Cost-Effectiveness Analysis of Four Common Diagnostic Methods for Clostridioides difficile Infection.

BACKGROUND: No studies have evaluated the cost-effectiveness of single and two-step different diagnostic test strategies for Clostridioides difficile infection (CDI), including direct and indirect costs. OBJECTIVE: To evaluate the cost-effectiveness of commonly available diagnostic tests for CDI including nucleic acid amplification testing (NAAT) alone, glutamate dehydrogenase followed by enzyme immunoassay for toxin (GDH/EIA), GDH then NAAT (GDH/NAAT), and NAAT then EIA (NAAT/EIA). DESIGN: Decision tree model from the US societal perspective with inputs derived from the literature. Willingness-to-pay threshold was set at $150,000 per quality-adjusted life year (QALY) gained. To assess the impact of uncertainty in model inputs on the findings, we performed one-way and probabilistic sensitivity analyses. PARTICIPANTS: We conducted the analysis to represent a population aged 65 years old with diarrhea who received a CDI diagnostic test. MAIN MEASURES: Incremental cost-effectiveness ratios (ICER) and incremental net monetary benefits (INMB). KEY RESULTS: NAAT alone was the most cost-effective approach overall; GDH/NAAT was the most cost-effective two-step option. NAAT alone led to the highest QALYs gained, at an incremental cost of $54,547 (vs. GDH/NAAT), $55,410 (vs. GDH/EIA), and $50,231 (vs. NAAT/EIA) per QALY gained. NAAT/EIA was not cost-effective compared to any other strategy. GDH/NAAT resulted in a higher QALY compared to GDH/EIA, at an incremental cost of $96,841 per QALY gained. Variability in the likelihood of comorbidities, CDI probability, and age at disease onset did not substantially change the results. One-way sensitivity analyses showed that results were most sensitive to likelihood of recurrence, followed by CDI mortality rate and probability of severe CDI. Probabilistic sensitivity analyses explored known uncertainties in the base case and confirmed the robustness of the results. CONCLUSIONS: NAAT alone and GDH/NAAT (among the two-step options) were the most cost-effective diagnostic test approaches for CDI.

A Case of Langerhans Cell Histiocytosis With Multifocal, Single-System GI Tract Involvement and Literature Review.

Langerhans cell histiocytosis (LCH) is the most common histiocytic disorder, characterized by the pathologic clonal proliferation and accumulation of immature Langerhans cells within organs. Multiple organ systems can be affected, resulting in a spectrum of clinical manifestations. Isolated gastrointestinal involvement in LCH is rare and usually presents in childhood as a multisystem disease and usually has poor outcomes. We describe a 20-year-old Hispanic female with multifocal, single-system gastrointestinal LCH. Initially diagnosed from a CD1a, S100, and CD207 (Langerin) positive appendix tissue after an appendectomy and confirmed multifocal with an endoscopy. She had a full clinical and endoscopic resolution of disease with cytarabine therapy.

Epidemiology of Admissions From the Emergency Department Among Febrile Infants Younger Than 90 Days in the United States, 2002 to 2012.

BACKGROUND AND OBJECTIVES: Febrile infants younger than 90 days are often subjected to invasive diagnostic evaluation and hospitalization to monitor for serious bacterial infection (SBI) despite recent changes in SBI risk and advances in diagnostics. Nationwide provider practices, over time, are unknown for this group. Our objective was to determine the likelihood of admission and associated complications of care for such infants, particularly those at lowest risk for SBI. METHODS: This is a retrospective cohort study including multisite emergency department (ED) visits using administrative data from the Pediatric Emergency Care Applied Research Network Core Data Project. We examined uncomplicated febrile infants younger than 90 days seen in the ED from 2002 to 2012 who did not have an explicit infectious diagnosis, critical illness, or chronic condition. RESULTS: We identified 38,224 infants, among whom, 11,600 (31%) were admitted. We observed a 3% increase in ED admission every year during the study period (P < 0.05). Age less than 30 days and black race were independent predictors of admission (P < 0.01). We identified 227 complications of care in the ED. Among those with a specified cause, 49% were attributed to antibiotic use or procedures related to the diagnosis and empiric treatment of suspected infection. CONCLUSIONS: Despite the decreasing risk of SBI and diagnostic advances during the study period, the odds of hospital admission increased for febrile infants at low risk for sepsis. We also provide first data on therapeutic and diagnostic test-related adverse events in this setting. These data provide further justification for a consensus guideline on management of such infants.

