Cryptococcal Meningitis: A Retrospective Cohort of a Brazilian Reference Hospital in the Post-HAART Era of Universal Access.

OBJECTIVE: Cryptococcus neoformans is a common opportunistic infection in adults with acquired immunodeficiency syndrome worldwide. However, limited data exist for HIV-infected patients in the post-HAART (highly active antiretroviral therapy) era in Brazil. The aim of this study was to describe the clinical characteristics and outcomes of cryptococcosis in a cohort of patients attending a teaching tertiary care hospital in southern Brazil after the introduction of HAART in Brazil. PATIENTS AND METHODS: A retrospective study was conducted in tertiary care hospital in southern Brazil. Detailed data on risk factors, clinical manifestations, diagnosis methods, treatment, and prognosis of patients with meningeal cryptococcosis were evaluated from January 2009 to December 2016. RESULTS: Seventy-nine cases of cryptococcal meningitis were identified. Most of the patients presented positive CSF (cerebrospinal fluid) cultures for Cryptococcus neoformans (96%). The prevalence of males and females with meningeal cryptococcosis was similar. The age of the patients ranged from 5 to 67 years. The median time of hospitalization was 28 days. The most common underlying disease was HIV (82%), followed by solid transplant (10%). Fever, nausea, vomiting, headache, and altered mental status were the most common clinical manifestations. Initial opening intracranial pressures varied from 30 to 130 cm H2O. CNS imaging abnormalities include hydrocephalus and hypodensities. Widened Virchow-Robin spaces were described in only 2 patients (2.5%). Induction treatment of the majority of the patients consisted of amphotericin B and flucytosine (67%) followed by amphotericin B and fluconazole (19%). Multivariate analysis of Cox regression identified headache at presentation, mechanical ventilation, CSF glucose <20 mg/dL, and CSF cryptococcal antigen ≥1 : 1000 for independent risk factors for death. All-cause 30-day and 60-day mortalities were 19% and 24%, respectively. CONCLUSIONS: Meningeal cryptococcosis mostly caused by C. neoformans continues to occur predominantly in HIV-infected adults despite HAART being widely distributed in Brazil. Cryptococcosis remains a significant opportunistic infection in solid organ transplant recipients. Despite adequate antifungal treatment and management of intracranial hypertension in a reference tertiary care hospital, mortality was high. Identification of risk factors and additional treatment modalities, especially for intracranial hypertension, are necessary to improve care for patients with cryptococcal meningitis.

Genetic diversity and antifungal susceptibility of Fusarium isolates in onychomycosis.

Fusarium species have emerged as an important human pathogen in skin disease, onychomycosis, keratitis and invasive disease. Onychomycosis caused by Fusarium spp. The infection has been increasingly described in the immunocompetent and immunosuppressed hosts. Considering onychomycosis is a difficult to treat infection, and little is known about the genetic variability and susceptibility pattern of Fusarium spp., further studies are necessary to understand the pathogenesis and better to define the appropriate antifungal treatment for this infection. Accordingly, the objective of this study was to describe the in vitro susceptibility to different antifungal agents and the genetic diversity of 35 Fusarium isolated from patients with onychomycosis. Fusarium spp. were isolated predominantly from female Caucasians, and the most frequent anatomical location was the nail of the hallux. Results revealed that 25 (71.4%) of isolates belonged to the Fusarium solani species complex, followed by 10 (28.5%) isolates from the Fusarium oxysporum species complex. Noteworthy, the authors report the first case of Neocosmospora rubicola isolated from a patient with onychomycosis. Amphotericin B was the most effective antifungal agent against the majority of isolates (60%, MIC ≤4 µg/mL), followed by voriconazole (34.2%, MIC ≤4 µg/mL). In general, Fusarium species presented MIC values >64 µg/mL for fluconazole, itraconazole and terbinafine. Accurate pathogen identification, characterisation and susceptibility testing provide a better understanding of pathogenesis of Fusarium in onychomycosis.

Animal Models and Antifungal Agents in Paracoccidioidomycosis: An Overview.

