Invasive Fungal Disease in Renal Transplant Recipients at a Brazilian Center: Local Epidemiology Matters.

INTRODUCTION: Invasive fungal disease (IFD) is an important complication after solid organ transplantation (SOT). A marked geographic variation in the epidemiology of IFD after kidney transplantation (KT) has been suggested by the results of previous studies. Nevertheless, data from Latin American centers are scarce. OBJECTIVE: This study sought to describe the epidemiology of IFD at a Brazilian KT center. METHODS: This study was a retrospective single-center cohort study that included patients who underwent KT between 1998 and 2009 and were followed up until July 2015. Cases of simultaneous kidney-pancreas transplantation were excluded. The primary study outcome was the occurrence of proven or probable IFD. RESULTS: Among 908 KT recipients, 44 cases of IFD occurred in 42 patients (4.6%). Cryptococcus spp. infection, diagnosed in 16 cases (36.3%), was the leading cause of IFD, followed by histoplasmosis in 10 cases (22.7%) and invasive candidiasis in 10 (22.7%). Sporotrichosis, mucormycosis, invasive aspergillosis, pulmonary Cladophialophora sp. infection, trichosporonosis and Saccharomyces cerevisiae fungemia occurred in 1 recipient each (2.3%). Two additional (4.5%) cases of unspecified mold infections were identified by histopathological analysis. Most cases of IFD (67%) occurred later than 6 months after transplantation. Previous use of antilymphocyte antibodies (P = .008) and corticosteroid pulse therapy (P < .001) were more frequent among cases of IFD occurring within the first 6 months after transplantation. CONCLUSIONS: The epidemiology of IFD in this Brazilian cohort was characterized by a large predominance of late infections and a high proportion of cases of cryptococcosis and histoplasmosis. These results highlight the considerable geographic variability of IFD epidemiology after KT.

Quality of antenatal care as a risk factor for early onset neonatal infections in Rio de Janeiro, Brazil

Background: Neonatal infection is a serious public health problem. The aim of this study was to assess the influence of the antenatal care on the risk of early-onset neonatal healthcare associated infection in two Brazilian maternities. Methods: Cohort study - Newborns admitted at two public neonatal intensive care units from 2008 to 2009 were included in the study. Data on antenatal and perinatal variables were collected from maternal prenatal cards and medical charts. Newborns were actively surveyed for early-onset neonatal healthcare associated infection, defined as a neonatal infection diagnosed within 48 h after birth. Multiple logistic regression was used to assess variables independently associated with early-onset neonatal healthcare associated infection. Results: 561 neonate-mother pairs were included in the study. Early-onset neonatal health-care associated infection was diagnosed in 283 neonates (51%), an incidence rate of 43.5/1000 live births. Neonates whose mothers had less then six antenatal visits were under risk significantly higher for early-onset neonatal healthcare associated infection (OR = 1.69, 95% CI = 1.11-2.57), after adjusting for birth weight, membranes ruptured for >18 h, maternal complications during delivery, maternal infection at admission, and hospital where patients received care. Conclusions: The risk of neonatal early-onset neonatal healthcare associated infection was significantly associated with insufficient number of antenatal care visits. Further studies assessing the quality of antenatal care and targeting its improvement are warranted. .

Quality of antenatal care as a risk factor for early onset neonatal infections in Rio de Janeiro, Brazil.

BACKGROUND: Neonatal infection is a serious public health problem. The aim of this study was to assess the influence of the antenatal care on the risk of early-onset neonatal healthcare associated infection in two Brazilian maternities. METHODS: Cohort study - Newborns admitted at two public neonatal intensive care units from 2008 to 2009 were included in the study. Data on antenatal and perinatal variables were collected from maternal prenatal cards and medical charts. Newborns were actively surveyed for early-onset neonatal healthcare associated infection, defined as a neonatal infection diagnosed within 48h after birth. Multiple logistic regression was used to assess variables independently associated with early-onset neonatal healthcare associated infection. RESULTS: 561 neonate-mother pairs were included in the study. Early-onset neonatal healthcare associated infection was diagnosed in 283 neonates (51%), an incidence rate of 43.5/1000 live births. Neonates whose mothers had less then six antenatal visits were under risk significantly higher for early-onset neonatal healthcare associated infection (OR=1.69, 95% CI=1.11-2.57), after adjusting for birth weight, membranes ruptured for >18h, maternal complications during delivery, maternal infection at admission, and hospital where patients received care. CONCLUSIONS: The risk of neonatal early-onset neonatal healthcare associated infection was significantly associated with insufficient number of antenatal care visits. Further studies assessing the quality of antenatal care and targeting its improvement are warranted.