Behavioral Economics Interventions to Improve Outpatient Antibiotic Prescribing for Acute Respiratory Infections: a Cost-Effectiveness Analysis.

BACKGROUND: Behavioral economics interventions have been shown to effectively reduce the rates of inappropriate antibiotic prescriptions for acute respiratory infections (ARIs). OBJECTIVE: To determine the cost-effectiveness of three behavioral economic interventions designed to reduce inappropriate antibiotic prescriptions for ARIs. DESIGN: Thirty-year Markov model from the US societal perspective with inputs derived from the literature and CDC surveillance data. SUBJECTS: Forty-five-year-old adults with signs and symptoms of ARI presenting to a healthcare provider. INTERVENTIONS: (1) Provider education on guidelines for the appropriate treatment of ARIs; (2) Suggested Alternatives, which utilizes computerized clinical decision support to suggest non-antibiotic treatment choices in lieu of antibiotics; (3) Accountable Justification, which mandates free-text justification into the patient's electronic health record when antibiotics are prescribed; and (4) Peer Comparison, which sends a periodic email to prescribers about his/her rate of inappropriate antibiotic prescribing relative to clinician colleagues. MAIN MEASURES: Discounted costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios. KEY RESULTS: Each intervention has lower costs but higher QALYs compared to provider education. Total costs for each intervention were $178.21, $173.22, $172.82, and $172.52, and total QALYs were 14.68, 14.73, 14.74, and 14.74 for the control, Suggested Alternatives, Accountable Justification, and Peer Comparison groups, respectively. Results were most sensitive to the quality-of-life of the uninfected state, and the likelihood and costs for antibiotic-associated adverse events. CONCLUSIONS: Behavioral economics interventions can be cost-effective strategies for reducing inappropriate antibiotic prescriptions by reducing healthcare resource utilization.

Impact of AHA's 2007 guideline change on incidence of infective endocarditis in infants and children.

Use a nationally representative sample to assess impacts of new clinical guidelines issued by the American Heart Association (AHA) in 2007 for many types of invasive procedures, with recommendations for significant decreases in antimicrobial prophylaxis use. STUDY DESIGN: Interrupted time series analyses of pediatric hospitalizations for Infective Endocarditis (IE), using the Nationwide Inpatient Sample (NIS) ICD-9-CM diagnostic codes, identified IE hospitalizations for patients <18 years old from 2001 to 2012. Changes in IE incidence before and after 2007 AHA guidelines were evaluated, with differences in IE clinical severity assessed using in-hospital mortality and length of stay. Analyses were stratified by pathogen type and age group (0-9 y/o and 10-17 y/o). RESULTS: With 3,748 patients in the study, we observed rising trends in IE incidence, but no significant difference between pre- and post-guideline. There was a significant trend increase for IE due to viridans group streptococci (VGS) for ages >10 years old, comparing pre-guideline to post-guideline periods, but not in children 0-9 years of age. Neither in-hospital mortality nor length of stay changed significantly during study. CONCLUSIONS: The data did not demonstrate an impact of the 2007 guideline changes on overall incidence of pediatric IE. However, a significant increase in disease incidence trend due to VGS was observed for the 10-17 year-old group, compared pre- and post-guideline.

Effectiveness of hospital-based postpartum procedures on pertussis vaccination among postpartum women.