Paracoccidioides brasiliensis is the etiologic agent of paracoccidioidomycosis, the most prevalent systemic mycosis in Latin America. The morbidity and mortality associated with paracoccidioidomycosis necessitate our understanding of fungal pathogenesis and discovering of new agents to treat this infection. Animal models have contributed much to the knowledge of fungal infections and their corresponding therapeutic treatments. This is true for animal models of the primary fungal pathogens such as P. brasiliensis. This review describes the development, details and utility of animal models of paracoccidioidomycosis for studying and developing the current antifungal agents used for therapy of this fungal disease and novel agents with antifungal properties against P. brasiliensis.

Association between Accessory Gene Regulator Polymorphism and Mortality among Critically Ill Patients Receiving Vancomycin for Nosocomial MRSA Bacteremia: A Cohort Study.

Background. Polymorphism of the accessory gene regulator group II (agr) in methicillin-resistant Staphylococcus aureus (MRSA) is predictive of vancomycin failure therapy. Nevertheless, the impact of group II agr expression on mortality of patients with severe MRSA infections is not well established. Objective. The goal of our study was to evaluate the association between agr polymorphism and all-cause in-hospital mortality among critically ill patients receiving vancomycin for nosocomial MRSA bacteremia. Methods. All patients with documented bacteremia by MRSA requiring treatment in the ICU between May 2009 and November 2011 were included in the study. Cox proportional hazards regression was performed to evaluate whether agr polymorphism was associated with all-cause in-hospital mortality. Covariates included age, APACHE II score, initial C-reactive protein plasma levels, initial serum creatinine levels, vancomycin minimum inhibitory concentration, vancomycin serum levels, and time to effective antibiotic administration. Results. The prevalence of group I and group II agr expression was 52.4% and 47.6%, respectively. Bacteremia by MRSA group III or group IV agr was not documented in our patients. The mean APACHE II of the study population was 24.3 (standard deviation 8.5). The overall cohort mortality was 66.6% (14 patients). After multivariate analysis, initial plasma C-reactive protein levels (P = 0.01), initial serum creatinine levels (P = 0.008), and expression of group II agr (P = 0.006) were positively associated with all-cause in-hospital mortality. Patients with bacteremia by MRSA with group II agr expression had their risk of death increased by 12.6 times when compared with those with bacteremia by MRSA with group I agr expression. Conclusion. Group II agr polymorphism is associated with an increase in mortality in critically ill patients with bacteremia by MRSA treated with vancomycin.

Cohort study of the impact of time to antibiotic administration on mortality in patients with febrile neutropenia.

The time to antibiotic administration (TTA) has been proposed as a quality-of-care measure in febrile neutropenia (FN); however, few data regarding the impact of the TTA on the mortality of adult cancer patients with FN are available. The objective of this study was to determine whether the TTA is a predictor of mortality in adult cancer patients with FN. A prospective cohort study of all consecutive cases of FN, evaluated from October 2009 to August 2011, at a single tertiary referral hospital in southern Brazil was performed. The TTA was assessed as a predictive factor for mortality within 28 days of FN onset using the Cox proportional hazards model. Kaplan-Meier curves were used for an assessment of the mortality rates according to different TTAs; the log-rank test was used for between-group comparisons. In total, 307 cases of FN (169 subjects) were evaluated. During the study period, there were 29 deaths. In a Cox regression analysis, the TTA was independently associated with mortality within 28 days (hazard ratio [HR], 1.18; 95% confidence interval [CI], 1.10 to 1.26); each increase of 1 h in the TTA raised the risk of mortality within 28 days by 18%. Patients with FN episodes with a TTA of ≤ 30 min had lower 28-day mortality rates than those with a TTA of between 31 min and 60 min (3.0% versus 18.1%; log-rank P = 0.0002). Early antibiotic administration was associated with higher survival rates in the context of FN. Efforts should be made to ensure that FN patients receive effective antibiotic therapy as soon as possible. A target of 30 min to the TTA should be adopted for cancer patients with FN.

