A multi-species outbreak of VIM-producing carbapenem-resistant bacteria in a burn unit and subsequent investigation of rapid development of cefiderocol resistance.

Carbapenem resistance due to metallo-ß-lactamases (MBLs) such as the Verona integron-encoded metallo-ß-lactamase (VIM) is particularly problematic due to the limited treatment options. We describe a case series of bacterial infections in a tertiary care hospital due to multi-species acquisition of a VIM gene along with our experience using novel ß-lactam antibiotics and antibiotic combinations to treat these infections. Four patients were treated with the combination of ceftazidime-avibactam and aztreonam, with no resistance to the combination detected. However, cefiderocol-resistant Klebsiella pneumoniae isolates were detected in two out of the five patients who received cefiderocol within 3 weeks of having started the antibiotic. Strain pairs of sequential susceptible and resistant isolates from both patients were analyzed using whole-genome sequencing. This analysis revealed that the pairs of isolates independently acquired point mutations in both the cirA and fiu genes, which encode siderophore receptors. These point mutations were remade in a laboratory strain of K. pneumoniae and resulted in a significant increase in the MIC of cefiderocol, even in the absence of a beta-lactamase enzyme or a penicillin-binding protein 3 (PBP3) mutation. While newer ß-lactam antibiotics remain an exciting addition to the antibiotic armamentarium, their use must be accompanied by diligent monitoring for the rapid development of resistance.

Cefepime vs Piperacillin-Tazobactam in Adults Hospitalized With Acute Infection: The ACORN Randomized Clinical Trial.

Importance: Cefepime and piperacillin-tazobactam are commonly administered to hospitalized adults for empirical treatment of infection. Although piperacillin-tazobactam has been hypothesized to cause acute kidney injury and cefepime has been hypothesized to cause neurological dysfunction, their comparative safety has not been evaluated in a randomized clinical trial. Objective: To determine whether the choice between cefepime and piperacillin-tazobactam affects the risks of acute kidney injury or neurological dysfunction. Design, Setting, and Participants: The Antibiotic Choice on Renal Outcomes (ACORN) randomized clinical trial compared cefepime vs piperacillin-tazobactam in adults for whom a clinician initiated an order for antipseudomonal antibiotics within 12 hours of presentation to the hospital in the emergency department or medical intensive care unit at an academic medical center in the US between November 10, 2021, and October 7, 2022. The final date of follow-up was November 4, 2022. Interventions: Patients were randomized in a 1:1 ratio to cefepime or piperacillin-tazobactam. Main Outcomes and Measures: The primary outcome was the highest stage of acute kidney injury or death by day 14, measured on a 5-level ordinal scale ranging from no acute kidney injury to death. The 2 secondary outcomes were the incidence of major adverse kidney events at day 14 and the number of days alive and free of delirium and coma within 14 days. Results: There were 2511 patients included in the primary analysis (median age, 58 years [IQR, 43-69 years]; 42.7% were female; 16.3% were Non-Hispanic Black; 5.4% were Hispanic; 94.7% were enrolled in the emergency department; and 77.2% were receiving vancomycin at enrollment). The highest stage of acute kidney injury or death was not significantly different between the cefepime group and the piperacillin-tazobactam group; there were 85 patients (n = 1214; 7.0%) in the cefepime group with stage 3 acute kidney injury and 92 (7.6%) who died vs 97 patients (n = 1297; 7.5%) in the piperacillin-tazobactam group with stage 3 acute kidney injury and 78 (6.0%) who died (odds ratio, 0.95 [95% CI, 0.80 to 1.13], P = .56). The incidence of major adverse kidney events at day 14 did not differ between groups (124 patients [10.2%] in the cefepime group vs 114 patients [8.8%] in the piperacillin-tazobactam group; absolute difference, 1.4% [95% CI, -1.0% to 3.8%]). Patients in the cefepime group experienced fewer days alive and free of delirium and coma within 14 days (mean [SD], 11.9 [4.6] days vs 12.2 [4.3] days in the piperacillin-tazobactam group; odds ratio, 0.79 [95% CI, 0.65 to 0.95]). Conclusions and Relevance: Among hospitalized adults in this randomized clinical trial, treatment with piperacillin-tazobactam did not increase the incidence of acute kidney injury or death. Treatment with cefepime resulted in more neurological dysfunction. Trial Registration: ClinicalTrials.gov Identifier: NCT05094154.

