The potential role of C-reactive protein in distinguishing cytomegalovirus from tuberculosis and bacterial infections in renal transplant recipients

Introduction: The delay in the diagnosis of infections can be deleterious in renal transplant recipients. Thus, laboratory tests leading to an earlier diagnosis are very useful for these patients. Purpose: To assess the behavior of C-reactive protein (CRP) in renal transplant recipients with a diagnosis of cytomegalovirus (CMV) infection, tuberculosis (TB) and bacterial infection (BI). Methods: A retrospective analysis of 129 patients admitted at our hospital, from 2006 to 2008 because of CMV, TB or BI, was carried out. Appropriate statistical analysis was done and values were expressed as medians, range. Results: When CRP levels were compared among the groups with CMV disease, TB or BI, the group with CMV disease presented lower levels of CRP (18.4 mg/L, 0.28-44 mg/L) than the TB and BI (p < 0.05) groups. The area under the receiver-operating characteristics curve, distinguishing CMV disease from TB/BI, was 0.96 (p < 0.0001), resulting in 100% sensitivity and 90.63% specificity to detect CMV disease when CRP < 44.5 mg/L. The subgroup analysis of CMV infection showed increasing levels of CRP (0.28, 16 and 29.5 mg/L) in the asymptomatic, symptomatic and invasive disease subgroups, respectively (p < 0.05). Conclusion: The measurement of CRP levels may be a useful tool for differentiating CMV infection from the other types (bacterial or TB) of infection in kidney transplant recipients.

Seasonal patterns of viral and bacterial infections among children hospitalized with community-acquired pneumonia in a tropical region

Community-acquired pneumonia (CAP) is a common cause of morbidity among children. Evidence on seasonality, especially on the frequency of viral and bacterial causative agents is scarce; such information may be useful in an era of changing climate conditions worldwide. To analyze the frequency of distinct infections, meteorological indicators and seasons in children hospitalized for CAP in Salvador, Brazil, nasopharyngeal aspirate and blood were collected from 184 patients aged < 5 y over a 21-month period. Fourteen microbes were investigated and 144 (78%) cases had the aetiology established. Significant differences were found in air temperature between spring and summer (p = 0.02) or winter (p < 0.001), summer and fall (p = 0.007) or winter (p < 0.001), fall and winter (p = 0.002), and on precipitation between spring and fall (p = 0.01). Correlations were found between: overall viral infections and relative humidity (p = 0.006; r = 0.6) or precipitation (p = 0.03; r = 0.5), parainfluenza and precipitation (p = 0.02; r = -0.5), respiratory syncytial virus (RSV) and air temperature (p = 0.048; r = -0.4) or precipitation (p = 0.045; r = 0.4), adenovirus and precipitation (p = 0.02; r = 0.5), pneumococcus and air temperature (p = 0.04; r = -0.4), and Chlamydia trachomatis and relative humidity (p = 0.02; r = -0.5). The frequency of parainfluenza infection was highest during spring (32.1%; p = 0.005) and that of RSV infection was highest in the fall (36.4%; p < 0.001). Correlations at regular strength were found between several microbes and meteorological indicators. Parainfluenza and RSV presented marked seasonal patterns.