Association between adherence to an antimicrobial stewardship program and mortality among hospitalised cancer patients with febrile neutropaenia: a prospective cohort study.

BACKGROUND: Initial management of chemotherapy-induced febrile neutropaenia (FN) comprises empirical therapy with a broad-spectrum antimicrobial. Currently, there is sufficient evidence to indicate which antibiotic regimen should be administered initially. However, no randomized trial has evaluated whether adherence to an antimicrobial stewardship program (ASP) results in lower rates of mortality in this setting. The present study sought to assess the association between adherence to an ASP and mortality among hospitalised cancer patients with FN. METHODS: We conducted a prospective cohort study in a single tertiary hospital from October 2009 to August 2011. All adult patients who were admitted to the haematology ward with cancer and FN were followed up for 28 days. ASP adherence to the initial antimicrobial prescription was determined. The mortality rates of patients who were treated with antibiotics according to the ASP protocol were compared with those of patients treated with other antibiotic regimens. The multivariate Cox proportional hazards model and propensity score were used to estimate 28-day mortality risk. RESULTS: A total of 307 FN episodes in 169 subjects were evaluated. The rate of adherence to the ASP was 53%. In a Cox regression analysis, adjusted for propensity scores and other potential confounding factors, ASP adherence was independently associated with lower mortality (hazard ratio, 0.36; 95% confidence interval, 0.14-0.92). CONCLUSIONS: Antimicrobial selection is important for the initial management of patients with FN, and adherence to the ASP, which calls for the rational use of antibiotics, was associated with lower mortality rates in this setting.

Detection of Treponema pallidum by semi-nested PCR in the cerebrospinal fluid of asymptomatic HIV-infected patients with latent syphilis.

BACKGROUND: Neurosyphilis diagnosis is frequently dependent upon the results of serological tests and cerebrospinal fluid abnormalities, but the reliability of findings in patients with HIV-1 infection has been questioned, especially in asymptomatic patients with latent syphilis. In this study, we present the data on the presence of T. pallidum DNA in CSF from asymptomatic HIV-infected patients with the diagnosis of syphilis. METHODS: CSF and serum samples were collected from 12 HIV-infected patients attending a tertiary care clinic located in southern Brazil, during the period 2012 to 2013. RESULTS: In CSF samples from five of 12 patients (40%), we detected T. pallidum DNA. Unexpectedly, in these patients, the CSF cell count, protein and glucose levels were normal. In addition, none of these 5 CSF samples presented a positive VDRL reaction. Serum VDRL titers were similar between patients with positive and negative CSF T. pallidum DNA. Most patients with detectable T. pallidum DNA presented low serum VDRL titers. A higher serum VDRL titer of 1:64 was observed in only one patient. CONCLUSIONS: Our results have shown that asymptomatic HIV-infected patients with evidence of latent syphilis and normal CSF might present detectable T. pallidum DNA in the CSF. The detection of T. pallidum DNA by our seminested PCR provides additional information beyond conventional CSF analysis for the diagnosis of neurosyphilis. The detection of T. pallidum DNA in CSF despite normal CSF findings in HIV-infected patients could also provide a different therapeutic approach including the use of intravenous aqueous crystalline penicillin.

Mortality related to coagulase-negative staphylococcal bacteremia in febrile neutropenia: A cohort study.

BACKGROUND: Coagulase-negative staphylococci (CoNS) are currently the most common isolates recovered from the blood of patients with cancer and febrile neutropenia (FN). OBJECTIVES: To assess the mortality associated with bloodstream infections (BSIs) caused by CoNS in cancer patients with FN. METHODS: A prospective cohort study was conducted in a single tertiary hospital from October 2009 to August 2011. Follow-ups were performed on all of the adult patients who were admitted to the hematology ward with cancer and FN. Bacteremia caused by CoNS was defined as two positive results of two independent cultures. Twenty-eight days after the onset of FN, the mortality rates of the patients with BSIs caused by CoNS were compared with those of patients with BSIs caused by other pathogens. RESULTS: A total of 169 subjects were evaluated. During the study period, 78 patients with BSIs were documented. Twenty-three BSIs (29.4%) were a result of CoNS. CoNS-induced bacteremia resulted in lower 28-day mortality compared with bacteremia caused by other pathogens (4.3% versus 32.7%; log-rank P=0.009). In a Cox proportional hazards regression analysis, BSIs caused by CoNS were independently associated with lower mortality (HR 0.09 [95% CI 0.01 to 0.74]). CONCLUSIONS: In adult patients with cancer and FN, BSIs caused by CoNS were associated with lower mortality compared with BSIs caused by other pathogens.

