The Leaders in Epidemiology, Antimicrobial Stewardship, and Public Health (LEAP) Fellowship, a Novel Training Program in Public Health for Infectious Diseases Physicians.

The severe acute respiratory syndrome coronavirus 2 pandemic demonstrated a critical need for partnerships between practicing infectious diseases (ID) physicians and public health departments. The soon-to-launch combined ID and Epidemic Intelligence Service fellowship can only address a fraction of this need, and otherwise US ID training lacks development pathways for physicians aiming to make careers working with public health departments. The Leaders in Epidemiology, Antimicrobial Stewardship, and Public Health (LEAP) fellowship is a model compatible with the current training paradigm with a proven track record of developing careers of long-term collaboration. Established in 2017 by the ID Society of America, Society for Healthcare Epidemiology of America, Pediatric ID Society, and supported by the Centers for Disease Control and Prevention, LEAP is a single-year in-place, structured training for senior trainees and early career ID physicians. In this viewpoint, we describe the LEAP fellowship, its outcomes, and how it could be adapted into ID training.

Impact of diagnostic stewardship interventions in the collection process of fungal blood cultures.

We implemented 2 interventions to improve utilization and contamination at our institution: kits to improve appropriate sample collection and an electronic order alert displaying appropriate indications of fungal blood cultures. An electronic order alert when ordering fungal blood cultures was associated with decreased utilization without decrease in positivity rate.

Mixed methods evaluation of handshake antimicrobial stewardship on adult inpatient medicine floors.

Objective: To evaluate the effects of handshake antimicrobial stewardship on medicine floors at a large tertiary care hospital. Design: Retrospective observational study. Setting: 1,278-bed academic hospital. Patients: Adults admitted to non-ICU medicine services. Interventions: A handshake stewardship team consisting of an infectious diseases (ID) physician and pharmacist reviewed charts of patients receiving antimicrobials on medicine floors without a formal ID consult. Recommendations were communicated in-person to providers and acceptance rates were examined with descriptive statistics. Additional data regarding program perception among providers were obtained via surveys. Antibiotic usage trends were extracted from National Healthcare Safety Network Antimicrobial Use option data and evaluated using an interrupted time-series analysis pre- and post-intervention. Results: The overall acceptance rate of interventions was 80%, the majority being recommendations either to discontinue (37%) or de-escalate therapy (28%). Medical residents and hospitalists rated the intervention favorably with 90% reporting recommendations were helpful all or most of the time. There was a statistically significant decrease in vancomycin (78 vs 70 DOT/1,000 d present (DP), p = 0.002) and meropenem (24 vs 17 DOT/1,000 DP, p = 0.007) usage and a statistically significant increase in amoxicillin-clavulanate usage (11 vs 15 DOT/1,000 DP, p < 0.001). Overall antibiotic usage remained unchanged by the intervention, though pre-intervention there was a nonsignificant overall increasing trend while post-intervention there was a nonsignificant decreasing trend in overall usage. There was no change in in-hospital mortality. Conclusion: The addition of handshake stewardship with adult medicine services was favorably viewed by participants and led to shifts in antibiotic usage.

Older adults' and caregivers' perceptions about urinary tract infection and asymptomatic bacteriuria guidelines: a qualitative exploration.

Objective: To explore older adults' and caregivers' knowledge and perceptions of guidelines for appropriate antibiotics use for bacteria in the urine. Design: Semi-structured qualitative interviews. Setting: Infectious disease clinics, community senior living facilities, memory care clinics, and general public. Participants: Patients 65 years or older diagnosed with a urinary tract infection (UTI) in the past two years, or caregivers of such patients. Methods: We conducted interviews between March and July 2023. We developed an interview guide based on the COM-B (capability, opportunity, motivation-behavior) behavior change framework. We thematically analyzed written transcripts of audio-recorded interviews using inductive and deductive coding techniques. Results: Thirty participants (21 patients, 9 caregivers) enrolled. Most participants understood UTI symptoms such as pain during urination and frequent urination. However, communication with multiple clinicians, misinformation, and unclear symptoms that overlapped with other health issues clouded their understanding of asymptomatic bacteriuria (ASB) and UTIs. Some participants worried that clinicians would be dismissive of symptoms if they suggested a diagnosis of ASB without prescribing antibiotics. Many participants felt that the benefits of taking antibiotics for ASB outweighed harms, though some mentioned fears of personal antibiotic resistance if taking unnecessary antibiotics. No participants mentioned the public health impact of potential antibiotic resistance. Most participants trusted information from clinicians over brochures or websites but wanted to review information after clinical conversations. Conclusion: Clinician-focused interventions to reduce antibiotic use for ASB should also address patient concerns during clinical visits, and provide standardized high-quality educational materials at the end of the visit.

