Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023241 (Legionella)
 6,990 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bacterial respiratory tract infections (RTIs), whether primary or subsequent to viral infection, are a frequent cause of morbidity and mortality worldwide. Treatment of these infections is most often empirical. Therefore, an antimicrobial's antibacterial spectrum must include the most likely pathogens: Streptococcus pneumoniae, the most frequent cause of community-acquired pneumonia (CAP), Haemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus, as well as atypicals such as Mycoplasma pneumoniae, Legionella pneumophila and Chlamydophila (Chlamydia) pneumoniae. In addition, knowledge of antimicrobial resistance among these key pathogens is imperative for physicians to choose the most appropriate therapeutic agent. The latest data from global surveillance studies indicates that high-level resistance to penicillin (MIC > or =2 mg/l) among isolates of S. pneumoniae varies widely by geographic location. Rates exceed 20% in the USA, Mexico, Japan, Saudi Arabia, Israel, Spain, France, Greece, Hungary, and the Slovak Republic. In South Africa, Hong Kong, Taiwan, and South Korea rates exceed 50%. Penicillin non-susceptibility--including isolates exhibiting high-level resistance and intermediate susceptibility (MIC 0.12-1 mg/l)--is frequently found in association with macrolide resistance, which is found at a prevalence of 70-80% in some Asian countries. Trimethoprim-sulfamethoxazole (TMP-SMX) and tetracycline resistance, either individually or combined with macrolide resistance as multiple resistance, is also associated with reduced susceptibility to penicillin. Another concern about antimicrobial resistance in respiratory tract pathogens is beta-lactamase production among isolates of H. influenzae and M. catarrhalis. However, respiratory fluoroquinolones, of which levofloxacin has been available for the longest time, currently remain active against the great majority of common bacterial respiratory pathogens, including atypicals.
 ...
PMID:Comparative antimicrobial susceptibility of respiratory tract pathogens. 1531 48

Moxifloxacin (Bay 12-8039) is a new 8 methoxy quinolone antibacterial. The MIC90 values are < or = 0.25 mg/l for Streptococcus pneumoniae (irrespective of penicillin susceptibility), Haemophilus influenzae (beta-lactamase positive or negative), Morexella catarrhalis, Bordetella pertussis, Legionella sp., Mycoplasma pneumoniae, Clamydia pneumoniae, Mycobacterium tuberculosis, methicillin-sensitive Staphylococcus aureus, beta-haemolytic streptococci (macrolide-sensitive or -resistant), Listeria sp., most Enterobacteriaceae, Salmonella sp., Shigella sp., Neisseria gonorrhoeae, N. menigitidis, Pasteurella spp., Vibrio spp. and Yersinia enterocolitica. For Mycobacterium intracellularae, methicillin-resistant S. aureus (MRSA), ciprofloxacin-resistant S. aureus, Citrobacter freundii, Providencia sp., Serratia sp., P. aeruginosa and other non-fermentive Gram-negative rods, MIC90s are in the range 0.5-4 mg/l. For anaerobic bacteria species, MIC90s are also in the range 0.25-4 mg/l. Moxifloxacin is bactericidal at concentrations 2- to 4-fold higher than the MIC and is rapidly bactericidal against most common pathogen groups at concentrations achieved in serum with a 400 mg dose that is between 0.5-4 mg/l. There is a post-antibiotic effect against Gram-positive and -negative bacteria. Resistant mutants are at present difficult to select in the laboratory but in general, moxifloxacin has poorer activity against strains resistant to ciprofloxacin compared to those which are susceptible. Animal and laboratory pharmacodynamic models indicate that the MIC and area under the serum concentration time curve predict outcome. Various animal models mainly of respiratory tract infection indicate equivalent or superior results compared to existing or other developmental agents. Human pharmacokinetics in healthy volunteers indicate linear pharmacokinetics over the dose range 50-800 mg/day. A single dose of 400 mg produces a maximum serum concentration of 2.5-4.5 mg/l, half-life of 11-15 h, AUC of 25-40 mg x h/l and volume of distribution of 2.5-3.5 L/kg. Protein binding is about 50% and two metabolites have been identified (M-1 and M-2). Bioavailability is > 85% and a minority of clearance is via the kidneys. No dose modification is required in renal impairment. Extra vascular penetration, where studied, is comparable to that of other quinolones. At present undergoing clinical trials, with a focus on respiratory tract infection, it is likely that moxifloxacin will provide effective therapy for pathogens with MICs of < or = 0.25-0.5 mg/l. The safety profile in a large number of human subjects is awaited.
 ...
PMID:Moxifloxacin (Bay 12-8039): a new methoxy quinolone antibacterial. 1599 72

Tetracycline antimicrobials are characterised by a broad-spectrum of antibacterial activity which includes Gram-positive, most Gram-negative, anaerobic and "atypical" (Legionella pneumophila, Chlamydophila pneumoniae and Mycoplasma pneumoniae) species. However, the original clinical utility of the tetracyclines has been compromised as a result of increasing resistance to them among previously susceptible, common pathogens. Research into structure-activity relationships among various tetracycline derivatives resulted in discovery of the 9-t- butylglycylamido tetracyclines, now known as the glycylcyclines, which are not affected by either specific efflux pump or ribosomal protection mechanisms of resistance. Tigecycline, 9-t-butylglycylamido-minocycline, is the first in the glycylcycline class to undergo clinical development. This review of published in vitro data clearly demonstrates the potent activity of tigecycline against a wide range of common hospital and community bacterial pathogens including those having acquired mechanisms of resistance to older congeners (tetracycline, minocycline and doxycycline). Its activity against multiply-resistant Staphylococcus spp, including glycopeptide-intermediate strains (GISA), Streptococcus pneumoniae, Enterococcus spp. (including vancomycin-resistant strains) and some extended-spectrum, beta-lactamase producing isolates of species of the Enterobacteriaceae, is particularly noteworthy.
 ...
PMID:Tigecyclin--the first glycylcycline to undergo clinical development: an overview of in vitro activity compared to tetracycline. 1628 53

