Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026936 (Mycoplasma)
 14,761 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this multicenter study was to identify the causative pathogens of community-acquired pneumonia (CAP) in Shanghai, China, and to determine their susceptibility to antimicrobial agents. Pathogens obtained from 389 patients with documented CAP during 2001-2003 were identified by multiple diagnostic tools that included bacterial culture, polymerase chain reaction (PCR), and specific immunological assays. Susceptibility of the bacterial isolates was tested by the broth microdilution method. A specific pathogen was identified in 39.8% (155/389) of the patients: Haemophilus influenzae (n=80), Klebsiella spp. (n=15), Streptococcus pneumoniae (n=12), Staphylococcus aureus (n=6), Moraxella catarrhalis (n=1), other gram-negative organisms (n=9), and atypical pathogens that comprised Mycoplasma pneumoniae (n=42), Chlamydia pneumoniae (n=17), and Legionella pneumophila (n=2). Most H. influenzae isolates were susceptible to ampicillin (88.3%), and all were susceptible to macrolides. Of the S. pneumoniae isolates, 75% (9/12) were susceptible to penicillin, while 25% (3/12) were intermediately susceptible. H. influenzae and atypical pathogens are among the most important pathogens of CAP. Ampicillin, cephalosporins, and the newer fluoroquinolones can be used as empirical therapy for CAP in the Shanghai area. The efficacy of monotherapy with newer macrolides for CAP caused by S. pneumoniae requires further evaluation.
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PMID:Community-acquired pneumonia in Shanghai, China: microbial etiology and implications for empirical therapy in a prospective study of 389 patients. 1676 84

The objective of this study was to determine the plasma and intrapulmonary pharmacokinetic parameters of intravenously administered levofloxacin in healthy volunteers. Three doses of either 750 mg or 1000 mg levofloxacin were administered intravenously to 4 healthy adult subjects (750 mg) to 20 healthy adult subjects divided into five groups of 4 subjects (1000 mg). Standardised bronchoscopy and timed bronchoalveolar lavage (BAL) were performed following administration of the last dose. Blood was obtained for drug assay prior to drug administration and at the time of BAL. Levofloxacin was measured in plasma, BAL fluid and alveolar cells (ACs) using a sensitive and specific combined high-performance liquid chromatographic tandem mass spectrometric technique (HPLC/MS/MS). Plasma, epithelial lining fluid (ELF) and AC pharmacokinetics were derived using non-compartmental methods. The maximum plasma drug concentration to minimum inhibitory concentration ratio (C(max)/MIC(90)) and the area under the drug concentration curve to minimum inhibitory concentration ratio (AUC/MIC(90)) during the dosing interval were calculated for potential respiratory pathogens with MIC(90) values from 0.03 microg/mL to 2 microg/mL. In the 1000 mg dose group, the C(max) (mean+/-standard deviation (S.D.)), AUC(0-8h) and half-life were: for plasma, 9.2+/-1.9 microg/mL, 103.6 microg h/mL and 7.45 h; for ELF, 25.8+/-7.9 microg/mL, 279.1 microg h/mL and 8.10h; and for ACs, 51.8+/-26.2 microg/mL, 507.5 microg h/mL and 14.32 h. In the 750 mg dose group, the C(max) values in plasma, ELF and ACs were 5.7+/-0.4, 28.0+/-23.6 and 34.2+/-18.7 microg/mL, respectively. Levofloxacin concentrations were significantly higher in ELF and ACs than in plasma at all time points. For pathogens commonly associated with community-acquired pneumonia, C(max)/MIC(90) ratios in ELF ranged from 12.9 for Mycoplasma pneumoniae to 859 for Haemophilus influenzae, and AUC/MIC(90) ratios ranged from 139 to 9303, respectively. The C(max)/MIC(90) ratios in ACs ranged from 25.9 for M. pneumoniae to 1727 for H. influenzae, and AUC/MIC(90) ratios ranged from 254 to 16917, respectively. The C(max)/MIC(90) and AUC/MIC(90) ratios provide a pharmacokinetic rationale for once-daily administration of a 1000 mg dose of levofloxacin and are favourable for the treatment of community-acquired respiratory pathogens.
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PMID:Intrapulmonary pharmacokinetics and pharmacodynamics of high-dose levofloxacin in healthy volunteer subjects. 1683 69