HISTORIQUE: Les staphylocoques à coagulase négative (SCoN) sont les isolats les plus prélevés dans le sang des patients atteints d'un cancer et d'une neutropénie fébrile (NF). OBJECTIFS: Évaluer la mortalité associée aux infections sanguines (IS) causées par les SCoN chez des patients atteints du cancer ayant une NF. MÉTHODOLOGIE: Les chercheurs ont mené une étude prospective de cohorte dans un seul hôpital de soins tertiaires entre octobre 2009 et août 2011. Ils ont assuré le suivi de tous les patients adultes atteints d'un cancer et d'une neutropénie fébrile qui avaient été hospitalisés à l'unité d'hématologie. Les bactériémies causées par les SCoN étaient définies comme deux résultats positifs dans deux cultures indépendantes. Vingt-huit jours après l'apparition de la NF, le taux de mortalité des patients atteints d'une IS causée par des SCoN était comparé à celui des patients ayant une IS causée par d'autres pathogènes. RÉSULTATS: Au total, les chercheurs ont évalué 169 sujets. Pendant la période de l'étude, ils ont répertorié 78 patients ayant une IS. Vingttrois IS (29,4 %) étaient causées par un SCoN. La bactériémie induite par un SCoN était responsable d'un taux de mortalité plus faible au bout de 28 jours que celle causée par d'autres pathogènes (4,3 % par rapport à 32,7 %; test de Mantel Haenzel P=0,009). Dans une analyse de régression des hasards proportionnels de Cox, les IS causées par un SCoN étaient associées indépendamment à un taux de mortalité plus faible (rapport de risque 0,09 [95 % IC 0,01 à 0,74]). CONCLUSIONS: Chez des patients adultes atteints du cancer et de NF, les IS causées par un SCoN s'associaient à un taux de mortalité moins élevé que celles causées par d'autres pathogènes.

Mortality predictors in patients with suspected sepsis in the emergency department of a tertiary care hospital: a retrospective cohort study.

BACKGROUND: Sepsis remains a worldwide major cause of hospitalization, mortality, and morbidity. To enhance the identification of patients with suspected sepsis at high risk of mortality and adverse outcomes in the emergency department (ED), the use of mortality predictors is relevant. This study aims to establish whether quick sofa (qSOFA) and the severity criteria applied in patients with suspicion of sepsis in a monitored ED are in fact predictors of mortality. METHODS: We performed a retrospective cohort study among adult patients with suspicion of sepsis at the ED of a tertiary care hospital in Brazil between January 1st, 2019 and December 31, 2020. All adult patients (ages 18 and over) with suspected sepsis that scored two or more points on qSOFA score or at least one point on the severity criteria score were included in the study. RESULTS: The total of patients included in the study was 665 and the average age of the sample was 73 ± 19 years. The ratio of men to women was similar. Most patients exhibited qSOFA ≥ 2 (58.80%) and 356 patients (53.61%) scored one point in the severity criteria at admission. The overall mortality rate was 19.7% (131 patients) with 98 patients (14.74%) having positive blood cultures, mainly showing Escherichia coli as the most isolated bacteria. Neither scores of qSOFA nor the severity criteria were associated with mortality rates, but scoring any point on qSOFA was considered as an independent factor for intensive care unit (ICU) admission (qSOFA = 1 point, p = 0.02; qSOFA = 2 points, p = 0.03, and qSOFA = 3 points, p = 0.04). Positive blood cultures (RR, 1.63;95% CI, 1.10 to 2.41) and general administration of vasopressors at the ED (RR, 2.14;95% CI, 1.44 to 3.17) were associated with 30-day mortality. The administration of vasopressors at the ED (RR, 2.25; CI 95%, 1.58 to 3.21) was found to be a predictor of overall mortality. CONCLUSIONS: Even though an association was found between qSOFA and ICU admission, there was no association of qSOFA or the severity criteria with mortality. Therefore, patients with a tendency toward greater severity could be identified and treated more quickly and effectively in the emergency department. Further studies are necessary to assess novel scores or biomarkers to predict mortality in sepsis patients admitted to the ED's initial care.

