Influence of extended-spectrum beta-lactams on gram-negative bacterial resistance.
OBJECTIVE
The influence of extended- spectrum beta-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 beta-lactams associated with significantly decreased susceptibilities of gram-negative bacteria to other beta-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.


CONCLUSIONS
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.
Clinical Outcomes Research, CPL Associates LLC, Buffalo, NY 14226, USA. paladino@cplassociates.com
Joseph A
JA
Paladino
Jenna L
JL
Sunderlin
Mendel E
ME
Singer
Martin H
MH
Adelman
Jerome J
JJ
Schentag
D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use; D002170:Canada; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006801:Humans; D010607:Pharmacy Service, Hospital; D016896:Treatment Outcome; D014481:United States; D018440:beta-Lactam Resistance; D047090:beta-Lactams / Q000494:pharmacology / Q000627:therapeutic use
D000900:Anti-Bacterial Agents; D047090:beta-Lactams