Development of the Three Antimicrobial Stewardship E's (TASE) Framework and Association Between Stewardship Interventions and Intended Results Analysis to Identify Key Facility-Specific Interventions and Strategies for Successful Antimicrobial Stewardship.

BACKGROUND: Successful antimicrobial stewardship (AS) interventions have been described previously. Currently, a uniform operational approach to planning and implementing successful AS interventions does not exist. From 2015 to 2019, concomitant vancomycin and piperacillin-tazobactam use (CVPTU) for >48 hours at Vanderbilt University Medical Center (VUMC) significantly decreased through AS efforts. We analyzed the interventions that led to this change and created a model to inform future intervention planning and development. METHODS: Adult admissions at VUMC from January 2015 to August 2019 were evaluated for CVPTU. The percentage of admissions receiving CVPTU for >48 hours, the primary outcome, was evaluated using statistical process control charts. We created the Three Antimicrobial Stewardship E's (TASE) framework and Association between Stewardship Interventions and Intended Results (ASIR) analysis to assess potential intensity and impact of interventions associated with successful change during this time period and to identify guiding principles for development of future initiatives. RESULTS: The mean percentage of admissions receiving CVPTU per month declined from 4.2% to 0.7%. Over 8 time periods, we identified 4 periods with high, 3 with moderate, and 1 with low intervention intensity. Continuous provider-level AS education was present throughout. Creation and dissemination of division and department algorithms and reinforcement via computerized provider order entry sets preceded the largest reduction in CVPTU and sustained prescribing practice changes. CONCLUSIONS: The TASE framework and ASIR analysis successfully identified pivotal interventions and strategies needed to effect and sustain change at VUMC. Further research is needed to validate the effectiveness of this framework as a stewardship intervention planning tool at our institution and others.

Severe Epididymo-Orchitis and Encephalitis Complicating Anti-PD-1 Therapy.

BACKGROUND: Immune checkpoint inhibitors such as pembrolizumab and nivolumab have emerged as active treatment options for patients with many cancers, including metastatic melanoma, but can also cause symptomatic or life-threatening immune-related adverse events, including encephalitis. Epididymitis and orchitis are rare complications of these therapies. CASE PRESENTATION: We describe herein a patient with metastatic melanoma who developed epididymo-orchitis followed by encephalitis while receiving pembrolizumab. The patient developed testicular pain and fever after his third dose of pembrolizumab; ultrasound evaluation demonstrated bilateral epididymo-orchitis. He then developed headaches, fever, and altered mental status over the next week and was admitted to the hospital. Lumbar puncture revealed inflammatory changes consistent with meningoencephalitis; he did not improve with broad-spectrum antibiotics, and an extensive workup for infectious etiologies, including cerebrospinal fluid testing using a clinical metagenomic next-generation sequencing assay, was negative. He received high-dose steroids for suspected autoimmune encephalitis, and both his orchitis and meningoencephalitis improved rapidly after one dose. He fully recovered after a 5-week taper of oral steroids. DISCUSSION: Here, we report a case of epididymo-orchitis complicating immune checkpoint inhibitor therapy. This patient subsequently developed severe encephalitis but rapidly improved with steroids. Clinicians should be aware of rare complications of these agents. KEY POINTS: Epididymo-orchitis is a rare and potentially life-threatening complication of anti-programmed death protein 1 (anti-PD-1) therapy.For patients on anti-PD-1 therapy who develop either epididymo-orchitis or epididymitis without clear infectious cause, immune-related adverse events should be considered in the differential diagnosis.If severe, epididymo-orchitis related to anti-PD-1 therapy may be treated with high-dose corticosteroids.

Effect of Statin Coadministration on the Risk of Daptomycin-Associated Myopathy.

