Emerging trends in candidemia: a higher incidence but a similar outcome.

The clinical presentation and outcome of candidemia has changed in recent years. We compared two 5-year periods (2000-2004 and 2005-2009) in a single institution. We recorded 419 candidemia episodes during the study period (124 in the first period and 295 in the second period). We observed a significant increase in the number of cases per 1000 admissions per year, from 0.57 in 2000 to 1.52 in 2009 (χ(2) LT <0.001). Candida albicans was the most frequently isolated species (42.2%), followed by Candida parapsilosis (34.4%) and Candida glabrata (12.9%). In the second period, episodes were associated with higher comorbidity and were more commonly nosocomial, with a more frequent catheter-related source and an increased rate of C. glabrata infection. No significant differences were observed in susceptibility by species during the study period. According to multivariate analysis, the independent factors associated with higher mortality were shock, age >50 years, elevated comorbidity score (Charlson index >6), and source of candidemia other than catheter. In contrast to the increase in comorbid conditions observed in recent years, mortality remained similar during both periods (~37% during the first month). This finding could be attributed to a significant increase in catheter-related candidemia and better outcome, as well as to a potential improvement in the management of antifungal therapy in recent years.

Voriconazole in the treatment of invasive mold infections in transplant recipients.

Mortality due to invasive mold infections in solid organ transplant recipients is very high despite therapy with amphotericin B, including lipid formulations. Voriconazole is a triazole with a good activity against molds, including Aspergillus spp. and Scedosporium spp. Experience with voriconazole is limited, but preliminary results in patients with these infections are promising. Reported here is the experience with voriconazole administered on a compassionate-use basis to five patients with invasive mold infections: four solid organ recipients and one patient with an autoimmune disorder. Four patients had invasive Aspergillus fumigatus infection (3 lung infections, 1 abdominal infection) and one had invasive ocular Scedosporium apiospermum infection. The MIC of voriconazole was < or =1 microg/ml for all isolates (NCCLS performance standards for microdilution assay, proposed standard M38-P). Voriconazole was administered as primary therapy in a patient with Scedosporium infection and, in patients with Aspergillus infections, after persistence of positive culture despite a cumulative dose of 3 g of a lipid formulation of amphotericin B. Voriconazole was administered for a median time of 80 days (range, 60-90 days). No visual disturbances were observed, but one patient presented a moderate increase in liver enzymes. An increase in the levels of immunosuppressive drugs (tacrolimus or cyclosporine) was detected in all patients during coadministration with voriconazole. A clinical response was observed in all patients (complete response, n=3; partial response, n=2), and a microbiological response was observed in all but one patient. Furthermore, a good relationship between the MIC of voriconazole and outcome was observed. Voriconazole is an effective and safe therapy for treatment of invasive mold infections in solid organ recipients. To avoid toxicity with this drug, however, the dosing of immunosuppressive drugs must be reduced.

Aspergillus antigenemia sandwich-enzyme immunoassay test as a serodiagnostic method for invasive aspergillosis in liver transplant recipients.

BACKGROUND: Invasive aspergillosis (IA) is an important cause of mortality in liver transplant patients. Clinical and microbiological diagnosis is difficult, and it is frequently achieved only after autopsy. Early diagnosis and antifungal therapy could improve the survival of these patients. METHODS: A retrospective case-control study of IA in liver transplant recipients (OLT) was performed to determine the value of the detection of galactomannan Aspergillus antigen in serum using a sandwich-ELISA test (Platelia, Sanofi Diagnostic Pasteur). Stored frozen serum specimens obtained during the posttransplantation period were used. RESULTS: Fourteen cases of IA were diagnosed in 240 OLT recipients (IA incidence: 5.8%) during 5 years with 13 deaths (mortality: 93%). Nine case patients and 33 control patients met the criteria required for being considered "valid" for antigenemia analysis. In five of the nine case patients, a serum sample was positive for Aspergillus antigenemia detection. The median value was 5.7 ng/ml (range: 1.6-6.6). Sensitivity of the test was 55.6%, specificity was 93.9%, the positive predictive value was 71.4%, and the negative predictive value was 88.6%. The likelihood ratio of a positive test was 9.2. CONCLUSIONS: Galactomannan detection in serum could be useful for an early diagnosis of IA in OLT recipients.