Sporotrichosis in renal transplant patients.

The current report describes two renal transplant recipients who presented with sporotrichosis. In addition, the authors review the general aspects of sporotrichosis in renal transplant recipients reported in the literature. Sporotrichosis is a rare fungal infection in transplant patients and has been reported primarily in renal transplant recipients not treated with antifungal prophylaxis. Extracutaneous forms of sporotrichosis without skin manifestations and no previous history of traumatic injuries have been described in such patients and are difficult to diagnose. Renal transplant recipients with sporotrichosis described in the present report were successfully treated with antifungal therapy including amphotericin B deoxycholate, lipid amphotericin B formulations, fluconazole and itraconazole.

Le présent rapport décrit deux greffés du rein qui ont présenté une sporotrichose. De plus, les auteurs ont examiné les aspects généraux de la sporotrichose chez des greffés du rein signalés dans les publications. La sporotrichose, une infection fongique rare chez les greffés, s'observe surtout chez des greffés du rein qui ne reçoivent pas de prophylaxie antifongique. Des formes extracutanées de sporotrichose, sans manifestations cutanées et sans antécédents de lésions traumatiques, ont été décrites chez ces patients, mais elles sont difficiles à diagnostiquer. Les greffés du rein atteints de sporotrichose décrits dans le présent rapport ont été traités avec succès à l'aide d'un antifongique, y compris le désoxycholated d'amphotéricine B, les formulations lipidiques d'amphotéricine B, le fluconazole et l'itraconazole.

The impact of serum vancomycin levels and minimum inhibitory concentrations of methicillin-resistant Staphylococcus aureus on mortality in patients with nosocomial pneumonia.

BACKGROUND: Vancomycin is the treatment of choice for methicillin-resistant Staphylococcus aureus (MRSA) infections; however, treatment failure is not uncommon, even when the minimum inhibitory concentration (MIC) of the MRSA strain is within the susceptible range for vancomycin. OBJECTIVE: To describe the relationship between molecular markers such as the mecA and agrII genes, serum vancomycin levels and vancomycin MICs, and the 30-day mortality rate of patients with nosocomial MRSA pneumonia in an intensive care unit (ICU). METHODS: The present study was a prospective cohort study including all patients with MRSA hospital-acquired pneumonia or ventilator-associated pneumonia who were admitted to the ICU of a tertiary care hospital between June 2009 and December 2011. The MIC for vancomycin was determined using the E-test and broth microdilution methods. Variables analyzed included age, sex, comorbid conditions, serum vancomycin trough concentration, the Acute Physiology and Chronic Health Evaluation II (APACHE) score and the presence of the agrII gene. The primary outcome was mortality at 30 days. RESULTS: Thirty-six (42.4%) patients died within 30 days of the index MRSA culture. A multiple regression analysis that included the variables of MIC (determined using the E-test or broth microdilution methods), APACHE II score, serum vancomycin level and the presence of agrII revealed that only the APACHE II score was related to the 30-day mortality rate (P=0.03). Seven patients (9.0%) with isolates exhibiting an MIC ≥1.5 µg/mL according to the E-test method died, and nine patients (11.6%) survived (P=0.76). Of the patients for whom MICs were determined using the broth microdilution method, 11 (14.1%) patients with MICs of 1.0 µg/mL died, and 16 (20.5%) survived (P=0.92). The median APACHE II score of survivors was 22.5, and the median score of nonsurvivors was 25.0 (P=0.03). The presence of the agrII gene was not related to the 30-day mortality rate. CONCLUSIONS: Patients with severe hospital-acquired pneumonia presented with MRSA isolates with low to intermediate vancomycin MICs in the ICU setting. At the Hospital de Clínicas de Porto Alegre (Porto Alegre, Brazil), the 30-day mortality rate was high, and was similar among patients with severe hospital-acquired pneumonia infected with MRSA isolates that exhibited MICs of ≤1.5 µg/mL determined using the E-test method and ≤1.0 µg/mL determined using the broth microdilution method in those who achieved optimal serum vancomycin levels. The APACHE II scores which provides an overall estimate of ICU mortality were independently associated with mortality in the present study, regardless of the MICs determined. Molecular markers, such as the agrII gene, were not associated with higher mortality in the present study.

