Larissa May

Better Tests, Better Care: Improved Diagnostics for Infectious Diseases

Abstract In this IDSA policy paper, we review the current diagnostic landscape, including unmet needs and emerging technologies, and assess the challenges to the development and clinical integration of improved tests. To fulfill the promise of emerging diagnostics, IDSA presents recommendations that address a host of identified barriers. Achieving these goals will require the engagement and coordination of a number of stakeholders, including Congress, funding and regulatory bodies, public health agencies, the diagnostics industry, healthcare systems, professional societies, and individual clinicians.

Impact of Pneumococcal Conjugate Vaccination of Infants on Pneumonia and Influenza Hospitalization and Mortality in All Age Groups in the United States

ABSTRACT A seven-valent pneumococcal conjugate vaccine (PCV7) introduced in the United States in 2000 has been shown to reduce invasive pneumococcal disease (IPD) in both vaccinated children and adults through induction of herd immunity. We assessed the impact of infant immunization on pneumococcal pneumonia hospitalizations and mortality in all age groups using Health Care Utilization Project State Inpatient Databases (SID) for 1996 to 2006 from 10 states; SID contain 100% samples of ICD9-coded hospitalization data for the selected states. Compared to a 1996–1997 through 1998–1999 baseline, by the 2005–2006 season, both IPD and pneumococcal pneumonia hospitalizations and deaths had decreased substantially in all age groups, including a 47% (95% confidence interval [CI], 38 to 54%) reduction in nonbacteremic pneumococcal pneumonia (ICD9 code 481 with no codes indicating IPD) in infants <2 years old and a 54% reduction (CI, 53 to 56%) in adults ≥65 years of age. A model developed to calculate the total burden of pneumococcal pneumonia prevented by infant PCV7 vaccination in the United States from 2000 to 2006 estimated a reduction of 788,838 (CI, 695,406 to 875,476) hospitalizations for pneumococcal pneumonia. Ninety percent of the reduction in model-attributed pneumococcal pneumonia hospitalizations occurred through herd immunity among adults 18 years old and older; similar proportions were found in pneumococcal disease mortality prevented by the vaccine. In the first seasons after PCV introduction, when there were substantial state differences in coverage among <5-year-olds, states with greater coverage had significantly fewer influenza-associated pneumonia hospitalizations among children, suggesting that PCV7 use also reduces influenza-attributable pneumonia hospitalizations. IMPORTANCE Pneumonia is the world’s leading cause of death in children and the leading infectious cause of death among U.S. adults 65 years old and older. Pneumococcal conjugate vaccination of infants has previously been shown to reduce invasive pneumococcal disease (IPD) among seniors through prevention of pneumococcal transmission from infants to adults (herd immunity). Our analysis documents a significant vaccine-associated reduction not only in IPD but also in pneumococcal pneumonia hospitalizations and inpatient mortality rates among both vaccinated children and unvaccinated adults. We estimate that fully 90% of the reduction in the pneumonia hospitalization burden occurred among adults. Moreover, states that more rapidly introduced their infant pneumococcal immunization programs had greater reductions in influenza-associated pneumonia hospitalization of children, presumably because the vaccine acts to prevent the pneumococcal pneumonia that frequently follows influenza virus infection. Our results indicate that seven-valent pneumococcal conjugate vaccine use has yielded far greater benefits through herd immunity than have previously been recognized. Pneumonia is the world’s leading cause of death in children and the leading infectious cause of death among U.S. adults 65 years old and older. Pneumococcal conjugate vaccination of infants has previously been shown to reduce invasive pneumococcal disease (IPD) among seniors through prevention of pneumococcal transmission from infants to adults (herd immunity). Our analysis documents a significant vaccine-associated reduction not only in IPD but also in pneumococcal pneumonia hospitalizations and inpatient mortality rates among both vaccinated children and unvaccinated adults. We estimate that fully 90% of the reduction in the pneumonia hospitalization burden occurred among adults. Moreover, states that more rapidly introduced their infant pneumococcal immunization programs had greater reductions in influenza-associated pneumonia hospitalization of children, presumably because the vaccine acts to prevent the pneumococcal pneumonia that frequently follows influenza virus infection. Our results indicate that seven-valent pneumococcal conjugate vaccine use has yielded far greater benefits through herd immunity than have previously been recognized.

Beyond traditional surveillance: applying syndromic surveillance to developing settings - opportunities and challenges.