Bacterial triggers and autoimmune rheumatic diseases

Autoimmune rheumatic diseases are generally considered as a multifactorial aetiology, mainly genetic susceptibility combined with environmental triggers of which bacteria are considered one of the most prominent. Among the rheumatic diseases where bacterial agents are more clearly involved as triggers are: reactive arthritis (ReA), rheumatic fever (RF) and Lyme disease. The role of bacterial infections in inducing other seronegative spondyloarthritis and antiphospholipid antibody syndrome has been hypothesized but is still not proven. The classic form of ReA is associated with the presence of HLA-B27 and is triggered by the urethritis or enteritis causing pathogens Chlamydia trachomatis and the enterobacteria Salmonella, Shigella, and Yersinia, respectively. But several other pathogens such as Brucella, Leptospira, Mycobacteria, Neisseria, Staphylococcus and Streptococcus have also been reported to cause ReA. RF is due to an autoimmune reaction triggered by an untreated throat infection by Streptococcus pyogenes in susceptible individuals. Carditis is the most serious manifestation of RF and HLA-DR7 is predominantly observed in the development of valvular lesions. Lyme disease is a tick-transmitted disease caused by the spirochete Borrelia burgdorferi. Knowledge is limited about how this spirochete interacts with human tissues and cells. Some data report that Borrelia burgdorferi can manipulate resident cells towards a pro- but also anti-inflammatory reaction and persist over a long period of time inside the human body or even inside human cells.

Metronidazole release using natural rubber latex as matrix

Natural Rubber Latex (NRL) can be used successfully in controlled release drug delivery due to their excellent matrix forming properties. Recently, NRL has shown to stimulate angiogenesis, cellular adhesion and the formation of extracellular matrix, promoting the replacement and regeneration of tissue. A dermatological delivery system comprising a topically acceptable, inert support impregnated with a metronidazole (MET) solution was developed. MET 2-(2- methyl- 5-nitro- 1H- imidazol- 1-yl) ethanol, has been widely used for the treatment of protozoa and anaerobic bacterial infections. MET is a nitroimidazole anti-infective medication used mainly in the treatment of infections caused by susceptible organisms, particularly anaerobic bacteria and protozoa. In a previous study, we have tested NRL as an occlusive membrane for GBR with promising results. One possible way to decrease the inflammatory process, it was incorporated the MET in NRL. MET was incorporated into the NRL, by mixing it in solution for in vitro protein delivery experiments. The solutions of latex and MET were polymerized at different temperatures, from -100 to 40 °C, in order to control the membrane morphology. SEM microscopy analysis showed that the number, size and distribution of pores in NRL membranes varied depending on polymerization temperature, as well as its overall morphology. Results demonstrated that the best drug-delivery system was the membrane polymerized at -100 °C, which does release 77,1% of its MET content for up 310 hours.

Perfil de prescrições e uso de antibióticos em infecções comunitárias

INTRODUÇÃO: O objetivo deste estudo foi conhecer os padrões de utilização de antibióticos no município de Sorocaba, avaliando o diagnóstico referido, a terapêutica empregada e sua utilização. MÉTODOS: Utilizou-se um instrumento de avaliação aplicado por 12 meses em usuários de antibióticos. Foram coletados dados de 403 usuários e referiram-se à: informações sociodemográficas e de saúde, diagnóstico e terapêutica. RESULTADOS: Encontrou-se grande utilização e a maior utilização prévia na faixa etária de 0-10 anos (p<0,05). As infecções com envolvimento pulmonar foram as mais citadas (p<0,05) e as penicilinas, os fármacos mais utilizados, presentes em 45,1% das prescrições. Tempo médio de terapêutica (8,9 dias) esteve abaixo do preconizado para otites. Em sinusites, 22% das prescrições não orientaram para o uso recomendado (10 dias). CONCLUSÕES: A inexistência e não utilização de protocolos terapêuticos têm resultado em grande diferença nos padrões de prescrição, levando a insucesso terapêutico e recidiva de infecções - situações frequentemente encontradas neste estudo.