The recent literature brings nothing new since it provides only fragmented, though undoubtedly useful, studies which remain within the prevalence interval for the different bacterias. The occurrence of germs varies with time and space; nevertheless, whatever the studied series and the site of the studies, the 3 most frequent causal germs belong to the following five strains: Streptococcus pneumoniae, Influenza A, Mycoplasma pneumoniae, Haemophilus influenzae, and Legionella pneumophila. Thus, 90% of all documented pneumoniae appear to be caused by the following pathogens: Pneumococcus; most frequent in hospitalized patients; Mycoplasma, Chlamydia and respiratory viruses were predominant in outpatients, with great variations; Staphylococcus and enterobacteriace may be encountered, mostly in elderlies with major debilitating diseases; association of germs, generally including pneumococcus, are increasingly identified. Last, in 25% to 50% of cases, the causal agent is not known. Recently, some Staphylococcus meticillin-resistant were identified. The diagnosis of viruses (as well as that of atypical bacterias) seems to have improved, thanks to the use of PCR though the interest of such a diagnosis remains questionable, except for epidemiological studies, as well as the relevance of this type of test in clinical practice. Nothing really new has come out on the epidemiology of acute bronchitis, while in bacterial exacerbation of COPD, attention focused on the colonizing or infective role of H. influenzae in the genesis of bronchus inflammation.
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PMID:[Current epidemiology of microbial low respiratory tract infections]. 1701 Nov 49

The objective of this study was to determine the plasma and intrapulmonary pharmacokinetic parameters of intravenously administered levofloxacin in subjects with stable chronic lung disease. Three doses of 1000 mg levofloxacin were administered once daily to 16 adult subjects divided into four groups of 4 subjects each. Standardised bronchoscopy and timed bronchoalveolar lavage (BAL) were performed at 4 h, 8 h, 12 h and 24 h following administration of the last dose. Blood was obtained for drug assay prior to drug administration, at the end of the last infusion (maximum concentration (Cmax)) and at the time of BAL. Levofloxacin was measured using a high-performance liquid chromatographic tandem mass spectrometric (HPLC/MS/MS) technique. Plasma, epithelial lining fluid (ELF) and alveolar cell (AC) pharmacokinetics were derived using non-compartmental methods. Cmax/MIC(90) and area under the concentration-time curve for 0-24 h after the last dose (AUC(0-24 h)/MIC(90) ratios were calculated for respiratory pathogens with minimum inhibitory concentrations for 90% of the organisms (MIC(90)) of 0.03-2 microg/mL. The Cmax (mean+/-standard deviation), AUC(0-24h) and half-life were, respectively, 9.2+/-2.7 microg/mL, 130 microg h/mL and 8.7 h for plasma, 22.8+/-12.9 microg/mL, 260 microg h/mL and 7.0 h for ELF and 76.3+/-28.7 microg/mL, 1492 microg h/mL and 49.5 h for ACs. Levofloxacin concentrations were quantitatively greater in ACs than in ELF or plasma at all time points, however only the differences between AC concentration and ELF or plasma concentrations in the 4-h and 8-h time groups were statistically significant. Cmax/MIC(90) and AUC/MIC(90) ratios in ELF were, respectively, 11.4 and 130 for Mycoplasma pneumoniae, 22.8 and 260 for Streptococcus pneumoniae, 91.2 and 1040 for Chlamydia pneumoniae and 760 and 8667 for Haemophilus influenzae. In ACs the ratios were 38.2 and 746 for M. pneumoniae, 76.3 and 1492 for S. pneumoniae, 305 and 5968 for C. pneumoniae and 2543 and 49 733 for H. influenzae. In conclusion, Cmax/MIC(90) and AUC/MIC(90) ratios provide a pharmacokinetic rationale for once-daily administration of a 1000 mg dose of levofloxacin and are favourable for the treatment of respiratory infection in patients with chronic lung disease.
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PMID:Intrapulmonary pharmacodynamics of high-dose levofloxacin in subjects with chronic bronchitis or chronic obstructive pulmonary disease. 1771 73

