Ligia C. Pierrotti

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.

Rhodotorula spp. isolated from blood cultures: clinical and microbiological aspects

The emergence of less common fungal pathogens has been increasingly reported in the last decade. We describe 25 cases of Rhodotorula spp. isolated from blood cultures at a large Brazilian tertiary teaching hospital from 1996-2004. We also investigated the in vitro activity of four antifungal drugs, using a standardized method. The median age of patients was 43 years. The majority of patients (88%) had a central venous catheter (CVC) and 10 (40%) were recipients of a bone marrow transplant. The episode was classified as a bloodstream infection (BSI) in 80% of the patients. Amphotericin B deoxycholate was the most common antifungal used and CVC was removed in 89.5% of the patients. Death occurred in four patients (17.4%), all classified as BSI. All strains were identified as R. mucilaginosa by conventional methods. Misidentification of the species was observed in 20% and 5% of the strains with the Vitek Yeast Biochemical Card and API 20C AUX systems, respectively. Amphotericin B demonstrated good in vitro activity (MIC50/90, 0.5 microg/ml) and the MICs for fluconazole were high for all strains (MIC50/90, >64 microg/ml).

Treatment of KPC-producing Enterobacteriaceae: suboptimal efficacy of polymyxins

Treatment of Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae infections (KPC-EI) remains a challenge. Combined therapy has been proposed as the best choice, but there are no clear data showing which combination therapy is superior. Our aim was to evaluate the effectiveness of antimicrobial regimens for treating KPC-EI. This was a retrospective cohort study of KPC-EI nosocomial infections (based on CDC criteria) between October 2009 and June 2013 at three tertiary Brazilian hospitals. The primary outcomes were the 30-day mortality for all infections and the 30-day mortality for patients with bacteraemia. Risk factors for mortality were evaluated by comparing clinical variables of survivors and nonsurvivors. In this study, 118 patients were included, of whom 78 had bacteraemia. Catheter-related bloodstream infections were the most frequent (43%), followed by urinary tract infections (n = 27, 23%). Monotherapy was used in 57 patients and combined treatment in 61 patients. The most common therapeutic combination was polymyxin plus carbapenem 20 (33%). Multivariate analysis for all infections (n = 118) and for bacteremic infections (n = 78) revealed that renal failure at the end of treatment, use of polymyxin and older age were prognostic factors for mortality. In conclusion, polymyxins showed suboptimal efficacy and combination therapy was not superior to monotherapy.

Immunogenicity and reactogenicity of 2009 influenza A (H1N1) inactivated monovalent non-adjuvanted vaccine in elderly and immunocompromised patients.

Background Immunosuppressed individuals present serious morbidity and mortality from influenza, therefore it is important to understand the safety and immunogenicity of influenza vaccination among them. Methods This multicenter cohort study evaluated the immunogenicity and reactogenicity of an inactivated, monovalent, non-adjuvanted pandemic (H1N1) 2009 vaccine among the elderly, HIV-infected, rheumatoid arthritis (RA), cancer, kidney transplant, and juvenile idiopathic arthritis (JIA) patients. Participants were included during routine clinical visits, and vaccinated according to conventional influenza vaccination schedules. Antibody response was measured by the hemagglutination-inhibition assay, before and 21 days after vaccination. Results 319 patients with cancer, 260 with RA, 256 HIV-infected, 149 elderly individuals, 85 kidney transplant recipients, and 83 with JIA were included. The proportions of seroprotection, seroconversion, and the geometric mean titer ratios postvaccination were, respectively: 37.6%, 31.8%, and 3.2 among kidney transplant recipients, 61.5%, 53.1%, and 7.5 among RA patients, 63.1%, 55.7%, and 5.7 among the elderly, 59.0%, 54.7%, and 5.9 among HIV-infected patients, 52.4%, 49.2%, and 5.3 among cancer patients, 85.5%, 78.3%, and 16.5 among JIA patients. The vaccine was well tolerated, with no reported severe adverse events. Conclusions The vaccine was safe among all groups, with an acceptable immunogenicity among the elderly and JIA patients, however new vaccination strategies should be explored to improve the immune response of immunocompromised adult patients. (ClinicalTrials.gov, NCT01218685)

Prevalence of antibodies to human herpesvirus-8 in populations with and without risk for infection in São Paulo State