Inpatient dermatological consultations in a university hospital

INTRODUCTION: Dermatology is primarily an outpatient specialty, but it also plays an important role in the care of inpatients. METHODS: We conducted a prospective study that recorded data from inpatient dermatology consultation request forms over a period of four months. The study evaluated 313 requests that led to 566 visits, 86 biopsies, 35 laboratory exams, 41 direct microscopic studies, 18 direct immunofluorescence analyses, 14 skin cultures and a few other exams. RESULTS: The most frequent requesting service was internal medicine (24%), followed by neurology (12%), cardiology (11%), infectious diseases and pediatrics (8% each) and psychiatry and general surgery (6% each). The most frequent diagnostic groups were infectious diseases (25%, divided into fungal infections (13%), bacterial infections (7%) and viral infections (5%)), eczemas (15%) and drug reactions (14%). To our knowledge, this is the first study to attempt to evaluate the impact of the consultations by asking multiple-choice questions that were analyzed by the authors. In 31% of the cases, the consultation was considered extremely relevant because it aided in managing the disease that led to admission or treated a potentially severe dermatological disease. In 58% of the cases, the consultation was considered important because it facilitated diagnosis and/or treatment of a dermatological disease that was unrelated to the reason for admission.

Características clínicas da fase aguda da infecção experimental de felinos pelo vírus da imunodeficiência felina

A infecção dos felinos pelo Vírus da Imunodeficiência Felina (FIV) resulta no desenvolvimento da síndrome de imunodeficiência dos felinos. Gengivite, perda de peso, linfadenomegalia generalizada, anemia, insuficiência renal crônica, complicações neurológicas, diarréia crônica e infecções bacterianas são encontradas frequentemente. A fase aguda da infecção pode ser assintomática, retardando o estabelecimento do diagnóstico e a implantação de medidas profiláticas para restringir o contágio e a transmissão do agente aos felinos suscetíveis. Com a finalidade de estudar as características clínicas da fase aguda da infecção, dez felinos jovens, sem definição racial, com oito meses de idade foram inoculados por via endovenosa com 1mL de sangue venoso de um gato portador do FIV subtipo B. A confirmação da infecção foi obtida através de teste sorológico em quatro e oito semanas pós-inoculação (p.i.) e por nested-PCR. Foram realizados hemogramas semanais, exame ultrassonográfico do abdômen quinzenais e exame oftalmológico mensal, durante doze semanas p.i. Discreta tendência a linfopenia na segunda semana p.i. e a neutropenia entre a quinta e sétima semana p.i., febre intermitente em alguns gatos, linfadenomegalia e hepato-esplenomegalia entre a quarta e a 12ª semana p.i. foram as alterações clínicas observadas. Apenas um gato apresentou uveíte unilateral direita. A fase aguda da infecção transcorreu com alterações clínicas inespecíficas. A linfadenomegalia e a hepato-esplenomegalia observadas no decorrer da infecção, refletindo hiperplasia linfóide, sugerem a necessidade de se realizar o teste sorológico para o FIV, em todos os gatos que se apresentarem com essas alterações, o que permitirá o diagnóstico precoce da infecção e a adoção de medidas profiláticas no sentido de minimizar a propagação da infecção.

Skewed Distribution of Circulating Activated Natural Killer T (NKT) Cells in Patients with Common Variable Immunodeficiency Disorders (CVID)

Common variable immunodeficiency disorder (CVID) is the commonest cause of primary antibody failure in adults and children, and characterized clinically by recurrent bacterial infections and autoimmune manifestations. Several innate immune defects have been described in CVID, but no study has yet investigated the frequency, phenotype or function of the key regulatory cell population, natural killer T (NKT) cells. We measured the frequencies and subsets of NKT cells in patients with CVID and compared these to healthy controls. Our results show a skewing of NKT cell subsets, with CD4+ NKT cells at higher frequencies, and CD8+ NKT cells at lower frequencies. However, these cells were highly activated and expression CD161. The NKT cells had a higher expression of CCR5 and concomitantly expression of CCR5+CD69+CXCR6 suggesting a compensation of the remaining population of NKT cells for rapid effector action.

