Érique José F. Peixoto de Miranda

High prevalence of the simultaneous excretion of polyomaviruses JC and BK in the urine of HIV-infected patients without neurological symptoms in São Paulo, Brazil

OBJECTIVE To evaluate the prevalence of the urinary excretion of BKV and JCV in HIV-infected patients without neurological symptoms. METHODS Urine samples from HIV-infected patients without neurological symptoms were tested for JC virus and BK virus by PCR. Samples were screened for the presence of polyomavirus with sets of primers complementary to the early region of JCV and BKV genome (AgT). The presence of JC virus or BK virus were confirmed by two other PCR assays using sets of primers complementary to the VP1 gene of each virus. Analysis of the data was performed by the Kruskal-Wallis test for numerical data and Pearson or Yates for categorical variables. RESULTS A total of 75 patients were included in the study. The overall prevalence of polyomavirus DNA urinary shedding was 67/75 (89.3%). Only BKV DNA was detected in 14/75 (18.7%) urine samples, and only JCV DNA was detected in 11/75 (14.7%) samples. Both BKV and JCV DNA were present in 42/75 (56.0%) samples. CONCLUSION In this study we found high rates of excretion of JCV, BKV, and simultaneous excretion in HIV+ patients. Also these results differ from the others available on the literature.

Role of quantitative CSF microscopy to predict culture status and outcome in HIV-associated cryptococcal meningitis in a Brazilian cohort

This retrospective study aimed to evaluate the clinical, laboratory, and quantitative cerebrospinal fluid (CSF) cryptococcal cell counts for associations with in-hospital outcomes of HIV-infected patients with cryptococcal meningitis. Ninety-eight HIV-infected adult patients with CSF culture-proven cryptococcal meningitis were admitted between January 2006 and June 2008 at a referral center in Sao Paulo, Brazil. Cryptococcal meningitis was the first AIDS-defining illness in 69%, of whom 97% (95/98) had known prior HIV infection. The median CD4+ T-cell count was 39 cells/μL (interquartile range 17-87 cells/μL). Prior antiretroviral therapy was reported in 50%. Failure to sterilize the CSF by 7-14 days was associated with baseline fungal burden of ≥ 10 yeasts/μL by quantitative CSF microscopy (odds ratio [OR] = 15.3, 95% confidence interval [CI] 4.1-56.7; P < 0.001) and positive blood cultures (OR = 11.5, 95% CI 1.2-109; P = 0.034). At 7-14 days, ≥ 10 yeasts/μL CSF was associated with positive CSF cultures in 98% versus 36% with <10 yeasts/μL CSF (P < 0.001). In-hospital mortality was 30% and was associated with symptoms duration for >14 days, altered mental status (P < 0.001), CSF white blood cell counts <5 cells/μL (P = 0.027), intracranial hypertension (P = 0.011), viral loads >50,000 copies/mL (P = 0.036), ≥ 10 yeasts/μL CSF at 7-14 days (P = 0.038), and intracranial pressure >50 cmH(2)0 at 7-14 days (P = 0.007). In conclusion, most patients were aware of their HIV status. Fungal burden of ≥ 10 yeasts/μL by quantitative CSF microscopy predicted current CSF culture status and may be useful to customize the induction therapy. High uncontrolled intracranial pressure was associated with mortality.

High rate of virologic suppression with darunavir/ritonavir plus optimized background therapy among highly antiretroviral-experienced HIV-infected patients: results of a prospective cohort study in São Paulo, Brazil

