infection control & hospital epidemiology july 2018, vol. 39, no. 7 original article


Hospital-Level Variability in Broad-Spectrum Antibiotic Use for Children With Acute Leukemia Undergoing Hematopoietic Cell Transplantation


Caitlin W. Elgarten, MD;1,2 Staci D. Arnold, MD, MPH, MBA;3 Yimei Li, PhD;1,2 Yuan-Shung V. Huang, MS;4 Marcie L. Riches, MD, MS;5 Jeffrey S. Gerber, MD, PhD, MSCE;2,4,6 Richard Aplenc, MD, PhD, MSCE;1,2,4 Wael Saber, MD, MS;7 Brian T. Fisher, DO, MPH, MSCE2,4,6


objective. To explore the prevalence and drivers of hospital-level variability in antibiotic utilization among hematopoietic cell transplant (HCT) recipients to inform antimicrobial stewardship initiatives.


design. Retrospective cohort study using data merged from the Pediatric Health Information System and the Center for International Blood and Marrow Transplant Research.


setting. The study included 27 transplant centers in freestanding children’s hospitals.


methods. The primary outcome was days of broad-spectrum antibiotic use in the interval from day of HCT through neutrophil engraft- ment. Hospital antibiotic utilization rates were reported as days of therapy (DOTs) per 1,000 neutropenic days. Negative binomial regression was used to estimate hospital utilization rates, adjusting for patient covariates including demographics, transplant characteristics, and severity of illness. To better quantify the magnitude of hospital variation and to explore hospital-level drivers in addition to patient-level drivers of variation, mixed-effects negative binomial models were also constructed.


results. Adjusted hospital rates of antipseudomonal antibiotic use varied from 436 to 1121 DOTs per 1,000 neutropenic days, and rates of broad-spectrum, gram-positive antibiotic use varied from 153 to 728 DOTs per 1,000 neutropenic days. We detected variability by hospital in choice of antipseudomonal agent (ie, cephalosporins, penicillins, and carbapenems), but gram-positive coverage was primarily driven by vancomycin use. Considerable center-level variability remained even after controlling for additional hospital-level factors. Antibiotic use was not strongly associated with days of significant illness or mortality.


conclusion. Among a homogenous population of children undergoing HCT for acute leukemia, both the quantity and spectrum of antibiotic exposure in the immediate posttransplant period varied widely. Antimicrobial stewardship initiatives can apply these data to optimize the use of antibiotics in transplant patients.


Infect Control Hosp Epidemiol 2018;39:797–805


Overuse and inappropriate selection of antibiotics have been described in most healthcare settings.1,2 With increasing anti- microbial resistance and limited new antibiotics under devel- opment, the identification off high-impact targets for antibiotic stewardship is critical.3 To this end, the Infectious Disease Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA) recommend assessing antibiotic utilization across institutions to quantify variability in practice and to provide a metric against which hospitals can benchmark their antibiotic use.4


Evaluating true differences in antibiotic utilization across


hospitals requires the analysis of patient and hospital character- istics to standardize comparisons. Previously published analytic approaches reveal considerable variability in antibiotic prescrib- ing across institutions, even after accounting for differences in patient populations.5–8 Alternatively, antibiotic use can be asses- sed within a more homogeneous population. This approach has been utilized in children with inflammatory bowel disease9 and acute lymphoblastic leukemia,10 demonstrating variability in utilization despite caring for groups with similar disease.


Affiliations: 1. Division of Oncology, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania; 2. Center for Clinical Epidemiology and Biostatistics,


Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania; 3. Aflac Cancer and Blood Disorders Center, Children’sHealthcare of Atlanta, Emory University, Atlanta, Georgia; 4. Center of Pediatric Clinical Effectiveness, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania; 5. Division of Hematology/Oncology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; 6. Division of Infectious Diseases, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania; 7. Center for International Blood and Marrow Transplant Research,Milwaukee, Wisconsin.


© 2018 by The Society for Healthcare Epidemiology of America. All rights reserved. 0899-823X/2018/3907-0005. DOI: 10.1017/ice.2018.96 Received January 17, 2018; accepted March 26, 2018; electronically published May 8, 2018


Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46  |  Page 47  |  Page 48  |  Page 49  |  Page 50  |  Page 51  |  Page 52  |  Page 53  |  Page 54  |  Page 55  |  Page 56  |  Page 57  |  Page 58  |  Page 59  |  Page 60  |  Page 61  |  Page 62  |  Page 63  |  Page 64  |  Page 65  |  Page 66  |  Page 67  |  Page 68  |  Page 69  |  Page 70  |  Page 71  |  Page 72  |  Page 73  |  Page 74  |  Page 75  |  Page 76  |  Page 77  |  Page 78  |  Page 79  |  Page 80  |  Page 81  |  Page 82  |  Page 83  |  Page 84  |  Page 85  |  Page 86  |  Page 87  |  Page 88  |  Page 89  |  Page 90  |  Page 91  |  Page 92  |  Page 93  |  Page 94  |  Page 95  |  Page 96  |  Page 97  |  Page 98  |  Page 99  |  Page 100  |  Page 101  |  Page 102  |  Page 103  |  Page 104  |  Page 105  |  Page 106  |  Page 107  |  Page 108  |  Page 109  |  Page 110  |  Page 111  |  Page 112  |  Page 113  |  Page 114  |  Page 115  |  Page 116  |  Page 117  |  Page 118  |  Page 119  |  Page 120  |  Page 121  |  Page 122  |  Page 123  |  Page 124  |  Page 125  |  Page 126  |  Page 127  |  Page 128  |  Page 129  |  Page 130  |  Page 131  |  Page 132  |  Page 133  |  Page 134  |  Page 135  |  Page 136  |  Page 137  |  Page 138  |  Page 139  |  Page 140  |  Page 141  |  Page 142  |  Page 143  |  Page 144