Relation Between Amoxicillin Concentration in Sputum of COPD Patients and Length of Hospitalization

Abstract

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.

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

“…In the presence of inflammation, the distribution of amoxicillin may be altered because of increased membrane permeability 25,26. As observed in this and our previous study a high level of C-reactive protein, a marker of systemic inflammation, was related to higher amoxicillin levels 17. C-reactive protein levels could therefore possibly be used as a marker to determine COPD patients in whom adequate concentrations could be reached.…”

“…We observed that intravenous administration was associated with a higher probability of reaching a sputum amoxicillin concentration ≥MIC 90 and led to higher serum concentrations (data not shown), but still 50% of patients had a concentration <MIC 90 . Further, due to the wide confidence interval that was observed with this probability and since we did not observe any differences in the numbers of patients who reached the MIC 90 between intravenous and oral administration in our earlier study,17 we cannot recommend a preference for use of either intravenous or oral administration to reach adequate amoxicillin sputum levels.…”

“…C-reactive protein levels could therefore possibly be used as a marker to determine COPD patients in whom adequate concentrations could be reached. However, this does not solve the problem of low concentrations in the majority of patients; this is a worrying feature, especially because our previous study showed that this is also associated with significantly worse clinical outcomes 17. This warrants further investigation into more optimal treatment in these patients.…”

Antibiotic treatment in acute exacerbation of COPD: patient outcomes with amoxicillin vs. amoxicillin/clavulanic acid—data from 43,636 outpatients

“…The serum profile of the amoxicillin component is the same, when administered with and without clavulanic acid [10,24], thus it would be very unlikely that AMC is inferior to AMX when administered in equal doses. A study group measured AMX in sputum samples from 33 hospitalized AECOPD patients treated with AMC and found longer hospitalization (7 vs 11 days) when AMX concentrations did not reach target (2 mg/L) [25]. Two third of their patients did not reach target in sputum.…”

Safety and Tolerability of Nebulized Amoxicillin-Clavulanic Acid in Patients with COPD (STONAC 1 and STONAC 2)

“…Some clinical studies have suggested that with regard to clinical efficacy of amoxicillin, sputum concentration is a better predictor of efficacy than serum concentration (6,7). Previous research has shown that an amoxicillin concentration in sputum higher than the Minimal Inhibiting Concentration of 90% (MIC90) reduced the mean length of hospitalization for a COPD exacerbation from 11 to 7 days (8). However, only one-third of the COPD patients receiving treatment either orally or intravenously reaches an amoxicillin concentration in sputum higher than the MIC90 (8,9).…”