Oral Antifungals Research Articles

Fractional CO2 laser in the management of onychomycosis

Context: Pharmacotherapy is the standard first-line management of onychomycosis (OM). Prolonged treatment courses have reported cure rates of only 40%–80%. Although lasers have been approved by the US Food and Drug Administration for the clearance of nail in OM, their efficacy in the first-line management is not established. In this context, we conducted a study with the aim to ascertain efficacy of fractional CO2 laser along with topical 1% terbinafine cream in the management of OM. Settings and Design: This was a single-arm observational study in OM administered treatment over 16 weeks and analyzed at 6 months after the initiation of treatment. Subjects and Methods: Treatment naive and others after a 3 month washout period were administered fractional CO2 laser using pulse energy of 110 mJ, a density of 256 spots/cm2, pulse interval of 0.5 mm, pulse duration of 0.1 ms, and a rectangular spot size of 2–10 mm length and 0.6–5 mm breadth, every 4 weeks for four sessions along with 1% topical terbinafine cream. Outcome was assessed with Onychomycosis Severity Index (OSI), Visual Analog Score, mycological cultures and potassium hydroxide (KOH) mount at 16 weeks and 6 months after initiation of treatment. Statistical Analysis Used: Paired t-test was used to compare the change in OSI. Results: Mycological evaluation at the end of 16 weeks revealed that 90% (45 nails) were KOH negative and 88% (44 nails) were culture negative. Evaluation at 6 months revealed that 86% (43 nails) were KOH negative and 88% (44 nails) were culture negative. OSI improvement compared to baseline was good to complete in 42 cases, and Visual analog Score revealed 36 nails showing 3+–4+ improvement. Conclusions: Fractional CO2 laser is a viable alternative to oral antifungals, especially when they are contraindicated such as in military aviators and in cases where drug interactions are suspected.

An Open Study to Evaluate Effectiveness and Tolerability of a Nail Oil Composed of Vitamin E and Essential Oils in Mild to Moderate Distal Subungual Onychomycosis

Background: Onychomycosis is the most common nail disease and can affect both fingernails and toenails. When possible, topical treatment is generally preferred both by patients and physicians because it is associated with lower risk of systemic side effects and drug interactions than oral antifungals, avoiding laboratory monitoring. Objective: The aim of our study was to evaluate the efficacy, tolerability, and patient’s compliance of a new topical antifungal containing vitamin E and essential oils of lime, oregano, and tea tree. Patients and Methods: We enrolled 20 patients with mild-moderate distal subungual onychomycosis due to dermatophytes or non-dermatophyte molds. The product was applied once daily on the periungual tissues and on the nail plate for 6 months. Follow-up without therapy continued for another 6 months in order to evaluate the product’s effect maintenance. Periodic evaluation of treatment efficacy was performed by standardized photography and mycological examination (KOH + culture) of the target nail at baseline (T0), after 3 months (T1) and 6 months (T2) of therapy, and after 6 months of follow-up (T3). Results: At the end of the 12-month study, the majority of patients achieved a complete cure of onychomycosis (78.5%). All patients were very satisfied by the treatment. No side effects were recorded. Conclusions: The results of our study indicate that this new topical antifungal containing vitamin E and essential oils of lime, oregano, and tea tree is an effective and safe option for topical therapy of onychomycosis. This topical antifungal nail oil restructures the nail appearance, improving patient’s adherence to therapy and reducing the risk of relapses, maintaining results over time.

