HIV care providers. These results have implications to engage more PLWH into care, particularly i... more HIV care providers. These results have implications to engage more PLWH into care, particularly in states that have increased access to primary care through healthcare expansions.
Although beta-lactam allergies are an emerging focus of stewardship programs and interventions, l... more Although beta-lactam allergies are an emerging focus of stewardship programs and interventions, less is publicly released regarding allergies to beta-lactamase inhibitors. This review presents and evaluates the data regarding allergic reactions with beta-lactamase inhibitors. Clavulanate, sulbactam, and tazobactam are beta-lactam-based beta-lactamase inhibitors that are combined with several penicillins or cephalosporins in order to preserve antimicrobial activity in the presence of beta-lactamases. Avibactam, relebactam, and vaborbactam are non-beta-lactam beta-lactamase inhibitors that are combined with cephalosporins or carbapenems in order to expand the antimicrobial activity against broader-spectrum beta-lactamases. Case reports document hypersensitivity reactions to clavulanate, sulbactam, and tazobactam, but not to avibactam, relebactam, or vaborbactam. Based on these reports and considering the chemical structures, cross-allergenicity with beta-lactams is likely with sulbactam and tazobactam. Considering the slightly altered beta-lactam structure, cross-allergenicity is less likely with clavulanate, but still possible. It appears that cross-allergenicity between beta-lactam antimicrobials and the newer, non-beta-lactam beta-lactamase inhibitors is unlikely. It is important for clinicians to perform allergy testing to both the beta-lactam and the beta-lactamase inhibitor in order to confirm the specific allergy and reaction type.
Therapeutic advances in infectious disease, Dec 10, 2017
Background: Candidemia represents a leading cause of healthcare-associated bloodstream infections... more Background: Candidemia represents a leading cause of healthcare-associated bloodstream infections with significant morbidity and mortality. Previous studies have demonstrated that comprehensive care bundles improve candidemia management but are time-consuming. Objective: To determine the impact of a one-time targeted candidemia intervention on time to initiation of adequate therapy compared to standard of care. Methods: This Institutional Review Board (IRB)-approved, quasi-experiment evaluated a targeted candidemia intervention involving a single phone call to the primary team providing recommendations for care. Daily follow-up was provided by the infectious diseases (ID) consult service. Two time periods were evaluated: pre-intervention (01 August 2012 to 31 July 2014) and post-intervention (01 October 2014 to 30 September 2016). The primary endpoint was time to adequate antifungal therapy (TTx) in the business hours (6 a.m. to 6 p.m. Monday through Friday) population (BHP). Secondary endpoints were TTx in the total population as well as infection-related length of stay (IF-LOS) and compliance with quality indicators (composite endpoint: ophthalmology (OPH) consult, repeat cultures, and ⩾14 days of adequate therapy). Results: In all, 117 patients were included (pre-intervention = 50, post-intervention = 67, BHP = 51). TTx decreased from 2 h 57 m to 2 h 12 m (p = 0.094) in the BHP and 3 h 30 m to 2 h 9 m (p = 0.021) in the total population. There was no difference in IF-LOS (p = 0.797), compliance with quality indicators (p = 0.343), or in-hospital mortality (p = 0.761). Post-intervention, there were more ID and OPH consults (p < 0.001). Conclusions: Our one-time candidemia intervention did not statistically decrease time to adequate therapy in the BHP, but did in the total population. No differences were found for other clinical outcomes, except increases in ID and OPH consults. Further studies are needed to examine whether a one-time intervention is non-inferior to a more comprehensive care bundle.
JACCP: journal of the American College of Clinical Pharmacy, Oct 8, 2021
IntroductionAdvances in technology and understanding of pharmacokinetic/pharmacodynamic relations... more IntroductionAdvances in technology and understanding of pharmacokinetic/pharmacodynamic relationships have prompted guideline updates and advances in precision dosing, but the role of clinical pharmacokinetics (PK) in pharmacy education remains inconsistent. Previous surveys of pharmacy school PK curricula revealed large variations in content, integration, and teaching tools but did not focus on antimicrobials or details of andragogy used.ObjectiveIdentify how antimicrobial PK is taught in pharmacy curricula across the United States, as well as instructor perceptions of current practices.MethodsAn online survey was distributed to 118 pharmacy programs across the United States in 2018. This 30‐minute questionnaire covered curriculum content, teaching strategies, assessment modalities, and perceptions.ResultsCompleted surveys were received from 53 programs (45% response rate) via relevant course coordinators. Among 35 traditional progressive curriculum programs (TPC), antimicrobial PK was taught in basic science (33, 94%), clinical PK (15, 43%), pharmacology (8, 23%), therapeutics (28, 80%), and skills lab courses (21, 65%). Among 18 integrated block curriculum programs (IBC), it was taught in foundations/principles (17, 94%), organ systems (12, 67%), and skills lab courses (9, 50%). On average, TPC programs had more courses with antimicrobial PK than IBC programs. Vancomycin and aminoglycosides were the most common antimicrobials taught (100%), while didactic lecturing was the predominant andragogy. Multiple choice was the primary assessment modality, being frequently used in 64% of TPC and 68% of IBC courses, respectively. Among respondents, 72% believed more time was needed to teach PK and 53% believed students were adequately prepared at the start of APPEs.ConclusionAntimicrobial PK instruction remains highly inconsistent in U.S. pharmacy schools and colleges. IBC programs may provide less opportunity for antimicrobial PK instruction, which conflicts with the desire for more instruction time. As clinical applications of antimicrobial PK change and expand, it is crucial that pharmacy education prioritizes PK education appropriately.
