Pharmacokinetic evaluation of liposomal amphotericin B (L-AMB) in patients with invasive fungal infection: Population approach in Japanese pediatrics.

The pharmacokinetic characteristics of liposomal amphotericin B (L-AMB; AmBisome(®)) in patients with invasive fungal infection were investigated. A population pharmacokinetic (PK) model in Japanese pediatric patients was developed based on 159 serum amphotericin B (AMPH-B) concentrations obtained in a post-marketing clinical study. The subjects were 39 patients with a mean age of 8.4 years (SD 4.5) and mean body weight of 27.1 kg (SD 14.1). A two-compartment PK model with zero-order input and first-order elimination was fitted to serum AMPH-B concentrations for L-AMB doses of 1.0, 2.5, and 5.0 mg/kg/day. Body weight showed significant correlations with PK parameters, such as clearance (CL) and distribution volume of the central compartment (Vc). The predicted Cmax/dose and AUC0-24/dose in Japanese pediatric patients were similar to those in non-Japanese pediatric patients and Japanese adult patients. Extremely large increases in Ctrough compared with predicted values were observed in some Japanese pediatric patients, but no relationships with demographic characteristics, clinical laboratory test values, or representative adverse drug reaction (decreased potassium) were found. The population PK parameters in this study are useful for simulating PK profiles of L-AMB and will be helpful for PK exposure comparisons among different populations and in investigations of pharmacokinetic-pharmacodynamic characteristics in patients. CHEMICAL COMPOUNDS: Amphotericin B Deoxycholate (PubChem CID:23668620); amphotericin B (PubChem CID:5280965); 3-nitrophenol (PubChem CID:11137); methanol (PubChem CID:887).

Race and invasive fungal infection in solid organ transplant recipients.

Health disparities in access to solid organ transplantation (SOT) and graft survival are well recognized, but there are limited data on the relationship of race to risk of invasive fungal infection (IFI) among SOT recipients. We conducted a case-control study using data from the Transplant-Associated Infection Surveillance Network (TRANSNET) to investigate race and IFI. Cases (n = 1,214) and controls (n = 16,550) were compared on demographic variables using chi-square, and the relationship between race and IFI was assesses with unconditional logistic regression. Compared to White transplant patients, Blacks had similar odds of developing IFI (OR = .97, 95% Cl 0.82-1.15, P = .7125), while participants who identified as other ethnicity were less likely to develop IFI (OR = .56, 95% Cl .41-.75, P < .001). Blacks, when compared to White patients, were at increased odds of developing cryptococcal infection (OR 2.19, 95% CI 1.35-3.54, P = .002). Despite pharmacogenetic differences, Black transplant recipients were not more likely overall to develop IFI compared to White transplant recipients.

Non-candidal fungal peritonitis in Far North Queensland: a case series.

BACKGROUND: Fungal peritonitis is a recognized complication in patients with end-stage renal failure treated with peritoneal dialysis (PD). Most infections are attributable to Candida species. In approximately one third of cases, the causative fungus is a non-Candida species. Recent reports in the literature show a rising incidence of non-candidal fungal peritonitis (NCFP). We report a case series of NCFP, together with two hitherto unreported species of fungi causing peritonitis, from a tropical geographic area (Far North Queensland). METHODS: This series of 10 cases of NCFP was identified from the PD peritonitis database in Far North Queensland between 1998 and 2010. All 10 patients were from the Aboriginal and Torres Strait Islander ethnic group, 8 of whom lived in remote locations. All but 1 patient had type 2 diabetes mellitus. Of the 10 cases, 7 occurred while the patients received continuous ambulatory PD. Only 1 patient avoided catheter removal, and 5 patients were permanently transferred to hemodialysis. No patient died as a result of the fungal infection. All 10 fungi represented different species. Most (6 of 10) were saprophytic; only 2 were normal skin flora. Two of the causative species (Chaetomium and Beauveria) have rarely been associated with any form of human infection. In 7 patients, the infection occurred during the wet season (November - April). All cases met clinical criteria for peritonitis. DISCUSSION AND CONCLUSIONS: The NCFP cases described in this series involved a variety of previously known fungal species and also two new species that have not been reported to cause disease in humans. Indigenous patients from Far North Queensland are particularly predisposed to infection with these exotic fungi as a result of environmental and social factors. Further understanding is desirable to help devise preventive strategies to avoid the consequences of catheter failure.

