Systemic Antifungal Treatment Research Articles

Disseminated coccidioidomycosis in a patient with juvenile idiopathic arthritis receiving infliximab

BackgroundCoccidioides immitis is a dimorphic fungus endemic to the arid climates of the Southwest United States, Mexico and parts of Central and South America. Human infection occurs through inhalation of spores with less than half of exposures progressing to a symptomatic state that primarily consists of pulmonary manifestations. Disseminated coccidioidomycosis is exceedingly rare, occurring in fewer than 1 % of symptomatic infections. Through hematogenous spread, the fungus can infect most organ systems and may be fatal without systemic antifungal treatment. Individuals with impaired cell-mediated immunity either from primary immunodeficiency disorders or secondary to immunosuppression with medications such as tumor necrosis factor alpha (TNF-α) inhibitors have increased risk of disseminated coccidioidomycosis and previous cases of coccidioidomycosis have been reported with biologic therapy.Case presentationWe present a case of disseminated coccidioidomycosis in a 16-year-old female with polyarticular juvenile idiopathic arthritis (JIA) being treated with prednisone, methotrexate, and infliximab. The patient presented with symptoms of meningeal irritation, bilateral choroidal lesions, and necrotizing peripheral pneumonia. Her infection was thought to be a reactivation of coccidioidomycosis given her history of resolved pneumonia that occurred after traveling to Arizona, New Mexico, and El Paso one year prior to presentation. Following diagnosis, she improved with discontinuation of her immunosuppressive medications and two weeks of intravenous amphotericin B and fluconazole with plans for lifetime treatment with fluconazole while immunosuppressed. Due to worsening arthritis, she will begin tofacitinib and continue close monitoring of chest x-rays and coccidioides antibody.ConclusionsPatients undergoing immunosuppressive therapy for rheumatological conditions are at increased risk of disseminated coccidioidomycosis and should be evaluated with high suspicion when presenting with atypical symptoms and history of travel to endemic regions.

Invasive infections with Purpureocillium lilacinum: clinical characteristics and outcome of 101 cases from FungiScope® and the literature.

ObjectivesTo provide a basis for clinical management decisions in Purpureocillium lilacinum infection.MethodsUnpublished cases of invasive P. lilacinum infection from the FungiScope® registry and all cases reported in the literature were analysed.ResultsWe identified 101 cases with invasive P. lilacinum infection. Main predisposing factors were haematological and oncological diseases in 31 cases (30.7%), steroid treatment in 27 cases (26.7%), solid organ transplant in 26 cases (25.7%), and diabetes mellitus in 19 cases (18.8%). The most prevalent infection sites were skin (n = 37/101, 36.6%) and lungs (n = 26/101, 25.7%). Dissemination occurred in 22 cases (21.8%). Pain and fever were the most frequent symptoms (n = 40/101, 39.6% and n = 34/101, 33.7%, respectively). Diagnosis was established by culture in 98 cases (97.0%). P. lilacinum caused breakthrough infection in 10 patients (9.9%). Clinical isolates were frequently resistant to amphotericin B, whereas posaconazole and voriconazole showed good in vitro activity. Susceptibility to echinocandins varied considerably. Systemic antifungal treatment was administered in 90 patients (89.1%). Frequently employed antifungals were voriconazole in 51 (56.7%) and itraconazole in 26 patients (28.9%). Amphotericin B treatment was significantly associated with high mortality rates (n = 13/33, 39.4%, P = <0.001). Overall mortality was 21.8% (n = 22/101) and death was attributed to P. lilacinum infection in 45.5% (n = 10/22).Conclusions P. lilacinum mainly presents as soft-tissue, pulmonary or disseminated infection in immunocompromised patients. Owing to intrinsic resistance, accurate species identification and susceptibility testing are vital. Outcome is better in patients treated with triazoles compared with amphotericin B formulations.

