Permethrin Resistance and Alternative Therapies in Scabies : A Systematic Review

Introduction: Scabies, caused by Sarcoptes scabiei var. hominis, affects over 200 million people globally, with permethrin 5% cream serving as first-line treatment for decades. However, emerging evidence suggests increasing permethrin treatment failures, raising concerns about resistance. This systematic review aims to synthesize evidence on permethrin resistance in scabies and evaluate the effectiveness and safety of alternative therapeutic options. Methods: A systematic review was conducted following PRISMA guidelines. We searched multiple databases for studies investigating permethrin resistance or alternative scabies treatments. Included studies comprised randomized controlled trials, cohort studies, case-control studies, case series (≥5 patients), systematic reviews, and meta-analyses reporting clinical outcomes in human patients with confirmed or clinically diagnosed scabies. A total of 144 studies met inclusion criteria and underwent data extraction for resistance evidence, alternative therapy details, comparative effectiveness, safety profiles, and clinical context. Results: Documented permethrin resistance demonstrated significant geographic heterogeneity, with European studies reporting cure rates as low as 27-31% compared to 73-96% in South Asian settings. Global treatment failure prevalence increased by 0.58% annually (95% CI not reported). Resistance mechanisms included voltage-gated sodium channel mutations and enhanced glutathione S-transferase activity. Alternative therapies showed variable effectiveness: two-dose oral ivermectin (200 μg/kg one week apart) achieved 78-100% cure versus 58% for single-dose (P=0.021); topical ivermectin 1% achieved 96-100% cure by four weeks; benzyl benzoate 25% showed 87% cure in some studies but caused burning in 24% of patients; sulfur preparations achieved 94.4-100% cure by four weeks with mild adverse effects. Combination permethrin-ivermectin therapy demonstrated superior efficacy (84.6% vs 67.5-70.7% for monotherapies, P