Specific Antifungal Therapy Research Articles

Surgical therapy and pathogen detection in endogenous endophthalmitis : Analysis of data from five German eye hospitals

Endogenous endophthalmitis results from hematogenous spread of bacterial or fungal infection in severely diseased patients. Specific systemic and intraocular therapy is required. The basis for this treatment is causal pathogen detection in blood culture or vitreous sample. However, functional results are limited. The current article provides practical hints for surgical therapy and pathogen detection in patients with endogenous endophthalmitis. Aretrospective analysis of anonymous data of 68male and female patients from 2018-2023 from five ophthalmology clinics in Germany was performed. Mean age of affected patients was 71.4years (31-96years). Surgical therapy included pars plana vitrectomy (ppV) and intravitreal injection (IVOM). In 44of 68patients (65%), 1-3 surgeries were performed, 4-6surgeries were required in 14/68 (21%) of patients, and 10or more surgeries were required in 4/68patients (6%). Pathogen detection was possible in 34% of vitreous specimens and in 11% of anterior chamber samples. Mean initial visual acuity was logMAR1.5. After treatment and amean follow-up of 2.5months, mean visual acuity was logMAR1.3. Preanalytical methods for specimen collection like the Freiburg endophthalmitis set to optimize pathogen detection are presented. Severe inflammatory intraocular reactions in endogenous endophthalmitis necessitate acombination of ppV and repeated IVOM. In addition to providing avitreous sample, ppV also serves to remove inflammatory fibrin membranes. Early pars plana vitrectomy with specific antibiotic or antifungal therapy should be sought in addition to the focus search and systemic therapy.

Мукормикоз у пациентов с COVID-19

Rhinocerebral mucormycosis is characterized by a severe course and is one of the late complications in patients who have undergone COVID-19. For the successful treatment of this disease, the earliest possible diagnosis and the appointment of specific conservative therapy in combination with surgical intervention are necessary. Objective. To study the risk factors for the development of invasive mycoses, the clinical manifestations of this pathology, and the results of its treatment in patients who underwent SARS-CoV-2. Research methods. Retrospective analysis of the case histories of 25 patients with mucormycosis. Demographic, subjective, and objective data (medical history, complaints, endoscopic examination), radiological techniques (CT scans), histological, microscopic and cultural studies as well as the results of medical and surgical treatment were analyzed. Result of the study. Groups of patients with comorbid pathology, potentially predisposed to the development of this disease, as well as groups of drugs, the use of which predisposes to the risk of developing mucormycosis, were identified. Conclusion. The predisposing background to the development of mucormycosis is hyperglycemic conditions and the use of high doses of corticosteroids and broad-spectrum antibiotics as part of the COVID-19 treatment protocol. According to epidemiological data, the largest number of cases of invasive rhinocerebral mucormycosis coincided with the highly virulent SARS-CoV-2 delta strain. Early initiation of specific antifungal therapy combined with surgery results in more effective treatment.

Antimicrobial peptide functionalized gold nanorods combining near-infrared photothermal therapy for effective wound healing

Photothermal therapy using laser activated gold nanorods (AuNRs) is a strategy for treatment of bacterial infections. Nevertheless, it also exerts cytotoxicity against human cells which leads to adverse effects in healthy human tissues and limits the applicable dose. Functionalization of AuNRs with a selective antimicrobial peptide (AMP) with higher selectivity for bacteria over human cells is a promising strategy for increasing the selectivity of the AuNRs for bacteria, hence increasing their cellular uptake by the bacteria in order to achieve stronger antimicrobial effects with lower doses of AuNRs without damaging the human cells. In this study, the surface of AuNRs was functionalized with a short AMP named C-At5 and the efficiency of the peptide functionalized AuNRs in killing gram-positive and gram-negative bacteria was evaluated in vitro as well as their potential for facilitating wound healing in a mouse model of wound infection with and without application of laser. The peptide-conjugated AuNRs exhibited higher antibacterial activity in vitro compared to the plain AuNRs both in the presence and absence of laser irradiation. Furthermore, AuNR@C-At5 had very low toxicity against human skin fibroblasts and human red blood cells indicating their higher biocompatibility compared to the plain AuNRs. Treatment of wounded mice with AuNR@C-At5 accelerated the wound healing process which was further enhanced by applying laser. The system developed in this study has great potential for customization for specific antimicrobial or antifungal therapy via conjugation of different types of AMPs with higher selectivity and can therefore serve as a guide for any future attempts in this regard.

