Clinical Impact of Multiplex Molecular Diagnostic Testing in Children With Acute Gastroenteritis Presenting to an Emergency Department: A Multicenter Prospective Study.

BACKGROUND: Multiplex molecular diagnostic panels have greatly enhanced detection of gastrointestinal pathogens. However, data on the impact of these tests on clinical and patient-centered outcomes are limited. METHODS: We conducted a prospective, multicenter, stepped-wedge trial to determine the impact of multiplex molecular testing at 5 academic children's hospitals on children presenting to the emergency department with acute gastroenteritis. Caregivers were interviewed on enrollment and 7-10 days after enrollment to determine symptoms, risk factors, subsequent medical visits, and impact on family members. During the pre-intervention period, diagnostic testing was performed at the clinician's discretion . During the intervention period, multiplex molecular testing was performed on all children, with results available to clinicians. The primary outcome was return visits to a healthcare provider within 10 days of enrollment. RESULTS: Potential pathogens were identified by clinician-ordered tests in 19 of 571 (3.3%) in the pre-intervention period compared with 434 of 586 (74%) in the intervention period; clinically relevant pathogens were detected in 2.1% and 15%, respectively. In the multivariate model, the intervention was associated with a 21% reduction in the odds of any return visit (odds ratio, 0.79; 95% confidence interval, .70-.90) after adjusting for potential confounders. Appropriate treatment was prescribed in 11.3% compared with 19.6% during the intervention period (P = .22). CONCLUSIONS: Routine molecular multiplex testing for all children who presented to the ED with acute gastroenteritis detected more clinically relevant pathogens and led to a 21% decrease in return visits. Additional research is needed to define patients most likely to benefit from testing. Clinical Trials Registration. NCT02248285.

Guide to Utilization of the Microbiology Laboratory for Diagnosis of Infectious Diseases: 2024 Update by the Infectious Diseases Society of America (IDSA) and the American Society for Microbiology (ASM).

The critical nature of the microbiology laboratory in infectious disease diagnosis calls for a close, positive working relationship between the physician and the microbiologists who provide enormous value to the health care team. This document, developed by experts in both adult and pediatric laboratory and clinical medicine, provides information on which tests are valuable and in which contexts, and on tests that add little or no value for diagnostic decisions. Sections are divided into anatomic systems, including Bloodstream Infections and Infections of the Cardiovascular System, Central Nervous System Infections, Ocular Infections, Soft Tissue Infections of the Head and Neck, Upper Respiratory Infections, Lower Respiratory Tract infections, Infections of the Gastrointestinal Tract, Intraabdominal Infections, Bone and Joint Infections, Urinary Tract Infections, Genital Infections, and Skin and Soft Tissue Infections; or into etiologic agent groups, including arboviral Infections, Viral Syndromes, and Blood and Tissue Parasite Infections. Each section contains introductory concepts, a summary of key points, and detailed tables that list suspected agents; the most reliable tests to order; the samples (and volumes) to collect in order of preference; specimen transport devices, procedures, times, and temperatures; and detailed notes on specific issues regarding the test methods, such as when tests are likely to require a specialized laboratory or have prolonged turnaround times. In addition, the pediatric needs of specimen management are also addressed. There is redundancy among the tables and sections, as many agents and assay choices overlap. The document is intended to serve as a reference to guide physicians in choosing tests that will aid them to diagnose infectious diseases in their patients.

A multicenter evaluation of viral bloodstream detections in children presenting to the Emergency Department with suspected systemic infection.

