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BACKGROUND: Fungal infection of the toenails, also called onychomycosis, is a common problem that causes damage to the nail's structure and physical appearance. For those severely affected, it can interfere with normal daily activities. Treatment is taken orally or applied topically; however, traditionally topical treatments have low success rates due to the nail's physical properties. Oral treatments also appear to have shorter treatment times and better cure rates. Our review will assist those needing to make an evidence-based choice for treatment.
OBJECTIVES: To assess the effects of oral antifungal treatments for toenail onychomycosis.
SEARCH METHODS: We searched the following databases up to October 2016: the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We also searched five trials registers and checked the reference lists of included and excluded studies for further references to relevant randomised controlled trials (RCTs). We sought to identify unpublished and ongoing trials by correspondence with authors and by contacting relevant pharmaceutical companies.
SELECTION CRITERIA: RCTs comparing oral antifungal treatment to placebo or another oral antifungal treatment in participants with toenail onychomycosis, confirmed by one or more positive cultures, direct microscopy of fungal elements, or histological examination of the nail.
DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane.
MAIN RESULTS: We included 48 studies involving 10,200 participants. Half the studies took place in more than one centre and were conducted in outpatient dermatology settings. The participants mainly had subungual fungal infection of the toenails. Study duration ranged from 4 months to 2 years.We assessed one study as being at low risk of bias in all domains and 18 studies as being at high risk of bias in at least one domain. The most common high-risk domain was 'blinding of personnel and participants'.We found high-quality evidence that terbinafine is more effective than placebo for achieving clinical cure (risk ratio (RR) 6.00, 95% confidence interval (CI) 3.96 to 9.08, 8 studies, 1006 participants) and mycological cure (RR 4.53, 95% CI 2.47 to 8.33, 8 studies, 1006 participants). Adverse events amongst terbinafine-treated participants included gastrointestinal symptoms, infections, and headache, but there was probably no significant difference in their risk between the groups (RR 1.13, 95% CI 0.87 to 1.47, 4 studies, 399 participants, moderate-quality evidence).There was high-quality evidence that azoles were more effective than placebo for achieving clinical cure (RR 22.18, 95% CI 12.63 to 38.95, 9 studies, 3440 participants) and mycological cure (RR 5.86, 95% CI 3.23 to 10.62, 9 studies, 3440 participants). There were slightly more adverse events in the azole group (the most common being headache, flu-like symptoms, and nausea), but the difference was probably not significant (RR 1.04, 95% CI 0.97 to 1.12; 9 studies, 3441 participants, moderate-quality evidence).Terbinafine and azoles may lower the recurrence rate when compared, individually, to placebo (RR 0.05, 95% CI 0.01 to 0.38, 1 study, 35 participants; RR 0.55, 95% CI 0.29 to 1.07, 1 study, 26 participants, respectively; both low-quality evidence).There is moderate-quality evidence that terbinafine was probably more effective than azoles for achieving clinical cure (RR 0.82, 95% CI 0.72 to 0.95, 15 studies, 2168 participants) and mycological cure (RR 0.77, 95% CI 0.68 to 0.88, 17 studies, 2544 participants). There was probably no difference in the risk of adverse events (RR 1.00, 95% CI 0.86 to 1.17; 9 studies, 1762 participants, moderate-quality evidence) between the two groups, and there may be no difference in recurrence rate (RR 1.11, 95% CI 0.68 to 1.79, 5 studies, 282 participants, low-quality evidence). Common adverse events in both groups included headache, viral infection, and nausea.Moderate-quality evidence shows that azoles and griseofulvin probably had similar efficacy for achieving clinical cure (RR 0.94, 95% CI 0.45 to 1.96, 5 studies, 222 participants) and mycological cure (RR 0.87, 95% CI 0.50 to 1.51, 5 studies, 222 participants). However, the risk of adverse events was probably higher in the griseofulvin group (RR 2.41, 95% CI 1.56 to 3.73, 2 studies, 143 participants, moderate-quality evidence), with the most common being gastrointestinal disturbance and allergic reaction (in griseofulvin-treated participants) along with nausea and vomiting (in azole-treated participants). Very low-quality evidence means we are uncertain about this comparison's impact on recurrence rate (RR 4.00, 0.26 to 61.76, 1 study, 7 participants).There is low-quality evidence that terbinafine may be more effective than griseofulvin in terms of clinical cure (RR 0.32, 95% CI 0.14 to 0.72, 4 studies, 270 participants) and mycological cure (RR 0.64, 95% CI 0.46 to 0.90, 5 studies, 465 participants), and griseofulvin was associated with a higher risk of adverse events, although this was based on low-quality evidence (RR 2.09, 95% CI 1.15 to 3.82, 2 studies, 100 participants). Common adverse events included headache and stomach problems (in griseofulvin-treated participants) as well as taste loss and nausea (in terbinafine-treated participants). No studies addressed recurrence rate for this comparison.No study addressed quality of life.
