Antibiotic Myths for the Infectious Diseases Clinician.

Antimicrobials are commonly prescribed and often misunderstood. With more than 50% of hospitalized patients receiving an antimicrobial agent at any point in time, judicious and optimal use of these drugs is paramount to advancing patient care. This narrative will focus on myths relevant to nuanced consultation from infectious diseases specialists, particularly surrounding specific considerations for a variety of antibiotics.

Principles of diagnostic stewardship: A practical guide from the Society for Healthcare Epidemiology of America Diagnostic Stewardship Task Force.

We provide an overview of diagnostic stewardship with key concepts that include the diagnostic pathway and the multiple points where interventions can be implemented, strategies for interventions, the importance of multidisciplinary collaboration, and key microbiologic diagnostic tests that should be considered for diagnostic stewardship. The document focuses on microbiologic laboratory testing for adult and pediatric patients and is intended for a target audience of healthcare workers involved in diagnostic stewardship interventions and all workers affected by any step of the diagnostic pathway (ie, ordering, collecting, processing, reporting, and interpreting results of a diagnostic test). This document was developed by the Society for Healthcare Epidemiology of America Diagnostic Stewardship Taskforce.

Harvesting the low-hanging fruit? Comparative assessment of intravenous to oral route antimicrobial conversion policy implementation.

Policies that promote conversion of antibiotics from intravenous to oral route administration are considered "low hanging fruit" for hospital antimicrobial stewardship programs. We developed a simple metric based on digestive days of therapy divided by total days of therapy for targeted agents and a method for hospital comparisons. External comparisons may help identify opportunities for improving prospective implementation.

Evaluation of an Opt-Out Protocol for Antibiotic De-Escalation in Patients With Suspected Sepsis: A Multicenter, Randomized, Controlled Trial.

BACKGROUND: Sepsis guidelines recommend daily review to de-escalate or stop antibiotics in appropriate patients. This randomized, controlled trial evaluated an opt-out protocol to decrease unnecessary antibiotics in patients with suspected sepsis. METHODS: We evaluated non-intensive care adults on broad-spectrum antibiotics despite negative blood cultures at 10 US hospitals from September 2018 through May 2020. A 23-item safety check excluded patients with ongoing signs of systemic infection, concerning or inadequate microbiologic data, or high-risk conditions. Eligible patients were randomized to the opt-out protocol vs usual care. Primary outcome was post-enrollment antibacterial days of therapy (DOT). Clinicians caring for intervention patients were contacted to encourage antibiotic discontinuation using opt-out language. If continued, clinicians discussed the rationale for continuing antibiotics and de-escalation plans. To evaluate those with zero post-enrollment DOT, hurdle models provided 2 measures: odds ratio of antibiotic continuation and ratio of mean DOT among those who continued antibiotics. RESULTS: Among 9606 patients screened, 767 (8%) were enrolled. Intervention patients had 32% lower odds of antibiotic continuation (79% vs 84%; odds ratio, 0.68; 95% confidence interval [CI], .47-.98). DOT among those who continued antibiotics were similar (ratio of means, 1.06; 95% CI, .88-1.26). Fewer intervention patients were exposed to extended-spectrum antibiotics (36% vs 44%). Common reasons for continuing antibiotics were treatment of localized infection (76%) and belief that stopping antibiotics was unsafe (31%). Thirty-day safety events were similar. CONCLUSIONS: An antibiotic opt-out protocol that targeted patients with suspected sepsis resulted in more antibiotic discontinuations, similar DOT when antibiotics were continued, and no evidence of harm. CLINICAL TRIALS REGISTRATION: NCT03517007.

The retromer complex regulates C. elegans development and mammalian ciliogenesis.

