Survival of HIV-infected patients after starting tuberculosis treatment: a prospective cohort study.

OBJECTIVES: To estimate the probability of survival and to evaluate risk factors for death in a cohort of persons living with human immunodeficiency virus (PLHIV) who had started tuberculosis (TB) treatment. METHODS: A prospective cohort study was conducted between June 2007 and December 2009 with HIV-infected patients who had started anti-tuberculosis treatment in the State of Pernambuco, Brazil. Survival data were analysed using the Kaplan-Meier estimator, the log-rank test and the Cox model. Hazard ratios and their respective 95%CIs were estimated. RESULTS: Of a cohort of 2310 HIV-positive individuals, 333 patients who had commenced treatment for TB were analysed. The mortality rate was 5.25 per 10,000 person-years (95%CI 4.15-6.63). The probability of survival at 30 months was 74%. Risk factors for death in the study population were being female, age ≥30 years, having anaemia, not using highly active antiretroviral therapy (HAART) during treatment for TB and disseminated TB. Protective factors for death were a CD4 lymphocyte count >200 cells/mm(3) and treatment for TB having started in an out-patient clinic. CONCLUSIONS: The use of HAART can prevent deaths among HIV-TB patients, corroborating the efficacy of starting HAART early in individuals with TB.

Comparative study of clinical characteristics of neutropenic and non-neutropenic adult cancer patients with bloodstream infections.

A total of 399 consecutive episodes of bloodstream infections in adult patients with haematologic malignancies and solid tumours were evaluated prospectively over a 26-month period, with the aim of determining the clinical characteristics and the microbiological profile of the patients relative to neutrophil count. The overall 30-day mortality rate was 32% (35% in non-neutropenic patients vs. 26% in neutropenic patients, p=0.05). Main diagnoses were solid tumours (33%) and lymphoma (29%). Most of the episodes of bloodstream infection (58%) occurred in non-neutropenic patients. Acute leukaemia and bone marrow transplantation predominated in the neutropenic group. Non-neutropenic patients tended to be older and to have a higher frequency of solid tumours and advanced or uncontrolled diseases. Indwelling central venous catheters were present in 51% of the episodes, with a predominance of long-term catheters in neutropenic haematologic patients. Concomitant infections were observed more frequently in non-neutropenic patients. There were 1,040 noninfectious comorbid conditions, most of which were present in non-neutropenic patients. The causative pathogens were predominantly gram-negative bacilli (56%). Escherichia coli and Klebsiella pneumoniae were isolated more frequently from neutropenic patients, while Staphylococcus aureus and Acinetobacter spp. were more frequent in non-neutropenic patients. Seventy-four percent of the episodes of candidaemia occurred in patients with central venous catheters, with non-albicans strains predominating. The results of this study highlight the heterogeneity of cancer patients with bloodstream infections and the value of stratifying risk factors and aetiologic agents according to neutrophil count.

Prospective evaluation of the epidemiology, microbiology, and outcome of bloodstream infections in adult surgical cancer patients.

The aim of this study was to describe the epidemiology and microbiology of bloodstream infections (BSIs) among adult surgical cancer patients and to determine independent factors that influence in-hospital mortality. The study enrolled 112 consecutive episodes of BSIs in adult surgical cancer patients during a 26-month period. The median age of the patients was 64.5 years, and crude in-hospital mortality was 19.6%. The median time from surgery to the index blood culture was 11 days and from index blood culture to death was 4.5 days. Seventy-five percent of the patients had an advanced tumor disease, 36.6% were under intensive care, and 68.7% had a central venous catheter in place at the time the bloodstream infection was diagnosed. Associated infected sites were present in 57.1% of the episodes. There were 328 noninfectious co-morbid conditions. Poor performance status, weight loss, hypoalbuminemia, and ventilatory support accounted for 67.4% of them. There was a predominance of aerobic gram-negative bacilli (62%), followed by gram-positive cocci (26.6%) and fungi (9.3%). The observed mortality rates associated with these organism groups were similar (23.6% vs 15% vs 28.6%, respectively; P=0.44). The most frequent organisms were Enterobacter spp., coagulase-negative staphylococci, Klebsiella spp., Acinetobacter spp., and fungi. Nonfermentative strains predominated in patients with catheters. Thirty-five (30.2%) pathogens were considered resistant. There was no significant difference in the mortality rate between patients with resistant and those with nonresistant organisms (20% vs 26%, respectively; P=0.49). Logistic regression analysis showed > or = 4 co-morbid conditions, advanced tumor, thoracic surgery, catheter retention, and pulmonary infiltrates as independent predictors of mortality. Medical and infection control measures addressing certain variables amenable to intervention might reduce the negative impact of postoperative infectious morbidity and mortality of BSIs in adult surgical cancer patients.

Bloodstream infection surveillance in a cancer centre: a prospective look at clinical microbiology aspects.