2110. Treatment of Coccidioidomycosis with Isavuconazole

BackgroundThere are limited prospective data available to guide the management of severe coccidioidomycosis. In particular, the treatment of disseminated coccidioidomycosis often requires extended courses of antifungal therapy, for which there are often intolerable side-effects, toxicities, and failures. In recent years, newer oral triazole antifungals with in vitro activity against Coccidioides have become available, but data are lacking on their efficacy in coccidioidomycosis. Isavuconazole lacks many of the toxicities of older triazole antifungals, such as QT prolongation and certain key drug interactions, making it an appealing option in selected patients.MethodsBased on pharmacy prescription history at two federal facilities in southern California, we identified adult patients with coccidioidomycosis who received isavuconazole from 2017 to 2019. Patient records were reviewed to identify age, sex, ethnicity, sites of infection, prior antifungal therapy, indication for switch to isavuconazole, duration of follow-up, and outcomes.Results12 patients were identified between the ages of 36 and 86 years; 3 were women. 6 were of Pacific Islander descent, 4 were African American, 1 European-American, and 1 Latino. 6 (50%) had significant pre-infection comorbidities. 8 (67%) had evidence of extrapulmonary dissemination, including 1 patient with meningitis. All but one had received prior treatment with other azoles; two had previously been treated with amphotericin B. Six (50%) were switched to isavuconazole due failure or progression of disease on prior therapy; 3 (25%) due to drug toxicity; and 2 (17%) due to drug interactions. Seven (58%) patients improved on isavuconazole; 4/12 (33%) were stable; one developed hepatotoxicity but improved on posaconazole, and one patient deteriorated.ConclusionIsavuconazole appears to be a promising agent for the treatment of coccidioidomycosis. Long-term follow-up will be required to assess the risks of toxicity, disease progression, or relapse. For patients who are clinically stable but with an extensive disease burden or toxicity from older agents, isavuconazole may present an amphotericin-sparing option. Disclosures All authors: No reported disclosures.

Oral antifungal: the safety and efficacy of oral itraconazole in dermatophytosis

Background: The systemic antifungals like Griseofulvin, Itraconazole, Terbinafine, Ketoconazole and Fluconazole are widely used for superficial fungal infection. Hepatotoxicity with oral antifungals is well established fact. The rate of transient asymptomatic changes in liver function tests accounts for about 0.5 - 10% of all patients treated with systemic antifungals. Clinical hepatic toxicity is seen less frequently. The aim of this study is to evaluate the effect of oral Itraconazole on hepatic function and it’s efficacy in patients with extensive dermatophytosis.Methods: The total of 524 patients with extensive dermatophytosis were included in our study which was conducted in a tertiary care hospital in Navi Mumbai.Results: Itraconazole, a systemic antifungal agent is efficiently used in treatment of superficial and deep mycoses. It inhibits fungal cytochrome P450 dependent enzyme and thus impaires conversion of lanosterol to ergosterol. Adverse reactions to itraconazole includes drug reactions, gastrointestinal upset, headache, dizziness, thrombocytopenia, gynecomastia, reversible edema of extremities and metabolic side effects like hypokalemia, and hypertriglyceridemia. The level of hepatic transaminases increases in about 1%-5% of patients who have received continuous therapy with systemic itraconazole. Clinical hepatitis rarely occurs in patients and, recovery generally ensues with the cessation of medication.Conclusions: The baseline and post treatment liver function test is important to monitor if patient is on higher dose and longer duration of itraconazole therapy. The screening for high risk patients like poor liver function test, history of alcoholism, history of liver disease should be taken before stating the therapy.

A unique multidrug-resistant clonal Trichophyton population distinct from Trichophyton mentagrophytes/Trichophyton interdigitale complex causing an ongoing alarming dermatophytosis outbreak in India: Genomic insights and resistance profile

There has been a considerable upsurge of extensive, treatment recalcitrant, dermatophytosis presenting as tinea corporis and tinea cruris in India since the past few years. Genome analysis of Trichophytonspecies causing severe superficial dermatophytosis in North India confirmed a unique clade related to the T.mentagrophytes/interdigitale complex, seeming to belong to an early diverging clade of the complex. The Indian Trichophyton species genomes were highly related showing only up to 42 SNPs between any two isolates confirming their clonal origin. Other genetic approaches such as ITS sequencing and multigene phylogeny used in this study were contradictory or inconclusive to show the differentiation of these isolates from T. mentagrophytes/T. interdigitale. Remarkably, high rates of resistance to all three commonly used oral antifungals, i.e., 36% for terbinafine (MICs 4 to ≥32 mg/L), 39.5% for fluconazole (MIC range 32 to ≥64 mg/L) and griseofulvin (Geometric mean MIC ≥ 4 mg/L) were observed. Two important amino acid substitutions (Leu393Phe or Phe397Leu) leading to a terbinafine resistant phenotype were found in the squalene epoxidase protein of all tested terbinafine resistant isolates. All 20 examined genomes presented a high mobility group (HMG) domain transcription factor gene corresponding to mating type (+). Of these, three isolates also showed positivity for both alpha-box and HMG in the genome which might indicate hybridization or an incomplete sexual cycle. Therefore, we highlight the potential of this organism to rapidly spread alleles that might be driving antifungal resistance among its population. This new population of Trichophyton with high rates of in vitro antifungal resistance seems to be driving an ongoing outbreak of dermatophytosis in India. Our study highlights difficulties in identifying isolates from the Trichophyton mentagrophytes/interdigitale clade of the genus using currently available molecular tools. High resistance rates of terbinafine warrant further clinical studies to assess its utility in the treatment of dermatophytosis caused by this clonal strain.