The mammalian retromer consists of subunits VPS26 (either VPS26A or VPS26B), VPS29 and VPS35, and a loosely associated sorting nexin (SNX) heterodimer or a variety of other SNX proteins. Despite involvement in yeast and mammalian cell trafficking, the role of retromer in development is poorly understood, and its impact on primary ciliogenesis remains unknown. Using CRISPR/Cas9 editing, we demonstrate that vps-26-knockout worms have reduced brood sizes, impaired vulval development and decreased body length, all of which have been linked to ciliogenesis defects. Although preliminary studies did not identify worm ciliary defects, and impaired development limited additional ciliogenesis studies, we turned to mammalian cells to investigate the role of retromer in ciliogenesis. VPS35 localized to the primary cilium of mammalian cells, and depletion of VPS26, VPS35, VPS29, SNX1, SNX2, SNX5 or SNX27 led to decreased ciliogenesis. Retromer also coimmunoprecipitated with the centriolar protein, CP110 (also known as CCP110), and was required for its removal from the mother centriole. Herein, we characterize new roles for retromer in C. elegans development and in the regulation of ciliogenesis in mammalian cells, suggesting a novel role for retromer in CP110 removal from the mother centriole.

Top Myths of Diagnosis and Management of Infectious Diseases in Hospital Medicine.

Antimicrobial agents are among the most frequently prescribed medications during hospitalization. However, approximately 30% to 50% or more of inpatient antimicrobial use is unnecessary or suboptimal. Herein, we describe 10 common myths of diagnosis and management that often occur in the hospital setting. Further, we discuss supporting data to dispel each of these myths. This analysis will provide hospitalists and other clinicians with a foundation for rational decision-making about antimicrobial use and support antimicrobial stewardship efforts at both the patient and institutional levels.

Optimizing the Management of Uncomplicated Gram-Negative Bloodstream Infections: Consensus Guidance Using a Modified Delphi Process.

BACKGROUND: Guidance on the recommended durations of antibiotic therapy, the use of oral antibiotic therapy, and the need for repeat blood cultures remain incomplete for gram-negative bloodstream infections. We convened a panel of infectious diseases specialists to develop a consensus definition of uncomplicated gram-negative bloodstream infections to assist clinicians with management decisions. METHODS: Panelists, who were all blinded to the identity of other members of the panel, used a modified Delphi technique to develop a list of statements describing preferred management approaches for uncomplicated gram-negative bloodstream infections. Panelists provided level of agreement and feedback on consensus statements generated and refined them from the first round of open-ended questions through 3 subsequent rounds. RESULTS: Thirteen infectious diseases specialists (7 physicians and 6 pharmacists) from across the United States participated in the consensus process. A definition of uncomplicated gram-negative bloodstream infection was developed. Considerations cited by panelists in determining if a bloodstream infection was uncomplicated included host immune status, response to therapy, organism identified, source of the bacteremia, and source control measures. For patients meeting this definition, panelists largely agreed that a duration of therapy of ~7 days, transitioning to oral antibiotic therapy, and forgoing repeat blood cultures, was reasonable. CONCLUSIONS: In the absence of professional guidelines for the management of uncomplicated gram-negative bloodstream infections, the consensus statements developed by a panel of infectious diseases specialists can provide guidance to practitioners for a common clinical scenario.

Effects of a Collaborative, Community Hospital Network for Antimicrobial Stewardship Program Implementation.

BACKGROUND: Individual hospitals may lack expertise, data resources, and educational tools to support antimicrobial stewardship programs (ASP). METHODS: We established a collaborative, consultative network focused on hospital ASP implementation. Services included on-site expert consultation, shared database for routine feedback and benchmarking, and educational programs. We performed a retrospective, longitudinal analysis of antimicrobial use (AU) in 17 hospitals that participated for at least 36 months during 2013-2018. ASP practice was assessed using structured interviews. Segmented regression estimated change in facility-wide AU after a 1-year assessment, planning, and intervention initiation period. Year 1 AU trend (1-12 months) and AU trend following the first year (13-42 months) were compared using relative rates (RR). Monthly AU rates were measured in days of therapy (DOT) per 1000 patient days for overall AU, specific agents, and agent groups. RESULTS: Analyzed data included over 2.5 million DOT and almost 3 million patient-days. Participating hospitals increased ASP-focused activities over time. Network-wide overall AU trends were flat during the first 12 months after network entry but decreased thereafter (RR month 42 vs month 13, 0.95, 95% confidence interval [CI]: .91-.99). Large variation was seen in hospital-specific AU. Fluoroquinolone use was stable during year 1 and then dropped significantly. Other agent groups demonstrated a nonsignificant downward trajectory after year 1. CONCLUSIONS: Network hospitals increased ASP activities and demonstrated decline in AU over a 42-month period. A collaborative, consultative network is a unique model in which hospitals can access ASP implementation expertise to support long-term program growth.