Background: Daptomycin-associated myopathy has been identified in 2%-14% of patients, and rhabdomyolysis is a known adverse effect. Although risk factors for daptomycin-associated myopathy are poorly defined, creatine phosphokinase (CPK) monitoring and temporary discontinuation of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or "statins," has been recommended. Methods: We conducted a single-center, retrospective, matched case-control risk factor analysis in adult and pediatric patients from 2004 to 2015. Patients in whom myopathy (defined as CPK values above the upper limit of normal) developed during daptomycin treatment were matched 1:1 to no-myopathy controls with at least the same duration of therapy. Risk factors independently associated with myopathy were determined using multivariable conditional logistic regression. Secondary analysis was performed in patients with rhabdomyolysis, defined as CPK values ≥10 times the upper limit of normal. Results: Of 3042 patients reviewed, 128 (4.2%) were identified as having daptomycin-associated myopathy, 25 (0.8%) of whom had rhabdomyolysis; 121 (95%) of the 128 were adults, and the mean duration of therapy before CPK elevation was 16.7 days (range, 1-58 days). In multivariate analysis, deep abscess treatment (odds ratio, 2.80; P = .03), antihistamine coadministration (3.50; P = .03), and statin coadministration (2.60; P = .03) were independent risk factors for myopathy. Obesity (odds ratio, 3.28; P = .03) and statin coadministration (4.67; P = .03) were found to be independent risk factors for rhabdomyolysis, and older age was associated with reduced risk (0.97; P = .05). Conclusions: Statin coadministration with daptomycin was independently associated with myopathy and rhabdomyolysis. This is the first study to provide strong evidence supporting this association. During coadministration, we recommend twice-weekly CPK monitoring and consideration of withholding statins.

Factors associated with recurrence and mortality in central line-associated bloodstream infections: a retrospective cohort study.

BACKGROUND: Central line-associated bloodstream infections (CLABSIs) are associated with increased mortality, hospital length of stay, and cost. Antimicrobial treatment guidelines for CLABSIs are primarily based on expert opinion. We hypothesized that shorter antimicrobial treatment duration is associated with decreased 60-day recurrence-free survival. METHODS: A retrospective cohort study of all adults with hospital-acquired CLABSIs (HA-CLABSIs) over 5 years at a single tertiary care academic hospital was performed. The time from the end of effective antimicrobial treatment until recurrence of infection or mortality, censored at 60 days after the end of antimicrobial treatment, represented the primary outcome. Effective antimicrobial treatment was defined as the administration of at least one antimicrobial to which the causative organism was sensitive. RESULTS: A total of 366 cases met eligibility criteria. The median Sequential Organ Failure Assessment (SOFA) score was 6 (interquartile range (IQR) 4-8). Patients were treated for a median of 15 (IQR 10-20) days with effective antimicrobials. The incidence of 60-day mortality or recurrence after completion of the antimicrobial course was 22.1% (81 patients). In a Cox proportional-hazards model, antimicrobial treatment duration (hazard ratio (HR) = 0.35; 95% confidence interval (CI) 0.26-0.48), SOFA score (HR = 1.16; 95% CI 1.09-1.22), and age (HR = 1.021; 95% CI = 1.004-1.037) were associated with mortality or recurrence. The effect of antimicrobial treatment duration appeared to plateau after 15 days. CONCLUSIONS: Longer antimicrobial treatment duration in patients with HA-CLABSIs is associated with improved recurrence-free survival during the first 60 days after infection. This effect appears to plateau after 15 days of treatment. Prospective studies are needed to definitively determine the optimal antimicrobial treatment duration for CLABSIs.

Epidemiology of Invasive Group A Streptococcal Infections in the United States, 2005-2012.

BACKGROUND: Invasive group A Streptococcus (GAS) infections are associated with significant morbidity and mortality rates. We report the epidemiology and trends of invasive GAS over 8 years of surveillance. METHODS: From January 2005 through December 2012, we collected data from the Centers for Disease Control and Prevention's Active Bacterial Core surveillance, a population-based network of 10 geographically diverse US sites (2012 population, 32.8 million). We defined invasive GAS as isolation of GAS from a normally sterile site or from a wound in a patient with necrotizing fasciitis (NF) or streptococcal toxic shock syndrome (STSS). Available isolates were emm typed. We calculated rates and made age- and race-adjusted national projections using census data. RESULTS: We identified 9557 cases (3.8 cases per 100 000 persons per year) with 1116 deaths (case-fatality rate, 11.7%). The case-fatality rates for septic shock, STSS, and NF were 45%, 38%, and 29%, respectively. The annual incidence was highest among persons aged ≥65 years (9.4/100 000) or <1 year (5.3) and among blacks (4.7/100 000). National rates remained steady over 8 years of surveillance. Factors independently associated with death included increasing age, residence in a nursing home, recent surgery, septic shock, NF, meningitis, isolated bacteremia, pneumonia, emm type 1 or 3, and underlying chronic illness or immunosuppression. An estimated 10 649-13 434 cases of invasive GAS infections occur in the United States annually, resulting in 1136-1607 deaths. In a 30-valent M-protein vaccine, emm types accounted for 91% of isolates. CONCLUSIONS: The burden of invasive GAS infection in the United States remains substantial. Vaccines under development could have a considerable public health impact.