AUTHORS' CONCLUSIONS: We found high-quality evidence that compared to placebo, terbinafine and azoles are effective treatments for the mycological and clinical cure of onychomycosis, with moderate-quality evidence of excess harm. However, terbinafine probably leads to better cure rates than azoles with the same risk of adverse events (moderate-quality evidence).Azole and griseofulvin were shown to probably have a similar effect on cure, but more adverse events appeared to occur with the latter (moderate-quality evidence). Terbinafine may improve cure and be associated with fewer adverse effects when compared to griseofulvin (low-quality evidence).Only four comparisons assessed recurrence rate: low-quality evidence found that terbinafine or azoles may lower the recurrence rate when compared to placebo, but there may be no difference between them.Only a limited number of studies reported adverse events, and the severity of the events was not taken into account.Overall, the quality of the evidence varied widely from high to very low depending on the outcome and comparison. The main reasons to downgrade evidence were limitations in study design, such as unclear allocation concealment and randomisation as well as lack of blinding.
Dermatology (1) Onychomycosis (6), Headache (4), Infections (4), more mentions
Viral, bacterial, and fungal infections are frequently encountered in clinical practice, resulting in numerous cutaneous manifestations. Although diagnosis of these infections has changed over time because of technological advancements, such as polymerase chain reaction, bedside diagnostic techniques still play an important role in diagnosis and management, enabling rapid and low-cost diagnosis and implementation of appropriate therapies. This 2-part article will review both common and infrequent uses of bedside diagnostic techniques that dermatologists can incorporate into daily practice. This article examines the utility of bedside tests for the diagnosis of viral, bacterial, and fungal infections. The second article in this series reviews the use of bedside diagnostics for parasitic and noninfectious disorders.
AbstractMycetoma is a chronic soft tissue infection caused by fungal or bacterial pathogens, and is endemic in tropical and subtropical regions. Cases in developed countries outside the mycetoma belt are rare and usually imported by immigrants. Sporadic cases have been reported in Israel. Unpublished cases in the participating medical centers are reported. In addition, a systematic review of the literature was performed. All published mycetoma cases diagnosed in Israel were included with relevant variables collected. Twenty-one cases of mycetoma were diagnosed in Israel between 1942 and 2015, including four unpublished cases and 17 published cases. The mean age at diagnosis was 42 years (range 23-73), and 16 of the patients were male. The foot was the primary involved organ. Fifteen patients were immigrants from Yemen, Ethiopia, and Sudan. Five cases were autochthonous. One case was travel related. Among patients who developed symptoms after immigration, the mean time from exposure to symptom onset was 5.6 years (range 1-10 years). The mean time from symptom onset to diagnosis was 6.6 years (range 0.2-35 years). The autochthonous cases demonstrate that Israel is endemic of mycetoma. The immigrant population represents two distinct waves of immigration to Israel in the past century. Two unpublished cases of Ethiopian immigrants are the first reported cases of mycetoma acquired in Ethiopia. The diagnostic and therapeutic challenges along with the epidemiological data emphasize the need of raising the awareness of physicians to this devastating condition even in developed countries.
Although increasingly frequent, little is known about the clinical presentation, radiological signs, and outcome of Candida vertebral osteomyelitis (CVO).We performed a nationwide retrospective study of laboratory-confirmed cases of CVO over a 10 year-period in France with a prolonged follow-up. We describe demographic, clinical, biological, and radiological characteristics of patients with CVO, patients' management, and long-term outcome and determine factors associated with a poor outcome.In total, 28 patients with laboratory-confirmed CVO were included. A prior systemic Candida infection was evidenced in 13/28 (46%), occurring a median of 6 weeks before CVO was diagnosed. Twenty-six of 28 (93%) had at least 1 underlying condition at risk of invasive fungal disease, and in 19/28 (68%) CVO was health-care related. C albicans was most frequently identified (21/28; 75%) Lumbo-sacral involvement was the most prevalent (20/28-71%). Nearly half patients had no fever at presentation, but all had pain. Initial antifungal therapy consisted in fluconazole in 15/28 (53%); surgery was needed in 5 (18%) cases.One-year mortality was 21% (6/28), directly related to fungal infection in 2 patients. Risk-factors associated with 1-year mortality were age (P=.02), a high Charlson comorbidity index (P = .001), and a shorter treatment duration (median, 3 months vs 6 months; P = .02). Among 22 patients who survived, the median follow up duration was 15.5 months (8-93.5); 10 had sequelae, consisting in pain in all and neurological deficit in one. A longer treatment duration was significantly associated with healing without sequelae (P = .04).CVO concerns patients with serious underlying conditions and risk-factors for invasive candidiasis. Prolonged antifungal treatment appears to improve survival without sequelae.