Development of an Electronic Definition for De-escalation of Antibiotics in Hospitalized Patients.

BACKGROUND: Antimicrobial stewardship programs (ASPs) promote the principle of de-escalation: moving from broad- to narrow-spectrum agents and stopping antibiotics when no longer indicated. A standard, objective definition of de-escalation applied to electronic data could be useful for ASP assessments. METHODS: We derived an electronic definition of antibiotic de-escalation and performed a retrospective study among 5 hospitals. Antibiotics were ranked into 4 categories: narrow-spectrum, broad-spectrum, extended-spectrum, and agents targeted for protection. Eligible adult patients were cared for on inpatient units, had antibiotic therapy for at least 2 days, and were hospitalized for at least 3 days after starting antibiotics. Number of antibiotics and rank were assessed at 2 time points: day of antibiotic initiation and either day of discharge or day 5. De-escalation was defined as reduction in either the number of antibiotics or rank. Escalation was an increase in either number or rank. Unchanged was either no change or discordant directions of change. We summarized outcomes among hospitals, units, and diagnoses. RESULTS: Among 39 226 eligible admissions, de-escalation occurred in 14 138 (36%), escalation in 5129 (13%), and antibiotics were unchanged in 19 959 (51%). De-escalation varied among hospitals (median, 37%; range, 31-39%, P < .001). Diagnoses with lower de-escalation rates included intra-abdominal (23%) and skin and soft tissue (28%) infections. Critical care had higher rates of both de-escalation and escalation compared with wards. CONCLUSIONS: Our electronic de-escalation metric demonstrated variation among hospitals, units, and diagnoses. This metric may be useful for assessing stewardship opportunities and impact.

Impact of FDA black box warning on fluoroquinolone and alternative antibiotic use in southeastern US hospitals.

We analyzed antibiotic use data from 29 southeastern US hospitals over a 5-year period to determine changes in antibiotic use after the fluoroquinolone US Food and Drug Administration (FDA) advisory update in 2016. Fluoroquinolone use declined both before and after the FDA announcement, and the use of select, alternative antibiotics increased after the announcement.Fluoroquinolones are among the 4 most commonly prescribed antibiotic classes.1,2 Postmarketing reports of serious adverse events linked to fluoroquinolones include tendonitis, neuropathy, hypoglycemia, psychiatric side effects, and possible aortic vessel rupture, leading to safety label changes in July 2008 and August 2013.3 In July 2016, the US Food and Drug Administration (FDA) strengthened the "black box" warning following an initial safety announcement in May 2016, recommending avoidance of fluoroquinolones for uncomplicated infections such as acute exacerbation of chronic bronchitis, uncomplicated urinary tract infections, and acute bacterial sinusitis.4 Concerns over safety and the association with Clostridiodes difficile infection have led inpatient antimicrobial stewardship programs (ASPs) to develop initiatives to promote avoidance of quinolones. The objective of this study was to quantify the effect of the 2016 FDA "black box" update on inpatient antibiotic use among a cohort of southeastern US hospitals.

Impact of the use of local fidaxomicin treatment algorithms for managing Clostridium difficile infection in hospitalized patients in southeastern United States.

