Influence of referral bias on the clinical characteristics of patients with Gram-negative bloodstream infection

Referral bias can influence the results of studies performed at tertiary-care centres. In this study, we evaluated demographic and microbiological factors that influenced referral of patients with Gram-negative bloodstream infection (BSI). We identified 2919 and 846 unique patients with Gram-negative BSI in a referral cohort of patients treated at Mayo Clinic Hospitals and a population-based cohort of Olmsted County, Minnesota, residents between 1 January 1998 and 31 December 2007, respectively. Multivariable logistic regression analysis was used to determine factors associated with referral. Elderly patients aged >= 80 years with Gram-negative BSI were less likely to be referred than younger patients [ odds ratio (OR) 0.43, 95% confidence intervals (CI) 0.30-0.62] as were females (OR 0.63, 95% CI 0.53-0.74). After adjusting for age and gender, bloodstream isolates of Escherichia coli (OR 0.50, 95% CI 0.43-0.58) and Proteus mirabilis (OR 0.49, 95% CI 0.30-0.82) were underrepresented in the referral cohort; and Pseudomonas aeruginosa (OR 2.26, 95% CI 1.70-3.06), Enterobacter cloacae (OR 2.31, 95% CI 1.53-3.66), Serratia marcescens (OR 2.34, 95% CI 1.33-4.52) and Stenotrophomonas maltophilia (OR 17.94, 95% CI 3.98-314.43) were overrepresented in the referral cohort. We demonstrated that demographic and microbiological characteristics of patients with Gram-negative BSI had an influence on referral patterns. These factors should be considered when interpreting results of investigations performed at tertiary-care centres.