A prospective clinical and microbiological surveillance study was conducted during a 26-month period to evaluate consecutive malignancy or post-bone marrow transplant patients with positive blood cultures. The study included 859 episodes of bloodstream infection (BSI) in 719 patients. There were 6.9 BSI episodes/1000 patient-days. Overall mortality was 25%. The median age of patients was 43 years, with 71% of episodes occurring in patients aged > 18 years. Patients with underlying haematology malignancies accounted for 38.2% of the episodes. An indwelling central vein catheter was present in 61% of episodes. BSI origin was unknown in 27% of episodes, associated with other sites in 49.6%, and catheter-related in 23.4%. There were 638 concomitant infection sites, of which the most common were pulmonary (28.4%), urinary tract (14.8%), and non-surgical skin or soft tissue (9.7%). In total, 1039 microorganisms were isolated within 48 h of the first blood culture, of which Gram-negative bacilli accounted for 56%. Among Klebsiella pneumoniae and Escherichia coli isolates, 37.8% and 8.9%, respectively, produced extended-spectrum beta-lactamases. High rates of ceftazidime resistance were detected among Acinetobacter spp. (40%) and Enterobacter spp. (51.2%). E. coli and K. pneumoniae were isolated frequently from haematology patients, and Enterobacter spp. from solid tumour patients. E. coli, K. pneumoniae and Pseudomonas aeruginosa were isolated more often from neutropenic than from non-neutropenic patients. Oxacillin resistance was detected in 18.7% of Staphylococcus aureus isolates. It was concluded that continuous multidisciplinary surveillance of BSI is warranted in this high-risk group of patients in order to develop strategies for antimicrobial resistance control and treatment of infectious complications.

Prospective evaluation of the epidemiology, microbiology, and outcome of bloodstream infections in hematologic patients in a single cancer center.

Bloodstream infections (BSIs) have an important impact on the outcome of cancer patients. A prospective cohort study was undertaken at a referral cancer center in order to describe the clinical and microbiological characteristics of patients with hematologic malignancies and BSIs and to identify independent predictors associated with mortality. The study enrolled 110 consecutive BSI episodes during an 18-month period. Patients were monitored for 30 days after the last positive blood culture. There were 10.24 BSI episodes per 1,000 patient-days. The median age of the patients was 25 years. Most patients had acute leukemia ( n=72). The origin of the BSI was unknown in 43.6% of the episodes and was associated with known sites in 32.7%. There were 58 concomitant infectious sites (lungs, 43%, and soft tissue, 22.4%) and 195 noninfectious comorbid factors (poor performance status, 30.2%; undernourishment, 14.3%). The median neutrophil count was 215 cells/mm(3). Indwelling catheters were present in 70% of the episodes. The majority of isolates obtained within the first 48 h of the BSI episode (61%) were gram-negative rods. Overall mortality was 24.5%. Multivariate analysis using logistic regression showed relapsed leukemia, poor performance status, recent weight loss, and ventilatory failure requiring ventilatory support as independent predictors of mortality. Hematologic cancer patients with BSIs should be regarded as a distinct group of patients at high risk of death. The knowledge of variables amenable to intervention would help diminish or prevent serious medical complications.

Prophylactic donor lymphocyte infusions after moderately ablative chemotherapy and stem cell transplantation for hematological malignancies: high remission rate among poor prognosis patients at the expense of graft-versus-host disease.

We investigated the use of 'prophylactic' donor lymphocyte infusions (DLI) containing 1 x 107 CD3+ cells, given at 30, 60 and 90 days post-allogeneic blood and marrow transplantation (BMT), following conditioning with fludarabine 30 mg/m(2)/4 days and melphalan 70 mg/m(2)/2 days. GVHD prophylaxis consisted of cyclosporin A (CsA) 2 mg/kg daily with early tapering by day 60. Our goals were the rapid achievement of chimerism and disease control, providing an immunological platform for DLIs to treat refractory patients with hematological malignancies. Twelve heavily pre-treated patients with life expectancy less than 6 months were studied; none were in remission. Diagnoses were AML (n = 4), MDS (n = 1), ALL (n = 3), CML (n = 3) and multiple myeloma (n = 1). Response rate was 75%. Three patients are alive at a median of 450 days (range, 450-540). Two patients are in remission of CML in blast crisis and AML for more than 14 months. Median survival is 116 days (range, 25-648). Six patients received 12 DLIs; three patients developed acute GVHD after the first infusion and were excluded from further DLIs, but no GVHD occurred among patients receiving subsequent DLIs. One patient with CML in blast crisis went into CR after the first DLI. The overall incidence of acute GVHD was 70%. Primary causes of death were infections (n = 3), acute GVHD (n = 3), chronic GVHD (n = 1) and disease relapse (n = 2). We observed high response and chimerism rates at the expense of an excessive incidence of GVHD. DLI given at day +30 post BMT caused GVHD in 50% of the patients, and its role in this setting remains unclear.