COPD: Journal of Chronic Obstructive Pulmonary Disease, 8:66–70, 2011
ISSN: 1541-2555 print / 1541-2563 online
Copyright C ; Informa Healthcare USA, Inc.
DOI: 10.3109/15412555.2011.558863
ORIGINAL RESEARCH
Relation Between Amoxicillin Concentration in Sputum of COPD Patients
and Length of Hospitalization
Marjolein Brusse-Keizer,1 Leonore ten Bokum,2 Kris Movig,3 Paul van der Valk,1 Huib Kerstjens,4
Job van der Palen,1,5 and Ron Hendrix6
Department of Pulmonary Medicine, Medisch Spectrum Twente, Enschede, the Netherlands,1 Department of Clinical Pharmacy,
Deventer Hospital, Deventer, The Netherlands,2 Department of Clinical Pharmacy, Medisch Spectrum Twente, Enschede, the
Netherlands,3 Department of Pulmonary Medicine, University Medical Center Groningen, and University of Groningen,
Groningen, the Netherlands,4 Department of Research Methodology, Measurement, and Data Analysis, University of Twente,
The Netherlands,5 Regional Laboratory of Public Health, Enschede, the Netherlands6
Amoxicillin is a widely used antibiotic in COPD. Little is known
about the transfer of amoxicillin into sputum of COPD patients.
The objective was to investigate the relationship between the
concentration of amoxicillin in sputum in hospitalized COPD
patients and length of hospitalization. To be effective against
bacterial pathogens, the amoxicillin concentration in target
tissues should be higher than the Minimal Inhibiting
Concentration (MIC) of 2 mg/l. Therefore, this was also used as
the cut-off value for the amoxicillin concentration in sputum, as
a marker for lung tissue concentration. Fifty-two COPD
in-patients with an exacerbation, treated with amoxicillin
clavulanic acid, were included in this cohort study. Of these
patients 7 also had pneumonia. Patients were divided in
patients with an amoxicillin sputum concentration ≥ 2 mg/l
and < 2 mg/l. Furthermore, inflammation markers in sputum
and serum and clinical parameters were obtained. Of the 33
patients with usable sputum, 11 had a concentration in sputum
≥ 2 mg/l. The mean length of hospitalization for patients with
concentrations below the MIC90 to common respiratory
pathogens was 11.0 days, while for patients with
concentrations at or above the MIC90 this was 7.0 days (p =
0.005). COPD patients admitted for an acute exacerbation of
COPD, with a sputum concentration of amoxicillin ≥ 2 mg/l had
a markedly reduced length of hospitalization compared to
patients with a concentration < 2 mg/l. It is worthwhile testing
whether individualized treatment based on sputum amoxicillin
concentrations of patients during hospitalization for acute
exacerbations can effectively reduce hospital stay.
Keywords: Chronic Obstructive Pulmonary Disease,
Anti-Bacterial Agents, Bacterial Infections, Therapeutics
INTRODUCTION
Patients with COPD are prone to exacerbations and these are
an important cause of morbidity and mortality. The manage-
ment of exacerbations is usually empirical and includes oral
corticosteroids combined with broad spectrum antibiotics,
such as amoxicillin clavulanic acid, to treat presumed bacte-
rial infection (1). However, evidence of the efficacy of adding
antibiotics is debatable, since some controlled studies showed
a clear benefit, whereas others did not (2–4).
Correspondence to: Marjolein Brusse-Keizer, PhD, Medisch Spectrum Twente, Department of Pulmonary Medicine, P.O Box 50000, 7500 KA
Enschede, The Netherlands, phone: 0031-53-4872643, fax: 0031-53-4872676. email: m.brusse-keizer@mst.nl