Impacts of risk-stratified inpatient penicillin allergy label delabeling on subsequent antimicrobial spectrum index and costs.

Penicillin allergy delabeling may benefit antimicrobial stewardship (AS). Cost of initial penicillin treatments following risk-stratified inpatient delabeling were compared to two hypothetical treatment regimens if delabeling had not occurred: (1) AS-guided and (2) Common Treatment. Penicillin allergy delabeling improved antimicrobial spectrum index, was cost-neutral, and averted unnecessary penicillin desensitizations.

Swab Testing to Optimize Pneumonia treatment with empiric Vancomycin (STOP-Vanc): study protocol for a randomized controlled trial.

Background: Vancomycin, an antibiotic with activity against Methicillin-resistant Staphylococcus aureus (MRSA), is frequently included in empiric treatment for community-acquired pneumonia (CAP) despite the fact that MRSA is rarely implicated in CAP. Conducting polymerase chain reaction (PCR) testing on nasal swabs to identify the presence of MRSA colonization has been proposed as an antimicrobial stewardship intervention to reduce the use of vancomycin. Observational studies have shown reductions in vancomycin use after implementation of MRSA colonization testing, and this approach has been adopted by CAP guidelines. However, the ability of this intervention to safely reduce vancomycin use has yet to be tested in a randomized controlled trial. Methods: STOP-Vanc is a pragmatic, prospective, single center, non-blinded randomized trial. Adult patients with suspicion for CAP who are receiving vancomycin and admitted to the Medical Intensive Care Unit at Vanderbilt University Medical Center will be screened for eligibility. Eligible patients will be enrolled and randomized in a 1:1 ratio to either receive MRSA nasal swab PCR testing in addition to usual care (intervention group), or usual care alone (control group). PCR testing results will be transmitted through the electronic health record to the treating clinicians. Primary providers of intervention group patients with negative swab results will also receive a page providing clinical guidance recommending discontinuation of vancomycin. The primary outcome will be vancomycin-free hours alive, defined as the number of hours alive and free of the use of vancomycin within the first seven days following trial enrollment estimated using a proportional odds ratio model. Secondary outcomes include 30-day all-cause mortality and time alive off vancomycin. Discussion: STOP-Vanc will provide the first randomized controlled trial data regarding the use of MRSA nasal swab PCR testing to guide antibiotic de-escalation. This study will provide important information regarding the effect of MRSA PCR testing and antimicrobial stewardship guidance on clinical outcomes in an intensive care unit setting. Trial registration: This trial was registered on ClinicalTrials.gov on February 22, 2024. (ClinicalTrials.gov identifier: NCT06272994).

Principles and Practice of Antimicrobial Stewardship Program Resource Allocation.

Antimicrobial Stewardship Programs (ASP) improve individual patient outcomes and clinical care processes while reducing antimicrobial-associated adverse events, optimizing operational priorities, and providing institutional cost savings. ASP composition, resources required, and priority focuses are influenced by myriad factors. Despite robust evidence and broad national support, individual ASPs still face challenges in obtaining appropriate resources. Though understanding the current landscape of ASP resource allocation, factors influencing staffing needs, and strategies required to obtain desired resources is important, acceptance of recommended staffing levels and appropriate ASP resource allocation are much needed to facilitate ASP sustainability and growth across the complex and diverse health care continuum.

An app a day: Results of pre- and post-surveys of knowledge, attitudes, and practices (KAP) regarding antimicrobial stewardship principles among nurses who utilized a novel learning platform.

