Figure 1. Cumulative discharge curve; Amoxicillin concentration in
sputum.
no other pathogens were isolated. Baseline characteristics of
the enrolled patients and the 19 patients without usable sputum were comparable (data not shown).
Of the 33 patients with usable sputum, 11 (33%) had a concentration in sputum ≥ 2 mg/l. All isolated organisms had a
MIC < 2 mg/L. The mean length of hospitalization for patients with concentrations < 2 mg/l was 11.0 days, while for
patients with concentrations ≥ 2 mg/l this was 7.0 days (p =
0.005) (see Figure 1). The crude hazard ratio of time to discharge in the patients with concentrations ≥ 2 mg/l as compared to < 2 mg/l was 3.02 (95% CI 1.34 – 6.81; p = 0.008).
Of the potential confounding variables displayed in Table
1, only smoking status (ex-smoker versus current smoker)
and CRP concentration in blood within 1 day after hospital
admission were univariately associated with an amoxicillin
concentration at or above and below the MIC90 of 2 mg/l.
These two variables were not associated with time to medical
discharge, so no adjustment for the relation between amoxicillin concentration and time to discharge was necessary.
To check whether the relationship between amoxicillin
concentration and hospital stay differed between patient with
an exacerbation with and without pneumonia, we performed
a separate analysis of amoxicillin concentration and length
of hospitalization for both groups. We observed that within
the patients with an exacerbation and pneumonia (n = 7),
there was no significant difference in length of hospitalization (1.4 days longer with low amoxicillin (p = 0.2), while in
the patients with an exacerbation without pneumonia (n =
26) the difference was increased (4.6 days (95%CI: 1.3–7.8;
p = 0.007),
DISCUSSION
Our study demonstrated that COPD patients admitted to the
hospital with an acute exacerbation of COPD who have a sputum concentration of amoxicillin ≥ 2 mg/l on the third day
of dosing have a markedly reduced length of hospitalization
compared to patients with a concentration < 2 mg/l.
Amoxicillin Level and Length of Hospital Stay
Host-related, as well as drug-related, factors may influence the penetration of antimicrobial drugs across the blood-bronchus and alveolar-capillary barriers. The most important
host-related factor is the integrity of the anatomical barriers which may be damaged by inflammation and mechanical injury (5). In the presence of inflammation, the distribution of antimicrobial agents in tissue compartments may
be altered because of an increase in membrane permeability
(19,20). Thus, for a drug such as amoxicillin clavulanic acid,
a beta-lactam, which does not cross membranes readily, the
penetration might increase in the presence of inflammation
(5).