Thoracic mucormycosis in immunocompetent patients

Mucormycosis is an invasive fungal infection. It is rare and commonly associated with fatal outcomes. We report two cases of thoracic mucormycosis in immunocompetent patients. First, is an immunocompetent child with mediastinal mass and extension into the pericardium and left atrium. The second is a young woman with a left pulmonary artery pseudoaneurysm. The first patient could not be salvaged while the second patient was successfully managed with surgical intervention and systemic antifungal treatment. Mucormycosis should be considered as a differential diagnosis in the management of immunocompetent patients in patients with pyrexia of unknown origin and a mediastinal mass. Early and aggressive surgical management along with systemic antifungal treatment improves the survival in this subset of patients.

Clinico-epidemiological profile of dermatophytosis

Introduction: Dermatophytosis have always been among the commonest infective dermatoses affecting nails, hairs and skin and is one of the common problems for which dermatology consultation is sought. The prevalence of dermatophytosis has been increasing since last decade because of environmental factors, irrational use of topic steroids and irregular systemic anti-fungal treatment. Aim: To determine clinical profile of dermatophytosis. Methods: The study was conducted in the Department of Dermatology, Venereology, Leprosy and Department of Microbiology, I.G.M.C, Shimla (H.P) between 1st July 2017 to 1st June 2018. All newly clinically suspected diagnosed patients of dermatophytosis above the age of 12 years. Results: A total of 315 clinically diagnosed patients with dermatophytosis were enrolled into the study. Majority of the patients were young adults aged 20-30 years (n=116) followed by aged between 50-60 years (n=72). The youngest and oldest age reported was 12 and 70 years, respectively. Majority of study group subjects were males i.e., 222 (70.47%) with male to female ratio 2.39:1. Approximately 81% patients had family history of the dermatophytosis. Approximately 13% patients had history of contacts with pets (dogs, cats and cattle). Diabetes mellitus (n=15) (53.5%) was the most common co-morbidity followed by psoriasis vulgaris (n=4) (14.2%). KOH positivity was reported in 48% (n=151) of the study subjects. Fungal culture was positive in 61% (n= 87) study subjects out of followed up patients (n=142). T. mentagrophytes was the most common dermatophyte isolated in 86.2% (n=75) of patients followed by T. rubrum in 12.6% (n=11) of the cases. Conclusion: Climatic conditions of Himachal Pradesh favour dermatophytosis in the population. Younger group of male population were having high prevalence.

A Case of Lingua Villosa Nigra (Black Hairy Tongue) in a 3-Month-Old Infant

Patient: Female, 3-month-oldFinal Diagnosis: Black hairy tongueSymptoms: Discolored tongueMedication:—Clinical Procedure: Gentle tongue brushingSpecialty: Pediatrics and NeonatologyObjective:Rare diseaseBackground:Black hairy tongue is a self-limiting, usually asymptomatic, benign lesion that most often affects men and people aged over 30–40 years. The lesion is extremely rare among newborns and infants. Lingua villosa nigra is characterized by the presence of elongated filiform papillae of the dorsum of the tongue, which gives a hairy appearance. The overgrown papillae can accumulate fungi, bacteria, pigments originating from food, or any other debris that can contribute to the discoloration of the tongue. The prognosis for black hairy tongue is positive. Gentle tongue brushing or scraping as well as the elimination of predisposing factors usually leads to cessation of the lesion.Case Report:A generally healthy, exclusively breastfed 3-month-old female baby was admitted to the Oral Pathology Department of Wrocław Medical University due to a persistent tongue lesion. Intraorally, dark, blackish, elongated tongue papillae were observed. Three weeks earlier, the baby’s pediatrician had diagnosed thrush and prescribed systemic antifungal treatment with Nystatinum, without prior mycological examination. The lesion did not resolve and the girl was referred to the Department of Oral Pathology. A meticulous medical and dietary interview revealed that since the 28th day of life the baby had been supplemented with vitamin C. This, together with an intraoral examination, led to the diagnosis of black hairy tongue. The lesion disappeared partially after 4 weeks of tongue brushing.Conclusions:To prevent infants from undergoing persistent and unnecessary treatment (topical or systemic drugs) or additional diagnostic procedures, such as biopsy, it is essential to be familiar with the characteristics of lingua villosa nigra as well as its origin and management. The consideration of this condition is invaluable for babies’ health and safety.