Lack of galectin-3 alters the balance of innate immune cytokines and confers resistance to Rhodococcus equi infection

Galectin-3 is a p-galactoside-binding lectin implicated in the fine-tuning of innate immunity. Rhodococcus equi, a facultative intracellular bacterium of macrophages, causes severe granulomatous bronchopneumonia in young horses and immunocompromised humans. The aim of this study is to investigate the role of galectin-3 in the innate resistance mechanism against R. equi infection. The bacterial challenge of galectin-3-deficient mice (gal3(-/-)) and their wild-type counterpart (gal3(+/+)) revealed that the LD50 for the gal3(-/-) mice was about seven times higher than that for the gal3(+/+) mice. When challenged with a sublethal dose, gal3(-/-) mice showed lower bacteria counts and higher production of IL-12 and IFN-gamma production, besides exhibiting a delayed although increased inflammatory reaction. Gal3(-/-) macrophages exhibited a decreased frequency of bacterial replication and survival, and higher transcript levels of IL-1 beta, IL-6, IL-10, TLR2 and MyD88. R. equi-infected gal3(+/+) macrophages showed decreased expression of TLR2, whereas R. equi-infected gal3(-/-) macrophages showed enhanced expression of this receptor. Furthermore, galectin-3 deficiency in macrophages may be responsible for the higher IL-1 beta serum levels detected in infected gal3(-/-) mice. Therefore galectin-3 may exert a regulatory role in innate immunity by diminishing IL-1 beta production and thus affecting resistance to R. equi infection.

Procalcitonin is useful in identifying bacteraemia among children with pneumonia

Empirical antibiotic use is prescribed in managing children with pneumonia worldwide. We assessed the usefulness of procalcitonin (PCT) and interferon-alpha (IFN-alpha) in differentiating viral from bacterial pneumonia. Among 159 hospitalized children, pneumonia was diagnosed based on clinical complaints plus pulmonary infiltrate. Aetiology was investigated for 9 viruses and 4 atypical and 3 typical bacteria. PCT and IFN-alpha were measured in the serum sample collected on admission. Eight patients had bacteraemic infections, 38 had non-bacteraemic typical infections, and 19 patients had atypical bacterial infections. Viral and unknown aetiology was established in 57 (36%) and 34 (21%) cases, respectively. Three patients with bacterial infection without collected blood culture were excluded. IFN-alpha (IU/ml) was detectable in 20 (13%) cases. The difference among median PCT values of the bacteraemic (4.22; 1.56-7.56), non-bacteraemic typical bacterial (1.47; 0.24-4.07), atypical bacterial (0.18; 0.06-1.03) and only viral (0.65; 0.11-2.22) subgroups was significant (p = 0.02). PCT was >= 2 ng/ml in 52 (33%) cases. The presence of IFN-alpha was associated with PCT <2 ng/ml (90% vs. 64%, p = 0.02). The negative predictive value (95% confidence interval) of PCT >= 2 ng/ml was 95% (89-100%), 89% (78-100%), 93% (85-100%) for differentiation of bacteraemic from viral, atypical bacterial and non-bacteraemic typical bacterial infection, respectively, and 58% (49-68%) for differentiation between bacterial and viral infection. PCT may be useful in identifying bacteraemia among children hospitalized with community-acquired pneumonia. IFN-alpha was uncommonly detected.

A new model of outbred genetically selected mice which present a strong acute inflammatory response in the absence of complement component C5

Mice selected for a strong (AIRmax) or weak (AIRmin) acute inflammatory response present different susceptibilities to bacterial infections, autoimmune diseases and carcinogenesis. Variations in these phenotypes have been also detected in AIRmax and AIRmin mice rendered homozygous for Slc11a1 resistant (R) and susceptible (S) alleles. Our aim was to investigate if the phenotypic differences observed in these mice was related to the complement system. AIRmax and AIRmin mice and AIRmax and AIRmin groups homozygous for the resistance (R) or susceptibility (S) alleles of the solute carrier family 11a1 member (Slc11a1) gene, formerly designated Nramp-1. While no difference in complement activity was detected in sera from AIRmax and AIRmin strains, all sera from AIRmax Slc11a1 resistant mice (AIRmax(RR)) presented no complement-dependent hemolytic activity. Furthermore, C5 was not found in their sera by immunodiffusion and, polymerase chain reaction and DNA sequencing of its gene demonstrated that AIRmax(RR) mice are homozygous for the C5 deficient (D) mutation previously described in A/J. Therefore, the C5D allele was fixed in homozygosis in AIRmax(RR) line. The AIRmax(RR) line is a new experimental mouse model in which a strong inflammatory response can be triggered in vivo in the absence of C5.

