Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0023241 (Legionella)
6,990 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Even if they represent only a minor percentage of all respiratory infections, acute pulmonary infections are the leading mortality cause from infectious diseases. Epidemiologic data amongst hospitalized patients with acute infections reveal mean mortality figures of 20%. The adequate assessment of severity criteria is fundamental so that patients can be oriented towards suitable hospitalized units. Risks factors to be considered are: other illnesses, age (greater than 60 years), breathing frequency greater than 30/min, diastolic blood pressure less than 60 mmHg, confusion, a PaO2 less than 60 Torr, a leukocytosis greater than 30,000 or less than 4,000/mm3, albuminemia less than 35 g/l and blood urea greater than 7 mmol/l. The association of these factors increases the risk of complications and mortality in a linear way. By contrast, the type of responsible organism is not relevant. Five microorganisms are responsible for 80 to 90% of documented acute pulmonary infections: pneumococci, Mycoplasma pneumoniae, Haemophilus influenzae, Legionella pneumophila, Myxovirus influenzae. However, direct examination of bacteriologic smear allows for a proper identification of the infectious agent in only 15% of cases. The clinician can therefore use epidemiologic, clinical and radiological findings to propose an oriented, though probable, antibiotic treatment. In these conditions, the initial treatment remains the association of an A type penicillin with an inhibitory effect on beta-lactamases and of a macrolide (or, eventually, of a fluoroquinolone) until results of bacteriologic investigations is known. No data is available to suggest the use of new third generation oral cephalosporins in the first intention treatment of acute severe pulmonary infections due to their low and inconsistent effect on pneumococcus.
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PMID:[Severe community-acquired pneumopathy. What initial antibiotics to use?]. 158 29

Azithromycin contains an aza-methyl substitution in the 15-membered aglycone ring and as such it is the prototype antibiotic of the azalide class, similar in mechanism of activity to the macrolides. It demonstrates a broad spectrum of activity against many aerobic and anaerobic Gram-positive species, and also inhibits a number of important aerobic and anaerobic Gram-negative bacteria. Significantly, azithromycin shows good activity against Haemophilus influenzae, an organism against which older macrolide antibiotics have proved disappointing. It is highly effective in inhibiting clinically significant intracellular pathogens such as Chlamydia trachomatis and Legionella. Bactericidal activity is seen for certain streptococci and for H. influenzae. Closely linked with azithromycin's microbiologic activity are its novel pharmacokinetics. Azithromycin moves rapidly from blood to tissue compartments where it remains for prolonged periods. Although serum concentrations remain low, the levels attained in the tissues (often greater than 2 mg/kg) are higher than the minimum inhibitory concentration for many common pathogens, and delivery of drug to infection sites by phagocytic cells contributes to these concentrations. This penetration into eukaryotic and prokaryotic cells may be responsible for azithromycin's expanded spectrum of activity, particularly against intracellular organisms. The use of antibiotic blood levels as breakpoints for susceptibility would appear to be inappropriate in the case of azalides. Rather, levels of drug at the tissue site of infection should be considered as guides to predicting efficacy. The in vitro activity of azithromycin, together with its unique tissue pharmacodynamics, define an agent that should demonstrate utility in infections of the respiratory tract, skin and skin structures, and certain sexually transmitted diseases.
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PMID:Clinical microbiology of azithromycin. 165 36

WIN 57273, a new fluoroquinolone, was four to 128-fold more active than ciprofloxacin and ofloxacin against Gram-positive bacteria. The MIC90 for Staphylococcus aureus was 0.015 mg/l and for S. epidermidis, 0.03 mg/l. All Lancefield group A, B, C, & G streptococci, Streptococcus bovis and S. pneumoniae were inhibited by less than or equal to 0.06 mg/l compared to 0.5 mg/l for tosufloxacin and 2 mg/l for ciprofloxacin. For anaerobic bacteria WIN 57273 had an MIC90 for bacteroides of 1 mg/l, and for Clostridium spp. 0.015.mg/l. WIN 57273 was less active than ciprofloxacin against Enterobacteriaceae, with an MIC90 of 1 mg/l, including aminoglycoside and cephalosporin-resistant isolates. The MIC90 of WIN 57273 for Pseudomonas aeruginosa was 2 mg/l, compared to 0.5 mg/l for ciprofloxacin. Haemophilus influenzae, Moraxella catarrhalis, Neisseria gonorrhoeae, and Legionella spp. were inhibited by 0.06 mg/l. WIN 57273 was more active against Gram-negative bacteria at acid pH, but activity was decreased by magnesium ions and an increase in inoculum. Resistant strains were selected after passage on antibiotic-containing agar.
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PMID:In-vitro activity of WIN 57273 compared to the activity of other fluoroquinolones and two beta-lactam antibiotics. 165 56