OBJECTIVE: Pertussis causes significant morbidity among adults, children, and especially infants. Since 2006, pertussis vaccination has been recommended for women after delivery. We conducted a prospective, controlled evaluation of in-hospital postpartum pertussis vaccination of birth mothers from October 2009 through July 2010 to evaluate the effectiveness of hospital-based procedures in increasing postpartum vaccination. STUDY DESIGN: The intervention and comparison hospitals are private community facilities, each with 2000-6000 births/year. At the intervention hospital, physician opt-in orders for tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine (Tdap) before discharge were implemented in November 2009, followed by standing orders in February 2010. The comparison hospital maintained standard practice. Randomly selected hospital charts of women after delivery were reviewed for receipt of Tdap and demographic data. We evaluated postpartum Tdap vaccination rates and conducted multivariate analyses to evaluate characteristics that are associated with vaccination. We reviewed 1264 charts (658 intervention hospital; 606 comparison hospital) from women with completed deliveries. RESULTS: Tdap postpartum vaccination was 0% at both hospitals at baseline. In the intervention hospital, the introduction of the opt-in order was followed by an increase in postpartum vaccination to 18%. The introduction of the standing order approach was followed by a further increase to 69% (P < .0001). No postpartum Tdap vaccinations were documented in the comparison hospital. Postpartum Tdap vaccination in the intervention hospital did not differ by demographic characteristics. CONCLUSION: In-hospital ordering procedures substantially increased Tdap vaccination coverage in women after delivery. Opt-in orders increased coverage that increased substantially with standing orders.

Changes in perceptions of antibiotic stewardship among neonatal intensive care unit providers over the course of a learning collaborative: a prospective, multisite, mixed-methods evaluation.

OBJECTIVE: To assess clinician perceptions towards the value and implementation of antibiotic stewardship (AS) in neonatal intensive care units (NICU). STUDY DESIGN: We performed a mixed-methods study of AS perceptions (prescribing appropriateness, importance, activity, capacity) using surveys and interviews in 30 California NICUs before and after a multicenter collaborative (Optimizing Antibiotic Use in California NICUs [OASCN]). RESULTS: Pre-OASCN, 24% of respondents felt there was "a lot of" or "some" inappropriate prescribing, often driven by fear of a bad outcome or reluctance to change existing practice. Clinicians reported statistically significant increases in AS importance (71 v 79%), perceived AS activity (67 v 87%), and more openness to change after OASCN (59 v 70%). We identified other concerns that lessen AS effort. CONCLUSION: OASCN increased perceived AS activity and openness to change in AS practices among NICU prescribers. Greater attention to subjective concerns should augment AS improvement.

SHEA NICU white paper series: Practical approaches for the prevention of viral respiratory infections.

This white paper provides clinicians and hospital leaders with practical guidance on the prevention and control of viral respiratory infections in the neonatal intensive care unit (NICU). This document serves as a companion to Centers for Disease Control and Prevention Healthcare Infection Control Practices Advisory Committee (HICPAC)'s "Prophylaxis and Screening for Prevention of Viral Respiratory Infections in Neonatal Intensive Care Unit Patients: A Systematic Review." It provides practical, expert opinion and/or evidence-based answers to frequently asked questions about viral respiratory detection and prevention in the NICU. It was developed by a writing panel of pediatric and pathogen-specific experts who collaborated with members of the HICPAC systematic review writing panel and the SHEA Pediatric Leadership Council to identify questions that should be addressed. The document has been endorsed by SHEA, the American Hospital Association (AHA), The Joint Commission, the Pediatric Infectious Diseases Society (PIDS), the Association for Professionals in Infection Control and Epidemiology (APIC), the Infectious Diseases Society of America (IDSA), and the National Association of Neonatal Nurses (NANN).

Cat scratch disease and other Bartonella infections.

First described in 1931, cat scratch disease remains the most commonly identified clinical syndrome associated with Bartonella infection. Over the last 20 years, however, the discovery and use of modern diagnostic tests has greatly expanded our understanding of the pathogenesis, clinical spectrum, and treatment options for Bartonella infections of all types. Indeed, each varies substantially depending on the infecting species and the immune status of the host.