Outcome of bacteremia caused by extended-spectrum ß-lactamase-producing Enterobacteriaceae after solid organ transplantation.

INTRODUCTION: Although infection with extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-E) has been recognized as an important cause of morbidity after solid organ transplantation, there are limited data on the outcome of this complication among transplant recipients. The objective of this study was to describe the outcome and factors associated with mortality among recipients of abdominal solid organ transplants with bloodstream infection caused by ESBL-E. PATIENTS AND METHODS: This study was a retrospective analysis of a case series of patients who had bacteremia caused by ESBL-E after undergoing renal or liver transplantation between January 2000 and September 2008 at a university-affiliated hospital in Rio de Janeiro, Brazil. The primary end point of the study was death within 30 days of the diagnosis of bacteremia. RESULTS: During the study period, 997 subjects underwent kidney (759 patients) or liver (238 patients) transplantation. Fifty-four episodes of bacteremia caused by ESBL-E were diagnosed in 39 patients (4%). Mortality after the first episode of ESBL-E bacteremia was 26% (10 deaths). In multiple logistic regression analysis, the Pitt bacteremia score (P = .005) and being on mechanical ventilation at the time of infection diagnosis (P = .02) were the only variables associated with mortality. Thirteen episodes of recurrent bacteremia occurred in 8 (28%) of the 29 patients who survived the first episode. Two (25%) of these 8 patients died during the course of a recurrent episode. CONCLUSIONS: Bacteremia caused by ESBL-E was associated with high mortality and high risk of recurrence. Factors associated with clinical severity at the time of infection diagnosis were the main predictors of mortality.

Results of implementation of preventive recommendations for tuberculosis after renal transplantation in an endemic area.

This retrospective cohort study assessed the results of the implementation of preventive recommendations for tuberculosis (TB) among renal transplant recipients in an endemic area (Rio de Janeiro, Brazil). Subjects were defined as at high risk for TB if they had latent tuberculosis infection (LTBI), reported recent close contact with individuals with TB or received a graft from a donor with LTBI. A 6-month course of isoniazid preventive therapy (IPT) was targeted to high-risk subjects. The study end point was TB confirmed by culture. Altogether, 535 patients were included. Median follow-up was 59 months. The overall cumulative incidence of TB was 2.1% while among the 274 patients in whom the preventive protocol was fully implemented, the incidence was only 0.7%. The incidence of TB among 75 high-risk recipients not treated with isoniazid (7%) was significantly higher than that observed in 209 untreated low-risk patients (1%, p = 0.006) and in 65 high-risk subjects that received IPT (no case, p = 0.03). In conclusion, the implementation of preventive recommendations for TB in an endemic area allowed the appropriate discrimination between high- and low-risk renal transplant recipients and was associated with long-term reduction in the incidence of this complication among high-risk subjects.

Severe infection in a lung transplant recipient caused by donor-transmitted carbapenem-resistant Acinetobacter baumannii.

We describe a case of proven donor transmission of carbapenem-resistant Acinetobacter baumannii, which resulted in severe infectious complications after lung transplantation. A single bla(OXA-23) positive strain, belonging to a new multilocus sequence type (ST231), was isolated from donor and recipient, who died 65 days after transplantation. This report highlights the current challenges associated with the potential transmission of multidrug-resistant infections through organ transplantation.

Urinary tract infections in renal transplant recipients: virulence traits of uropathogenic Escherichia coli.

