Acute Bacterial Pneumonia Research Articles

The changing spectrum of pulmonary disease in patients with HIV infection on antiretroviral therapy

The pulmonary manifestations of HIV disease in 2005 can be divided into two sets of presentations. For patients who do not have access to care, and who are not taking antiretroviral or chemoprophylactic drugs, opportunistic infections and neoplasms continue to occur. Pulmonary disease caused by Streptococcus pneumoniae, Pneumocystis carinii (now known as Pneumocystis jiroveci pneumonia; PCP), Mycobacterium tuberculosis, lymphoma, and Kaposi’s sarcoma present much as they did in the 1980s. Management has improved in terms of new diagnostic, therapeutic, and preventive strategies, as reviewed in guidelines issued jointly by the National Institutes of Health, Centers for Disease Control and Prevention, and Infectious Disease Society of America (available online at http://www.aidsinfo.nih.gov).

Actinomycoses and Nocardia pulmonary infections

Actinomycosis and nocardiosis are uncommon pulmonary infections with distinct morphologic features. Both infections most commonly present as chronic, debilitating illnesses with radiographic manifestations simulating lung cancer or tuberculosis. Immunocompromised hosts, however, may develop fulminant disease resembling acute bacterial pneumonia. The purpose of this review is primarily to review the clinical features, diagnosis, and management of actinomycosis and nocardiosis. Treatment of actinomycosis is usually simple, requiring long-term, high-dose intravenous penicillin. Short-course chemotherapy, however, has recently been reported to be successful. Pulmonary nocardiosis is an important cause of opportunistic infection in immunosuppressed patients, and the incidence of this infection is increasing. The sulfonamides are still first-line agents in the management of nocardiosis, but resistance is most common among N. farcinica and N. otitidiscaviarum isolates. Carbapenems should be used as an alternative treatment for severely ill patients. Broth microdilution, E-test (AB Biodisk, Solna, Sweden) and BACTEC (Becton Dickinson, Sparks, Maryland, USA) radiometric method may be more useful in the routine clinical laboratory for antimicrobial testing of aerobic actinomycetes. The practical distinction between the two diseases is in the matter of therapy. Diagnosis depends on a high degree of suspicion so as to alert the microbiology and pathology laboratories to employ special methods to identify the organisms. Early recognition and prompt treatment usually results in complete cure.

Influenza diagnosis and management

Influenza is already an important cause of illness and death each year in Australia and the impact of future pandemics will be many times greater. Compared with other respiratory viral illnesses, influenza is more severe in itself as well as being more likely to result in complications. These range from milder conditions such as otitis media and sinusitis to acute bronchitis, viral pneumonia and bacterial pneumonia. There are also a number of less common non-respiratory complications, including myocarditis, encephalitis, rhabdomyolysis and nephritis. In addition, a substantial component of severe disease and death from influenza is due to exacerbations of pre-existing cardiac conditions, respiratory disease or diabetes. Accurate diagnosis is the basis of the proper management of patients, understanding of the epidemiology of this virus, and detecting the entry and spread of new influenza strains.

Protective effect of endogenous β-adrenergic tone on lung fluid balance in acute bacterial pneumonia in mice

Some investigators have reported that endogenous beta-adrenoceptor tone can provide protection against acute lung injury. Therefore, we tested the effects of beta-adrenoceptor inhibition in mice with acute Escherichia coli pneumonia. Mice were pretreated with propranolol or saline and then intratracheally instilled with live E. coli (10(7) colony-forming units). Hemodynamics, arterial blood gases, plasma catecholamines, extravascular lung water, lung permeability to protein, bacterial counts, and alveolar fluid clearance were measured. Acute E. coli pneumonia was established after 4 h with histological evidence of acute pulmonary inflammation, arterial hypoxemia, a threefold increase in lung vascular permeability, and a 30% increase in extravascular lung water as an increase in plasma catecholamine levels. beta-Adrenoceptor inhibition resulted in a marked increase in extravascular lung water that was explained by both an increase in lung vascular permeability and a reduction in net alveolar fluid clearance. The increase in extravascular lung water with propranolol pretreatment was not explained by an increase in systemic or vascular pressures. The increase in lung vascular permeability was explained in part by anti-inflammatory effects of beta-adrenoceptor stimulation because plasma macrophage inflammatory protein-2 levels were higher in the propranolol pretreatment group compared with controls. The decrease in alveolar fluid clearance with propranolol was explained by a decrease in catecholamine-stimulated fluid clearance. Together, these results indicate that endogenous beta-adrenoceptor tone has a protective effect in limiting accumulation of extravascular lung water in acute severe E. coli pneumonia in mice by two mechanisms: 1) reducing lung vascular injury and 2) upregulating the resolution of alveolar edema.