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Introduction. Carbapenem-resistant Enterobacteriaceae (CRE) are an urgent threat in the USA and a... more Introduction. Carbapenem-resistant Enterobacteriaceae (CRE) are an urgent threat in the USA and are associated with adverse clinical and economic outcomes. Several studies have evaluated risk factors for acquiring CRE versus carbapenem-susceptible Enterobacteriaceae , identifying antibiotic use and length of hospital stay as major players. However, no studies have compared risk factors for CRE colonization versus infection. Hypothesis/Gap Statement. Patients with CRE infection will have different risk factors and worse clinical outcomes than patients with CRE colonization. Aim. To assess clinical outcomes in patients with CRE infection versus CRE colonization. Methodology. A retrospective cohort of adult patients admitted between 1 June 2013 and 31 July 2018 with the first positive CRE culture from any source was performed. Patients were divided into two groups: CRE infection versus CRE colonization. Data collected included demographics, comorbidities, past antimicrobial usage and clinical outcomes (length of stay, in-hospital mortality). The primary outcome was infection-related length of stay. Data analysis was performed utilizing SPSS with a two-sided P value of less than 0.05 considered statistically significant. Results. A total of 56 patients were included (32 with infection; 24 with colonization). Baseline characteristics were similar between both groups. Infected patients were more likely to have higher actual body weight compared to colonized patients (P=0.03). CRE-infected patients had a longer infection-related hospital stay [12 days (5–20) and 7.5 days (1–13), respectively; P=0.08], but in-hospital mortality was similar between infected and colonized patients (37.5 and 29.2 %, respectively; P=0.30). Patients with infection were more likely to have previous exposure to levofloxacin (P=0.02) and trimethoprim/sulfamethoxazole (P=0.03) for a median of 9 days compared to those with colonization. The most common source of CRE in infected patients was the blood compared to respiratory sources in colonized patients. Conclusion. CRE infection as opposed to colonization was more common in patients with previous exposure to levofloxacin and trimethoprim/sulfamethoxazole and those with higher actual body weight.
TO THE EDITOR-We read with interest the article by Humphries and Hindler on the challenges of ant... more TO THE EDITOR-We read with interest the article by Humphries and Hindler on the challenges of antimicrobial susceptibility testing (AST) in light of the changing resistance and regulatory landscape [1]. Many of the issues highlighted potentially hamper antimicrobial stewardship efforts
As antimicrobial stewardship increasingly receives worldwide attention for improving patient care... more As antimicrobial stewardship increasingly receives worldwide attention for improving patient care by optimizing antimicrobial therapy, programs are evaluating new tools that may augment antimicrobial stewardship activities. Biomarkers are objective, accurate, and reproducible measures that provide information about medical conditions. A systematic literature search using PubMed/MEDLINE databases was performed to evaluate the use of novel biomarkers as additions to the antimicrobial stewardship armamentarium. Procalcitonin may help clinicians discriminate between bacterial and viral infections, help with antimicrobial discontinuation decisions, and predict mortality. Beta-D-glucan, Candida albicans germ tube antibody, and galactomannan are useful in suspected fungal infections, and may reduce inappropriate antifungal use. Adrenomedullin and soluble triggering receptor on myeloid cells-1 may be useful for mortality prediction and the determination of a need for empiric antibacterials. Although studies evaluating these biomarkers are promising, these biomarkers are not without limitations and should be used in combination with clinical signs, symptoms, or other biomarkers. For successful implementation of biomarker use, stewardship programs should consider the populations most likely to benefit, without using them indiscriminately in all patients. Antimicrobial stewardship programs should facilitate education of clinicians through institutional guidelines to ensure the appropriate use and interpretation of these biomarkers. As the incidence of antimicrobial resistance increases in clinical settings, antimicrobial stewardship programs (ASPs) are focusing efforts on the appropriate diagnosis of infections and the subsequent use of antimicrobials. In many cases, clinical and diagnostic uncertainty Accepted Article This article is protected by copyright. All rights reserved. of the origin or cause of infection leads to unnecessary antimicrobial prescribing or continuation. 1 Furthermore, diagnostic uncertainty may result in missed opportunities to initiate therapy, resulting in delayed time to antimicrobial therapy and poor outcomes. 2 As ASPs receive international attention and recognition for improving patient care by optimizing antimicrobial therapy, program directors and participants are constantly evaluating tools that may assist in improving efficiency. Traditional biomarkers (white blood count, C-reactive protein, etc.) have been used clinically by both medical and antimicrobial stewardship teams to make treatment decisions. In recent years, novel biomarkers have been increasingly used to assist clinical decision-making, including those made by ASPs. Novel biomarkers, when used in conjunction with other strategies in an antimicrobial stewardship program, can play an important role in improving diagnostic uncertainty and antimicrobial use. The purpose of this review is to evaluate procalcitonin, beta-D-glucan, Candida albicans germ tube antibody, galactomannan, adrenomedullin, and soluble triggering receptor on myeloid cells-1 as possible biomarker additions to the antimicrobial stewardship armamentarium, particularly for suspected sepsis or pneumonia. Methods A systematic literature search using PubMed/MEDLINE databases was performed using each biomarker name separately and then combined with search terms including infection, antimicrobial stewardship, sepsis, diagnosis, pneumonia, respiratory infections, fungal infections, candidiasis, candidemia, aspergillus, and outcomes. The researchers reviewed trials published in English from 1946 to November 2017 and examined article titles and abstracts for possible inclusion. References within articles of interest were evaluated to capture additional sources.
