Melissa Orzechowski Xavier

Diagnosis of invasive aspergillosis in lung transplant recipients by detection of galactomannan in the bronchoalveolar lavage fluid.

Background. Galactomannan (GM) detection in serum samples has been used to diagnose invasive aspergillosis (IA). Limited sensitivity has been observed in lung transplant recipients, for whom bronchoalveolar lavage (BAL) testing has been advocated. Because airway colonization with Aspergillus species occurs frequently in these patients, false-positive GM results have been reported if the cutoff validated for sera is used (i.e., 0.5). Methods. Herein, we prospectively studied BAL fluid samples from 60 lung transplant patients to determine the optimal cutoff for BAL GM testing. Only one sample per patient was studied. BAL samples were vortexed and processed according to the manufacturers instructions for serum samples. Sensitivity, specificity, and likelihood ratios were calculated in reference to proven or probable IA cases using receiver operating characteristic analysis. Results. Eight patients had IA during the study (incidence 13.3%), including four patients with proven IA. Aspergillosis increased 5-fold the risk of death in lung transplant recipients. The positive predictive value of a positive BAL GM test at the 0.5 cutoff was low (24.2%). Raising the cutoff improved test specificity without compromising sensitivity. The best cutoff was defined at 1.5 (sensitivity 100% and specificity 90.4%). Conclusions. This study reinforces the importance of BAL GM testing in lung transplant recipients, particularly to exclude the diagnosis of IA. To minimize the frequency of false-positive results, a higher test cutoff should be applied to BAL samples, in comparison with serum samples.

Cryptococcosis in children

Cryptococcosis is a systemic-opportunistic mycosis caused by two species of the encapsulated yeast-like organism, Cryptococcus neoformans and C. gattii, which cause infection in immunocompromised individuals and in immunologically normal hosts, respectively. Most susceptible to infection are patients with T-cell deficiencies. The spectrum of disease ranges from asymptomatic pulmonary lesions to disseminated infection with meningoencephalitis. After the emergence of AIDS, cryptococcal infections have become much more common. The mycosis occurs less frequently in children than in adults. The purpose of this article is to discuss the aetiology, clinical presentation, predisposing conditions and outcomes in cases of cryptococcosis in children. Emphasis is placed upon paediatric cases occuring in Brazil and in particular to highlight the difference between cases diagnosed in Porto Alegre (South - subtropical climate) and in Belem (North - equatorial climate).

Voriconazole therapeutic drug monitoring: focus on safety

Importance of the field: Voriconazole has been widely used for the treatment of invasive fungal diseases, particularly invasive aspergillosis. Drug–drug interactions are, however, the main drawback associated with voriconazole use, since this drug suffers from extensive hepatic metabolism. Areas covered in this review: This article reviews the current literature on voriconazole therapeutic drug monitoring, with a special focus on drug safety. What the reader will gain: An update on voriconazole metabolism, drug interactions, toxicity and the relation of these with voriconazole drug concentrations. Take home message: Therapy with voriconazole may be better guided by measuring voriconazole concentrations in the plasma.

Cross-Reactivity of Paracoccidioides brasiliensis, Histoplasma capsulatum, and Cryptococcus Species in the Commercial Platelia Aspergillus Enzyme Immunoassay

ABSTRACT Cross-reactivity in the Platelia Aspergillus enzyme immunoassay was evaluated using 120 sera from patients with paracoccidioidomycosis, histoplasmosis, and cryptococcosis. At a cutoff value of 0.5, positivity rates were 50%, 67%, and 50%, respectively. The implications for these findings are discussed.

Histoplasmosis in children

Histoplamosis is the most common primary systemic mycosis in the USA and is becoming more common as an opportunistic infection in HIV patients worldwide. In children the rate of asymptomatic infection is high. However, in infants with an immature immunological system, disseminated disease may occur. The clinical picture is variable depending on the immunological status. At the onset of the infection clinical manifestations are non specific (headache, fever, cough and nausea). Usually, these symptoms are self-limited and improve without treatment. However, patients with disseminated diseases present with prolonged fever, malaise, cough and weight loss. Hepatosplenomegaly is frequent in infants. Chest radiographs may be normal in 40 to 50% of patients with disseminated disease but findings such as lobar or diffuse infiltrates, cavitations, hilar adenopathy, or any combination of these may be found. Frequently, the clinical presentation is misdiagnosed as tuberculosis. Skin tests, serological reaction and specific cultures are used for diagnosis confirmation. Treatment indications and regimens are similar to those for adults, except that amphotericin B deoxycholate is usually well tolerated in children.