INTRODUCTION: Onychomycosis and nail psoriasis can be embarrassing to patients, so improving the appearance of affected nails should be one of the key short-term goals of treatment.
METHODS: An 8-week open-label multicenter study was conducted to assess whether K101-03, a marketed topical treatment containing propylene glycol, glycerol, urea, and lactic acid, could produce rapid cosmetic improvements in affected nails. Adult patients with a big toenail or thumbnail (the "target" nail) affected by onychomycosis (n = 72) or psoriasis (n = 34) or both (n = 1) applied K101-03 to their affected nails once a day for 8 weeks. During and after treatment, patients rated the overall appearance of their target nail on a 4-point scale. They also assessed whether thickening, discoloration, brittleness, and softness of the target nail had improved since baseline. Adverse events (AEs) that occurred between the first application of K101-03 and the end of treatment were recorded and categorized according to severity and relationship to K101-03.
RESULTS: After 8 weeks of K101-03 treatment, 92.2% of patients (95% confidence interval [CI] 87.06-97.40) reported at least some improvement in the target nail. After 1 week of treatment, 78.3% of patients with onychomycosis (95% CI 68.53-87.99) reported at least some improvement in the target nail, and 55.1% of them reported that discoloration of their target nail had improved. Three patients reported a total of 5 AEs, none of which were judged to be related to K101-03.
CONCLUSIONS: In summary, K101-03 was well tolerated in patients with onychomycosis or nail psoriasis and rapidly improved their nails.
BACKGROUND: Chromoblastomycosis is a deep fungal infection characterized by a complex cellular granuloma. The aim of this study was to analyze the arrangement of cells responsible for the granuloma configuration of this disease by semiquantification of the cellular components of chromoblastomycosis skin biopsies.
METHODS: The cells of cutaneous biopsies slides from 100 patients with untreated chromoblastomycosis were stained with hematoxylin-eosin and the granuloma cells were evaluated by microscopic examination of the elements of each granuloma and semiquantified the number of cells through its expressivity in crosses and the histopathological variables. Their presences were coded in degrees of intensity and classified in two categories: low expression and high expression. The cells that constitute the granulomas were separated into three groups: A, B and C.
RESULTS: The chromoblastomycotic granuloma analysed by this semiquantification of its cellular components showed that there was high expression of the elements setting up a mixed organized mycotic granuloma. It was observed that mononuclear phagocytic system (A), polymorphonuclear phagocytic system (B) and lymphoplasmocytic infiltrate (C) were located around the fungus.
CONCLUSIONS: The results indicated that the granuloma present in the cutaneous lesion of chromoblastomycosis is the mixed organized mycotic granuloma with high expression of the cellular components.
Granuloma (9), Chromoblastomycosis (5), Infections (1), more mentions
Chronic hyperplastic candidiasis (CHC) is described within the oral mucosa and the most commonly affected sites are the buccal commissures, cheeks, palate and tongue. In the oral, pharyngeal, and laryngeal mucosae, verrucous epidermal hyperplasia (VEH), pseudocarcinomatous hyperplasia (PCH), epithelial dysplasia, and a verrucous clinical appearance have all been reported in association with CHC.
Infectious Diseases (2) Candidiasis (2), Hyperplasia (2), more mentions
Nail psoriasis and onychomycosis can often be hard to differentiate clinically and may coexist, complicating each other's course. The aim of this study was to determine the prevalence of onychomycosis among patients with nail psoriasis not being treated with immunosuppressive agents, which constitute an independent risk factor for fungal infections. A cross-sectional study was performed. All adult patients with nail psoriasis who were not receiving antifungal and/or immunosuppressive treatment were recruited at the 2nd University Dermatology Department of Aristotle University of Thessaloniki from 10/2016 till 02/2017. If onychomycosis was clinically suspected, nail samples were collected and direct microscopy with 15% KOH solution and culture were performed. Target-NAPSI and DLQI score were also calculated. Of the 23 patients recruited, 20 were men and 3 were women, with a mean age of 53.43 years (48.25, 58.62), a mean target-NAPSI score of 10.72 (9.62, 11.77) and a mean DLQI score of 10.17 (7.46, 12.89). A total of 34.78% of patients tested positive for onychomycosis. Yeast were isolated in 37.50% of cases, non-dermatophyte filamentous fungi in 37.50% and T. rubrum in 12.50%. The prevalence of onychomycosis among nail psoriasis patients is higher than that among the general population of Greece (15%-20%). Yeast and moulds predominate in infection cases of nail psoriasis patients.