Oral Posaconazole or Intravenous-Oral Itraconazole in Preventing Invasive Fungal Diseases for Patients with Acute Leukemia

Background and Objectives: Invasive fungal diseases (IFDs) are major and lethal infectious complications for patients with neutropenia after chemotherapy for acute leukemia (AL). We aimed to compare the use of oral posaconazole vs. itraconazole in an intravenous-oral regimen for primary antifungal prophylaxis in terms of efficacy, adverse events and costs among neutropenic patients with AL after chemotherapy. Methods: This single-center, retrospective study enrolled patients with AL. Prophylaxis with oral posaconazole or intravenous-oral itraconazole (intravenous formulation × 2 days + oral suspension) was administered for patients recovering from neutropenia after chemotherapy. Propensity-score matching was used to assemble a cohort of patients with similar baseline characteristics. Results: Among 342 eligible episodes from 186 patients, 110 episodes received oral posaconazole and 110 episodes received itraconazole in sequential regimen had similar propensity scores and were included in the analyses. The incidence of breakthrough IFDs was 0.0% (0/110) and 0.0% (0/110) in the posaconazole group and itraconazole group, while the incidence of proven, probable and possible IFDs was 1.8% (2/110) and 8.2% (9/110), respectively (P=0.030). In clinical failure analysis, the failure rate of posaconazole group was lower as compared to the itraconazole group (2.7% vs. 10.9%, P=0.016). The proportion of patients who needed systemic antifungal treatment were lower in posaconazole group than that in itraconazole group (2.7% vs. 10.0%, P=0.027). Five cases (4.5%) experienced adverse events possibly associated with posaconazole and thirteen cases (11.8%) with itraconazole (P=0.049). There was no significant difference of survival between patients on posaconazole or itraconazole. The acquisition costs of posaconazole were higher than those of itraconazole (P=0.000). Conclusions: Both oral posaconazole and intravenous-oral itraconazole are effective in preventing IFDs for acute leukemia patients recovering from neutropenia after chemotherapy, while posaconazole is slightly better. Oral posaconazole is safer and more tolerable but costs higher than intravenous-oral itraconazole. Disclosures No relevant conflicts of interest to declare.

Laboratory monitoring during antifungal treatment of paediatric tinea capitis.

Griseofulvin and terbinafine are considered effective first-line therapies for tinea capitis (TC). Haematological dyscrasias and hepatic injury are possible adverse effects with both drugs. There is a debate in the literature regarding the necessity of laboratory monitoring during griseofulvin and terbinafine treatment. We aimed at assessing the prevalence and severity of haematological and hepatic laboratory test abnormalities in a paediatric cohort of African immigrants in Tel-Aviv with TC who were treated with Terbinafine or Griseofulvin. We conducted a retrospective study of all TC cases diagnosed and treated at the paediatric dermatology clinic, Tel-Aviv Medical centre, between June 2013 and March 2019. Epidemiologic, clinical and laboratory data were collected. Our cohort included 321 patients of whom 225 (70%) were treated with Griseofulvin and 96 (30%) with Terbinafine. We identified a total of 64 (20%) patients with haematological or hepatic laboratory test abnormalities that in most cases (96.3%) were considered as mild. No difference in laboratory abnormalities prevalence was identified between the griseofulvin and terbinafine groups (21.3% and 16.6%, respectively). Only one patient treated with Griseofulvin revealed significantly increased levels of hepatic aminotransferases that required discontinuation of treatment. Mild elevation in hepatic transaminases is relatively common among paediatric patients treated with systemic antifungal treatment for TC. However, significant laboratory abnormalities are extremely rare and may be diagnosed and addressed early through periodic laboratory tests monitoring.

Comparative study between the effect of topical tazarotene 0.1 gel alone vs its combination with tioconazole nail paint in treatment of onychomycosis.