BACKGROUND: Fever is a common symptom in children presenting to the Emergency Department (ED). We aimed to describe the epidemiology of systemic viral infections and their predictive values for excluding serious bacterial infections (SBIs), including bacteremia, meningitis and urinary tract infections (UTIs) in children presenting to the ED with suspected systemic infections. METHODS: We enrolled children who presented to the ED with suspected systemic infections who had blood cultures obtained at seven healthcare facilities. Whole blood specimens were analyzed by an experimental multiplexed PCR test for 7 viruses. Demographic and laboratory results were abstracted. RESULTS: Of the 1114 subjects enrolled, 245 viruses were detected in 224 (20.1%) subjects. Bacteremia, meningitis and UTI frequency in viral bloodstream-positive patients was 1.3, 0 and 10.1% compared to 2.9, 1.3 and 9.7% in viral bloodstream-negative patients respectively. Although viral bloodstream detections had a high negative predictive value for bacteremia or meningitis (NPV = 98.7%), the frequency of UTIs among these subjects remained appreciable (9/89, 10.1%) (NPV = 89.9%). Screening urinalyses were positive for leukocyte esterase in 8/9 (88.9%) of these subjects, improving the ability to distinguish UTI. CONCLUSIONS: Viral bloodstream detections were common in children presenting to the ED with suspected systemic infections. Although overall frequencies of SBIs among subjects with and without viral bloodstream detections did not differ significantly, combining whole blood viral testing with urinalysis provided high NPV for excluding SBI.

Prediction of Adverse Outcomes in Pediatric Acute Hematogenous Osteomyelitis.

BACKGROUND: Clinicians cannot reliably predict complications of acute hematogenous osteomyelitis (AHO). METHODS: Consecutive cases of AHO from 2 pediatric centers in the United States were analyzed retrospectively to develop clinical tools from data obtained within 96 hours of hospitalization to predict acute and chronic complications of AHO. Two novel composite prediction scores derived from multivariable logistic regression modeling were compared with a previously published severity of illness (SOI) score, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) using area under the receiver operating characteristic curve analyses. RESULTS: The causative organisms were identified in 73% of 261 cases. Bacteremia (45%), abscesses (38%), and associated suppurative arthritis (23%) were relatively common. Acute or chronic complications occurred in 24% and 11% of patients, respectively. Multivariable logistic regression identified bone abscess (odds ratio [OR], 2.3 [95% confidence interval {CI}, 1.0-5.2]), fever > 48 hours (OR, 2.7 [95% CI, 1.2-6.0]), suppurative arthritis (OR, 3.2 [95% CI, 1.3-7.5]), disseminated disease (OR, 4.6 [95% CI, 1.5-14.3]), and delayed source control (OR, 5.1 [95% CI, 1.4-19.0]) as strong predictors of acute complications. In a separate model, CRP ≥ 100 mg/L at 2-4 days after antibiotics (OR, 2.7 [95% CI, 1.0-7.3]), disseminated disease (OR, 3.3 [95% CI, 1.1-10.0]), and requirement for bone debridement (OR, 6.7 [95% CI, 2.1-21.0]) strongly predicted chronic morbidity. These variables were combined to create weighted composite prediction scores for acute (A-SCORE) and chronic (C-SCORE) osteomyelitis, which were superior to SOI, CRP, and ESR and had negative predictive values > 90%. CONCLUSIONS: Two novel composite clinical scores were superior to existing tools to predict complications of pediatric AHO.

Opportunities Revealed for Antimicrobial Stewardship and Clinical Practice with Implementation of a Rapid Respiratory Multiplex Assay.

Few studies assess the utility of rapid multiplex molecular respiratory panels in adult patients. Previous multiplex PCR assays took hours to days from order time to result. We analyze the clinical impact of switching to a molecular assay with a 3-h test-turnaround-time (TAT). We performed a retrospective review of adult patients who presented to our emergency departments with respiratory symptoms and had a respiratory viral panel (xTAG RVP; RVP) or respiratory pathogen panel (ePlex RP; RPP) within 48 h of presentation. The average TATs for the RVP and RPP were 27.9 and 3.0 h, respectively (P < 0.0001). In RVP-positive and RPP-positive patients, 68.9 and 44.5% of those with normal chest imaging received antibiotics (P = 0.013), while 95.4 and 89.6% of those with abnormal imaging received antibiotics, respectively (P = 0.187). There was no difference in antibiotic duration in RVP-positive and RPP-positive patients with abnormal chest imaging (6.2 and 6.0 days, respectively; P = 0.923) and normal chest imaging (4.5 and 4.3 days, respectively; P = 0.922). Fewer patients were admitted in the RPP-positive compared to the RVP-positive group (76.9 and 88.6%, respectively; P = 0.013), while the proportion of admissions were similar among RPP-negative and RVP-negative patients (85.3 and 87.1%, P = 0.726). Switching to a multiplex respiratory panel with a clinically actionable TAT is associated with reduced hospital admissions and, in admitted adults without focal radiographic findings, reduced antibiotic initiation. Opportunities to further mitigate inappropriate antibiotic use may be realized by combining rapid multiplex PCR with provider education, clinical decision-care algorithms, and active antibiotic stewardship.