S1.5a Epidemiology of myotic keratitis in developing countries

S1.5 Mycotic keratitis, September 21, 2022, 11:00 AM - 12:30 PM Mycotic keratitis (corneal infection due to a fungal etiology) is a well-recognized ophthalmological emergency warranting rapid initiation of specific antifungal therapy. However, the magnitude of the problem of mycotic keratitis in the community, especially in the Indian subcontinent and the developing world, is, perhaps, less apparent. A minimal annual incidence estimate of 1051, 787 cases (23.6/100 000 population [popln]) globally has recently been reported, with the highest rates being in Asia (33.9/100 000 popln, an absolute number of 939 895) and Africa (13.5/100 000; 75 196); if all culture-negative cases are assumed to be fungal, especially where the incidence of mycotic keratitis is known to be high, then the annual incidence would be about 1480 916 cases. A fungal etiology has been found to account for a very high proportion (> 45%) of microbial keratitis cases in countries in the Indian subcontinent. Countries where a fungal etiology accounts for >25% of microbial keratitis mostly tend to abut the equator. Interestingly, the proportion of microbial keratitis patients with a proven fungal etiology shows a significant negative correlation with the gross domestic product per capita. Although it is clear that the most common fungal species are Fusarium, Aspergillus, and Candida species, marked regional variations in fungal etiology have been noted. It is important to realize that sensitivity of the culture of ocular fungal pathogens can vary, depending on the pathogen, as well as the competence of the testing laboratory. For some countries, multiple reports over time have been noted, with there being some evidence of an increasing trend in the proportion of all microbial keratitis cases being diagnosed as mycotic keratitis. Even in a single geographical location, cases of mycotic keratitis may be higher than the yearly average at certain times of the year, such as during the harvest or windy seasons, or when there is increased relative humidity. A disturbing statistic to note is that, in 8%-11% of patients with mycotic keratitis, the affected eye needs to be removed, representing an irreversible annual loss of 84 143-115 697 eyes. It is recognized that many people suffering from mycotic keratitis in rural distant communities never present to health care workers due to financial and other constraints. Hence, the actual number of people afflicted by mycotic keratitis, man-days lost due to the disease and during therapy, and reduced quality of life due to persistent disability (corneal scarring) in the Indian subcontinent and developing countries requires further study.

Introducing biomarkers for invasive fungal disease in haemato-oncology patients: a single-centre experience.

ObjectivesBiomarkers for invasive fungal disease (IFD) have been shown to reduce antifungal prescriptions in neutropaenic haemato-oncology patients. Our study aimed to assess the real-life impacts of introducing a novel biomarker-based pathway, incorporating serum galactomannan and Aspergillus PCR, for pyrexial haemato-oncology admissions.MethodsPatients with neutropaenic fever were identified prospectively after introduction of the new pathway from 2013-2015. A historical group of neutropaenic patients who had blood cultures taken from 2009-2012 was generated for comparison. Clinical details including demographics, underlying diagnosis, investigations, radiology and antimicrobial treatment were obtained.ResultsProspective data from 308 patients was compared to retrospective data from 302 patients. The proportion of patients prescribed an antifungal medication was unchanged by the pathway (p=0.79), but the pattern was different with more patients receiving targeted antifungals (p=0.04). A negative serum galactomannan test was not sufficient evidence to withhold therapy with 17.2% of those episodes felt to have possible or probable IFD by EORTC/MSG criteria. There was no difference in 30-day mortality (p=0.21) or 1-year mortality (p=0.57) following introduction of the pathway.ConclusionsBiomarkers can be used safely as part of a multidisciplinary approach to the diagnosis of IFD in neutropaenic haemato-oncology patients. Whilst they do not necessarily result in antifungal therapy being withheld, they can allow more confident diagnosis of IFD and more specific antifungal therapy in selected cases.

