Temporal association between antibiotic use and resistance in Klebsiella pneumoniae at a tertiary care hospital

Background: beta-Lactam/beta-lactamase inhibitors (BLBLIs) were introduced into clinical practice as an alternative to carbapenems for treating multi-drug-resistant Klebsiella pneumoniae infections. However, little is known about the relationship between BLBLI treatment and antimicrobial resistance. In this study, we investigated the trends and the temporal association between antibiotic use and antimicrobial resistance in K. pneumoniae isolates obtained between 2012 and 2016. Methods: Data regarding quarterly consumption (total number of prescriptions per quarter) of all BLBLIs, all third-generation cephalosporins, and all fluoroquinolones at a tertiary care hospital were obtained from the Korean Health Insurance Review and Assessment Service. Susceptibility data (isolation rate of antibiotic resistance per quarter) were obtained from the existing database of the same tertiary hospital. Regression analysis was used to analyze annual trends and cross-correlations to assess the temporal association on a quarterly basis between antibiotic consumption and antibiotic resistance in K. pneumoniae. Results: The rate of resistance to piperacillin/tazobactam in K. pneumoniae significantly increased over the study period (p < 0.01). The consumption of all BLBLIs was also found to be significantly correlated with the rate of resistance to piperacillin/tazobactam (beta = 0.66; p < 0.01), ceftazidime (beta = 0.54; p = 0.02), and levofloxacin (beta = -0.60; p = 0.01) with two-quarter lags. Furthermore, the consumption of all third-generation cephalosporins was significantly correlated with rates of K. pneumoniae resistance to ceftazidime (beta = 0.64; p < 0.01) with a two quarter lag and levofloxacin (beta = 0.50; p = 0.03) with a quarter lag. The consumption of all fluoroquinolones correlated with resistance rates to ceftazidime (beta = 0.14; p < 0.01) with a two-quarter lag. Conclusions: The rate of resistance to piperacillin/tazobactam in K. pneumoniae increased significantly over the study period and was significantly correlated with BLBLI consumption. While BLBLIs can potentially be utilized as an alternative to carbapenems, our findings reinforce concerns of resistance to these drugs. Further research is needed to understand the implications on resistance of utilizing BLBLIs as a carbapenem-sparing option.