Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0032285 (pneumonia)
 54,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Successful treatment of community-acquired pneumonia (CAP) can have substantial implications. As rates of antibiotic resistance of Streptococcus pneumoniae--the most common pathogen of CAP-increase, so does the likelihood that first-line pharmacotherapy will fail. Thus, the cost effectiveness and budgetary effects of treating CAP with amoxicillin/ clavulanate (AMX/CLA) extended-release (ER) and clarithromycin ER were analyzed. The model considers incidence of macrolide and AMX/ CLA-susceptible and nonsusceptible S. pneumoniae in empiric therapy. Clinical cure rates from multicenter clinical trials and published literature were used to calculate average treatment costs and success. Amoxicillin/ clavulanate ER resulted in a higher percentage of patients cured compared with clarithromycin ER (88.7% vs. 82.4%, respectively) and lower average per-patient treatment costs (dollar 437.70 vs. dollar 548.14, respectively).
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PMID:A cost-effectiveness analysis of antibiotic therapy in macrolide-resistant community-acquired pneumonia. 1626 33

CFTR (cystic fibrosis transmembrane conductance regulator) is expressed by both neutrophils and platelets. Lack of functional CFTR could lead to severe lung infection and inflammation. Here, we found that mutation of CFTR (F508del) or inhibition of CFTR in mice led to more severe thrombocytopenia, alveolar neutrocytosis and bacteriosis, and lower lipoxin A4/MIP-2 (macrophage inhibitory protein-2) or lipoxin A4/neutrophil ratios in the BAL (bronchoalveolar lavage) during acute E. coli pneumonia. In vitro, inhibition of CFTR promotes MIP-2 production in LPS-stimulated neutrophils; however, lipoxin A4 could dose-dependently suppress this effect. In LPS-induced acute lung inflammation, blockade of PSGL-1 (P-selectin glycoprotein ligand-1) or P-selectin, antagonism of PAF by WEB2086, or correction of mutated CFTR trafficking by KM11060 could significantly increase plasma lipoxin A4 levels in F508del relevant to wildtype mice. Concurrently, F508del mice had higher plasma platelet activating factor (PAF) levels and PAF-AH activity compared to wildtype under LPS challenge. Inhibiting hydrolysis of PAF by a specific PAF-AH (PAF-acetylhydrolase) inhibitor, MAFP, could worsen LPS-induced lung inflammation in F508del mice compared to vehicle treated F508del group. Particularly, depletion of platelets in F508del mice could significantly decrease plasma lipoxin A4 and PAF-AH activity and deteriorate LPS-induced lung inflammation compared to control F508del mice. Taken together, lipoxin A4 and PAF are involved in E. coli or LPS-induced lung inflammation in CFTR-deficient mice, suggesting that lipoxin A4 and PAF might be therapeutic targets for ameliorating CFTR-deficiency deteriorated lung inflammation.
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PMID:Lipoxin A4 and platelet activating factor are involved in E. coli or LPS-induced lung inflammation in CFTR-deficient mice. 2467 Nov 73

Bacterial uptake by phagocytic cells is a vital event in the clearance of invading pathogens such as Streptococcus pneumoniae. A major role of the P-selectin glycoprotein ligand-1 (PSGL-1) on leukocytes against invasive pneumococcal disease is described in this study. Phagocytosis experiments using different serotypes demonstrated that PSGL-1 is involved in the recognition, uptake and killing of S. pneumoniae. Co-localization of several clinical isolates of S. pneumoniae with PSGL-1 was demonstrated, observing a rapid and active phagocytosis in the presence of PSGL-1. Furthermore, the pneumococcal capsular polysaccharide and the main autolysin of the bacterium--the amidase LytA--were identified as bacterial ligands for PSGL-1. Experimental models of pneumococcal disease including invasive pneumonia and systemic infection showed that bacterial levels were markedly increased in the blood of PSGL-1-/- mice. During pneumonia, PSGL-1 controls the severity of pneumococcal dissemination from the lung to the bloodstream. In systemic infection, a major role of PSGL-1 in host defense is to clear the bacteria in the systemic circulation controlling bacterial replication. These results confirmed the importance of this receptor in the recognition and clearance of S. pneumoniae during invasive pneumococcal disease. Histological and cellular analysis demonstrated that PSGL-1-/- mice have increased levels of T cells migrating to the lung than the corresponding wild-type mice. In contrast, during systemic infection, PSGL-1-/- mice had increased numbers of neutrophils and macrophages in blood, but were less effective controlling the infection process due to the lack of this functional receptor. Overall, this study demonstrates that PSGL-1 is a novel receptor for S. pneumoniae that contributes to protection against invasive pneumococcal disease.
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PMID:PSGL-1 on Leukocytes is a Critical Component of the Host Immune Response against Invasive Pneumococcal Disease. 2697 45