Human herpesvirus 8 (HHV-8) is a newly described herpesvirus that is etiologically associated with all forms of Kaposis sarcoma (KS). Seroepidemiological studies have shown high prevalence rates of HHV-8 antibodies among men who have sex with men (MSM) and AIDS patients, African children, Brazilian Amerindians, and elderly individuals in certain regions of Europe. The aim of the present study was to determine the prevalence of HHV-8 antibodies in healthy children and young adults from different cities in São Paulo State, and in a population at high risk for HHV-8 infection: HIV-negative MSM, and AIDS patients with and without KS. Antibodies to HHV-8 latency-associated nuclear antigen and lytic-phase antigens were detected by immunofluorescence assays. In 643 healthy children and young adults from the general population attending a vaccination program for yellow fever in ten different cities in São Paulo State, the prevalence of HHV-8 antibodies detected by the presence of latent or lytic antigens ranged from 1.0 to 4.1% in the different age groups (mean=2.5%). In the MSM group, the prevalence was 31/95 (32.6%). In the group of patients with AIDS, the prevalence was 39.2% (51/130) for non-KS patients and 98.7% (77/78) for AIDS patients with the diagnosis of KS confirmed by histopathological examination. We conclude that HHV-8 has a restricted circulation among healthy children and young adults in the general population of São Paulo State and a high prevalence among MSM and AIDS patients.

Detection of human herpesvirus 8 DNA and antibodies to latent nuclear and lytic-phase antigens in serial samples from aids patients with Kaposi's sarcoma.

Abstract Background : human herpesvirus 8 (HHV-8) have recently implicated in the etiology of Kaposis sarcoma (KS), but the pathophysiologic and immunologic interactions between HHV-8 and the human host are incompletely understood. Objective : this paper intends to present partial results of a follow-up study of KS patients, designed to investigate HHV-8 viremia and antibody response. Methods : ninety-six paired serial samples (PBMCs and sera) were obtained from 12 aids patients with KS who received HAART prior or just after entry in the study. HHV-8 DNA was detected by nested-PCR and antibodies to HHV-8 latent nuclear antigen (LANA) and lytic antigen by immunofluorescence assay (IFA). Results : HHV-8 DNA was detected in 33.3% of the first PBMC samples. Among the eight PCR negative patients, four presented positive samples during the follow-up and four remained negative. Five patients had intermittent viremia. Fifteen of the 96 PBMC samples were PCR positive (15.6%). Four of 39 samples (10.2%) from patients classified as stadio II and 11 of the 53 samples (20.7%) from patients in stadio IV were PCR positive ( P =0.2). Six patients (50%) had anti-LANA antibodies at the entry in the study. Among the six seronegative patients, two seroconverted 2 months later and four patients remained seronegative during the 5–8 months of follow-up. All patients had anti-lytic antibodies since the first sample. Conclusion : the presence of HHV-8 viremia could be related to the severity of KS and could be intermittent even under HAART. A longer follow-up is needed to confirm these results.

Clinical features and outcomes of tuberculosis in kidney transplant recipients in Brazil: a report of the last decade

Among kidney transplant recipients (KTRs), tuberculosis is one of the most common opportunistic infections and is associated with high morbidity and mortality. The aim of this study was to describe the incidence, clinical features, and prognosis of tuberculosis in KTRs.

First report of a clinical isolate of Candida haemulonii in Brazil

The spectrum of Candida species associated with invasive fungal infections is evolving. New microbiology diagnostic tools, the increasing number of immunosuppressed patients with invasive devices and the use of prophylaxis with fluconazole could contribute to this phenomenon (1). In recent years, an increasing number of rare species with reduced susceptibility to antifungal molecules have been described, including C. ciferrii, C. inconspicua, C. guilliermondii, C. humicola, C. lambica, C. lipolytica, C. norvegensis, C. palmioleophila, C. rugosa, C. valida, C. fermentati, and C. lusitaniae (2)-(5). Data from the SENTRY Antimicrobial Surveillance Program-Fungal Objective (5) concerning bloodstream infections from 2008 and 2009 show that 4.5% of 348 episodes from 10 centers in Latin America were caused by species other than C. albicans, C. glabrata, C. parapsilosis, C. tropicalis, and C. krusei. In 1984, Lavarde et al. (6) reported the first clinical isolate of C. haemulonii from a blood culture. Since then, rare cases of human infections with C. haemulonii have been reported worldwide, including central venous catheter (CVC)-related bloodstream infections in patients from Argentina, Korea, and China (7)-(11); in preterm neonates receiving parenteral nutrition in Kuwait (12); and in a 37-year-old French patient with osteomyelitis of the left hallux (13). This pathogen has not been identified in previous reports of candidemia from Brazil (14)-(17). The present paper reports for the first time a case of fungemia caused by C. haemulonii in a tertiary hospital in the city of Sao Paulo. Clinical features and laboratory analyses, including phenotypic and molecular identification and antifungal susceptibility testing (AST), are described.