Onychomycosis (OM) is a chronic fungal infection of the nail caused by dermatophytes, yeasts, and nondermatophytes. Tioconazole is one of the topical antifungal belonging to imidazole derivatives. Tazarotene is a synthetic retinoid, with immunomodulating properties and anti-inflammatory activity. To evaluate the efficacy of tazarotene 0.1% gel alone in comparison with its combination with tioconazole nail paint in the treatment of onychomycosis. Forty patients presented with onychomycosis, subjected to a full history taking, clinical examination, and nail examination, which includes a clinical, dermoscopic, assessment of severity by using Onychomycosis Severity Index (OSI), KOH examination, and fungal culture. There was a statistically significant increase in the response of treatment in patients treated by a combination of tazarotene and tioconazole compared to tazarotene alone through (decrease in OSI, dermoscopic features, and mycological clearance). Tazarotene had antifungal activity specially against Aspergillus niger while its combination with tioconazole gave better results and can be used as an adjuvant to the standard systemic or topical antifungal treatment for OM.

DIFFICULT DIAGNOSIS AND MANAGEMENT OF FUNGAL INJURY

A 56-year-old smoker had asymptomatic lesions on the hard palate and reported osteopenia, asthma, and chronic allergic rhinitis with "odors" and continued use of bronchodilators and antiallergics. Initial treatment was nystatin oral solution for 15 days and subsequent incisional biopsy for histopathologic and mycological evaluation. The histopathologic report pointed to infection by fungal agent–producing sporangia and endospores, being a case of difficult diagnosis because of the rarity of the infection, suggesting the possibility of rhinosporidiosis, but the mycological report did not observe fungal structures in the sample. The patient opted for systemic antifungal treatment with itraconazole (Sporanox (Janssen-Cilag)) rather than the surgical treatment of choice. After 6 months the lesion did not regress, corroborating with the literature, which shows that the systemic treatment for this type of lesion is not ineffective. Surgical resection becomes necessary for resolution of the condition. A 56-year-old smoker had asymptomatic lesions on the hard palate and reported osteopenia, asthma, and chronic allergic rhinitis with "odors" and continued use of bronchodilators and antiallergics. Initial treatment was nystatin oral solution for 15 days and subsequent incisional biopsy for histopathologic and mycological evaluation. The histopathologic report pointed to infection by fungal agent–producing sporangia and endospores, being a case of difficult diagnosis because of the rarity of the infection, suggesting the possibility of rhinosporidiosis, but the mycological report did not observe fungal structures in the sample. The patient opted for systemic antifungal treatment with itraconazole (Sporanox (Janssen-Cilag)) rather than the surgical treatment of choice. After 6 months the lesion did not regress, corroborating with the literature, which shows that the systemic treatment for this type of lesion is not ineffective. Surgical resection becomes necessary for resolution of the condition.

Tinea corporis: an updated review.

BackgroundTinea corporis is a common fungal infection that mimics many other annular lesions. Physicians must familiarize themselves with this condition and its treatment.ObjectiveThis article aimed to provide a narrative updated review on the evaluation, diagnosis, and treatment of tinea corporis.MethodsA PubMed search was performed with Clinical Queries using the key term ‘tinea corporis.’ The search strategy included clinical trials, meta-analyses, randomized controlled trials, observational studies, and reviews. The search was restricted to the English language. The information retrieved from the mentioned search was used in the compilation of the present article.ResultsTinea corporis typically presents as a well-demarcated, sharply circumscribed, oval or circular, mildly erythematous, scaly patch or plaque with a raised leading edge. Mild pruritus is common. The diagnosis is often clinical but can be difficult with prior use of medications, such as calcineurin inhibitors or corticosteroids. Dermoscopy is a useful and non-invasive diagnostic tool. If necessary, the diagnosis can be confirmed by microscopic examination of potassium hydroxide wet-mount preparations of skin scrapings from the active border of the lesion. Fungal culture is the gold standard to diagnose dermatophytosis especially if the diagnosis is in doubt and results of other tests are inconclusive or the infection is widespread, severe, or resistant to treatment. The standard treatment of tinea corporis is with topical antifungals. Systemic antifungal treatment is indicated if the lesion is multiple, extensive, deep, recurrent, chronic, or unresponsive to topical antifungal treatment, or if the patient is immunodeficient.ConclusionThe diagnosis of tinea corporis is usually clinical and should pose no problem to the physician provided the lesion is typical. However, many clinical variants of tinea corporis exist, rendering the diagnosis difficult especially with prior use of medications, such as calcineurin inhibitors or corticosteroids. As such, physicians must be familiar with this condition so that an accurate diagnosis can be made and appropriate treatment initiated.

