This study attempted to determine the cost-effectiveness of therapies for dermatophyte toenail onychomycosis in the United States in 2001. The antimycotic agents evaluated were ciclopirox 8% nail lacquer and the oral agents terbinafine, itraconazole (pulse), itraconazole (continuous), fluconazole, and griseofulvin. A treatment algorithm for the management of onychomycosis was developed, and a meta-analysis was carried out to determine the average mycologic and clinical response rates for the various agents. The cost of the regimen was figured as the sum of the costs of drug acquisition, medical management, and management of adverse effects. The expected cost of management and disease-free days were determined, and a sensitivity analysis was conducted. It was concluded that ciclopirox 8% nail lacquer, which has recently become available in the larger size of 6.6 mL, is a cost-effective agent for the management of toenail onychomycosis. (J Am Podiatr Med Assoc 92(5): 272-286, 2002)
Onychomycosis is a very common disease, especially in podiatric medical practice. It can be associated with significant patient distress, major disability and pain, and is challenging to treat successfully. This is a case study of a 41-year-old man with distal lateral subungual onychomycosis of 5 years' duration. Forty percent of the great toenail was affected and a total of six toenails were involved. Baseline fungal cultures were positive for Trichophyton rubrum. This patient was treated with efinaconazole 10% solution, a new topical antifungal, once daily for 48 weeks. Mycological cure was noted at the first assessment period (12 weeks), and compete cure was seen at follow-up. This case study alerts physicians to a promising new topical treatment for onychomycosis under development, and to the importance of mycological cure as an early indicator of treatment success.
Placebo cure rates vary among randomized clinical trials for onychomycosis, but the factors influencing these cure rates have not been systematically investigated. The PubMed database and reference sections of relevant publications were searched for randomized controlled trials of dermatophyte toenail onychomycosis that included a placebo control and that assessed cure rates. From 21 studies, the pooled mean ± SD placebo cure rates regarding mycological, clinical, and complete cure were 8.7% ± 3.7%, 3.4% ± 2.2%, and 1.2% ± 1.4%, respectively. There was no statistically significant difference between oral and topical treatments. None of the cure rates significantly correlated with any of the participant or study design characteristics analyzed. Placebo cure rates in randomized controlled trials of toenail onychomycosis are relatively low and are independent of the study characteristics.
Because of the ubiquitous nature of dermatophytes and a lack of an adaptive immune response in the nail plate, recurrence and relapse rates associated with superficial fungal infections are high (10%–53%). Cured or improved dermatophytosis patients could become reinfected if exposed to fungal reservoirs, such as an infected shoe, sock, or textile. To prevent this, footwear, sock, and textile sanitization methods can be used. To provide insight into effective sanitization options, the focus of this article is to review footwear, sock, and textile sanitization studies conducted throughout history (1920–2016). Thirty-three studies are covered in this review, encompassing techniques ranging from formaldehyde fumigation and foot powder application, to more modern approaches such as UV light and silver-light irradiation technologies. Older sanitization methods (eg, boiling, use of chlorine and salts) are quite limited in their practicality, as they can result in health complications and ruin shoe integrity. Newer approaches to shoe and sock sanitization, such as ozone application and UV irradiation, have shown very promising results. Further research is still needed with these modern techniques, as knowledge gaps and cost prevent the creation of standardized parameters for successful use. By combining sanitization methods with other preventative measures, protection against reinfection may be enhanced.
Mycological culture is the traditional method for identifying infecting agents of onychomycosis despite high false-negative results, slower processing, and complications surrounding nondermatophyte mold (NDM) infections. Molecular polymerase chain reaction (PCR) methods are faster and suited for ascertaining NDM infections.
To measure agreement between culture and PCR methods for identification of infecting species of suspected onychomycosis, single toenail samples from 167 patients and repeated serial samples from 43 patients with suspected onychomycosis were processed by culture and PCR for identification of 16 dermatophytes and five NDMs. Agreement between methods was quantified using the kappa statistic (κ).
The methods exhibited fair agreement for the identification of all infecting organisms (single samples: κ = 0.32; repeated samples: κ = 0.38). For dermatophytes, agreement was moderate (single samples: κ = 0.44; repeated samples: κ = 0.42). For NDMs, agreement was poor with single samples (κ = 0.16) but fair with repeated samples (κ = 0.25). Excluding false-negative reports from analyses improved agreement between methods in all cases except the identification of NDMs from single samples.
Culture was three or four times more likely to report a false-negative result compared with PCR. The increased agreement between methods observed by excluding false-negative reports statistically clarifies and highlights the major discord caused by false-negative cultures. The increased agreement of NDM identification from poor to fair with repeated sampling along with their poor agreement in the single samples, with and without false-negatives, affirms the complications of NDM identification and supports the recommendation that serial samples help confirm the diagnosis of NDM infections.
Reports of mixed infections with nondermatophyte molds (NDMs) and dermatophytes in onychomycosis are rare, possibly owing to the inhibition of NDM growth during traditional culture. We sought to determine the prevalence of mixed infections in onychomycosis using molecular identification.
Molecular analyses were used to identify infecting organisms directly from at least two serial great toenail samples from each of the 44 patients.