BACKGROUND: Urinary tract infection (UTI) is the most common infectious complication after renal transplantation. Most infections are caused by uropathogenic Escherichia coli (UPEC). There are limited data on the prevalence of virulence traits among UPEC isolated from renal transplant recipients. This study compared the phenotypic and genotypic profiles of UPEC strains isolated from recipients with those from control patients. METHODS: E coli isolates that caused UTI in recipients versus nonimmunosuppressed control patients were characterized according to phylogenetic group and the presence of urovirulence genes pap1/pap2; sfa1/sfa2; afa1/afa2; aer1/aer2; and cnf1/cnf2. RESULTS: Thirty-six UPEC isolates from recipients and another 27 from control individuals were included in the study. The proportion of episodes of pyelonephritis in recipients (50%) versus control subjects (41%) was similar (P = .46). However, secondary bacteremia was observed only among recipients (n = 8; P < .001). There was no significant difference in the distribution of phylogenetic groups or the prevalence of analyzed virulence traits between UPEC isolated from the 2 groups. Nevertheless, strains associated with secondary bacteremia in recipients showed a higher prevalence of mannose-resistant hemagglutination (P = .013). CONCLUSION: The phenotypic and genotypic characteristics of UPEC isolated from recipients were similar to those from control patients at a tertiary care center. Secondary bacteremia in recipients was associated with a higher prevalence of mannose-resistant hemagglutination.

Effectiveness of highly active antiretroviral therapy using non-brand name drugs in Brazil.

In Brazil, HIV-infected individuals receive drugs (including non-brand name drugs which comprise locally produced generics and drugs that have not been tested in bioequivalence trials) free of charge from the government. The objective of the present study was to evaluate the effectiveness of highly active antiretroviral therapy (HAART) in Rio de Janeiro, Brazil, where non-brand drugs are widely used. For this purpose, we estimated the proportion of subjects with virologic failure (plasma HIV viral load greater than 400 copies/mL at 6 months after initiation of treatment). This was a retrospective cohort study of drug-naive HIV-infected subjects who initiated HAART. Subjects were included in the analysis if they were 18 years of age or older, were treatment naive, started HAART with a minimum of 3 drugs, and had available information on blood plasma HIV-1 viral load after 6 months on therapy. All subjects used antiretrovirals in dosing regimens recommended by the Brazilian National Advisory Committee for Antiretroviral Therapy. Chart reviews were conducted in three settings: at two public health outpatient units, at one clinical trial unit and at one private office. No comparisons of the effectiveness of non-brand name with the effectiveness of brand name drugs were made. We present results for 485 patients; of these, 354 (73%), 55 (11%), and 76 (16%) were seen at the public health outpatient units, private office, and clinical trial unit, respectively. Virologic failure was observed in 119 (25%) of the subjects. This study demonstrates the effectiveness of HAART in a setting where non-brand name drugs are widely used.

Effectiveness of highly active antiretroviral therapy using non-brand name drugs in Brazil

In Brazil, HIV-infected individuals receive drugs (including non-brand name drugs which comprise locally produced generics and drugs that have not been tested in bioequivalence trials) free of charge from the government. The objective of the present study was to evaluate the effectiveness of highly active antiretroviral therapy (HAART) in Rio de Janeiro, Brazil, where non-brand drugs are widely used. For this purpose, we estimated the proportion of subjects with virologic failure (plasma HIV viral load greater than 400 copies/mL at 6 months after initiation of treatment). This was a retrospective cohort study of drug-naive HIV-infected subjects who initiated HAART. Subjects were included in the analysis if they were 18 years of age or older, were treatment naive, started HAART with a minimum of 3 drugs, and had available information on blood plasma HIV-1 viral load after 6 months on therapy. All subjects used antiretrovirals in dosing regimens recommended by the Brazilian National Advisory Committee for Antiretroviral Therapy. Chart reviews were conducted in three settings: at two public health outpatient units, at one clinical trial unit and at one private office. No comparisons of the effectiveness of non-brand name with the effectiveness of brand name drugs were made. We present results for 485 patients; of these, 354 (73 percent), 55 (11 percent), and 76 (16 percent) were seen at the public health outpatient units, private office, and clinical trial unit, respectively. Virologic failure was observed in 119 (25 percent) of the subjects. This study demonstrates the effectiveness of HAART in a setting where non-brand name drugs are widely used.