With an increasing number of antimicrobial stewardship-related articles published each year, atte... more With an increasing number of antimicrobial stewardship-related articles published each year, attempting to stay current is challenging. The Southeastern Research Group Endeavor (SERGE-45) identified antimicrobial stewardship-related peer-reviewed literature that detailed an actionable intervention for 2018. The top 13 publications were selected using a modified Delphi technique. These manuscripts were reviewed to highlight the actionable intervention used by antimicrobial stewardship programs to provide key stewardship literature for teaching and training as well as to identify potential intervention opportunities within one's institution.
The elderly population can be divided into three distinct age groups: 65-74 years (young-old), 75... more The elderly population can be divided into three distinct age groups: 65-74 years (young-old), 75-84 years (middle-old), and 85? years (old-old). Despite evidence of a shift in leading causes for mortality in the elderly from infectious diseases to chronic conditions, infections are still a serious cause of death in this population. These patients are at increased risk due to weakened immune systems, an increased prevalence of underlying comorbidities, and decreased physiologic reserves to fight infection. Additionally, elderly patients, especially adults in institutional settings, are at an increased risk of colonization and subsequent infection with methicillin-resistant Staphylococcus aureus at a rate that is five times higher than in younger individuals, causing an increase in empiric and definitive vancomycin use. Elderly patients have unique characteristics that make dosing vancomycin a challenge for clinicians, such as increased volume of distribution and decreased renal function. Using the best available evidence, it is recommended to initiate lower empiric maintenance doses and monitor vancomycin serum concentrations earlier than steady state to accurately calculate drug elimination and make appropriate dose adjustments. Key Points Elderly patients are at increased risk for infection, especially with methicillin-resistant Staphylococcus aureus. Debate still exists over how to calculate creatinine clearance in elderly patients. Dosing vancomycin is challenging in elderly patients, and lower empiric maintenance dosing with earlier concentration monitoring is advised.
The American Journal of Pharmaceutical Education, 2019
To describe admission scores, including multiple miniinterview (MMI), pre-pharmacy average (PPA) ... more To describe admission scores, including multiple miniinterview (MMI), pre-pharmacy average (PPA) and Pharmacy College Admission Test (PCAT), and covariates (age, prior degree, re-application, gender), in cohorts admitted in 2011 and 2012 to the PharmD program at University of Toronto. To determine predictive validity of admission scores and covariates, with respect to year 3 grade point average (GPA), year 4 advanced pharmacy practice experience (APPE) rotations, and scores on Pharmacy Examining Board of Canada (PEBC) Qualifying Examinations: multiple choice question (MCQ) and objective structured clinical examination (OSCE). Methods: Descriptive statistics and correlations were determined for admission scores and covariates. Multiple linear regression analyses were conducted with PPA, PCAT composite, and MMI scores as predictor variables. Dependent variables were Year 3 GPA, APPE scores (community and institutional), PEBC-MCQ and OSCE scores. Results: Consenting students admitted in 2011 and 2012 with matched PEBC scores totaled 229 (56.8% female) and 219 (64.8% female), respectively.
Background. Children with osteomyelitis transitioned to oral step-down therapy experience similar... more Background. Children with osteomyelitis transitioned to oral step-down therapy experience similar outcomes to those treated with outpatient parenteral antibiotic therapy (OPAT). Compared with OPAT, oral therapy has lower costs and avoids catheter complications. However, few studies have specifically compared patient outcomes between those receiving oral therapy vs. OPAT for osteomyelitis with associated bacteremia caused by MRSA. Methods. We performed a retrospective cohort study comparing early oral therapy (EOT), defined as transition to oral therapy at or prior to discharge vs. use of OPAT at discharge. We identified hospitalized children <19 years of age with MRSA osteomyelitis with bacteremia between 2007 and 2014 from three children's hospitals. The primary outcome was treatment failure within 6 months of discharge, defined as unplanned change in antibiotic after discharge, development of chronic osteomyelitis, need for an operative procedure after discharge, or recrudescence of bacteremia. The secondary outcome was treatment-related events, defined as documented adverse drug events in the medical record and/or central venous catheter complications. Betweengroup comparisons were made using Fisher exact test for binomial distributions and the Wilcoxon rank-sum test for continuous variables. Results. We included 61 patients with MRSA osteomyelitis with bacteremia. Twenty-five patients (41%) received EOT and 36 (59%) received OPAT. Duration of bacteremia and hospital length of stay was similar between groups (Table 1). Clindamycin was the most commonly used antibiotic in both the EOT (24/25; 96%) and OPAT (22/36; 61%) groups. Clinical failure occurred in 1/25 (4%) children receiving EOT and in 5/36 (14%) in the OPAT group (95% CI of difference: −29 to 6%; P = 0.38, Table 1). Treatmentrelated adverse events occurred in 1/25 (4%) children receiving EOT compared with 9/36 (25%) receiving OPAT (95% CI of difference: −49 to-7%; P = 0.04, Table 1). Conclusion. Children receiving EOT for MRSA osteomyelitis with bacteremia did not experience higher rates of clinical failure and had fewer treatment-related complications compared with OPAT. Oral step-down therapy can be considered for children with MRSA osteomyelitis with bacteremia.