Antifungal Drug Use for Onychomycosis.

Onychomycoses are fungal nail infections affecting predominantly toenails, and mainly caused by dermatophyte fungi, molds and some Candida species. Nail infections can be mild with purely cosmetic implications, but they can also negatively influence quality of life. The deep-seated nature of fungi within the nail plate, prolonged treatment, poor patient adherence, frequent recurrences, and development of resistance to various antimicrobial agents make onychomycosis difficult to successfully treat. When and how should clinicians prescribe systemic and topical antifungal drugs for onychomycosis? A narrative review was undertaken of the current literature identified in Medline, Scopus, CINAHL, the Cochrane library, and Google Scholar. Treatment is often lengthy and requires persistence and patient education. Definitive mycological diagnosis, and an individualized evaluation of risks and benefits of different treatments are imperative before initiating therapy. The choice of treatment can be influenced by the age and general health of the patient, the causative organism, the number of affected nails, and the extent of nail involvement. Oral antifungals offer greater likelihood of a cure than topicals, but oral therapy carries greater risks and requires closer monitoring. Oral terbinafine is the treatment of choice, followed by itraconazole pulse regimen. The newly approved topical agents, efinaconazole and tavaborole, were superior to placebo in clinical trials and appear to produce slightly improved mycological cure rates compared to previous topicals, but further direct comparisons are needed. The treatment of onychomycosis can be challenging, as most therapeutic options are lengthy, expensive and potentially unsuccessful.

Selection of Oral Antifungals for Initial Maintenance Therapy in Chronic Pulmonary Aspergillosis: A Longitudinal Analysis.

There are limited data for direct comparisons of the efficacy of oral itraconazole (ITCZ) and oral voriconazole (VRCZ) therapy in the treatment of chronic pulmonary aspergillosis (CPA). We conducted a retrospective, follow-up, observational study of CPA patients enrolled in 2 previous multicenter trials. Of the 273 CPA patients, 59 and 101 patients started maintenance therapy with oral ITCZ and oral VRCZ, respectively, just after the end of acute intravenous therapy in each trial. At the end of the observation period in this follow-up study (median observation period, 731 days), the percentage of patients who showed improvement was lower in the ITCZ group than in the VRCZ group (18.2% vs 40.0%). However, after including stable patients, the percentages were 50.9% and 52.6%, respectively, in the ITCZ and VRCZ groups, which were not significantly different (P = .652). Multivariable Cox regression analysis showed no significant influence of the choice of initial maintenance treatment (ITCZ or VRCZ) on overall mortality as well as CPA-associated mortality. Multivariable logistic regression showed that oral ITCZ selection for initial maintenance therapy was an independent risk factor for hospital readmission and switching to other antifungal agents (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.3-7.5 and OR, 5.7; 95% CI, 2.0-15.7, respectively). Oral VRCZ for initial maintenance therapy showed better effectiveness than oral ITCZ for clinical improvement in CPA patients. There was no difference in crude mortality between initial maintenance therapy with VRCZ and ITCZ, especially in elderly CPA patients. UMIN000007055.

Treatment of Selected Canine Dermatological Conditions in Portugal - A Research Survey.

IntroductionStaphylococcus pseudintermedius and Malassezia pachydermatis often cause skin diseases in dogs.Material and MethodsAn online survey was e-mailed to veterinary practices nationwide covering demographics, diagnosis methods, and oral and topical treatment options. Of the 740 surveys sent, 100 complete replies were obtained.ResultsThe majority of clinicians were unaware of the existence of the International Society for Companion Animal Infectious Diseases guidelines or did not follow them (53%). Oral antibiotics were used universally for superficial bacterial folliculitis treatment, particularly amoxicillin-clavulanic acid (100%), cephalexin (94%), enrofloxacin (67%), or marbofloxacin (60%). For fold dermatitis (FD) and otitis externa (OE), oral antibiotics were also given as treatment in 88% and 82% of cases, respectively. Oral antifungals were often prescribed for generalised Malassezia dermatitis (85%), FD (70%), and OE (59%). S. pseudintermedius and M. pachydermatis were frequently treated topically, particularly with antibacterials or antifungals only, or a combination of antibacterials, antifungals, and glucocorticoids. Alternative options such as honey-based products were not frequently used.ConclusionOur survey suggests that oral antibiotics are overused by Portuguese clinicians despite the spread of antibiotic resistant S. pseudintermedius. Oral antibiotics and antifungals are commonly prescribed for skin conditions manageable with topical treatments.

