Amoxicillin concentrations in relation to beta-lactamase activity in sputum during exacerbations of chronic obstructive pulmonary disease

Marjolein Brusse-Keizer, Paul van der Valk, Rogier W. van der Zanden, Lars Nijdam, Jacobus Adrianus Maria van der Palen, Ron Hendrix, Kris Movig

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Abstract

Background: Acute exacerbations of chronic obstructive pulmonary disease (COPD) are often treated with antibiotics. Theoretically, to be maximally effective, the antibiotic concentration at sites of infection should exceed the minimum inhibitory concentration at which 90% of the growth of potential pathogens is inhibited (MIC90). A previous study showed that most hospitalized COPD patients had sputum amoxicillin concentrations <MIC90 when treated with amoxicillin/clavulanic acid. Those with adequate sputum concentrations had better clinical outcomes. Low amoxicillin concentrations can be caused by beta-lactamase activity in the lungs. This study investigated whether patients with sputum amoxicillin concentrations <MIC90 had higher beta-lactamase activity in sputum than patients with a concentration ≥MIC90. Methods: In total, 23 patients hospitalized for acute exacerbations of COPD and treated with amoxicillin/clavulanic acid were included. Sputum and serum samples were collected at day 3 of treatment to determine beta-lactamase activity in sputum and amoxicillin concentrations in both sputum and serum. Results: We found no difference in beta-lactamase activity between patients with sputum amoxicillin concentrations <MIC90 and ≥MIC90 (P=0.79). Multivariate logistic regression analysis showed no significant relationship between beta-lactamase activity and sputum amoxicillin concentrations <MIC90 or ≥MIC90 (odds ratio 0.53; 95% confidence interval 0.23–1.2; P=0.13). Amoxicillin concentrations were <MIC90 in 78% of sputum samples and in 30% of serum samples. Conclusion: In patients treated with amoxicillin/clavulanic acid for an acute exacerbation of COPD, sputum beta-lactamase activity did not differ between those with sputum amoxicillin concentrations <MIC90 or ≥MIC90. The finding that the majority of patients had sputum amoxicillin concentrations <MIC90 suggests that current treatment with antibiotics for acute exacerbations of COPD should be optimized.
Original languageEnglish
Pages (from-to)455-461
Number of pages7
JournalInternational journal of chronic obstructive pulmonary disease
Volume10
DOIs
Publication statusPublished - 2015

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Amoxicillin
beta-Lactamases
Sputum
Chronic Obstructive Pulmonary Disease
Amoxicillin-Potassium Clavulanate Combination
Anti-Bacterial Agents
Serum
Microbial Sensitivity Tests
Logistic Models
Odds Ratio
Regression Analysis

Keywords

  • IR-97232
  • METIS-311782

Cite this

@article{d526f95a72f846d0bd48deac48d55bd8,
title = "Amoxicillin concentrations in relation to beta-lactamase activity in sputum during exacerbations of chronic obstructive pulmonary disease",
abstract = "Background: Acute exacerbations of chronic obstructive pulmonary disease (COPD) are often treated with antibiotics. Theoretically, to be maximally effective, the antibiotic concentration at sites of infection should exceed the minimum inhibitory concentration at which 90{\%} of the growth of potential pathogens is inhibited (MIC90). A previous study showed that most hospitalized COPD patients had sputum amoxicillin concentrations <MIC90 when treated with amoxicillin/clavulanic acid. Those with adequate sputum concentrations had better clinical outcomes. Low amoxicillin concentrations can be caused by beta-lactamase activity in the lungs. This study investigated whether patients with sputum amoxicillin concentrations <MIC90 had higher beta-lactamase activity in sputum than patients with a concentration ≥MIC90. Methods: In total, 23 patients hospitalized for acute exacerbations of COPD and treated with amoxicillin/clavulanic acid were included. Sputum and serum samples were collected at day 3 of treatment to determine beta-lactamase activity in sputum and amoxicillin concentrations in both sputum and serum. Results: We found no difference in beta-lactamase activity between patients with sputum amoxicillin concentrations <MIC90 and ≥MIC90 (P=0.79). Multivariate logistic regression analysis showed no significant relationship between beta-lactamase activity and sputum amoxicillin concentrations <MIC90 or ≥MIC90 (odds ratio 0.53; 95{\%} confidence interval 0.23–1.2; P=0.13). Amoxicillin concentrations were <MIC90 in 78{\%} of sputum samples and in 30{\%} of serum samples. Conclusion: In patients treated with amoxicillin/clavulanic acid for an acute exacerbation of COPD, sputum beta-lactamase activity did not differ between those with sputum amoxicillin concentrations <MIC90 or ≥MIC90. The finding that the majority of patients had sputum amoxicillin concentrations <MIC90 suggests that current treatment with antibiotics for acute exacerbations of COPD should be optimized.",
keywords = "IR-97232, METIS-311782",
author = "Marjolein Brusse-Keizer and {van der Valk}, Paul and {van der Zanden}, {Rogier W.} and Lars Nijdam and {van der Palen}, {Jacobus Adrianus Maria} and Ron Hendrix and Kris Movig",
note = "Open Access",
year = "2015",
doi = "10.2147/COPD.S70355",
language = "English",
volume = "10",
pages = "455--461",
journal = "International journal of chronic obstructive pulmonary disease",
issn = "1176-9106",
publisher = "Dove Medical Press Ltd.",

}

Amoxicillin concentrations in relation to beta-lactamase activity in sputum during exacerbations of chronic obstructive pulmonary disease. / Brusse-Keizer, Marjolein; van der Valk, Paul; van der Zanden, Rogier W.; Nijdam, Lars; van der Palen, Jacobus Adrianus Maria; Hendrix, Ron; Movig, Kris.