A Guide to Utilization of the Microbiology Laboratory for Diagnosis of Infectious Diseases: 2018 Update by the Infectious Diseases Society of America and the American Society for Microbiology.

The critical nature of the microbiology laboratory in infectious disease diagnosis calls for a close, positive working relationship between the physician/advanced practice provider and the microbiologists who provide enormous value to the healthcare team. This document, developed by experts in laboratory and adult and pediatric clinical medicine, provides information on which tests are valuable and in which contexts, and on tests that add little or no value for diagnostic decisions. This document presents a system-based approach rather than specimen-based approach, and includes bloodstream and cardiovascular system infections, central nervous system infections, ocular infections, soft tissue infections of the head and neck, upper and lower respiratory infections, infections of the gastrointestinal tract, intra-abdominal infections, bone and joint infections, urinary tract infections, genital infections, and other skin and soft tissue infections; or into etiologic agent groups, including arthropod-borne infections, viral syndromes, and blood and tissue parasite infections. Each section contains introductory concepts, a summary of key points, and detailed tables that list suspected agents; the most reliable tests to order; the samples (and volumes) to collect in order of preference; specimen transport devices, procedures, times, and temperatures; and detailed notes on specific issues regarding the test methods, such as when tests are likely to require a specialized laboratory or have prolonged turnaround times. In addition, the pediatric needs of specimen management are also emphasized. There is intentional redundancy among the tables and sections, as many agents and assay choices overlap. The document is intended to serve as a guidance for physicians in choosing tests that will aid them to quickly and accurately diagnose infectious diseases in their patients.

A Guide to Utilization of the Microbiology Laboratory for Diagnosis of Infectious Diseases: 2018 Update by the Infectious Diseases Society of America and the American Society for Microbiology.

The critical nature of the microbiology laboratory in infectious disease diagnosis calls for a close, positive working relationship between the physician/advanced practice provider and the microbiologists who provide enormous value to the healthcare team. This document, developed by experts in laboratory and adult and pediatric clinical medicine, provides information on which tests are valuable and in which contexts, and on tests that add little or no value for diagnostic decisions. This document presents a system-based approach rather than specimen-based approach, and includes bloodstream and cardiovascular system infections, central nervous system infections, ocular infections, soft tissue infections of the head and neck, upper and lower respiratory infections, infections of the gastrointestinal tract, intra-abdominal infections, bone and joint infections, urinary tract infections, genital infections, and other skin and soft tissue infections; or into etiologic agent groups, including arthropod-borne infections, viral syndromes, and blood and tissue parasite infections. Each section contains introductory concepts, a summary of key points, and detailed tables that list suspected agents; the most reliable tests to order; the samples (and volumes) to collect in order of preference; specimen transport devices, procedures, times, and temperatures; and detailed notes on specific issues regarding the test methods, such as when tests are likely to require a specialized laboratory or have prolonged turnaround times. In addition, the pediatric needs of specimen management are also emphasized. There is intentional redundancy among the tables and sections, as many agents and assay choices overlap. The document is intended to serve as a guidance for physicians in choosing tests that will aid them to quickly and accurately diagnose infectious diseases in their patients.

Multicenter Evaluation of BioFire FilmArray Meningitis/Encephalitis Panel for Detection of Bacteria, Viruses, and Yeast in Cerebrospinal Fluid Specimens.