Aspergillus niger causing tracheobronchitis and invasive pulmonary aspergillosis in a lung transplant recipient: case report

A case of invasive aspergillosis caused by Aspergillus niger in a lung transplant recipient is described. The patient presented hyperglycemia starting postoperatively, with other complications such as cytomegalovirus infection. The associated predisposing factors and other implications are discussed. Aspergillus niger seems to be a fungal species of low virulence that requires the presence of a severely immunosuppressed host to cause invasive disease.

Invasive pulmonary aspergillosis due to a mixed infection caused by Aspergillus flavus and Aspergillus fumigatus

Invasive pulmonary aspergillosis is typically caused by a single Aspergillus species, most frequently Aspergillus fumigatus. Here we report that a lung transplant recipient developed invasive aspergillosis due to a mixed infection caused by Aspergillus flavus and A. fumigatus. The implications for this unusual finding are discussed.

The performance of real-time PCR, galactomannan, and fungal culture in the diagnosis of invasive aspergillosis in ventilated patients with chronic obstructive pulmonary disease (COPD).

Emerging reports have associated chronic pulmonary obstructive disease (COPD) with invasive aspergillosis (IA), particularly in patients treated with mechanical ventilation and/or corticosteroids. This is a multicentre study in which COPD patients demonstrating a new lung infiltrate while being mechanically ventilated were prospectively evaluated for the presence of IA. From the 47 patients studied, Aspergillus fumigatus was recovered in culture in two patients (4.2%). While serum galactomannan (GM) was negative for 94% of patients, GM levels in respiratory samples were >0.5, >1.0 and >1.5 for 74.5, 40.5, and 21.3% of patients, respectively. PCR was positive for 10 patients in the study but did not differentiate Aspergillus colonization from infection. The combination of PCR and GM in respiratory samples may be an interesting alternative to diagnose IA in COPD patients.

Atividade inibitória do óleo essencial de orégano em fungos de importância médica e veterinária

ABSTRACT The in vitro activity of Origanum vulgare essential oil against fungal isolates was evaluated. A total of 27 clinical isolates were used, including: C. albicans, S. schenckii, M. pachydermatis , Aspergillus flavus , and A. fumigatus. Microdilution in broth technique (NCCLS M27-A2 and M-38) was used and susceptibility was expressed as Minimum Inhibitory Concentration (MIC). Essential oil was obtained by hydrodistillation in Clevenger and analyzed by gas chromatography, showing the presence of 4-terpineol, alpha-terpineol, 4-terpinene, thymol and carvacrol, as the main compounds. Origanum oil MIC for C. albicans varied from 125 to 50 0μ L/mL; for S. schenckii, from 250 to 500μ L/mL; for M. pachydermatis, from 15 to 30μ L/mL; and for Aspergillus, from 30 to 60 uf06d L/mL. Isolates sensitivity showed to the origanum oil stimulates the accomplishment of new studies, including in vivo tests, contributing to the search of alternative treatments to mycosis. Keywords: fungal, essential oil, origanum

Galactomannan detection from piperacillin-tazobactam brands available in the Brazilian market

Piperacillin-tazobactam is a broad spectrum antimicrobial agent that can cause false-positive results in the commercial Platelia Aspergillus EIA test. So far, no study has been performed in Latin America to evaluate the clinical implication of this finding. Here we studied the potential for galactomannan detection in piperacillin-tazobactam batches commercialized in the Brazilian market. Five batches from distinct laboratories were tested in duplicate in the Platelia Aspergillus EIA according to the manufacturers instructions. Only one drug showed crossreaction at a cut-off of 0.5. Human serum was spiked with this particular drug aiming to mimic achievable piperacillin-tazobactam concentrations in the serum. Results were all negative for galactomannan detection, even at high drug concentrations. Results from this pilot study suggest that piperacillin-tazobactam might not be a clinically significant cause of false-positive results in the Platelia Aspergillus EIA test in Brazil.