While overall survival with multiple myeloma (MM) has improved, patients suffer from overwhelming... more While overall survival with multiple myeloma (MM) has improved, patients suffer from overwhelming tumor burden, MM-associated comorbidities, and frequent relapses requiring administration of salvage therapies. As a result, this vicious cycle is often characterized by cumulative immunodeficiency stemming from a combination of disease- and treatment-related factors leading to neutropenia, T-cell deficiency, and hypogammaglobulinemia. Infectious etiologies differ based on the duration of MM and treatment-related factors, such as number of previous treatments and cumulative dose of corticosteroids. Herein, we present the case of a patient who was receiving pomalidomide without concomitant corticosteroids for MM and was later found to have cryptococcosis, as well as findings from a literature review. Most cases of cryptococcosis are reported in patients with late-stage MM, as well as those receiving novel anti-myeloma agents, such as pomalidomide, in combination with corticosteroids or following transplantation. However, it is likely cryptococcosis may be underdiagnosed in this population. Due to the cumulative immunodeficiency present in patients with MM, clinicians must be suspicious of cryptococcosis at any stage of MM.
Background. Obesity is a major medical issue nationally, with rates continually increasing. In ob... more Background. Obesity is a major medical issue nationally, with rates continually increasing. In obese patients, minimal data exist for appropriate dosing of acyclovir to decrease the rates of nephrotoxicity. The purpose of this study was to determine the prevalence of and risk factors associated with acyclovir-induced nephrotoxicity. Methods. A retrospective case-control of patients who received intravenous acyclovir for >48 hours at the University of Mississippi Medical Center over a 4-year period were evaluated to elucidate the prevalence of acyclovir-induced nephrotoxicity. Additionally, risk factors for the development of nephrotoxicity, including the effect of obesity and dosing strategy, were assessed. Results. One hundred fifteen patients were included in the study. A total of 24 (21%) patients developed nephrotoxicity after acyclovir exposure and were in the Risk (9.6%), Injury (4.3%), and Failure (7%) categories, defined by the RIFLE criteria. Neither acyclovir dosage, fluid status, nor baseline characteristics, other than obesity, varied between those who developed nephrotoxicity vs those who did not. Independent predictors of nephrotoxicity were obesity (odds ratio [OR], 3.2; 95% confidence interval [CI], 1.19-8.67) and receipt of vancomycin (OR, 4.73; 95% CI, 1.57-14.25). No differences in vancomycin dosing or concentrations were observed between the patients who developed nephrotoxicity and those who did not. Conclusions. In this study, nephrotoxicity occurred in 21% of patients receiving acyclovir. Concomitant vancomycin receipt and obesity led to higher rates of toxicity. Efforts should be made to target obese patients on acyclovir plus vancomycin and discontinue therapy in patients not warranting antiviral coverage to minimize chances of toxicity.
Journal of Clinical Pharmacy and Therapeutics, Nov 19, 2013
Fungal infections pose a constant risk to critically ill and immunosuppressed patients. The echin... more Fungal infections pose a constant risk to critically ill and immunosuppressed patients. The echinocandin antifungals give practitioners an arsenal of agents with apparently lower toxicity relative to older agents. The objective of this commentary is to review the cardiac toxicity of the echinocandin antifungals in the light of recent evidence and published case reports. Three case reports detail cardiac decompensation following the initiation of anidulafungin and caspofungin and corroborate ex vivo laboratory results, in which rat hearts exposed to anidulafungin and caspofungin had significantly decreased cardiac contractility. Our hypothesized mechanism of toxicity of anidulafungin and caspofungin is mitochondrial toxicity. The clinical corroboration of the ex vivo work presented above highly suggests that the cardiac toxicity seen with some of the echinocandin antifungals is a cause and effect pattern, not a chance finding.
Introduction. Staphylococcus spp. represent the leading cause of hospital-acquired infections and... more Introduction. Staphylococcus spp. represent the leading cause of hospital-acquired infections and second-most frequent pathogen in bloodstream infections. Methicillin-susceptible S. aureus (MSSA) comprise approximately half of all S. aureus isolates. Standard-of-care therapies (SOCTs) display high treatment success but require frequent dosing, are problematic in penicillin allergic patients, and are nephrotoxic. Ceftriaxone may represent an alternative treatment option. Methods. Adult patients hospitalized from January 2015 through June 2016 with positive MSSA blood cultures and treated with SOCT or ceftriaxone for ≥48 hours were included. Exclusion criteria were receipt of vancomycin or concomitant systemic antimicrobials with activity against MSSA, polymicrobial infections, and pregnant patients. Additional data collected included demographics, source/site of infection, and treatment. e primary endpoint was clinical cure (normalization of white blood cell count and temperature within 7 days and clearance of bloodstream within 7 days). Readmission within 60 days, length of stay, and discharge disposition were collected. Results. A total of 43 patients were included: 23 receiving SOCT and 20 receiving ceftriaxone group. Sixteen patients received SOCT prior to ceftriaxone while 4 patients were initiated on ceftriaxone. Clinical cure was observed in 18/23 (78%) and 10/20 (50%), respectively (P � 0.052). Clinical failure was driven by leukocytosis despite clearance of their bloodstream infection in 3/23 (13%) SOCT group compared to 8/20 (40%) in the ceftriaxone group (P � 0.043). Six patients (SOCT: 2, ceftriaxone: 4; p � 0.669) had infection-related readmissions, and 1 death per group was observed. Conclusion. Ceftriaxone poses a reasonable alternative to consider for MSSA bacteremia when cost and feasibility are concerns for outpatient parenteral therapy after initial clearance of bloodstream infections.
Keeping abreast of the antimicrobial stewardship-related articles published each year is challeng... more Keeping abreast of the antimicrobial stewardship-related articles published each year is challenging. The Southeastern Research Group Endeavor (SERGE-45) identified antimicrobial stewardship-related, peer-reviewed literature that detailed an "actionable" intervention among hospitalized populations during 2021. The top 13 publications were selected using a modified Delphi technique. These manuscripts were reviewed to highlight "actionable" interventions used by antimicrobial stewardship programs in hospitalized populations to capture potentially effective strategies for local implementation.