[Cryptococcosis not associated with AIDS. Clinical study of seven patients]. / Criptococosis no asociada al sida: estudio clínico de siete pacientes.

BACKGROUND: The aim of the present was to study the clinical characteristics, the diagnostic methods, response to treatment and the evolution of cryptococcosis not associated with AIDS. METHODS: Seven cases studied in the Hospital Ramon y Cajal of Madrid, Spain over a 19-year period (1980-1998). Diagnosis was determined by LCR culture, blood or other clinical samples. RESULTS: Four patients were males with a mean age of 45.1 years (range: 23-69 years). All except one case presented a predisposing disease and three received corticoids and/or immunosuppressive drugs. Six patients presented meningitis and one pneumonia. The meningitis showed a subacute course with pleocytosis, hypoglycorrhachia and hyperproteinorrhachia in most of the patients. Chinese ink staining, culture and the cryptococcic antigen of LCR were positive in all the cases of meningitis evaluated. All the patients were initially treated with amphotericin and fluorocytosin. This schedule was substituted in two cases by amphotericin lipid formulas because of adverse effects and by fluconazol as an elective choice in one case. The evaluation was favorable in all the patients. One patient presented meningeal and cutaneous recurrence. Three patients died, although none did so during the acute episode or as a consequence of the infection. CONCLUSIONS: Cryptococcosis not associated with AIDS is rare in Sapin. It usually evolves with subacute hypoglucorrhachic meningitis and the conventional diagnostic techniques (Chinese ink staining, cryptococcic antigen and culture) provide adequate profitability. Response to treatment with amphotericin and fluorocytosis is usually favorable, although there are therapeutic alternatives which are adequate for selected cases.

A reevaluation of nystatin in prophylaxis and treatment of oropharyngeal candidiasis.

The incidence of oropharyngeal candidiasis is growing. The species of the genus Candida are extremely frequent among human colonizers. The changes in the yeast-human interaction by aging, debilitating, and immunosuppressive diseases, and the more aggressive medical interventions can explain this phenomenon. Antifungals are used both in prophylaxis and therapy, but the number of available agents remains scarce. Acquired resistance to the more commonly used antifungal agents, the azole compounds, is also an increasing threat, Policies for antifungal use should be established in order to maintain the therapeutic possibilities of the current compounds, The widespread use of systemic azoles, agents useful in deep mycosis, may increasingly exert a selective power for resistant variants. Superficial infections, such as oropharyngeal candidiasis, can be successfully controlled by nystatin, a classic polyene, which is very well tolerated and has very low rates of resistance. This review on the importance of oropharyngeal candidiasis emphasizes this therapeutic possibility, and is complemented by in vitro studies documenting the excellent activity of nystatin on both azole-susceptible and resistant strains.

Selection of Candida glabrata strains with reduced susceptibility to azoles in four liver transplant patients with invasive candidiasis.

The cases of four liver transplant recipients who developed invasive candidiasis (2 cholangitis, 1 perihepatic abscess, 1 candidemia) due to azole-resistant, Candida glabrata are reported. Three patients were receiving azolic compounds (2 itraconazole, 1 fluconazole) when the infection was diagnosed. All four patients received fluconazole as intestinal decontamination during the first three weeks post transplantation. The infections occurred two months after transplantation in all patients, and in one patient Candida infection was the direct cause of death. Infection of the biliary tree was the origin of candidiasis in three patients; the fourth patient developed neutropenic-related candidemia. Fluconazole MICs exceeded 16 micrograms/ml in all cases; itraconazole MICs were 16, 2, 1, and 2 micrograms/ml, respectively. The potential role of Candida species other than albicans in these patients after administration of azole agents is discussed.

Correlation between in vitro resistance to fluconazole and clinical outcome of oropharyngeal candidiasis in HIV-infected patients.

Fifty episodes of oropharyngeal candidiasis in HIV-infected patients were analyzed prospectively in order to evaluate the clinical response to fluconazole. The minimum inhibitory concentrations (MICs) of fluconazole for the Candida strains isolated from the pharynx were correlated with the clinical response. Treatment with fluconazole (100 mg/day) was successful in 86% of the cases. A good clinical outcome followed in 97% of the cases when a strain sensitive to fluconazole was isolated. This figure fell to 22% when the strain was resistant to fluconazole (p < 0.001). The rate of post-treatment colonization was high (87%), and selection of non-albicans Candida species occurred in 23% of the cases. In conclusion, fluconazole treatment for oropharyngeal candidiasis of HIV-infected patients was useful in most cases, but less sensitive non-albicans species can be selected. Most treatment failures were associated with increased MICs of fluconazole for the strains isolated before treatment; therefore, susceptibility testing is recommended as an aid in clinical decision-making for the use of the azole group of drugs.