The Impact of Centers for Medicare & Medicaid Services SEP-1 Core Measure Implementation on Antibacterial Utilization: A Retrospective Multicenter Longitudinal Cohort Study With Interrupted Time-Series Analysis.

BACKGROUND: The impact of the US Centers for Medicare & Medicaid Services (CMS) Severe Sepsis and Septic Shock: Management Bundle (SEP-1) core measure on overall antibacterial utilization is unknown. METHODS: We performed a retrospective multicenter longitudinal cohort study with interrupted time-series analysis to determine the impact of SEP-1 implementation on antibacterial utilization and patient outcomes. All adult patients admitted to 26 hospitals between 1 October 2014 and 30 September 2015 (SEP-1 preparation period) and between 1 November 2015 and 31 October 2016 (SEP-1 implementation period) were evaluated for inclusion. The primary outcome was total antibacterial utilization, measured as days of therapy (DOT) per 1000 patient-days. RESULTS: The study cohort included 701 055 eligible patient admissions and 4.2 million patient-days. Overall antibacterial utilization increased 2% each month during SEP-1 preparation (relative rate [RR], 1.02 per month [95% confidence interval {CI}, 1.00-1.04]; P = .02). Cumulatively, the mean monthly DOT per 1000 patient-days increased 24.4% (95% CI, 18.0%-38.8%) over the entire study period (October 2014-October 2016). The rate of sepsis diagnosis/1000 patients increased 2% each month during SEP-1 preparation (RR, 1.02 per month [95% CI, 1.00-1.04]; P = .04). The rate of all-cause mortality rate per 1000 patients decreased during the study period (RR for SEP-1 preparation, 0.95 [95% CI, .92-.98; P = .001]; RR for SEP-1 implementation, .98 [.97-1.00; P = .01]). Cumulatively, the monthly mean all-cause mortality rate/1000 patients declined 38.5% (95% CI, 25.9%-48.0%) over the study period. CONCLUSIONS: Announcement and implementation of the CMS SEP-1 process measure was associated with increased diagnosis of sepsis and antibacterial utilization and decreased mortality rate among hospitalized patients.

A modified Delphi approach to develop a trial protocol for antibiotic de-escalation in patients with suspected sepsis.

Background: Early administration of antibiotics in sepsis is associated with improved patient outcomes, but safe and generalizable approaches to de-escalate or discontinue antibiotics after suspected sepsis events are unknown. Methods: We used a modified Delphi approach to identify safety criteria for an opt-out protocol to guide de-escalation or discontinuation of antibiotic therapy after 72 hours in non-ICU patients with suspected sepsis. An expert panel with expertise in antimicrobial stewardship and hospital epidemiology rated 48 unique criteria across 3 electronic survey rating tools. Criteria were rated primarily based on their impact on patient safety and feasibility for extraction from electronic health record review. The 48 unique criteria were rated by anonymous electronic survey tools, and the results were fed back to the expert panel participants. Consensus was achieved to either retain or remove each criterion. Results: After 3 rounds, 22 unique criteria remained as part of the opt-out safety checklist. These criteria included high-risk comorbidities, signs of severe illness, lack of cultures during sepsis work-up or antibiotic use prior to blood cultures, or ongoing signs and symptoms of infection. Conclusions: The modified Delphi approach is a useful method to achieve expert-level consensus in the absence of evidence suifficient to provide validated guidance. The Delphi approach allowed for flexibility in development of an opt-out trial protocol for sepsis antibiotic de-escalation. The utility of this protocol should be evaluated in a randomized controlled trial.

Evaluation of a hybrid antimicrobial restriction process at a large academic medical center.

