Cryptococcal meningitis in an immunocompetent patient.

Cryptococcal meningitis is a fungal infection that is most commonly thought of as an opportunistic infection affecting immunocompromised patients, classically patients with Human Immunodeficiency (HIV) infection. It is associated with a variety of complications including disseminated disease as well as neurologic complications including intracranial hypertension, cerebral infarcts, vision loss and other neurologic deficits. It is diagnosed by lumbar puncture with CSF studies, including fungal culture and cryptococcal antigen testing. We present a case of cryptococcal meningitis and fungemia in a previously healthy male patient who presented after multiple emergency department visits with persistent headache. After multiple visits, he underwent a lumbar puncture consistent with cryptococcal infection, and he was admitted to the hospital for initiation of antifungal therapy. His workup revealed no known underlying condition leading to immune compromise.

Secondary free-flap reconstruction following ablation for acute invasive fungal sinusitis.

OBJECTIVE: Acute invasive fungal sinusitis (AIFS) is a frequently fatal infection for which extensive and debilitating surgical debridement is a mainstay of therapy. Resulting defects are often composite in nature, mandating free tissue-transfer reconstruction. Outcomes data for free flap reconstruction are limited. The purpose of this study was to examine surgical outcomes and survival in patients undergoing free flap transfer following invasive fungal sinusitis. STUDY DESIGN: Retrospective case series. METHODS: Between 1995 and 2015, patients undergoing operative debridement for AIFS were identified. Surgical records were used to identify survivors of acute infection who subsequently underwent free flap reconstructive surgery. Patient demographics, cause of immune compromise, defect description, flap type, perioperative complications, indications for revision surgery, functional outcomes, and long-term survival were reviewed. RESULTS: Forty-four patients were treated for AIFS, of those, 30 (68%) survived acute infection. Ten patients underwent maxillectomy, six with orbital exenteration, and were designated candidates for reconstruction. Eight patients underwent reconstruction. Median time from debridement to reconstruction was 67.5 days. Flap types included latissimus dorsi, scapula, anterolateral thigh, rectus, radial forearm, and fibula. Median follow-up was 7.7 months. No perioperative complications were encountered, and all subjects remained disease-free, able to speak and eat normally without prosthetic supplementation. Seven patients (87%) are currently alive. CONCLUSION: Reconstruction of defects left by invasive fungal sinusitis using free-tissue transfer resulted in successful flap survival, with no disease recurrence for all defects and flap types reviewed. Survivors of AIFS are able to tolerate midface reconstruction, with favorable functional outcomes and survival rates. LEVEL OF EVIDENCE: 4. Laryngoscope, 127:815-819, 2017.

Epidemiology of invasive aspergillosis and risk factors in non neutropaenic patients.

INTRODUCTION: Invasive aspergillosis is a major cause of mortality in allogeneic bone marrow transplant recipients and patients treated for blood malignancies. The diagnostic tools, treatments and preventive strategies, essentially developed for neutropaenic patients, have not been assessed in populations whose immune systems are considered to be competent. STATE OF THE ART: Beside the standard picture of chronic Aspergillus infection, the incidence of invasive aspergillosis is increasing in non neutropaenic patients, such as those with chronic lung diseases or systemic disease treated with long-term immunosuppressive drugs and solid organ transplant recipients. This study reviews the specific features of invasive aspergillosis in non neutropaenic subjects (NNS) and discusses the value of the diagnostic tools and treatment in this population. PROSPECTS: A better understanding of the pathophysiology and the epidemiological characteristics of invasive aspergillosis would provide a means of adapting the staging and classification of the disease for NNS. CONCLUSIONS: Invasive aspergillosis is under diagnosed in NNS who may already be colonised when they receive immunosuppressive treatment; this can lead to an adverse outcome in patients who are considered to be a moderate risk population.

Invasive candidiasis in long-term patients at a multidisciplinary intensive care unit: Candida colonization index, risk factors, treatment and outcome.

The incidence of fungal infections in hospitalized patients has increased, and due to demographic changes and increasingly advanced medical methods, the intensive care units (ICU) have emerged as epicentres for fungal infections. The aim of the present study was to investigate Candida colonization pattern and colonization index (CI), in combination with other risk factors and its relation to invasive candida infection (ICI), in 59 consecutive patients with at least 7 d length of stay (LOS) at a multidisciplinary ICU. Surveillance samples were collected on d 7 and then weekly during the ICU stay. In addition, immunological status was monitored by measuring the histocompatibility leukocyte antigen-DR (HLA-DR). In the present study with a patient population burdened by several risk factors for ICI, 17% acquired an invasive infection. Overall ICU mortality was 30%. We could demonstrate that both a high colonization index and recent extensive gastroabdominal surgery were significantly correlated with ICI, while a decreased level of HLA-DR (< or = 70%) was not predictive for ICI in this high-risk population. The results indicate that ICU patients exposed to extensive gastroabdominal surgery would benefit from early antifungal prophylaxis.

