It is well established and accepted that fungi are a major contributing factor in nail dystrophy. It has also been recognized that bacteria play a crucial role in onycholysis. However, the bacteria and fungi that can be grown on culture media in the laboratory are only a small fraction of the total diversity that exists in nature. Contemporary studies have revealed that fungi and bacteria often form physically and metabolically interdependent consortia that harbor properties and pathogenicity distinct from those of their individual components. Metagenomic DNA “shotgun” sequencing has proved useful in determining microbial etiology in clinical samples, effective for not only bacteria but also fungi, archaea, and viruses.
Thirty-nine consecutive nail and subungual debris samples with suspected onychomycosis were sent for laboratory analysis using three examination techniques: DNA sequencing, polymerase chain reaction analysis, and standard fungal culture. The nail plate and surrounding areas were disinfected with an ethyl alcohol swab before nail sampling. Samples from 16 patients were analyzed for suspected onychomycosis with DNA sequencing, searching a database of 25,000 known pathogens. These results were compared with 15 real-time polymerase chain reaction screening assays and eight fungal cultures sampled with the same methods.
The DNA sequencing detected 32 species of bacteria and 28 species of fungi: 50% were solely bacterial, 6.3% were solely fungal, and 43.7% were mixed communities of bacteria and fungi.
Toenails tested with DNA sequencing demonstrated the presence of both bacteria and fungi in many samples. Further work is required to fully investigate its relevance to nail pathology and treatment.
Recently, there has been a resurgence of interest in potential phototherapy technologies for the local treatment of bacterial and fungal infection. Currently, onychomycosis is the principle disease that is the target of these phototherapies in podiatric medicine. Some of these technologies are currently undergoing in vitro and in vivo trials approved by institutional review boards. The three light-based technologies are ultraviolet light therapy, near infrared photo-inactivation therapy, and photothermal ablative antisepsis. Each of these technologies have markedly dissimilar mechanisms of action. In this review, each technology will be discussed from the perspectives of history, photobiology, individual mechanism of action, safety, and potential clinical efficacy, with data presented from published material. This review is intended to give podiatric physicians detailed information on state-of-the-art infectious disease phototherapy. (J Am Podiatr Med Assoc 99(4): 348–352, 2009)
A prospective epidemiologic survey on the prevalence of foot disease in Hong Kong found foot disease in 64% of patients screened. All of the patients were ethnically Chinese. Of the conditions specified in the questionnaire, fungal foot infection, tinea pedis, and toenail onychomycosis were the most frequently encountered conditions, followed by metatarsal corns, eczema, psoriasis, and pes planus. Vascular disease, osteoarticular pathology, diabetes mellitus, obesity, atopy, and participation in sports were the main factors coexisting with the foot conditions. Of the study population, 17% and 21% reported that their quality of life was affected by pain and discomfort, respectively. These percentages are much lower than those obtained in other studies; it may therefore be inferred that foot complaints are being neglected by the ethnic Chinese population in Hong Kong. (J Am Podiatr Med Assoc 92(8): 450-456, 2002)
Six hundred twenty-nine Medicare patients were evaluated for the presence of onychauxic toenails that in the judgment of the examiners required reduction. Forty-two percent of this group had five or fewer toenails requiring reduction and 24.3% had six or more toenails requiring reduction. Statistics reported by a regional Medicare-contracted carrier for the years 1997 to 1999 showed that 95% of claims submitted for nail debridement were for six or more nails and 5% were for five or fewer nails. The 1999 Medicare Part B data listed the top 300 Current Procedural Terminology (CPT) foot-care codes in order of utilization. Code 11721 (debridement of six or more nails) was number one. National statistics from the Health Care Financing Administration in 1999 indicated approximately a 5:1 ratio in favor of CPT code 11721 (six or more nails). In contrast, this study found a ratio of 2:1 in favor of CPT code 11720 (five or fewer nails). (J Am Podiatr Med Assoc 93(5): 388-391, 2003)
Background: The Noveon is a unique dual-wavelength near-infrared diode laser used to treat onychomycosis. The device operates at physiologic temperatures that are thermally safe for human tissue. It uses only 870- and 930-nm near-infrared light, wavelengths that have unique photolethal effects on fungal pathogens. These wavelengths lack the teratogenic danger presented by ultraviolet light and the photoablation toxic plume associated with pulsed Nd:YAG lasers.
Methods: In this randomized controlled study, treatments followed a predefined protocol and laser parameters and occurred on days 1, 14, 42, and 120. Toes were cultured and evaluated, and measurements were taken from standardized photographs obtained periodically during the 180 day follow-up period.
Results: We treated mycologically confirmed onychomycosis in 26 eligible toes (ten mild, seven moderate, and nine severe). All of the patients were followed-up for 180 days. An independent expert panel, blinded regarding treatment versus control, found that at 180 days, 85% of the eligible treated toenails were improved by clear nail linear extent (P = .0015); 65% showed at least 3 mm and 26% showed at least 4 mm of clear nail growth. Of the 16 toes with moderate to severe involvement, ten (63%) improved, as shown by clear nail growth of at least 3 mm (P = .0112). Simultaneous negative culture and periodic acid–Schiff was noted in 30% at 180 days.
Conclusions: These results indicate a role for this laser in the treatment of onychomycosis, regardless of degree of severity. Ease of delivery and the lack of a need to monitor blood chemistry are attractive attributes. (J Am Podiatr Med Assoc 100(3): 166–177, 2010)
Regarding antibiotic-loaded cements, there is an abundant amount of literature regarding the antibacterial in vitro inhibitory and clinical applications for the treatment of osteomyelitis. The opposite can be said about literature regarding in vitro antifungal-loaded cement drug delivery for the treatment of fungal osteomyelitis.