Case‐control study of medical history and idiopathic pulmonary fibrosis in Japan

A few epidemiological studies have indicated that a patient's past medical history may contribute to the risk of developing idiopathic pulmonary fibrosis (IPF). A relationship between a history of selected disorders and the risk of IPF was assessed in a multicentre hospital-based case-control study in Japan. Included in the study were 104 patients of IPF, aged 40 years or over, who had been diagnosed within the previous 2 years, in accordance with the most recent criteria. Control subjects, aged 40 years or over, consisted of 56 hospitalized patients diagnosed as having acute bacterial pneumonia and four outpatients with the common cold. Adjustment was made for age, gender, region, pack-years of smoking, employment status, occupational exposure and BMI. Medical histories of hypertension, hyperlipidaemia, coronary heart disease, diabetes mellitus, hepatitis C virus infection, tuberculosis, asthma, atopic dermatitis and allergic rhinitis were not statistically significantly associated with the risk of IPF, although cases were more likely to have suffered from allergic rhinitis and less likely to have been asthmatics than control subjects. Having a child with a history of allergic rhinitis, but not of asthma or atopic dermatitis, was significantly related to an increased risk of IPF. These findings suggest that a genetic predisposition to allergic rhinitis may be associated with an increased risk of IPF.

Childhood Vaccination and Nontargeted Infectious Disease Hospitalization

It has been hypothesized that multiple-antigen vaccines, such as measles-mumps-rubella vaccine, or aggregated vaccine exposure could lead to immune dysfunction, resulting in nontargeted infectious diseases as a result of an "overload" mechanism. To evaluate the relationship between routinely administered childhood vaccines (Haemophilus influenzae type b; diphtheria-tetanus-inactivated poliovirus; diphtheria-tetanus-acellular pertussis-inactivated poliovirus; whole-cell pertussis; measles-mumps-rubella; oral poliovirus) and hospitalization for nontargeted infectious diseases. Population-based cohort comprising all children born in Denmark from 1990 through 2001 (N = 805 206). Longitudinal information was collected on type and number of vaccine doses received and hospitalization with infectious diseases, specifically acute upper respiratory tract infection, viral and bacterial pneumonia, septicemia, viral central nervous system infection, bacterial meningitis, and diarrhea. Rate ratios for each type of infectious disease according to vaccination status. During 2,900,463 person-years of follow-up, 84,317 cases of infectious disease hospitalization were identified. Out of 42 possible associations (6 vaccines and 7 infectious disease categories), the only adverse association was for Haemophilus influenzae type b vaccine and acute upper respiratory tract infection (rate ratio, 1.05; 95% confidence interval, 1.01-1.08 comparing vaccinated participants with unvaccinated participants). This one adverse association of 42 possible outcomes was within the limits of what would be expected by chance alone and the effect was not temporal or dose-response. When considering aggregated vaccine exposure, we found no adverse associations between an increasing number of vaccinations and infectious diseases. These results do not support the hypotheses that multiple-antigen vaccines or aggregated vaccine exposure increase the risk of nontargeted infectious disease hospitalization.