We conducted a retrospective review of a hybrid antimicrobial restriction process demonstrating adherence to appropriate use criteria in 72% of provisional-only orders, in 100% of provisional orders followed by ID orders, and in 97% of ID-initiated orders. Therapy interruptions occurred in 24% of provisional orders followed by ID orders.

Experiences from the Missouri Antimicrobial Stewardship Collaborative: A mixed methods study.

We performed a mixed-methods study to evaluate antimicrobial stewardship program (ASP) uptake and to assess variability of program implementation in Missouri hospitals. Despite increasing uptake of ASPs in Missouri, there is wide variability in both the scope and sophistication of these programs.

Surgical Upper Extremity Infections in Immunosuppressed Patients: A Comparative Analysis With Diagnosis and Treatment Recommendations for Hand Surgeons.

Background: Immunosuppression is encountered in patients with oncologic, transplant, and autoimmune disorders. The purpose of this study is to provide guidance for physicians treating surgical hand and upper extremity (UE) infections in immunosuppressed (IS) patients. Methods: We retrospectively reviewed our database of patients presenting with UE infections over 3 years. IS patients were matched randomly to non-IS patients. Patient background, infection presentation, surgical evaluation, and microbiology variables were recorded. Infection variables included mechanism, location, and type. Outcomes included inpatient length of stay (LOS) and need for repeat drainage. Results: We identified 35 IS and 35 non-IS out of 409 UE infection patients. Patients most commonly had a hematologic malignancy (34%) as their IS class, and the most frequent immunosuppressive medication was glucocorticoids (57%). IS patients were more likely to be older and less likely to have a history of drug abuse or hepatitis C virus infections. IS infections were more likely to have idiopathic mechanisms, more likely to involve deeper anatomy such as joints, bone, tendon sheath, or muscle/fascia, and less likely to present with leukocytosis. IS cultures more commonly exhibited atypical Mycoplasma or fungus. There was no difference between IS and non-IS patients regarding LOS or recurrent drainage. Conclusions: Mechanism and white blood cell count are less reliable markers of infection severity in IS patients. Physicians treating infections in IS patients should maintain a higher suspicion for deeper involved anatomy and atypical microbiology. Nonetheless, with careful inpatient management and closer surveillance, outcomes in IS patients can approach that of non-IS patients.

Risk factors predicting Candida infective endocarditis in patients with candidemia.

Candida infective endocarditis (CIE) is a rare but serious complication of candidemia. Incidence and risk factors associated with CIE among candidemic patients are poorly defined from small cohorts. Identification of clinical predictors associated with this entity may guide more judicious use of cardiac imaging. We conducted a retrospective analysis of all inpatients aged ≥18 years diagnosed with candidemia at our institution. CIE was diagnosed by fulfilling two of the major Duke criteria: specifically a vegetation(s) on echocardiogram and positive blood cultures for Candida spp. We used univariable and multivariable regression analyses to identify risk factors associated with CIE. Of 1,873 patients with candidemia, 47 (2.5%) were identified to have CIE. In our multivariable logistic model, existing valvular heart disease was associated with a higher risk for CIE (adjusted odds ratio [aOR], 7.66; 95% confidence interval [CI], 2.95-19.84). Predictors that demonstrated a decreased risk of CIE included infection with C. glabrata (aOR, 0.17; 95% CI, 0.04-0.69), hematologic malignancy (aOR, 0.09; 95% CI, 0.01-0.68), and receipt of total parenteral nutrition (aOR, 0.38; 95% CI, 0.16-0.91). The 90-day crude mortality for CIE was 48.9%, similar to the overall non-CIE mortality of 41.9% (P = .338). We identified a set of clinical factors that can predict the presence of CIE among patient with candidemia. These findings may reduce the need for unnecessary expensive and invasive imaging studies in a subset of patients with a lower risk profile for endocarditis and alternative infection source.

Effect of infectious disease consultation on mortality and treatment of patients with candida bloodstream infections: a retrospective, cohort study.

