Penetration of piperacillin into bronchial mucosa and sputum.

Marlin, G. E.; Burgess, Keith R.; Burgoyne, J; Funnell, G R; Guinness, Michael

doi:10.1136/thx.36.10.774

Cited by 47 publications

(16 citation statements)

References 21 publications

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“…The relative proportion of drug in the intracellular and extracellular components is important, because a major determinant of the total drug concentration in a tissue is the degree of intracellular penetration and accumulation. Thus, the fluoroquinolones and macrolides, which accumulate in the intracellular environment, have higher concentrations in bronchial biopsy specimens than in serum, whereas 3-lactams which do not penetrate cell membranes to any significant degree have lower concentrations in bronchial biopsy specimens than in serum (25,(39)(40)(41). Despite these facts, there are few published data on the constituents of bronchial biopsy specimens in terms of tissue types, and there are no data on the relative amounts of intra-and extracellular water.…”

Section: Introductionmentioning

confidence: 84%

“…AMs reside in this microenviron- (7,47). This sputum pooling invalidates measurements of antimicrobial agent concentrations with respect to the time of dosing and allows time for the degradation of antimicrobial agents, e.g., by P-lactamases (58 (25,39,40). However, the major criticism is that the most relevant information is the relative amount of drug in the interstitial fluid and cellular fluid (49).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Pulmonary disposition of antimicrobial agents: methodological considerations

Baldwin

Honeybourne

Wise

1992

Antimicrob Agents Chemother

166

119

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Section: Introductionmentioning

confidence: 84%

Section: Introductionmentioning

confidence: 99%

Pulmonary disposition of antimicrobial agents: methodological considerations

Baldwin

Honeybourne

Wise

1992

Antimicrob Agents Chemother

166

119

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“…Previous observations have shown peak latamoxef [9] and piperacillin [7] spu tum concentrations to be 9 and 10%, re spectively, of serum values. In these re ports, however, secretions were obtained for analysis by bronchoscopy in non-CF patients with acute infection.…”

Section: Discussionmentioning

confidence: 99%

Penetration of Latamoxef, Cef operazone and Piperacillin into the Sputum of Patients with Cystic Fibrosis

et al. 1985

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Concentrations of latamoxef, cefoperazone and piperacillin, administered intravenously, were measured in serum and sputum of cystic fibrosis patients with recurrent pulmonary infections, chronically colonized with Pseudomonas aeruginosa. Serum pharmacokinetic data were consistent with prior reports. Peak sputum to peak serum concentrations were approximately 3% for each antimicrobial. However, the more prolonged sputum concentrations of piperacillin were reflected in greater areas under the sputum concentration-time curve and a longer duration above the MIC₅₀ of tested P. aeruginosa strains for that drug.

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“…In the lung, the sites of infection which have previously been investigated with regard to antibiotic penetration are sputum and bronchial secretions (10,13,17), bronchial mucosa (7,9,10) and alveolar fluid, and macrophages (2,4,12). It has been suggested (7,9,13) 4,500% penetrations [9,17]) than the other quinolones, but as yet there is no agreed-upon explanation for this and verification of these data should be undertaken.…”

Section: Discussionmentioning

confidence: 99%

Concentrations of oral lomefloxacin in serum and bronchial mucosa

Baldwin

Honeybourne

Andrews

et al. 1990

Antimicrob Agents Chemother

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The bronchial mucosal concentrations of lomefloxacin were determined for specimens obtained by fiber-optic bronchoscopy and compared with simultaneous concentrations in serum. The 23 patients studied were given an oral dose of 400 mg once daily for 4 days to achieve steady-state levels. The median concentration in serum was 2.5 ,ug/ml (range, 1.0 to 5 ,ug/ml), and the median bronchial mucosal concentration was 5.0 ,ug/g (range, 0.7 to 18.6 ,Lg/g). The median percent penetration was 177% (range, 69 to 541%). The concentrations in serum and mucosa exceeded the MIC for 90% of strains of organisms causing bronchial infections but not sufficiently to recommend lomefloxacin for the routine treatment of pneumococcal infections.The likely clinical efficacy of antibiotics may be predicted from the concentrations of the agent in the tissues and secretions which are the usual sites of infection. In the respiratory tract, antibiotic concentrations in sputum have been determined, but these can be unreliable (1, 13). The bronchial mucosa is probably the main site of acute bacterial infection in patients with chronic bronchitis and bronchiectasis (5) and, therefore, it is reasonable to measure drug concentrations at this site. Several quinolones have been found to attain higher bronchial mucosal and lung tissue concentrations than simultaneous concentrations in serum (7,9,17). The aim of this study was, therefore, to assess the concentration of a new quinolone, lomefloxacin, in human bronchial mucosa.Lomefloxacin is a fluoroquinolone with a broad spectrum of in vitro activity against clinically important gram-positive and gram-negative aerobes and anaerobes, including the majority of organisms responsible for lower respiratory tract infections, including Staphylococcus aureus (18). Like the other quinolones, it also has activity against Legionella pneumophila and Mycoplasma pneumoniae (6). It has a prolonged serum half-life, and it is therefore appropriately given as a once-daily dose (16). MATERIALS AND METHODSA total of 23 patients (14 male and 9 female) undergoing fiber-optic bronchoscopy for diagnostic purposes were studied. The indication for bronchoscopy was focal radiological abnormality in 19 patients and hemoptysis in 4 patients. The final diagnosis was squamous cell carcinoma in seven patients, and in the remainder, no abnormality was found. Ages ranged from 40 to 65 years (mean, 57 years). Lomefloxacin was self-administered in a dose of 400 mg once daily, in the morning, for 4 days, with the final dose of lomefloxacin given on the morning of the bronchoscopy, making a total of 4 doses. A standard premedication of 160 mg of 4% nebulized lignocaine, 0.6 mg of intramuscular atropine, and 2.5 to 5 mg of intravenous midazolam was used. Bronchial biopsies were taken from the subcarinae of macroscopically normal bronchi (absence of erythema, nodularity, or edema) and immediately placed in a humidity chamber. Any specimens macroscopically contaminated * Corresponding author. with blood were discarded. A serum sample for det...

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Penetration of piperacillin into bronchial mucosa and sputum.

Cited by 47 publications

References 21 publications

Pulmonary disposition of antimicrobial agents: methodological considerations

Pulmonary disposition of antimicrobial agents: methodological considerations

Penetration of Latamoxef, Cef operazone and Piperacillin into the Sputum of Patients with Cystic Fibrosis

Concentrations of oral lomefloxacin in serum and bronchial mucosa

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