Estimating the cost of inappropriate antibiotic prophylaxis prior to dental procedures.

Inappropriate dental antibiotic prescriptions to prevent infective endocarditis in the United States results in ∼$31 million in excess costs to the healthcare system and patients. This includes out-of-pocket costs ($20.5 million), drug costs ($2.69 million) and adverse event costs (eg, Clostridioides difficile and hypersensitivity) of $5.82 million (amoxicillin), $1.99 million (clindamycin), and $380,849 (cephalexin).

SHEA Neonatal Intensive Care Unit (NICU) White Paper Series: Practical approaches for the prevention of central-line-associated bloodstream infections.

This document is part of the "SHEA Neonatal Intensive Care Unit (NICU) White Paper Series." It is intended to provide practical, expert opinion, and/or evidence-based answers to frequently asked questions about CLABSI detection and prevention in the NICU. This document serves as a companion to the CDC Healthcare Infection Control Practices Advisory Committee (HICPAC) Guideline for Prevention of Infections in Neonatal Intensive Care Unit Patients. Central line-associated bloodstream infections (CLABSIs) are among the most frequent invasive infections among infants in the NICU and contribute to substantial morbidity and mortality. Infants who survive CLABSIs have prolonged hospitalization resulting in increased healthcare costs and suffer greater comorbidities including worse neurodevelopmental and growth outcomes. A bundled approach to central line care practices in the NICU has reduced CLABSI rates, but challenges remain. This document was authored by pediatric infectious diseases specialists, neonatologists, advanced practice nurse practitioners, infection preventionists, members of the HICPAC guideline-writing panel, and members of the SHEA Pediatric Leadership Council. For the selected topic areas, the authors provide practical approaches in question-and-answer format, with answers based on consensus expert opinion within the context of the literature search conducted for the companion HICPAC document and supplemented by other published information retrieved by the authors. Two documents in the series precede this one: "Practical approaches to Clostridioides difficile prevention" published in August 2018 and "Practical approaches to Staphylococcus aureus prevention," published in September 2020.

Accurate subspecies-level identification of clinically significant Mycobacterium avium and Mycobacterium intracellulare by whole-genome sequencing.

Whole genome sequencing (WGS) of Mycobacterium avium complex (MAC) isolates in the clinical laboratory setting allows for rapid and reliable subspecies identification of a closely related complex of human pathogens. We developed a bioinformatics pipeline for accurate subspecies identification and tested 74 clinical MAC isolates from various anatomical sites. We demonstrate that reliable subspecies level identification of these common and clinically significant MAC isolates, including M. avium subsp. hominissuis (most dominant in causing lower respiratory tract infections in our cohort), M. avium subsp. avium, M. intracellulare subsp. intracellulare, and M. intracellulare subsp. chimaera, can be achieved by analysis of only two marker genes (rpoB and groEL/hsp65). We then explored the relationship between these subspecies and anatomical site of infection. Further, we conducted an in silico analysis and showed our algorithm also performed well for M. avium subsp. paratuberculosis but failed to consistently identify M. avium subsp. silvaticum and M. intracellulare subsp. yongonense, likely due to a lack of available reference genome sequences; all the 3 subspecies were not found in our clinical isolates and rarely reported to cause human infections. Accurate MAC subspecies identification may provide the tool and opportunity for better understanding of the disease-subspecies dynamics in MAC infections.

Blood culture procedures and practices in the neonatal intensive care unit: A survey of a large multicenter collaborative in California.

