Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0519030 (Klebsiella)
 21,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Burkholderia cepacia is recognized as an important pathogen in the lung infections of patients with cystic fibrosis. An inducible beta-lactamase activity has been associated with increased resistance to beta-lactam antibiotics in clinical isolates of B. cepacia. In this study, we report the revised sequence of the penA gene, which encodes the inducible penicillinase of B. cepacia, and show that it belongs to the molecular class A beta-lactamases and exhibits a high degree of similarity to the chromosomal beta-lactamase of Klebsiella oxytoca. Analysis of the nucleotide sequence of the DNA region directly upstream of the penA coding sequence revealed an open reading frame (penR), the transcription of which was oriented opposite to that of penA and whose initiation was 130 bp away from that of penA. Two potential ribosome-binding sites and two overlapping -10 and -35 promoter sequences were identified in the intercistronic region. The predicted translation product of penR was a polypeptide of 301 amino acids with an estimated molecular size of 33.2 kDa. The deduced polypeptide of penR showed a high degree of similarity with AmpR-like transcriptional activators of class A and C beta-lactamases, with identities of 59 and 58.7% with Pseudomonas aeruginosa PAO1 AmpR and Proteus vulgaris B317 CumR, respectively. The N-terminal portion of B. cepacia PenR was predicted to include a helix-turn-helix motif, which may bind the LysR motif identified in the intercistronic region. Induction of PenA by imipenem was shown to be dependent upon the presence of PenR. Expression of the cloned B. cepacia penA and penR genes in Escherichia coli SNO302 (ampD) resulted in a high basal and hyperinducible PenA activity. These results suggest that the regulation of the PenA penicillinase of B. cepacia 249 is similar to that observed in other class A and class C beta-lactamases that are under the control of a divergently transcribed AmpR-like regulator.
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PMID:Characterization of the penA and penR genes of Burkholderia cepacia 249 which encode the chromosomal class A penicillinase and its LysR-type transcriptional regulator. 937 40

A 79-year old woman, with a history of hypertension, presented with clinical features of congestive heart failure, fever, a purpuric rash, and left lower quadrant abdominal tenderness. Contrast computed tomography scan of the abdomen showed features of acute diverticulitis, and blood culture was subsequently positive for Klebsiella pneumoniae. Histological examination of a biopsy of the rash confirmed a diagnosis of leukocytoclastic vasculitis (LCV). The bacteremia responded to intravenous amoxycillin/clavulanic acid and gentamicin and the rash subsided. This case represents the first case of LCV complicating K. pneumoniae bacteremia in the English literature. The English literature on bacteria-associated LCV is reviewed. Taking aside organisms such as Rickettsia that cause endothelial invasion, the associated bacterial species tends to be subacute or chronic pathogens e.g. Mycoplasma pneumoniae, Mycobacterium tuberculosis, and Yersinia enterocolitica; or the disease process is of a subacute or chronic nature e.g. endocarditis, bronchiectesis, and cystic fibrosis, leading to prolonged exposure to pathogens that apparently cause acute pyogenic infections, such as K. pneumoniae.
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PMID:Leukocytoclastic vasculitis complicating Klebsiella pneumoniae bacteremia. 1097 80

Matrilysin (matrix metalloproteinase-7) is expressed by mucosal epithelia throughout the body and functions in host defense by activating murine intestinal alpha-defensins. In normal adult human lung, matrilysin is expressed at low levels in the airway epithelium, but is markedly up-regulated in cystic fibrosis (CF). Because CF lungs support a heavy bacterial load, we assessed if relevant CF pathogens regulate matrilysin expression in human lung epithelial cells. Indeed, acute infection with Pseudomonas aeruginosa (but not Staphylococcus aureus, Haemophilus influenzae, or Klebsiella pneumoniae) induced the expression of matrilysin in Calu-3 lung epithelial cells. Increased matrilysin mRNA levels were detectable at 3 h post-infection and peaked at a 25-fold induction between 6 and 8 h. Both P. aeruginosa CF isolates and laboratory strains induced matrilysin expression to similar levels. Flagellin, the monomeric precursor of bacterial flagella, was identified as the inductive factor released by P. aeruginosa that regulated matrilysin expression. In addition, flagellin-null mutants failed to stimulate matrilysin expression in cultured cells or in lungs infected in vivo. These data show that P. aeruginosa (and specifically flagellin) potently stimulates matrilysin expression in lung epithelial cells and may mediate the overexpression of this proteinase in CF lungs.
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PMID:Regulation of matrilysin expression in airway epithelial cells by Pseudomonas aeruginosa flagellin. 1152 77