1413. A Phase IIa Efficacy, Safety, Tolerability and Pharmacokinetic (PK) Study of Encochleated Amphotericin B in Patients with Mucocutaneous (Esophogeal, Oropharyngeal, Vulvovaginal) Candidiasis Who are Refractory or Intolerant to Standard Non-Intravenous Therapies

BackgroundCurrent oral therapeutic options for chronic mucocutaneous candidiasis (CMC) are often associated with resistance and toxicity. Amphotericin B (AMB) has broad fungicidal activity and markedly resists emergence of resistance but requires parenteral administration and monitoring for significant nephrotoxicity, which worsens with chronic treatment. Encochleated amphotericin B (CAMB) is a novel oral formulation of AMB. In animal models, CAMB demonstrates antifungal activity with similar efficacy as intraperitoneal AMB deoxycholate, but without the associated toxicity. This on-going patient volunteer study assesses the efficacy, safety, tolerability and PK of CAMB in patients with CMC who are refractory or intolerant to standard oral azole antifungals.MethodsFour patients have completed the clinical protocol treatment period: 3 patients with STAT3 deficient Hyper IgE syndrome and CMC, and one patient with chronic esophageal candidiasis. Eligible patients were dose escalated (Figure 1), with option of enrolling in an extension phase. Serial plasma PK samples were collected over 24 hours over the study period, with data available from two patients (Figure 2). ResultsCAMB was well tolerated by all four patients, and all are currently on the extension phase (Figure 3). There was significant improvement in clinical severity symptom scores of esophageal and oropharyngeal symptoms; CAMB01 achieved reduction in clinical symptoms by 57% (800 mg/day), CAMB02 by 85% (400 mg/day), CAMB03 50% (800 mg/day) and CAMB04 50% (800 mg/day). CAMB02 maintained higher plasma PK exposure throughout the study compared with CAMB01, a possible explanation for clinical response at a lower 400 mg/day dose. Reported adverse events were grade 1, mostly nausea and dizziness. There were no signs of liver, kidney or hematologic toxicity in any of the patients, with CAMB01 and CAMB02 receiving study drug for ~1 year.ConclusionCAMB was well tolerated in patient volunteers with long-standing symptomatic azole-resistant CMC. All four patients have met the primary endpoint of achieving 3 50% clinical response. CAMB is a promising oral therapy for patients with history of CMC, with potential use in treatment and prophylaxis of invasive fungal infections.Disclosures M. Lionakis, Matinas BioPharma Inc: Research Support, Research support. R. Lu, Matinas BioPharma Inc: Employee and Shareholder, Salary. R. Mannino, Matinas BioPharma Inc: Employee and Shareholder, Salary.

Incidence of steroid modified tinea in tertiary care centre Lucknow

<p class="abstract"><strong>Background:</strong> Rampant use and abuse of topical steroids has led to increase in number of cases of superficial dermatophytosis of skin, nail and hair. In most of the cases they are resistant to topical as well as oral antifungals even after prolong course of treatment. Our study aims to analyse epidemiological and microbiological profile of steroid modified tinea (SMT).</p><p class="abstract"><strong>Methods:</strong> Clinically diagnosed tinea patients with history of usage of topical steroids were included in our study. Detailed history was taken and clinical examination along with KOH mount and culture was done.<strong></strong></p><p class="abstract"><strong>Results:</strong> 980 patients were screened of which 550 patients with history of using topical steroids were included in our study. Most common age group was 20 to 29 years with male: female of ratio approximately 3:1 and disseminated form was the most common variety. KOH mount was positive in 76% cases and culture was positive in 72% cases. Most common species came out to be <em>T. Mentagrophytes</em> followed by <em>T. rubrum</em>. Among non-dermatophyte group, Candida was the commonest.</p><p class="abstract"><strong>Conclusions:</strong> There is<strong> </strong>rise in incidence of dermatophytosis, especially steroid modified one and cases of disseminated tinea are rising.</p>