BACKGROUND: Candida bloodstream infection is associated with high mortality. Infectious disease consultation improves outcomes in several infections, including Staphylococcus aureus and cryptococcosis, as well as multidrug-resistant organisms. We aimed to examine the association between infectious disease consultation and differences in management with mortality in candida bloodstream infections. METHODS: In this retrospective, single-centre cohort study, we reviewed the medical charts of all patients admitted to Barnes-Jewish Hospital (St Louis, MO, USA), a tertiary referral centre, aged 18 years or older with candida bloodstream infection from 2002 to 2015. We collected data for demographics, comorbidities, predisposing factors, all-cause mortality, antifungal use, central-line removal, and ophthalmological and echocardiographic evaluation to assess 90-day all-cause mortality between individuals with and without an infectious disease consultation. For the survival analysis we used Cox proportional hazards model with inverse weighting by propensity score to assess the effects of infectious disease consultation on mortality and differences in management. FINDINGS: Between Jan 1, 2002, and Dec 31, 2015, of 1794 patients assessed for eligibility, we analysed 1691 patients with candida bloodstream infection; 776 (45·9%) who had an infectious disease consultation and 915 (54·1%) who did not have an infectious disease consultation. All 1691 patients were included in the analysis. None were missing data. Most underlying comorbidities were evenly distributed between groups. 90-day mortality was lower in the infectious disease consultation group than in patients who did not receive an infectious disease consultation (29% [222/776] vs 51% [468/915]; p<0·0001). In the model with inverse weighting by the propensity score, infectious disease consultation was associated with a hazard ratio of 0·81 (95% CI 0·73-0·91; p<0·0001) for mortality. In the consultation group, median duration of antifungal therapy was longer (18 [IQR 14-35] vs 14 [6-20] days; p<0·0001) and central-line removal (587 [76%] of 776 vs 538 [59%] of 915; p<0·0001), echocardiography use (442 [57%] of 776 vs 305 [33%] of 915; p<0·0001), and ophthalmological examination (412 [53%] of 776 vs 160 [17%] of 915; p<0·0001) were more frequently done. Fewer patients in the infectious disease consultation group were not treated (13 [2%] of 776 vs 128 [14%] of 915; p<0·0001). INTERPRETATION: Patients with candida bloodstream infection receiving an infectious disease consultation have lower mortality. This finding might be attributable to these individuals receiving a higher number of non-pharmacological, evidence-based interventions and lower amounts of non-treatment. These data suggest that an infectious disease consultation should be an integral part of clinical care of patients with candida bloodstream infection. FUNDING: Astellas Global Development Pharma, Washington University Institute of Clinical and Translational Sciences, and the Agency for Healthcare Research and Quality.

Creation and assessment of a clinical predictive model for candidaemia in patients with candiduria.

Candidaemia is the most common clinical presentation of invasive candidiasis and is a major cause of morbidity and mortality. Candiduria is a predictor for candidaemia; however, patient characteristics that are associated with concurrent candidaemia in the setting of candiduria are unclear. Identifying these characteristics could aid in the early detection of systemic disease. We performed a retrospective cohort analysis of hospitalised patients with candiduria at our institution over a 13-year period. Our evaluation of patient characteristics included demographics, comorbidities, medications, procedures, devices, vital signs and laboratory values. We developed a multivariable logistic model to identify factors associated with candidaemia in patients with candiduria. We identified 4240 patients with candiduria, 263 (6.2%) of whom had candidaemia. Predictors for increased risk of candidaemia with candiduria included hospitalisations > 12 days, central venous catheter, parenteral nutrition, haematological and gynaecological malignancy, and receipt of ß-lactam/ß-lactamase inhibitors. Vital signs and laboratory values associated with candidaemia included elevated heart rate, temperature and creatinine, along with neutropenia and neutrophilia. Factors that demonstrated a decreased risk of candidaemia included diabetes mellitus, gastrostomy and urinary catheter with antibiotic use. The c-statistic was 0.741 (95% CI, 0.710-0.772). We identified a set of clinical characteristics that can predict the presence of candidaemia with candiduria.

A Cluster of Cefepime-induced Neutropenia During Outpatient Parenteral Antimicrobial Therapy.

A cluster of cefepime-induced neutropenia (CIN) was identified from June 2017 to May 2018 in a regional outpatient parenteral antimicrobial therapy population. Our data suggest prolonged courses of cefepime (≥2 weeks), administered by rapid intravenous push, were associated with a higher risk of CIN.

Assessment of inappropriate antibiotic prescribing among a large cohort of general dentists in the United States.