HIV care providers. These results have implications to engage more PLWH into care, particularly i... more HIV care providers. These results have implications to engage more PLWH into care, particularly in states that have increased access to primary care through healthcare expansions.
Although beta-lactam allergies are an emerging focus of stewardship programs and interventions, l... more Although beta-lactam allergies are an emerging focus of stewardship programs and interventions, less is publicly released regarding allergies to beta-lactamase inhibitors. This review presents and evaluates the data regarding allergic reactions with beta-lactamase inhibitors. Clavulanate, sulbactam, and tazobactam are beta-lactam-based beta-lactamase inhibitors that are combined with several penicillins or cephalosporins in order to preserve antimicrobial activity in the presence of beta-lactamases. Avibactam, relebactam, and vaborbactam are non-beta-lactam beta-lactamase inhibitors that are combined with cephalosporins or carbapenems in order to expand the antimicrobial activity against broader-spectrum beta-lactamases. Case reports document hypersensitivity reactions to clavulanate, sulbactam, and tazobactam, but not to avibactam, relebactam, or vaborbactam. Based on these reports and considering the chemical structures, cross-allergenicity with beta-lactams is likely with sulbactam and tazobactam. Considering the slightly altered beta-lactam structure, cross-allergenicity is less likely with clavulanate, but still possible. It appears that cross-allergenicity between beta-lactam antimicrobials and the newer, non-beta-lactam beta-lactamase inhibitors is unlikely. It is important for clinicians to perform allergy testing to both the beta-lactam and the beta-lactamase inhibitor in order to confirm the specific allergy and reaction type.
Therapeutic advances in infectious disease, Dec 10, 2017
Background: Candidemia represents a leading cause of healthcare-associated bloodstream infections... more Background: Candidemia represents a leading cause of healthcare-associated bloodstream infections with significant morbidity and mortality. Previous studies have demonstrated that comprehensive care bundles improve candidemia management but are time-consuming. Objective: To determine the impact of a one-time targeted candidemia intervention on time to initiation of adequate therapy compared to standard of care. Methods: This Institutional Review Board (IRB)-approved, quasi-experiment evaluated a targeted candidemia intervention involving a single phone call to the primary team providing recommendations for care. Daily follow-up was provided by the infectious diseases (ID) consult service. Two time periods were evaluated: pre-intervention (01 August 2012 to 31 July 2014) and post-intervention (01 October 2014 to 30 September 2016). The primary endpoint was time to adequate antifungal therapy (TTx) in the business hours (6 a.m. to 6 p.m. Monday through Friday) population (BHP). Secondary endpoints were TTx in the total population as well as infection-related length of stay (IF-LOS) and compliance with quality indicators (composite endpoint: ophthalmology (OPH) consult, repeat cultures, and ⩾14 days of adequate therapy). Results: In all, 117 patients were included (pre-intervention = 50, post-intervention = 67, BHP = 51). TTx decreased from 2 h 57 m to 2 h 12 m (p = 0.094) in the BHP and 3 h 30 m to 2 h 9 m (p = 0.021) in the total population. There was no difference in IF-LOS (p = 0.797), compliance with quality indicators (p = 0.343), or in-hospital mortality (p = 0.761). Post-intervention, there were more ID and OPH consults (p < 0.001). Conclusions: Our one-time candidemia intervention did not statistically decrease time to adequate therapy in the BHP, but did in the total population. No differences were found for other clinical outcomes, except increases in ID and OPH consults. Further studies are needed to examine whether a one-time intervention is non-inferior to a more comprehensive care bundle.
JACCP: journal of the American College of Clinical Pharmacy, Oct 8, 2021
IntroductionAdvances in technology and understanding of pharmacokinetic/pharmacodynamic relations... more IntroductionAdvances in technology and understanding of pharmacokinetic/pharmacodynamic relationships have prompted guideline updates and advances in precision dosing, but the role of clinical pharmacokinetics (PK) in pharmacy education remains inconsistent. Previous surveys of pharmacy school PK curricula revealed large variations in content, integration, and teaching tools but did not focus on antimicrobials or details of andragogy used.ObjectiveIdentify how antimicrobial PK is taught in pharmacy curricula across the United States, as well as instructor perceptions of current practices.MethodsAn online survey was distributed to 118 pharmacy programs across the United States in 2018. This 30‐minute questionnaire covered curriculum content, teaching strategies, assessment modalities, and perceptions.ResultsCompleted surveys were received from 53 programs (45% response rate) via relevant course coordinators. Among 35 traditional progressive curriculum programs (TPC), antimicrobial PK was taught in basic science (33, 94%), clinical PK (15, 43%), pharmacology (8, 23%), therapeutics (28, 80%), and skills lab courses (21, 65%). Among 18 integrated block curriculum programs (IBC), it was taught in foundations/principles (17, 94%), organ systems (12, 67%), and skills lab courses (9, 50%). On average, TPC programs had more courses with antimicrobial PK than IBC programs. Vancomycin and aminoglycosides were the most common antimicrobials taught (100%), while didactic lecturing was the predominant andragogy. Multiple choice was the primary assessment modality, being frequently used in 64% of TPC and 68% of IBC courses, respectively. Among respondents, 72% believed more time was needed to teach PK and 53% believed students were adequately prepared at the start of APPEs.ConclusionAntimicrobial PK instruction remains highly inconsistent in U.S. pharmacy schools and colleges. IBC programs may provide less opportunity for antimicrobial PK instruction, which conflicts with the desire for more instruction time. As clinical applications of antimicrobial PK change and expand, it is crucial that pharmacy education prioritizes PK education appropriately.