Trends in susceptibility to antimicrobials were assessed from United States participants using 4488 isolates in the MYSTIC Program, 1999 (10 centers) through 2000 (15 centers). Diverse types of hospitals (general service, university, cancer, federal, pediatric, cystic fibrosis) were enrolled from 13 states. In 2000, oxacillin-susceptible staphylococci were 100% susceptible to meropenem, imipenem, and cefepime; but only 88% of strains were susceptible to ceftazidime. Among Enterobacteriaceae, > or = 96% of Enterobacter spp., Citrobacter spp., and Serratia spp. were susceptible to meropenem, imipenem, and cefepime; but ceftazidime, ceftriaxone, and piperacillin/tazobactam had 5-20% resistance rates. Extended-spectrum beta-lactamase resistance rates in Klebsiella spp. and Escherichia coli (6-7% and 3-5%, respectively) were stable over 2 years. Acinetobacter spp. were 78-81% susceptible to carbapenems but only 63-72% susceptible to ciprofloxacin. Meropenem, tobramycin, and piperacillin/tazobactam were the most active against Pseudomonas aeruginosa, but ciprofloxacin inhibited only 74% in 2000. Overall, meropenem remained the most potent agent, especially against ceftazidime- or piperacillin/tazobactam-resistant strains.
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PMID:Antimicrobial resistance trends in medical centers using carbapenems: report of 1999 and 2000 results from the MYSTIC program (USA). 1177 56

The most common hepatic complications of cystic fibrosis (CF) are steatosis, fibrosis, biliary cirrhosis, atretic gallbladder, cholelithiasis, and sclerosing cholangitis. Cholestatic liver disease is a slow progressive disorder, but will stabilize for many patients. CF patients may suffer from the consequences of their liver disease and without liver transplantation, variceal hemorrhage, malnutrition, or end-stage liver disease can lead to death. Prospective data were collected and reviewed on 311 liver transplants performed in 283 patients at the Children's Medical Center of Dallas between October 1984 and November 2000. Ten children received an orthotopic liver transplant (OTLX) for end-stage liver disease associated with cystic fibrosis. Pulmonary function tests were obtained preoperatively in all cases. There were nine boys and one girl. Six are currently alive, and four are dead. Both patient and graft survival was 5.75 yr. Among those currently alive, mean patient and graft survival is 7.71 yr (range 0.10-12.62 yr). Mean patient and graft survival of those who died was 2.35 yr (range 0.78-5.33 yr). No survivor required re-transplantation and currently, all have normal serum aminotransferase values. Chronic sinusitis was not a significant pre- or post-transplant morbidity, although systematic radiographic evaluation of the sinuses did not occur. Pulmonary deaths occurred in three patients from pulmonary hemorrhage, pulmonary infection with Aspergillus and Candida glabrata, and acute bronchopneumonia associated with polymicrobial sepsis because of Pseudomonas, Klebsiella, and Candida albicans 1.44, 0.78, and 1.83 yr, respectively, after transplantation. The fourth death was associated with chronic rejection, and occurred 5.33 yr after transplantation. All non-survivors were below the 5th percentile for height and weight at the time of liver transplantation. Mean age at transplantation was 9.72 yr (range 1.23-19.09, median 9.61). Survivors were transplanted at a younger age than non-survivors (mean of 9.21 yr vs. 10.66 yr), and had shorter waiting times from diagnosis of end-stage liver disease to transplantation (6.87 months vs. 13.83 months). Eighty percentage (n = 8) of patients had pretransplant variceal bleeds (83% of survivors, 75% of non-survivors). While all non-survivors had a history of meconium ileus and preoperative need of pancreatic enzymes, only 67% of those alive experienced these complications. Preoperative forced vital capacity FVC was 103% for survivors and 95% for non-survivors. The corresponding numbers for forced expiratory flow (FEF) 25-75 were 74-84% respectively. Preoperative Aspergillus was identified in 30% of patients (n = 3). Two of these patients are alive. Cystic fibrosis constitutes an indication for 3.5% of pediatric liver transplants. Evaluation and transplantation for end-stage liver disease associated with cystic fibrosis should be undertaken at an early age. Most deaths were associated with pulmonary/septic events, and occurred less than 2 yr after OLTX. Those children who did not survive had poor growth and nutrition, prolonged waiting times prior to transplantation, were transplanted at an older age, and had a higher incidence of pancreatic insufficiency and meconium ileus. The presence of Aspergillus in the sputum does not constitute a contraindication for OLTX.
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PMID:Liver transplantation for cholestasis associated with cystic fibrosis in the pediatric population. 1265 48