PSS51 - ANALYSIS OF TOPICAL PREPARATIONS FOR TREATMENT OF ONYCHOMYCOSIS IN UKRAINE

Therapeutic options for onychomycosis include oral and topical antifungals. Since topical medicines are used both in monotherapy, and in combination therapy, the aim of this work was to conduct comparative analysis of topical preparations for treatment of onychomycosis included into clinical protocol and State Formulary of Ukraine. comparative analysis of topical medicines included into clinical protocol and State Formulary of Ukraine, 10th edition. Clinical protocol for treatment of onychomycosis (CP) was approved by Ministry of Health of Ukraine in 2012. It recommends three onycholytic preparations with urea to remove infected nail plate, and than to treat a nail bed with either antifungal lacquer or topical preparation with ketoconazole, terbinafine, oxiconazole, miconazole, chlornitrophenol, undecylenic acid, combination preparation with ketoconazole and salicylic acid. The last preparations are listed without indication of a preferred dosage form. State Formulary of Ukraine, 10th (SFU) was approved by Ministry of Health of Ukraine in 2018. SFU also recommends applying antifungals onto nail bed after nail plate removal, but it does not recommend any onycholytic preparations. Furthermore, among 42 topical antifungal preparations included into SFU, only four antifungals are recommended for onychomycosis treatment. These are bifonazole cream, econazole cream, gel and cream with miconazole. Neither ketoconazole nor other topical antifungal preparation listed in CP, except of miconazole, are specified by SFU to be effective for onychomycosis. Antifungal lacquers are not included into SFU at all. There are gaps between CP and SFU. CP should be reviewed in accordance to data of evidence-based medicine. Despite the fact that a new edition of SFU was recently published, it does not include antifungal lacquers, which are broadly used and recommended, for example, by British National Formulary. Thus, it is also necessary to analyze antifungal nail lacquers for making decision about including them into SFU.

In vivo antifungal activity of dipyrithione against Trichophyton rubrum on guinea pig dermatophytosis models.

The treatment of dermatophytosis has improved considerably over the past several decades following the introduction of the oral antifungals such as azoles and amphotericin B. However, these drugs have had limited success because the treated fungi often develop drug resistance, resulting in recurrence when applied in various topical formulations. Thus, there are constant needs for new topical agents that are effective against dermatophytosis. Dipyrithione is an attractive candidate to become an antifungal agent due to its broad spectrum of antimicrobial activities. In this study, we determined that dipyrithione could potently inhibit the growth of Trichophyton rubrum, which is the most common cause of dermatophytosis. The MIC50 value of dipyrithione against T. rubrum was measured as 6.03 μM, as compared with miconazole (MIC50: 1.38 μM). Additionally, the compound caused morphological changes in the fungi, which was examined using the morphological interference assay. The in vivo experiment further revealed that dipyrithione had a healing effect on the skin of guinea pigs infected with T. rubrum. Our studies have demonstrated that dipyrithione had a potent antifungal activity in vitro and in vivo, suggesting that it could be formulated as a potential antifungal lead compound in search for novel therapeutic agents against dermatophytosis.

A Rare Case of Isolated Retro-orbital Fungal Granuloma

We report here the first case of retro-orbital fungal granuloma caused by Aspergillus versicolor. A 52-year-old male presented with protrusion of left eye associated with pain in the left eye and watering of the left eye for 6 months duration. Left eye examination showed axial proptosis, and fundus examination revealed blurring of the nasal disc margin. Diagnostic nasal endoscopy revealed an irregular pinkish proliferative mass medial to the middle turbinate. Plain computed tomography of the orbits showed a retrobulbar intraconal lesion in the left orbit. The patient was taken up for endoscopic orbital and optic nerve decompression with debulking or retro-orbital mass under general anesthesia. Culture on Sabouraud's dextrose agar grew Aspergillus species. The patient was started on oral itraconazole 100 mg twice daily, and over the course of 2 months, the left eye proptosis reduced significantly. Review at 2 years postoperatively did not reveal any recurrence of symptoms. Endoscopic clearance of the disease combined with oral antifungals is the appropriate modality of therapy for aspergillosis.