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Introduction. Carbapenem-resistant Enterobacteriaceae (CRE) are an urgent threat in the USA and a... more Introduction. Carbapenem-resistant Enterobacteriaceae (CRE) are an urgent threat in the USA and are associated with adverse clinical and economic outcomes. Several studies have evaluated risk factors for acquiring CRE versus carbapenem-susceptible Enterobacteriaceae , identifying antibiotic use and length of hospital stay as major players. However, no studies have compared risk factors for CRE colonization versus infection. Hypothesis/Gap Statement. Patients with CRE infection will have different risk factors and worse clinical outcomes than patients with CRE colonization. Aim. To assess clinical outcomes in patients with CRE infection versus CRE colonization. Methodology. A retrospective cohort of adult patients admitted between 1 June 2013 and 31 July 2018 with the first positive CRE culture from any source was performed. Patients were divided into two groups: CRE infection versus CRE colonization. Data collected included demographics, comorbidities, past antimicrobial usage and clinical outcomes (length of stay, in-hospital mortality). The primary outcome was infection-related length of stay. Data analysis was performed utilizing SPSS with a two-sided P value of less than 0.05 considered statistically significant. Results. A total of 56 patients were included (32 with infection; 24 with colonization). Baseline characteristics were similar between both groups. Infected patients were more likely to have higher actual body weight compared to colonized patients (P=0.03). CRE-infected patients had a longer infection-related hospital stay [12 days (5–20) and 7.5 days (1–13), respectively; P=0.08], but in-hospital mortality was similar between infected and colonized patients (37.5 and 29.2 %, respectively; P=0.30). Patients with infection were more likely to have previous exposure to levofloxacin (P=0.02) and trimethoprim/sulfamethoxazole (P=0.03) for a median of 9 days compared to those with colonization. The most common source of CRE in infected patients was the blood compared to respiratory sources in colonized patients. Conclusion. CRE infection as opposed to colonization was more common in patients with previous exposure to levofloxacin and trimethoprim/sulfamethoxazole and those with higher actual body weight.
TO THE EDITOR-We read with interest the article by Humphries and Hindler on the challenges of ant... more TO THE EDITOR-We read with interest the article by Humphries and Hindler on the challenges of antimicrobial susceptibility testing (AST) in light of the changing resistance and regulatory landscape [1]. Many of the issues highlighted potentially hamper antimicrobial stewardship efforts
As antimicrobial stewardship increasingly receives worldwide attention for improving patient care... more As antimicrobial stewardship increasingly receives worldwide attention for improving patient care by optimizing antimicrobial therapy, programs are evaluating new tools that may augment antimicrobial stewardship activities. Biomarkers are objective, accurate, and reproducible measures that provide information about medical conditions. A systematic literature search using PubMed/MEDLINE databases was performed to evaluate the use of novel biomarkers as additions to the antimicrobial stewardship armamentarium. Procalcitonin may help clinicians discriminate between bacterial and viral infections, help with antimicrobial discontinuation decisions, and predict mortality. Beta-D-glucan, Candida albicans germ tube antibody, and galactomannan are useful in suspected fungal infections, and may reduce inappropriate antifungal use. Adrenomedullin and soluble triggering receptor on myeloid cells-1 may be useful for mortality prediction and the determination of a need for empiric antibacterials. Although studies evaluating these biomarkers are promising, these biomarkers are not without limitations and should be used in combination with clinical signs, symptoms, or other biomarkers. For successful implementation of biomarker use, stewardship programs should consider the populations most likely to benefit, without using them indiscriminately in all patients. Antimicrobial stewardship programs should facilitate education of clinicians through institutional guidelines to ensure the appropriate use and interpretation of these biomarkers. As the incidence of antimicrobial resistance increases in clinical settings, antimicrobial stewardship programs (ASPs) are focusing efforts on the appropriate diagnosis of infections and the subsequent use of antimicrobials. In many cases, clinical and diagnostic uncertainty Accepted Article This article is protected by copyright. All rights reserved. of the origin or cause of infection leads to unnecessary antimicrobial prescribing or continuation. 1 Furthermore, diagnostic uncertainty may result in missed opportunities to initiate therapy, resulting in delayed time to antimicrobial therapy and poor outcomes. 2 As ASPs receive international attention and recognition for improving patient care by optimizing antimicrobial therapy, program directors and participants are constantly evaluating tools that may assist in improving efficiency. Traditional biomarkers (white blood count, C-reactive protein, etc.) have been used clinically by both medical and antimicrobial stewardship teams to make treatment decisions. In recent years, novel biomarkers have been increasingly used to assist clinical decision-making, including those made by ASPs. Novel biomarkers, when used in conjunction with other strategies in an antimicrobial stewardship program, can play an important role in improving diagnostic uncertainty and antimicrobial use. The purpose of this review is to evaluate procalcitonin, beta-D-glucan, Candida albicans germ tube antibody, galactomannan, adrenomedullin, and soluble triggering receptor on myeloid cells-1 as possible biomarker additions to the antimicrobial stewardship armamentarium, particularly for suspected sepsis or pneumonia. Methods A systematic literature search using PubMed/MEDLINE databases was performed using each biomarker name separately and then combined with search terms including infection, antimicrobial stewardship, sepsis, diagnosis, pneumonia, respiratory infections, fungal infections, candidiasis, candidemia, aspergillus, and outcomes. The researchers reviewed trials published in English from 1946 to November 2017 and examined article titles and abstracts for possible inclusion. References within articles of interest were evaluated to capture additional sources.
