Implementing the Infectious Diseases Society of America Antimicrobial Stewardship Core Curriculum: Survey Results and Real-World Strategies to Guide Fellowship Programs.

Background: The Infectious Diseases Society of America (IDSA) developed the Core Antimicrobial Stewardship (AS) Curriculum to meet the increasing demand for infectious diseases (ID) providers with AS expertise. Notable diversity in implementation approaches has been observed among ID fellowship programs using the curriculum. We sought to describe individual approaches and develop a curriculum implementation roadmap. Methods: We surveyed ID fellowship programs that had previously implemented the IDSA Core AS curriculum. The survey included questions regarding program characteristics, curriculum participants and presentation format, resources and barriers, and implementation strategies. Commonly reported program features were summarized in the context of the self-reported implementation strategies. Implementation guides were developed based on the most common characteristics observed. Results: Of 159 programs that had purchased the curriculum, 37 responded, and 34 (21%) were included in the analysis. The curriculum was primarily taught by AS physicians (85%) and AS pharmacists (47%). The most common conference structure was a longitudinal conference series (32%), and eLearning was the most common presentation format. Limited AS faculty time (76%) and limited first-year fellow availability (62%) were frequently reported as barriers, and dedicated AS curricular time was a resource available to most programs (67%); implementation guides were created for these 3 program features. Conclusions: Programs reported a variety of implementation barriers and resources, with several common themes emerging, allowing for the development of tailored curriculum planners for 3 commonly observed program characteristics. This work will equip fellowship programs with curriculum implementation strategies and guide future enhancements of the IDSA Core and Advanced AS curricula.

Contribution of the patient microbiome to surgical site infection and antibiotic prophylaxis failure in spine surgery.

Despite modern antiseptic techniques, surgical site infection (SSI) remains a leading complication of surgery. However, the origins of SSI and the high rates of antimicrobial resistance observed in these infections are poorly understood. Using instrumented spine surgery as a model of clean (class I) skin incision, we prospectively sampled preoperative microbiomes and postoperative SSI isolates in a cohort of 204 patients. Combining multiple forms of genomic analysis, we correlated the identity, anatomic distribution, and antimicrobial resistance profiles of SSI pathogens with those of preoperative strains obtained from the patient skin microbiome. We found that 86% of SSIs, comprising a broad range of bacterial species, originated endogenously from preoperative strains, with no evidence of common source infection among a superset of 1610 patients. Most SSI isolates (59%) were resistant to the prophylactic antibiotic administered during surgery, and their resistance phenotypes correlated with the patient's preoperative resistome (P = 0.0002). These findings indicate the need for SSI prevention strategies tailored to the preoperative microbiome and resistome present in individual patients.

Asymptomatic bacteriuria in critical-access hospitals: Prevalence and patient characteristics driving treatment.

We evaluated the prevalence and treatment of asymptomatic bacteriuria (ASB) in 17 critical-access hospitals. Among 891 patients with urine cultures from September 2021 to June 2022, 170 (35%) had ASB. Also, 76% of patients with ASB received antibiotics for a median duration of 7 days, demonstrating opportunities for antimicrobial stewardship.

How to disagree better: utilizing advocacy-inquiry techniques to improve communication and spur behavior change.

The ability to provide feedback to a colleague is a key skill required for professional growth and patient safety. However, these conversations are limited by time constraints, differences in values, and a culture of "noninterference." This advocacy-inquiry-identify-teach framework creates an organized approach to initiating successful "challenging" conversations with peers.

Defining the Optimal Antibiotic Duration in Necrotizing Skin and Soft Tissue Infections: Clinical Experience from a Quaternary Referral Center.

Background: Early initiation of broad-spectrum antibiotic agents is a cornerstone of the care of necrotizing skin and soft tissue infections (NSTI). However, the optimal duration of antibiotic agents is unclear. We sought to characterize antibiotic prescribing patterns for patients with NSTI, as well as associated complications. Patients and Methods: Using an NSTI registry, we characterized antibiotic use at a quaternary referral center. Kaplan-Meier analyses were used to describe overall antibiotic duration and relative to operative source control, stratified by presence of other infections that independently influenced antibiotic duration. Factors associated with successful antibiotic discontinuation were identified using logistic regression. Results: Between 2015 and 2018, 441 patients received antibiotic agents for NSTI with 18% experiencing a complicating secondary infection. Among those without a complicating infection, the median duration of antibiotic administration was 9.8 days (95% confidence interval [CI], 9.2-10.5) overall, and 7.0 days after the final debridement. Perineal NSTI received fewer days of antibiotic agents (8.3 vs. 10.6) compared with NSTI without perineal involvement. White blood cell (WBC) count and fever were not associated with failure of antibiotic discontinuation, however, a chronic wound as the underlying infection etiology was associated with greater odds of antibiotic discontinuation failure (odds ratio [OR], 4.33; 95% CI, 1.24-15.1). Conclusions: A seven-day course of antibiotic agents after final operative debridement may be sufficient for NSTI without any secondary complicating infections, because clinical characteristics do not appear to be associated with differences in successful antibiotic discontinuation.