In recent years, Streptococcus pneumoniae and Haemophilus influenzae, two of the most common pathogens causing bronchopulmonary infections, have developed resistance towards beta-lactam antibiotics in many areas of the globe. In some countries, resistance rates are so high that treatment with penicillin can not be recommended as the therapy of choice. Unfortunately, many S. pneumoniae strains resistant to penicillins are also resistant to co-trimoxazole and erythromycin, and even to the novel macrolides. Present fluoroquinolones may have to be used in such resistant cases. The fluoroquinolones possess a superior activity against H. influenzae and other pathogens causing bronchitis and pneumonia. Fluoroquinolones have a favourable pharmacokinetic profile including penetration into sputum, bronchial fluid, alveolar lining fluid and alveolar macrophages, and therapeutic concentrations and ratios are superior to those of the beta-lactams. Fluoroquinolones have been shown to produce better results than the comparative agents in bronchitis and, in cystic fibrosis, they achieve a definite clinical amelioration in paediatric patients without substantial additional toxicity. Their use in legionnaires' disease has not been confirmed and their place in the treatment of community-acquired pneimonias - particularly those caused by Mycoplasma pneumoniae and Chlamydia trachomatis and the TWAR agent - deserves further investigation.
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PMID:Fluoroquinolones in bronchopulmonary infections. 1861 78

Garenoxacin mesylate hydrate (GRN) is a novel oral des-fluoro(6) quinolone with potent antimicrobial activity against common respiratory pathogens, including resistant strains. It has favourable pharmacokinetic profiles for maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC), with good penetration into sputum and otorhinolaryngological tissues. In clinical studies, the efficacy of GRN ranged from 92% to 96% in patients with bacterial pneumonia, mycoplasma pneumonia, chlamydial pneumonia and acute bronchitis. Efficacy was 85% in acute infectious exacerbations of chronic respiratory disease and ranged from 81% to 95% in otorhinolaryngological infections. Bacterial eradication was 90.9% for Staphylococcus aureus, 99.2% for Streptococcus pneumoniae, 98.2% for Haemophilus influenzae, 96.6% for Moraxella catarrhalis, 100% for penicillin-resistant S. pneumoniae, 100% for beta-lactamase-negative ampicillin-resistant H. influenzae and beta-lactamase-positive H. influenzae, and 96.2% for beta-lactamase-positive M. catarrhalis. Garenoxacin concentrations in plasma and tissues using GRN 400mg once a day were higher than the MIC90 (minimum inhibitory concentration for 90% of the organisms) of major causative pathogens. The trough concentration (Cmin) in plasma was 1.92 microg/mL, a level that was higher than the mutant prevention concentration, suggesting that GRN is unlikely to induce the selection of resistant strains during treatment. In clinical studies, GRN did not produce class adverse effects of fluoroquinolones such as QTc prolongation, blood glucose abnormality or severe liver damage. No serious adverse events were observed during the trials. The results indicate that GRN is very effective in treating patients with upper and lower respiratory tract infections.
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PMID:Clinical studies of garenoxacin. 1879 Jun 8

Tracheal aspirates were collected from 176 hospitalized antibiotic-pretreated children with community-acquired pneumonia. Haemophilus influenzae and Streptococcus pneumoniae were detected by both culture and target-enriched multiplex (TEM)-PCR whereas Mycoplasma pneumoniae and Chlamydia pneumoniae were detected by TEM-PCR only. TEM-PCR detected more S. pneumoniae (32 vs. 7) and H. influenzae (29 vs. 23) than did culture. TEM-PCR detected an additional 26 M. pneumoniae and 1 C. pneumoniae. TEM-PCR significantly enhances the pathogen-specific diagnosis of CAP in children.
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PMID:Culture versus polymerase chain reaction for the etiologic diagnosis of community-acquired pneumonia in antibiotic-pretreated pediatric patients. 1903 66

