model to predict mdr-gnb colonization and infection 1217
control interventions. However, universal microbiological surveillance for every patient that is admitted to identify MDR-GNB colonized patients is both time and resource consuming.12,13 A risk-stratified surveillance strategy to iden- tify patients harboring MDR-GNB prior to the implementa- tion of stringent infection control interventions is a more reasonable and field-applicable approach. Several predictive models have been developed by researchers with the aim of stratifying patients at risk of antimicrobial-resistant GNB colonization or infection. However, these models have limitations, including the use of a retrospective study design,14–17 a narrow focus on a specific antimicrobial-resistant organism, such as MDR Acinetobacter baumannii or extended-spectrum β–lactamase-producing Enterobacteriaceae,14–21 the use of an inpatient study population,16–18,21 or the need for prior culture results as a predictive variable.16–21 Studies using clinical culture results may only misclassify patients colonized with antimicrobial-resistant GNB as noncolonized, which inevitably introduces an information and classification biases in these studies.14–18,21 Therefore, to develop an MDR-GNB prediction model that addresses these limitations, a prospective, active- surveillance, culture-based study that targets community patients is required to assist first-line physicians in their risk-stratification and clinical decisions. We hypothesized that certain clinical characteristics could
independently predict different risk levels of colonization by MDR-GNB. A prediction model integrating information regarding these factors could effectively stratify patients with differential risks of MDR-GNB colonization. We also hypothesized that the risk of infection with MDR-GNB was correlated with the risk ofMDR-GNB colonization. We aimed to develop a score-based prediction system that more accu- rately identified community-based patients at risk of being colonized by MDR-GNB at the time of hospital admission and at risk of subsequent infection during hospitalization.
patients and methods Study Design and Setting
The National Taiwan University Hospital is a 2,200-bed teaching hospital providing both primary and tertiary care in northern Taiwan. The hospital has a busy emergency depart- ment (ED) with more than 100,000 visits annually, with 20% of hospitalized patients admitted through the ED. We con- ducted this ED-based prospective study to develop an MDR- GNB colonization prediction model (COP model) in the first stage of this study, which was then tested in the second stage of the study via the field applicability of this model in identifying
ED patients at risk of developing MDR-GNB infection. In the first stage, conducted from April 1, 2009, to September 30, 2009, 995 ED patients were enrolled and underwent active microbiological surveillance before admission. Clinical and microbiological data collected at this stage were used in the derivation and validation of the COP model. The second stage,
conducted from September 1, 2015, to November 30, 2015, in which 998 ED patients were enrolled, was designed to assess the usefulness of the COP model in predicting the occurrence ofMDR-GNB infection during the subsequent hospitalization course. The study was approved by the institutional review board of the hospital, and the requirement for written consent was waived.
Selection of Participants
In the first stage of this study, all adult patients (≥16 years of age) who stayed at the ED Observation and Extended Care Area awaiting admission to the medical wards were actively screened by research nurses every Tuesday and Thursday during the study period. After an explanation of the study was given and oral consent was obtained, patientswere interviewed using a standardized recording form by a single study investi- gator. Universal active surveillance cultures from anterior nares swab, posterior pharyngeal wall (throat) swab, urine, and areas of skin breakdown if presented were consistently col- lected by a single research nurse. To achieve high compliance with active surveillance within the ED setting, we did not obtain perianal swab cultures. Clinical cultures to identify potential infection were also collected based on the judgment of the ED primary care phy- sician. We reviewed all early clinical cultures (within 48 hours of admission)14,15 for every study patient to prevent the active surveillance cultures from missing any potential MDR-GNB colonized cases.22 A patient was identified as MDR-GNB colonized if the patient had a positive culture result for MDR- GNBfrom either the active surveillance culture or early clinical culture obtained within 48 hours of admission. In the second stage of this study, all adult patients (≥16 years
of age) who stayed at the ED Observation and Extended Care Area awaiting admission to the medical wards were evaluated for the risk of developing an MDR-GNB infection using the COP model scoring form. This scoring form included different point scores for a range of independent predictors identified in the first stage of this study. Decision-driven clinical cultures were ordered and medications or other treatments were provided by the primary care physicians without any knowledge of the results of the COP model evaluation.
Definition of MDR-GNB
We defined MDR-GNB as Enterobacteriaceae or glucose non- fermentative gram-negative bacilli (NFGNB) with resistance to at least 3 different antimicrobial classes. For Enterobacteriaceae, MDR was defined as resistance to at least 3 classes of the following agents: third- or fourth-generation cephalosporins, aminoglycosides, fluoroquinolones, ampicillin/sulbactam, and carbapenems (ertapenem was included in the 2015 [second] stage of the study). For NFGNB, MDR was defined as resis- tance to at least 3 classes of the following agents: anti- pseudomonal cephalosporins (ceftazidime or cefepime),
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