Antibiotic prescribing patterns for bacterial superinfection of mpox: A retrospective cohort study in an urban center.

Bacterial superinfection and antibiotic prescribing in the setting of the current mpox outbreak are not well described in the literature. This retrospective observational study revealed low prevalence (11%) of outpatient antibiotic prescribing for bacterial superinfection of mpox lesions; at least 3 prescriptions (23%) were unnecessary.

Genomic reconstruction and directed interventions in a multidrug-resistant Shigellosis outbreak in Seattle, WA, USA: a genomic surveillance study.

BACKGROUND: Shigella spp have been associated with community-wide outbreaks in urban settings. We analysed a sustained shigellosis outbreak in Seattle, WA, USA, to understand its origins and mechanisms of antimicrobial resistance, define ongoing transmission patterns, and optimise strategies for treatment and infection control. METHODS: We did a retrospective study of all Shigella isolates identified from stool samples at the clinical laboratories at Harborview Medical Center and University of Washington Medical Center (Seattle, WA, USA) from May 1, 2017, to Feb 28, 2022. We characterised isolates by species identification, phenotypic susceptibility testing, and whole-genome sequencing. Demographic characteristics and clinical outcomes of the patients were retrospectively examined. FINDINGS: 171 cases of shigellosis were included. 78 (46%) patients were men who have sex with men (MSM), and 88 (52%) were people experiencing homelessness (PEH). Although 84 (51%) isolates were multidrug resistant, 100 (70%) of 143 patients with data on antimicrobial therapy received appropriate empirical therapy. Phylogenomic analysis identified sequential outbreaks of multiple distinct lineages of Shigella flexneri and Shigella sonnei. Discrete clonal lineages (ten in S flexneri and nine in S sonnei) and resistance traits were responsible for infection in different at-risk populations (ie, MSM, PEH), enabling development of effective guidelines for empirical treatment. The most prevalent lineage in Seattle was probably introduced to Washington State via international travel, with subsequent domestic transmission between at-risk groups. INTERPRETATION: An outbreak in Seattle was driven by parallel emergence of multidrug-resistant strains involving international transmission networks and domestic transmission between at-risk populations. Genomic analysis elucidated not only outbreak origin, but directed optimal approaches to testing, treatment, and public health response. Rapid diagnostics combined with detailed knowledge of local epidemiology can enable high rates of appropriate empirical therapy even in multidrug-resistant infection. FUNDING: None.

A single-centre experience rolling out an antibiotic stewardship intervention prior to and during the SARS-CoV-2 pandemic 2019-2022.

Background: Antibiotics are prescribed to nearly one-half of patients with viral respiratory tract infections (RTI) in outpatient settings. This use is ineffective and may cause undue harm and excess cost from unnecessary antibiotic exposure. We implemented a multifaceted intervention to address inappropriate antibiotic prescribing for viral RTI. Here, we discuss the impact over 4 years, before and during the SARS-CoV-2 pandemic. Methods: This observational study describes the implementation and initial impact of a multimodal stewardship intervention on inappropriate antibiotic prescribing for viral RTIs in outpatient care settings at a single centre. We tracked the rate of visits for viral RTI as well as antibiotic prescribing for viral RTIs in urgent care, primary care and the emergency department between January 2018 and March 2022. Data were collected 1 year prior to implementation and 3 years after implementation. The primary outcome - the rate of inappropriate antibiotics prescribed for viral RTIs - was described by calendar year (CY) to review changes after the stewardship intervention. Results: In CY2018, the year prior to implementation of targeted RTI antimicrobial stewardship, the rate of inappropriate RTI antibiotics prescribed was 10% in urgent care, 11% in primary care and 18% in the emergency department (ED). During the first CY of the intervention, rates were 8% in urgent care, 10% in primary care and 16% in the ED. In CY2020, the second year of the intervention, inappropriate RTI antibiotics were prescribed in 5% of urgent care and 3% primary care RTI visits and 15% of ED RTI visits. These rates were similar in CY2021 and the first 3 months of CY2022. Over 30,000 visits for RTIs were seen annually in CY2018 and CY2019. Annual RTI visits dropped to 20,222 in CY2020 and 14,172 in CY2021. Conclusion: Although total visits for non-COVID RTIs decreased by approximately 50% during the first 2 years of the SARS-CoV-2 pandemic, an antimicrobial stewardship intervention was associated with decreases in inappropriate antibiotic prescribing for RTIs. This was maintained throughout 2 years of the pandemic.This article is part of the Antibiotic stewardship Special Issue: https://www.drugsincontext.com/special_issues/antimicrobial-stewardship-a-focus-on-the-need-for-moderation.

