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

Abstract

BackgroundAcute 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 <LMIC90 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.MethodsIn 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.ResultsWe 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.ConclusionIn 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.

Effect of an antimicrobial drug on lung microbiota in healthy dogs

“…For example, the salivary microbiota was shown to be more resilient to disturbance after antimicrobial drug administration compared to that of the gut [9]. Another explanation would be that in healthy individuals, such as the dogs in this study, the permeability of the alveolar-capillary wall is lower than in diseased lungs [30], leading to a limited penetration of AC into the parenchyma and airways and therefore a limited effect on the LM. Indeed it has been shown that amoxicillin concentration in the sputum in man may differ according to different host- and drug-related factors, such as alveolar-capillary permeability [31, 32].…”

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

“…Two third of their patients did not reach target in sputum. In another study by the same group [ 26 ] with 23 hospitalized AECOPD patients 78% of the patients did not reach target in sputum. Oral (500 mg TID/QID) vs intravenously (1000 mg QID) administration was highly associated with the likelihood of reaching target sputum concentration.…”

Is the demonstration of bioequivalence for clavulanic acid required in amoxicillin–clavulanic acid orally administered immediate-release products?

“…reported no difference in β‐lactamase activity between patients (treated for chronic obstructive pulmonary disease) with sputum amoxicillin concentrations <MIC 90 and ≥MIC 90 . No significant relationship was found between β‐lactamase activity and sputum amoxicillin concentrations <MIC 90 and ≥MIC 90 . Co‐amoxiclav is effective for treating infections caused by β‐lactamase‐producing Gram‐negative organisms.…”

“…No significant relationship was found between b-lactamase activity and sputum amoxicillin concentrations <MIC 90 and ≥MIC 90 . [11] Co-amoxiclav is effective for treating infections caused by b-lactamase-producing Gram-negative organisms. However, Co-amoxiclav combination does not provide any clinical advantage over amoxicillin alone in treating infections where resistance mechanism does not involve b-lactamase such as infections caused by S. pneumoniae.…”