Lung inflammation resulting from bacterial infection of the respiratory mucosal surface in diseases such as cystic fibrosis and pneumonia contributes significantly to the pathology. A major consequence of the inflammatory response is the recruitment and accumulation of polymorphonuclear cells (PMNs) at the infection site. It is currently unclear what bacterial factors trigger this response and exactly how PMNs are directed across the epithelial barrier to the airway lumen. An in vitro model consisting of human PMNs and alveolar epithelial cells (A549) grown on inverted Transwell filters was used to determine whether bacteria are capable of inducing PMN migration across these epithelial barriers. A variety of lung pathogenic bacteria, including Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa are indeed capable of inducing PMN migration across A549 monolayers. This phenomenon is not mediated by LPS, but requires live bacteria infecting the apical surface. Bacterial interaction with the apical surface of A549 monolayers results in activation of epithelial responses, including the phosphorylation of ERK1/2 and secretion of the PMN chemokine IL-8. However, secretion of IL-8 in response to bacterial infection is neither necessary nor sufficient to mediate PMN transepithelial migration. Instead, PMN transepithelial migration is mediated by the eicosanoid hepoxilin A3, which is a PMN chemoattractant secreted by A549 cells in response to bacterial infection in a protein kinase C-dependent manner. These data suggest that bacterial-induced hepoxilin A3 secretion may represent a previously unrecognized inflammatory mechanism occurring within the lung epithelium during bacterial infections.
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PMID:Polymorphonuclear cell transmigration induced by Pseudomonas aeruginosa requires the eicosanoid hepoxilin A3. 1549 23

Infections caused by multi-resistant Gram-negative bacteria, particularly Pseudomonas aeruginosa, are increasing worldwide. In patients with cystic fibrosis (CF), resistance in P. aeruginosa to numerous anti-pseudomonal agents is becoming common. The absence since 1995, of new substances active against resistant Gram-negative bacteria, has caused increasing concern. Colistin, an old antibiotic also known as polymyxin E, has attracted more interest recently because of its significant activity against multi-resistant P. aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae, and the low resistance rates to it. Because its use as an anti-pseudomonal agent was displaced by the potentially less toxic aminoglycosides in 1970s, our knowledge of this drug is limited. However, there has been a significant recent increase in the data gathered on colistin, focussing on its chemistry, antibacterial activity, mechanism of action and resistance, pharmacokinetics, pharmacodynamics and new clinical application. It is likely that colistin will be an important antimicrobial option against multi-resistant Gram-negative bacteria, for some years to come.
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PMID:Evaluation of colistin as an agent against multi-resistant Gram-negative bacteria. 1664 33

The emergence of multidrug-resistant gram-negative bacteria and the lack of new antibiotics to combat them have led to the revival of polymyxins, an old class of cationic, cyclic polypeptide antibiotics. Polymyxin B and polymyxin E (colistin) are the 2 polymyxins used in clinical practice. Most of the reintroduction of polymyxins during the last few years is related to colistin. The polymyxins are active against selected gram-negative bacteria, including Acinetobacter species, Pseudomonas aeruginosa, Klebsiella species, and Enterobacter species. These drugs have been used extensively worldwide for decades for local use. However, parenteral use of these drugs was abandoned approximately 20 years ago in most countries, except for treatment of patients with cystic fibrosis, because of reports of common and serious nephrotoxicity and neurotoxicity. Recent studies of patients who received intravenous polymyxins for the treatment of serious P. aeruginosa and Acinetobacter baumannii infections of various types, including pneumonia, bacteremia, and urinary tract infections, have led to the conclusion that these antibiotics have acceptable effectiveness and considerably less toxicity than was reported in old studies.
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PMID:Colistin: the revival of polymyxins for the management of multidrug-resistant gram-negative bacterial infections. 1582 37