Rapid diagnosis and treatment of infectious meningitis and encephalitis are critical to minimize morbidity and mortality. Comprehensive testing of cerebrospinal fluid (CSF) often includes Gram stain, culture, antigen detection, and molecular methods, paired with chemical and cellular analyses. These methods may lack sensitivity or specificity, can take several days, and require significant volume for complete analysis. The FilmArray Meningitis/Encephalitis (ME) Panel is a multiplexed in vitro diagnostic test for the simultaneous, rapid (∼1-h) detection of 14 pathogens directly from CSF specimens: Escherichia coli K1, Haemophilus influenzae, Listeria monocytogenes, Neisseria meningitidis, Streptococcus pneumoniae, Streptococcus agalactiae, cytomegalovirus, enterovirus, herpes simplex virus 1 and 2, human herpesvirus 6, human parechovirus, varicella-zoster virus, and Cryptococcus neoformans/Cryptococcus gattii We describe a multicenter evaluation of 1,560 prospectively collected CSF specimens with performance compared to culture (bacterial analytes) and PCR (all other analytes). The FilmArray ME Panel demonstrated a sensitivity or positive percentage of agreement of 100% for 9 of 14 analytes. Enterovirus and human herpesvirus type 6 had agreements of 95.7% and 85.7%, and L. monocytogenes and N. meningitidis were not observed in the study. For S. agalactiae, there was a single false-positive and false-negative result each, for a sensitivity and specificity of 0 and 99.9%, respectively. The specificity or negative percentage of agreement was 99.2% or greater for all other analytes. The FilmArray ME Panel is a sensitive and specific test to aid in diagnosis of ME. With use of this comprehensive and rapid test, improved patient outcomes and antimicrobial stewardship are anticipated.

Extragenital Infections Caused by Chlamydia trachomatis and Neisseria gonorrhoeae: A Review of the Literature.

In the United States, sexually transmitted diseases due to Chlamydia trachomatis and Neisseria gonorrhoeae continue to be a major public health burden. Screening of extragenital sites including the oropharynx and rectum is an emerging practice based on recent studies highlighting the prevalence of infection at these sites. We reviewed studies reporting the prevalence of extragenital infections in women, men who have sex with men (MSM), and men who have sex only with women (MSW), including distribution by anatomical site. Among women, prevalence was found to be 0.6-35.8% for rectal gonorrhea (median reported prevalence 1.9%), 0-29.6% for pharyngeal gonorrhea (median 2.1%), 2.0-77.3% for rectal chlamydia (median 8.7%), and 0.2-3.2% for pharyngeal chlamydia (median 1.7%). Among MSM, prevalence was found to be 0.2-24.0% for rectal gonorrhea (median 5.9%), 0.5-16.5% for pharyngeal gonorrhea (median 4.6%), 2.1-23.0% for rectal chlamydia (median 8.9%), and 0-3.6% for pharyngeal chlamydia (median 1.7%). Among MSW, the prevalence was found to be 0-5.7% for rectal gonorrhea (median 3.4%), 0.4-15.5% for pharyngeal gonorrhea (median 2.2%), 0-11.8% for rectal chlamydia (median 7.7%), and 0-22.0% for pharyngeal chlamydia (median 1.6%). Extragenital infections are often asymptomatic and found in the absence of reported risk behaviors, such as receptive anal and oral intercourse. We discuss current clinical recommendations and future directions for research.

Performance of the molecular Alere I influenza A&B test compared to that of the xpert flu A/B assay.

Data on the performance of rapid molecular point-of-care use platforms for diagnosis of influenza are lacking. We validated nasopharyngeal (NP) flocked specimens in universal transport medium (UTM) and evaluated the clinical sensitivity and specificity of the Alere i influenza A&B test compared to those of the Xpert flu A/B assay. The Alere i influenza A&B test had an overall sensitivity and specificity of 93.8% and 62.5% for influenza A, respectively, and of 91.8% and 53.6% for influenza B, respectively. The poor specificity was due to influenza virus samples determined positive for both type A and B.

Multicenter evaluation of the BioFire FilmArray gastrointestinal panel for etiologic diagnosis of infectious gastroenteritis.

