Choosing more effective antimicrobial combinations for empiric antimicrobial therapy of serious gram-negative rod infections using a dual cross-table antibiogram

BackgroundEarly antimicrobial therapy with antibiotics effective in vitro is a powerful predictor of a favorable outcome with gram-negative rod bacteremia or pneumonia. Most clinicians rely on institutional antibiograms based on testing patient isolates with individual antimicrobials when choosing initial empiric regimens for suspected gram-negative sepsis and use 2 antibiotics at the outset to maximize the likelihood that the infecting species will be susceptible to at least 1 of those used. Current hospital antibiograms do not take into account cross-resistance among different antimicrobials, which would seem of importance in selecting initial combination regimens for serious gram-negative bacillary infections.MethodsWe examined the in vitro efficacy of various potential dual antimicrobial combinations by cross-table susceptibility analysis for bloodstream and lower respiratory tract isolates of Enterobacteraciae and Pseudomonas aeruginosa from patients hospitalized in our university hospital during 2004-2006 using SafetySurveillor software (Premier Inc, Charlotte, NC). Effective regimens were defined as dual combinations in which the isolate was susceptible in vitro to at least 1 of the 2 antibiotics.ResultsIndividual antimicrobial susceptibilities for the 604 hospital-wide and 145 intensive care unit gram-negative bloodstream or lower respiratory tract isolates ranged from 81% to 91%. The most effective dual combinations were imipenem based (95% for the hospital as a whole, 92%-95% susceptible in the intensive care unit), and some combinations were significantly superior (P < .05). Combination β-lactam antimicrobials were also effective.ConclusionTraditional hospital susceptibility reporting of individual antibiotic susceptibilities is currently used to guide empiric antimicrobial therapy. Cross-resistance analyses allow selection of initial dual regimens that are more likely to be effective in vitro and, most importantly, clinically. Double β-lactam regimens were among the most effective regimens; empiric use of such combinations may be underutilized and warrants reexamination.