OBJECTIVE: To describe variation in blood culture practices in the neonatal intensive care unit (NICU). DESIGN: Survey of neonatal practitioners involved with blood culturing and NICU-level policy development. PARTICIPANTS: We included 28 NICUs in a large antimicrobial stewardship quality improvement program through the California Perinatal Quality Care Collaborative. METHODS: Web-based survey of bedside blood culture practices and NICU- and laboratory-level practices. We evaluated adherence to recommended practices. RESULTS: Most NICUs did not have a procedural competency (54%), did not document the sample volume (75%), did not receive a culture contamination report (57%), and/or did not require reporting to the provider if <1 mL blood was obtained (64%). The skin asepsis procedure varied across NICUs. Only 71% had a written procedure, but ≥86% changed the needle and disinfected the bottle top prior to inoculation. More than one-fifth of NICUs draw a culture from an intravascular device only (if present). Of 13 modifiable practices related to culture and contamination, NICUs with nurse practitioners more frequently adopted >50% of practices, compared to units without (92% vs 50% of units; P < .02). CONCLUSIONS: In the NICU setting, recommended practices for blood culturing were not routinely performed.

Evaluation of diagnostic and therapeutic approaches for suspected influenza A(H1N1)pdm09 infection, 2009-2010.

To assess adherence to real-time changes in guidelines for influenza diagnosis and use of oseltamivir during the 2009 influenza A(H1N1) pandemic, we reviewed medical records of patients with confirmed or suspected influenza-like illness (ILI) and those with no viral testing in a large Los Angeles (California, USA) hospital. Of 882 tested patients, 178 had results positive for influenza; 136 of the remaining patients received oseltamivir despite negative or no results. Oseltamivir use was consistent with national recommendations in >90%. Of inpatients, children were less likely than adults to have ILI at testing and to receive oseltamivir if ILI was found. Of outpatients, children were more likely to have positive test results; 20% tested did not have ILI or other influenza signs and symptoms. Twenty-five of 96 test-positive patients and 13 of 19 with lower respiratory tract disease were, inappropriately, not treated. Variations between practice and national recommendations could inform clinical education in future influenza seasons.

Treatment and Epidemiology of Third-Generation Cephalosporin-Resistant Urinary Tract Infections.

BACKGROUND AND OBJECTIVES: Limited data are available on the contemporary epidemiology, clinical management, and health care utilization for pediatric urinary tract infection (UTI) due to third-generation cephalosporin-resistant Enterobacterales (G3CR) in the United States. The objective is to describe the epidemiology, antimicrobial treatment and response, and health care utilization associated with G3CR UTI. METHODS: Multisite, matched cohort-control study including children with G3CR UTI versus non-G3CR UTI. UTI was defined as per American Academy of Pediatrics guidelines, and G3CR as resistance to ceftriaxone, cefotaxime, or ceftazidime. We collected data from the acute phase of illness to 6 months thereafter. RESULTS: Among 107 children with G3CR UTI and 206 non-G3CR UTI with documented assessment of response, the proportion with significant improvement on initial therapy was similar (52% vs 57%; odds ratio [OR], 0.81; 95% confidence interval [CI], 0.44-1.50). Patients with G3CR were more frequently hospitalized at presentation (38% vs 17%; OR, 3.03; 95% CI, 1.77-5.19). In the follow-up period, more patients with G3CR had urine cultures (75% vs 53%; OR, 2.61; 95% CI, 1.33-5.24), antimicrobial treatment of any indication (53% vs 29%; OR, 2.82; 95% CI, 1.47-5.39), and subspecialty consultation (23% vs 6%; OR, 4.52; 95% CI, 2.10-10.09). In multivariate analysis, previous systemic antimicrobial therapy remained a significant risk factor for G3CR UTI (adjusted OR, 1.91; 95% CI, 1.06-3.44). CONCLUSIONS: We did not observe a significant difference in response to therapy between G3CR and susceptible UTI, but subsequent health care utilization was significantly increased.

Cat Scratch Disease and Bartonellaceae: The Known, the Unknown and the Curious.