Cerebral Cryptococcomas: A Systematic Scoping Review of Available Evidence to Facilitate Diagnosis and Treatment.

Background: Recommendations for managing patients with cerebral cryptococcomas are scarce across multiple clinical guidelines. Due to the deficiency of high-quality data coupled with an increasing number of at-risk patients, the purpose of this review is to describe the demographic characteristics, causative pathogen, intracranial imaging, surgical and/or pharmacological interventions, as well as outcomes of patients with cerebral cryptococcomas to improve recognition and management. Methods: We conducted a scoping review in accordance with the PRISMA guidelines using PubMed and Web of Science. Reports were included if the following details were presented: (1) site of infection; (2) treatment details which at least include the specific antifungal therapy administered, if applicable; and (3) patient outcome. Results: A total of 40 records representing 47 individual patients were included, of which the median age was 48.5 years, 75% were male, and 60% reported a significant past medical, surgical, or social history. C. neoformans was isolated more often than C. gattii (74% vs. 26%, respectively). Patients most often presented with headache, altered mental status and/or confusion, and vomiting occurring over a median of 30 days; though few were noted to have significant findings on physical examination. More than 50% of patients had a single cerebral cryptococcoma lesion, whereas perilesional edema was present in 73% of cases. Surgical intervention occurred in 49% of patients. An amphotericin B-based formulation was administered as “induction” therapy to 91% of patients, but combined with flucytosine or fluconazole in only 58%, for an overall median of 42 days. Fifty two percent of patients received “maintenance” therapy for a median of 126 days, in which fluconazole was most often used. Corticosteroids were administered to approximately 30% of patients for a median of 31.5 days. Overall, mortality was 34%. Conclusion: Based on our findings, management should include antifungal therapy for a minimum of 6 months with considerations for concomitant corticosteroids in the setting of perilesional edema, as well as surgical intervention. Emphasis should be placed on providing well-documented treatment details in future case reports and series to allow for the development of more concise evidence-based recommendations.

Clinical and microbiological features and outcomes of mucormycosis in critically ill patients

Mucormycosis is a rare invasive fungal infection with high mortality in patients with severe underlying predisposing factors causing immunosuppression. The exact incidence of mucormycosis and the optimal therapeutic approach is difficult to determine, especially in severe cases, due to the rarity of the disease. The new second-generation triazole isavuconazole provides an alternative treatment option which may represent a potential benefit in severe cases. A retrospective case series was conducted of patients with a positive laboratory culture for Mucorales and consistent clinical findings who required intensive care treatment. Patient characteristics including demographics, comorbidities, microbiological analysis, specific antifungal therapy and clinical outcome were analysed. Fifteen critically ill patients with Mucorales detected between 2016 and 2019 were included in this study; the crude mortality rate was 100%. At the time of diagnosis of mucormycosis, 80% of subjects had relevant medical immunosuppression and 53.3% of subjects had neutropenia. Manifestation of mucormycosis was pulmonary in 53.3% of subjects, rhino-orbital in 20% of subjects and disseminated in 26.7% of subjects. Notably, 40% of all patients had received antifungal prophylaxis prior to mucormycosis, mainly with posaconazole due to underlying haematological malignancy, thus possibly representing break-through infections. Antifungal therapy for invasive mucormycosis was administered in 80% of subjects for a median duration of 16 days. In this retrospective cohort analysis of intensive care patients, the prognosis of mucormycosis was extremely poor. An aggressive strategy for diagnosis and treatment is essential for intensive care patients with mucormycosis. There is a need for further research to determine if combination therapy in higher dosages or prompt surgery is beneficial in severe critically ill patients.