A Double-Blinded, Prospective Study to Define Antigenemia and Quantitative Real-Time Polymerase Chain Reaction Cutoffs to Start Preemptive Therapy in Low-Risk, Seropositive, Renal Transplanted Recipients

Background Cytomegalovirus (CMV) disease occurs in 16% to 20% of low-risk, CMV-positive renal transplant recipients. The cutoffs for quantitative real-time polymerase chain reaction (qPCR) or phosphoprotein (pp65) antigenemia (pp65emia) for starting preemptive therapy have not been well established. Methods We measured qPCR and pp65emia weekly from day 7 to day 120 after transplantation, in anti-CMV immunoglobulin G–positive donor and recipient pairs. Patients and physicians were blinded to the test results. Suspicion of CMV disease led to the order of new tests. In asymptomatic viremic patients, the highest pp65emia and qPCR values were used, whereas we considered the last value before diagnosis in those with CMV disease. Results We collected a total of 1,481 blood samples from 102 adult patients. Seventeen patients developed CMV disease, 54 presented at least one episode of viremia that cleared spontaneously, and 31 never presented viremia. Five patients developed CMV disease after the end of the study period. The median (95% confidence interval) pp65emia and qPCR values were higher before CMV disease than during asymptomatic viremia (6 [9–82] vs. 3 [1–14] cells/106 cells; P<0.001 and 3,080 [1,263–15,605] vs. 258 [258–1,679] copies/mL; P=0.008, respectively). The receiver operating characteristic curve showed that pp65emia 4 cells/106 cells or greater showed a sensitivity and specificity to predict CMV disease of 69% and 81%, respectively (area, 0.769; P=0.001), with a positive predictive value of 37% and a negative predictive value of 93%. For qPCR 2,000 copies/mL or higher, the positive predictive value and negative predictive value were 57% and 91%, respectively (receiver operating characteristic area, 0.782; P=0.000). Conclusion With these cutoffs, both methods are appropriate for detecting CMV disease.

Infection Related to Implantable Central Venous Access Devices in Cancer Patients: Epidemiology and Risk Factors

OBJECTIVE To describe the epidemiology of infections related to the use of implantable central venous access devices (CVADs) in cancer patients and to evaluate measures aimed at reducing the rates of such infections. DESIGN Prospective cohort study. SETTING Referral hospital for cancer in São Paulo, Brazil. PATIENTS We prospectively evaluated all implantable CVADs employed between January 2009 and December 2011. Inpatients and outpatients were followed until catheter removal, transfer to another facility, or death. METHODS Outcome measures were bloodstream infection and pocket infection. We also evaluated the effects that the creation of a multidisciplinary team for CVAD care, avoiding in-hospital implantation of CVADs, and limiting CVAD insertion in neutropenic patients have on the rates of such infections. RESULTS During the study period, 966 CVADs (mostly venous ports) were implanted in 933 patients, for a combined total of 243,792 catheter-days. We identified 184 episodes of infection: 154 (84%) were bloodstream infections, 21 (11%) were pocket infections, and 9 (5%) were surgical site infections. During the study period, the rate of CVAD-related infection dropped from 2.2 to 0.24 per 1,000 catheter-days ([Formula: see text]). Multivariate analysis revealed that relevant risk factors for such infection include surgical reintervention, implantation in a neutropenic patient, in-hospital implantation, use of a cuffed catheter, and nonchemotherapy indication for catheter use. CONCLUSIONS Establishing a multidisciplinary team specifically focused on CVAD care, together with systematic reporting of infections, appears to reduce the rates of infection related to the use of these devices.