OBJECTIVES To assess the virologic and immunological response of darunavir/ritonavir plus optimized background therapy in highly antiretroviral-experienced HIV-infected patients in Brazil. METHODS Prospective cohort study carried out in a tertiary center in Sao Paulo, Brazil. Three-class antiretroviral-experienced patients with confirmed virologic failure began darunavir/ritonavir plus optimized background therapy (nucleoside/tide reverse transcriptase inhibitors ± raltegravir ± enfuvirtide ± maraviroc) after performing a genotypic resistance assay. Clinical evaluation and laboratory tests were collected at baseline and at weeks 12, 24, and 48. Multivariate analysis was performed to identify predictors of virologic response at 48 weeks. RESULTS Ninety-two patients were included. The median of darunavir resistant mutation was 1 (range 0-6). The median genotypic sensitivity score in the optimized background therapy was 2 (interquartile range 1-2). At week 48, 83% (95% CI: 75-90%) had an HIV RNA level <50 copies/mL and the median CD4 cell count was 301 (interquartile range 224-445) cells/mm(3). Baseline HIV RNA >100000 copies/mL was inversely associated with virologic success at week 48 (HR: 0.22, 95% CI: 0.06-0.85, p=0.028). CONCLUSIONS Darunavir/ritonavir plus optimized background therapy was a highly effective salvage regimen under clinical routine conditions in a referral center in Brazil, which is similar to the reported in high-income countries.

Immune reconstitution inflammatory syndrome associated with pulmonary sarcoidosis in an HIV-infected patient: an immunohistochemical study

Sarcoidosis has been rarely described in literature as a cause of interstitial pulmonary disease associated with AIDS. This study reports a case of immune reconstitution inflammatory syndrome associated with pulmonary sarcoidosis in a patient with a history of previous pulmonary tuberculosis concomitant with HIV infection. Results of the immunohistochemical study of samples from the resected right lower lobe are described. Pathological findings suggest a role of Th1, Th2 and Th17 response in IRIS associated sarcoidosis.

SUSCEPTIBILITY TO ANTIBIOTICS IN URINARY TRACT INFECTIONS IN A SECONDARY CARE SETTING FROM 2005-2006 AND 2010-2011, IN SÃO PAULO, BRAZIL: DATA FROM 11,943 URINE CULTURES

Introduction: Urinary tract infection (UTI) has a high incidence and recurrence, therefore, treatment is empirical in the majority of cases. Objectives: The aim of this study was to analyze the urine cultures performed at a secondary hospital, during two periods, 2005-2006 and 2010-2011, and to estimate the microbial resistance. Patients and methods: We analyzed 11,943 aerobic urine cultures according to basic demographic data and susceptibility to antibiotics in accordance with the Clinical and Laboratory Standards Institute (CLSI) for Vitek 1 and 2. Results: Most of our cohort consisted of young adult females that were seen at the Emergency Department. E. coli was the most frequent (70.2%) among the 75 species isolated. Resistance of all isolates was ≥ 20% for trimethoprim/sulfamethoxazole (TMP/SMX), norfloxacin, nitrofurantoin, cefazolin and nalidixic acid. Although E. coli was more susceptible (resistance ≥ 20% for TMP/SMX and nalidixic acid) among all of the isolates, when classified by the number and percentage of antibiotic resistance. Global resistance to fluoroquinolones was approximately 12%. Risk factors for E. coli were female gender and an age less than 65 years. Men and patients older than 65 years of age, presented more resistant isolates. Extended spectrum beta-lactamases (ESBL) were identified in 173 out of 5,722 Gram-negative isolates (3.0%) between 2010 and 2011. Conclusion: E. coli was the most frequent microbe isolated in the urine cultures analyzed in this study. There was a significant evolution of bacterial resistance between the two periods studied. In particular, the rise of bacterial resistance to fluoroquinolones was concerning.

Lack of Association Between Subclinical Hypothyroidism and Carotid-Femoral Pulse Wave Velocity in a Cross-Sectional Analysis of the ELSA-Brasil.

