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Rationale: Increasing evidence supports a key role for the transcription factor nuclear factor (NF)-kappaB in the host response to pneumococcal infection. Control of NF-kappaB activity is achieved through interactions with the IkappaB family of inhibitors, encoded by the genes NFKBIA, NFKBIB, and NFKBIE. Rare NFKBIA mutations cause immunodeficiency with severe bacterial infection, raising the possibility that common IkappaB gene polymorphisms confer susceptibility to common bacterial disease.Objectives: To determine whether polymorphisms in NFKBIA, NFKBIB, and NFKBIE associate with susceptibility to invasive pneumococcal disease (IPD) and thoracic empyema.Methods: We studied the frequencies of 62 single-nucleotide polymorphisms (SNPs) across NFKBIA, NFKBIB, and NFKBIE in individuals with IPD and control subjects (n=1,060). Significantly associated SNPs were then studied in a group of individuals with thoracic empyema and a second control group (n=632).Measurements and Main Results: Two SNPs in the NFKBIA promoter region were associated with protection from IPD in both the initial study group and the pneumococcal empyema subgroup. Significant protection from IPD was observed for carriage of mutant alleles at these two loci on combining the groups (SNP rs3138053: Mantel-Haenszel 2x2 chi2=13.030, p=0.0003; odds ratio [OR], 0.60; 95% confidence interval [CI], 0.45-0.79; rs2233406: Mantel-Haenszel 2x2 chi2=18.927, p=0.00001; OR, 0.55; 95% CI, 0.42-0.72). An NFKBIE SNP associated with susceptibility to IPD but not pneumococcal empyema. None of the NFKBIB SNPs associated with IPD susceptibility.Conclusions: NFKBIA polymorphisms associate with susceptibility to IPD. Genetic variation in an inhibitor of NF-kappaB therefore not only causes a very rare immunodeficiency state but may also influence the development of common infectious disease. [ABSTRACT FROM AUTHOR]

Background: Antibiotic choices for pleural infection are uncertain as its bacteriology is poorly described.Methods: Pleural fluid from 434 pleural infections underwent standard culture and a screen for bacteria by amplification and sequencing of bacterial 16S ribosomal RNA gene.Results: Approximately 50% of community-acquired infections were streptococcal, and 20% included anaerobic bacteria. Approximately 60% of hospital-acquired infections included bacteria frequently resistant to antibiotics (methicillin-resistant Staphylococcus aureus, 25%; Enterobacteriaceae, 18%; Pseudomonas spp., 5%, enterococci, 12%). Mortality was increased in hospital-acquired infection (hospital, 17/36 [47%]; community, 53/304 [17%]; relative risk, 4.24; 95% confidence interval, 2.07-8.69; p < 0.00001; chi(2), 1 df = 17.47) and in gram-negative (10/22 [45%]), S. aureus (15/34 [44%]), or mixed aerobic infections (13/28 [46%]), compared with streptococcal infection (23/137 [17%]) and infection including anaerobic bacteria (10/49 [20%]; p < 0.00001, chi(2), 4 df = 23.35).Conclusion: Pleural infection differs bacteriologically from pneumonia and requires different treatment. Antibiotics for community-acquired infection should treat aerobic and anaerobic bacteria. Hospital-acquired, gram-negative S. aureus and mixed aerobic infections have a high mortality rate. [ABSTRACT FROM AUTHOR]

Background: Intrapleural fibrinolytic agents are used in the drainage of infected pleural-fluid collections. This use is based on small trials that did not have the statistical power to evaluate accurately important clinical outcomes, including safety. We conducted a trial to clarify the therapeutic role of intrapleural streptokinase.Methods: In this double-blind trial, 454 patients with pleural infection (defined by the presence of purulent pleural fluid or pleural fluid with a pH below 7.2 with signs of infection or by proven bacterial invasion of the pleural space) were randomly assigned to receive either intrapleural streptokinase (250,000 IU twice daily for three days) or placebo. Patients received antibiotics and underwent chest-tube drainage, surgery, and other treatment as part of routine care. The number of patients in the two groups who had died or needed surgical drainage at three months was compared (the primary end point); secondary end points were the rates of death and of surgery (analyzed separately), the radiographic outcome, and the length of the hospital stay.Results: The groups were well matched at baseline. Among the 427 patients who received streptokinase or placebo, there was no significant difference between the groups in the proportion of patients who died or needed surgery (with streptokinase: 64 of 206 patients [31 percent]; with placebo: 60 of 221 [27 percent]; relative risk, 1.14 [95 percent confidence interval, 0.85 to 1.54; P=0.43), a result that excluded a clinically significant benefit of streptokinase. There was no benefit to streptokinase in terms of mortality, rate of surgery, radiographic outcomes, or length of the hospital stay. Serious adverse events (chest pain, fever, or allergy) were more common with streptokinase (7 percent, vs. 3 percent with placebo; relative risk, 2.49 [95 percent confidence interval, 0.98 to 6.36]; P=0.08).Conclusions: The intrapleural administration of streptokinase does not improve mortality, the rate of surgery, or the length of the hospital stay among patients with pleural infection. [ABSTRACT FROM AUTHOR]