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:C0348321 (Haemophilus)
15,372 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Azithromycin is a new macrolide which accumulates in high concentrations in human phagocytes. The cellular to extracellular ratio (C/E) of azithromycin concentrations (fixed extracellular concentration 1 mg/L) in human polymorphonuclear leucocytes (PMN) were significantly affected by small increases in the environmental temperature (C/E 20.3 +/- 2 and 59.4 +/- 6 at 37 degrees C and 40 degrees C, respectively). PMN-associated azithromycin was not affected by the presence of different concentrations of human serum. The intracellular accumulation of azithromycin decreased slightly (C/E approximately 5) when cells were activated with PMA or opsonized with zymosan. The phagocytosis of opsonized Staphylococcus aureus or Haemophilus influenzae, however, slightly increased the intracellular concentrations of azithromycin. At different extracellular concentrations, azithromycin did not affect the production of hydrogen peroxide and superoxide radicals by PMN. The intracellular survival of H. influenzae in human PMN was abolished in the presence of concentrations higher than 0.125 mg/L of azithromycin. Under the same experimental conditions, however, azithromycin did not show any intracellular activity against S. aureus.
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PMID:Factors affecting the intracellular accumulation and activity of azithromycin. 776 86

Some recently marketed macrolide antimicrobial agents possess physiochemical, antimicrobial, and pharmacokinetic advantages that enable their wider clinical use against Haemophilus influenzae infections. A five-laboratory study assessed the validity of existing or proposed azithromycin, clarithromycin, and erythromycin interpretive criteria for tests with H. influenzae isolates. National Committee for Clinical Laboratory Standards (NCCLS) methods, criteria, and quality-control guidelines were used. A total of 350 H. influenzae strains were processed, including fresh clinical isolates (250 strains) and replicate tests of 100 stock cultures sampling strains isolated from 1984 to 91. Azithromycin interpretive criteria (susceptible at < or = 4 micrograms/ml, > or = 12 mm) produced a 99.8% absolute agreement between the minimum inhibitory concentrations and disk diffusion results (0.2% false-susceptible error). Clarithromycin breakpoint criteria (susceptible at < or = 8 micrograms/ml, > or = 13 mm; and resistant at > or = 32 micrograms/ml, < or = 10 mm) produced high minor interpretive error, but < or = 1% combined false-susceptible and false-resistant discrepancies. Erythromycin interpretive guidelines were initially proposed for susceptible at < or = 0.5 microgram/ml, > or = 26 mm. This categorizes nearly all H. influenzae strains as resistant to this older macrolide. The NCCLS should consider the proposed erythromycin criteria for publication in appropriate tables, and a class drug should also be selected (azithromycin) that would best predict macrolide-class susceptibility for those agents indicated by the US Food and Drug Administration for H. influenzae infection chemotherapy (azithromycin and clarithromycin). No serious interpretive problems were observed with the current NCCLS criteria using Haemophilus test medium.
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PMID:Validation of NCCLS macrolide (azithromycin, clarithromycin, and erythromycin) interpretive criteria for Haemophilus influenzae tested with the Haemophilus test medium. National Committee for Clinical Laboratory Standards. 792 21

Clinical efficacy of azithromycin and erythromycin was compared in an open trial in 32 and 18 patients with acute sinusitis respectively. The following pathogens were isolated: Haemophilus influenzae (29.8 per cent), Streptococcus pneumoniae (19.1 per cent), Staphylococcus aureus (10.6 per cent), Streptococcus faecalis (8.5 per cent) and other microbes (8.5 per cent). Azithromycin was administered in a dose of 500 mg on day 1. During the following 4 days it was administered in a dose of 250 mg. Erythromycin was administered in a dose of 500 mg 4 times a day for 8 to 10 days. 91.2 per cent of the aerobic microflora were sensitive to azitromycin and 85.3 per cent were sensitive to erythromycin. One of 14 strains of H. influenzae proved to be resistant to azithromycin, 3 strains were resistant to erythromycin. Complete recovery was stated in 90.6 per cent of the cases treated with azithromycin and 66.7 per cent of the cases treated with erythromycin.
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PMID:[Comparative clinical effectiveness and tolerance of azithromycin (sumamed) and erythromycin in patients with sinusitis]. 806 Jan 76

MICs of erythromycin, clarithromycin, and azithromycin for 852 recent clinical isolates were determined by broth microdilution methods. Frequency distribution curves, scattergrams, and regression analyses were used to compare in vitro activities and describe cross-resistance. Clarithromycin was the most active drug against Bacteroides spp. but the least active against Haemophilus influenzae. Azithromycin was most active against H. influenzae, Moraxella catarrhalis, Pasteurella multocida, and Fusobacterium spp. but the least active against Streptococcus spp. and Enterococcus spp. All three drugs had equivalent activities against Staphylococcus spp. and gram-positive anaerobes. None of the three drugs was particularly active against members of the family Enterobacteriaceae or nonfermentative gram-negative bacilli, although concentrations of 4 micrograms of azithromycin per ml inhibited some strains of the family Enterobacteriaceae (particularly Escherichia coli and Citrobacter diversus) and Acinetobacter baumannii. Although relative drug activities varied by organism, organisms relatively susceptible to one were relatively susceptible to all and organisms relatively resistant to one were relatively resistant to all; an exception was fusobacteria, which were usually susceptible only to azithromycin. Cross-susceptibility and cross-resistance were, therefore, the rule (except for Fusobacterium spp.), although the percentage of susceptible organisms could be varied considerably on the basis of the selection of breakpoints.
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PMID:Erythromycin, clarithromycin, and azithromycin: use of frequency distribution curves, scattergrams, and regression analyses to compare in vitro activities and describe cross-resistance. 825 27