Clinical significance of Candida isolation from dystrophic fingernails.

Candida onychomycosis mostly involves fingernails. Yet, in contrast to dermatophytes, Candida isolation from dystrophic fingernails does not prove casualty, as sample contamination and non-pathogenic Candida growth occur. Characterising treatment outcome of Candida-positive dystrophic nails is crucial to avoid unnecessary treatment. To investigate predicators associated with treatment outcome among Candida-positive dystrophic fingernails. A retrospective cohort study was carried out among 108 adults with Candida-positive dystrophic fingernails not cured with adequate systemic anti-fungal course. Diagnosis was based on a single mycological culture. Patients with treatment failure (n=85; 78.7% of the cases) were compared to patients with partial response (mild to almost cure; n=23; 21.3% of the cases) at 9 to 12months following treatment initiation. Treatment failure was significantly associated with primary onycholysis (odds ratio [OR] 2.8; 95% confidence interval [CI] 1.1-7.4) and prolonged dystrophy (12.8 vs. 3.7years in average), compared to partial treatment response. Non-responders had lower odds to present with distal lateral subungual onychomycosis, compared to partial responders (OR 0.3; 95% CI 0.1-0.7). Demographic and mycological characteristics, as well as number of nails affected, co-presence of paronychia, and treatment regime were not found to be associated with treatment response. Candida-positive primary onycholysis was shown to be non-responsive to systemic anti-fungal treatment, suggesting that anti-fungal treatment is not indicated. For other clinical scenarios, high proportions of treatment non-response suggest that determining causality of Candida should not be based on a single positive mycological culture.

Clinical profile of Tinea pseudoimbricata: an observational study from a tertiary care institution in western Maharashtra, India

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; Topical steroid-modified tinea corporis and tinea cruris is on the rise due to the ease of availability of over-the-counter potent topical corticosteroid preparations and their inappropriate use, alters the true morphology of lesion. As there is paucity of literature about increasing prevalence and varied presentation of this condition, we aimed to study the clinical profile and dermoscopic features of &lt;em&gt;Tinea pseudoimbricata&lt;/em&gt; due to topical steroid abuse. We present a case-series of 77 cases of a distinct morphological pattern with central erythematous, scaly, pruritic concentrically spreading plaques with raised and scaly borders known as &lt;em&gt;Tinea pseudoimbricata&lt;/em&gt;.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; We evaluated 77 clinically diagnosed patients of &lt;em&gt;Tinea pseudoimbricata&lt;/em&gt; with positive 10% potassium hydroxide examination and culture. Dermoscopy was performed in all patients. The demographic, clinical, and mycological features of each patient were recorded on a predesigned proforma.&lt;strong&gt;&lt;/strong&gt;&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; There were 52 male and 25 female patients with a mean age of 28.66 and a mean disease duration of 7.6 months. There was a history of application of potent or super-potent topical steroid for varying durations. Culture isolates were &lt;em&gt;Trichophyton rubrum&lt;/em&gt; species. Dermoscopic analysis showed features of steroid abuse.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; Injudicious and inappropriate use of topical steroid causes &lt;em&gt;Tinea pseudoimbricata&lt;/em&gt;; a special subset of tinea incognito, which is very common now a days. This should alert the dermatologist about the steroid abuse and requires systemic anti-fungal treatment for prolong time.&lt;/p&gt;

Tinea Capitis: An Updated Review.