Occupational and Environmental Factors and Idiopathic Pulmonary Fibrosis in Japan

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease of unknown etiology. Environmental factors, especially occupational agents, may be of great importance in the manifestation of IPF. We examined the relationship between occupational and environmental factors and IPF in Japan. A multicenter hospital-based case-control study was performed in 2001. Included were 102 cases aged 40 years or over who were within 2 years of having been diagnosed in accordance with the most recent criteria. Controls, aged 40 years or over, were 55 hospitalized patients diagnosed as having acute bacterial pneumonia and four outpatients with common colds. Data on occupational and environmental factors were obtained from a questionnaire. Multiple logistic regression analysis was used to estimate the adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of IPF for single factors with adjustment for age, sex and region. Compared with controls, cases were more likely to have been managers, officials or production workers and less likely to have been protective service or materials handling workers. Clerical and related work was significantly related to a decreased risk of IPF after further adjustment for pack-years of smoking (OR = 0.42; 95% CI = 0.18-0.95). Exposure to metal dust was significantly associated with an increased risk of IPF (OR = 9.55; 95% CI = 1.68-181.12). From 20.0 to 39.9 pack-years of smoking was significantly associated with an increased risk of IPF (OR = 3.23; 95% CI = 1.01-10.84). Our results appear to confirm data from previous epidemiologic studies. Metal dust exposure may be a particularly important risk factor for IPF.

Vegetable, Fruit, and Cereal Intake and Risk of Idiopathic Pulmonary Fibrosis in Japan

Aims: There has been little interest in the role of nutrition in prevention of idiopathic pulmonary fibrosis (IPF). We investigated the relationship between dietary intake of vegetables, fruit, cereals, antioxidants, and fiber and the risk of IPF in Japan. Methods: Included were 104 cases aged 40 years or over who were within 2 years of the diagnosis in accordance with the most recent criteria. Controls aged 40 years or over comprised 56 hospitalized patients diagnosed as having acute bacterial pneumonia and 4 outpatients with common cold. Information on dietary factors was collected using a validated self-administered diet history questionnaire. Adjustment was made for age, sex, region, pack-years of smoking, employment status, occupational exposure, saturated fatty acid intake, and body mass index. Results: Consumption of fruit in the second and third quartiles was associated with a statistically significant reduced risk of IPF. Although not statistically significant, a beneficial association between soluble fiber intake and IPF was found. No statistically significant dose-response relationship was observed between intake of green and yellow vegetables, other vegetables, cereals, β-carotene, vitamins C and E, or insoluble fiber and the risk of IPF. Conclusion: Our findings suggest that fruit intake may confer protection against the development of IPF.

Postbariatric surgery deaths, which fall under the jurisdiction of the coroner.

Obesity has attained epidemic proportions in the United States, with more than 50% of adults classified as overweight or obese. If untreated, morbidly obese patients have a 1 in 7 chance of reaching normal life expectancy. The surgical treatment of obesity has emerged as the most effective treatment modality in long-term weight control and has become increasingly popular, with attendant postoperative complications and death. We performed a cross-sectional, coroner based, 2-year retrospective review of archival case records for decedents who died following bariatric surgery for the treatment of obesity to identify underlying causes of death and forensic characteristics of this cohort. Fifteen (0.5%) out of 3097 archival cases died following bariatric surgery, with approximately 73% of decedents dying within 6 months of surgery. The underlying causes of death in 80% of decedents were natural comorbidities of obesity, with cardiovascular diseases (33%) being the most frequent causes of death, followed by gastrointestinal diseases (20%), acute pulmonary thromboembolism (13%), and acute bacterial pneumonia (13%). The majority of decedents were white females who remained morbidly obese after bariatric surgery. Only 2 decedents died of direct inadvertent/accidental surgical complications.