Outcome of infections caused by multiple drug-resistant bacteria in liver transplant recipients.

OBJECTIVE: To evaluate the impact of infections caused by multiple-drug-resistant (MDR) bacteria on the clinical outcome of liver transplant recipients. METHODS: Retrospective study including all episodes of bacterial infection diagnosed in patients undergoing liver transplantation from January 19, 1999, to June 30, 2002. The diagnosis of bacterial infection required microbiological documentation. Mortality associated with episodes of infection by MDR bacteria was compared to that observed after antibiotic-susceptible bacterial infections. RESULTS: Among 99 patients undergoing liver transplantation during the study period, there were 57 episodes of bacterial infections. Gram-negative bacilli were the predominant etiologic agents (76%) and Pseudomonas aeruginosa was the most frequent bacterial species found in these cases (23 isolates, 28%). Thirty-six episodes of infection (63%) were caused by MDR bacteria. Mean time after transplantation to the diagnosis of infection was 17 days. Mortality associated with episodes of MDR bacterial infections (nine deaths, 25%) was not significantly different from that observed during episodes of antibiotic-susceptible bacteria (five deaths, 24%; P =.92). CONCLUSION: These data suggest that resistance to multiple antimicrobial agents does not have an impact on the mortality associated to bacterial infections in liver transplant recipients.

Chemoprophylaxis for tuberculosis and survival of HIV-infected patients in Brazil.

OBJECTIVE: To study the impact of chemoprophylaxis for tuberculosis on the survival of HIV-infected patients with a positive tuberculin skin test. DESIGN: Prospective observational cohort study. SETTING: Outpatient clinic of a university hospital, in Rio de Janeiro, Brazil. PATIENTS: Two-hundred and ninety-seven patients with a positive tuberculin skin test (reaction > or = 5mm) who were admitted to the cohort between January 1991 and December 1994. Follow-up ended on September 30, 1998. INTERVENTION: The use of chemoprophylaxis for tuberculosis. MAIN OUTCOME MEASURES: Death was the primary outcome variable. The occurrence of tuberculosis was studied as a secondary outcome. Cox regression models were used in these analyses. RESULTS: The median follow-up time was 43.6 months. Chemoprophylaxis was used by 128 (43%) of the patients. The use of chemoprophylaxis was associated with a reduction in risk for tuberculosis (hazard ratio, 0.38; 95% confidence interval, 0.14-1.04; P = 0.05). In a regression model adjusted for baseline CD4 cell count, chemoprophylaxis was associated with longer survival (hazard ratio, 0.24; 95% confidence interval, 0.09-0.65; P = 0.002). CONCLUSIONS: Anti-tuberculosis chemoprophylaxis was associated with a substantially prolonged survival among purified protein derivative-positive HIV-infected patients in Brazil. These data have important implications for the clinical care of patients with HIV infection in areas of the world with a high prevalence of Mycobacterium tuberculosis infection.

HIV disease progression and V3 serotypes in Brazil: is B different from B-Br?

HIV-1 serotype B-Br (GWGR) is rare in the United States but predominates in Brazil. Differences in prognosis for patients infected with serotype B-Br or serotype B (GPGR) have not been addressed previously. In this prospective cohort study, we compared the rate of disease progression between patients infected with the HIV-1 V3 serotype B or B-Br in Brazil. Progression to AIDS or death was studied by the Kaplan-Meier and Cox proportional hazard methods. Among 445 HIV-infected patients who were tested with a specific enzyme immune assay, 204 (46%) had serotype B-Br infection and 127 (28%) had serotype B infection. Both groups were similar with regard to baseline CD4+ cell count, serum HIV RNA viral load, initial clinical stage, and the proportions who were treated with antiretroviral drugs. Patients with serotype B infection were significantly younger (p = 0.005) and tended to report homosexual behavior more frequently (p = 0.08). Mean follow-up was 30 +/- 13.5 months. During the study period, 41 (32%) patients infected with serotype B and 44 (22%) infected with serotype B-Br developed AIDS (p = 0.03). In a regression model adjusted for age and risk factor for HIV infection, progression to AIDS was faster in patients infected with serotype B (hazard ratio [HR] 1.59; 95% CI, 1.03-2.43; p = 0.03). A similar trend was observed in a model that considered AIDS or death as the outcome (HR, 1.43; 95% CI, 0.95-2.0; p = 0.09). These results suggest that patients infected with closely related HIV-1 serotypes may differ in the rate of progression to AIDS and indicate that serotype should be taken into account in HIV vaccine studies in Brazil.

