Tânia Mara Varejão Strabelli

Mychophenolate Mofetil Increased Chagas Disease Reactivation in Heart Transplanted Patients: Comparison Between Two Different Protocols

Heart transplantation (HT) remains the treatment of choice for advanced chagasic cardiomyopathy. New immunosuppression protocols have provided better control of rejection (RJ) and cardiac allograft vasculopathy. However, their influence on infection and Chagas disease reactivation (CDR) is not well established. The aim of this study was to compare the CDR rate in patients under two different immunosuppression protocols. We studied 39 chagasic patients who had undergone orthotopic HT between April, 1987 and June, 2004. They were divided into two groups, one taking azathioprine (group 1 = 24 patients) and the other taking mycophenolate mofetil (group 2 = 15 patients), in the standard doses (2 mg/kg/day and 2 g/day, respectively), beside prednisone and cyclosporine, in equivalent doses. The number of CDR and RJ episodes were analyzed in the first and second years after HT. CDR rates were 8%± 5% at 1 year and 12%± 6% at 2 years of follow‐up in group 1. Otherwise, patients in group 2 presented CDR rates of 75%± 10% and 81%± 9% at the same periods, respectively (p < 0.0001, hazard ratio = 6.06). When comparing RJ rates in the first year after HT, both groups had similar behavior under both immunosuppression protocols (p = 0.88). These data show that current prescribed doses of mycophenolate mofetil increase the early risk of CDR without changing RJ incidence in this period.

Cytomegalovirus infection in transplant recipients

Cytomegalovirus infection is a frequent complication after transplantation. This infection occurs due to transmission from the transplanted organ, due to reactivation of latent infection, or after a primary infection in seronegative patients and can be defined as follows: latent infection, active infection, viral syndrome or invasive disease. This condition occurs mainly between 30 and 90 days after transplantation. In hematopoietic stem cell transplantation in particular, infection usually occurs within the first 30 days after transplantation and in the presence of graft-versus-host disease. The major risk factors are when the recipient is cytomegalovirus seronegative and the donor is seropositive as well as when lymphocyte-depleting antibodies are used. There are two methods for the diagnosis of cytomegalovirus infection: the pp65 antigenemia assay and polymerase chain reaction. Serology has no value for the diagnosis of active disease, whereas histology of the affected tissue and bronchoalveolar lavage analysis are useful in the diagnosis of invasive disease. Cytomegalovirus disease can be prevented by prophylaxis (the administration of antiviral drugs to all or to a subgroup of patients who are at higher risk of viral replication) or by preemptive therapy (the early diagnosis of viral replication before development of the disease and prescription of antiviral treatment to prevent the appearance of clinical disease). The drug used is intravenous or oral ganciclovir; oral valganciclovir; or, less frequently, valacyclovir. Prophylaxis should continue for 90 to 180 days. Treatment is always indicated in cytomegalovirus disease, and the gold-standard drug is intravenous ganciclovir. Treatment should be given for 2 to 3 weeks and should be continued for an additional 7 days after the first negative result for viremia.

Bacterial and fungal pneumonias after lung transplantation.

OBJECTIVE The aim of this study was to evaluate the epidemiology of bacterial and fungal pneumonia in lung transplant (LT) recipients and to assess donor-to-host transmission of these microorganisms. MATERIALS AND METHODS We retrospectively studied all positive cultures from bronchoalveolar lavage (BAL) of 49 lung transplant recipients and their donors from August 2003 to April 2007. RESULTS There were 108 episodes of pneumonia during a medium follow-up of 412 days (range, 1-1328 days). The most frequent microorganisms were: Pseudomonas aeruginosa (n = 36; 33.3%), Staphylococcus aureus (n = 29; 26.8%), and Aspergillus spp. (n = 18; 16%). Other fungal infections were due to Fusarium spp., Cryptococcus neoformans, and Paracoccidioides brasiliensis. Of the 31 donors with positive BAL, 15 had S. aureus. There were 21 pretransplant colonized recipients (43%) and 16 of them had suppurative underlying lung disease. P. aeruginosa was the most frequent colonizing organism (59% of pretransplant positive cultures). There were 11 episodes of bacteremia and lungs were the source in 5 cases. Sixteen deaths occurred and 6 (37.5%) were due to infection. Statistical analyses showed association between pretransplant colonizing microorganisms from suppurative lung disease patients and pneumonias after lung transplantation (RR = 4.76; P = .04; 95% CI = 1.02-22.10). No other analyzed factor was significant. CONCLUSIONS Bacterial and fungal infections are frequent and contribute to higher mortality in lung transplant recipients. P. aeruginosa is the most frequent agent of respiratory infections. This study did not observe any impact of donor lung organisms on pneumonia after lung transplantation. Nevertheless, we demonstrated an association between pretransplant colonizing microorganisms and early pneumonias in suppurative lung transplant recipients.