Neutrophil Serine Proteinases Inactivate Surfactant Protein D by Cleaving within a Conserved Subregion of the Carbohydrate Recognition Domain

Surfactant protein D (SP-D) plays important roles in innate immunity including the defense against bacteria, fungi, and respiratory viruses. Because SP-D specifically interacts with neutrophils that infiltrate the lung in response to acute inflammation and infection, we examined the hypothesis that the neutrophil-derived serine proteinases (NSPs): neutrophil elastase, proteinase-3, and cathepsin G degrade SP-D. All three human NSPs specifically cleaved recombinant rat and natural human SP-D dodecamers in a time- and dose-dependent manner, which was reciprocally dependent on calcium concentration. The NSPs generated similar, relatively stable, disulfide cross-linked immunoreactive fragments of approximately 35 kDa (reduced), and sequencing of a major catheptic fragment definitively localized the major sites of cleavage to a highly conserved subregion of the carbohydrate recognition domain. Cleavage markedly reduced the ability of SP-D to promote bacterial aggregation and to bind to yeast mannan in vitro. Incubation of SP-D with isolated murine neutrophils led to the generation of similar fragments, and cleavage was inhibited with synthetic and natural serine proteinase inhibitors. In addition, neutrophils genetically deficient in neutrophil elastase and/or cathepsin G were impaired in their ability to degrade SP-D. Using a mouse model of acute bacterial pneumonia, we observed the accumulation of SP-D at sites of neutrophil infiltration coinciding with the appearance of approximately 35-kDa SP-D fragments in bronchoalveolar lavage fluids. Together, our data suggest that neutrophil-derived serine proteinases cleave SP-D at sites of inflammation with potential deleterious effects on its biological functions.

Essential contribution of monocyte chemoattractant protein-1/C-C chemokine ligand-2 to resolution and repair processes in acute bacterial pneumonia.

Neutrophil infiltration is the first step in eradication of bacterial infection, but neutrophils rapidly die after killing bacteria. Subsequent accumulation of macrophage lineage cells, such as alveolar macrophages (AMs), is essential to remove dying neutrophils, which are a source of injurious substances. Macrophage lineage cells can promote tissue repair, by producing potential growth factors including hepatocyte growth factor (HGF). However, it remains elusive which factor activates macrophage in these processes. Intratracheal instillation of Pseudomonas aeruginosa caused neutrophil infiltration in the airspace; subsequently, the numbers of total AMs and neutrophil ingested AMs were increased. Bronchoalveolar lavage (BAL) fluid levels of monocyte chemoattractant protein (MCP)-1/CC chemokine ligand-2 (CCL2), a potent macrophage-activating factor, were increased before the increases in the number of AM ingesting neutrophils and HGF levels in BAL fluid. Immunoreactive MCP-1 proteins were detected in alveolar type II epithelial cells and AMs only after P. aeruginosa infection. The administration of anti-MCP-1/CCL2 Abs reduced the increases in the number of AM-ingesting neutrophils and HGF levels in BAL fluid, and eventually aggravated lung tissue injury. In contrast, the administration of MCP-1/CCL2 enhanced the increases in the number of AM ingesting neutrophils and HGF levels in BAL fluid, and eventually attenuated lung tissue injury. Furthermore, MCP-1/CCL2 enhanced the ingestion of apoptotic neutrophils and HGF production by a mouse macrophage cell line, RAW 267.4, in a dose-dependent manner. Collectively, MCP-1/CCL2 has a crucial role in the resolution and repair processes of acute bacterial pneumonia by enhancing the removal of dying neutrophils and HGF production by AMs.

Amoxicillin/clavulanate potassium extended release tablets: a new antimicrobial for the treatment of acute bacterial sinusitis and community-acquired pneumonia

Community-acquired bacterial respiratory tract infections are among the most common health disorders requiring medical care and are associated with substantial morbidity, mortality, and direct and indirect costs. Recent increases in the prevalence of antimicrobial resistance have resulted in reduced susceptibility of the most common respiratory tract bacterial pathogens to a number of antimicrobials. Amoxicillin/clavulanate potassium extended release (ER) tablets (Augmentin XR™, GlaxoSmithKline) is a new formulation of amoxicillin/clavulanate that retains activity against β-lactamase-producing organisms whilst increasing the activity against Streptococcus pneumoniae through elevated and sustained plasma amoxicillin concentrations. The bilayer tablet provides immediate release of clavulanate and both immediate and sustained release of amoxicillin to maintain therapeutic concentrations of amoxicillin over longer periods of the dosing interval. In clinical trials of acute bacterial sinusitis (ABS) and community-acquired pneumonia (CAP), amoxicillin/clavulanate ER was shown to have excellent bacteriological and clinical success rates, even in patients infected with antimicrobial-resistant pathogens, and was found to be generally well tolerated. Amoxicillin/clavulanate ER is approved in the US for the treatment of patients with ABS or CAP caused by β-lactamase-producing pathogens (ie, Haemophilus influenzae, Moraxella catarrhalis, Haemophilus parainfluenzae, Klebsiella pneumoniae, or methicillin-susceptible Staphylococcus aureus) and S. pneumoniae with reduced susceptibility to penicillin (penicillin minimum inhibitory concentration = 2.0 μg/ml).