Rapid molecular severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing in hospital employees with mild, nonspecific respiratory symptoms facilitates expedient return to work.

Nonspecific respiratory symptoms overlap with coronavirus disease 2019 (COVID-19). Prompt diagnosis of COVID-19 in hospital employees is crucial to prevent nosocomial transmission. Rapid molecular SARS-CoV-2 testing was performed for 115 symptomatic employees. The case positivity rate was 2.6%. Employees with negative tests returned to work after 80 (±28) minutes.

Prevalence and treatment of asymptomatic bacteriuria at academic and critical-access hospitals-Opportunities for stewardship efforts.

Asymptomatic bacteriuria (ASB) is common among hospitalized patients and often leads to inappropriate antimicrobial use. Data from critical-access hospitals are underrepresented. To target antimicrobial stewardship efforts, we measured the point prevalence of ASB and detected a high frequency of ASB overtreatment across academic, community, and critical-access hospitals.

Experience with two antimicrobial prescribing tools in ambulatory care settings.

We compared experiences with The Multifaceted Intervention to Improve Prescribing for Acute Respiratory Infection for Adult and Children in Emergency Department and Urgent Care Settings versus Choosing Wisely to evaluate inappropriate antimicrobial prescribing in ambulatory care. Both identified the same clinics, diagnoses, and antibiotics for high-yield antibiotic stewardship interventions.

Variants of Concern Are Overrepresented Among Postvaccination Breakthrough Infections of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in Washington State.

Across 20 vaccine breakthrough cases detected at our institution, all 20 (100%) infections were due to variants of concern (VOCs) and had a median Ct of 20.2 (IQR, 17.1-23.3). When compared with 5174 contemporaneous samples sequenced in our laboratory, VOCs were significantly enriched among breakthrough infections (P < .05).

Characterization of Secondary Bacterial Infections and Antibiotic Use in Mechanically Ventilated Patients With COVID-19 Induced Acute Respiratory Distress Syndrome.

BACKGROUND: COVID-19 has a widely variable clinical syndrome that is difficult to distinguish from bacterial sepsis, leading to high rates of antibiotic use. Early studies indicate low rates of secondary bacterial infections (SBIs) but have included heterogeneous patient populations. Here, we catalogue all SBIs and antibiotic prescription practices in a population of mechanically ventilated patients with COVID-19 induced acute respiratory distress syndrome (ARDS). METHODS: This was a retrospective cohort study of all patients with COVID-19 ARDS requiring mechanical ventilation from 3 Seattle, Washington hospitals in 2020. Data were obtained via electronic and manual review of the electronic medical record. We report the incidence and site of SBIs, mortality, and antibiotics per day using descriptive statistics. RESULTS: We identified 126 patients with COVID-19 induced ARDS during the study period. Of these patients, 61% developed clinical infection confirmed by bacterial culture. Ventilator associated pneumonia was confirmed in 55% of patients, bacteremia in 20%, and urinary tract infection (UTI) in 17%. Staphylococcus aureus was the most commonly isolated bacterial species. A total of 97% of patients received antibiotics during their hospitalization, and patients received nearly one antibiotic per day during their hospital stay. CONCLUSIONS: Mechanically ventilated patients with COVID-19 induced ARDS are at high risk for secondary bacterial infections and have extensive antibiotic exposure.

Anti-SARS-CoV-2 Antibody Levels Measured by the AdviseDx SARS-CoV-2 Assay Are Concordant with Previously Available Serologic Assays but Are Not Fully Predictive of Sterilizing Immunity.