Mixed infections were present in 41% of the patients (18 of 44). A single coinfecting NDM was the most common mixed infection and was detected in 34% of patients with onychomycosis (15 of 44), with Fusarium oxysporum present in 14% (6 of 44), Scopulariopsis brevicaulis in 9% (4 of 44), Acremonium spp in 2% (1 of 44), Aspergillus spp in 4.5% (2 of 44), and Scytalidium spp in 4.5% (2 of 44). Mixed infections with two NDMs were found in 7% of patients (3 of 44).
Mixed onychomycosis infections may be more prevalent than previously reported.
Onychomycosis is estimated to occur in approximately 10% of the global population, with most cases caused by Trichophyton rubrum. Some persistent onychomycosis is caused by mixed infections of T rubrum and one or more co-infecting nondermatophyte molds (NDMs). In onychomycosis, T rubrum strain types may naturally switch and may also be triggered to switch in response to antifungal therapy. T rubrum strain types in mixed infections of onychomycosis have not been characterized.
T rubrum DNA strains in mixed infections of onychomycosis containing co-infecting NDMs were compared with a baseline North American population through polymerase chain reaction amplification of ribosomal DNA tandemly repetitive subelements (TRSs) 1 and 2. The baseline DNA strain types were determined from 102 clinical isolates of T rubrum. The T rubrum DNA strain types from mixed infections were determined from 63 repeated toenail samples from 15 patients.
Two unique TRS-2 types among the clinical isolates contributed to four unique TRS-1 and TRS-2 strain types. Six TRS-1 and TRS-2 strain types represented 92% of the clinical isolates of T rubrum. Four TRS-1 and TRS-2 strain types accounted for 100% of the T rubrum within mixed infections.
Four unique North American T rubrum strains were identified. In support of a shared ancestry, the T rubrum DNA strain types found in mixed infections with NDMs were among the most abundant types. A population of T rubrum strains in mixed infections of onychomycosis has been characterized, with more than one strain detected in some nails. The presence of a co-infecting NDM in mixed infections may contribute to failed therapy by stabilizing the T rubrum strain type, possibly preventing the antifungal therapy–induced strain type switching observed with infections caused by T rubrum alone.
Laser systems are a new treatment area for onychomycosis. As of January 2012, the US Food and Drug Administration (FDA) has approved four laser systems for the “temporary increase of clear nail in onychomycosis.” The FDA has approved these devices on the basis of “substantial equivalence” to predicate devices with similar technical specifications and applications. Laser therapy appears to be a promising alternative to traditional pharmacotherapy, but these systems have been tested in only limited clinical trials; therefore, it is not possible to compare their efficacy to the oral and topical drugs currently used in the treatment of onychomycosis. (J Am Podiatr Med Assoc 102 (5): 428-430, 2012)
New therapies for onychomycosis continue to be developed, yet treatments are seldom directly compared in randomized controlled trials. The objective of this study was to compare the rates of mycological cure for oral and topical onychomycosis treatments using network meta-analysis. A systematic review of the literature on onychomycosis treatments published before March 25, 2013, was performed, and data were analyzed using network meta-analysis. Terbinafine, 250 mg, therapy was significantly superior to all treatments except itraconazole, 400 mg, pulse therapy; itraconazole, 200 mg, therapy was significantly superior to fluconazole and the topical treatments; and fluconazole, efinaconazole, ciclopirox, terbinafine nail solution, and amorolfine treatments were significantly superior to only placebo. These results support the superiority of 12-week continuous terbinafine, 250 mg, therapy and itraconazole, 400 mg, pulse therapy (1 week per month for 3 months) while suggesting the equivalence of topical therapies. These results reflect findings from the literature and treatment efficacy observed in clinical practice.
Background: A high rate of false-negative dermatophyte detection is observed when the most common laboratory methods are used. These methods include microscopic observation of potassium hydroxide–digested nail clippings and culture methods using agar-based media supplemented with cycloheximide, chloramphenicol, and gentamicin to isolate dermatophytes. Microscopic detection methods that use calcofluor white staining or periodic acid–Schiff staining may also be substituted for and have previously been reported to be more sensitive than potassium hydroxide–digested nail clippings.
Methods: Trichophyton rubrum infections were detected directly from nails in a double-round polymerase chain reaction assay that uses actin gene–based primers. This method was compared with detection of fungal hyphae by using calcofluor white fluorescence microscopy of nail samples collected from 83 patients with onychomycosis who were undergoing antifungal drug therapy.
Results: Twenty-six of 83 samples (31.3%) were found to be positive by calcofluor white fluorescence microscopy, and 21 of 83 samples (25.3%) yielded positive results for T rubrum when actin gene–based primers in a double-round polymerase chain reaction assay were used. When calcofluor white fluorescence microscopy and polymerase chain reaction assay were used, the combined detection was 46.9% compared with 31.3% when calcofluor microscopy and culture of nail samples on Sabouraud’s dextrose agar supplemented with cycloheximide, chloramphenicol, and gentamicin were used.
Conclusions: These results suggest that the use of a direct DNA protocol is an alternative method for detecting Trichophyton infections. When this protocol is used, the presence of T rubrum DNA is directly detected. However, the viability of the dermatophyte is not addressed, and further methods need to be developed for the detection of viable T rubrum directly from nail samples. (J Am Podiatr Med Assoc 98(3): 224–228, 2008)