Vasopressin versus Norepinephrine in Patients with Vasoplegic Shock After Cardiac Surgery: The VANCS Randomized Controlled Trial.

Background: Vasoplegic syndrome is a common complication after cardiac surgery and impacts negatively on patient outcomes. The objective of this study was to evaluate whether vasopressin is superior to norepinephrine in reducing postoperative complications in patients with vasoplegic syndrome. Methods: This prospective, randomized, double-blind trial was conducted at the Heart Institute, University of Sao Paulo, Sao Paulo, Brazil, between January 2012 and March 2014. Patients with vasoplegic shock (defined as mean arterial pressure less than 65 mmHg resistant to fluid challenge and cardiac index greater than 2.2 l · min−1 · m−2) after cardiac surgery were randomized to receive vasopressin (0.01 to 0.06 U/min) or norepinephrine (10 to 60 &mgr;g/min) to maintain arterial pressure. The primary endpoint was a composite of mortality or severe complications (stroke, requirement for mechanical ventilation for longer than 48 h, deep sternal wound infection, reoperation, or acute renal failure) within 30 days. Results: A total of 330 patients were randomized, and 300 were infused with one of the study drugs (vasopressin, 149; norepinephrine, 151). The primary outcome occurred in 32% of the vasopressin patients and in 49% of the norepinephrine patients (unadjusted hazard ratio, 0.55; 95% CI, 0.38 to 0.80; P = 0.0014). Regarding adverse events, the authors found a lower occurrence of atrial fibrillation in the vasopressin group (63.8% vs. 82.1%; P = 0.0004) and no difference between groups in the rates of digital ischemia, mesenteric ischemia, hyponatremia, and myocardial infarction. Conclusions: The authors’ results suggest that vasopressin can be used as a first-line vasopressor agent in postcardiac surgery vasoplegic shock and improves clinical outcomes.

Cytomegalovirus colitis in immunocompetent critically ill patients

OBJECTIVES Cytomegalovirus (CMV) is a ubiquitous virus and its reactivation may lead to CMV end-organ disease (CMV EOD) in immunocompromised patients and also in immunocompetent patients when they are critically ill. We aimed to investigate the frequency and the clinical features of proven CMV EOD in previously non-immunosuppressed patients admitted to our institution. METHODS From January 2000 to March 2013, the records of all patients with a histopathological diagnosis of CMV EOD at our teaching hospital were reviewed retrospectively. CMV EOD was diagnosed histologically by the identification of true cytomegalic viral inclusion involving endothelial, stromal, and/or epithelial cells on hematoxylin and eosin staining, and was subsequently confirmed by immunohistochemistry using specific antibody against CMV antigens. Immunocompromised patients were excluded. RESULTS CMV EOD manifesting as colitis was diagnosed in 14 previously immunocompetent intensive care unit (ICU) patients. The mean age of the patients was 64 years. All had co-morbidities and developed shock before CMV EOD. The major manifestation was gastrointestinal bleeding. The in-hospital mortality rate was 71.4% despite specific treatment with ganciclovir. CONCLUSIONS Despite being a rare condition, lower gastrointestinal bleeding in this profile of ICU patients could be the clinical manifestation of CMV colitis, and intensivists should be alert to this condition.

Staphylococcus aureus bacteremia: what is the impact of oxacillin resistance on mortality?

In order to analyse the impact of oxacillin resistance on the mortality of Staphylococcus aureus bacteremia, and to assess the antimicrobial susceptibility of community-acquired strains in two large university hospitals (the Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo and the Instituto Central do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo), we carried out a four-month-long prospective cohort study, which included 163 consecutive cases of S. aureus bacteremia. Of these, 140 (85.9%) were hospital-acquired, 9 (5.5%) were community-acquired and 14 (8.6%) were of indeterminate origin. No cases of community-acquired infection by oxacillin-resistant S. aureus was identified. Among hospital-acquired infections, oxacillin-resistant S. aureus was responsible for 64.3% of cases. Mortality up to 15 days after diagnosis of bacteremia was 27% (18/67) for infections caused by susceptible strains and 33% (32/96) for infections caused by oxacillin-resistant strains (p=0.10). The following independent risk factors for the acquisition of oxacillin-resistant S. aureus were identified in multiple logistical regression analysis: age over 60 years, use of corticoids; presence of a central vascular catheter, and previous use of antibiotics.

Infective endocarditis due to Bartonella spp. and Coxiella burnetii: experience at a cardiology hospital in Sao Paulo, Brazil.