Candidemia in immunocompromised and immunocompetent critically ill patients: a prospective comparative study.

The purpose of this study was to compare the risk factors, clinical manifestations, and outcome of candidemia in immunocompromised (IC) and nonimmunocompromised (NIC) critically ill patients. Data were collected prospectively over a 2-year period (02/2000-01/2002) from patients in a 25-bed, medical-surgical intensive care unit (ICU). Eligible for participation in this study were patients who developed candidemia during their ICU stay. Patients under antifungal therapy and with a confirmed systemic fungal infection prior to the diagnosis of candidemia were excluded. Cultures of blood, urine, and stool were performed for all patients in the study, and all patients underwent endoscopy/biopsy of the esophagus for detection of Candida. Smears and/or scrapings of oropharyngeal and esophageal lesions were examined for hyphae and/or pseudohyphae and were also cultured for yeasts. During the study period, 1,627 patients were hospitalized in the ICU, 57% for primary medical reasons and 43% for surgical reasons. After application of the study's inclusion and exclusion criteria, 24 patients with candidemia (9 IC and 15 NIC) were analyzed. Total parenteral nutrition was more common in IC than in NIC patients (9/9 [100%] vs 8/15 [53%], p = 0.02). Oropharyngeal candidiasis was detected in 5 of 9 (55.5%) IC patients and in 1 of 15 (6.5%) NIC patients (p = 0.015). Esophageal candidiasis was also more common in IC than in NIC patients (4/9 [44%] vs 0/15 [0%], p = 0.012). Among the 9 IC patients, all except 2 died, resulting in a crude mortality of 78%; among the 15 NIC patients, 9 died, resulting in a crude mortality of 60% (p > 0.05). Autopsy was performed in two IC and in six NIC patients, with disseminated candidiasis found in one IC patient. Oropharyngeal and esophageal candidiasis are frequent in IC patients with candidemia. In contrast, this coexistence is rare in NIC critically ill patients with Candida bloodstream infections. A high mortality was noted in both IC and NIC critically ill patients with candidemia.

Candidemia due to Candida tropicalis: clinical, epidemiologic, and microbiologic characteristics of 188 episodes occurring in tertiary care hospitals.

Candida tropicalis is the 2nd most frequent agent of candidemia in Brazil (20-24%). We attempted to characterize the epidemiology, microbiology, and outcome of candidemia due to C. tropicalis by comparing patients with candidemia due to C. tropicalis with those with candidemia due to Candida albicans. Among the 924 episodes of candidemia, 188 (20%) were caused by C. tropicalis. These cases were compared with 384 candidemias due to C. albicans. C. tropicalis was the 2nd most frequent species in adults (21.6%) and elderly patients (23.2%), and 3rd in neonates (11.9%) and children (18.5%). Cancer was the most frequent underlying disease, and in adults and elderly patients, diabetes was the 2nd most frequent underlying disease. The only difference between C. tropicalis and C. albicans candidemia was a higher proportion of neutropenic patients in C. tropicalis candidemia. C. tropicalis is a leading cause of candidemia in Brazil, and its epidemiology is similar to that of C. albicans.

Invasive aspergillosis following hematopoietic cell transplantation: outcomes and prognostic factors associated with mortality.

BACKGROUND: Invasive aspergillosis (IA) is a leading cause of infection-related mortality following hematopoietic cell transplantation (HCT). The aim of this study was to determine the probability of survival and prognostic factors associated with outcomes over a long period of time. METHODS: Cases of proven and probable IA diagnosed in HCT recipients at the Fred Hutchinson Cancer Research Center from 1 January 1990 through 31 December 2004 were included. Patient data were collected from a prospectively maintained database and by retrospective clinical chart review. Survival was estimated using Kaplan-Meier curves, and Cox regression models were used for multivariable analyses. RESULTS: Four hundred five cases were identified. The probability of survival at 90 days after diagnosis was higher for patients identified as having IA between 2002 and 2004 than for patients whose IA was diagnosed in preceding years (45% vs. 22%; P<.001). Risk factors independently associated with all-cause mortality include impairment in pulmonary function before HCT, receipt of human leukocyte antigen-mismatched stem cells, neutropenia, elevated bilirubin and creatinine levels, receipt of corticosteroids at > or =2 mg/kg per day, disseminated and proven IA, and IA occurring >40 days after HCT. Factors associated with a decreased risk of all-cause mortality included receipt of nonmyeloablative conditioning and peripheral blood stem cells. In a subanalysis of attributable mortality restricted to patients receiving antifungal therapy, receipt of voriconazole was independently associated with protection from IA-related death. CONCLUSIONS: There has been a significant decrease in mortality in patients with a diagnosis of IA following HCT in recent years, coinciding with multiple changes in transplantation practices, including use of nonmyeloablative conditioning regimens, receipt of peripheral blood stem cells, more prompt diagnosis of IA, and use of voriconazole.

