Person: Rhee, Chanu
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Rhee
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Chanu
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Rhee, Chanu
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Publication Improving documentation and coding for acute organ dysfunction biases estimates of changing sepsis severity and burden: a retrospective study(BioMed Central, 2015) Rhee, Chanu; Murphy, Michael; Li, Lingling; Platt, Richard; Klompas, MichaelIntroduction: Claims-based analyses report that the incidence of sepsis-associated organ dysfunction is increasing. We examined whether coding practices for acute organ dysfunction are changing over time and if so, whether this is biasing estimates of rising severe sepsis incidence and severity. Methods: We assessed trends from 2005 to 2013 in the annual sensitivity and incidence of discharge ICD-9-CM codes for organ dysfunction (shock, respiratory failure, acute kidney failure, acidosis, hepatitis, coagulopathy, and thrombocytopenia) relative to standardized clinical criteria (use of vasopressors/inotropes, mechanical ventilation for ≥2 consecutive days, rise in baseline creatinine, low pH, elevated transaminases or bilirubin, abnormal international normalized ratio or low fibrinogen, and decline in platelets). We studied all adult patients with suspected infection (defined by ≥1 blood culture order) at two US academic hospitals. Results: Acute organ dysfunction codes were present in 57,273 of 191,695 (29.9 %) hospitalizations with suspected infection, most commonly acute kidney failure (60.2 % of cases) and respiratory failure (28.9 %). The sensitivity of all organ dysfunction codes except thrombocytopenia increased significantly over time. This was most pronounced for acute kidney failure codes, which increased in sensitivity from 59.3 % in 2005 to 87.5 % in 2013 relative to a fixed definition for changes in creatinine (p = 0.019 for linear trend). Acute kidney failure codes were increasingly assigned to patients with smaller creatinine changes: the average peak creatinine change associated with a code was 1.99 mg/dL in 2005 versus 1.49 mg/dL in 2013 (p <0.001 for linear decline). The mean number of dysfunctional organs in patients with suspected infection increased from 0.32 to 0.59 using discharge codes versus 0.69 to 0.79 using clinical criteria (p <0.001 for both trends and comparison of the two trends). The annual incidence of hospitalizations with suspected infection and any dysfunctional organ rose an average of 5.9 % per year (95 % CI 4.3, 7.4 %) using discharge codes versus only 1.1 % (95 % CI 0.1, 2.0 %) using clinical criteria. Conclusions: Coding for acute organ dysfunction is becoming increasingly sensitive and the clinical threshold to code patients for certain kinds of organ dysfunction is decreasing. This accounts for much of the apparent rise in severe sepsis incidence and severity imputed from claims.Publication Epidemiology of Inappropriate Empiric Antibiotic Therapy for Bacteremia Based on Discordant In vitro Susceptibilities: Risk factors and Taxon-level Variation in Burden and Outcome in 156 US hospitals, 2000–2014(Oxford University Press, 2017) Kadri, Sameer S; Lai, Yi Ling; Ricotta, Emily; Strich, Jeffrey; Babiker, Ahmed; Dekker, John P; Palmore, Tara N; Rhee, Chanu; Klompas, Michael; Hooper, David; Powers, John H; Danner, Robert L; Adjemian, JenniferAbstract Background: Discordance between in vitro susceptibility and empiric antibiotic therapy is inextricably linked to antibiotic resistance and decreased survival in bloodstream infections (BSI). However, its prevalence, patient- and hospital-level risk factors, and impact on outcome in a large cohort and across different pathogens remain unclear. Methods: We examined in vitro susceptibility interpretations for bacterial BSI and corresponding antibiotic therapy among inpatient encounters across 156 hospitals from 2000 to 2014 in the Cerner Healthfacts database. Discordance was defined as nonsusceptibility to initial therapy administered from 2 days before pathogen isolation to 1 day before final susceptibility reporting. Discordance prevalence was compared across taxa; risk factors and its association with in-hospital mortality were evaluated by logistic regression. Adjusted odds ratios (aOR) were estimated for pathogen-, patient- and facility-level factors. Results: Of 33,161 unique encounters with BSIs, 4,219 (13%) at 123 hospitals met criteria for discordant antibiotic therapy, ranging from 3% for pneumococci to 55% for E. faecium. Discordance was higher in recent years (2010–2014 vs. 2005–2009) and was associated with older age, lower baseline SOFA score, urinary (vs. abdominal) source and hospital-onset BSI, as well as ≥500-bed, Midwestern, non-teaching, and rural hospitals. Discordant antibiotic therapy increased the risk of death [aOR = 1.3 [95% CI 1.1–1.4]). Among Gram-negative taxa, discordant therapy increased risk of mortality associated with Enterobacteriaceae (aOR = 1.3 [1.0–1.6]) and non-fermenters (aOR = 1.7 [1.1–2.5]). Among Gram-positive taxa, risk of mortality from discordant therapy