BACKGROUND: The purpose of this study was to assess dental antibiotic prescribing trends over time, to quantify the number and types of antibiotics dentists prescribe inappropriately, and to estimate the excess health care costs of inappropriate antibiotic prescribing with the use of a large cohort of general dentists in the United States. METHODS: We used a quasi-Poisson regression model to analyze antibiotic prescriptions trends by general dentists between January 1, 2013, and December 31, 2015, with the use of data from Express Scripts Holding Company, a large pharmacy benefits manager. We evaluated antibiotic duration and appropriateness for general dentists. Appropriateness was evaluated by reviewing the antibiotic prescribed and the duration of the prescription. RESULTS: Overall, the number and rate of antibiotic prescriptions prescribed by general dentists remained stable in our cohort. During the 3-year study period, approximately 14% of antibiotic prescriptions were deemed inappropriate, based on the antibiotic prescribed, antibiotic treatment duration, or both indicators. The quasi-Poisson regression model, which adjusted for number of beneficiaries covered, revealed a small but statistically significant decrease in the monthly rate of inappropriate antibiotic prescriptions by 0.32% (95% confidence interval, 0.14% to 0.50%; P = .001). CONCLUSIONS: Overall antibiotic prescribing practices among general dentists in this cohort remained stable over time. The rate of inappropriate antibiotic prescriptions by general dentists decreased slightly over time. PRACTICAL IMPLICATIONS: From these authors' definition of appropriate antibiotic prescription choice and duration, inappropriate antibiotic prescriptions are common (14% of all antibiotic prescriptions) among general dentists. Further analyses with the use of chart review, administrative data sets, or other approaches are needed to better evaluate antibiotic prescribing practices among dentists.

Outpatient Antibiotic Prescription Trends in the United States: A National Cohort Study.

OBJECTIVETo characterize trends in outpatient antibiotic prescriptions in the United StatesDESIGNRetrospective ecological and temporal trend study evaluating outpatient antibiotic prescriptions from 2013 to 2015SETTINGNational administrative claims data from a pharmacy benefits manager PARTICIPANTS. Prescription pharmacy beneficiaries from Express Scripts Holding CompanyMEASUREMENTSAnnual and seasonal percent change in antibiotic prescriptionsRESULTSApproximately 98 million outpatient antibiotic prescriptions were filled by 39 million insurance beneficiaries during the 3-year study period. The most commonly prescribed antibiotics were azithromycin, amoxicillin, amoxicillin/clavulanate, ciprofloxacin, and cephalexin. No significant changes in individual or overall annual antibiotic prescribing rates were found during the study period. Significant seasonal variation was observed, with antibiotics being 42% more likely to be prescribed during February than September (peak-to-trough ratio [PTTR], 1.42; 95% confidence interval [CI], 1.39-1.61). Similar seasonal trends were found for azithromycin (PTTR, 2.46; 95% CI, 2.44-3.47), amoxicillin (PTTR, 1.52; 95% CI, 1.42-1.89), and amoxicillin/clavulanate (PTTR, 1.78; 95% CI, 1.68-2.29).CONCLUSIONSThis study demonstrates that annual national outpatient antibiotic prescribing practices remained unchanged during our study period. Furthermore, seasonal peaks in antibiotics generally used to treat viral upper respiratory tract infections remained unchanged during cold and influenza season. These results suggest that inappropriate prescribing of antibiotics remains widespread, despite the concurrent release of several guideline-based best practices intended to reduce inappropriate antibiotic consumption; however, further research linking national outpatient antibiotic prescriptions to associated medical conditions is needed to confirm these findings.Infect Control Hosp Epidemiol 2018;39:584-589.

Creation and Assessment of a Clinical Predictive Calculator and Mortality Associated With Candida krusei Bloodstream Infections.