BACKGROUND There is little available data on carotid–femoral pulse wave velocity (cf-PWV) in subjects with subclinical hypothyroidism (SCH). We aimed to analyze the association between SCH and cf-PWV using baseline data from the Brazilian Longitudinal Study of Adult Health (ELSA–Brasil). METHODS We included subjects with normal thyroid function (thyrotropin (TSH): 0.4–4.0 mIU/l, and normal free thyroxine (FT4: 0.8–1.9ng/dl) and SCH (TSH > 4.0 mIU/l and normal FT4) evaluated for cf-PWV in a cross-sectional analysis. We excluded individuals using medications that interfere in thyroid function, antihypertensives, or diuretics, and subjects with chronic kidney disease or previous cardiovascular disease. Generalized linear and logistic regression models evaluated cf-PWV as a dependent variable and SCH as an independent variable, adjusted for cardiovascular risk factors. RESULTS Of 8,341 subjects (52.3% women), 7,878 (94.4%) were euthyroid and 463 (5.6%) showed SCH. The median age was 50 years (interquartile range: 44–56). The groups differed by age, sex, body mass index, glomerular filtration rate, and C-reactive protein. SCH was not associated with cf-PWV in the full-adjusted linear model (&bgr; = −0.039; P = 0.562) and with cf-PWV >75th percentile in the full-adjusted logistic model (odds ratio = 0.94; 95% confidence interval = 0.72–1.22). CONCLUSION In a large sample, SCH was not associated with increased cf-PWV.

Cuidados paliativos no paciente com HIV/AIDS internado na unidade de terapia intensiva.

Objective To describe the characteristics of patients with HIV/AIDS and to compare the therapeutic interventions and end-of-life care before and after evaluation by the palliative care team. Methods This retrospective cohort study included all patients with HIV/AIDS admitted to the intensive care unit of the Instituto de Infectologia Emílio Ribas who were evaluated by a palliative care team between January 2006 and December 2012. Results Of the 109 patients evaluated, 89% acquired opportunistic infections, 70% had CD4 counts lower than 100 cells/mm3, and only 19% adhered to treatment. The overall mortality rate was 88%. Among patients predicted with a terminally ill (68%), the use of highly active antiretroviral therapy decreased from 50.0% to 23.1% (p = 0.02), the use of antibiotics decreased from 100% to 63.6% (p < 0.001), the use of vasoactive drugs decreased from 62.1% to 37.8% (p = 0.009), the use of renal replacement therapy decreased from 34.8% to 23.0% (p < 0.0001), and the number of blood product transfusions decreased from 74.2% to 19.7% (p < 0.0001). Meetings with the family were held in 48 cases, and 23% of the terminally ill patients were discharged from the intensive care unit. Conclusion Palliative care was required in patients with severe illnesses and high mortality. The number of potentially inappropriate interventions in terminally ill patients monitored by the palliative care team significantly decreased, and 26% of the patients were discharged from the intensive care unit.

The long-term impact of a program to prevent central line-associated bloodstream infections in a surgical intensive care unit.

Central line-associated bloodstream infections (CLABSIs) are an important type of healthcare-associated infection in intensive care units (ICUs) with high mortality rates and high healthcare costs (1). According to the World Health Organization (WHO), CLABSIs are also the most common cause of healthcare-associated infections of the bloodstream (2). In the United States, the median rate ranges from 1.8 to 5.2 per 1,000 catheter days, according to the Centers for Disease Control and Prevention (CDC) (3). Each year, 100,000 cases and 30,000 deaths occur among patients in ICUs (4). In limited-resource countries, CLABSI rates range from 1.6 to 44.6 cases per 1,000 central line days in adult and pediatric ICUs and from 2.6 to 60.0 cases per 1,000 central line days in neonatal ICUs. CLABSIs are associated with significant additional mortality, with an odds ratio ranging from 2.8 to 9.5 (5). The optimal intervention method for reducing the incidence of CLABSIs has not been definitively identified, but some studies have proven that many practical, low-cost, low-technology educational measures related to inserting and maintaining central lines not only may be successful and effective but can also be sustained (3,4,6)–(10). Within this scenario, the CDC has recommended that an education program be implemented for healthcare personnel (6). The objective of this study was to describe the long-term impact of a program for decreasing CLABSI rates in a surgical ICU in Sao Paulo, Brazil.