Background: Nurses perform several functions that are integral for antimicrobial stewardship (AMS). However, nurses are underrepresented in research and underutilized in implementation of AMS interventions. The objective of this pilot study was to assess the effect of asynchronous microlearning on inpatient nursing staff knowledge, attitudes, and practices (KAP) regarding AMS principles. Methods: A team of pharmacists, physicians, and nurses developed 9 case-based, multiple-choice questions with accompanying educational explanations on associated AMS principles. One case was delivered to participants daily via an institutional web-based application (QuizTime). A KAP survey with 20 questions on a 5-point Likert scale was administered before and after the intervention. Survey results were compared using a Wilcoxon signed-rank test. Results: Participants' mean survey score after the intervention demonstrated statistically significant improvement for 18 (90%) of 20 items compared to before the intervention. Participants' confidence improved in key AMS activities: (1) differentiating between colonization and infection (mean difference, 0.63; P < .001), (2) identifying unnecessary urine cultures and inappropriate treatment of urinary tract infections (mean difference, 0.94; P < .001), (3) recognizing opportunities for intravenous to oral therapy conversion (mean difference, 1.07; P < .001), and (4) assessing for antibiotic-associated adverse effects (mean difference, 0.54; P < .001). Conclusions: Nursing education provided through an asynchronous, microlearning format via a mobile platform resulted in statistically significant improvement in most KAP topics. Nurses are integral members of a multidisciplinary AMS team, and novel education methods can help equip them with the necessary AMS tools. This pilot study forms the basis for expanded AMS educational efforts in all healthcare professionals.

Invasive pneumococcal disease and pandemic (H1N1) 2009, Denver, Colorado, USA.

Pneumococcal pneumonia was a complication during previous influenza pandemics but was not evident initially during pandemic (H1N1) 2009. During October 2009 in Denver, Colorado, USA, invasive pneumococcal disease (IPD) and pandemic (H1N1) 2009 peaked simultaneously, which suggests a link. We compared cases of IPD in October 2009 with cases in February 2009, the most recent peak month of seasonal influenza. During October 2009, we observed 58 IPD cases, which was 3× the average number of IPD cases that usually occur in October in Denver. Patients with IPD in October 2009 were younger and more likely to have chronic lung disease than patients who had IPD in February 2009; a total of 10/47 patients had influenza, and 33/53 patients had influenza-like illness. Thus, ≈17%-62% cases of IPD may have been associated with pandemic (H1N1) 2009. Pneumococcal disease prevention strategies should be emphasized during future influenza pandemics.

Changes in antimicrobial utilization during the coronavirus disease 2019 (COVID-19) pandemic after implementation of a multispecialty clinical guidance team.

OBJECTIVE: Evaluate changes in antimicrobial use during COVID-19 and after implementation of a multispecialty COVID-19 clinical guidance team compared to pre-COVID-19 antimicrobial use. DESIGN: Retrospective observational study. SETTING: Tertiary-care academic medical center. PARTICIPANTS: Internal medicine and medical intensive care unit (MICU) provider teams and hospitalized COVID-19 patients. METHODS: Difference-in-differences analyses of antibiotic days of therapy per 1,000 patient days present (DOT) for internal medicine and MICU teams treating COVID-19 patients versus teams that did not were performed for 3 periods: before COVID-19, initial COVID-19 period, and after implementation of a multispecialty COVID-19 clinical guidance team which included daily, patient-specific antimicrobial stewardship recommendations. Patient characteristics associated with antibiotic DOT were evaluated using multivariable Poisson regression. RESULTS: In the initial COVID-19 period, compared to the pre-COVID-19 period, internal medicine and MICU teams increased weekly antimicrobial use by 145.3 DOT (95% CI, 35.1-255.5) and 204.0 DOT (95% CI, -16.9 to 424.8), respectively, compared to non-COVID-19 teams. In the intervention period, internal medicine and MICU COVID-19 teams both had significant weekly decreases of 362.3 DOT (95% CI, -443.3 to -281.2) and 226.3 DOT (95% CI, -381.2 to -71.3). Of 131 patients hospitalized with COVID-19, 86 (65.6%) received antibiotics; no specific patient factors were significantly associated with an expected change in antibiotic days. CONCLUSIONS: Antimicrobial use initially increased for COVID-19 patient care teams compared to pre-COVID-19 levels but significantly decreased after implementation of a multispecialty clinical guidance team, which may be an effective strategy to reduce unnecessary antimicrobial use.