The appropriate treatment and control of infectious gastroenteritis depend on the ability to rapidly detect the wide range of etiologic agents associated with the disease. Clinical laboratories currently utilize an array of different methodologies to test for bacterial, parasitic, and viral causes of gastroenteritis, a strategy that suffers from poor sensitivity, potentially long turnaround times, and complicated ordering practices and workflows. Additionally, there are limited or no testing methods routinely available for most diarrheagenic Escherichia coli strains, astroviruses, and sapoviruses. This study assessed the performance of the FilmArray Gastrointestinal (GI) Panel for the simultaneous detection of 22 different enteric pathogens directly from stool specimens: Campylobacter spp., Clostridium difficile (toxin A/B), Plesiomonas shigelloides, Salmonella spp., Vibrio spp., Vibrio cholerae, Yersinia enterocolitica, enteroaggregative E. coli, enteropathogenic E. coli, enterotoxigenic E. coli, Shiga-like toxin-producing E. coli (stx1 and stx2) (including specific detection of E. coli O157), Shigella spp./enteroinvasive E. coli, Cryptosporidium spp., Cyclospora cayetanensis, Entamoeba histolytica, Giardia lamblia, adenovirus F 40/41, astrovirus, norovirus GI/GII, rotavirus A, and sapovirus. Prospectively collected stool specimens (n = 1,556) were evaluated using the BioFire FilmArray GI Panel and tested with conventional stool culture and molecular methods for comparison. The FilmArray GI Panel sensitivity was 100% for 12/22 targets and ≥94.5% for an additional 7/22 targets. For the remaining three targets, sensitivity could not be calculated due to the low prevalences in this study. The FilmArray GI Panel specificity was ≥97.1% for all panel targets. The FilmArray GI Panel provides a comprehensive, rapid, and streamlined alternative to conventional methods for the etiologic diagnosis of infectious gastroenteritis in the laboratory setting. The potential advantages include improved performance parameters, a more extensive menu of pathogens, and a turnaround time of as short as 1 h.

Viral respiratory tract infections in the neonatal intensive care unit: the VIRIoN-I study.

OBJECTIVE: To determine the frequency of respiratory viral infections among infants who were evaluated for late-onset sepsis in the neonatal intensive care units (NICUs) of Parkland Memorial Hospital, Dallas, Texas; and Women & Infants Hospital, Providence, Rhode Island. STUDY DESIGN: Prospective cohort study conducted from January 15, 2012 to January 31, 2013. Infants in the NICU were enrolled if they were inborn, had never been discharged home, and were evaluated for sepsis (at >72 hours of age) and antibiotic therapy was initiated. Infants had a nasopharyngeal specimen collected for detection of respiratory viruses by multiplex polymerase chain reaction within 72 hours of the initiation of antibiotic therapy. Their medical records were reviewed for demographic, clinical, radiographic, and laboratory data until NICU discharge. RESULTS: During the 13-month study, 8 of 100 infants, or 8 (6%) of the 135 sepsis evaluations, had a respiratory virus detected by polymerase chain reaction (2, enterovirus/rhinovirus; 2, rhinovirus; 2, coronaviruses; and 2, parainfluenza-3 virus). By bivariate analysis, the infants with viral detection were older (41 vs 11 days; P = .007), exposed to individuals with respiratory tract viral symptoms (37% vs 2%; P = .003), tested for respiratory viruses by provider (75% vs 11%; P < .001), and had lower total neutrophil counts (P = .02). In multivariate regression analysis, the best predictor of viral infection was the caregivers' clinical suspicion of viral infection (P = .006). CONCLUSIONS: A total of 8% of infants, or 6% of all NICU sepsis evaluations, had a respiratory virus detected when evaluated for bacterial sepsis. These findings argue for more respiratory viral testing of infants with suspected sepsis using optimal molecular assays to establish accurate diagnoses, prevent transmission, and inform antibiotic stewardship efforts.

Etiologies of bloody diarrhea in children presenting with acute gastroenteritis to US emergency departments.

Among 111 children presenting with bloody diarrhea in a multicenter study of molecular testing in US emergency departments, we found viral pathogens in 18%, bacteria in 48%, protozoa in 2%, and no pathogens detected in 38%.