Willingness to participate in HIV vaccine trials among men who have sex with men in Rio de Janeiro, Brazil. Projeto Praça Onze Study Group.

Evaluation of HIV vaccines requires high-risk individuals willing to participate in a vaccine trial. We investigated the willingness to participate in HIV vaccine trials of initially HIV-seronegative homosexual men enrolled in an HIV seroincidence cohort study. Of 815 initially HIV-seronegative participants, 569 (69.8%) reported willingness to participate in an HIV vaccine trial. Altruism was the primary reason given for wanting to participate. Fear of HIV infection from the study's immunizations and a vaccine-induced positive HIV test result were the main reasons for not wanting to participate. Of the 34 study subjects who eventually had HIV seroconversion, 29 (85%) had indicated a willingness to participate. In a univariate analysis, factors associated with willingness to participate included HIV seroconversion during follow-up (odds ratio [OR]. 2.6; p =.04), low educational level (OR, 1.6; p =.005), low family income (p =.02), and exchanging sex for housing, food, or clothing (OR 6.1; p =.005). Students were less likely to be willing to participate in a trial (OR, 0.7; p = .03), as well as those who reported sex at the first encounter (OR, 0.7; p = .05). In a multivariate analysis, low education level, infection with Condyloma, and exchanging sex for housing, food, or clothing were positively associated with willingness to participate, whereas being a student and reporting sex at first encounter were negatively associated. In general, factors indicative of high-risk of HIV infection were associated with a higher willingness. These data demonstrate that this high-risk homosexual male cohort has a high willingness to participate in HIV vaccine trials.

Gender and survival after AIDS in Rio de Janeiro, Brazil.

The relation between gender and survival after a diagnosis of AIDS was studied in a cohort of patients with HIV infection in Rio de Janeiro, Brazil. During the study period, 124 of 617 patients (20%) developed AIDS. Of this group, 91 patients were men and 33 were women. There were no gender related differences regarding the access to antiretroviral therapy or to prophylaxis for Pneumocystis carinii pneumonia. Survival was shorter among women (hazard ratio [HR] = 4.43; p < .001) after adjustment for age and AIDS-defining condition. Adjusting for CD4+ and CD8+ counts reduced the difference between genders (HR = 3.33; p = .017). These results suggest that survival after an AIDS diagnosis may be shorter among women than men in Brazil. Further studies are needed to determine the factors that may be negatively influencing the prognosis of women with AIDS in Brazil.

PIP: The association between gender and survival after AIDS diagnosis was investigated through use of data from an ongoing HIV cohort study in Rio de Janeiro, Brazil. Among the 617 patients (425 men and 192 women) enrolled in this study, 124 AIDS cases were diagnosed during 1991-95. There was no significant difference between the proportion of men (21%) and women (17%) who progressed to AIDS. The median age at AIDS diagnosis was 35 years for men and 38 years for women. CD4 and CD8 counts were available at the time of AIDS diagnosis for 57 men and 20 women. Median CD4 counts were similar for men and women (86/cu. mm and 95/cu. mm, respectively), but women had significantly lower mean CD8 counts (494/cu. mm) than men (870/cu. mm). There were 33 deaths (36%) among men and 17 (52%) among women. The median survival time after AIDS diagnosis was 20.4 months for men and 11 months for women. Survival remained shorter among women after adjustment for age and AIDS-defining condition (hazard ratio, 4.43). Adjustment for CD4 and CD8 counts reduced the difference between genders (hazard ratio, 3.33). The observed difference in survival between men and women could be due, in part, to reduced T-cell homeostasis at the time of AIDS diagnosis in women.