Introduction:
Recalcitrant dermatophytic infections of the glabrous skin (tinea corporis/cruris/faciei) pose a huge challenge to healthcare systems. Combinations of oral and topical drugs may potentially improve cure rates but the same has never been objectively assessed for this condition in laboratory or clinical studies.The presentstudy was undertaken with an aim of identifying synergistic combinations of oral and topical antifungals by testing clinical isolates obtained from patients with recalcitrant tinea corporis/cruris.
Materials and Methods:
Forty two patients with tinea corporis/cruris who had failed oral antifungals or had relapsed within 4 weeks of apparent clinical cure were recruited. Twenty one isolates were identified on sequencing (all
T.mentagrophytes/interdigitale species complex
) andwere subjected to antifungal susceptibility testing (AFST) andsqualene epoxidase (SQLE) gene mutation analysis. Finally, five isolates – four with underlying SQLE gene mutations, and one wild type strain, were chosen for checkerboard studies using various combinations of antifungal agents.
Results:
Most isolates (n=16) showed high MICs to TRB (0.5->16μg/ml), with SQLE gene mutations present in all isolates with MICs ≥0.5μg/ml. Synergistic interactions were seen with combinations of itraconazole with luliconazole, TRB and ketoconazole, PGMC with luliconazole and with the triple combination of Propylene glycol Monocaprylate (PGMC) with luliconazole and ketoconazole.
Conclusions:
In vitro
synergistic interactions provide a sound scientific basis for possible clinical use of antifungal combinations. Hence, these synergistic combinations may be tested for clinical utility in the wake of rising resistance among dermatophytic infections of the glabrous skin.
Acne vulgaris is a multifactorial skin disease associated with the colonization of Propionibacterium acnes. Antibiotics are a mainstay of treatment for acne, yet the emergence of resistance against the currently approved antibiotics is a serious concern. In this case report, a slow responder had multiple Propionibacterium acnes isolates with varied levels of sensitivity to the conventional antibiotics. The bacterial isolates obtained from acne samples collected from the patient were analyzed for phylogeny, and was found to be largely restricted to two different lineage patterns. Propionibacterium acnes phylotype IA1, which is considered to be pathogenic, displayed clindamycin sensitivity, but phylotype IB, which is associated with commensals, exhibited high clindamycin resistance. Sensitivity analysis revealed uniform resistance to macrolides, but susceptibility to tetracycline and nadifloxacin. These results implicate Propionibacterium acnes in the pathophysiology of acne vulgaris, although the lines between commensal and pathological phylotypes may be blurred. Switching the patient to a combination of minocycline and nadifloxacin resulted in a significant improvement in the clinical lesions. Such a science-driven judicious selection of antibiotics can minimize the probability of development of resistance, and might be the way forward in the treatment of acne.
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