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

Figures & data

Table 1 Baseline patient demographic and clinical characteristics

Characteristic	n=23
Age, years (SD)	71.0 (8.9)
Sex
Male (%)	17 (74%)
Female (%)	6 (26%)
GOLD classification
I (%)	2 (9%)
II (%)	6 (26%)
III (%)	8 (35%)
IV (%)	7 (30%)
Route of administration of amoxicillin/clavulanic acid
Oral (%)	15 (65%)
Intravenous (%)	8 (35%)
Median daily dose of clavulanic acid, mg (IQR)	375 (375–800)
Median concentration of amoxicillin
In serum, mg/L (IQR)	4.7 (0.72–6.35)
In sputum, mg/L (IQR)	0.6 (0.00–1.74)
Median beta-lactamase activity, as % of reference (IQR)	0.34 (0.26–0.58)
Median CRP concentration at admission, mg/L (IQR)	40 (25–152)
Patients with both exacerbation of COPD and pneumonia	11 (48%)
Simultaneous use of other antibiotics	5 (22%)

Abbreviations: COPD, chronic obstructive pulmonary disease; CRP, C-reactive protein; GOLD, Global Initiative for Chronic Obstructive Lung Disease; IQR, interquartile range; SD, standard deviation.

Figure 1 Flowchart of study inclusion.

Figure 2 Scatter diagram of amoxicillin sputum concentration and beta-lactamase activity.

Table 2 Potential confounders: association with beta-lactamase activity

	Association with beta-lactamase activity
	Median beta-lactamase activity (% of reference) (IQR)	P-value
Sex
Male	0.34 (0.25–0.60)	0.86
Female	0.36 (0.23–0.85)
Exacerbation with pneumonia
No	0.33 (0.27–0.46)	0.31
Yes	0.55 (0.18–0.69)
GOLD classification
I	0.55 (0.48–0.55)	0.46
II	0.44 (0.27–0.61)
III	0.30 (0.12–0.50)
IV	0.36 (0.24–0.67)
Route of administration
Oral	0.31 (0.18–0.48)	0.06
Intravenous	0.57 (0.33–0.67)
Concurrent use of other antibiotics
No	0.34 (0.24–0.59)	0.77
Yes	0.36 (0.28–0.59)
Clavulanic acid, daily dose (mg)
375	0.28 (0.17–0.37)	0.08
500	0.48 (0.33–0.48)
800	0.57 (0.33–0.67)
	Correlation with beta- lactamase activity (Spearman’s rho)	P-value
Age	−0.05	0.81
Amoxicillin level in serum mg/L	0.22	0.30
CRP concentration at admission mg/L	−0.37	0.09

Abbreviations: CRP, C-reactive protein; GOLD, Global Initiative for Chronic Obstructive Lung Disease; IQR, interquartile range.

Table 3 Potential confounders: association with <MIC₉₀ or ≥MIC₉₀

	Association with <MIC90 or ≥MIC90 in sputum (n=23)
	<MIC90 in sputum	≥MIC90 in sputum	P-value
Route of administration
Oral, n (%)	14 (93)	1 (7)	0.03
Intravenous, n (%)	4 (50)	4 (50)
Median daily clavulanic acid dose, mg (IQR)	375 (375–575)	800 (589–800)	0.04
Median CRP concentration at admission, mg/L (IQR)	38 (21–57)	197 (56–206)	0.06

Abbreviations: CRP, C-reactive protein; IQR, interquartile range; MIC, minimum inhibitory concentration.