Since the early 1900s, Bartonella species were known only to cause human disease resulting from very restricted geographic (bartonellosis) or environmental influences ("trench fever"). In the 1990s, and in parallel, cat scratch disease and bacillary angiomatosis were definitively linked to Bartonella species. Subsequently, widespread use of modern diagnostic methods revealed the broad ecologic niche of this organism and greatly expanded our knowledge of the epidemiology and clinical presentations associated with this genus. A large number of reservoirs and vectors involved with Bartonella propagation and transmission to humans have been identified; cats and various arthropods remain the most well-studied to date. Though not completely understood, it appears that specific immune-modulated interactions between the infecting species and host-related factors play a major role in the observed breadth of human clinical syndromes associated with Bartonellae, the large differences in immunopathologic features of tissue samples among different syndromes and potentially the varied responses to antimicrobial therapy. Further, the clinical management for cat scratch disease in particular is quite variable among clinicians, reflecting a poor evidence base. No preventive measures have been developed beyond suggestions to avoid at-risk behavior with known vectors.

Safety and immunogenicity of an inactivated subvirion influenza A (H5N1) vaccine.

BACKGROUND: Influenza A (H5N1) viruses could cause a severe worldwide epidemic, with high attack rates, large numbers of deaths and hospitalizations, and wide disruption. Effective vaccines against these viruses in humans are urgently needed. METHODS: We conducted a multicenter, double-blind two-stage study involving 451 healthy adults 18 to 64 years of age who were randomly assigned in a 2:2:2:2:1 ratio to receive two intramuscular doses of a subvirion influenza A (H5N1) vaccine of 90, 45, 15, or 7.5 microg of hemagglutinin antigen or placebo. The subjects were followed for the safety analysis for 56 days. Serum samples obtained before each vaccination and again 28 days after the second vaccination were tested for H5 antibody by microneutralization and hemagglutination inhibition. RESULTS: Mild pain at the injection site was the most common adverse event for all doses of vaccine. The frequency of a serum antibody response was highest among subjects receiving doses of 45 microg or 90 microg. Among those who received two doses of 90 microg, neutralization antibody titers reached 1:40 or greater in 54 percent, and hemagglutination-inhibition titers reached 1:40 or greater in 58 percent. Neutralization titers of 1:40 or greater were seen in 43 percent, 22 percent, and 9 percent of the subjects receiving two doses of 45, 15, and 7.5 microg, respectively. No responses were seen in placebo recipients. CONCLUSIONS: A two-dose regimen of 90 mug of subvirion influenza A (H5N1) vaccine does not cause severe side effects and, in the majority of recipients, generates neutralizing antibody responses typically associated with protection against influenza. A conventional subvirion H5 influenza vaccine may be effective in preventing influenza A (H5N1) disease in humans. (ClinicalTrials.gov number, NCT00115986.).

Compliance with multiple-dose vaccine schedules among older children, adolescents, and adults: results from a vaccine safety datalink study.

OBJECTIVES: We studied compliance with multiple-dose vaccine schedules, assessed factors associated with noncompliance, and examined timeliness of series completion among older children, adolescents, and adults. METHODS: We conducted a large, multisite, retrospective cohort study of older children, adolescents, and adults in the Vaccine Safety Datalink population from 1996 through 2004. We quantified the rates of completion of all required doses for varicella, hepatitis A, and hepatitis B vaccines according to their recommended schedules. RESULTS: Among those who received a first dose of varicella (n = 16 075), hepatitis A (n = 594 917), and hepatitis B (n = 590 445) vaccine, relatively few completed the series (55%-65% for hepatitis B vaccine and 40%-50% for hepatitis A and varicella vaccines in most age groups). Compliance was lowest among adolescents (35.9%) and Medicaid recipients (29.7%) who received varicella vaccine and among younger adult age groups who received hepatitis A vaccine (25%-35% across those age groups). Even among series completers, there was a relatively long interval of undervaccination between the first and last doses. CONCLUSIONS: Compliance with multiple-dose vaccine series among older children, adolescents, and adults is suboptimal. Further evaluations of strategies to improve compliance in these populations are needed.