One of the chemical features that distinguishes the 15-membered ring azalide azithromycin from the 14-membered ring macrolide compound erythromycin is the former's increased stability at acid pH. Azithromycin also differs pharmacokinetically from erythromycin, an important feature being azithromycin's ability to achieve high tissue concentrations, with the agent being delivered to the sites of infection by direct uptake and by targeted delivery via phagocytes. High tissue concentrations are maintained for prolonged periods because of azithromycin's long half-life, leading to once-daily dosing for 3 or 5 days. Notable microbiological features of azithromycin are in-vitro activity against many pyogenic bacteria (e.g. Neisseria gonorrhoeae and Moraxella catarrhalis), as well as organisms against which beta-lactam antibiotics are usually ineffective (e.g. Legionella and Chlamydia spp.), organisms that are resistant to benzylpenicillin and erythromycin (e.g. Haemophilus influenzae) and organisms for which satisfactory therapy is limited (e.g. Toxoplasma gondii and the Mycobacterium avium-intracellulare complex). These properties of azithromycin suggest that it might be a useful agent for the treatment of a wide range of bacterial infections.
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PMID:Azithromycin--review of key chemical, pharmacokinetic and microbiological features. 881 41

Azithromycin reaches high concentrations in phagocytic and other host cells, suggesting that they may transport this agent to specific sites of infection. Models of localized infection (Haemophilus influenzae middle ear infection in gerbils, Streptococcus pyogenes implanted contaminated paper disc and Streptococcus pneumoniae pneumonia in mice) that induced severe inflammatory response after challenge were used to explore this hypothesis. Animals were given a single 100 or 50 mg/kg po dose of azithromycin at various times from 2 to 120 h following introduction of a pathogen or sterile medium. When azithromycin was given during a period of little or no inflammation, there was marginal difference between concentrations found in infected or non-infected sites (bulla, disc, lung). However, when the compound was given during a period of inflammation, considerably higher drug concentrations were found in infected sites than in non-infected sites at 5-24 h after dosing (0.38-0.44 mg/c compared with 0.07-0.14 mg/L of bulla wash; 1.01-1.75 micrograms compared with < or = 0.01-0.03 microgram at the disc site; 1.72-5.28 mg/kg compared with 0.7-1.53 mg/kg of lung). When the observation periods were extended to include 48, 56 or 96 h after dosing, the ratio of azithromycin infection site concentration: serum concentration steadily increased with time in all model systems (middle ear, implanted disc and pneumonia), reflecting the maintenance of concentrations at the sites of infection, while serum concentrations declined. Bioassay of cell pellets and supernatants, obtained from pooled bulla washes of gerbils treated with azithromycin during a period of inflammation, revealed that cellular components accounted for about 75% of the azithromycin detected. These data show that increased azithromycin concentrations occur at sites of localized infection. This correlates with the presence of inflammation and is associated with the cellular components of the inflammatory response. Therefore, phagocytes may be important vehicles for delivering azithromycin to and sustaining azithromycin concentrations at sites of infection.
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PMID:Correlation of increased azithromycin concentrations with phagocyte infiltration into sites of localized infection. 881 42

In an open, multicentre study, the clinical and bacteriological efficacy, safety and tolerance of azithromycin and roxithromycin were compared in a total of 204 adults with acute lower respiratory tract infections (LRTIs) [acute bronchitis, acute infectious exacerbations of chronic bronchitis (AIECBs), or pneumonia]. Following treatment with 500 mg/day azithromycin administered orally once daily for 3 days, a satisfactory clinical response of cure or improvement was recorded in 91/99 (91.9%) evaluable patients at the post-therapy evaluation (day 10-14). Of the 94 evaluable patients treated with roxithromycin (150 mg given orally twice daily for 10 days), 82 (87.2%) were classified as cured or improved at post-therapy. The main pathogens isolated before treatment were Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus species, Haemophilus influenzae and Moraxella catarrhalis. In the 46 azithromycin-treated patients evaluated both clinically and bacteriologically, 92.0% of pathogens were eradicated; H. influenzae persisted in one azithromycin-treated patient with acute bronchitis who was classed as clinically improved. In the roxithromycin group, 81.1% of the pathogens were eradicated in 35 patients; S. aureus persisted in one clinically cured patient with acute bronchitis, and H. influenzae persisted in one patient with AIECB and one with pneumonia, and Haemophilus species in one with AIECB, who were all classified as clinically improved. Azithromycin was well tolerated with a lower incidence of adverse events than that recorded in the roxithromycin treatment group. Treatment was not discontinued due to adverse events in any of the azithromycin-treated patients, whereas two roxithromycin-treated patients were withdrawn from treatment due to vomiting and/or dyspepsia.
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PMID:Efficacy, safety and tolerability of azithromycin versus roxithromycin in the treatment of acute lower respiratory tract infections. 881 52