In: International journal of chronic obstructive pulmonary disease, Vol. 10, 2015, p. 455-461.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Amoxicillin concentrations in relation to beta-lactamase activity in sputum during exacerbations of chronic obstructive pulmonary disease

AU - Brusse-Keizer, Marjolein

AU - van der Valk, Paul

AU - van der Zanden, Rogier W.

AU - Nijdam, Lars

AU - van der Palen, Jacobus Adrianus Maria

AU - Hendrix, Ron

AU - Movig, Kris

N1 - Open Access

PY - 2015

Y1 - 2015

N2 - Background: Acute exacerbations of chronic obstructive pulmonary disease (COPD) are often treated with antibiotics. Theoretically, to be maximally effective, the antibiotic concentration at sites of infection should exceed the minimum inhibitory concentration at which 90% of the growth of potential pathogens is inhibited (MIC90). A previous study showed that most hospitalized COPD patients had sputum amoxicillin concentrations <MIC90 when treated with amoxicillin/clavulanic acid. Those with adequate sputum concentrations had better clinical outcomes. Low amoxicillin concentrations can be caused by beta-lactamase activity in the lungs. This study investigated whether patients with sputum amoxicillin concentrations <MIC90 had higher beta-lactamase activity in sputum than patients with a concentration ≥MIC90. Methods: In total, 23 patients hospitalized for acute exacerbations of COPD and treated with amoxicillin/clavulanic acid were included. Sputum and serum samples were collected at day 3 of treatment to determine beta-lactamase activity in sputum and amoxicillin concentrations in both sputum and serum. Results: We found no difference in beta-lactamase activity between patients with sputum amoxicillin concentrations <MIC90 and ≥MIC90 (P=0.79). Multivariate logistic regression analysis showed no significant relationship between beta-lactamase activity and sputum amoxicillin concentrations <MIC90 or ≥MIC90 (odds ratio 0.53; 95% confidence interval 0.23–1.2; P=0.13). Amoxicillin concentrations were <MIC90 in 78% of sputum samples and in 30% of serum samples. Conclusion: In patients treated with amoxicillin/clavulanic acid for an acute exacerbation of COPD, sputum beta-lactamase activity did not differ between those with sputum amoxicillin concentrations <MIC90 or ≥MIC90. The finding that the majority of patients had sputum amoxicillin concentrations <MIC90 suggests that current treatment with antibiotics for acute exacerbations of COPD should be optimized.

AB - Background: Acute exacerbations of chronic obstructive pulmonary disease (COPD) are often treated with antibiotics. Theoretically, to be maximally effective, the antibiotic concentration at sites of infection should exceed the minimum inhibitory concentration at which 90% of the growth of potential pathogens is inhibited (MIC90). A previous study showed that most hospitalized COPD patients had sputum amoxicillin concentrations <MIC90 when treated with amoxicillin/clavulanic acid. Those with adequate sputum concentrations had better clinical outcomes. Low amoxicillin concentrations can be caused by beta-lactamase activity in the lungs. This study investigated whether patients with sputum amoxicillin concentrations <MIC90 had higher beta-lactamase activity in sputum than patients with a concentration ≥MIC90. Methods: In total, 23 patients hospitalized for acute exacerbations of COPD and treated with amoxicillin/clavulanic acid were included. Sputum and serum samples were collected at day 3 of treatment to determine beta-lactamase activity in sputum and amoxicillin concentrations in both sputum and serum. Results: We found no difference in beta-lactamase activity between patients with sputum amoxicillin concentrations <MIC90 and ≥MIC90 (P=0.79). Multivariate logistic regression analysis showed no significant relationship between beta-lactamase activity and sputum amoxicillin concentrations <MIC90 or ≥MIC90 (odds ratio 0.53; 95% confidence interval 0.23–1.2; P=0.13). Amoxicillin concentrations were <MIC90 in 78% of sputum samples and in 30% of serum samples. Conclusion: In patients treated with amoxicillin/clavulanic acid for an acute exacerbation of COPD, sputum beta-lactamase activity did not differ between those with sputum amoxicillin concentrations <MIC90 or ≥MIC90. The finding that the majority of patients had sputum amoxicillin concentrations <MIC90 suggests that current treatment with antibiotics for acute exacerbations of COPD should be optimized.

KW - IR-97232

KW - METIS-311782

U2 - 10.2147/COPD.S70355

DO - 10.2147/COPD.S70355

M3 - Article

VL - 10

SP - 455

EP - 461

JO - International journal of chronic obstructive pulmonary disease

JF - International journal of chronic obstructive pulmonary disease

SN - 1176-9106

ER -