J, Xia P, Wang W, et al. A systematic analysis of the global, regional, and national burden of fungal skin diseases from 1990 to 2021. Front Epidemiol. 2024;4:1489148.
Ameen M. Epidemiology of superficial fungal infections. Clin Dermatol. 2010;28(2):197-201.
Moskaluk AE, VandeWoude S. Current Topics in Dermatophyte Classification and Clinical Diagnosis. Pathogens. 2022;11(9):957.
Khanna D, Bharti S. Luliconazole for the treatment of fungal infections: an evidence-based review. Core Evid. 2014;9:113-24.
Koga H, Nanjoh Y, Kaneda H, Yamaguchi H, Tsuboi R. Short-Term Therapy with Luliconazole, a Novel Topical Antifungal Imidazole, in Guinea Pig Models of Tinea Corporis and Tinea Pedis. Antimicrob Agents Chemother. 2012;56(6):3138-43.
Pai V, Ganavalli A, Kikkeri N. Antifungal resistance in dermatology. Indian J Dermatol. 2018;63(5):361.
Ramage G, Rajendran R, Sherry L, Williams C. Fungal Biofilm Resistance. Int J Microbiol. 2012;2012:1-14.
Kaur J, Nobile CJ. Antifungal drug-resistance mechanisms in Candida biofilms. Curr Opin Microbiol. 2023;71:102237.
Kim JW, Lee JS, Choi YJ, Kim C. The Multifaceted Functions of Lactoferrin in Antimicrobial Defense and Inflammation. Biomolecules. 2025;15(8):1174.
Kuipers ME, De Vries HG, Eikelboom MC, Meijer DKF, Swart PJ. Synergistic Fungistatic Effects of Lactoferrin in Combination with Antifungal Drugs against Clinical Candida Isolates. Antimicrob Agents Chemother. 1999;43(11):2635-41.
Krupinska AM, Bogucki Z. Lactoferrin as a potential therapeutic for the treatment of Candida-associated denture stomatitis. J oral biosci. 2024;66(2):308-13.
Kobayashi T, Kakeya H, Miyazaki T, Izumikawa K, Yanagihara K, Ohno H, et al. Synergistic Antifungal Effect of Lactoferrin with Azole Antifungals against Candida albicans and a Proposal for a New Treatment Method for Invasive Candidiasis. Jpn J Infect Dis. 2011;64(4):292-6.
Dlugosz A, Wroblewska J, Kolaczyk P, Wroblewska W. The Role of Lactoferrin in Combating Candida spp. Infections Through Regulation of Oxidative Stress, Immune Response, and Nutritional Support in Women and Newborns. Molecules. 2025;30(11):2416.
Fais R, Di Luca M, Rizzato C, Morici P, Bottai D, Tavanti A, et al. The N-Terminus of Human Lactoferrin Displays Anti-biofilm Activity on Candida parapsilosis in Lumen Catheters. Front Microbiol. 2017;8:2218.
Curvelo J, Moraes DCD, Anjos CAD, Portela MB, Soares RMA. Histatin 5 and human lactoferrin inhibit biofilm formation of a fluconazole resistant Candida albicans clinical isolate. An Acad Bras Cienc. 2019;91(1):e20180045.
Fernandes KE, CarterDA. The Antifungal Activity of Lactoferrin and Its Derived Peptides: Mechanisms of Action and Synergy with Drugs against Fungal Pathogens. Front Microbiol. 2017;8:2.
Samal A, Singh BSTP, Kar BR, Mohapatra L. Comparison of Efficacy of Luliconazole 1% w/w Cream Versus Amorolfine 0.25% w/w Cream in the Treatment of Tinea cruris: A Single-center, Randomized, Double-blind, Non-inferiority Study. J Pure Appl Microbiol. 2024;18(4):2885-94.
Gupta AK, Daigle D. A critical appraisal of once-daily topical luliconazole for the treatment of superficial fungal infections. Infect Drug Resist. 2016;9:1-6.
Watanabe S, Takahashi H, Nishikawa T, Takiuchi I, Higashi N, Nishimoto K, et al. A comparative clinical study between 2 weeks of luliconazole 1% cream treatment and 4 weeks of bifonazole 1% cream treatment for tinea pedis. Mycoses. 2006;49(3):236-41.
Rizzi M, Manzoni P, Germano C, Quevedo MF, Sainaghi PP. Lactoferrin, a Natural Protein with Multiple Functions in Health and Disease. Nutrients. 2025;17(21):3403.
Coccolini C, Berselli E, Blanco-Llamero C, Fathi F, Oliveira M, Krambeck K, et al. Biomedical and Nutritional Applications of Lactoferrin. Int J Pept Res Ther. 2023;29:71.
Downloads
Published
How to Cite
Issue
Section