Miltefosine Administration in Cats with Refractory Sporotrichosis

Background: Sporotrichosis is a zoonosis caused by fungi of the Sporothrix schenckii complex. Cats have important zoonotic potential due to the high parasite load found in the cutaneous lesions. Refractory cases to antifungal therapy are increasing, becoming a public health problem. Miltefosine is a drug with high in vitro activity against Sporothrix brasiliensis. However, this efficacy has not been confirmed in vivo yet and administration has not been studied in the feline species. This study aimed to evaluate the effectiveness and safety of miltefosine administration in cats with resistant sporotrichosis.Materials, Methods & Results: Ten cats with refractory sporotrichosis were included in this study. Inclusion criteria were previous diagnosis for sporotrichosis associated with therapy with oral antifungals (itraconazole and/or potassium iodide) for more than one year, followed by one of these conditions: incomplete clinical remission, worsening of disease during treatment or recurrence after conventional treatment. Cats underwent clinical and dermatological examinations. Data on lifestyle and previous treatments were provided by the owners. Fungal culture and histochemical techniques were performed in all cats before miltefosine treatment. Blood samples were collected before and during the study for laboratory tests, such as blood count, blood urea nitrogen (BUN), serum creatinine, alanine aminotransferase (ALT) and alkaline phosphatase, as well as serology for Feline Immunodeficiency (FIV) and Feline Leukemia (FeLV). Miltefosine was prescribed at a dosage of 2 mg/kg orally every 24 h. The animals were monitored by phone during the whole process and reassessed on days 0, 15, 30 and 45 of the treatment. Out of 10 cats, lesions were present on the nose in nine, ears in four, periocular areas in one and limbs in four. One cat received treatment for 45 days, six for 30 days, one for 21 days, one for 15 days and one for 3 days. One cat showed no response to the treatment and nine showed disease progression. Hyporexia and weight loss were the most frequent clinical signs related to miltefosine treatment, followed by sialorrhea, vomiting and diarrhea. Few adverse effects on hematology and biochemistry (mainly renal and hepatic parameters) were observed during the study. Hematocrit decrease was observed in four animals. However, only one cat had hematocrit decrease below normal values (anemia), which was already present before miltefosine administration. Other cats had a decrease of five points. Three cats showed elevation in leucometria and four in plasma protein. In relation to renal and hepatic biochemistry, one animal showed a BUN increase and another one showed a transient increase in ALT. Two animals started the treatment with increased ALT but had no problems during the study and values decreased even during the miltefosine administration.Discussion: Although two cats showed sialorrhea, most owners did not report difficulty in administering the drug orally, representing an advantage of this medication. Weight loss, secondary to gastrointestinal changes, was the most clinically relevant alteration. The most frequent hematological alteration was hematocrit decrease and only the animal that started the study with 20% hematocrit ended the study with anemia. Renal and hepatic parameters were not significant in the cats of this study. Miltefosine did not lead to sporotrichosis remission in this small population of cats, which reveals that, despite its in vitro efficacy against Sporothrix spp., the drug is not effective in vivo in the feline species. Further studies are needed to investigate the efficacy of this drug in a larger number of cats, and possible reasons for its in vivo ineffectiveness.

COMBINATION ANTIFUNGAL THERAPY FOR ONYCHOMYCOSIS

Onychomycosis is a fungal infection of the nail unit including the nail matrix, the nail bed and the nail plate by both dermatophyte and non-dermatophyte agents. It is disturbs not only cosmetic disfigurement, but also it may have an impact on patients’ emotional, social and occupational functioning, finally affecting the overall quality of life. The incidence rate tends to increase, management of onychomycosis is still challenging. Important problems regarding antifungal monotherapy have experienced many failures and recurrences. In general, pharmacological approaches for onychomycosis can be topical or oral antifungal. Antifungal monotherapies often lead to failure treatment, also high incidence of recurrence. One strategy for this problem is a combination antifungal therapy. In vitro studies show the synergistic effect of using combination two antifungals (both oral antifungal or combination topical and oral antifungal), hence it is mycologically or clinically expected to increase the success rate of onychomycosis therapy. This review tries to evaluate the previous study exploring the effectiveness of antifungal combination therapies on onychomycosis. Two oral antifungals usually used are terbinafine as fungicidal agent and itraconazole as fungistatic agent. There is combination between topical and oral antifungal such as itraconazole or terbinafine with amorolfine or ciclopirox, also other combination like griseofulvin and amorolfone or tioconazole. All the combination therapies show better result than monotherapy alone, but it is still difficult to conclude whether antifungal combinations in onychomycosis will increase effectiveness due to variations in therapeutic duration, result definition, and statistical evaluation on existing studies. Further research is required with longer duration of observation, uniform patient criteria and definition of success, random control and blinding to minimize bias.

