Plasma and sputum erythromycin concentrations in chronic bronchitis.

Marlin, G. E.; Davis, Phyllis; Rutland, J; Berend, Norbert

doi:10.1136/thx.35.6.441

Cited by 18 publications

(11 citation statements)

References 20 publications

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“…As the concentrations of EM studied, 0.05, 0.5 and 5 mg?mL -1 , correspond to the sputum levels of EM in patients with chronic bronchitis (0.10-0.60 mg?mL -1 ) treated with 500 mg of EM t.i.d. [14], the findings from this study should, therefore, reflect the in vivo situation. There were no obvious dose-dependent effects and the highest concentration of EM used (5 mg?mL…”

Section: Discussionmentioning

confidence: 99%

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Effects of erythromycin onPseudomonas aeruginosaadherence to collagen and morphologyin vitro

Tsang¹,

Ng²,

Ho³

et al. 2003

Eur Respir J

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The airways of patients with bronchiectasis and cystic fibrosis are often chronically colonised by Pseudomonas aeruginosa (PA), which is virtually impossible to eradicate. Low-dose erythromycin (EM), for unknown mechanisms, is efficacious in bronchiectasis and diffuse panbronchiolitis.In this study, an in vitro model to investigate PA adherence to human type IV basement collagen was developed by using scanning electron microscopy (SEM). There were significantly less PA bacilli per 20 random SEM fields (4,0006) when PA was cultured in 0.05, 0.5 and 5 mg?mL -1 of EM compared with control (absence of EM). Adherence density (20 SEM fields?log -1 inocular size) for PA obtained from no EM (56.8¡43.16) was significantly higher than that obtained from 0.05, 0.5, and 5 mg?mL -1 EM (21.5¡17.56, 23.3¡16.65, and 21.4¡12.65 respectively). By using SEM it was found that PA, when incubated in EM (0.05, 0.5, 5 mg?mL -1 ) had a significant reduction in its diagonal length, radius, height, volume and surface area.It is possible, therefore, that these misshaped Pseudomonas aeruginosa bacilli are more susceptible to host defence mechanisms, while at the same time less adherent to the basement membrane of the airway in vivo. Therefore, this could help explain the clinical efficacy of low-dose erythromycin therapy on patients with Pseudomonas aeruginosa infection. Eur Respir J 2003; 21: 401-406.

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Section: Discussionmentioning

confidence: 99%

“…For example, the ratio of sputum to serum macrolides is generally around 10% [14]. PA in the airways of patients with bronchiectasis and CF is, therefore, almost certainly exposed only to subminimal inhibitory concentrations (MIC) of EM.…”

mentioning

confidence: 99%

Effects of erythromycin onPseudomonas aeruginosaadherence to collagen and morphologyin vitro

Tsang¹,

Ng²,

Ho³

et al. 2003

Eur Respir J

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“…Tetracyclines do not show a similar relationship between concentrations in bronchial secretions and the degree of inflammation (25,32,36). There is some controversy for the aminoglycosides, with gentamicin levels apparently not correlating with inflammation while tobramycin and amikacin do show correlations (14,53).…”

Section: Introductionmentioning

confidence: 99%

“…These data will be reported in detail separately, but they show that concentrations in AMs are six to eight times those in ELF, which corresponds to the intracellular to extracellular concentration ratio observed in vitro (20). (14,20,28,33,36,39,50). It has been suggested that the concentrations at sites of infection may fall sufficiently to allow relapse of infection, because of reestablishment of normal barriers to movement (45).…”

Section: Introductionmentioning

confidence: 99%

“…The macrolides have penetration ratios of 5 to >500%. Unfortunately, data are very variable for the most commonly used macrolide erythromycin, with one study (14) reporting a level of erythromycin in sputum that was 5% of that in serum, and others (36) (12). It follows that the principal determinant of the value of the site of infection-to-serum ratio is the degree to which the antimicrobial agent concentrates in the cellular component.…”

Section: Introductionmentioning

confidence: 99%

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Pulmonary disposition of antimicrobial agents: in vivo observations and clinical relevance

Baldwin

Honeybourne

Wise

1992

Antimicrob Agents Chemother

111

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Delivering Antibacterials to the Lungs

et al. 2002

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An important determinant of clinical outcome of a lower respiratory tract infection may be sterilization of the infected lung, which is also dependent on sustained antibacterial concentrations achieved in the lung. For this reason, recently there has been increased interest in measuring the concentration of antimicrobial agents at different potential sites of infection in the lung. Levels of antibacterials are now measured in bronchial mucosa, epithelial lining fluid (ELF) and alveolar macrophages, as well as in sputum. Penicillins and cephalosporins reach only marginal concentrations in bronchial secretions, whereas fluoroquinolones and macrolides have been shown to achieve high concentrations. The extent of penetration of different antibacterials into the bronchial mucosa is relatively high. This is also true for beta-lactams, although their tissue concentrations never reach blood concentrations. Antibacterials penetrate less into the ELF than into the bronchial mucosa, but fluoroquinolones appear to concentrate more into alveolar lavage than into bronchial mucosa. Pulmonary pharmacokinetics is a very useful tool for describing how drugs behave in the human lung, but it does not promote an understanding of the pharmacological effects of a drug. More important, instead, is the correlation between pulmonary disposition of the drug and its minimum inhibitory concentration (MIC) values for the infectious agent. The addition of bacteriological characteristics to in vivo pharmacokinetic studies has triggered a 'pharmacodynamic approach'. Pharmacodynamic parameters integrate the microbiological activity and pharmacokinetics of an anti-infective drug by focusing on its biological effects, particularly growth inhibition and killing of pathogens. Drugs that penetrate well and remain for long periods at the pulmonary site of infection often induce therapeutic responses greater than expected on the basis of in vitro data. However, although the determination of antibacterial concentrations at the site of infection in the lung has been suggested to be important in predicting the therapeutic efficacy of antimicrobial treatment during bacterial infections of the lower respiratory tract, some studies have demonstrated that pulmonary bacterial clearance is correlated more closely to concentrations in the serum than to those in the lung homogenates, probably because they better reflect antibacterial concentration in the interstitial fluid.

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Plasma and sputum erythromycin concentrations in chronic bronchitis.

Cited by 18 publications

References 20 publications

Effects of erythromycin onPseudomonas aeruginosaadherence to collagen and morphologyin vitro

Effects of erythromycin onPseudomonas aeruginosaadherence to collagen and morphologyin vitro

Pulmonary disposition of antimicrobial agents: in vivo observations and clinical relevance

Delivering Antibacterials to the Lungs

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