With the availability of widespread SARS-CoV-2 vaccination, high-throughput quantitative anti-spike protein serological testing will likely become increasingly important. Here, we investigated the performance characteristics of the recently FDA-authorized semiquantitative anti-spike protein AdviseDx SARS-CoV-2 IgG II assay compared to the FDA-authorized anti-nucleocapsid protein Abbott Architect SARS-CoV-2 IgG, Roche Elecsys anti-SARS-CoV-2-S, EuroImmun anti-SARS-CoV-2 enzyme-linked immunosorbent assay (ELISA), and GenScript surrogate virus neutralization assays and examined the humoral response associated with vaccination, natural protection, and vaccine breakthrough infection. The AdviseDx assay had a clinical sensitivity at 14 days after symptom onset or 10 days after PCR detection of 95.6% (65/68; 95% confidence interval [CI], 87.8 to 98.8%), with two discrepant individuals seroconverting shortly thereafter. The AdviseDx assay demonstrated 100% positive percent agreement with the four other assays examined using the same symptom onset or PCR detection cutoffs. Using a recently available WHO international standard for anti-SARS-CoV-2 antibody, we provide assay unit conversion factors to international units for each of the assays examined. We performed a longitudinal survey of healthy vaccinated individuals, finding that median AdviseDx immunoglobulin levels peaked 7 weeks after first vaccine dose at approximately 4,000 IU/ml. Intriguingly, among the five assays examined, there was no significant difference in antigen binding level or neutralizing activity between two seropositive patients protected against SARS-CoV-2 infection in a previously described fishing vessel outbreak and five health care workers who experienced vaccine breakthrough of SARS-CoV-2 infection, all with variants of concern. These findings suggest that protection against SARS-CoV-2 infection cannot currently be predicted exclusively using in vitro antibody assays against wild-type SARS-CoV-2 spike. Further work is required to establish protective correlates for SARS-CoV-2 infection.

Finding the path of least resistance: Locally adapting the MITIGATE toolkit in emergency departments and urgent care centers.

The MITIGATE toolkit was developed to assist urgent care and emergency departments in the development of antimicrobial stewardship programs. At the University of Washington, we adopted the MITIGATE toolkit in 10 urgent care centers, 9 primary care clinics, and 1 emergency department. We encountered and overcame challenges: a complex data build, choosing feasible outcomes to measure, issues with accurate coding, and maintaining positive stewardship relationships. Herein, we discuss solutions to challenges we encountered to provide guidance for those considering using this toolkit.

Occurrence and Timing of Subsequent Severe Acute Respiratory Syndrome Coronavirus 2 Reverse-transcription Polymerase Chain Reaction Positivity Among Initially Negative Patients.

Using data for 20 912 patients from 2 large academic health systems, we analyzed the frequency of severe acute respiratory syndrome coronavirus 2 reverse-transcription polymerase chain reaction test discordance among individuals initially testing negative by nasopharyngeal swab who were retested on clinical grounds within 7 days. The frequency of subsequent positivity within this window was 3.5% and was similar across institutions.

Follow-up blood cultures in E. coli and Klebsiella spp. bacteremia-opportunities for diagnostic and antimicrobial stewardship.

Uncomplicated Enterobacteriaceae bacteremia is usually transient and may not require follow-up blood cultures (FUBC). This is a retrospective observational study conducted at a university-affiliated urban teaching hospital in Seattle, WA. All patients ≥ 18 years hospitalized between July 2014 and August 2019 with ≥ 1 positive blood culture for either Escherichia coli or Klebsiella species were included. The primary outcome was to determine the number and frequency of FUBC obtained, and the detection rate for positive FUBC. There were 335 episodes of E. coli and Klebsiella spp. bacteremia with genitourinary (54%) being the most common source. FUBC were sent in 299 (89.3%) patients, with a median of 3 (interquartile range (IQR): 2, 4) sets of FUBC drawn per patient. Persistent bacteremia occurred in 37 (12.4%) patients. In uncomplicated E. coli and Klebsiella spp. bacteremia, when the pre-test probability of persistent bacteremia is relatively low, FUBC may not be necessary in the absence of predisposing factors.

Postprescription Review With Threat of Infectious Disease Consultation and Sustained Reduction in Meropenem Use Over Four Years.

BACKGROUND: Following a meropenem shortage, we implemented a postprescription review with feedback (PPRF) in November 2015 with mandatory infectious disease (ID) consultation for all meropenem and imipenem courses > 72 hours. Providers were made aware of the policy via an electronic alert at the time of ordering. METHODS: A retrospective study was conducted at the University of Washington Medical Center (UWMC) and Harborview Medical Center (HMC) to evaluate the impact of the policy on antimicrobial consumption and clinical outcomes pre- and postintervention during a 6-year period. Antimicrobial use was tracked using days of therapy (DOT) per 1000 patient-days, and data were analyzed by an interrupted time series. RESULTS: There were 4066 and 2552 patients in the pre- and postintervention periods, respectively. Meropenem and imipenem use remained steady until the intervention, when a marked reduction in DOT/1000 patient-days occurred at both hospitals (UWMC: percentage change -72.1% (95% confidence interval [CI] -76.6, -66.9), P < .001; HMC: percentage change -43.6% (95% CI -59.9, -20.7), P = .001). Notably, although the intervention did not address antibiotic use until 72 hours after initiation, there was a significant decline in meropenem and imipenem initiation ("first starts") in the postintervention period, with a 64.9% reduction (95% CI 58.7, 70.2; P < .001) at UWMC and 44.7% reduction (95% CI 28.1, 57.4; P < .001) at HMC. CONCLUSIONS: PPRF and mandatory ID consultation for meropenem and imipenem use beyond 72 hours resulted in a significant and sustained reduction in the use of these antibiotics and notably impacted their up-front usage.