Identification and Antibiotic Susceptibility Patterns of Clinical Blood Culture Isolates Not Identified by a Rapid Microarray Diagnostic System.

The use of molecular-based diagnostic testing, such as the Luminex Verigene system, to rapidly identify the most common bacterial isolates from blood cultures is an important tool that reduces the duration of inappropriate antibiotics and decreases mortality. However, 5 to 15% of microorganisms recovered from blood culture are unable to be identified by the Verigene Gram-negative (BC-GN) or Gram-positive (BC-GP) assays. In this retrospective, observational study, we evaluate the identities and antimicrobial susceptibility patterns of 229 isolates that were not identified by either the Verigene BC-GN or BC-GP assay. The results presented here suggest that important, clinically relevant information about antimicrobial susceptibility patterns can still be inferred even when isolates are not identified by Verigene. We also examined changes in antibiotic use for patients with "unidentified" Verigene results at our institution and found that this subgroup represents an opportunity to optimize empirical antibiotic therapy. IMPORTANCE Rapid diagnostic testing to identify bloodstream pathogens has arisen as an important tool both to ensure adequate antimicrobial therapy is given early and to aid in antimicrobial stewardship by allowing for more rapid deescalation of inappropriate antimicrobial therapy. However, there is a paucity of data regarding the significance of isolates that are not able to be identified by rapid diagnostic testing. In this study, we report the identification to the species level and antimicrobial susceptibilities among isolates that were not identified by one such rapid diagnostic platform, the Verigene system. This study provides important insight into how a strong understanding of the strengths and limitations of a given rapid diagnostic platform, coupled with insight into local antibiotic susceptibility patterns, can allow for more nuanced and thoughtful empirical antibiotic selection.

Antimicrobial de-escalation in patients with high-risk febrile neutropenia: Attitudes and practices of adult hospital care providers.

In a survey of adult hospital providers regarding antibiotic use in the treatment of febrile neutropenia, clinical fellows, and pharmacists showed higher comfort levels with early antimicrobial de-escalation compared to hematology-oncology and transplant infectious diseases physicians. These frontline team members are ideal partners to champion antimicrobial stewardship interventions in febrile neutropenia.

Risk factors for mortality and progression to severe COVID-19 disease in the Southeast region in the United States: A report from the SEUS Study Group.

OBJECTIVE: Identify risk factors that could increase progression to severe disease and mortality in hospitalized SARS-CoV-2 patients in the Southeast region of the United States. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, retrospective cohort including 502 adults hospitalized with laboratory-confirmed COVID-19 between March 1, 2020, and May 8, 2020 within 1 of 15 participating hospitals in 5 health systems across 5 states in the Southeast United States. METHODS: The study objectives were to identify risk factors that could increase progression to hospital mortality and severe disease (defined as a composite of intensive care unit admission or requirement of mechanical ventilation) in hospitalized SARS-CoV-2 patients in the Southeast United States. RESULTS: In total, 502 patients were included, and 476 of 502 (95%) had clinically evaluable outcomes. The hospital mortality rate was 16% (76 of 476); 35% (177 of 502) required ICU admission and 18% (91 of 502) required mechanical ventilation. By both univariate and adjusted multivariate analyses, hospital mortality was independently associated with age (adjusted odds ratio [aOR], 2.03 for each decade increase; 95% confidence interval [CI], 1.56--2.69), male sex (aOR, 2.44; 95% CI, 1.34-4.59), and cardiovascular disease (aOR, 2.16; 95% CI, 1.15-4.09). As with mortality, risk of severe disease was independently associated with age (aOR, 1.17 for each decade increase; 95% CI, 1.00-1.37), male sex (aOR, 2.34; 95% CI, 1.54-3.60), and cardiovascular disease (aOR, 1.77; 95% CI, 1.09-2.85). CONCLUSIONS: In an adjusted multivariate analysis, advanced age, male sex, and cardiovascular disease increased risk of severe disease and mortality in patients with COVID-19 in the Southeast United States. In-hospital mortality risk doubled with each subsequent decade of life.

Antimicrobial stewardship staffing: How much is enough?