Rhodotoruliosis: An Emerginag Opportunistic Mycosis of Humans and Animals

Rhodotoruliosis is an opportunistic emerging mycotic disease that affects both humans and animals. The source of infection is exogenous; and disease can occur in sporadic as well as epidemic form. The disease is caused by Rhodotorula, basidiomycetous yeast that lives as a saprophyte in the environment. Rhodotorula glutinis, R. mucilaginosa (R.rubra), and R. minuta are the most frequently encountered species of Rhodotorula. The species can be isolated from a wide range of sources in nature, including the soil, air, ocean, plants, dairy products, and the household environment. Fungemia, meningitis, ventriculitis, peritonitis, endocarditis, keratitis, endophtalmitis, hydrosalpinx, oral ulcer and lymphadenitis have all been linked to the fungus in humans. It causes skin infections in chicken, sea lion, and cat, lung infection in sheep, epididymitis in dog, and mastitis in cow and buffalo. The organism is an opportunist, taking advantage of immunosuppressive circumstances, indwelling devices, and antibiotic exposure. In order to confirm the diagnosis of rhodotoruliosis, laboratory assistance is required. The direct demonstration of Rhodotorula in the clinical specimens and its isolation in pure and luxuriant growth still considered the gold standard of diagnosis. Amphotericin B or one of its lipid formulations appears to be the medication of choice for treating the patient. The infection due to Rhodotorula especially in immunosuppressed individuals can be life threatening if the treatment is delayed. Prognosis of systemic disease in compromised subject may be grave. Early diagnosis is essential to start specific antifungal therapy of rhodotorulosiosis to prevent serious complications.

Pulmonary infection due to Acrophialophora fusispora in a patient with underlying mixed connective tissue disease and chronic pulmonary aspergillosis

BACKGROUND Acrophialophora fusispora is an emerging opportunistic fungus rarely implicated in human infections. Here, we report the first case of pulmonary infection due to A. fusispora from India. CASE DESCRIPTION A 59-year-old male, farmer by occupation was admitted to AIIMS, Jodhpur, Rajasthan, India, with complaints of cough and expectoration of yellowish sputum for last one month and gradually progressive shortness of breath for 20 days. He had past history of pulmonary tuberculosis and was a known case of COPD for last five years. He was diagnosed with mixed connective tissue disease (MCTD) for which he had been receiving treatment with azathioprine and prednisolone for 3 months. CECT of chest revealed cystic bronchiectatic changes with findings suggestive of aspergilloma. Serum Aspergillus fumigatus specific IgG levels were elevated suggestive of chronic pulmonary aspergillosis (CPA). He was tested positive for influenza A (H1N1) by RT-PCR and received treatment with oral oseltamivir but to no clinical benefit. Culture of sputum on two subsequent occasions showed growth of a fungus which was identified as Acrophialophora fusispora based on characteristic microscopic morphology and rDNA ITS sequencing. Treatment with oral itraconazole showed marked symptomatic improvement. He was discharged from the hospital with oral itraconazole to be continued for 6 months. Follow-up visit after 3 months showed significant clinical and radiological improvement. CONCLUSION Molecular sequencing can reliably identify A. fusispora which is crucial for initiating specific antifungal therapy. Further studies are encouraged to determine the prevalence of such infections so as to plan optimal management and improve patient outcomes.

Yeast Infections after Esophagectomy: A Retrospective Analysis

Esophageal malignancy is a disease with poor prognosis. Curative therapy incorporates surgery and is burdensome with high rates of infection morbidity and mortality. The role of yeast as causative organisms of post-esophagectomy infections is poorly defined. Consequently, the benefits of specific antifungal prophylactic therapy in improving patient outcome are unclear. Therefore, this study aimed at investigating the incidence of yeast infections at the University Medical Center Groningen among 565 post-esophagectomy patients between 1991 and 2017. The results show that 7.3% of the patients developed a yeast infection after esophageal resection with significantly increased incidence among patients suffering from diabetes mellitus. For patients with yeast infections, higher Acute Physiology and Chronic Health Evaluation (APACHE) II scores, more frequent intensive care unit readmissions, prolonged hospital stays and higher mortality rates were observed. One-year survival was significantly lower for patients with a yeast infection, as well as diabetes mellitus and yeast-positive pleural effusion. We conclude that the incidence of yeast infections following esophagectomy is considerable, and that patients with diabetes mellitus are at increased risk. Furthermore, yeast infections are associated with higher complication rates and mortality. These observations encourage further prospective investigations on the possible benefits of antifungal prophylactic therapy for esophagectomy patients.

