Aims: Amoxicillin-clavulanate is extensively used in European hospitals. Whether the hospital use of amoxicillin-clavulanate is associated with nonsusceptibility to third-generation cephalosporins (3GC) in Klebsiella pneumoniae is unknown. Our aim was to assess the relationship between the hospital use of amoxicillin-clavulanate and 3GC nonsusceptibility in K. pneumoniae and Escherichia coli.
Methods: Yearly data of antibiotic use and 3GC nonsusceptibility in K. pneumoniae and E. coli were obtained from 33 French hospitals between 2011 and 2016. Decreased susceptibility to 3GC and Extended-Spectrum Beta-Lactamase (ESBL) production were modelled from antibiotic use with linear mixed models on years 2011 to 2015, and validated on year 2016.
Results: Nonsusceptibility to 3GC increased in K. pneumoniae and E. coli. In a multivariable model that included year and use of 3GC and fluoroquinolones as explanatory variables, amoxicillin-clavulanate use was protective against 3GC nonsusceptibility in K. pneumoniae (incidence rate ratio [IRR], 0.992 [0.988-0.997]), and with ESBL production in K. pneumoniae (IRR, 0.989 [0.985-0.992]). The correlation coefficient between observed and predicted numbers of 3GC-nonsusceptible K. pneumoniae in 2016 was 0.95 (95% confidence interval, 0.89-0.98). There was no significant association between amoxicillin-clavulanate use and 3GC nonsusceptibility in E. coli.
Conclusion: Amoxicillin-clavulanate hospital use was protective against nonsusceptibility to 3GC in K. pneumoniae. Conversely, it was not associated with susceptibility to 3GC in E. coli. To decrease the hospital use of 3GC and fluoroquinolones, and 3GC nonsusceptibility in K. pneumoniae, it may be acceptable to increase the hospital use of amoxicillin-clavulanate. Interventional studies are necessary to confirm this hypothesis.
Keywords: Escherichia coli; Klebsiella pneumoniae; amoxicillin-clavulanate; antibiotic use; ecological study; linear mixed model; resistance; third-generation cephalosporins.