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.
 ...
PMID:[Guidelines for treatment of pneumonia in intensive care units]. 1680 48

Survival and replication inside host cells by Brucella spp. requires a type IV secretion system (T4SS), encoded by the virB locus. However, the identity of the molecules secreted by the T4SS has remained elusive. We hypothesized that proteins translocated by the T4SS would be co-regulated with the virB operon. The LuxR family regulator VjbR, known to regulate virB, bound a fragment of the virB promoter containing an 18 bp palindromic motif (virB promoter box), showing that VjbR regulated the virB operon directly. To identify virB co-regulated genes, we searched the Brucella suis 1330 and B. abortus 2308 genomes for genes with an upstream virB promoter box. One hundred and forty-four promoters in the two genomes contained the virB promoter box, including those of fliC encoding flagellin and cgs encoding cyclic beta-glucan synthetase. Thirteen of these proteins were tested for VirB-dependent translocation into macrophages using a beta-lactamase reporter assay. This analysis resulted in the identification of the proteins encoded by BAB1_1652 (VceA) and BR1038/BAB1_1058 (VceC) as novel protein substrates of the Brucella T4SS. VceC could also be translocated by the Legionella pneumophila Dot/Icm T4SS into host cells. Our results suggest that VjbR co-ordinates expression of the T4SS and at least two of its secreted substrates.
 ...
PMID:Identification of VceA and VceC, two members of the VjbR regulon that are translocated into macrophages by the Brucella type IV secretion system. 1901 40

CEM-101 is a novel fluorinated macrolide-ketolide with potent activity against bacterial pathogens that are susceptible or resistant to other macrolide-lincosamide-streptogramin B (MLS(B))-ketolide agents. CEM-101 is being developed for oral and parenteral use in moderate to moderately severe community-acquired bacterial pneumonia. The objective of this study was to assess the activity of CEM-101 and comparators against contemporary respiratory tract infection (RTI) isolates. A worldwide sample of organisms was used, including Streptococcus pneumoniae [n=168; 59.3% erythromycin-resistant and 18 multidrug-resistant (MDR) serogroup 19A strains], Moraxella catarrhalis (n=21; 11 beta-lactamase positive), Haemophilus influenzae (n=100; 48 beta-lactamase positive), Haemophilus parainfluenzae and Haemophilus haemolyticus (n=12), and Legionella pneumophila (n=30). Testing and interpretation were performed using reference Clinical and Laboratory Standards Institute methods. CEM-101 was very potent against S. pneumoniae [minimum inhibitory concentration for 90% of the organisms (MIC90)=0.25 mg/L; highest MIC at 0.5 mg/L] and was 2- and > or =32-fold more active than telithromycin and clindamycin, respectively. CEM-101 also demonstrated potent activity against S. pneumoniae MDR-19A strains (MIC90=0.5 mg/L). CEM-101 was the most potent antimicrobial agent tested against L. pneumophila, with all MIC values at < or = 0.015 mg/L (telithromycin MIC90=0.03 mg/L). CEM-101 was as potent as azithromycin against Haemophilus spp. RTI pathogens (MIC90=2 mg/L), with no variations for beta-lactamase production. CEM-101 MIC values against M. catarrhalis were all at < or =0.5mg/L. Interestingly, CEM-101 potency was ca. 6 log(2) dilutions greater than telithromycin MIC results among 44 beta-haemolytic streptococci having telithromycin MICs > or = 2 mg/L. CEM-101 exhibited the greatest potency and widest spectrum of activity against RTI pathogens among the tested MLS(B)-ketolide agents (azithromycin, clarithromycin, erythromycin, telithromycin, clindamycin and quinupristin/dalfopristin) and was comparable overall with levofloxacin.
 ...
PMID:Antimicrobial characterisation of CEM-101 activity against respiratory tract pathogens, including multidrug-resistant pneumococcal serogroup 19A isolates. 2021 48

Among the bacterial secretion systems, the Type III, IV, and VI secretion systems enable bacteria to secrete proteins directly into a target cell. This specific form of secretion, referred to as translocation, is essential for a number of pathogens to alter or kill targeted cells. The translocated proteins, called effector proteins, can directly interfere with the normal processes of the targeted cells, preventing elimination of pathogens and promoting their multiplication. The function of effector proteins varies greatly depending on the considered pathogen and the targeted cell. In addition, there is often no magic bullet, and the number of effector proteins can range from a handful to hundreds, with, for instance, a substrate of over 300 effector proteins of the Icm/Dot Type IV secretion system in the human pathogen Legionella pneumophila. Identifying, detecting, and monitoring the translocation of each of the effector proteins represents an active field of research and is key to understanding the bacterial molecular weaponry. Translational fusion of an effector with a reporter protein of known activity remains the best method to monitor effector translocation. The development of a fluorescent substrate for the TEM-1 beta-lactamase has turned this antibiotic-resistant protein into a highly versatile reporter system for investigating protein transfer events associated with microbial infection of host cells. Here we describe a simple protocol to assay the translocation of an effector protein by the Icm/Dot system of the human pathogen Legionella pneumophila.
 ...
PMID:Monitoring Effector Translocation using the TEM-1 Beta-Lactamase Reporter System. 2866 32


<< Previous 1 2 3 4 5