In recent years, a number of newer macrolides have been developed. One such antibiotic is azithromycin, which has a 15-membered ring structure and is classed as an azalide. The limitations of erythromycin and the discovery of pathogenic bacteria such as Campylobacter, Legionella and Chlamydia species provide incentives to study the usefulness of newer antibiotics of this class. Azithromycin has good activity against staphylococci, streptococci, Moraxella catarrhalis and other rapidly growing pyogenic bacteria. The good activity of azithromycin against Haemophilus influenzae (MIC90 0.5 mg/l) is particularly important as erythromycin has only marginal activity against this organism. Azithromycin has also been shown to be more potent than the macrolides against Enterobacteriaceae. In common with erythromycin and tetracycline, the agent has good activity against Legionella, Chlamydia and Campylobacter. Opportunistic infections involving Toxoplasma gondii and Pneumocystis carinii are an increasing problem and azithromycin is particularly interesting in view of its activity against these difficult-to-treat organisms.
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PMID:Spectrum of activity of azithromycin. 166 24

The in vitro activities of temafloxacin, ciprofloxacin, and ofloxacin against gram-negative bacteria are compared. The 90% minimal inhibitory concentrations (MIC90s) of temafloxacin for respiratory pathogens such as Haemophilus influenzae, Moraxella catarrhalis, Neisseria meningitidis, Bordetella pertussis, and Legionella pneumophila are less than or equal to 0.06 micrograms/mL. Temafloxacin is also active against bacterial agents of sexually transmitted diseases, including Neisseria gonorrhoeae (MIC90 less than or equal to 0.015 micrograms/mL) and Chlamydia trachomatis (MIC90 0.25 micrograms/mL). For strains of Enterobacteriaceae, Campylobacter, Vibrio, Aeromonas, and Acinetobacter, temafloxacin is generally inhibitory at less than or equal to 0.5 micrograms/mL. The MIC90 of temafloxacin for Pseudomonas aeruginosa is higher than that of ciprofloxacin, approximately 4 micrograms/mL versus 0.5 micrograms/mL. This activity, combined with its pharmacokinetic characteristics, should make temafloxacin an effective antimicrobial agent against infections caused by gram-negative bacteria.
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PMID:In vitro activity of temafloxacin against gram-negative bacteria: an overview. 166 90

The ability to examine the bacterial genome directly eliminates the problems associated with the variable expression of proteins which may be encountered with protein-based typing or 'fingerprinting' techniques. Bacterial DNA is extracted by a rapid method, digested with a restriction endonuclease and the resulting fragments separated by gel electrophoresis to give a characteristic banding pattern. The choice of restriction endonuclease for a particular bacterial species is critical; an enzyme which cuts frequently results in an indistinct pattern which is difficult to interpret. A banding pattern consisting of a readily discernible number of discrete bands, usually about 20 or less in number, is preferable. Fragments in the 1-10 kb size range enable short separation times while larger fragments are desirable if interpretation is complicated by the presence of plasmid bands. This approach has enabled differentiation of isolates within Staphylococcus aureus (including methicillin-resistant S. aureus), non-typable Haemophilus influenzae, Neisseria meningitidis, Moraxella catarrhalis, Legionella pneumophila and enterococci, indistinguishable by conventional methods. Restriction enzyme digestion of chromosomal DNA provides a highly discriminatory method of bacterial characterization suitable for epidemiological studies.
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PMID:Restriction enzyme analysis of chromosomal DNA and its application in epidemiological studies. 167 12

Choosing appropriate antimicrobial therapy for patients with pneumonia requires knowledge of the etiologic agents seen in specific kinds of patients at specific times and places. For community-acquired pneumonia, there is an important difference in the agents seen in the normal and the compromised host. The normal host most often presents with viral, mycoplasmal, or pneumococcal pneumonia. The exact place of Chlamydia pneumoniae is still under study. A normal host who aspirates is at risk of anaerobic pneumonia. Normal hosts with influenza may acquire superinfection with Streptococcus pneumoniae, Haemophilus influenzae, or Staphylococcus aureus. Under specific epidemiologic conditions, community-acquired pneumonia may be due to Legionella species, Yersinia pestis, Francisella tularensis, Coxiella burnetii, Chlamydia psittaci, a mycotic agent, or tuberculosis. Patients with chronic bronchitis and emphysema are predisposed to H. influenzae, Moraxella catarrhalis, and S. pneumoniae infections. HIV-infected patients are likely to have Pneumocystis carinii pneumonia and pneumonia due to cytomegalovirus, S. pneumoniae, and H. influenzae. Patients with diabetes, nursing-home patients, hospitalized patients, immuno-compromised patients, and patients with recent antibiotic therapy are predisposed to pneumonia due to Gram-negative aerobic bacilli of enteric and environmental origin. Initial therapy should be directed at the likely organism or organisms based on hospital susceptibility surveillance. In the normal host with community-acquired pneumonia, the therapy will often be penicillin G or erythromycin. In the patient predisposed to Gram-negative pneumonia, a third-generation cephalosporin with or without an aminoglycoside is the usual choice.
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PMID:Pneumonia. Patient profiles, choice of empiric therapy, and the place of third-generation cephalosporins. 173 Jan 86

