A case of Haemophilus parainfluenzae pneumonia.
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A 41 year old woman presented with community acquired pneumonia (CAP) which failed to resolve following treatment with amoxycillin and cefaclor prior to referral. Quantitative culture of sputum revealed a pure growth of Haemophilus parainfluenzae and, following antibiotic susceptibility testing of the isolate, ciprofloxacin was prescribed resulting in resolution of the infection. Immunological investigations showed that the patient had a high titre of H parainfluenzae specific IgM. The combination of a pure growth of H parainfluenzae, a response to appropriate antimicrobial therapy, and the presence of a specific antibody response indicated that this organism had a pathogenic role in the patient's pneumonia and should be considered in the differential diagnosis of CAP. (+info)
Acquisition of expression of the Pseudomonas aeruginosa ExoU cytotoxin leads to increased bacterial virulence in a murine model of acute pneumonia and systemic spread.
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Pseudomonas aeruginosa is the nosocomial bacterial pathogen most commonly isolated from the respiratory tract. Animal models of this infection are extremely valuable for studies of virulence and immunity. We thus evaluated the utility of a simple model of acute pneumonia for analyzing P. aeruginosa virulence by characterizing the course of bacterial infection in BALB/c mice following application of bacteria to the nares of anesthetized animals. Bacterial aspiration into the lungs was rapid, and 67 to 100% of the inoculum could be recovered within minutes from the lungs, with 0.1 to 1% of the inoculum found intracellularly shortly after infection. At later time points up to 10% of the bacteria were intracellular, as revealed by gentamicin exclusion assays on single-cell suspensions of infected lungs. Expression of exoenzyme U (ExoU) by P. aeruginosa is associated with a cytotoxic effect on epithelial cells in vitro and virulence in animal models. Insertional mutations in the exoU gene confer a noncytotoxic phenotype on mutant strains and decrease virulence for animals. We used the model of acute pneumonia to determine whether introduction of the exoU gene into noncytotoxic strains of P. aeruginosa lacking this gene affected virulence. Seven phenotypically noncytotoxic P. aeruginosa strains were transformed with pUCP19exoUspcU which carries the exoU gene and its associated chaperone. Three of these strains became cytotoxic to cultured epithelial cells in vitro. These strains all secreted ExoU, as confirmed by detection of the ExoU protein with specific antisera. The 50% lethal dose of exoU-expressing strains was significantly lower for all three P. aeruginosa isolates carrying plasmid pUCP19exoUspcU than for the isogenic exoU-negative strains. mRNA specific for ExoU was readily detected in the lungs of animals infected with the transformed P. aeruginosa strains. Introduction of the exoU gene confers a cytotoxic phenotype on some, but not all, otherwise-noncytotoxic P. aeruginosa strains and, for recombinant strains that could express ExoU, there was markedly increased virulence in a murine model of acute pneumonia and systemic spread. (+info)
CXC chemokine receptor CXCR2 is essential for protective innate host response in murine Pseudomonas aeruginosa pneumonia.
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Pulmonary infection due to Pseudomonas aeruginosa has emerged as a leading cause of mortality. A vigorous host response is required to effectively clear the organisms from the lungs. This host defense is dependent on the recruitment and activation of neutrophils and macrophages. A family of chemotactic cytokines (chemokines) has been shown to participate in this protective response. In this study, we assessed the role of the ELR(+) (glutamic acid-leucine-arginine motif positive) CXC chemokines and their CXC chemokine receptor (CXCR2) in lung antibacterial host defense. The intratracheal administration of Pseudomonas to mice resulted in the time-dependent influx of neutrophils to the lung, peaking at 12 to 24 h after inoculation. The influx of neutrophils was associated with a similar time-dependent expression of the ELR(+) CXC chemokines, KC, macrophage inflammatory protein 2 (MIP-2), and lipopolysaccharide-induced CXC chemokine (LIX). Selective neutralization of MIP-2 or KC resulted in modest changes in neutrophil influx but no change in bacterial clearance or survival. However, neutralization of CXCR2 resulted in a striking increase in mortality, which was associated with a marked decrease in neutrophil recruitment and bacterial clearance. Conversely, the site-specific transgenic expression of KC resulted in enhanced clearance of bacteria after Pseudomonas challenge. This study indicates that ELR(+) CXC chemokines are critical mediators of neutrophil-mediated host defense in Pseudomonas pneumonia. (+info)
Pseudomonas aeruginosa cell-to-cell signaling is required for virulence in a model of acute pulmonary infection.
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Cell-to-cell signaling controls many virulence genes in Pseudomonas aeruginosa. We tested the virulence of las and rhl quorum-sensing mutants in neonatal mice. A lasI rhlI double mutant was nearly avirulent, and the respective single mutant strains were reduced in virulence compared with the wild-type strain. Quorum sensing plays a role in P. aeruginosa pneumonia in neonatal mice. (+info)
Community-acquired pneumonia: development of a bedside predictive model and scoring system to identify the aetiology.