BACKGROUND: Clostridium difficile-associated diarrhea (CDAD) is a major public health threat that results in increased length of stay, hospital readmissions, deaths, and economic burden. CDAD treatment is often guided by severity of disease. Although various tools exist to determine CDAD severity, real-world data evaluating the use of such tools in treatment algorithms are sparse. METHODS: A local CDAD treatment pathway was developed independently to guide fidaxomicin prescribing at wellStar Health System (WellStar) and at Lee Health (LH) and Sarasota Memorial Hospital (SMH). Each algorithm was designed locally by the stewardship pharmacist and was utilized to identify patients at high risk for C. difficile recurrence. Patient and clinical data was retrospectively gathered to evaluate the utility and outcomes of the treatment pathway. RESULTS: There were 262 patients that received fidaxomicin at these three hospitals during the study time period. Only 30% at WellStar and 20% at LH or SMH met the study criteria and adhered to the pathway requirements. After completion of fidaxomicin, 30-day recurrence rates at WellStar was 0 and at LH and SMH 7%. Clinical cure rates were 83% in WellStar and 93% in LH and SMH. CONCLUSIONS: The results from these two pathways show positive outcomes for the use of fidaxomicin in patients at high risk for CDAD recurrence. This data supports the potential utility of fidaxomicin against CDAD.

Feasibility and Value of Developing a Regional Antibiogram for Community Hospitals.

OBJECTIVETo determine the feasibility and value of developing a regional antibiogram for community hospitals.DESIGNMulticenter retrospective analysis of antibiograms.SETTING AND PARTICIPANTSA total of 20 community hospitals in central and eastern North Carolina and south central Virginia participated in this study.METHODSWe combined antibiogram data from participating hospitals for 13 clinically relevant gram-negative pathogen-antibiotic combinations. From this combined antibiogram, we developed a regional antibiogram based on the mean susceptibilities of the combined data.RESULTSWe combined a total of 69,778 bacterial isolates across 13 clinically relevant gram-negative pathogen-antibiotic combinations (median for each combination, 1100; range, 174-27,428). Across all pathogen-antibiotic combinations, 69% of local susceptibility rates fell within 1 SD of the regional mean susceptibility rate, and 97% of local susceptibilities fell within 2 SD of the regional mean susceptibility rate. No individual hospital had >1 pathogen-antibiotic combination with a local susceptibility rate >2 SD of the regional mean susceptibility rate. All hospitals' local susceptibility rates were within 2 SD of the regional mean susceptibility rate for low-prevalence pathogens (<500 isolates cumulative for the region).CONCLUSIONSSmall community hospitals frequently cannot develop an accurate antibiogram due to a paucity of local data. A regional antibiogram is likely to provide clinically useful information to community hospitals for low-prevalence pathogens.Infect Control Hosp Epidemiol 2018;39:718-722.

Diary methods: capturing life as it is lived.

In diary studies, people provide frequent reports on the events and experiences of their daily lives. These reports capture the particulars of experience in a way that is not possible using traditional designs. We review the types of research questions that diary methods are best equipped to answer, the main designs that can be used, current technology for obtaining diary reports, and appropriate data analysis strategies. Major recent developments include the use of electronic forms of data collection and multilevel models in data analysis. We identify several areas of research opportunities: 1. in technology, combining electronic diary reports with collateral measures such as ambulatory heart rate; 2. in measurement, switching from measures based on between-person differences to those based on within-person changes; and 3. in research questions, using diaries to (a) explain why people differ in variability rather than mean level, (b) study change processes during major events and transitions, and (c) study interpersonal processes using dyadic and group diary methods.

Sensitivity to status-based rejection: implications for African American students' college experience.

The authors proposed a process model whereby experiences of rejection based on membership in a devalued group can lead people to anxiously expect, readily perceive, and intensely react to status-based rejection. To test the model, the authors focused on race-based rejection sensitivity (RS-race) among African Americans. Following the development and validation of the RS-Race Questionnaire (Studies 1 and 2), the authors tested the utility of the model for understanding African American students' experiences at a predominantly White university (Study 3). Students high in RS-race experienced greater discomfort during the college transition, less trust in the university, and relative declines in grades over a 2- to 3-year period. Positive race-related experiences, however, increased feelings of belonging at the institution among students high in RS-race.