With an increasing number of antimicrobial stewardship-related articles published each year, atte... more With an increasing number of antimicrobial stewardship-related articles published each year, attempting to stay current is challenging. The Southeastern Research Group Endeavor (SERGE-45) identified antimicrobial stewardship-related peer-reviewed literature that detailed an actionable intervention for 2018. The top 13 publications were selected using a modified Delphi technique. These manuscripts were reviewed to highlight the actionable intervention used by antimicrobial stewardship programs to provide key stewardship literature for teaching and training as well as to identify potential intervention opportunities within one's institution.
The elderly population can be divided into three distinct age groups: 65-74 years (young-old), 75... more The elderly population can be divided into three distinct age groups: 65-74 years (young-old), 75-84 years (middle-old), and 85? years (old-old). Despite evidence of a shift in leading causes for mortality in the elderly from infectious diseases to chronic conditions, infections are still a serious cause of death in this population. These patients are at increased risk due to weakened immune systems, an increased prevalence of underlying comorbidities, and decreased physiologic reserves to fight infection. Additionally, elderly patients, especially adults in institutional settings, are at an increased risk of colonization and subsequent infection with methicillin-resistant Staphylococcus aureus at a rate that is five times higher than in younger individuals, causing an increase in empiric and definitive vancomycin use. Elderly patients have unique characteristics that make dosing vancomycin a challenge for clinicians, such as increased volume of distribution and decreased renal function. Using the best available evidence, it is recommended to initiate lower empiric maintenance doses and monitor vancomycin serum concentrations earlier than steady state to accurately calculate drug elimination and make appropriate dose adjustments. Key Points Elderly patients are at increased risk for infection, especially with methicillin-resistant Staphylococcus aureus. Debate still exists over how to calculate creatinine clearance in elderly patients. Dosing vancomycin is challenging in elderly patients, and lower empiric maintenance dosing with earlier concentration monitoring is advised.
The American Journal of Pharmaceutical Education, 2019
To describe admission scores, including multiple miniinterview (MMI), pre-pharmacy average (PPA) ... more To describe admission scores, including multiple miniinterview (MMI), pre-pharmacy average (PPA) and Pharmacy College Admission Test (PCAT), and covariates (age, prior degree, re-application, gender), in cohorts admitted in 2011 and 2012 to the PharmD program at University of Toronto. To determine predictive validity of admission scores and covariates, with respect to year 3 grade point average (GPA), year 4 advanced pharmacy practice experience (APPE) rotations, and scores on Pharmacy Examining Board of Canada (PEBC) Qualifying Examinations: multiple choice question (MCQ) and objective structured clinical examination (OSCE). Methods: Descriptive statistics and correlations were determined for admission scores and covariates. Multiple linear regression analyses were conducted with PPA, PCAT composite, and MMI scores as predictor variables. Dependent variables were Year 3 GPA, APPE scores (community and institutional), PEBC-MCQ and OSCE scores. Results: Consenting students admitted in 2011 and 2012 with matched PEBC scores totaled 229 (56.8% female) and 219 (64.8% female), respectively.
Background. Children with osteomyelitis transitioned to oral step-down therapy experience similar... more Background. Children with osteomyelitis transitioned to oral step-down therapy experience similar outcomes to those treated with outpatient parenteral antibiotic therapy (OPAT). Compared with OPAT, oral therapy has lower costs and avoids catheter complications. However, few studies have specifically compared patient outcomes between those receiving oral therapy vs. OPAT for osteomyelitis with associated bacteremia caused by MRSA. Methods. We performed a retrospective cohort study comparing early oral therapy (EOT), defined as transition to oral therapy at or prior to discharge vs. use of OPAT at discharge. We identified hospitalized children <19 years of age with MRSA osteomyelitis with bacteremia between 2007 and 2014 from three children's hospitals. The primary outcome was treatment failure within 6 months of discharge, defined as unplanned change in antibiotic after discharge, development of chronic osteomyelitis, need for an operative procedure after discharge, or recrudescence of bacteremia. The secondary outcome was treatment-related events, defined as documented adverse drug events in the medical record and/or central venous catheter complications. Betweengroup comparisons were made using Fisher exact test for binomial distributions and the Wilcoxon rank-sum test for continuous variables. Results. We included 61 patients with MRSA osteomyelitis with bacteremia. Twenty-five patients (41%) received EOT and 36 (59%) received OPAT. Duration of bacteremia and hospital length of stay was similar between groups (Table 1). Clindamycin was the most commonly used antibiotic in both the EOT (24/25; 96%) and OPAT (22/36; 61%) groups. Clinical failure occurred in 1/25 (4%) children receiving EOT and in 5/36 (14%) in the OPAT group (95% CI of difference: −29 to 6%; P = 0.38, Table 1). Treatmentrelated adverse events occurred in 1/25 (4%) children receiving EOT compared with 9/36 (25%) receiving OPAT (95% CI of difference: −49 to-7%; P = 0.04, Table 1). Conclusion. Children receiving EOT for MRSA osteomyelitis with bacteremia did not experience higher rates of clinical failure and had fewer treatment-related complications compared with OPAT. Oral step-down therapy can be considered for children with MRSA osteomyelitis with bacteremia.