Improved method of determining the susceptibility of Candida albicans to fluconazole.

The MICs of fluconazole for four reference strains of Candida albicans were determined in one laboratory by the macrobroth dilution method recommended by the National Committee for Clinical Laboratory Standards (NCCLS) and by a modified version of the method which incorporated microbroth dilution, RPMI 1640 medium supplemented with glucose and the reading of MIC endpoints by spectrophotometry. The results obtained by the two methods were within one two-fold dilution. In addition, the susceptibilities of 58 clinical isolates of C. albicans to fluconazole were determined in two laboratories by the modified NCCLS method. Close interlaboratory agreement was observed, 98.2% of MICs varying by no more than one two-fold dilution.

Native valve endocarditis due to Candida parapsilosis: a late complication after bone marrow transplantation-related fungemia.

A case of Candida parapsilosis endocarditis observed 16 months after BMT is reported. The patient, a 35-year-old female with CML, suffered from Candida parapsilosis fungemia on day +22 after BMT. In spite of treatment with amphotericin B, fluconazole and catheter withdrawal, the same yeast was isolated > 1 year later from a vegetation on an old rheumatic mitral valve. Although the patient remained in complete cytogenetical and hematological remission, in vitro tests showed reduced phagocytic and chemotactic capacity of neutrophils and monocytes. This case stresses the need of prolonged therapy for patients with candidemia after BMT.

[Pulmonary mucormycosis in leukemic patients. Apropos of 2 cases]. / Mucormicosis pulmonar en pacientes leucémicos. A propósito de dos casos.

Mucormycosis is a rare fungal infection that has been described mainly in oncologic and diabetic patients. We here report the cases of two leukaemic patients in whom pulmonary mucormycosis was diagnosed. Prompt diagnosis, therapy with amphotericin B and surgery when possible, are the cornerstones in the treatment of this fungal infection. Although infrequent, this infection must be suspected in oncohaematological patients with lung infiltrates.

Serological diagnosis of neurobrucellosis.

The presence of antibodies was determined in the serum and cerebrospinal fluid in six patients with neurobrucellosis using the Rose Bengal test, the microdilution agglutination test, and the Coombs' test. Four of the patients were followed up for more than three months. The Rose Bengal test and the microagglutination test were positive in cerebrospinal fluid in five of the six cases at some stage. The Coombs' test was positive in cerebrospinal fluid in every patient and in one was the only positive serological test. Cerebrospinal fluid positivity is not excluded by low titres or negative results of antibodies in the serum for any of the three methods. A Coombs' test or some equivalent must always be made on the cerebrospinal fluid to diagnose neurobrucellosis.

A replica plating technique for in vitro study of susceptibility of Candida albicans to miconazole, econazole and ketoconazole: some data for standardization.

We report our studies in vitro on the activity of ketoconazole (KZ), econazole and miconazole on 115 isolates of Candida albicans of clinical origin tested by an agar dilution method with three different culture media: yeast morphology agar, Sabouraud maltose agar and Casitone agar (CA). The antifungal effects of the imidazole compounds (IC) were strongest in CA. Eighty percent of the strains were inhibited by 0.1 micrograms/ml of KZ, the most active drug. The frequent appearance of "veil growth" at higher concentrations of the IC made the exact determination of the minimal inhibitory concentration (MIC) difficult. Microscopic examination of the growth on plates at the highest drug dilutions was performed and the results compared with a replica plating technique of IC plates on other plates with antibiotic-free media. The following were observed: a) a residual capacity of cell division of Candida strains even in the presence of high antifungal concentrations to which they are considered sensitive; and b) a certain viability (7% of the cases) of some fungal cells in the residual growth, particularly in those strains with higher conventional MIC. A standardized methodology is needed for the clinical evaluation of the susceptibility tests of Candida to the imidazolic compounds.