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Although initial presentation has been commonly used to select empirical therapy in patients with community-acquired pneumonia (CAP), few studies have provided a quantitative estimation of its value. The objective of this study was to analyse whether a combination of basic clinical and laboratory information performed at bedside can accurately predict the aetiology of pneumonia. A prospective study was developed among patients admitted to the Emergency Department University Hospital Arnau de Vilanova, Lleida, Spain, with CAP. Informed consent was obtained from patients in the study. At entry, basic clinical (age, comorbidity, symptoms and physical findings) and laboratory (white blood cell count) information commonly used by clinicians in the management of respiratory infections, was recorded. According to microbiological results, patients were assigned to the following categories: bacterial (Streptococcus pneumoniae and other pyogenic bacteria), virus-like (Mycoplasma pneumoniae, Chlamydia spp and virus) and unknown pneumonia. A scoring system to identify the aetiology was derived from the odds ratio (OR) assigned to independent variables, adjusted by a logistic regression model. The accuracy of the prediction rule was tested by using receiver operating characteristic curves. One hundred and three consecutive patients were classified as having virus-like (48), bacterial (37) and unknown (18) pneumonia, respectively. Independent predictors related to bacterial pneumonia were an acute onset of symptoms (OR 31; 95% CI, 6-150), age greater than 65 or comorbidity (OR 6.9; 95% CI, 2-23), and leukocytosis or leukopenia (OR 2; 95% CI, 0.6-7). The sensitivity and specificity of the scoring system to identify patients with bacterial pneumonia were 89% and 94%, respectively. The prediction rule developed from these three variables classified the aetiology of pneumonia with a ROC curve area of 0.84. Proper use of basic clinical and laboratory information is useful to identify the aetiology of CAP. The prediction rule may help clinicians to choose initial antibiotic therapy. (+info)
Evaluation of vaccines to prevent childhood pneumonia: lessons relevant to planning tuberculosis vaccine trials.
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Bacterial pneumonia in children is usually caused by one of the two leading pathogens, Streptococcus pneumoniae (pneumococcus) and Haemophilus influenzae, either type b (Hib) or nonencapsulated types. Hib conjugate vaccines suitable for use in infants have been available for about a decade, and experience with a trial of one of these vaccines in Africa showed that the vaccines can prevent Hib pneumonia, as well as other manifestations of Hib disease. It also showed that vaccine trials can provide useful estimates of the role of Hib in childhood pneumonia. Trials of pneumococcal conjugate vaccines that are currently under way have been designed to estimate disease burden and efficacy. A major risk of vaccine trials that use bacteriologic end points is that the vaccine may affect the diagnostic test itself, creating a misleading impression of efficacy. Trials of future tuberculosis vaccines are discussed in light of these experiences. It is important that the trials are designed to measure the effect on all clinical disease, as well as strict microbiological end points. The existence of bacille Calmette-Guerin (BCG) complicates future trials, and such trials should take into account possible nonspecific effects of BCG in addition to its effect on tuberculosis. (+info)
Local antibiotic guidelines for adult community-acquired pneumonia (CAP): a survey of UK hospital practice in 1999.
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We investigated the guidelines in British hospitals for the management of adults admitted with community-acquired pneumonia (CAP). A questionnaire was sent to one consultant respiratory physician in each of the 263 hospitals in the British Thoracic Society (BTS) Directory of Training Posts and Services. Two hundred and thirteen (81%) responses were received: 178 (84%) had written CAP guidelines, of which 123 (69%) printed copies were received. For non-severe CAP a single antibiotic (74% of guidelines-most frequently amoxycillin or ampicillin) was the usual recommendation with the combination of a beta-lactam and a macrolide the second most frequent (24%). The latter combination was recommended for severe CAP in 81% of guidelines. Clostridium difficile-associated diarrhoea had influenced guideline recommendations, or was commented on as a concern, in 18% of responses. Written guidelines for antibiotic therapy in adults with CAP exist in most British hospitals and follow broadly the 1993 BTS guidelines, although combination therapy is used not infrequently for non-severe CAP. (+info)
Interleukin-10 gene therapy-mediated amelioration of bacterial pneumonia.
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Respiratory infection by Actinobacillus pleuropneumoniae causes a highly pathogenic necrotizing pleuropneumonia with severe edema, hemorrhage and fever. Acute infection is characterized by expression of inflammatory cytokines, including interleukin-1 (IL-1), IL-6 and IL-8. To determine if high level production of inflammatory cytokines contributed to disease pathogenesis, we investigated if inhibiting macrophage activation with adenovirus type 5-expressed IL-10 (Ad-5/IL-10) reduced the severity of acute disease. Porcine tracheal epithelial cells infected with Ad-5/IL-10 produced bioactive human IL-10. When pigs were intratracheally infected with A. pleuropneumoniae, pigs pretreated with Ad-5/IL-10 showed a significant reduction in the amount of lung damage when compared to adenovirus type 5-expressing beta-galactosidase (Ad-5/beta-Gal)-treated and untreated pigs. In addition, serum zinc levels were unchanged, the lung weight/body weight ratio (an indicator of vascular leakage) was significantly reduced, and lung pathology scores were reduced. Myeloperoxidase activity in lung lavage fluid samples, an indicator of neutrophil invasion, was decreased to levels similar to that seen in pigs not infected with A. pleuropneumoniae. Reduction in inflammatory cytokine levels in lung lavage fluid samples correlated with the clinical observations in that pigs pretreated with Ad-5/IL-10 showed a corresponding reduction of IL-1 and tumor necrosis factor (TNF) compared with untreated and Ad-5/beta-Gal-treated pigs. IL-6 levels were unaffected by pretreatment with Ad-5/IL-10, consistent with observations that IL-6 was not derived from alveolar macrophages. Since inflammatory cytokines are expressed at high levels in acute bacterial pleuropneumonia, these results indicate that macrophage activation, involving overproduction of IL-1 and TNF, is a prime factor in infection-related cases of massive lung injury. (+info)