Tinea capitis is a common and, at times, difficult to treat, fungal infection of the scalp. This article aimed to provide an update on the evaluation, diagnosis, and treatment of tinea capitis. A PubMed search was performed in Clinical Queries using the key term "tinea capitis". The search strategy included meta-analyses, randomized controlled trials, clinical trials, observational studies, and reviews. The search was restricted to English literature. The information retrieved from the above search was used in the compilation of the present article. Patents were searched using the key term "tinea capitis" at www.freepatentsonline.com. Tinea capitis is most often caused by Trichophyton tonsurans and Microsporum canis. The peak incidence is between 3 and 7 years of age. Non-inflammatory tinea capitis typically presents as fine scaling with single or multiple scaly patches of circular alopecia (grey patches); diffuse or patchy, fine, white, adherent scaling of the scalp resembling generalized dandruff with subtle hair loss; or single or multiple patches of well-demarcated area (s) of alopecia with fine-scale, studded with broken-off hairs at the scalp surface, resulting in the appearance of "black dots". Inflammatory variants of tinea capitis include kerion and favus. Dermoscopy is a highly sensitive tool for the diagnosis of tinea capitis. The diagnosis can be confirmed by direct microscopic examination with a potassium hydroxide wetmount preparation and fungal culture. It is desirable to have mycologic confirmation of tinea capitis before beginning a treatment regimen. Oral antifungal therapy (terbinafine, griseofulvin, itraconazole, and fluconazole) is considered the gold standard for tinea capitis. Recent patents related to the management of tinea capitis are also discussed. Tinea capitis requires systemic antifungal treatment. Although topical antifungal therapies have minimal adverse events, topical antifungal agents alone are not recommended for the treatment of tinea capitis because these agents do not penetrate the root of the hair follicles deep within the dermis. Topical antifungal therapy, however, can be used to reduce transmission of spores and can be used as adjuvant therapy to systemic antifungals. Combined therapy with topical and oral antifungals may increase the cure rate.

Unaccountable use of systemic antifungal treatment leads to change in guidelines and stewardship in a district general hospital

Background Antifungal resistance is a global emergency of increasing prevalence, yet only 11% of NHS Trusts have an antifungal stewardship programme. Given the high mortality and cost associated with invasive fungal infections, it is paramount to optimise investigations and judicious use of systemic antifungals. Hospital guidelines often focus on empirical treatment, omitting diagnostics. Methods Patients prescribed systemic antifungals were identified using pharmacy records over a 1 year period in a district general hospital in London. Electronic patient records were interrogated for microbiological, serological, histopathological and radiological investigations based on national recommendations. Audit standards were designed to meet the NHS England Medicines Optimisation and Stewardship CQUIN. Results 31 adult patients were identified. Microbiological evidence of fungal infection was demonstrated in 15/31 patients (48%). 60% were speciated and 47% underwent susceptibility testing. Three patients had beta-D-glucan tests; two patients had histopathological testing; 19 patients underwent imaging, of which 42% were reported as consistent with possible fungal infection. Conclusion 9 (29%) patients had no obvious indication for antifungal treatment. Systemic antifungal treatment is not without toxicity and cost and contributes to resistance. In view of this, we updated the hospital guideline to include a guide to diagnostics, incorporated antifungals into our antimicrobial stewardship ward round and submitted this audit to NHS England CQUIN. Further work will evaluate whether these changes impact upon current practice. References Micallef C et al. Med. Microbiol. 2017;66(11):1581-1589 Fisher MC et al. Science 2018;360(6390):739-742 Schelenz S et al. Lancet Infect Dis 2015;15(4):461–74

Eumycetoma caused by Alternaria alternata in an immunocompetent host: A rare case report

Mycetoma is a chronic granulomatous subcutaneous infection caused by either true fungi (eumycetoma) or filamentous anaerobic bacteria (actinomycetoma). Herein, we report a case of mycetoma foot due to a rare opportunistic fungus in a male farmer. He presented with swelling and sinuses discharging pus and bloodstained black granules on the right foot for 6 years. A final diagnosis of eumycetoma (caused by Alternaria alternata) with bone involvement in immunocompetent patient was confirmed on the basis of histopathology and culture. Opportunistic fungi most commonly cause infection in immunocompromised hosts. Although mycetoma caused by opportunistic and saprophytic fungi responds relatively well to systemic antifungal treatment, few cases such as ours might require amputation. Clinically, it is difficult to comprehend the exact etiological agent. Proper diagnosis and radiological investigation are necessary for the precise identification of the etiological agent and extent of spread which in turn dictate choice of treatment.