Combination of a Rapid Diagnostic Assay and Antimicrobial Stewardship Intervention for Gram-Negative Bacteremia.

Background: Traditional blood cultures for gram-negative bacteremia can take up to 72 hours or more to return results, prolonging the duration of empiric broad-spectrum intravenous antibiotics. The Accelerate Pheno system provides rapid identification and susceptibilities for blood cultures in gram-negative bacteremia. Current data on its clinical utility are mixed overall, so the system requires further research. Methods: A multicenter, retrospective quasi-experimental study was conducted comparing the Accelerate Pheno rapid diagnostic system with antimicrobial stewardship intervention and traditional blood cultures alone. Results: A total of 264 patients with blood cultures with gram-negative bacteria growth were included in the final analysis (102 pre-intervention, 162 post-intervention). The antimicrobial stewardship team made 364 recommendations in 152/162 (93.8%) patients in the post group. Duration of intravenous therapy was shorter (P < .001) for the post-intervention group (median, 4.0 days) compared with the pre-intervention group (median, 7.5 days). Hospital length of stay was also shorter (P < .001) for the post-intervention group (median, 5.1 days) compared with the pre-intervention group (median, 7.0 days). Readmission rates within 30 days were reduced (P = .042) post-intervention (13.0%) compared with pre-intervention (22.6%). In the post-intervention group, a larger proportion of patients were transitioned to oral therapy at any point (126/162, 77.8%) compared with pre-intervention (62/102, 60.8%; P < .001). Conclusions: These results suggest that the Accelerate Pheno system, with active review and intervention by a multidisciplinary antimicrobial stewardship team, is a useful tool in improving both patient-centric and antimicrobial stewardship outcomes.

Executive summary: a guide to utilization of the microbiology laboratory for diagnosis of infectious diseases: 2013 recommendations by the Infectious Diseases Society of America (IDSA) and the American Society for Microbiology (ASM)(a).

The critical role of the microbiology laboratory in infectious disease diagnosis calls for a close, positive working relationship between the physician and the microbiologists who provide enormous value to the health care team. This document, developed by both laboratory and clinical experts, provides information on which tests are valuable and in which contexts, and on tests that add little or no value for diagnostic decisions. Sections are divided into anatomic systems, including Bloodstream Infections and Infections of the Cardiovascular System, Central Nervous System Infections, Ocular Infections, Soft Tissue Infections of the Head and Neck, Upper Respiratory Infections, Lower Respiratory Tract infections, Infections of the Gastrointestinal Tract, Intraabdominal Infections, Bone and Joint Infections, Urinary Tract Infections, Genital Infections, and Skin and Soft Tissue Infections; or into etiologic agent groups, including Tickborne Infections, Viral Syndromes, and Blood and Tissue Parasite Infections. Each section contains introductory concepts, a summary of key points, and detailed tables that list suspected agents; the most reliable tests to order; the samples (and volumes) to collect in order of preference; specimen transport devices, procedures, times, and temperatures; and detailed notes on specific issues regarding the test methods, such as when tests are likely to require a specialized laboratory or have prolonged turnaround times. There is redundancy among the tables and sections, as many agents and assay choices overlap. The document is intended to serve as a reference to guide physicians in choosing tests that will aid them to diagnose infectious diseases in their patients.

A guide to utilization of the microbiology laboratory for diagnosis of infectious diseases: 2013 recommendations by the Infectious Diseases Society of America (IDSA) and the American Society for Microbiology (ASM)(a).