Colistin, an antibiotic almost abandoned for intravenous administration for many years due to its reported toxicity, has been recently reintroduced in clinical practice due to the emergence of multidrug-resistant gram-negative bacteria and the lack of development of new antibiotics to combat them. To assess the safety and effectiveness of intravenous colistin, in combination with other antimicrobial agents, in the treatment of serious infections in patients without cystic fibrosis, a retrospective cohort study in a 450-bed tertiary-care hospital in Athens, Greece, was performed. Patients who were hospitalized from 1 October 2000 to 31 January 2004 and received intravenous colistin for more than 72 h were further analyzed. The primary outcome measure was the in-hospital mortality; secondary end points were the clinical outcome of the infections and the occurrence of colistin toxicity. Fifty patients received intravenous colistin with a median (mean) daily dose of 3 (4.5) million IU for 16.5 (21.3) days for the management of 54 episodes of infections due to multidrug-resistant gram-negative bacteria. The predominant infections were pneumonia (33.3%), bacteremia (27.8%), urinary tract infection (11.1%), and intra-abdominal infection (11.1%). The responsible pathogens were Acinetobacter baumannii (51.9%), Pseudomonas aeruginosa (42.6%), and Klebsiella pneumoniae (3.7%) strains (no pathogen was isolated from one case). In-hospital mortality was 24% (12/50 patients). Clinical response (cure or improvement) of the infection was observed in 66.7% of episodes (36/54). In the studied group, serum creatinine levels were decreased, at the end of colistin treatment, by an average of 0.2 +/- 1.3 mg/dl compared to baseline levels. Deterioration of renal function during colistin therapy was observed in 4/50 patients (8%). Coadministration of other antimicrobial agents with spectrum against gram-negative microorganisms and the absence of a control group constitute the major limitations of this study. The use of intravenous colistin for the treatment of infections due to multidrug-resistant gram-negative bacteria appears to be safe and effective.
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PMID:Combination therapy with intravenous colistin for management of infections due to multidrug-resistant Gram-negative bacteria in patients without cystic fibrosis. 1604 15

Patients affected by pneumonia can be admitted in Intensive Care Units (ICUs) independently by the setting where the infection has been acquired (community, hospital, long-term care facilities); even more frequently pneumonia can develop in patients already hospitalized in ICU especially in those requiring mechanical ventilation for different reasons. Within the severe community acquired pneumonia requiring admission in ICU, the most frequently responsible micro-organisms are mainly represented by Streptococcus pneumoniae, but also by Legionella and Haemophilus. Pseudomonas aeruginona, anyway, cannot be excluded. The most recent Canadian and American guidelines for treatment of the above mentioned infections suggest the use of a combination therapy with beta-lactams (ceftriaxone, cefotaxime, ampicillin/sulbactam, piperacillin/tazobactam) and a new generation macrolide or respiratory fluoroquinolone. In case of allergy to beta-lactams, the association fluoroquinolone-clindamycin should be preferred. Whenever a Pseudomonas etiology is suspected because of the presence of risk factors such as COPD, cystic fibrosis, bronchiectasis, previous and/or frequent therapies with antibiotics and/or steroids, the same guidelines suggest the use of an anti-pseudomonas beta-lactam (such as piperacillin/tazobactam, carbapenems, cefepime) associated with an anti-pseudomonas fluoroquinolone (high doses ciprofloxacin). An anti-pseudomonas beta-lactam plus an aminoglycoside or aminoglicosyde plus fluoroquinolone can be an alternative. Early onset Hospital Acquired Pneumonia (HAP) and early onset Ventilator Associated Pneumonia (VAP) in patients without risk factors for multi-resistant etiological agents are generally sustained by S. pneumoniae, H. influenzae, methicillin-susceptible Staphylocccus aureus e Gram negative enteric rods. These infections can be treated with one of the following antibiotics: ceftriaxone or fluoroquinolones (moxifloxacin or ciprofloxacin or levofloxacin) or ampicillin/sulbactam or ertapenem. Late onset VAP and HAP in patients with risk factors for multi-resistant, by contrast, should be treated with a combination therapy: in case of defined or suspected P. aeruginosa, Klebsiella pneumoniae (ESbL+), Acinetobacter sp etiology, it is required the use of an anti-pseudomonas cephalosporin or an anti-pseudomonas carbapenem or b-lactam + beta-lactamase inhibitor associated with an anti-pseudomonas fluoroquinolone or an aminoglicoside. The possible presence of MRSA or Legionella pneumophila suggests the use of anti-Gram positive antibiotics such as glycopeptides or linezolid. These quidelines confirm the role of ciprofloxacin combined with beta-lactams whenever P. aeruginosa, Klebsiella pneumoniae (ESbL+), Acinetobacter sp. etiology is suspected.
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PMID:[Guidelines for treatment of pneumonia in intensive care units]. 1680 48


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