Dosing of Antimycotic Treatment in Sepsis–Induced Liver Dysfunction by Functional Liver Testing with LiMAx®

Background Sepsis-treatment is one of the major challenges in our time. Especially fungal infections play an important role in patient's morbidity and mortality. In patients with septic shock, liver function is often significantly impaired and therefore also hepatic drug metabolism is altered. Case Presentation We report about a 56-year-old man suffering from invasive fungal infection with multiorgan failure, after complicated medical history due to symptomatic infrarenal aortic aneurysm. On the first postoperative day, a CT scan was undertaken due to massive back pain showing renal infarction on both sides. As qualitative and quantitative renal function was impaired, hemodialysis was started immediately. Subsequently, the patient developed a compartment syndrome of the left leg and underwent fasciotomy. On admission day 7, the patient presented with hematochezia leading to colonoscopy. During this procedure, an ischemic colitis was observed. As conservative treatment failed, the patient underwent Hartmann's procedure due to progredient ischemia followed by a worsening of the clinical status due to sepsis. The patient suffered from an invasive fungal infection with Candida spp. and Aspergillus spp. Systemic antifungal treatment was initiated. Although azoles are considered first-line treatment in these cases we chose the echinocandin caspofungin for its presumed lower impact on liver function compared to azoles like voriconazole or Amphothericin B. However, caspofungin is also metabolised in the liver and can cause hepatotoxic effects. Therefore we measured metabolic liver function capacity using LiMAx®and adapted the patient's dose of caspofungin to the evaluated liver function capacity to achieve an effective and liver-protective level of the active drug. After complicated medical history with 15 weeks of hospital stay, the patient was discharged in general good condition. Conclusions To our knowledge, this is the first report that relates antimycotic drug dosing to a functional liver test. We provide a new approach for sepsis treatment considering liver function capacity to optimize dosage of hepatically metabolised drugs with potential hepatotoxic effects.

Immune Parameters for Diagnosis and Treatment Monitoring in Invasive Mold Infection.

Infections caused by invasive molds, including Aspergillus spp., can be difficult to diagnose and remain associated with high morbidity and mortality. Thus, early diagnosis and targeted systemic antifungal treatment remains the most important predictive factor for a successful outcome in immunocompromised individuals with invasive mold infections. Diagnosis remains difficult due to low sensitivities of diagnostic tests including culture and other mycological tests for mold pathogens, particularly in patients on mold-active antifungal prophylaxis. As a result, antifungal treatment is rarely targeted and reliable markers for treatment monitoring and outcome prediction are missing. Thus, there is a need for improved markers to diagnose invasive mold infections, monitor response to treatment, and assist in determining when antifungal therapy should be escalated, switched, or can be stopped. This review focuses on the role of immunologic markers and specifically cytokines in diagnosis and treatment monitoring of invasive mold infections.

Invasive Fungal Sinusitis: Risk Factors for Visual Acuity Outcomes and Mortality.

Invasive fungal sinusitis is a rare but potentially lethal disease that primarily affects immunocompromised patients. The purpose of this study was to review an academic medical center's experience in the presentation, diagnosis, and treatment of invasive fungal sinusitis. A retrospective chart review was performed at a single institution over a 17-year period. Medical records, radiographic imaging, and operative reports were analyzed. Bivariate and multivariable analyses were performed to determine factors that affected visual acuity outcomes and mortality. Fifty-five patients with histopathologically confirmed invasive fungal sinusitis were included. The average duration of follow up was 1.8 ± 2.6 years (range: 1 week to 10 years). The most common causes of immunosuppression were hematologic malignancy (45%), diabetes (31%), and organ transplantation (9%). At presentation, 35% of individuals were neutropenic (absolute neutrophil count < 500/μl). All patients received systemic antifungal treatment. A surgical intervention was performed on 50 patients (91%), and all but one had functional endoscopic sinus surgery. Nine (16%) patients underwent orbital exenteration. Multivariable analysis of visual acuity outcomes demonstrated that individuals infected with Zygomycota had 6-7 lines worse vision than those infected with Ascomycota (mean difference in logMAR 0.66, 95% confidence interval 0.27 to 1.06, p = 0.001). Patients who had functional endoscopic sinus surgery had 7-8 lines better visual acuity than those without functional endoscopic sinus surgery (mean difference in logMAR -0.76, 95% confidence interval -1.13 to -0.38, p < 0.001). The overall death rate due to infection was 24%. Bivariate models demonstrated no difference in mortality in patients receiving exenteration versus those who did not (p = 0.14). Multivariable analysis of mortality demonstrated that neutropenia increased mortality (adjusted odds ratio 10.05, 95% confidence interval 1.49 to 67.67, p = 0.02). Having a greater number of surgeries was associated with an increased rate of survival (adjusted odds ratio 0.39, 95% confidence interval 0.15 to 0.96, p = 0.04). Invasive fungal sinusitis is an aggressive disease with significant mortality. Patients with neutropenia had a lower rate of survival, and infection with Zygomycota was associated with worse visual acuity outcomes. Those having functional endoscopic sinus surgery had better final visual acuity, and an increased number of surgeries was associated with a decreased chance of death. Exenteration yielded no observed survival benefit.Endoscopic sinus debridement portends better visual acuity outcomes in patients with invasive fungal sinusitis, whereas exenteration yields no difference in survival benefit.