2021 Young Investigator Award Winner: Anatomic Gradients in the Microbiology of Spinal Fusion Surgical Site Infection and Resistance to Surgical Antimicrobial Prophylaxis.

STUDY DESIGN: Retrospective hospital-registry study. OBJECTIVE: To characterize the microbial epidemiology of surgical site infection (SSI) in spinal fusion surgery and the burden of resistance to standard surgical antibiotic prophylaxis. SUMMARY OF BACKGROUND DATA: SSI persists as a leading complication of spinal fusion surgery despite the growth of enhanced recovery programs and improvements in other measures of surgical quality. Improved understandings of SSI microbiology and common mechanisms of failure for current prevention strategies are required to inform the development of novel approaches to prevention relevant to modern surgical practice. METHODS: Spinal fusion cases performed at a single referral center between January 2011 and June 2019 were reviewed and SSI cases meeting National Healthcare Safety Network criteria were identified. Using microbiologic and procedural data from each case, we analyzed the anatomic distribution of pathogens, their differential time to presentation, and correlation with methicillin-resistant Staphylococcus aureus screening results. Susceptibility of isolates cultured from each infection were compared with the spectrum of surgical antibiotic prophylaxis administered during the index procedure on a per-case basis. Susceptibility to alternate prophylactic agents was also modeled. RESULTS: Among 6727 cases, 351 infections occurred within 90 days. An anatomic gradient in the microbiology of SSI was observed across the length of the back, transitioning from cutaneous (gram-positive) flora in the cervical spine to enteric (gram-negative/anaerobic) flora in the lumbosacral region (correlation coefficient 0.94, P < 0.001). The majority (57.5%) of infections were resistant to the prophylaxis administered during the procedure. Cephalosporin-resistant gram-negative infection was common at lumbosacral levels and undetected methicillin-resistance was common at cervical levels. CONCLUSION: Individualized infection prevention strategies tailored to operative level are needed in spine surgery. Endogenous wound contamination with enteric flora may be a common mechanism of infection in lumbosacral fusion. Novel approaches to prophylaxis and prevention should be prioritized in this population.Level of Evidence: 3.

Outcomes of ß-Hemolytic Streptococcal Necrotizing Skin and Soft-tissue Infections and the Impact of Clindamycin Resistance.

BACKGROUND: ß-Hemolytic streptococci are frequently implicated in necrotizing soft-tissue infections (NSTIs). Clindamycin administration may improve outcomes in patients with serious streptococcal infections. However, clindamycin resistance is growing worldwide, and resistance patterns in NSTIs and their impact on outcomes are unknown. METHODS: Between 2015 and 2018, patients with NSTI at a quaternary referral center were followed up for the outcomes of death, limb loss, and streptococcal toxic shock syndrome. Surgical wound cultures and resistance data were obtained within 48 hours of admission as part of routine care. Risk ratios for the association between these outcomes and the presence of ß-hemolytic streptococci or clindamycin-resistant ß-hemolytic streptococci were calculated using log-binomial regression, controlling for age, transfer status, and injection drug use-related etiology. RESULTS: Of 445 NSTIs identified, 85% had surgical wound cultures within 48 hours of admission. ß-Hemolytic streptococci grew in 31%, and clindamycin resistance was observed in 31% of cultures. The presence of ß-hemolytic streptococci was associated with greater risk of amputation (risk ratio, 1.80; 95% confidence interval, 1.07-3.01), as was the presence of clindamycin resistance among ß-hemolytic streptococci infections (1.86; 1.10-3.16). CONCLUSIONS: ß-Hemolytic streptococci are highly prevalent in NSTIs, and in our population clindamycin resistance was more common than previously described. Greater risk of limb loss among patients with ß-hemolytic streptococci-particularly clindamycin-resistant strains-may portend a more locally aggressive disease process or may represent preexisting patient characteristics that predispose to both infection and limb loss. Regardless, these findings may inform antibiotic selection and surgical management to maximize the potential for limb salvage.