Abstract:  Bartonella spp. and Coxiella burnetii are recognized as causative agents of blood culture–negative endocarditis (BCNE) in humans and there are no studies of their occurrences in Brazil. The purpose of this study is to investigate Bartonella spp. and C. burnetii as a causative agent of culture‐negative endocarditis patients at a cardiology hospital in São Paulo, Brazil. From January 2004 to December 2004 patients with a diagnosis of endocarditis at our Institute were identified and recorded prospectively. They were considered to have possible or definite endocarditis according to the modified Duke criteria. Those with blood culture–negative were tested serologically using the indirect immunofluorescent assay (IFA) for Bartonella henselae, B. quintana, and C. burnetii. IFA‐IgG titers >800 for Bartonella spp. and C. burnetii were considered positive. A total of 61 patients with endocarditis diagnosis were evaluated, 17 (27%) were culture‐negative. Two have had IgG titer greater than 800 (≥3,200) against Bartonella spp. and one against C. burnetii (phase I and II≥6,400). Those with Bartonella‐induced endocarditis had a fatal disease. Necropsy showed calcifications and extensive destruction of the valve tissue, which is diffusely infiltrated with mononuclear inflammatory cells predominantly by foamy macrophages. The patient with C. burnetii endocarditis received specific antibiotic therapy. Reports of infective endocartitis due to Bartonella spp. and C. burnetii in Brazil reveal the importance of investigating the infectious agents in culture‐negative endocarditis.

Endocardite por Coxiella burnetii (febre Q): doença rara ou pouco diagnosticada? Relato de caso

Q fever is a zoonosis of worldwide distribution that is caused by Coxiella burnetii. However, reports of this disease in Brazil are rare. Seroepidemiological studies have shown relatively high frequencies of antibodies against Coxiella burnetii in populations with occupational exposure. In humans, it can be manifested clinically as acute or chronic disease. Endocarditis is the most frequent chronic form of Q fever and the form with the greatest morbidity and mortality. We report a severe case of endocarditis due to Coxiella burnetii acquired in Brazil that had a fatal outcome, despite specific antibiotic therapy and valve surgery treatment.

Uso prático de um índice de risco de complicações após cirurgia cardíaca

BACKGROUND: The identification of risk factors for postoperative complications in cardiac patients with surgical indication may influence the therapeutic decision. OBJECTIVE: To describe the experience of a Cardiology hospital in the validation and practical use of a preoperative risk score. METHODS:To validate TUMANs score, chosen by considering morbidity and mortality, 300 adult patients were prospectively evaluated before elective cardiac surgery with the use of extracorporeal circulation (ECC). Patients with a score of zero to five were considered as being low risk; from six to nine, as moderate risk and a score higher than 10 as high risk for cardiac, infectious, neurological, pulmonary and renal complications, as well as death. RESULTS: The TUMAN classification showed a statistically significant association with the occurrence of infectious complications (p = 0.010), with the other postoperative complications (p = 0.034) and death (p <0.001). Pulmonary infection was the most frequent infectious complication (15.3%) and Infected patients had a longer ICU stay duration (p = 0.001) and more prolonged hospitalization (p = 0001). After routine use, a new review of 154 patients operated in 2005, confirmed the validity of this score in the identification of those with the highest risk of postoperative infections. CONCLUSION: TUMANs score was chosen as it uses variables that can be promptly obtained, classifies in the same system the most frequently performed surgeries and predicts risk of postoperative complications, in addition to mortality. Its continued use in this hospital has been able to identify the group of patients with increased risk of complications, especially infectious ones, although it was not useful in the prediction of individual risk.

Perioperative cefuroxime pharmacokinetics in cardiac surgery

OBJECTIVE The objective was to investigate the plasma levels and to compare the pharmacokinetics of cefuroxime during and after surgery in adult patients with elective indication for coronary artery bypass grafting. METHODS Seventeen patients received three 1.5-g bolus IV doses of cefuroxime, one every 12 hrs. Serial blood samples (3 mL) were collected 1, 3, 6, 9, and 12 hrs after the first dose (given during the intervention) and after the second and third doses (postsurgery). Blood samples were centrifuged and stored frozen until being assayed. For assessment of the cefuroxime plasma levels by liquid chromatography, only 200 microL of plasma were required. Determination of cefuroxime plasma levels was followed by a pharmacokinetic (PK)-modeling using PK Solutions 2.0 software. RESULTS The kinetic parameters obtained remained unchanged after the first, second, and the third dose as follows: elimination half-life: 1.8 h, 1.9 h, and 1.8 h; clearance: 1.4, 1.5, and 1.5 mL/min/kg, respectively. Additionally, the apparent volume of distribution did not change during and after the intervention: 0.19, 0.25, and 0.22 L/kg, after the first, second, and the third dose, respectively. Since the drug has a low volume of distribution, plasma levels obtained after a 1.5-g IV bolus injection of cefuroxime decreased rapidly due to the high plasma clearance, with a consequent short half-life. CONCLUSIONS The kinetic disposition of cefuroxime remains unaltered in patients undergoing coronary artery bypass grafting; to reduce the fluctuation in plasma concentrations so that the antibiotic prophylaxis in the peri-operative period is guaranteed, the dose regimen should be reviewed.