Coordinated expression of tracheal antimicrobial peptide and inflammatory-response elements in the lungs of neonatal calves with acute bacterial pneumonia.

Lung tissue removed from neonatal calves with acute Mannheimia haemolytica pneumonia showed that rapid up-regulation of the basal mRNA expression of tracheal antimicrobial peptide (TAP), NF-kappa B, and intercellular adhesion molecule 1 occurred after infection; TAP and interleukin 8 expression were highly correlated. This work suggests that the coordinated expression of beta-defensin and inflammatory elements occurs during bacterial pneumonia.

Platelet endothelial cell adhesion molecule-1 in neutrophil emigration during acute bacterial pneumonia in mice and rats

Platelet endothelial cell adhesion molecule-1 in neutrophil emigration during acute bacterial pneumonia in mice and rats

Very late antigen-4 in CD18-independent neutrophil emigration during acute bacterial pneumonia in mice

Very late antigen-4 in CD18-independent neutrophil emigration during acute bacterial pneumonia in mice

Oral dosing of dexamethasone was as effective as intramuscular dosing for outpatient treatment of children with moderate croup

Rittichier KK, Ledwith CA. Outpatient treatment of moderate croup with dexamethasone: intramuscular versus oral dosing. Pediatrics2000 Dec; 106 : 1344 –8 [OpenUrl][1][Abstract/FREE Full Text][2] QUESTION: Is oral administration of dexamethasone...

A Comparison of Classification Algorithms to Automatically Identify Chest X-Ray Reports That Support Pneumonia

We compared the performance of expert-crafted rules, a Bayesian network, and a decision tree at automatically identifying chest X-ray reports that support acute bacterial pneumonia. We randomly selected 292 chest X-ray reports, 75 (25%) of which were from patients with a hospital discharge diagnosis of bacterial pneumonia. The reports were encoded by our natural language processor and then manually corrected for mistakes. The encoded observations were analyzed by three expert systems to determine whether the reports supported pneumonia. The reference standard for radiologic support of pneumonia was the majority vote of three physicians. We compared (a) the performance of the expert systems against each other and (b) the performance of the expert systems against that of four physicians who were not part of the gold standard. Output from the expert systems and the physicians was transformed so that comparisons could be made with both binary and probabilistic output. Metrics of comparison for binary output were sensitivity (sens), precision (prec), and specificity (spec). The metric of comparison for probabilistic output was the area under the receiver operator characteristic (ROC) curve. We used McNemar's test to determine statistical significance for binary output and univariate z-tests for probabilistic output. Measures of performance of the expert systems for binary (probabilistic) output were as follows: Rules—sens, 0.92; prec, 0.80; spec, 0.86 (Az, 0.960); Bayesian network—sens, 0.90; prec, 0.72; spec, 0.78 (Az, 0.945); decision tree—sens, 0.86; prec, 0.85; spec, 0.91 (Az, 0.940). Comparisons of the expert systems against each other using binary output showed a significant difference between the rules and the Bayesian network and between the decision tree and the Bayesian network. Comparisons of expert systems using probabilistic output showed no significant differences. Comparisons of binary output against physicians showed differences between the Bayesian network and two physicians. Comparisons of probabilistic output against physicians showed a difference between the decision tree and one physician. The expert systems performed similarly for the probabilistic output but differed in measures of sensitivity, precision, and specificity produced by the binary output. All three expert systems performed similarly to physicians.

