Table 2.

Select Limitations of Existing Observational Studies Comparing Noncarbapenem β-Lactam Antibiotics and Carbapenems for the Treatment of Extended-Spectrum β-Lactamase Infections

• Inconsistent criteria for extended-spectrum β-lactamase production

• Confounding by indication (ie, ill-appearing patients more likely to receive the more “aggressive” therapy, ie, carbapenems)

• Differences in outcomes definitions

• Delays in initiating appropriate antibiotic therapy

• Classification issues for patients initially receiving empiric noncarbapenem β-lactam therapy, then transitioned to carbapenem therapy

• Large proportions of patients receiving combination antibiotic therapy

• Often single-center experiences

• Sample sizes limit sufficient power to detect differences between treatment approaches, if such differences exist

• Insufficient subgroups for analysis (eg, proportion of Escherichia coli vs Klebsiella pneumoniae, proportion of blaCTX-M vs blaSHV)

• Disproportionate numbers of patients with low-inoculum and high-inoculum infections

• Differences in antibiotic susceptibility criteria utilized

• Differences in local epidemiology of in vitro activity of noncarbapenem β-lactams

• Insufficient data on dosing regimens

• Insufficient data on clinical outcomes with extended-infusion β-lactam therapy