Antimicrobial stewardship improves patient care and reduces antimicrobial resistance, inappropriate use, and adverse outcomes. Despite high-profile mandates for antimicrobial stewardship programs across the healthcare continuum, descriptive data, and recommendations for dedicated resources, including appropriate physician, pharmacist, data analytics, and administrative staffing support, are not robust. This review summarizes the current literature on antimicrobial stewardship staffing and calls for the development of minimum staffing recommendations.

Description of a pharmacist-driven safety algorithm in Staphylococcus aureus bacteremia: Compliance, interventions, and good saves.

OBJECTIVE: To evaluate the impact of a pharmacist-driven Staphylococcus aureus bacteremia (SAB) safety bundle supported by leadership and to compare compliance before and after implementation. DESIGN: Retrospective cohort study with descriptive and before-and-after analyses. SETTING: Tertiary-care academic medical center. PATIENTS: All patients with documented SAB, regardless of the source of infection, were included. Patients transitioned to palliative care were excluded from before-and-after analysis. METHODS: A pharmacist-driven safety bundle including documented clearance of bacteremia, echocardiography, removal of central venous catheters, and targeted intravenous therapy of at least 2 weeks duration was implemented in November 2015 and was supported by leadership with stepwise escalation for nonresponse. A descriptive analysis of all patients with SAB during the study period included pharmacy interventions, acceptance rates, and escalation rates. A pre-post implementation analysis of 100 sequential patients compared bundle compliance and descriptive parameters. RESULTS: Overall, 391 interventions were made in the 20-month period following implementation, including 20 "good saves" avoiding potentially major adverse events. No statistically significant differences in complete bundle compliance were detected between the periods (74% vs 84%; P = .08). However, we detected a significant increase in echocardiography after the bundle was implemented (83% vs 94%; P = .02) and fewer patients received suboptimal definitive therapy after the bundle was implemented (10% vs 3%; P = .045). CONCLUSIONS: This pharmacist-driven SAB safety bundle with leadership support showed improvement in process measures, which may have prevented major adverse events, even with available infectious diseases (ID) consultation. It provides a critical safety net for institutions without mandatory ID consultation or with limited antimicrobial stewardship resources.

Analysis of a high-prescribing state's 2016 outpatient antibiotic prescriptions: Implications for outpatient antimicrobial stewardship interventions.

OBJECTIVE: To identify prescriber characteristics that predict antibiotic high-prescribing behavior to inform statewide antimicrobial stewardship interventions. DESIGN: Retrospective analysis of 2016 IQVIA Xponent, formerly QuintilesIMS, outpatient retail pharmacy oral antibiotic prescriptions in Tennessee. SETTING: Statewide retail pharmacies filling outpatient antibiotic prescriptions. PARTICIPANTS: Prescribers who wrote at least 1 antibiotic prescription filled at a retail pharmacy in Tennessee in 2016. METHODS: Multivariable logistic regression, including prescriber gender, birth decade, specialty, and practice location, and patient gender and age group, to determine the association with high prescribing. RESULTS: In 2016, 7,949,816 outpatient oral antibiotic prescriptions were filled in Tennessee: 1,195 prescriptions per 1,000 total population. Moreover, 50% of Tennessee's outpatient oral antibiotic prescriptions were written by 9.3% of prescribers. Specific specialties and prescriber types were associated with high prescribing: urology (odds ratio [OR], 3.249; 95% confidence interval [CI], 3.208-3.289), nurse practitioners (OR, 2.675; 95% CI, 2.658-2.692), dermatologists (OR, 2.396; 95% CI, 2.365-2.428), physician assistants (OR, 2.382; 95% CI, 2.364-2.400), and pediatric physicians (OR, 2.340; 95% CI, 2.320-2.361). Prescribers born in the 1960s were most likely to be high prescribers (OR, 2.574; 95% CI, 2.532-2.618). Prescribers in rural areas were more likely than prescribers in all other practice locations to be high prescribers. High prescribers were more likely to prescribe broader-spectrum antibiotics (P < .001). CONCLUSIONS: Targeting high prescribers, independent of specialty, degree, practice location, age, or gender, may be the best strategy for implementing cost-conscious, effective outpatient antimicrobial stewardship interventions. More information about high prescribers, such as patient volumes, clinical scope, and specific barriers to intervention, is needed.