was significantly higher for S. aureus (aOR = 1.3 [1.1–1.6]) but unchanged for streptococcal or enterococcal BSIs. Conclusion: The prevalence of discordant antibiotic therapy displayed extensive taxon-level variability and was associated with patient and institutional factors. Discordance detrimentally impacted survival in Gram-negative and S. aureus BSIs. Understanding reasons behind observed differences in discordance risk and their impact on outcomes could inform stewardship efforts and guidelines for empiric therapy in sepsis. Disclosures All authors: No reported disclosures.Publication Epidemiologic Investigation of a Cluster of Neuroinvasive Bacillus cereus Infections in 5 Patients With Acute Myelogenous Leukemia(Oxford University Press, 2015) Rhee, Chanu; Klompas, Michael; Tamburini, Fiona B.; Fremin, Brayon J.; Chea, Nora; Epstein, Lauren; Halpin, Alison Laufer; Guh, Alice; Gallen, Rachel; Coulliette, Angela; Gee, Jay; Hsieh, Candace; Desjardins, Christopher A.; Pedamullu, Chandra Sekhar; DeAngelo, Daniel J.; Manzo, Veronica E.; Folkerth, Rebecca Dunn; Milner, Danny A.; Pecora, Nicole; Osborne, Matthew; Chalifoux-Judge, Diane; Bhatt, Ami S.; Yokoe, Deborah S.Background. Five neuroinvasive Bacillus cereus infections (4 fatal) occurred in hospitalized patients with acute myelogenous leukemia (AML) during a 9-month period, prompting an investigation by infection control and public health officials. Methods. Medical records of case-patients were reviewed and a matched case-control study was performed. Infection control practices were observed. Multiple environmental, food, and medication samples common to AML patients were cultured. Multilocus sequence typing was performed for case and environmental B cereus isolates. Results. All 5 case-patients received chemotherapy and had early-onset neutropenic fevers that resolved with empiric antibiotics. Fever recurred at a median of 17 days (range, 9–20) with headaches and abrupt neurological deterioration. Case-patients had B cereus identified in central nervous system (CNS) samples by (1) polymerase chain reaction or culture or (2) bacilli seen on CNS pathology stains with high-grade B cereus bacteremia. Two case-patients also had colonic ulcers with abundant bacilli on autopsy. No infection control breaches were observed. On case-control analysis, bananas were the only significant exposure shared by all 5 case-patients (odds ratio, 9.3; P = .04). Five environmental or food isolates tested positive for B cereus, including a homogenized banana peel isolate and the shelf of a kitchen cart where bananas were stored. Multilocus sequence typing confirmed that all case and environmental strains were genetically distinct. Multilocus sequence typing-based phylogenetic analysis revealed that the organisms clustered in 2 separate clades. Conclusions. The investigation of this neuroinvasive B cereus cluster did not identify a single point source but was suggestive of a possible dietary exposure. Our experience underscores the potential virulence of B cereus in immunocompromised hosts.Publication Improving Documentation and Coding for Acute Organ Dysfunction Biases Severe Sepsis Surveillance Over Time(Oxford University Press, 2015) Rhee, Chanu; Murphy, Michael; Li, Lingling; Platt, Richard; Klompas, MichaelPublication Sepsis and the theory of relativity: measuring a moving target with a moving measuring stick(BioMed Central, 2016) Klompas, Michael; Rhee, ChanuPublication Diagnosing sepsis is subjective and highly variable: a survey of intensivists using case vignettes(BioMed Central, 2016) Rhee, Chanu; Kadri, Sameer S.; Danner, Robert L.; Suffredini, Anthony F.; Massaro, Anthony; Kitch, Barrett T.; Lee, Grace; Klompas, MichaelBackground: Sepsis is the focus of national quality improvement programs and a recent public reporting measure from the Centers for Medicare and Medicaid Services. However, diagnosing sepsis requires interpreting nonspecific signs and can therefore be subjective. We sought to quantify interobserver variability in diagnosing sepsis. Methods: We distributed five case vignettes of patients with suspected or confirmed infection and organ dysfunction to a sample of practicing intensivists. Respondents classified cases as systemic inflammatory response syndrome, sepsis, severe sepsis, septic shock, or none of the above. Interobserver variability was calculated using Fleiss’ κ for the five-level classification, and for answers dichotomized as severe sepsis/septic shock versus not-severe sepsis/septic shock and any sepsis category (sepsis, severe sepsis, or septic shock) versus not-sepsis. Results: Ninety-four physicians completed the survey. Most respondents (88 %) identified as critical care specialists; other specialties included pulmonology (39 %), anesthesia (19 %), surgery (9 %), and emergency medicine (9 %). Respondents had been in practice for a median of 8 years, and 90 % practiced at academic hospitals. Almost all respondents (83 %) felt strongly or somewhat confident in their ability to apply the traditional consensus sepsis definitions. However, overall interrater agreement in sepsis diagnoses was poor (Fleiss’ κ 0.29). When responses were dichotomized into severe sepsis/septic shock versus not-severe sepsis/septic shock or any sepsis category versus not-sepsis, agreement was still poor (Fleiss’ κ 0.23 and 0.18, respectively). Seventeen percent of respondents classified one of the five cases as severe sepsis/septic shock, 27.7 % rated two cases, 33.0 % respondents rated three cases, 19.2 % rated four cases, and 3.2 % rated all five cases as severe sepsis/septic shock. Among respondents who felt strongly confident in their ability to use sepsis definitions (n = 45), agreement was no better (Fleiss’ κ 0.28 for the five-category classification, and Fleiss’ κ 0.21 for the dichotomized severe sepsis/septic shock classification). Cases were felt to be extremely or very realistic in 74 % of responses; only 3 % were deemed unrealistic. Conclusions: Diagnosing sepsis is extremely subjective and variable. Objective criteria and standardized methodology are needed to enhance consistency and comparability in sepsis research, surveillance, benchmarking, and reporting. Electronic supplementary material The online version of this article (doi:10.1186/s13054-016-1266-9) contains supplementary material, which is available to authorized users.Publication Using Procalcitonin to Guide Antibiotic Therapy(Oxford University Press, 2016) Rhee, ChanuAbstract Procalcitonin levels rise in response to systemic inflammation, especially of bacterial origin. Multiple randomized controlled trials have demonstrated that procalcitonin-based algorithms can safely reduce antibiotic use in 2 clinical scenarios. First, in stable, low-risk patients with respiratory infections, procalcitonin levels of <0.25 µg/L can guide the decision to withhold antibiotics or stop therapy early. Second, in critically ill patients with suspected sepsis, clinicians should not initially withhold antibiotics, but procalcitonin levels of <0.5 µg/L or levels that decrease by ≥80% from peak can guide discontinuation once patients stabilize. The recent stop antibiotics on procalcitonin guidance study (SAPS), the largest procalcitonin trial to date, demonstrated reduction in both antibiotic exposure and mortality in critically ill patients. Although procalcitonin is ready for routine use, future research should examine optimal strategies for implementation in hospitals, its real-world impact on clinical outcomes and costs, its applicability to immunocompromised patients, and the generalizability of trials to the US population.Publication Impact of Procalcitonin (PCT)-Guided Antibiotic Therapy on Mortality in Critically Ill Patients: A Systematic Review and Meta-Analysis of 18 Randomized Controlled Trials(Oxford University Press, 2017) Pepper, Dominique; Sun, Junfeng; Rhee, Chanu; Welsh, Judith; Powers, John H; Danner, Robert L; Kadri, SameerAbstract Background: Procalcitonin (PCT)-guided antibiotic therapy has been shown to reduce antibiotic use in critically ill patients with suspected or proven infection, but its impact on mortality remains uncertain. Our meta-analysis examines the effect of PCT-guided antibiotic therapy on survival in critically ill patients. Methods: We searched PubMed, the Cochrane Library, Scopus, Web of Science, EMBASE and clinicaltrials.gov electronic databases up to October 2016. The meta-analysis was restricted to randomized controlled trials (RCTs) of critically ill patients receiving PCT-guided antibiotic treatment and reporting survival or antibiotic duration. Study quality was assessed using the Cochrane risk of bias tool. Two reviewers conducted all review stages independently, and a third reviewer adjudicated any differences. Data was pooled using random-effects meta-analysis. Results: Of the 18 RCTs selected (n = 5,183 patients; Table), 17 assessed mortality and 11 assessed antibiotic duration; 8 scored ≥3 and 10 scored ≤2 out of 6 on the risk of bias assessment. Compared with controls, PCT-guided antibiotic treatment was associated with a significant reduction in mortality (20.7% vs. 23.0%; risk ratio [RR] 0.90[95% CI, 0.81–0.99], I2=0%; Figure 1). Survival benefit was retained in the RCT subset with a lower risk of bias (score ≥ 3; RR 0.87 [95% CI, 0.77,0.98], I2=0%; Figure 2) but not with higher risk (score ≤ 2; RR 0.98 [95% CI, 0.80–1.20], I2=0%). Our analysis of the effect of PCT-guided antibiotic therapy on antibiotic duration displayed significant heterogeneity (I2=61.2%, P = 0.004), which precluded reporting on aggregate effect. Important limitations were: single center RCT (n = 9), lack of double blinding (all studies) and variable protocol non-adherence and timeframes examined for mortality. Conclusion: In a meta-analysis of RCTs of critically ill patients with suspected or proven infection, PCT-guided antibiotic treatment was associated with a significant reduction in mortality. The observed survival benefit was weighted towards RCTs of relatively higher quality. However, the plausibility of this finding, as well as the impact of protocol non-adherence on outcome needs further study. Funded by Intramural NIH and NCI Contract# HHSN261200800001E Disclosures All authors: No reported disclosures.