Influence of extended-spectrum β-lactams on gram-negative bacterial resistance

Purpose. The influence of extended- spectrum β-lactams on gram-negative bacterial resistance was studied. Methods. Hospital pharmacists were asked to provide data on antimicrobial use and bacterial susceptibilities. Defined daily doses per 1000 patient-days of cefepime, ceftazidime, ceftriaxone, and piperacillin–tazobactam were assessed for significant associations with gram-negative susceptibility. To account for midyear changes in usage patterns and the lag between changes in usage and resistance, susceptibility over two-year periods was evaluated. Results. Susceptibility data of more than 300,000 gram-negative isolates, representing 10 species of interest, were provided by 82 U.S. hospitals. Two-year periods ( n = 45) were evaluable for 25 hospitals, containing 159 hospital-years of data and 204,513 clinical isolates. Use of cefepime increased, while use of ceftazidime, ceftriaxone, and piperacillin–tazobactam decreased. Excluding Pseudomonas aeruginosa, bacteria were most susceptible to cefepime, followed by piperacillin–tazobactam, ceftriaxone, and ceftazidime. Significantly decreased susceptibilities of gram-negative bacteria to the antibiotics themselves were observed with ceftazidime ( Enterobacter aerogenes ) and ceftriaxone ( Escherichia coli ). Extended-spectrum β-lactams associated with significantly decreased susceptibilities of gram-negative bacteria to other β-lactams included cefepime ( E. aerogenes and E. coli susceptibility to ceftazidime), ceftazidime ( Enterobacter cloacae susceptibility to cefepime), ceftriaxone ( E. cloacae susceptibility to cefepime), piperacillin–tazobactam ( E. cloacae, Klebsiella pneumoniae, and P. aeruginosa susceptibility to cefepime). There were insufficient susceptibility data to allow for impact analysis for piperacillin–tazobactam. Conclusion. Use of cefepime, ceftazidime, ceftriaxone, and piperacillin–tazobactam was associated with variably changing susceptibilities of several key gram-negative bacteria, either to themselves or to each other. Despite the increased use of cefepime, gram-negative bacterial susceptibility to cefepime remained high.