HISTORIQUE: La vancomycine est le traitement de première intention des infections par le Staphylococcus aureus résistant à la méthicilline (SARM), mais les échecs thérapeutiques ne sont pas rares, même lorsque la concentration minimale inhibitrice (CMI) de la souche de SARM se situe dans la plage susceptible de vancomycine. OBJECTIF: Décrire le lien entre les marqueurs moléculaires comme les gènes mecA et agrII, le taux de vancomycine sérique et la CMI de vancomycine, et le taux de mortalité au bout de 30 jours des patients atteints d'une pneumonie à SARM d'origine nosocomiale à l'unité de soins intensifs (USI). MÉTHODOLOGIE: La présente étude prospective de cohorte incluait tous les patients ayant une pneumonie à SARM d'origine nosocomiale ou d'une pneumonie acquise sous ventilation mécanique qui ont été hospitalisés à l'USI d'un hôpital de soins tertiaires entre juin 2009 et décembre 2011. Les chercheurs ont déterminé la CMI de la vancomycine au moyen des méthodes d'E-test et de microdilution en bouillon. Les variables qu'ils ont analysées sont l'âge, le sexe, les états comorbides, la concentration minimale de vancomycine sérique, le score APACHE (évaluation de physiologie aiguë et de maladie chronique II) et la présence du gène agrII. La mortalité au bout de 30 jours était l'issue primaire. RÉSULTATS: Trente-six patients (42,4 %)sont décédés dans les 30 jours suivant la culture de référence du SARM. Une analyse de régression multiple qui incluait les variables de la CMI (déterminée au moyen des méthodes d'E-test ou de microdilution en bouillon, le score APACHE II, le taux de vancomycine sérique et la présence du gène f agrII a révélé que seul le score APACHE II était lié au taux de mortalité au bout de 30 jours (P=0,03). Sept patients (9,0 %) dont les isolats présentaient une CMI d'au moins 1,5 µg/mL d'après la méthode d'E-test sont décédés, et neuf patients (11,6 %) ont survécu (P=0,76). Chez les patients dont la CMI a été déterminée au moyen de la méthode de microdilution en bouillon, 11 (14,1 %) ayant une CMI de 1,0 µg/mL sont décédés et 16 (20,5 %) ont survécu (P=0,92). Les survivants avaient un score APACHE II médian de 22,5, et les non-survivants, de 25,0 (P=0,03). La présence du gène agrII n'était pas liée au taux de décès au bout de 30 jours. CONCLUSIONS: Les patients ayant une grave pneumonie d'origine nosocomiale présentaient des isolats de SARM à la CMI faible à intermédiaire à la vancomycine à l'USI. Au Hospital de Clínicas de Porto Alegre (Porto Alegre, Brésil), le taux de mortalité au bout de 30 jours était élevé, tout comme chez les patients atteints d'une grave pneumonie d'origine nosocomiale infectés par des isolats du SARM dont la CMI était égale ou inférieure à 1,5 µg/mL d'après par la méthode d'E-test (ou égale ou inférieure à 1,0 µg/mL d'après la méthode de microdilution en bouillon) qui ont atteint des taux optimaux de vancomycine sérique. Les scores APACHE II qui procurent une évaluation globale de la mortalité à l'USI s'associaient de manière indépendante avec la mortalité dans la présente étude, quelle que soit la CMI établie. De plus, les marqueurs moléculaires, tels que le gène agrII, n'étaient pas liés à un taux de mortalité plus élevé y.