A 9-year study comparing risk factors and the outcome of paediatric and adults with nosocomial candidaemia.

Although there are numerous studies of candidaemia in adults, data on paediatrics are still limited. The aim of this study was to compare risk factors, aetiology, therapy, and the outcome of nosocomial candidaemia among paediatric and adult patients in a large Brazilian tertiary hospital (1995-2003). During this period, 78 paediatrics and 113 adults were studied. Species other than Candida albicans caused 78.2% of episodes of candidaemia in paediatrics. Compared to adults, paediatrics received more frequently broad-spectrum antibiotics, vasopressors, blood transfusions, arterial catheter, chest tube, cardiothoracic surgery, mechanical ventilation, and parenteral nutrition. Candidaemia caused by Candida parapsilosis was more common in paediatrics, as was the isolation of Candida spp. from catheters. Amphotericin B treatment was more common in paediatrics. Mortality rate was higher in adults than in paediatrics with nosocomial candidaemia. We reinforce the necessity of continuous epidemiologic surveillance to follow the dynamics of candidaemia.

Differences in clinical and laboratory diagnostic characteristics of penicilliosis marneffei in human immunodeficiency virus (HIV)- and non-HIV-infected patients.

We compared the clinical and laboratory features of human immunodeficiency virus (HIV)- and non-HIV-infected patients with penicilliosis marneffei. HIV-infected patients had a higher incidence of fungemia. A total of 85.7% of the HIV-negative patients had underlying diseases including hematologic malignancies or had received therapy with corticosteroids or cytotoxic agents. By a Penicillium marneffei-specific mannoprotein Mp1p enzyme-linked immunosorbent assay, serum antigen titers were found to be higher in HIV-positive patients, whereas serum antibody levels were found to be higher in HIV-negative patients.

Improving efficacy of antifungal therapy by polymerase chain reaction-based strategy among febrile patients with neutropenia and cancer.

Early detection of fungal infections in and corresponding early treatment of febrile patients with neutropenia and cancer have been important issues and continue to be major challenges for clinicians. The use of nested PCR to make therapeutic decisions was studied. Sequential blood samples obtained from 42 patients with neutropenia and cancer were tested by nested PCR and culture. Instead of the empirical antifungal therapy strategy, amphotericin B treatment was initiated only for patients who had 2 consecutive positive results by nested PCR. A reduced mortality rate was observed for febrile patients with neutropenia and cancer who had fungal infections. Thus, this strategy, combined with the nested PCR for early detection of fungal infection in febrile patients with neutropenia, may be used as a guideline for antifungal therapy.

Experimental model of progressive disseminated trichosporonosis in mice with latent trichosporonemia.

Trichosporon asahii and Trichosporon mucoides are the most common strains of fungi that cause disseminated trichosporonosis, a severe opportunistic infection in immunocompromised hosts. We have previously established a nested PCR assay using serum samples for detection of both strains. Here we describe a new experimental animal model for investigating the underlying mechanisms of disseminated trichosporonosis. T. asahii (OMU239, a clinical isolate from a patient with acute myelogenous leukemia) and 8-week-old ICR male mice were used in all experiments. A suspension of T. asahii (3 x 10(6) CFU/animal) was injected into the caudal vein of each mouse after immunosuppression with cyclophosphamide (200 mg/kg of body weight/day for 2 days) and prednisolone (30 mg/kg/day for 1 day). Mice were then divided into four subgroups (R0, R1, R2, and R3) based on the time of reimmunosuppression. The latter was performed using the same drugs 1 week (group R1), 2 weeks (group R2), and 3 weeks (group R3) after fungal infection. Reimmunosuppression was not performed in group R0. The 5-week-survival rates of mice after T. asahii infection were 0% for group R1, 50% for group R2, 80% for group R3, and 80% for group R0. There was a significant difference in the survival rates between group R1 and either group R0 or R3 (P < 0.05). Fungal clearance in peripheral blood and various organs of group R1 and R2 was delayed relative to that of group R0 but was similar to the control in group R3 in spite of reimmunosuppression. Our results suggest that the critical period for the development of disseminated trichosporonosis in our model is shorter than 3 weeks after T. asahii infection. We concluded that mice during this critical period were in a state of latent trichosporonemia. Comparison of the survival rates suggests that the nested PCR assay was more useful than blood culture and glucuronoxylomannan antigen assay in the detection of this latent trichosporonemia.

