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)

Azithromycin is a new acid-stable 15-membered-ring macrolide that exhibits an extended half-life and excellent tissue distribution, including distribution in the lung. We compared its in vivo activity with that of erythromycin using two models of Streptococcus pneumoniae pneumonia, namely, a model of acute infection in Swiss mice and a model of subacute infection in C57BL/6j mice. Female mice were infected by oral delivery into the trachea of 10(5) CFU of a virulent serotype 3 strain of S. pneumoniae (P 4241). Prophylactic and therapeutic treatments were given orally (p.o.) or subcutaneously (s.c.) by various regimens. In the model of subacute infection, a single dose of azithromycin, 25 mg/kg, given p.o. 7 h before infection protected 92% of the mice, while erythromycin was completely ineffective. In the model of acute infection, a single dose of azithromycin, 50 mg/kg, given s.c. 24 h prior to challenge protected 80% of the mice, whereas only 35% of the mice survived with erythromycin, 50 mg/kg, 1 h before challenge. Therapy, which was studied exclusively in the model of subacute infection, was initiated 48 h postinfection. Two doses of 12.5 mg/kg given p.o. 12 h apart resulted in 80% survival of mice treated with azithromycin versus 7% survival of mice treated with erythromycin. Pulmonary clearance of bacteria was consistent with the survival rates. Two doses (25 mg/kg) of azithromycin given s.c. at 48 and 65 h after infection led to complete clearance of bacteria from the lungs and blood, whereas erythromycin-treated mice remained bacteremic. The pharmacokinetics of azithromycin account for its superior efficacy against S. pneumoniae pneumonia relative to the efficacy of erythromycin.
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PMID:Prophylactic and therapeutic activities of azithromycin in a mouse model of pneumococcal pneumonia. 165 49

Azithromycin is a new macrolide antimicrobial. The distribution to the potential sites of pulmonary infection was assessed after the administration of a single 500 mg oral dose to 22 patients undergoing fibreoptic bronchoscopy. Concentrations of azithromycin in sputum, bronchial mucosa, eptihelial lining fluid (ELF) and alveolar macrophages (AM) were determined at intervals up to 96 h after dosing. The mean serum concentration was low at 12 h (0.13 micrograms.ml-1, SEM 0.05) but was still detectable at 96 h (0.01 micrograms.ml-1). In contrast, peak sputum ELF, bronchial mucosal and AM levels were found at 48 h. Bronchial mucosal concentrations were significantly greater than ELF concentrations, which were in turn greater than sputum concentrations. Mean peak AM concentrations were sixfold greater than bronchial mucosal concentrations (23 micrograms.ml-1, SEM 5.1 and 3.89 micrograms.ml-1, SEM 1.2, respectively). The high intracellular concentrations indicate that azithromycin is likely to be effective for sensitive intracellular pathogens and the favourable penetration into sputum, ELF and bronchial mucosa suggest that it should be useful in pneumonia and bronchial infections.
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PMID:Azithromycin concentrations at the sites of pulmonary infection. 196 11

Azithromycin, a recently introduced antibiotic, offers the potential advantages of short-course administration and lower toxicity compared to other macrolides. Approved for the treatment of mild pneumonia, this drug was investigated in a study of patients hospitalized for community-acquired pneumonia. In an open-labelled randomized study, oral azithromycin was compared with intravenous benzylpenicillin in patients suspected to have pneumococcal pneumonia. Azithromycin was also compared with erythromycin, both administered orally, in all other patients. Three hundred thirty-four patients with community-acquired pneumonia were hospitalized, 108 of whom were randomized; 104 could be evaluated. A need for intravenous therapy was the most common reason for exclusion. In the pneumococcal group, 35 patients received azithromycin and 29 benzylpenicillin. The clinical and radiological success rate achieved with azithromycin (83%) was considerably higher than that achieved with benzylpenicillin (66%), though the difference was not significant. In the non-pneumococcal group, 19 patients received azithromycin and 21 erythromycin; no differences in the success rate were found (79% and 76%, respectively). Eight patients on azithromycin had a blood culture positive for Streptococcus pneumoniae; in three of these patients therapy was changed. None of the five patients with pneumococcal bacteraemia who received benzylpenicillin required a change in therapy. It is concluded that oral azithromycin, administered as short-course therapy, is an appropriate antibiotic for treating patients with community-acquired pneumonia. However, it is not yet certain that azithromycin is a good choice for patients with pneumococcal bacteraemia.
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PMID:Efficacy and safety of azithromycin versus benzylpenicillin or erythromycin in community-acquired pneumonia. 761 57