The azalide antibacterial agent azithromycin is a semisynthetic acid-stable erythromycin derivative with an expanded spectrum of activity and improved tissue pharmacokinetic characteristics relative to erythromycin. The drug is noted for its activity against some Gram-negative organisms associated with respiratory tract infections, particularly Haemophilus influenzae. Azithromycin has similar activity to other macrolides against Streptococcus pneumoniae and Moraxella catarrhalis, and is active against atypical pathogens such as Legionella pneumophila, Chlamydia pneumoniae and Mycoplasma pneumoniae. Once-daily administration of azithromycin is made possible by the long elimination half-life of the drug from tissue. Azithromycin is rapidly and highly concentrated in a number of cell types after absorption, including leucocytes, monocytes and macrophages. It undergoes extensive distribution into tissue, from where it is subsequently eliminated slowly. A 3-day oral regimen of once-daily azithromycin has been shown to be as effective as 5- to 10-day courses of other more frequently administered antibacterial agents [such as erythromycin, amoxicillin-clavulanic acid and phenoxymethylpenicillin (penicillin V)] in patients with acute exacerbations of chronic bronchitis, pneumonia, sinusitis, pharyngitis, tonsillitis and otitis media. Adverse effects of azithromycin are mainly gastrointestinal in nature and occur less frequently than with erythromycin. Azithromycin is likely to prove most useful as a 3-day regimen in the empirical management of respiratory tract infections in the community. Its ease of administration and 3-day duration of therapy, together with its good gastrointestinal tolerability, should optimise patient compliance (the highest level of which is achieved with once-daily regimens). Azithromycin is also likely to be useful in the hospital setting, particularly for outpatients and for those unable to tolerate erythromycin.
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PMID:Azithromycin. A review of its pharmacological properties and use as 3-day therapy in respiratory tract infections. 888 83

To provide optimal management for the child with community-acquired pneumonia, the clinician must take multiple factors into consideration. The etiology of pneumonia is difficult to determine and initial choice of therapy is based on the frequency of pathogens in various age groups, local antibiotic resistance patterns of the organisms, clinical presentation, and epidemiological data. Streptococcus pneumoniae and Haemophilus influenzae remain the most common bacterial pathogens outside the newborn period. Increasing numbers of multidrug-resistant strains of S pneumoniae in the United States and Europe, the decline in H influenzae type b because of current vaccination strategies, and increasing recognition of nontypeable H influenzae as etiologic agents of pneumonia have prompted reconsideration of the drug of choice. Amoxicillin and its derivatives or oral cephalosporins are the drugs of choice for initial therapy for mild to moderate disease. For severe disease or if beta-lactamase producing organisms are a concern, extended spectrum cephalosporins are indicated. Pneumococcal pneumonia unresponsive to penicillin therapy may warrant the use of extended spectrum cephalosporins or vancomycin. For older children in whom mycoplasma is a significant cause of pneumonia, the new macrolides have provided additional options for the clinician. Azithromycin and clarithromycin are efficacious, well tolerated, and require less frequent dosing intervals. The introduction of ceftriaxone, a third-generation cephalosporin with a broad spectrum of activity and prolonged half-life, allows once-a-day intramuscular therapy that can be administered on an outpatient basis. With the availability of parenteral outpatient therapy, hospital admission is no longer required for the treatment of most cases of serious community-acquired pneumonia.
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PMID:Antimicrobial therapy of pneumonia in infants and children. 888 71

Azithromycin (AZM) was studied for its clinical efficacy in pediatric infections. The study on AZM was carried out in 43 patients whose diagnoses were given as follows: pharyngitis in five cases, tonsillitis in one, bronchitis in four, pneumonia in four, Mycoplasma pneumonia in 14, scarlet fever in nine, impetigo in four, pyodermia in one and Campylobacter enteritis in one. The patients received AZM once daily at 1.6 approximately 20.0 mg/kg body weight for three to five days. Effectiveness of AZM was evaluated in 39 cases and the drug was rated "excellent" in 15, "good" in 19, "fair" in one, "poor" in four, resulting in an efficacy rate of 87.2%. Twenty bacterial isolates were identified as causative isolates in 19 patients: Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, Haemophilus influenzae, Campylobacter jejuni and Mycoplasma pneumoniae. AZM eradicated 16 isolates but four persisted after therapy. One patient complained of loose stool, while two patients were found with decreases in white blood cell counts, and seven showed increases in eosinophils. However, no serious case of adverse event was reported.
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PMID:[Clinical evaluation of azithromycin in pediatric infections]. 898 54


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