Micosis superficiales en atletas de la Facultad de Ciencias de la Educación, Universidad de Carabobo / Surface mycosis in athletes from the School of Education, University of Carabobo

Las dermatofitosis constituyen uno de los problemas de salud más frecuente a nivel mundial, con mayor incidencia en países tropicales y subtropicales, más frecuentemente en el sexo masculino. Los atletas están en constante predisposición a sufrir de infecciones micóticas por la variabilidad de las condiciones individuales así como ambientales. El objetivo fue determinar la prevalencia de los agentes etiológicos causantes de micosis superficiales en los atletas de la Facultad de Ciencias de la Educación de la Universidad de Carabobo. La muestra estuvo representada por 71 atletas de diferentes disciplinas que presentaban lesiones sospechosas de micosis superficiales en piel y uñas, realizándoles un examen directo con KOH, Cinta adhesiva, cultivo en Agar Lactrimel. Los aislados obtenidos se les practicó un examen directo con azul de lactofenol y microcultivo para identificar el agente etiológico. Se encontró en los atletas 63,4% de lesiones por dermatofitos identificando las especies T. rubrum (23,9%), T. mentagrophytes (19,7%) y E. floccosum (19,7%) y 36,6% de lesiones por levaduras identificando Malassezia furfur (29,6%) y Malassezia ovalis(7,1%) siendo el sexo masculino el más afectado. Estos hallazgos son relevantes debido a que estos agentes se aprovechan de condiciones desfavorables para colonizar y ocasionar lesiones que pudiesen disminuir el rendimiento deportivo del atleta.

Dermatophytosis is one of the most common health problems worldwide, with greater incidence in tropical and subtropical countries, most often in males. Athletes are constantly predisposed to suffering from fungal infections due to the variability of individual and environmental conditions. The objective was to determine the prevalence of etiological agents causing superficial mycosis in athletes from the School of Educational Sciences at the University of Carabobo. The sample was represented by 71 athletes from different disciplines that had lesions suspected of being surface mycosis on skin and nails; a direct examination was made with KOH, adhesive tape and cultivation on Lactrimel agar. The obtained isolates were examined directly with lactophenol blue and microculture to identify the etiologic agent. It was found that 63.4% of the athletes had lesions by dermatophytes, identifying the species T. rubrum (23.9%), T. mentagrophytes (19.7%) and E. floccosum (19.7%); in 36.6% of lesions, the yeast Malassezia furfur (29.6%) and Malassezia ovalis (7.1%) were identified; males were the most affected. The findings are relevant because these agents take advantage of adverse conditions to colonize and cause lesions that could decrease athletic performance.

Infectious complications in kidney transplant: a Lebanese perspective.

OBJECTIVES: Infections remain a frequent, potentially life-threatening complication of kidney transplant. SUBJECTS AND METHODS: Between 1998 and 2006, we evaluated the incidence of infections in 114 kidney transplant patients, with a 1-year follow-up. All patients received a posttransplant anti-infectious prophylaxis regimen. Induction therapy was given to 94 patients (82.4%), and maintenance immunosuppression consisted of calcineurin inhibitor (cyclosporin microemulsion or tacrolimus), together with mycophenolate mofetil and prednisone. RESULTS: In total, 56 patients (49.1%) developed a total of 95 infections up to 1-year after kidney transplant, including 46 in-hospital infections in 38 patients. Bacterial infections were the most frequent (97.8%), and were mainly urinary, followed by drain, central line catheter, and pulmonary infections. The most-frequent isolated bacteria were E. coli, followed by Klebsiella, Acinetobacter, and Pseudomonas. No viral infections were detected. Up to 1 year after discharge from the hospital, 49 infections occurred in 26 patients, of which 79.5% were bacterial; mainly urinary tract infections due to E. coli, in addition to 7 cases of cytomegalovirus, 1 herpes, and 2 cases of fungal infections. CONCLUSIONS: This is the first Lebanese study that deals with posttransplant infections in kidney transplant patients and underscores the importance of close patient monitoring and follow-up. Comparison with international data shows similar patterns.

Invasive fungal infections in patients with systemic lupus erythematosus: experience from affiliated hospitals of Catholic University of Korea.