Newer Topical Treatments in Skin and Nail Dermatophyte Infections.

Dermatophytes are amongst the most common causative agents of fungal infections worldwide and widespread in the developing countries. Various studies have found the significantly rising trend of this infection in India especially in last 4-5 years. The growing epidemic of recurrent/chronic dermatophytosis has led to the need for newer antifungal agents and/or preparations. Furthermore, resistance to commonly used topical and oral antifungals has increased alarmingly. Significantly increasing resistance has led to state of anxiety in physicians and significant distress to the patients socially, emotionally, and financially. Newer formulations or newer derivatives of existing drug classes and few newer drug classes are being developed to tackle this menace. Other forms of local therapies including lasers and photodynamic therapy are still in developmental phase and still need to be optimized in terms of dosing schedule, frequency of use and duration of therapy. Moreover, cost of these therapies remained most important obstacle in developing countries like India. We are hereby reviewing the newer formulations of topical therapies and drugs/interventions in experimental phase.

Recalcitrant Candidal Corneal Ulcer- A Therapeutic Challenge

We are hereby presenting a case of recalcitrant fungal corneal ulcer caused by Candida Albicans which did not respond to conventional treatment methods of fungal corneal ulcer ie oral and topical antifungals. The fungal keratitis responded to intrastromal Amphotericin B; thereby highlighting the importance of newer treatment modalities in management of recalcitrant fungal keratitis, e.g. intrastromal and intracameral antifungals. The keratitis started to heal rapidly after the first intrastromal injection of Amphotericin B, and healed completely after three intrastromal injections administered at fortnightly intervals; with residual corneal scarring and vascularization.

Successful management of bee sting induced Aspergillus fumigatus endophthalmitis and scleritis

Ocular bee stings are known to cause corneal melts, corneal infiltrates, cataracts, and secondary glaucoma. Our patient presented with scleritis, corneal infiltrates, and endophthalmitis after a ocular bee sting. Topical treatment led to resolution of anterior segment inflammation, but the scleritis and vitreous inflammation worsened. Vitrectomy with intravitreal antibiotics was done and scrapings from the scleral abscess showed growth of Aspergillus fumigatus on culture. Repeat vitrectomy with silicone oil was needed for retinal detachment. Oral and intravitreal antifungals led to resolution of inflammation with attached retina. This is the first reported case of bee sting-induced fungal endophthalmitis with scleritis.

Erratum: Intracutaneous pharmacokinetics of oral antifungals and their relevance in recalcitrant cutaneous dermatophytosis: Time to revisit basics.

[This corrects the article DOI: 10.4103/ijdvl.IJDVL_1012_16].

Pityrosporum folliculitis: A retrospective review of 110 cases

Pityrosporum folliculitis is an under-recognized eruption of the face and upper portion of the trunk that may be confused with, or occur simultaneously with, acne vulgaris. We sought to characterize risk factors for Pityrosporum folliculitis, its clinical presentation, and its response to treatment. A retrospective chart review was performed on all patientsage 0 to 21years seen at our facility from 2010 to 2015 with Pityrosporum folliculitis confirmed by a potassium hydroxide preparation. Of 110 qualifying patients, more than 75% had acne that had recently been treated with antibiotics, and when recorded, 65% reported pruritus. Clinical examination demonstrated numerous 1- to 2-mm monomorphic papules and pustules that were typically on the forehead extending into the hairline and on the upper portion of the back. The most common treatment was ketoconazole shampoo, which led to improvement or resolution in most cases. Some patients required oral azole antifungals. This study was retrospective and relied on providers describing and interpreting the clinical findings and potassium hydroxide preparations. No standard grading system was used. Unlike classic acne vulgaris, Pityrosporum folliculitis was more common after antibiotic use. It presented as fine monomorphic, pruritic papules and pustules along the hairline and on the upper portion of the back, and it improved with topical or oral azole antifungal therapy.