Cryptococcal meningitis in HIV-negative patient with liver cirrhosis due to hepatitis C

©2011 Elsevier Editora Ltda. All rights reserved. Dear Editor, Before AIDS, cryptococcal meningitis, a disease caused by the basidiomycete fungus Cryptococcus neoformans, occurred at an incidence rate of one case per one million person-years.1 After AIDS, transplants and the use of immunosuppressive therapies, the incidence rate increased tenfold.1,2 We report a case of a 46-year-old male with a history of headache, confusion, nausea and vomiting for one month. The patient also had type 2 diabetes mellitus, in use of metformin, with good control, and liver cirrhosis due to hepatitis C. Treatment with pegylated interferon and ribavirin had begun two months before clinical presentation. After the second dose of interferon, pancytopenia was observed (hemoglobin: 10.9 g/dL, leukocytes: 3,660 cells/μL, platelets: 36,000/μL), decompensated cirrhosis and diabetes mellitus, characterized by moderate ascites and grade 3 hepatic encephalopathy, which overlapped the clinical symptoms described above, despite treatment with therapeutic doses of furosemide, spironolactone, lactulose, NPH and regular human insulin. Patient was listed for liver transplantation. Model of End-Stage Liver Disease (MELD) score equals 14 points. At presentation, cerebrospinal fluid (CSF) showed 21 cells/mL, total protein = 96 mg/dL, glucose = 34 mg/dL (serum glucose: 290 mg/dL), positive India ink staining and cryptococcal antingen titer greater than 1/1,024. Culture for C. neoformans was positive in the CSF, but negative in blood, bone marrow and ascites. Central nervous system computed tomography and magnetic resonance imaging has showed only mild supratentorial hydrocephalous. Patient evolved with intracranial hypertension (the first opening pressure: 36 cmH2O), without improvement by lumbar puncture. Ventriculoperitoneal shunt was performed after two units of apheresis platelets transfusion. The patient was treated with amphotericin B lipid complex 5 mg/kg/day for 30 days and 5-fluorocytosine 100 mg/kg/day for 14 days until three negative cultures for C. neoformans were obtained. During treatment, he presented elevated creatinine (2.0 mg/dL), but without requiring dialysis. There was no worsening of pancytopenia during treatment. Strict monitoring of renal and liver function and bone marrow was performed. Before starting fluconazole 800 mg/day, the patient has presented bloodstream infection associated with central venous catheter by Enterococcus faecalis, and despite appropriate treatment with vancomycin for 10 days, the patient progressed with septic shock syndrome and multiple organ dysfunction syndrome (MODS) and died 40 days after admission. Cryptococcosis affects the central nervous system in 51.3% of HIV-negative patients, after the introduction of azole agents in the market, and in 39% of patients with cirrhosis, as suggested by the two largest studies in the literature.3,4 The peritoneum is the site most associated with cryptococcal infection in cirrhotic patients (45%).4 In 306 HIV-negative patients, the underlying causes were steroids (28%), organ transplant (18%), chronic shortage of organs (liver, respiratory and renal) (18%), neoplasm (18%), rheumatic diseases (13%), and unknown risk factor (22%).3 Malnutrition, in addition to compromised phagocytosis, immunoglobulins and cellular immunity result in increased risk of cryptococcosis in cirrhotic patients.4 The case fatality rate associated with cryptococcosis in cirrhotic patients is 83%, 92% of which attributed to cryptococcosis. In 53% of cases, death occurs in the second week of diagnosis. Culture positivity is 67% and India ink in around 50% in cirrhotic patients and HIV-negative, respectively.1,2

Thyrotrophin levels and coronary artery calcification: Cross-sectional results of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

There is little information about the association between thyrotrophin (TSH) levels and coronary artery calcification (CAC). Our aim was to analyse the association between TSH quintiles and subclinical atherosclerosis measured by CAC, using baseline data from the Brazilian Longitudinal Study of Adult Health (ELSA‐Brasil).