Dermatology (9) Psoriasis (8), Onychomycosis (7), Infections (2), more mentions
Invasive Candida infection is the fourth most common bloodstream infection. Blood cultures are the current gold standard diagnostic method, however false negatives remain a clinical challenge. We developed a new technique measuring Candida reactive T cells as diagnostic read-out for invasive Candida infection. In a pilot study, we followed the treatment course of a patient with an invasive Candida infection of the lumbar vertebral spine. We present the case of the 56 year old patient with HIV-associated Burkitt lymphoma who developed septic shock during chemotherapy induced neutropenia. For the first time, we provide flow cytometry based diagnostics with Candida reactive T cells for invasive candidiasis with comprehensive MRI imaging. The Candida reactive T cell assay has potential to complement current diagnostic assays for invasive Candida infection and thus to support targeted treatment. This article is protected by copyright. All rights reserved.
BACKGROUND: Neutropenic patients developing acute disseminated candidiasis may present with skin lesions.
AIMS: To evaluate the epidemiology of acute disseminated candidiasis with skin lesions in neutropenic patients, taking into consideration changes caused by different prophylactic strategies.
SOURCES: A systematic review of English articles using PubMed (1963-2016) was performed. We asked the following questions: (1) What Candida species are more frequently involved in this syndrome? (2) Has antifungal prophylaxis changed the species causing skin lesions? (3) What are the typical patterns of skin lesions? (4) What is the frequency of skin lesions in neutropenic patients with candidemia or acute disseminated candidiasis? (5) Has antifungal prophylaxis decreased the incidence of acute disseminated candidiasis with skin lesions?
CONTENT: Among 183 studies, 33 were selected, reporting 100 cases of acute disseminated candidiasis with skin lesions in neutropenic patients. It occurred more frequently in the setting of induction therapy for de novo or relapsed acute leukemia, and the most frequent species were C. tropicalis (68%) and C. krusei (15%). Diffuse maculopapular lesions predominated in cases caused by C. tropicalis and nodular and papular lesions in cases caused by C. krusei. Prophylaxis with fluconazole was reported in six cases; C. krusei in five, and C. ciferri in one. The death rate was 46.3%.
IMPLICATIONS: Two patterns were recognized: disseminated maculopapular lesions caused by C. tropicalis in patients not receiving fluconazole prophylaxis, occurring in 39-44% of neutropenic patients with acute disseminated candidiasis, and nodular lesions caused by C. krusei in patients on fluconazole prophylaxis, occurring less frequently.
Oral infections caused by Candida species, the most commonly isolated human fungal pathogen, are frequently associated with biofilms. Although Candida albicans is the predominant organism found in patients with oral thrush, a biofilm infection, there is an increasing incidence of oral colonization and infections caused by non- albicans Candida species, including C. glabrata, C. dubliniensis, and C. tropicalis, which are frequently more resistant to antifungal treatment. While single-species Candida biofilms have been well studied, considerably less is known about the dynamics of mixed- Candida species biofilms and how these dynamics are altered by antifungal treatment. To address these questions, we developed a quantitative polymerase chain reaction-based approach to determine the precise species composition of mixed- Candida species biofilms formed by clinical isolates and laboratory strains in the presence and absence of clinically relevant concentrations of 3 commonly used antifungals: fluconazole, caspofungin, and amphotericin B. In monospecies biofilms, fluconazole exposure favored growth of C. glabrata and C. tropicalis, while caspofungin generally favored significant growth of all species to a varying degree. Fluconazole was not effective against preformed mixed- Candida species biofilms while amphotericin B was potent. As a general trend, in mixed- Candida species biofilms, C. albicans lost dominance in the presence of antifungals. Interestingly, presence in mixed versus monospecies biofilms reduced susceptibility to amphotericin B for C. tropicalis and C. glabrata. Overall, our data suggest that antifungal treatment favors the growth of specific non- albicans Candida species in mixed- Candida species biofilms.
The causal agents of blastomycosis, Blastomyces dermatitidis and Blastomyces gilchristii, belong to a group of thermally dimorphic fungi that can infect healthy and immunocompromised individuals. Following inhalation of mycelial fragments and spores into the lungs, Blastomyces spp convert into pathogenic yeast and evade host immune defenses to cause pneumonia and disseminated disease. The clinical spectrum of pulmonary blastomycosis is diverse. The diagnosis of blastomycosis requires a high degree of clinical suspicion and involves culture-based and non-culture-based fungal diagnostic tests. The site and severity of infection, and the presence of underlying immunosuppression or pregnancy, influence the selection of antifungal therapy.