Healthcare-associated infections (HAIs) occurring in patients treated in an intensive care unit (ICU) are serious complications in the treatment process. Aetiological factors of these infections can have an impact on treatment effects, treatment duration and mortality. The aim of the study was to determine the prevalence and microbiological profile of HAIs in patients hospitalized in an ICU over a span of 10 years. The active surveillance method was used to detect HAIs in adult patients who spent over 48 h in a general ICU ward located in southern Poland between 2007 and 2016. The study was conducted in compliance with the methodology recommended by the Healthcare-associated Infections Surveillance Network (HAI-Net) of the European Centre for Disease Prevention and Control (ECDC). During the 10 years of the study, 1849 patients hospitalized in an ICU for a total of 17,599 days acquired 510 with overall HAIs rates of 27.6% and 29.0% infections per 1000 ICU days. Intubation-associated pneumonia (IAP) posed the greatest risk (15.2 per 1000 ventilator days), followed by CLA-BSI (8.0 per 1000 catheter days) and CA-UTI (3.0 per 1000 catheter days). The most common isolated microorganism was Acinetobacter baumannii (25%) followed by Coagulaase-negativ staphylococci (15%), Escherichia coli (9%), Pseudomonas aeruginosa (8%), Klebsiella pneumoniae (7%), Candida albicans (6%). Acinetobacter baumannii in 87% and were classified as extensive-drug resistant (XDR). In summary, in ICU patients pneumonia and bloodstream infections were the most frequently found. Acinetobacter baumannii strains were most often isolated from clinical materials taken from HAI patients and showed resistance to many groups of antibiotics. A trend of increasing resistance of Acinetobacter baumannii to carbapenems was observed.
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PMID:Incidence, Microbiological Profile and Risk Factors of Healthcare-Associated Infections in Intensive Care Units: A 10 Year Observation in a Provincial Hospital in Southern Poland. 2932 51

Objective: Legionella is a waterborne pathogen that causes a severe form of pneumonia called Legionnaires' diseases, which is normally acquired by inhalation of aerosols containing Legionella originating from natural and man-made water systems. The aim of this study was to describe the level of antimicrobial susceptibility of environmental Legionella spp. strains to preferred and recommended therapeutic agents to treat Legionella disease. Methods: The minimum inhibitory concentrations (MICs) of 60 environmental Legionella spp. strains were tested using the broth dilution method. Susceptibility testing was performed for 12 antimicrobial agents: macrolides (erythromycin, azithromycin [AZI], and clarithromycin [CLA]), fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin, and gemifloxacin), a ketolide (telithromycin), cefotaxime (CEF), tigecycline (TIG), doxycycline (DOX), and rifampicin (RIF). Results: All tested strains of Legionella spp. were inhibited by low concentrations of fluoroquinolones and macrolides. Regarding the macrolides, CLA was the most active antibiotic, and AZI was the least active. RIF was the most effective antibiotic against the isolates in vitro. All isolates were inhibited by the following antibiotics (in decreasing order of their MICs): DOX>CEF>TIG. Conclusions: No resistance against these drugs was detected, and all isolates were inhibited by low concentrations of the tested antibiotics. Susceptibility testing of environmental Legionella spp. isolates must be monitored often to detect and evaluate the possible development of antibiotic resistance.
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PMID:Antimicrobial Susceptibility Patterns of Legionella spp. Strains Isolated from Water Systems in Morocco. 3212 20

Introduction: In recent years, an increase in healthcare-associated infections (HAIs) caused by resistant pathogens, which is a clinically troublesome trend, has been observed. The aim of the study was to analyze the microbial factors of HAIs and the drug resistance of microorganisms to selected antibiotics and their consumption. Material and Methods: The retrospective study included 3708 patients hospitalized in the intensive care unit (ICU) of the University Teaching Hospital in Wroclaw, who were diagnosed with 742 HAIs in the period from 1 January 2011 to 31 December 2018. The aim of the study was the analysis of microorganisms isolated in the respective clinical forms of HAIs, including the occurrence of "alert pathogens", presence of multidrug-resistant (MDR) strains, and consumption of selected antibiotics. Findings: During the study period, 846 microorganisms were cultured in patients with HAIs, and among them, Acinetobacter baumannii MDR represented 31.8%; Klebsiella pneumoniae ESBLs, 11.3%; Pseudomonas aeruginosa MDR, 4.1% and MRSA, 2.2%; and Enterococcus spp. vancomycin-resistant enterococci (VRE), 1.3%. Among all the pathogens, Gram-negative bacteria (GNB) were dominant (71.6%). Gram-positive bacteria and fungi accounted for 21.6% and 7%, respectively. The total number of strains responsible for ventilator-associated pneumonia (VAP), urinary tract infection (UTI), and central line-associated blood stream infection (CLA-BSI) was as follows: 458 (54.1%), 274 (32.4%), and 114 (13.5%), respectively. Among the etiological factors of VAP, there was a prevalence of A. baumannii MDR (41.9%), as well as in the case of UTI (21.9%). With regards to CLA-BSI, MRCNS (29.8%) was the dominant pathogen. The "alert pathogens" accounted for 54.7% of all the analyzed strains. The MDR strains represented 72.6% and 9.7% among A. baumannii and P. aeruginosa, respectively. In the years 2011 vs. 2018, an increase in infections with MDR bacilli was observed, 34.6% vs. 61.0% (p = 0.0008), respectively, including A. baumannii MDR 16.54% vs. 34.56 % (p = 0.0009) and Enterobacterales ESBL+/AMPC 11.8% vs. 15.44 % (p = 0.3921). Resistance to methicillin was confirmed in 35.2% of S. aureus strains. Resistance to vancomycin was found among 30.9% of Enterococcus spp. The observed period was marked by an increase in the consumption of carbapenems: 197.7 vs. 235.9 defined daily dose (DDD)/1000 patients-days. Conclusions: Gram-negative bacteria were found to be dominant pathogens in healthcare-associated infections. The most frequently cultured pathogens were multidrug-resistant A. baumannii, K. pneumoniae ESBL(+), and P. aeruginosa. The study showed an increase in the incidence of "alert pathogens" and MDR bacilli, as well as the tendency of a growing resistance to antibiotics during the observed period. Microbiological analysis of HAIs and the consumption of antibiotics is the necessary element of the proper antibiotic policy in hospitals.
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PMID:Characteristics of Microbial Factors of Healthcare-Associated Infections Including Multidrug-Resistant Pathogens and Antibiotic Consumption at the University Intensive Care Unit in Poland in the Years 2011-2018. 3297 35