We report a 67-year-old male with pneumonia in which Chlamydia pneumoniae was identified by serologic studies as the causative agent. After initial treatment failure with amoxicillin + clavulanic acid, pneumonia was successfully treated with the administration of oral azithromycin, 500 mg per day, for three days. Azithromycin is a new macrolide which has a long half-life and superior action to erythromycin. It provides a new and alternative choice in the treatment of Chlamydia pneumoniae infection in the future.
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PMID:Azithromycin in the treatment of pneumonia caused by Chlamydia pneumoniae: report of a case. 786 68

We investigated the in vitro and in vivo activities of macrolides against Mycoplasma pneumoniae. In vitro MICs of azithromycin, erythromycin, clarithromycin, and roxithromycin were determined. Azithromycin was the most potent antimicrobial agent tested in vitro. Its MIC for 90% of the strains was 0.00024 micrograms/ml. MICs for 90% of the strains of erythromycin, clarithromycin, and roxithromycin were 0.0156, 0.0078, and 0.03125 micrograms/ml, respectively. In vivo activities were assessed in a pulmonary infection model with Syrian golden hamsters. We evaluated the in vivo effects on reduction of viable M. pneumoniae cell counts and on reduction of microscopic and macroscopic histopathologies for azithromycin, erythromycin, and clarithromycin given at 10 mg/kg once daily for 1 and 3 days and given at 15 mg/kg twice daily for 2.5 and 5 days. Azithromycin was significantly more effective than erythromycin or clarithromycin in the same regimens. Especially at 10 mg/kg once daily for 1 day, only azithromycin was significantly effective in the reduction of viable M. pneumoniae cells and histopathologies. These results show that azithromycin is more efficacious than the other drugs tested against M. pneumoniae pneumonia in hamsters. These data suggest that clinical studies of macrolides in human patients are warranted.
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PMID:In vitro and in vivo activities of macrolides against Mycoplasma pneumoniae. 803 Oct 48

Azithromycin is an azalide antibiotic with activity against many of the respiratory pathogens and with marked tissue affinity. In a prospective study, the efficacy of a short-course of azithromycin was evaluated in 25 patients with community-acquired pneumococcal pneumonia. Gram-positive diplococci were abundant in the sputum smears of all patients, and Streptococcus pneumoniae was isolated in the sputum cultures of 15; one patient had pneumococcal bacteremia, as well. Azithromycin was administered at a single dose of 1,000 mg on day 1, and 500 mg on subsequent days for a total of three days in 19 patients, five days in four patients, two and four days in one patient each. Defervescence occurred within 24 hours after the first dose. The overall clinical cure and bacteriologic eradication rates were 96% and 93%, respectively. One patient with pneumococcal bacteremia failed to respond and died in respiratory failure. Side-effects were encountered in three (12%) patients. In conclusion, three-day therapy with a total azithromycin dose of 1,500 mg seems effective and safe in patients with community-acquired pneumococcal pneumonia and no underlying pulmonary condition.
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PMID:Efficacy of a three-day course of azithromycin in the treatment of community-acquired pneumococcal pneumonia. Preliminary report. 807 80

A clinical, retrospective and non-comparative study was undertaken to assess the clinical efficacy and tolerability of azithromycin in the treatment of community-acquired pneumonia caused by Legionella pneumophila. A total of 16 patients with a serologically confirmed diagnosis of Legionnaires' diseases were included. Azithromycin was administered orally at a total dose of 1.5 g for either 3 or 5 days. All patients were no side-effects requiring discontinuation of the treatment. Further increase of abnormal baseline liver function was recorded in 2 patients and in 1 patient mild, transient eosinophilia. Equal clinical efficacy and tolerability were observed with the 3- and 5-day dosage regimen. These results indicate that azithromycin given at a standard dose of 1.5 g is effective and well tolerated in the treatment of Legionnaires' disease.
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PMID:Azithromycin for treatment of community acquired pneumonia caused by Legionella pneumophila: a retrospective study. 858 43

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


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