Aspergillus fumigatus and Candida (ATCC 1023ATCC, Manassas, Virginia) were plated on antibiotic/antifungal-free plates. Voriconazole- and amphotericin B–impregnated calcium sulfate and hydroxyapatite (HA) disks, calcium sulfate + HA control disks, and control polymethylmethacrylate disks were laid separately onto plates separately inoculated with Aspergillus and Candida spp. The zones of inhibition obtained were measured in millimeters at 24, 36, and 96 hours.
Etest (bioMérieux, Marcy l'Etoile, France) results demonstrated susceptibility of Aspergillus and Candida to amphotericin B and voriconazole. The zone of inhibition data demonstrated that voriconazole and amphotericin B retained their antifungal activity when mixed into the calcium sulfate + HA bone void filler and eluted at biologically effective antifungal concentrations over 96 hours.
The calcium sulfate + HA bone void filler is a biocompatible ceramic carrier vehicle that can successfully deliver the antifungal drugs voriconazole and amphotericin B in the adjunctive treatment of fungal osteomyelitis. It is a reliable strategy in the local delivery of antifungal drugs to an area of osteomyelitis.
Topical onychomycosis therapies are usually inadequate, and patient compliance to systemic therapies is poor. Recently, interest in laser therapy for the treatment of onychomycosis has increased. We sought to investigate the efficacy of long-pulsed Nd:YAG laser therapy for onychomycosis.
Thirty patients with mycologically confirmed onychomycosis received long-pulsed 1064-nm Nd:YAG laser therapy, moving the beam in a spiral pattern over the whole nail plate two times, with a 1-minute pause between passes. Laser therapy was performed with a spot diameter of 4 mm at a speed of 25 mm/sec once weekly for 4 weeks using fluencies ranging from 40 to 60 J/cm2, depending on the thickness of the nail plate. Patients were evaluated in terms of clinical improvement and mycologic cure.
Thirty patients started and 15 completed the study. Mycologic cure was achieved in nine patients (60%), of whom eight (89%) were infected with Trichophyton sp. Complete clinical improvement was achieved in seven patients (47%), all of whom were infected with Trichophyton sp. Mycologic cure was not achieved in one of two patients infected with Epidermophyton or in either patient in whom the agent was Candida or Aspergillus; complete clinical improvement did not occur in any of these patients. No serious adverse events were observed.
Based on these results, long-pulsed Nd:YAG laser can be used as an effective treatment for onychomycosis, but further studies are needed to draw firmer conclusions.
We sought to evaluate the efficacy of efinaconazole topical solution, 10%, in patients with onychomycosis and coexisting tinea pedis.
We analyzed 1,655 patients, aged 18 to 70 years, randomized (3:1) to receive efinaconazole topical solution, 10%, or vehicle from two identical multicenter, double-blind, vehicle-controlled 48-week studies evaluating safety and efficacy. The primary end point was complete cure rate (0% clinical involvement of the target toenail and negative potassium hydroxide examination and fungal culture findings) at week 52. Three groups were compared: patients with onychomycosis and coexisting interdigital tinea pedis on-study (treated or left untreated) and those with no coexisting tinea pedis.
Treatment with efinaconazole topical solution, 10%, was significantly more effective than vehicle use irrespective of the coexistence of tinea pedis or its treatment. Overall, 352 patients with onychomycosis (21.3%) had coexisting interdigital tinea pedis, with 215 of these patients (61.1%) receiving investigator-approved topical antifungal agents for their tinea pedis in addition to their randomized onychomycosis treatment. At week 52, efinaconazole complete cure rates of 29.4% were reported in patients with onychomycosis when coexisting tinea pedis was treated compared with 16.1% when coexisting tinea pedis was not treated. Both cure rates were significant compared with vehicle (P = .003 and .045, respectively), and in the latter subgroup, no patients treated with vehicle achieved a complete cure.
Treatment of coexisting tinea pedis in patients with onychomycosis enhances the efficacy of once-daily topical treatment with efinaconazole topical solution, 10%.
Eumycetoma, caused by fungi, is a neglected tropical disease. It is endemic in the “mycetoma belt” countries but rare in North America. We report a case of pedal eumycetoma in the state of Maryland. A 51-year-old male immigrant from Guatemala presented with multiple, enlarging nodules on the dorsal surface of his left great toe present for 1 year, and a new one in the left arch area present for 6 months. The nodular lesions were surgically excised in two separate operations. Pathologic evaluation of all nodules revealed eumycetomas characterized by the Splendore-Hoeppli phenomenon, showing an amorphous eosinophilic center filled with numerous fungal hyphae, observed on periodic acid-Schiff–stained slides, with a surrounding cuff of neutrophils. Polymerase chain reaction–based sequencing identified Cladosporium cladosporioides in the tissues. The patient was further treated with oral fluconazole for 2 months. The patient recovered well postoperatively and had no recurrence at 20-month follow-up. In conclusion, even though eumycetoma is regarded as a rare disease in North America, its incidence may be higher than reported because of millions of immigrants from endemic regions in the United States, which highlights the need to raise awareness of this devastating disease in the medical community. Eumycetoma needs to be differentiated from other infectious and noninfectious benign and malignant lesions. Optimal treatment includes surgical excision with antifungal therapy.