SUN-338 SUBCUTANEOUS PHAEOHYPHOMYCOSIS IN A RENAL TRANSPLANT RECIPIENT

Subcutaneous Phaeohyphomycosis caused by dematiaceous fungi has rarely been described in a renal transplant recipient. 30 year-old male, deceased renal transplant recipient done in January 2018, Induction with ATG and on triple immunosuppression with normal graft function. November 2018 - Presented with a progressively enlarging swelling of 6.0x3.5cms over the anterior aspect of the left thigh following trauma. I&D done, initiated on IV antibiotics. KOH Stain showed fungal elements(Fig 1A), pus sent for fungal culture and treated with Fluconazole. December 2018:Presented with recurrence of swelling. USG revealed a collection measuring 6.6X3.5cms with loculations. Repeat I&D and punch Biopsy was done. Punch biopsy-Revealed inflammatory cystic lesion lined by palisades of histiocytes along with lymphocytes, plasmacells, neutrophils and giant cells along with fungal hyphae.(Fig 1B, PAS stain) Fungal stain–Darkly pigmented septal hyphal forms consistent with Phaeohyphomycosis. Fungal culture-Phaeohyphomycosis Treated with T.Voriconazole 200 mg BID for 14 days followed by T.Itraconazole 200 mg BID. The lesion healed completely within 2 weeks. January2019: Recurrence of the swelling.USG-subcutaneous abscess measuring 11.5X6cms with loculations. Enbloc Excision was done. Histopathology -Suppurative granulomatous inflammation. Pus swab for fungal culture–Darkly pigmented Septate non-sporulating hyphae s/o Phaeohyphomycosis. Patient was restarted on Tab.Voriconazole, modified the doses of immunosuppressive agents. After one month autologous skin grafting was done. Patient improved and discharged with normal renal function. May 2019 - Patient developed a new swelling in upper part of left thigh proximal to previous swelling, USG showed collection with multiple areas of air foci in subcutaneous plane. Wide local excision was done. Histopathology : Fungal hyphae s/o Phaeohyphomycosis with vascular invasion. Patient restarted on T.Voriconazole again and modified the dose of immunosuppressive agents. Patient have normal graft function and planned for skin grafting of the raw area but deferred in view of repeated culture positive with K.Pneumonia and Acinetobacter. In our case, despite specific antifungal therapy and least immunosuppressive medication, there was persistence of fungal infection with further proximal spread requiring surgical intervention. Sreejith et al, from JIPMER, India reported a series of seven cases of Subcutaneous Phaeohyphomycosis in a Renal Transplant Recipients.1In this series no patient responded to long term Itraconazole treatment, and ultimately requiring surgical excision Surgical management by wide local excision along with Antifungal treatment appears to be a better mode of treatment for Subcutaneous phaeohyphomycosis.

Pulmonary infection due to Acrophialophora fusispora in a patient with underlying mixed connective tissue disease and chronic pulmonary aspergillosis

BACKGROUND Acrophialophora fusispora is an emerging opportunistic fungus rarely implicated in human infections. Here, we report the first case of pulmonary infection due to A. fusispora from India. CASE DESCRIPTION A 59-year-old male, farmer by occupation was admitted to AIIMS, Jodhpur, Rajasthan, India, with complaints of cough and expectoration of yellowish sputum for last one month and gradually progressive shortness of breath for 20 days. He had past history of pulmonary tuberculosis and was a known case of COPD for last five years. He was diagnosed with mixed connective tissue disease (MCTD) for which he had been receiving treatment with azathioprine and prednisolone for 3 months. CECT of chest revealed cystic bronchiectatic changes with findings suggestive of aspergilloma. Serum Aspergillus fumigatus specific IgG levels were elevated suggestive of chronic pulmonary aspergillosis (CPA). He was tested positive for influenza A (H1N1) by RT-PCR and received treatment with oral oseltamivir but to no clinical benefit. Culture of sputum on two subsequent occasions showed growth of a fungus which was identified as Acrophialophora fusispora based on characteristic microscopic morphology and rDNA ITS sequencing. Treatment with oral itraconazole showed marked symptomatic improvement. He was discharged from the hospital with oral itraconazole to be continued for 6 months. Follow-up visit after 3 months showed significant clinical and radiological improvement. CONCLUSION Molecular sequencing can reliably identify A. fusispora which is crucial for initiating specific antifungal therapy. Further studies are encouraged to determine the prevalence of such infections so as to plan optimal management and improve patient outcomes.

