Trends in Ceftazidime and Ciprofloxacin Resistance among U.S. Inpatient Klebsiella pneumoniae and Escherichia coli Isolates, 1999–2006

Background: Resistance to fluoroquinolones and 3^rd and 4^th generation cephalosporins has increased dramatically among clinical isolates of K. pneumoniae and E. coli in the last decade. Trends in the development of these resistant organisms have not been described at a national level using a large sample size.

Objective: To quantify national trends in susceptibility to ceftazidime and ciprofloxacin among inpatient K. pneumoniae and E. coli isolates.

Methods: The Surveillance Network Database--USA, a nationally representative database of susceptibility records from ~300 U.S. hospitals, was used to assess trends in resistance over the period 1999–2006. Inpatient isolates of K. pneumonia and E. coli that were tested for susceptibility against ceftazidime or ciprofloxacin were included in the analysis. Data were filtered to retain only the first isolate of each organism from a patient in a given year. The χ² test for linear trend was used to assess significance of yearly trends in susceptibility levels.

Results: A total of 185,704 inpatient K. pneumoniae isolates and 518,801 inpatient E. coli isolates were submitted to the database from 1999 to 2006. For K. pneumoniae, ceftazidime resistance increased from 6.9% of isolates tested in 1999 to 12.3% in 2006 (P<0.001) and ciprofloxacin resistance increased from 6.0% in 1999 to 14.2% in 2006 (P<0.001). For E. coli, ceftazidime resistance increased from 2.0% of isolates tested in 1999 to 2.7% in 2006 (P<0.001) and ciprofloxacin resistance increased from 4.7% in 1999 to 26.1% in 2006 (P<0.001). Among 124,832 K. pneumoniae isolates tested against both ceftazidime and ciprofloxacin, 71% of ceftazidime-resistant strains were also ciprofloxacin-resistant, and 64% of ciprofloxacin-resistant strains were also ceftazidime-resistant. Among 327,248 E. coli isolates tested for resistance against ceftazidime and ciprofloxacin, 78% of ceftazidime-resistant strains were also ciprofloxacin-resistant, whereas only 11% of ciprofloxacin-resistant strains were also ceftazidime-resistant.

Conclusions: Ceftazidime and ciprofloxacin resistance increased over the period 1999–2006 among inpatient isolates of both K. pneumoniae and E. coli. Ciprofloxacin resistance among E. coli showed a particularly large increase over the study period. Ciprofloxacin resistance and ceftazidime resistance were often observed together for K. pneumoniae isolates. For E. coli isolates, while ceftazidime-resistant isolates were often ciprofloxacin-resistant, ciprofloxacin resistance was often present in the absence of ceftazidime resistance. In spite of sharing some common resistance mechanisms, the acquisition of ceftazidime and fluoroquinolone resistance and the drivers behind their development may differ between E. coli and K. pneumoniae.