We aimed to detect causative pathogens in cerebrospinal fluid (CSF) collected from patients diagnosed with bacterial meningitis by real-time polymerase chain reaction (PCR). In addition to Streptococcus pneumoniae, Haemophilus influenzae, and Mycoplasma pneumoniae described previously, five other pathogens, Neisseria meningitidis, Escherichia coli, Streptococcus agalactiae, Staphylococcus aureus, and Listeria monocytogenes, were targeted, based on a large-scale surveillance in Japan. Results in CSF from neonates and children (n=150), and from adults (n=18) analyzed by real-time PCR with molecular beacon probes were compared with those of conventional culturing. The total time from DNA extraction from CSF to PCR analysis was 1.5 h. The limit of detection for these pathogens ranged from 5 copies to 28 copies per tube. Nonspecific positive reactions were not recognized for 37 microorganisms in clinical isolates as a negative control. The pathogens were detected in 72.0% of the samples by real-time PCR, but in only 48.2% by culture, although the microorganisms were completely concordant. With the real-time PCR, the detection rate of H. influenzae from CSF was high, at 45.2%, followed by S. pneumoniae (21.4%), S. agalactiae (2.4%), E. coli (1.8%), L. monocytogenes (0.6%), and M. pneumoniae (0.6%). The detection rate with PCR was significantly better than that with cultures in patients with antibiotic administration (chi2=18.3182; P=0.0000). In conclusion, detection with real-time PCR is useful for rapidly identifying the causative pathogens of meningitis and for examining the clinical course of chemotherapy.
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PMID:Rapid detection of eight causative pathogens for the diagnosis of bacterial meningitis by real-time PCR. 1939 18

According to the recommendations of the Swedish Community-Acquired Pneumonia (CAP) guidelines, the selection of empirical antibiotic therapy should be based on the CRB-65 rule. The guidelines recommend empirical therapy directed predominantly against Streptococcus pneumoniae for patients with low CRB-65 scores and broad-spectrum therapy for patients with high CRB-65 scores. In order to study the utility of the recommendations, we analyzed the data from an aetiological study previously performed on 235 hospitalized adult CAP patients at our medical centre. A definite, probable, or possible bacterial aetiology was noted in 194 cases (83%), including 112 cases (48%) with S. pneumoniae aetiology. The following frequencies of definite-probable aetiologies were noted in the patients with CRB-65 score 0-1 (n=155) and CRB-65 score 2-4 (n=80): S. pneumoniae 30% and 35%, Haemophilus influenzae 6.5% and 14% (p=0.063), Mycoplasma pneumoniae 15% and 5.0% (p=0.019), Chlamydophila species 2.6% and 1.2%, Legionella pneumophila 1.9% and 0%, and Staphylococcus aureus 1.3% and 1.2%, respectively. The high frequency of S. pneumoniae in the study supports the recommendations to predominantly cover this bacterium in the empirical therapy of patients with low CRB-65 scores. In the case of treatment failure in these patients, the study indicates that coverage against M. pneumoniae and H. influenzae should be considered.
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PMID:Definite, probable, and possible bacterial aetiologies of community-acquired pneumonia at different CRB-65 scores. 2014 90

Resistance to macrolides and beta-lactams has increased sharply amongst key respiratory pathogens, leading to major concern. A novel series of acylides was designed to overcome this resistance and was evaluated for in vitro and in vivo activity. This series of acylides was designed starting from clarithromycin by changing the substitution on the desosamine nitrogen, followed by conversion to 3-O-acyl and 11,12-carbamate. Minimum inhibitory concentrations (MICs) of acylides were determined against susceptible as well as macrolide-lincosamide-streptogramin B (MLS(B))--and penicillin-resistant Streptococcus pneumoniae, Streptococcus pyogenes and Moraxella catarrhalis by the agar dilution method. Microbroth MICs for Haemophilus influenzae were determined according to Clinical and Laboratory Standards Institute guidelines. In vivo efficacy was determined by target organ load reduction against S. pneumoniae 3579 (ermB). The bactericidal potential of promising acylides was also determined. MICs of these compounds against S. pneumoniae, S. pyogenes, H. influenzae and M. catarrhalis were in the range of 0.06-2, 0.125-1, 1-16 and 0.015-0.5 microg/mL, respectively, irrespective of their resistance pattern. Mycoplasma pneumoniae and Legionella pneumophila showed MIC ranges of 0.004-0.125 microg/mL and 0.004-0.03 microg/mL, respectively. The acylides also showed better activity against telithromycin-resistant S. pneumoniae strains. Compounds with a 4-furan-2-yl-1H-imidazolyl side chain on the carbamate (RBx 10000296) showed a target organ load reduction of >3 log(10) colony-forming units/mL and concentration-dependent bactericidal potential against S. pneumoniae 994 mefA and H. influenzae strains. This novel and potent series of acylides active against antibiotic-resistant respiratory pathogens should be further investigated.
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PMID:Activity of a novel series of acylides active against community-acquired respiratory pathogens. 2049 66


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