Isolated bilateral renal mucormycosis in apparently immunocompetent patients-a case series from India and review of the literature.

ABSTRACTBackgroundIsolated renal mucormycosis (IRM) is a potentially fatal disease affecting immunocompromised hosts. IRM affecting apparently immunocompetent patients is rare, with few previous reports, mostly from India. We describe 10 cases of bilateral IRM with no underlying risk factors.MethodsWe performed a retrospective analysis of cases of IRM from our hospital information system admitted between 2009 and 2016. We analyzed the data of this cohort of IRM, including epidemiological characteristics, clinical presentation, diagnostic procedures, treatment details and outcome.ResultsIn all, 10 cases of bilateral IRM were identified. All of them were males with a mean age of 24.7 years (range 10–42). Most patients were initially managed as acute bacterial pyelonephritis with acute kidney injury. A total of eight patients were diagnosed antemortem. Diagnostic clues include sepsis not controlled with broad-spectrum antibiotics and enlarged kidneys with or without hypodensities on ultrasound/computed tomography imaging. Three patients also gave a specific history of passing white flakes in their urine. Eight patients received specific antifungal therapy with amphotericin B with or without posaconazole. Three patients in whom the disease was apparently confined to the pelvicalyceal system underwent local irrigation with Amp-B. One patient underwent bilateral nephrectomy. Four patients succumbed to the disease while five patients were successfully treated. One patient was discharged against medical advice.ConclusionsIRM is a rare, life-threatening disease associated with high mortality even in immunocompetent individuals. Typical clinical and radiological findings and a high index of suspicion may help in early diagnosis, but definitive diagnosis requires histopathological and/or microbiological confirmation. Early and rapid diagnosis along with aggressive multidisciplinary management including initiation of specific antifungal therapy with or without surgical debridement is vital for a successful outcome.

Можливості хірургічного лікування аспергільозу легень

Мета. Поділитися власним досвідом хірургічного лікування аспергільозу легень.
 Матеріали і методи. За останні 10 років у клініці перебували 14 хворих з аспергільозом легень. У 11 (78,6%) хворих діагностовано аспергілому легені, у 3 (21,4%) - інвазивний аспергільоз після проведення біопсії легені. Резекційні втручання виконані 8 (57,1%) пацієнтам з аспергіломою. Відмовлено в операції внаслідок значних дихальних розладів 3 (21,4%) хворим. Середній вік пацієнтів - (42,6 ± 15,7) року. Всі пацієнти до і після оперативного втручання отримували специфічну протигрибкову терапію.
 Результати. Виконано такі оперативні втручання: 3 (37,5%) плевропульмонектомії, 4 (50,0%) лобектомії, 1 (12,5%) типову резекцію піраміди та S3 справа. У 1 (12,5%) пацієнтки під час оперативного втручання виконано інтраплевральну торакопластику. Середня тривалість операції склала (235,6 ± 77,6) хв, середня інтраопераційна крововтрата - (314 ± 331,9) мл.
 Висновки. Хірургічне лікування аспергільозу легень є досить складним завданням і має багато невирішених питань. Систематизація власного досвіду та досвіду, про який повідомляють інші дослідники, дає змогу покращити результати лікування.

Fungal and Parasitic CNS Infections.