BackgroundAll countries need effective disease surveillance systems for early detection of outbreaks. The revised International Health Regulations [IHR], which entered into force for all 194 World Health Organization member states in 2007, have expanded traditional infectious disease notification to include surveillance for public health events of potential international importance, even if the causative agent is not yet known. However, there are no clearly established guidelines for how countries should conduct this surveillance, which types of emerging disease syndromes should be reported, nor any means for enforcement.DiscussionThe commonly established concept of syndromic surveillance in developed regions encompasses the use of pre-diagnostic information in a near real time fashion for further investigation for public health action. Syndromic surveillance is widely used in North America and Europe, and is typically thought of as a highly complex, technology driven automated tool for early detection of outbreaks. Nonetheless, low technology applications of syndromic surveillance are being used worldwide to augment traditional surveillance.SummaryIn this paper, we review examples of these novel applications in the detection of vector-borne diseases, foodborne illness, and sexually transmitted infections. We hope to demonstrate that syndromic surveillance in its basic version is a feasible and effective tool for surveillance in developing countries and may facilitate compliance with the new IHR guidelines.

A call to action for antimicrobial stewardship in the emergency department: approaches and strategies.

Antimicrobial resistance is a mounting public health concern. Emergency departments (EDs) represent a particularly important setting for addressing inappropriate antimicrobial prescribing practices, given the frequent use of antibiotics in this setting that sits at the interface of the community and the hospital. This article outlines the importance of antimicrobial stewardship in the ED setting and provides practical recommendations drawn from existing evidence for the application of various strategies and tools that could be implemented in the ED including advancement of clinical guidelines, clinical decision support systems, rapid diagnostics, and expansion of ED pharmacist programs.

The frequency of influenza and bacterial coinfection: a systematic review and meta‐analysis

Coinfecting bacterial pathogens are a major cause of morbidity and mortality in influenza. However, there remains a paucity of literature on the magnitude of coinfection in influenza patients.

Antibacterial Drug Shortages From 2001 to 2013: Implications for Clinical Practice

BACKGROUND Previous studies have described drug shortages; however, there has been no comprehensive evaluation focusing on US antibacterial shortages. METHODS Drug shortage data from the University of Utah Drug Information Service database were analyzed, with a focus on antibacterial agents from 2001 to 2013. We used descriptive statistics to describe trends in drug shortages, analyze drug classes commonly affected, and investigate whether drugs experienced multiple periods of shortages. RESULTS One hundred forty-eight antibacterial drugs were on shortage over the 13-year study period, with 26 drugs still active on shortage as of December 2013. The median number of new shortages per year was 10 (interquartile range [IQR], 7). The number of drugs on shortage increased at a rate of 0.35 additional drugs every month (95% confidence interval, .22-.49) from July 2007 to December 2013 (P < .001). The median shortage duration was 188 days (IQR, 366.5). Twenty-two percent of drugs experienced multiple shortage periods. CONCLUSIONS There were a substantial number of drug shortages from 2001 to 2013, with a dramatic rise in shortages since 2007. Shortages of agents used to treat multidrug-resistant infections are of concern due to continued transmission and limited treatment options.

Multisite exploration of clinical decision making for antibiotic use by emergency medicine providers using quantitative and qualitative methods

OBJECTIVES To explore current practices and decision making regarding antimicrobial prescribing among emergency department (ED) clinical providers. METHODS We conducted a survey of ED providers recruited from 8 sites in 3 cities. Using purposeful sampling, we then recruited 21 providers for in-depth interviews. Additionally, we observed 10 patient-provider interactions at one of the ED sites. SAS 9.3 was used for descriptive and predictive statistics. Interviews were audio recorded, transcribed, and analyzed using a thematic, constructivist approach with consensus coding using NVivo 10.0. Field and interview notes collected during the observational study were aligned with themes identified through individual interviews. RESULTS Of 150 survey respondents, 76% agreed or strongly agreed that antibiotics are overused in the ED, while half believed they personally did not overprescribe. Eighty-nine percent used a smartphone or tablet in the ED for antibiotic prescribing decisions. Several significant differences were found between attending and resident physicians. Interview analysis identified 42 codes aggregated into the following themes: (1) resource and environmental factors that affect care; (2) access to and quality of care received outside of the ED consult; (3) patient-provider relationships; (4) clinical inertia; and (5) local knowledge generation. The observational study revealed limited patient understanding of antibiotic use. Providers relied heavily upon diagnostics and provided limited education to patients. Most patients denied a priori expectations of being prescribed antibiotics. CONCLUSIONS Patient, provider, and healthcare system factors should be considered when designing interventions to improve antimicrobial stewardship in the ED setting.