A Prospective, Randomized, Multicenter Comparative Study of Clinafloxacin Versus a Ceftriaxone-based Regimen in the Treatment of Hospitalized Patients with Community-acquired Pneumonia

In an open-label, phase 3, randomized, multicenter study, clinafloxacin (200 mg/d) was compared to ceftriaxone (2 g/d; with or without erythromycin) in 527 patients with acute community-acquired bacterial pneumonia (CAP). Primary efficacy parameters were clinical cure rate and microbiologic eradication rates (by pathogen and by patient) determined 5-9 d post-therapy (test of cure; TOC). Clinical cure rates at TOC for the 2 treatment groups were equivalent in the intention-to-treat (clinafloxacin 79.3, ceftriaxone 78.6%), clinically evaluable (clinafloxacin 88.1, ceftriaxone 85.0%), modified intention-to-treat (clinafloxacin 82.6, ceftriaxone 86.9%) and microbiologically evaluable populations (clinafloxacin 86.2, ceftriaxone 86.2%). Microbiologic eradication rates were similar in the 2 treatment groups. Both drugs were tolerated. Treatment of hospitalized CAP patients with clinafloxacin is a reasonable choice, especially when a resistant pathogen is anticipated.

Quantifying the Characteristics of Unambiguous Chest Radiography Reports in the Context of Pneumonia

Rationale and Objectives The purpose of this study was to statistically identify some characteristics of unambiguous (ie, clear) chest radiography reports in the context of acute bacterial pneumonia. Materials and Methods Seven physicians individually read 292 chest radiography reports to determine if they contained radiologic evidence of pneumonia. Unambiguous reports were defined as those that physicians unanimously classified as supporting or not supporting the diagnosis of pneumonia. Ambiguous reports were assigned degrees of ambiguity on the basis of how much disagreement they caused among the physicians. Characteristics of unambiguous reports as described in the literature were manually quantified and assigned to every report. To identify characteristics that statistically distinguished unambiguous from ambiguous reports, the authors performed an ordinal logistic regression analysis for which the dependent variable was the number of dissenting votes the report received and the independent variables were the quantified characteristics of the report. Results Six independent variables were statistically significantly associated with unambiguous reports ( P < .05). Three were positively associated: an interpretation of whether findings supported the diagnosis of pneumonia in reports with pneumonia-related observations, short sentences, and redundancy of pneumonia-related observations. Three were negatively associated: high use of uncertainty modifiers for pneumonia-related observations, use of only descriptive terms to describe pneumonia-related observations, and insufficient amount of pneumonia-related information. Conclusion The most influential characteristic of an unambiguous chest radiography report was an interpretation of whether the radiograph supported the diagnosis of pneumonia when findings could be indicative.

YKL-40, a matrix protein of specific granules in neutrophils, is elevated in serum of patients with community-acquired pneumonia requiring hospitalization.

The serum concentration of YKL-40, a matrix protein of specific granules in neutrophils, was determined by RIA in 90 patients hospitalized with pneumonia of suspected bacterial origin. Of these, 64 were followed prospectively during antibiotic treatment with blood samples taken on day 0 (on admission and the start of treatment) and on days 1, 3, 5, 7, 10, and 21. Serum YKL-40 at admission was increased in patients with Streptococcus pneumoniae pneumonia (median, 893 microgram/L; 95% confidence interval [CI], 704-1560), compared with healthy subjects (median, 102 microgram/L; 95% CI, 64-247 microgram/L; P<.001) and in patients with pneumonia of unknown etiology (median, 448 microgram/L; 95% CI, 334-700; P<.05). Peak YKL-40 serum values were observed on day 1 and thereafter declined steeply to almost normal by day 3. During the first 10 days, there was a close relation between serum YKL-40 and markers of specific granules of neutrophils (serum lactoferrin and neutrophil gelatinase-associated lipocalin), which suggests that serum YKL-40 reflects exocytosis of specific granules of neutrophils in persons with acute bacterial pneumonia.