Central nervous system fungal infections can be broadly divided into those that infect a healthy host such as Cryptococcus, Coccidioides, Histoplasma, Blastomyces, Sporothrix spp., and those that cause opportunistic infections in an immunocompromised host such as Candida, Aspergillus, Zygomycetes, Trichosporon spp. The clinical manifestations of central nervous system fungal infections commonly seen in children in clinical practice include a chronic meningitis or meningoencephalitis syndrome, brain abscess, rhino-cerebral syndrome and rarely, a fungal ventriculitis. Fungal central nervous system infections should be suspected in any child with subacute to chronic febrile encephalopathy or meningitis with or without raised intracranial pressure, seizures, orbital pain and/or sero-sanguinous nasal discharge. Diagnosis is corroborated by cerebrospinal fluid analysis, culture and PCR, special stains, serological tests and neuroimaging. Management of fungal central nervous system infections include specific antifungal therapy and supportive measures for associated problems, management of underlying predisposing condition and surgical intervention in cases with localized disease, abscess or presence of simultaneous foreign body such as intracranial shunts. In addition to the fungi, several parasitic infections can cause central nervous system infections in children. Of these, authors briefly discuss cerebral malaria, and amebic meningo-encephalitis.

Allergic bronchopulmonary aspergillosis in patients with asthma: Results of a prospective study

To estimate the frequency of fungal sensitization and the incidence of allergic bronchopulmonary aspergillosis (ABPA) in asthmatic patients. A total of 140 asthmatic patients were examined. They underwent allergologic (skin tests for fungal allergens, estimation of total and fungal allergen-specific IgE levels) and mycological (microscopy and inoculation of respiratory biosubstrates) examinations. Chest computed tomography, when indicated, was done. A group of patients with ABPA and that of patients with severe asthma and fungal sensitization were identified. The frequency of fungal sensitization in asthmatic patients was 36%; the main allergenic fungi were Aspergillus and Alternaria. The incidence of ABPA was as high as 4% in the patients with asthma and 11% in those with severe asthma and fungal sensitization. The given current diagnostic criteria will assist practitioners to identify ABPA, to prevent its progression, and to initiate specific anti-inflammatory and antifungal therapy in due time.

Basic principles unveil an unusual diagnosis

Answer: C-Candida Meningitis. Severe hypoglycorrhachia occurs in the setting of subarachnoid hemorrhage, glucose transport defects, infectious meningitis, meningeal carcinomatosis, inflammatory, and autoimmune conditions. Candida’s morphology (small unicellular yeast) allows its spread through the blood–brain barrier into the subarachnoid space and meninges, unlike dimorphic and hyphae organisms. It may present with cerebral micro or macro-abscesses, meningitis, and vascular complications. Our patient’s MRI pattern of nodular pachymeningeal (gray arrow), and leptomeningeal (white arrow) enhancement, along with micro-abscesses (black arrow); and hypoglycorrhachia, and history of active intravenous heroin use suggested a yeast fungal infection [[1]Mathur M. Johnson C.E. Sze G. Fungal infections of the central nervous system.Neuroimag Clin North America. 2012; 22: 609-632Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar]. Specific antifungal therapy was added to the empirical antibiotic coverage initiated in the emergency room, with rapid clinical improvement. Subsequently, CSF smear identified Candida Albicans 12 h after admission. CSF cultures confirmed the diagnosis. An expedient identification of fungal central nervous system infections is critical to minimize their progression and control life-threatening complications (i.e. seizure, stroke, and hydrocephalus) [[2]Sanchez-Portocarrero J. Perez-Cecilia E. Corral O. et al.The central nervous system and infection by Candida species.Diagn Microbiol Infect Dis. 2000; 37: 169-179Abstract Full Text Full Text PDF PubMed Scopus (146) Google Scholar] (Fig. 1). No financial disclosure to report. Basic principles unveil an unusual diagnosisJournal of Clinical NeuroscienceVol. 42PreviewA 59 year-old man with medical history significant for current intravenous heroin abuse presented with status epilepticus. Cerebrospinal fluid (CSF) showed 317 neutrophils, 45 red blood cells, lactate 6.7 mm/L, protein 140 md/dl, and glucose 24 mg/dl. Glucose CSF/serum ratio was 0.14. Opening pressure was 23 cm of water. Cytology studies and HIV were negative. MRI was performed, illustrated in the figure. What is the most likely diagnosis? Full-Text PDF

Pulmonary Cryptococcosis in the Immunocompetent Patient-Many Questions, Some Answers.

