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This study aims to measure the costs associated with overtesting and overdiagnosis of C. difficile infection. By leveraging PCR cycle threshold data, the true infection can be differentiated from colonization, and determinants of costs in these groups can be identified.
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Measuring the Cost of Overtesting and Overdiagnosis of C. difficile Infection • Division of Infectious Diseases & International Health • Department of Medicine, School of Medicine • Gregory R. Madden, MD • Costi D. Sifri, MD • McIntire School of Commerce • David C. Smith, PhD
Asymptomatic Colonization • Predisposing antibiotics • Toxins A/B • Spore-forming bacteria • Leading cause of healthcare-associated infection • C. difficile Infection Image: David Goulding, Wellcome Trust / Flickr cc Jose S, Madan R. Neutrophil-mediated inflammation in the pathogenesis of Clostridium difficile infections. Anaerobe. 2016;41:85-90. Yang Z, Zhang Y, Huang T, Feng H. Glucosyltransferase activity of Clostridium difficile Toxin B is essential for disease pathogenesis. Gut Microbes. 2015;6(4):221-224.
C. difficile infection costs the US $5.4 Billion annually1,2 • $7,286-$11,285 per hospitalized case3,4 • Additional 5 days length of stay3 • The Cost of C. difficile Polage CR, et al. JAMA Intern Med 2015; 175:1792-1801 Desai K, et al. BMC Infect Dis 2016; 16:303 Magee G, et al. Am J Infect Control 2015; 43:1148-53 Zimlichman E, et al. JAMA Intern Med 2013; 173:2039-46
+ Toxin B Gene PCR C. difficile Negative ~15% of Hospitalized Patients C. difficile Colonization C. difficile Infection >25% of Hospitalized Patients Diarrhea
C. difficile Negative C. difficile Colonization What is the Cost of Overdiagnosis?
C. difficile PCR Cycle Threshold GeneXpert CTMaximum Cutoff = 37.0. Estimated limit of detection of 1,657 colony-forming units.
Low PCR CT (≤26.0 - 28.0): • +Toxin EIA, +CCNA1 • ↑ Symptoms (duration of diarrhea, pain)2 • clinically severe CDI1,3 • LowPCR Cycle Threshold = Likely Infected Kamboj M, et al. J Infect. 2018; 76:369-75 Pollock NR. J ClinMicrobiol. 2016; 54:259-64 Garvey MI, et al. Antimicrob Resist Infect Control. 2017; 6:217
High PCR CT (≥30.85) is associated with: >98% negative predictive value for 3 other (more specific tests) combined. • High PCR Cycle Threshold = Likely Colonized Adapted from: Senchyna F, Gaur RL, Gombar S, Truong CY, Schroeder LF, Banaei N. Clostridium difficile PCR Cycle Threshold Predicts Free Toxin. Tang Y-W, editor. J ClinMicrobiol. American Society for Microbiology; 2017 Sep;55(9):2651–60.
Measuring the Cost of Overtesting and Overdiagnosis of C. difficile infection.
Aim: What are the costs associated with C. difficile overtesting and overdiagnosis? • leverage PCR cycle threshold data to differentiate true infection versus colonization and identify determinants of costs in these groups • Measuring the Cost of Overtesting and Overdiangnosis of C. difficile infection.
~1,800 positive tests (Jan 2014-June 2018) • C. difficile Real-Time PCR Cycle Threshold
≤28.0 (81% PPV for (+) CCNA)1 = Likely “True” Infection • Measuring the Cost of Overtesting and Overdiagnosis of C. difficile infection. >30.85 (>98% NPV for (-) CCNA)2 =Likely Colonization
Patients testing as “Colonized” could be more expensive to treat independent of outcome of Real-Time PCR Test Confounding patient characteristics that could be correlated with “Colonized” grouping and also raise costs: • Age • Antibiotic Exposure • Charlson Comorbidity Index (CCI) • Length of Stay • ICU Location at Time of Diagnosis • Sepsis • Acute Kidney Injury • Elevated WBC Count To account for confounding factors, will employ a propensity scorematching estimator as a multivariate and nonlinear control for confounding factors • Measurement issue: Selection bias