Candidemia presents several challenges to the intensive care unit (ICU) community. Recognition and treatment of this infection is frequently delayed, with dramatic clinical deterioration and death often preceding the detection of Candida in blood cultures. Identification of individual patients at the highest risk for developing candidemia remains an imperfect science; the role of antifungal therapy before culture diagnosis is yet to be fully defined in the ICU. The absence of well-established molecular techniques for early detection of candidemia hinders efforts to reduce the heavy clinical and economic impact of this infection. Echinocandins are the recommended antifungal drug class for the treatment of ICU candidemia.
Monitoring fungal ecology and resistance to antifungal agents within intensive care units (ICU) is essential for the management of invasive fungal infections. Therefore, a retrospective descriptive study was carried in the ICU of Nimes University Hospital, France, from 2007 to 2016. As the majority of invasive fungal infections in ICU are caused by Candida species, the study objectives were to describe Candida species distribution, to assess candidaemia incidence and to monitor the antifungal drug susceptibility of Candida isolates and the consumption of antifungal agents. Among the recorded invasive Candida infections (n=244), 43% were intra-abdominal and 22% bloodstream infections. Candida albicans was the most frequent species (55.8%), followed by Candida glabrata (14.1%), Candida tropicalis (10%), Candida parapsilosis (8%) and Candida krusei (5.3%). Candidaemia incidence was 4.49 per 1000 admissions. The mean consumption of antifungal agents was of 170.5 defined daily doses (DDD) for 1000 hospital days (HD) per year. Changes in antifungal drug consumption were observed, with an increased use of echinocandins (from 17.96 DDD/1000 HD in 2007 to 48.76 DDD/1000 HD in 2016), and the total treatment cost tripled during the study period. No significant change in fungal ecology or in the emergence of resistant species was observed; indeed, only 1.1% of isolates presented an unusual resistance to antifungal agents.
Infectious Diseases (1) Infections (4), Candidiasis (1), more mentions
BACKGROUND: Candidiasis and certain types of cancer are related to immunocompromised status. This study aimed to evaluate whether Candida infection (CI) is associated with subsequent cancer risk in Taiwan.
METHODS: Data from the National Health Insurance system of Taiwan were used to evaluate the association between CI and cancer risk. The CI cohort comprised 34,829 patients. Each patient was randomly frequency matched with one person from the general population without CI on the basis of age, sex, year of index date of CI diagnosis, and other characteristics to generate the control group. We used Cox's proportional hazard regression analysis to estimate the effects of CI on subsequent cancer risk.
RESULTS: Compared with the control group, patients with CI had a significantly higher risk of overall cancer (adjusted hazard ratio = 1.19, 95% confidence interval = 1.09-1.30). For subsite analysis, the risks of hematologic malignancy and head and neck, pancreatic, skin, and thyroid cancers were significantly higher in the CI group. Stratified analyses by sex, age, and follow-up time revealed different patterns.
CONCLUSION: Our study suggested that CI can significantly increase overall and some individual cancer risks, which is partially compatible with previous findings.
Vulvovaginal candidiasis (VVC) is a global health problem affecting ∼75% of women at least once in their lifetime. Here we examined the epidemiology of VVC in a patient cohort to identify the causative organisms associated with VVC. Biofilm-forming capacity and antifungal sensitivity profiles were also assessed. We report a shifting prevalence of Candida species with heterogeneous biofilm-forming capacity, which is associated with altered antifungal drug sensitivity.
Stereotactic needle biopsy, a standard of care for acquiring deep-seated pathology, has limitations and risks in some situations. We present an uncommon case with basal ganglia dematiaceous mycetoma. Due to the firm consistency of the lesion, the initial stereotactic needle biopsy failed to provide a diagnosis. In a second operation, transtubular excisional biopsy was successfully performed to remove the entire mycetoma. We reviewed recent case series of transtubular approaches to deep-seated brain lesions and suggest this method could be a rescue for a non-diagnostic stereotactic needle biopsy and even may be the approach of choice in some cases.
Patients in the intensive care unit are exposed to multiple stressors that predispose them to invasive fungal infections (IFIs), which carry high morbidity and mortality. Getting acquainted with the diagnostic methods and therapies is imperative for patient safety and for providing high-quality health care. This article focuses on the most frequent IFIs: invasive candidiasis and invasive aspergillosis.