The purpose of study was to determine the nature, outcomes and associated risk factors of invasive fungal infection (IFI) in patients with systemic lupus erythematosus (SLE), and compare the incidence of IFI in patients with rheumatoid arthritis (RA). A total of 1155 patients with SLE and 2004 patients with RA were retrospectively reviewed between 1992 and 2007. Twelve cases of IFI patients were identified in SLE patients (6 Aspergillus spp.; 5 Cryptococcus spp.; 1 Candida spp.). The incidence of IFI was significantly higher in patients with SLE than RA (1.04 vs. 0.15%). Among 12 patients with SLE, 10 had high Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores (>or=8). The most commonly involved organ was the lung (n = 6), followed by the meninges (n = 4). Most of SLE patients with IFI (91.7%) had taken steroids prior to IFI. Three SLE patients resulted in death. Notably, these patients were all infected with Aspergillus spp. The mortality was associated with the presence of leukopenia, high anti-DNA antibodies and high SLEDAI. Collectively, IFI is more common in patients with SLE than in patients with RA. High disease activity in patients with SLE might contribute to increased risk of IFI. In addition, mortality was associated with aspergillus infection, leukopenia and high anti-DNA antibodies.

Trends in mortality due to invasive mycotic diseases in the United States, 1980-1997.

To determine national trends in mortality due to invasive mycoses, we analyzed National Center for Health Statistics multiple-cause-of-death record tapes for the years 1980 through 1997, with use of their specific codes in the International Classification of Diseases, Ninth Revision (ICD-9 codes 112.4-118 and 136.3). In the United States, of deaths in which an infectious disease was the underlying cause, those due to mycoses increased from the tenth most common in 1980 to the seventh most common in 1997. From 1980 through 1997, the annual number of deaths in which an invasive mycosis was listed on the death certificate (multiple-cause [MC] mortality) increased from 1557 to 6534. In addition, rates of MC mortality for the different mycoses varied markedly according to human immunodeficiency virus (HIV) status but were consistently higher among males, blacks, and persons > or =65 years of age. These data highlight the public health importance of mycotic diseases and emphasize the need for continuing surveillance.

Liposomal amphotericin B for prophylaxis of invasive fungal infections in high-risk paediatric patients with chemotherapy-related neutropenia: interim analysis of a prospective study.

Invasive fungal infections (IFI) are a major cause of morbidity and mortality in patients with cancer. A retrospective analysis of children with cancer at high risk for IFI treated at Münster University Hospital showed that the incidence (7.4% vs. 1.8%) and lethality (28.1% vs. 0) of documented IFI were lower in patients receiving systemic antifungal prophylaxis with liposomal amphotericin B (l-AmB) in comparison to a historical control group. To determine whether this decline in incidence and lethality was due to antifungal prophylaxis or was produced by advances in diagnostic procedures and early empirical antifungal therapy, a prospective study was initiated. Patients in the prophylaxis arm received thrice-weekly 1 mg kg(-1) body weight l-AmB, whilst patients in the early intervention arm received no prophylaxis. Diagnostic procedures and antifungal therapy for suspected or proven IFI were initiated as clinically indicated for all patients. The primary endpoint of the study was the incidence of IFI. Secondary endpoints were the use of therapeutic doses of l-AmB, the safety of prophylactic l-AmB, and the total consumption of l-AmB for antifungal therapy. The interim analysis after 1 year showed no differences between the two approaches with respect to the incidence of IFI and to safety issues.

Disseminated Penicillium marneffei infection: a report of five cases in Singapore.

Penicillium marneffei has emerged as an important opportunistic pathogen in HIV-infected patients in Southeast Asia. We report the first 5 cases of P. marneffei diagnosed in Singapore. All the patients were HIV-infected and were either Thai nationals or had frequently travelled to Thailand. Fever, weight loss, anaemia and papular skin lesions were common clinical manifestations in our patients, all of whom had the organism isolated from blood. Skin biopsy specimens showed histological evidence of P. marneffei in 2 patients. In 1 patient each, the organism grew in cultures of specimens from bone marrow and respiratory secretions. Amphotericin B therapy followed by itraconazole were used in 3 of our 5 patients and was associated with good clinical response and outcome.

Disseminating infection with Scytalidium dimidiatum in a granulocytopenic child.

A 13-year-old Moroccan boy in The Netherlands developed fever and a lesion resembling ecthyma gangrenosum on the abdomen during cytostatic drug treatment for a lymphoblastic B-cell lymphoma. Scytalidium dimidiatum was cultured from blood and the abdominal skin lesion. The patient was successfully treated with amphotericin B. The fungus Scytalidium dimidiatum is a fairly common plant pathogen in tropical and subtropical countries and is known to cause dermatomycoses in humans in these areas. This case demonstrates that it is necessary to be aware that immigrants from these areas can import their own fungal flora, some members of which may cause life-threatening disease in the case of patients with immune suppression.