Background. There are no prospective data regarding the management of pulmonary cryptococcosis in the immunocompetent patient. Clinical guidelines recommend oral fluconazole for patients with mild to moderate symptoms and amphotericin B plus flucytosine followed by fluconazole for severe disease. It is unclear whether patients who have histological evidence of Cryptococcus neoformans but negative cultures will even respond to drug treatment. We evaluated and managed a patient whose presentation and course raised important questions regarding the significance of negative cultures, antifungal choices, duration of therapy, and resolution of clinical, serologic, and radiographic findings.Methods. In addition to our experience, to answer these questions we reviewed available case reports and case series regarding immunocompetent patients with pulmonary cryptococcosis for the last 55 years using the following definitions: Definite - Clinical and/or radiographic findings of pulmonary infection and respiratory tract isolation of C. neoformans without other suspected etiologies; Probable - Clinical and radiographic findings of pulmonary infection, histopathologic evidence of C. neoformans, and negative fungal cultures with or without a positive cryptococcal polysaccharide antigen.Results. Pulmonary cryptococcosis resolves in most patients with or without specific antifungal therapy. Clinical, radiographic, and serologic resolution is slow and may take years.Conclusions. Persistently positive antigen titers are most common in untreated patients and may remain strongly positive despite complete or partial resolution of disease. Respiratory fungal cultures are often negative and may indicate nonviable organisms.

Candida infective endocarditis: an observational cohort study with a focus on therapy.

Candida infective endocarditis is a rare disease with a high mortality rate. Our understanding of this infection is derived from case series, case reports, and small prospective cohorts. The purpose of this study was to evaluate the clinical features and use of different antifungal treatment regimens for Candida infective endocarditis. This prospective cohort study was based on 70 cases of Candida infective endocarditis from the International Collaboration on Endocarditis (ICE)-Prospective Cohort Study and ICE-Plus databases collected between 2000 and 2010. The majority of infections were acquired nosocomially (67%). Congestive heart failure (24%), prosthetic heart valve (46%), and previous infective endocarditis (26%) were common comorbidities. Overall mortality was high, with 36% mortality in the hospital and 59% at 1 year. On univariate analysis, older age, heart failure at baseline, persistent candidemia, nosocomial acquisition, heart failure as a complication, and intracardiac abscess were associated with higher mortality. Mortality was not affected by use of surgical therapy or choice of antifungal agent. A subgroup analysis was performed on 33 patients for whom specific antifungal therapy information was available. In this subgroup, 11 patients received amphotericin B-based therapy and 14 received echinocandin-based therapy. Despite a higher percentage of older patients and nosocomial infection in the echinocandin group, mortality rates were similar between the two groups. In conclusion, Candida infective endocarditis is associated with a high mortality rate that was not impacted by choice of antifungal therapy or by adjunctive surgical intervention. Additionally, echinocandin therapy was as effective as amphotericin B-based therapy in the small subgroup analysis.

Comparison of mycotic keratitis with nonmycotic keratitis: an epidemiological study.

Purpose. This work aims to study the problems encountered with and the different epidemiological features of patients with fungal keratitis. Patients and Methods. All cases with keratitis attending the Outpatient Clinic of Ophthalmology Department at Tanta University Hospital during three years from the first of January 2011 to the end of December 2013 were selected and carefully examined and cases with mycotic keratitis were further examined and investigated. Results. From 66303 attendants during this period with different complaints, there were 361 cases (0.54%) with mycotic keratitis and 473 cases (0.71%) of nonmycotic origin. Mycotic keratitis is common between 40 and 60 years, more in farmers (64%), families with large number and large crowding index, rural than urban residence, and patients with outdoor water sources and insanitary sewage disposal. Positive fungal cultures were obtained in 84.5% and were negative in 15.5% of cases in spite of their typical clinical findings for diagnosis and their improvement with antifungal therapy. Conclusion. Mycotic keratitis is more frequent in farmers, rural areas, outdoor water supply, insanitary sewage disposal, and patients preceded with organic trauma. Atypical clinical findings were found in some cases and not all cases improved with specific antifungal therapy.