High prevalence of Pneumocystis jirovecii colonization in Brazilian cystic fibrosis patients.

A high rate of Pneumocystis jirovecii colonization was observed in Brazilian cystic fibrosis (CF) patients (13 out of 34; 38.2%) who underwent bronchoscopy between March 2006 and August 2009 at the Hospital de Clinicas de Porto Alegre, Brazil. Bronchoalveolar lavage samples were collected from these patients and studied by nested PCR amplification of the mitochondrial gene coding for the large subunit ribosomal RNA (mtLSUrDNA). The observed rate of colonization was higher than that reported in European populations. Genotypic characterization of the mtLSUrDNA locus revealed a predominance of the polymorphisms 85C/248C (genotype 1) and 85T/248C (genotype 3), with all samples possessing the wild-type genotype of dihydropteroate synthase. These findings suggest that cystic fibrosis patients could be an important reservoir and source of P. jirovecii infection. Further studies are required to elucidate the role of this common fungal colonization in the evolution of CF patients.

Intra-abdominal cryptococcosis by Cryptococcus gattii: case report and review.

Although abdominal cryptococcomas and visceral cryptococcal lymphadenitis as part of disseminated fungal infection have been reported mostly in HIV-infected patients, localized intra-abdominal involvement due to Cryptococcus gattii has not been previously described in non-HIV-infected patients. In general, a smaller proportion of cryptococcosis is caused by C. gattii. We report here on a type II diabetic HIV-negative patient who presented with a localized intra-abdominal cryptococcal mass due to C. gattii. In addition, we review the general aspects of intra-abdominal and gastrointestinal involvement by Cryptococcus neoformans in the literature and discuss the importance of identifying the C. neoformans varieties and C. gattii in routine laboratories.

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.

Pneumocystis jirovecii colonization in patients treated with infliximab.

BACKGROUND: Infliximab, a chimeric antitumour necrosis factor (TNF) monoclonal antibody, has become an established effective therapy for inflammatory rheumatic disease. However, TNF is a critical factor in host defence, and the suppression of its biological activity may be associated with the increased risk of opportunistic infections. The frequent use of infliximab in clinical practice has identified Pneumocystis jirovecii pneumonia (PcP) as a serious complication. Individuals colonized with Pneumocystis may be at high risk of development of PcP when they have undergone immunosuppression. Hence, we addressed the question of the frequency of Pneumocystis colonization among patients treated with infliximab. DESIGN: We examined 125 oropharyngeal washes collected from 78 individuals with rheumatoid arthritis, 30 with ankylosing spondylitis and 17 with psoriatic arthritis, half of them underwent infliximab therapy, using a real-time polymerase chain reaction assay that employs specific primers from a portion of the mitochondrial large-subunit rRNA gene of P. jirovecii. RESULTS: Pneumocystis jirovecii colonization was detected in 32 (25·6%) patients. In a multivariate regression model, only duration of infliximab treatment for more than 3 years and use of corticosteroid were significantly and independently associated with risk of Pneumocystis colonization. However, the effect of corticosteroid on P. jirovecii colonization rate was not linearly dose dependent as showed other logistic regression analysis. CONCLUSIONS: There is a high rate of P. jirovecii colonization among patients with rheumatologic diseases treated with infliximab. The identification of patients colonized by P. jirovecii before starting the treatment with infliximab could be a strategy for PcP prevention.

Gastrointestinal paracoccidioidomycosis: an overview.

