Tobramycin Therapy of Infections Due to Pseudomonas aeruginosa in Patients with Cystic Fibrosis: Effect of Dosage and Concentration of Antibiotic in Sputum

McCrae, W. Morrice; Raeburn, J. A.; Hanson, E. Jerome

doi:10.1093/infdis/134.supplement_1.s191

Cited by 43 publications

(10 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The value of tobramycin in the treatment of chronic P. aeruginosa lung infection in CF is well documented (7,8,13,14,22,38,42). Because of a low ratio between therapeutic and toxic levels, a major limitation in the use of aminoglycosides is the development of nephro-and acousticovestibular toxicity (3,17).…”

Section: Discussionmentioning

confidence: 99%

Cumulative and acute toxicity of repeated high-dose tobramycin treatment in cystic fibrosis

Pedersen¹,

Jensen²,

Osterhammel³

et al. 1987

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Cumulative and acute toxicity of repeated high-dose tobramycin treatment in cystic fibrosis

Pedersen¹,

Jensen²,

Osterhammel³

et al. 1987

Antimicrob Agents Chemother

View full text Add to dashboard Cite

“…Depending on the minimal inhibitory concentrations of the P. aeruginosa strains tested, only pectively. In most marginally effective or inadequate peak levels in s activity could be sputum have been found after a high aminoglytions despite ade-coside dose administered intramuscularly or inbramycin in blood travenously (3,4,(6)(7)(8). In addition, the drug tivities in serum.…”

Section: Methodsmentioning

confidence: 99%

“…As far as purulent bronchitis is concerned, bronchial secretions represent a close approximation to the infected site, and it has been suggested that the antibiotic level in bronchial secretions could be an important determinant of therapeutic efficacy (2,5,6). Therefore, we investigated the possibility of achieving appropriate antimicrobial activity against Pseudomonas aeruginosa in bronchial secretions of patients receiving high doses of amikacin and tobramycin given as continuous infusions.…”

mentioning

confidence: 99%

Anti-Pseudomonas activity in bronchial secretions of patients receiving amikacin or tobramycin as a continuous infusion

Mombelli¹,

Coppens²,

Thys³

et al. 1981

Antimicrob Agents Chemother

View full text Add to dashboard Cite

The penetration of amikacin and tobramycin into bronchial secretions and the resulting anti-Pseudomonas activity were assessed in two groups of tracheostomized or intubated patients with tracheobronchial infection and purulent bronchial secretions. The aminoglycosides were administered as continuous, high-dose intravenous infusions. The mean drug concentrations in serum and bronchial secretions were 12.8 and 2.0 ,ug/ml for amikacin and 3.6 and 0.7 ,ug/ml for tobramycin. The bronchial secretion/serum ratios varied over a wide range: from 9.6 to 22.8% (average, 14.9%) for amikacin and from 3 to 39.3% (average, 17.5%) for tobramycin. Sustained anti-Pseudomonas activities in bronchial secretions were achieved only in patients with very high aminoglycoside levels in serum. In most patients, however, no anti-Pseudomonas activity could be detected within bronchial secretions despite therapeutic levels of amikacin and tobramycin and adequate bactericidal activities in serum.

show abstract

“…This could be due mainly to two factors. On one hand, the penetration of the aminoglycosides through the blood/bronchus barrier appears in most studies to be relatively poor, the ratios between the peak bronchial and serum levels are in the range of 10 to 30% (Pennington & Reynolds, 1973;Pennington & Reynolds, 1975;McCrae, Raeburn & Hanson, 1976;Bergogne-Berezin, Even & Berthelot, 1978). On the other hand, a partial bioinactivation of these antibiotics occurs in purulent sputum: we have shown that the inactivation of netilmicin by sputum may be correlated with the degree of purulence of the secretions (Thys & Klastersky, 1980a).…”

Section: Introductionmentioning

confidence: 99%

Peak or sustained antibiotic serum levels for optimal tissue penetration

Thys

Klastersky

Mombelli

1981

Journal of Antimicrobial Chemotherapy

View full text Add to dashboard Cite

A comparative study of the levels of netilmicin in bronchial secretions after intermittent and during continuous intravenous injections was performed. During the first 2 h, the areas under the drug concentration curves in the bolus injection experiment were greater in serum and in bronchial secretions (206 and 150% respectively) than those associated with the continuous infusion (P<0 i 001); however, during the 8 h experimental period, the areas under the curves were similar in serum and bronchial secretions with the two modes of administration. The percentages of penetration of netilmicin from the blood to the bronchial lumen were also similar with the two modes of administration (19%). After intramuscular administration of amikacin (75 and 125 mg/kg twice daily), the peak bronchial secretion levels of the drug were 44 and 10-1 mg/1 respectively and the trough levels about 1 mg/1. During continuous iv injection of amikacin (7-12 mg/kg/8 h), the drug level in the bronchial secretions was only 20 mg/1 and the percentage of penetration was 14*9%; adequate anXi-Pseudomonas activity in bronchial secretions was rarely achieved. It is therefore suggested that intermittent injections of aminoglycosides can result in at least transitory higher bronchial secretion levels than continuous injection: the intermittent schedule of antibiotic administration could therefore be recommended in the treatment of bronchopulmonary infections since it has been suggested that the concentration of antibiotic in bronchial secretions could be important in the outcome of these infections.

show abstract

Tobramycin Therapy of Infections Due to Pseudomonas aeruginosa in Patients with Cystic Fibrosis: Effect of Dosage and Concentration of Antibiotic in Sputum

Cited by 43 publications

References 5 publications

Cumulative and acute toxicity of repeated high-dose tobramycin treatment in cystic fibrosis

Cumulative and acute toxicity of repeated high-dose tobramycin treatment in cystic fibrosis

Anti-Pseudomonas activity in bronchial secretions of patients receiving amikacin or tobramycin as a continuous infusion

Peak or sustained antibiotic serum levels for optimal tissue penetration

Contact Info

Product

Resources

About