BACKGROUND: Candida krusei bloodstream infection (CK BSI) is associated with high mortality, but whether this is due to underlying comorbidities in affected patients or the organism itself is unknown. Identifying patient characteristics that are associated with CK BSI is crucial for clinical decision-making and prognosis. METHODS: We conducted a retrospective analysis of hospitalized patients with Candida BSI at our institution between 2002 and 2015. Data were collected on demographics, comorbidities, medications, procedures, central lines, vital signs, and laboratory values. Multivariable logistic and Cox regression were used to identify risk factors associated with CK and mortality, respectively. RESULTS: We identified 1873 individual patients who developed Candida BSI within the study period, 59 of whom had CK BSI. CK BSI was predicted by hematologic malignancy, gastric malignancy, neutropenia, and the use of prophylactic azole antifungals, monoclonal antibodies, and ß-lactam/ß-lactamase inhibitor combinations. The C-statistic was 0.86 (95% confidence interval, 0.81-0.91). The crude mortality rates were 64.4% for CK BSI and 41.4% for non-CK BSI. Although CK was associated with higher mortality in univariable Cox regression, this relationship was no longer significant with the addition of the following confounders: lymphoma, neutropenia, glucocorticoid use, chronic liver disease, and elevated creatinine. CONCLUSIONS: Six patient comorbidities predicted the development of CK BSI with high accuracy. Although patients with CK BSI have higher crude mortality rates than patients with non-CK BSI, this difference is not significant when accounting for other patient characteristics.

An evaluation of dental antibiotic prescribing practices in the United States.

BACKGROUND: Antibiotic prescribing practices among general dentists and dental specialists in the United States remains poorly understood. The purpose of this study was to compare prescribing practices across dental specialties, evaluate the duration of antibiotics dentists prescribed, and determine variation in antibiotic selection among dentists. METHODS: The authors performed a retrospective cross-sectional analysis of dental care provider specialties linked to deidentified antibiotic claims data from a large pharmacy benefits manager during the 2015 calendar year. RESULTS: As a group, general dentists and dental specialists were responsible for more than 2.9 million antibiotic prescriptions, higher than levels for several other medical and allied health care provider specialties. Antibiotic treatment duration generally was prolonged and commonly included broad-spectrum agents, such as amoxicillin clavulanate and clindamycin. Although amoxicillin was the most commonly prescribed antibiotic among all dental specialties, there was substantial variation among other antibiotics each specialty selected. The most common antibiotic treatment durations were 7 and 10 days. CONCLUSIONS: This study's results demonstrate that dentists frequently prescribe antibiotics for prolonged periods and often use broad-spectrum antibiotics. Further studies are necessary to evaluate the appropriateness of these antibiotic prescribing patterns. PRACTICAL IMPLICATIONS: The clinically significant variation in antibiotic selection and treatment duration identified among all dental specialties in this study population implies that further research and guidance into the treatment of dental infections is necessary to improve and standardize antibiotic prescribing practices.

Pharmacokinetic drug evaluation of tedizolid for the treatment of skin infections.

INTRODUCTION: Tedizolid is indicated for the treatment of acute bacterial skin and skin structure infections (ABSSSI). Although tedizolid shares many similar properties with linezolid, another oxazolidinone used to treat ABSSSI, the two antibiotics have several key differences. Areas covered: This review provides a detailed summary of the overall pharmacodynamics, pharmacokinetics, clinical efficacy, and safety of tedizolid for the treatment of ABSSSI. Expert opinion: Compared to other antibiotics used for ABSSSI, tedizolid has several advantages. Tedizolid has a long half-life, allowing for once daily dosing. Tedizolid also has broad spectrum of activity against Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus, Coagulase-negative Staphylococci, and Enterococci - including isolates demonstrating resistance to linezolid. It is available in both oral and intravenous formulations, and, has outstanding oral bioavailability, allowing for oral-step down therapy. There is also some evidence that, tedizolid has fewer significant interactions with serotonin reuptake inhibitors or monoamine oxidase inhibitors than linezolid. Finally, thrombocytopenia may occur less often with tedizolid than linezolid. However, these benefits must be weighed against the financial cost of tedizolid and the availability of alternative antibiotic choices.

Effective Antibiotic Conservation by Emergency Antimicrobial Stewardship During a Drug Shortage.

We present the first description of an antimicrobial stewardship program (ASP) used to successfully manage a multi-antimicrobial drug shortage. Without resorting to formulary restriction, meropenem utilization decreased by 69% and piperacillin-tazobactam by 73%. During the shortage period, hospital mortality decreased (P=.03), while hospital length of stay remained unchanged. Infect Control Hosp Epidemiol 2017;38:356-359.