Selection of a surrogate beta-lactam testing agent for initial susceptibility testing of doripenem, a new carbapenem

Abstract

Doripenem, a broad-spectrum parenteral carbapenem, has potency and pharmacokinetic/pharmacodynamic features most similar to imipenem and meropenem. Because of potential delays in release of commercial testing devices post-regulatory approval (US Food and Drug Administration), "surrogate markers" offer immediate susceptibility guidance for doripenem use. Cross-susceptibility analysis of reference MIC values compared imipenem, meropenem, and ertapenem with doripenem for 8 groupings of recent bacterial isolates (19308 strains). Use of proposed carbapenem or oxacillin surrogate testing agents until doripenem-containing commercial systems are available provides 89.1% to 100.0% absolute categorical agreement with <0.1% false-susceptible error, a level of accuracy recommending interim clinical application. Generally, isolates that are susceptible to other tested carbapenems can be considered susceptible to doripenem; however, some organisms that are intermediate or resistant to imipenem or meropenem may be susceptible to doripenem and will require additional susceptibility testing.