Paracoccidioidomycosis is the most prevalent mycosis in Latin America. Although the lungs are the primary site of infection, physicians often see patients because of disseminated disease. Imported paracoccidioidomycosis has been described in different regions of the world in patients who lived in endemic areas. Gastrointestinal disease owing to P. brasiliensis is rarely recognized in life because of nonspecific clinical manifestations. Gastrointestinal disease can present as part of progressive dissemination of infection or as a result of local complications from a silent healing process. This review will summarize the salient features of gastrointestinal paracoccidioidomycosis.

Continuous infusion of amphotericin B deoxycholate: an innovative, low-cost strategy in antifungal treatment.

The combination of amphotericin B and sodium deoxycholate is the formulation most used in clinical practice. The development of new agents such as amphotericin with lipid formulations, caspofungin, voriconazole and other azolic derivatives, promoted alternatives to amphotericin B deoxycholate. However, because of the high cost of these new drugs, their use is difficult in a scenario of limited resources. A few strategies have been devised to make the use of amphotericin B deoxycholate less toxic. In this review, we seek to describe the accumulated knowledge about this molecule, with focus on its use in continuous infusion, which appears to be an alternative to reduce toxicity, while maintaining its clinical efficacy.

Histoplasma capsulatum sinusitis: case report and review.

Histoplasma capsulatum has not typically been associated with sinusitis in either immunocompetent or immunocompromised hosts. We report a case of sinusitis caused by H. capsulatum in a patient with chronic lymphocytic leukemia and discuss the reported cases of this rare clinical manifestation of histoplasmosis in the medical literature.

Evaluation of Identification and Susceptibility for Candida Spp. Isolated Directly from Positive Blood Culture Bottles.

Determination of the susceptibility profile of isolates of Candida from blood culture bottles is extremely important for correctly guiding patient pharmacotherapy. The aim of this study was to compare the results of analysis of Candida isolated directly from blood culture bottles by the VITEK MS MALDI-TOF identification system and the fluconazole disk diffusion assay with those of standard identification methods. Testing directly from the bottle allowed results 24 to 48 hours quicker than the standard method. There was a categorical agreement of 51.64% (47 of 91 samples) between the results of analysis directly from the bottle and analysis by the standard method. Regarding species identification, there was 96.15% agreement for Candida parapsilosis (25 of 26 samples). Categorical agreement between the rapid and standard disk diffusion methods was 95%, and the agreement between the rapid disk diffusion method and the broth microdilution method was 97%. Only minor errors in the rapid method were observed: 3 (5%) in the standard disk diffusion method and 2 (3%) in the broth microdilution method. Our study concluded that the rapid disk diffusion method for fluconazole is a fast, easy, reproducible, and consistent method. Its timely implementation for testing antifungal agents in the clinical microbiology laboratory can help reduce profile release times, thus helping to determine the most appropriate antifungal treatment.

[Mixed fungal infection in a diabetic patient]. / Infección múltiple fúngica en un paciente diabético.

BACKGROUND: Mixed fungal infections although undervalued, are more common than mentioned in the scientific literature. These infections have a poor prognosis for the patient. OBJECTIVES: We present an unusual case of a 61-year-old diabetic male who had a rhino-orbito-sinusal zygomycosis in 2001. After surgical debridement of the infected parts, along with antifungal therapy with liposomal amphotericin B, the patient started improving. Several years later the patient was hospitalized due to a similar problem and was diagnosed of rhino-orbito-cerebral zygomycosis. METHODS: In both episodes, a histopathological examination and cultures were performed on the sinus lesions. Tissue sections were stained with haematoxylin and eosin, Giemsa, periodic acid-Schiff (PAS) and Grocott's methenamine silver, and cultures specific for fungi were performed. RESULTS: The histopathology studies revealed the presence of bacteria, actinomyces and a mixed infection by at least four different fungi, all of them well differentiated by their morphology. Despite the rapid diagnosis the patient died due to spreading to the central nervous system. CONCLUSIONS: Mixed infections by fungi are rare, but due to the high incidence of immunodeficiencies they could occur more often than reported. We would like to alert on the possibility of acquired mixed infection by fungi which have shown to be high aggressive and have a worse prognostic in patients with underlying diseases.