Improved cure of bacterial vaginosis with single dose of tinidazole (2 g), Lactobacillus rhamnosus GR-1, and Lactobacillus reuteri RC-14: a randomized, double-blind, placebo-controlled trial

Bacterial vaginosis (BV) is the most prevalent vaginal infection worldwide and is characterized by depletion of the indigenous lactobacilli. Antimicrobial therapy is often ineffective. We hypothesized that probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 might provide an adjunct to antimicrobial treatment and improve cure rates. Sixty-four Brazilian women diagnosed with BV were randomly assigned to receive a single dose of tinidazole (2 g) supplemented with either 2 placebo capsules or 2 capsules containing L. rhamnosus GR-1 and L. reuteri RC-14 every morning for the following 4 weeks. At the end of treatment (day 28), the probiotic group had a significantly higher cure rate of BV (87.5%) than the placebo group (50.0%) (p = 0.001). In addition, according to the Gram-stain Nugent score, more women were assessed with ""normal`` vaginal microbiota in the probiotic group (75.0% vs. 34.4% in the placebo group; p = 0.011). This study shows that probiotic lactobacilli can provide benefits to women being treated with antibiotics for an infectious condition.

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.

Bacterial colonization in hemodialysis temporary dual lumen catheters: A prospective study

Aims. The use of hemodialysis temporary dual-lumen catheters is often complicated by infections, which may be a significant cause of death among patients with end stage renal disease (ESRD). The aim of this study was to assess the incidence of bacteremia and bacterial colonization related to non-tunneled, non-cuffed, dual-lumen temporary catheters in patients with ESRD submitted to hemodialysis. Methods. This study included 29 patients with ESRD. After catheter implantation, patients were monitored throughout the period of catheter permanence by means of blood samples collected weekly from a peripheral vein. Bacteria were isolated and identified according to CLSI recommendations. When catheters were removed for any reason, their tips were evaluated microbiologically. Results. A total of 194 blood samples from the 29 patients implanted with 55 catheters were analyzed. Of these, 15.5% (30 samples) demonstrated bacterial growth, principally Staphylococcus epidermidis (64.5%). Twenty patients (68.9%) presented at least one positive blood culture during follow-up. The median time for catheter colonization was 18.5 days (95% CI: 16.8-30.3). Of the 55 catheters implanted, 28 (50.9%) showed bacterial colonization, corresponding to 23.4 episodes/1000 catheter/days and 9.2 episodes of bacteremia /1000 catheter/days. Fifteen of 28 catheter tips analyzed showed bacterial growth (53.5%). In 14 of these (93.3%), there was agreement between the isolates from the catheter tip and blood cultures. Of 24 episodes of positive blood cultures from 20 different patients in 17 episodes (70.8%), the patients showed no clinical signs or symptoms of bacteremia. Conclusions. The high incidence of catheter colonization, the correlation between blood and catheter tip cultures, and the occurrence of frequent cases of asymptomatic bacteremia justify the proposal of routine peripheral blood collections to monitor patients undergoing hemodialysis with temporary dual-lumen catheters.

The role of respiratory viral infections among children hospitalized for community-acquired pneumonia in a developing country

We report an investigation for 16 bacteria and viruses among 184 children hospitalized with pneumonia in Salvador, Brazil. Etiology was established in 144 (78%) cases. Viral, bacterial, and mixed infections were found in 110 (60%), 77 (42%), and 52 (28%) patients, respectively. Rhinovirus (21%) and Streptococcus pneumoniae (21%) were the most common pathogens. Our results demonstrate the importance of viral and pneumococcal infections among those patients.