We made an open, noncomparative evaluation of ofloxacin, 400 mg orally bid for 10 days, in 98 subjects with community-acquired pneumonia or pathogen-confirmed bronchitis. Thirty-nine (40%) of the subjects were treated in the hospital and 59 (60%) were treated as outpatients. The mean age of those treated was 56.2 years; 73 (74%) of the subjects either were more than 60 years old or had a history of chronic obstructive pulmonary disease, or both. There were 95 organisms initially isolated in sputum, aspirate, or lavage fluid; all were susceptible to ofloxacin, and none acquired resistance during therapy. Haemophilus influenzae was the most common pathogen (19 isolates), followed by Streptococcus pneumoniae (18) and Staphylococcus aureus (10). Clinical responses included cure in 70 patients (71%), improvement in 26 (27%), and failure in two (2%). After 10 days of therapy, pathogens persisted in two cases; in one case, Streptococcus salivarius was isolated, though it remained susceptible to ofloxacin, and in the other, Klebsiella pneumoniae was accompanied by superinfection due to a resistant strain of Serratia marcescens. We included in this study three confirmed cases of atypical pneumonia successfully treated with ofloxacin, two of them due to Mycoplasma pneumonia and one to Legionella pneumophila. Ofloxacin was well tolerated. Our data indicate that ofloxacin is effective and safe as specific and empiric treatment for many lower respiratory tract infections.
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PMID:Oral ofloxacin therapy for lower respiratory tract infection. 173 27

A prominent 19 kDa surface antigen of Legionella pneumophila, cloned in Escherichia coli, was found to be intimately associated with peptidoglycan. The DNA region encoding this antigen was mapped on an 11.9 kb plasmid by means of deletion analysis and transposon mutagenesis. PhoA+ gene fusions, gene-rated by TnphoA insertions into this region, confirmed the presence of a gene encoding a secreted protein. PhoA+ transposon insertions were also associated with loss of the 19 kDa antigen in immunoassays using a monoclonal antibody (mAb1E9) and the replacement of the 19 kDa antigen with larger fusion proteins in immunoblots using Legionella immune serum. A 1540bp PstI fragment carrying the gene was sequenced, and the open reading frame encoding the antigen was identified. The gene encodes a polypeptide 176 amino acid residues long and 18913Da in size. The presence of a signal sequence of 22 amino acids with a consensus sequence for cleavage by signal peptidase II indicates that the antigen is a lipoprotein, and striking similarity with peptidoglycan-associated lipoproteins (PALs) from E. coli (51% amino acid homology) and Haemophilus influenzae (55% homology) is noted. We conclude that the 19kDa antigen of L. pneumophila is the structural equivalent of the PAL found in other Gram-negative species and suggest that its post-translational acylation may explain its potency as an immunogen.
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PMID:Characterization of a Legionella pneumophila gene encoding a lipoprotein antigen. 176 77

The protein PpIA (19 kD) cloned from a genomic library of Legionella pneumophila, Philadelphia 1, represents a peptido-glycan associated outer membrane protein in recombinant E. coli K-12 and L. pneumophila. It exhibits distinct sequence homology to lipoproteins of Haemophilus influenzae and E. coli. A ppIA specific DNA probe generated by PCR was used in Southern hybridizations of chromosomal DNA of Legionella strains and other Gram-negative pathogens. Under conditions of high stringency, hybridization could only be observed in L. pneumophila isolates, but all other Legionella strains tested displayed hybridization under lower stringency. No signals appeared after hybridization of chromosomal DNA from a variety of other bacteria. Using anti-PpIA monospecific polyclonal antibodies in Western blots, it was demonstrated that PpIA related proteins of nearly the same size are found in all L. pneumophila isolates and in a variety of, but not all, the Legionella species analysed here.
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PMID:Phenotype versus genotype of the 19 kD peptido-glycan associated protein of Legionella (PpIA), among Legionellae and other gram-negative bacteria. 181 89


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