Risk‐Based Input‐Output Analysis of Influenza Epidemic Consequences on Interdependent Workforce Sectors

Outbreaks of contagious diseases underscore the ever-looming threat of new epidemics. Compared to other disasters that inflict physical damage to infrastructure systems, epidemics can have more devastating and prolonged impacts on the population. This article investigates the interdependent economic and productivity risks resulting from epidemic-induced workforce absenteeism. In particular, we develop a dynamic input-output model capable of generating sector-disaggregated economic losses based on different magnitudes of workforce disruptions. An ex post analysis of the 2009 H1N1 pandemic in the national capital region (NCR) reveals the distribution of consequences across different economic sectors. Consequences are categorized into two metrics: (i) economic loss, which measures the magnitude of monetary losses incurred in each sector, and (ii) inoperability, which measures the normalized monetary losses incurred in each sector relative to the total economic output of that sector. For a simulated mild pandemic scenario in NCR, two distinct rankings are generated using the economic loss and inoperability metrics. Results indicate that the majority of the critical sectors ranked according to the economic loss metric comprise of sectors that contribute the most to the NCRs gross domestic product (e.g., federal government enterprises). In contrast, the majority of the critical sectors generated by the inoperability metric include sectors that are involved with epidemic management (e.g., hospitals). Hence, prioritizing sectors for recovery necessitates consideration of the balance between economic loss, inoperability, and other objectives. Although applied specifically to the NCR, the proposed methodology can be customized for other regions.

Trends in Antibiotic Resistance in Coagulase-Negative Staphylococci in the United States, 1999 to 2012

ABSTRACT Coagulase-negative staphylococci (CoNS) are important bloodstream pathogens that are typically resistant to multiple antibiotics. Despite the concern about increasing resistance, there have been no recent studies describing the national prevalence of CoNS pathogens. We used national resistance data over a period of 13 years (1999 to 2012) from The Surveillance Network (TSN) to determine the prevalence of and assess the trends in resistance for Staphylococcus epidermidis, the most common CoNS pathogen, and all other CoNS pathogens. Over the course of the study period, S. epidermidis resistance to ciprofloxacin and clindamycin increased steadily from 58.3% to 68.4% and from 43.4% to 48.5%, respectively. Resistance to levofloxacin increased rapidly from 57.1% in 1999 to a high of 78.6% in 2005, followed by a decrease to 68.1% in 2012. Multidrug resistance for CoNS followed a similar pattern, and this rise and small decline in resistance were found to be strongly correlated with levofloxacin prescribing patterns. The resistance patterns were similar for the aggregate of CoNS pathogens. The results from our study demonstrate that the antibiotic resistance in CoNS pathogens has increased significantly over the past 13 years. These results are important, as CoNS can serve as sentinels for monitoring resistance, and they play a role as reservoirs of resistance genes that can be transmitted to other pathogens. The link between the levofloxacin prescription rate and resistance levels suggests a critical role for reducing the inappropriate use of fluoroquinolones and other broad-spectrum antibiotics in health care settings and in the community to help curb the reservoir of resistance in these colonizing pathogens.

Adult asthma exacerbations and environmental triggers: a retrospective review of ED visits using an electronic medical record

BACKGROUND Despite familiarity with triggers for asthma, there is little recent study on the association of triggers with the emergency department (ED) presentation of adult asthma exacerbation. METHODS Retrospective electronic chart review of adult patients treated in an urban teaching hospital ED with chief complaint and diagnostic coding related to asthma and upper respiratory tract infection (URI) was conducted. Monthly aeroallergen data and environmental conditions were obtained from a local allergen extract laboratory and local government sources. Data analysis was performed using Newey-West time series regression modeling with adjustment for autocorrelation or ordinary least squares linear regression modeling using outcome variables of asthma visits and admissions. RESULTS There were 56, 747 visits, with 554 asthma visits and 1,514 URI visits. Asthma visits (R(2) = 0.631) were positively correlated with tree pollen counts (correlation coefficient = 0.458 [0.152-0.765]) and average humidity (correlation coefficient = 1.528 [0.296-2.760]). Asthma admissions (R(2) = 0.480) were negatively correlated with average temperature (correlation coefficient = -0.557 [-1.052 to -0.061]) when adjusting for confounding by fine particulate matter. CONCLUSIONS The ED acute asthma exacerbation presentation is positively correlated with tree pollen and humidity, whereas need for admission is associated with dropping temperatures. These results reinforce the need for vigilance during periods of increased risk and perhaps focused preventative strategies.