Risk factors and outcomes of patients with ocular involvement of candidemia.

BackgroundOcular involvement of candidemia can result in serious complications, including vision loss. This study investigated the risk factors for ocular involvement in patients with candidemia and the outcomes of treatment.MethodsEpisodes of candidemia in hospitalized adults who underwent ophthalmic examinations within 2 weeks of candidemia onset between January 2014 and May 2017 were retrospectively reviewed. Their demographic characteristics, antifungal treatments, and visual outcomes were evaluated.ResultsDuring the study period, 438 adults were diagnosed with candidemia, with 275 (62.8%) undergoing ophthalmic examinations within 2 weeks. Of these 275 patients, 59 (21.5%) had fundoscopic abnormalities suggestive of ocular involvement, including 51 with chorioretinitis and eight with Candida endophthalmitis. Eleven patients were symptomatic. Persistent candidemia (adjusted odd ratio [aOR], 2.55; 95% confidence interval [CI], 1.29–5.08; P = 0.01), neutropenia during the preceding 2 weeks (aOR, 2.92; 95% CI, 1.14–7.53; P = 0.03), and C. albicans infection (aOR, 2.15; 95% CI, 1.09–4.24; P = 0.03) were independently associated with ocular involvement. Among the 24 patients with neutropenia, 41.7% had ocular involvements at the initial examination. Ophthalmologic examination even before the neutrophil recovery was positive in one-third of neutropenic patients. Out of the 37 patients in whom ocular outcomes after 6 weeks were available, 35 patients showed favorable or stable fundoscopic findings. Two patients had decreased visual acuity despite the stable fundoscopic finding.ConclusionNeutropenia within two weeks of candidemia was a risk factor for ocular involvement. More than 80 percent of patients with ocular involvements were asymptomatic, emphasizing the importance of routine ophthalmic examinations. The median 6 weeks of systemic antifungal treatment resulted in favorable outcomes in 89.2% of patients.

Rhinosinusal mucormycosis: Literature review and some particular cases

Abstract Rhinosinusal mucormycosis is a life-threatening disease caused by fungus of the order Mucorales, which commonly affects individuals with diabetes and those in immunocompromised states. It is the most common form of mucormycosis with a high mortality rate (50-80%). Treatment options include reversal of the underlying risk factors when it is possible, systemic antifungal medication and radical surgical debridement. Prognosis is reserved because of the high potential of invasiveness, so diagnosis and early treatment are essential. Herein, we make a review about the most important features of this pathology and we report two cases of rhinosinusal mucormycosis with similar presentations who followed the same treatment protocol – extended surgical debridement of the necrotic tissue combined with systemic antifungal treatment (Amphotericin B). Complete recovery was achieved in one patient, whereas in the other one, due to late presentation, massive extension and incomplete surgical debridement, the disease was complicated with multiple organ dysfunction and cerebral stroke. By presenting these cases, we would like to point out the importance of early diagnosis, appropriate medical and surgical therapy to obtain a significant survival rate in patients with this fatal disease.