Phialemonium fungemia: two documented nosocomial cases.

Two fungal isolates recovered from the blood of two immunosuppressed patients are described as Phialemonium curvatum. One patient died, while the other, who was infected with Exophiala jeanselmei at the same time, survived after successful treatment with itraconazole. Analysis of internal transcribed spacer sequences demonstrated that the isolates belonged to the same strain and that the source of infection was probably a catheter. The taxonomic position of P. curvatum is discussed, and Phialemonium dimorphosporum is considered a synonym. The in vitro inhibitory activities of six antifungal agents (amphotericin B, itraconazole, ketaconazole, miconazole, flucytosine, and fluconazole) were determined against seven isolates of Phialemonium. Except for flucytosine, all of them were remarkably effective. Phialemonium should be added to the list of potential causes of nosocomial fungemia in cancer patients.

Disseminated cryptococcosis with cutaneous lesions.

A case of disseminated cryptococcosis in an HIV-negative patient presenting with cutaneous lesions is described for the first time in Egypt. The patient, a 16-year-old male, presented with cough, expectoration, loss of weight, and cutaneous lesions, mainly on the face and trunk. The lesions consisted of vegetating crusted plaques discharging purulent to sanguinous fluid and flattened, shiny, erythematous to brownish plaques. Anorexia, headache and personality changes soon followed. Histopathological examination of lesions was highly suggestive of a deep mycosis, particularly cryptococcosis. The fulminant disease advanced with central nervous system involvement. The progression was not arrested when systemic antifungal therapy was administered late in the disease course. Pathological examination of lungs, liver, pancreas and spleen revealed disseminated infection with no evidence of other underlying pathology. Disseminated cryptococcosis is a morbid infection, rare in an area where heightened awareness and raised index of suspicion will surely allow earlier diagnosis, management and better prognosis.

Invasive aspergillosis in systemic lupus erythematosus.

Invasive aspergillosis is seldomly described in systemic lupus erythematosus. We present two cases of aspergillosis and review 21 cases reported between 1957 and 1994. The typical clinical presentation is fever and cough in a hospitalized SLE patient previously treated with corticosteroids, immunosuppressors, and broad-spectrum antibiotics. Unlike aspergillosis in other conditions, granulocytopenia is uncommon. Chest radiographs show diffuse or patchy infiltration of lung fields. Diagnosis was suspected premortem in 2 patients. Aspergillus fumigatus was identified or isolated in sputum or parenchimal tissues in the majority of cases. Twenty-two patients died (95%). The finding of hyphae in the sputum of a systemic lupus erythematosus patient with a suggestive clinical picture should lead to bronchoscopy, bronchoalveolar lavage, and lung biopsy. Proof of diagnosis will come from the demonstration of hyphae in tissues and isolation of aspergillus from tissue cultures. Long-term therapy with amphotericin B alone or in combination with fluorocytosine or itraconazole may help improve survival.

Aeromonas hydrophila myonecrosis accompanying mucormycosis five years after bone marrow transplantation.

A 36-year-old man, five years after bone marrow transplantation for aplastic anemia, was admitted with myonecrosis of the forearm after he had immersed his hand in sewage water several days prior to his admission. Blood cultures and specimens taken from the necrotic tissue of the arm all grew Aeromonas hydrophila. Following extension of the infection, the patient underwent amputation of the arm but ultimately died of cerebral mucormycosis. The epidemiology of Aeromonas infections is discussed and the literature of Aeromonas myonecrosis is reviewed.

Overwhelming myocarditis due to Fusarium oxysporum following bone marrow transplantation.

Disseminated infection by Fusarium is being increasingly reported in immunocompromised patients. We report the first case of Fusarium oxysporum disseminated infection with well-documented fungal myocarditis. Despite antifungal therapy and hematologic recovery, the patient died in cardiogenic shock, myocardial involvement clearly contributing to the fatal outcome.