The critical role of the microbiology laboratory in infectious disease diagnosis calls for a close, positive working relationship between the physician and the microbiologists who provide enormous value to the health care team. This document, developed by both laboratory and clinical experts, provides information on which tests are valuable and in which contexts, and on tests that add little or no value for diagnostic decisions. Sections are divided into anatomic systems, including Bloodstream Infections and Infections of the Cardiovascular System, Central Nervous System Infections, Ocular Infections, Soft Tissue Infections of the Head and Neck, Upper Respiratory Infections, Lower Respiratory Tract infections, Infections of the Gastrointestinal Tract, Intraabdominal Infections, Bone and Joint Infections, Urinary Tract Infections, Genital Infections, and Skin and Soft Tissue Infections; or into etiologic agent groups, including Tickborne Infections, Viral Syndromes, and Blood and Tissue Parasite Infections. Each section contains introductory concepts, a summary of key points, and detailed tables that list suspected agents; the most reliable tests to order; the samples (and volumes) to collect in order of preference; specimen transport devices, procedures, times, and temperatures; and detailed notes on specific issues regarding the test methods, such as when tests are likely to require a specialized laboratory or have prolonged turnaround times. There is redundancy among the tables and sections, as many agents and assay choices overlap. The document is intended to serve as a reference to guide physicians in choosing tests that will aid them to diagnose infectious diseases in their patients.

Reducing Clostridium difficile incidence, colectomies, and mortality in the hospital setting: a successful multidisciplinary approach.

BACKGROUND: Health care associated Clostridium difficile infections are a major cause of morbidity and mortality in hospitals. In the United States, from 2000 through 2009, discharge diagnoses from hospitals in the United States that included C. difficile increased from 139,000 to 336,600, and the yearly national excess hospital cost associated with hospital-onset C. difficile is estimated to be upwards of $1.3 billion. METHODS: A hospitalwide, multidisciplinary approach was undertaken at Rhode Island Hospital (Providence), a tertiary care hospital. The hospital plan entailed six interventions: (1) develop a C. difficile hospital infection control plan based on a risk assessment; (2) monitor hospitalwide morbidity and mortality associated with C. difficile infection; (3) improve sensitivity of C. difficile toxin detection in stool specimens using a polymerase chain reaction-based nucleic acid amplification assay; (4) enhance environmental cleaning of patient rooms and equipment; (5) develop a C. difficile infection treatment plan; and (6) conduct other interventions. The incidence of health care-associated C. difficile infection was assessed from January 2006 through the third quarter of 2012; the number of colectomies and mortality associated with C. difficile infection were determined from January 2005 through the third quarter of 2012. RESULTS: The incidence of health care-associated C. difficile infection decreased from a peak of 12.2/1,000 discharges during the second quarter of 2006 to 3.6/1,000 discharges during the third quarter of 2012. The yearly mortality in patients with health care-associated C. difficile infection was reduced from a peak of 52 in 2006 to 19 in 2011, with 13 such cases in the first three quarters of 2012. CONCLUSIONS: A hospitalwide multidisciplinary approach can reduce health care-associated C. difficile infection morbidity and mortality.

Clinical Impact of Multiplex Molecular Diagnostic Testing in Children with Acute Gastroenteritis Presenting to An Emergency Department: A Multicenter Prospective Study.

Background: Multiplex molecular diagnostic panels have greatly enhanced detection of gastrointestinal pathogens. However, data on the impact of these tests on clinical and patient-centered outcomes are limited. Methods: We conducted a prospective, multicenter, stepped-wedge trial to determine the impact of multiplex molecular testing at five academic children's hospitals in children presenting to the ED with acute gastroenteritis. Caregivers were interviewed on enrollment and again 7-10 days after enrollment to determine symptoms, risk factors, subsequent medical visits, and impact on family members. During the pre-intervention period, diagnostic testing was performed at the discretion of clinicians. During the intervention period, multiplex molecular testing was performed on all children with results available to clinicians. Primary outcome was return visits to a health care provider within 10 days of enrollment. Results: Potential pathogens were identified by clinician ordered tests in 19/571 (3.3%) in the pre-intervention period compared to 434/586 (74%) in the intervention period; clinically relevant pathogens were detected in 2.1% and 15% respectively. In the multivariate model adjusting for potential confounders, the intervention was associated with a 21% reduction in the odds of any return visit (OR 0.79; 95% CI 0.70-0.90). Appropriate treatment was prescribed in 11.3% compared to 19.6% during the intervention period(P=0.22). Conclusions: Routine molecular multiplex testing for all children presenting to the ED with AGE detected more clinically relevant pathogens and led to a 21% decrease in return visits. Additional research is needed to define patients most likely to benefit from testing.