While overall survival with multiple myeloma (MM) has improved, patients suffer from overwhelming... more While overall survival with multiple myeloma (MM) has improved, patients suffer from overwhelming tumor burden, MM-associated comorbidities, and frequent relapses requiring administration of salvage therapies. As a result, this vicious cycle is often characterized by cumulative immunodeficiency stemming from a combination of disease- and treatment-related factors leading to neutropenia, T-cell deficiency, and hypogammaglobulinemia. Infectious etiologies differ based on the duration of MM and treatment-related factors, such as number of previous treatments and cumulative dose of corticosteroids. Herein, we present the case of a patient who was receiving pomalidomide without concomitant corticosteroids for MM and was later found to have cryptococcosis, as well as findings from a literature review. Most cases of cryptococcosis are reported in patients with late-stage MM, as well as those receiving novel anti-myeloma agents, such as pomalidomide, in combination with corticosteroids or following transplantation. However, it is likely cryptococcosis may be underdiagnosed in this population. Due to the cumulative immunodeficiency present in patients with MM, clinicians must be suspicious of cryptococcosis at any stage of MM.
Background. Obesity is a major medical issue nationally, with rates continually increasing. In ob... more Background. Obesity is a major medical issue nationally, with rates continually increasing. In obese patients, minimal data exist for appropriate dosing of acyclovir to decrease the rates of nephrotoxicity. The purpose of this study was to determine the prevalence of and risk factors associated with acyclovir-induced nephrotoxicity. Methods. A retrospective case-control of patients who received intravenous acyclovir for >48 hours at the University of Mississippi Medical Center over a 4-year period were evaluated to elucidate the prevalence of acyclovir-induced nephrotoxicity. Additionally, risk factors for the development of nephrotoxicity, including the effect of obesity and dosing strategy, were assessed. Results. One hundred fifteen patients were included in the study. A total of 24 (21%) patients developed nephrotoxicity after acyclovir exposure and were in the Risk (9.6%), Injury (4.3%), and Failure (7%) categories, defined by the RIFLE criteria. Neither acyclovir dosage, fluid status, nor baseline characteristics, other than obesity, varied between those who developed nephrotoxicity vs those who did not. Independent predictors of nephrotoxicity were obesity (odds ratio [OR], 3.2; 95% confidence interval [CI], 1.19-8.67) and receipt of vancomycin (OR, 4.73; 95% CI, 1.57-14.25). No differences in vancomycin dosing or concentrations were observed between the patients who developed nephrotoxicity and those who did not. Conclusions. In this study, nephrotoxicity occurred in 21% of patients receiving acyclovir. Concomitant vancomycin receipt and obesity led to higher rates of toxicity. Efforts should be made to target obese patients on acyclovir plus vancomycin and discontinue therapy in patients not warranting antiviral coverage to minimize chances of toxicity.
Journal of Clinical Pharmacy and Therapeutics, Nov 19, 2013
Fungal infections pose a constant risk to critically ill and immunosuppressed patients. The echin... more Fungal infections pose a constant risk to critically ill and immunosuppressed patients. The echinocandin antifungals give practitioners an arsenal of agents with apparently lower toxicity relative to older agents. The objective of this commentary is to review the cardiac toxicity of the echinocandin antifungals in the light of recent evidence and published case reports. Three case reports detail cardiac decompensation following the initiation of anidulafungin and caspofungin and corroborate ex vivo laboratory results, in which rat hearts exposed to anidulafungin and caspofungin had significantly decreased cardiac contractility. Our hypothesized mechanism of toxicity of anidulafungin and caspofungin is mitochondrial toxicity. The clinical corroboration of the ex vivo work presented above highly suggests that the cardiac toxicity seen with some of the echinocandin antifungals is a cause and effect pattern, not a chance finding.
Introduction. Staphylococcus spp. represent the leading cause of hospital-acquired infections and... more Introduction. Staphylococcus spp. represent the leading cause of hospital-acquired infections and second-most frequent pathogen in bloodstream infections. Methicillin-susceptible S. aureus (MSSA) comprise approximately half of all S. aureus isolates. Standard-of-care therapies (SOCTs) display high treatment success but require frequent dosing, are problematic in penicillin allergic patients, and are nephrotoxic. Ceftriaxone may represent an alternative treatment option. Methods. Adult patients hospitalized from January 2015 through June 2016 with positive MSSA blood cultures and treated with SOCT or ceftriaxone for ≥48 hours were included. Exclusion criteria were receipt of vancomycin or concomitant systemic antimicrobials with activity against MSSA, polymicrobial infections, and pregnant patients. Additional data collected included demographics, source/site of infection, and treatment. e primary endpoint was clinical cure (normalization of white blood cell count and temperature within 7 days and clearance of bloodstream within 7 days). Readmission within 60 days, length of stay, and discharge disposition were collected. Results. A total of 43 patients were included: 23 receiving SOCT and 20 receiving ceftriaxone group. Sixteen patients received SOCT prior to ceftriaxone while 4 patients were initiated on ceftriaxone. Clinical cure was observed in 18/23 (78%) and 10/20 (50%), respectively (P � 0.052). Clinical failure was driven by leukocytosis despite clearance of their bloodstream infection in 3/23 (13%) SOCT group compared to 8/20 (40%) in the ceftriaxone group (P � 0.043). Six patients (SOCT: 2, ceftriaxone: 4; p � 0.669) had infection-related readmissions, and 1 death per group was observed. Conclusion. Ceftriaxone poses a reasonable alternative to consider for MSSA bacteremia when cost and feasibility are concerns for outpatient parenteral therapy after initial clearance of bloodstream infections.
Keeping abreast of the antimicrobial stewardship-related articles published each year is challeng... more Keeping abreast of the antimicrobial stewardship-related articles published each year is challenging. The Southeastern Research Group Endeavor (SERGE-45) identified antimicrobial stewardship-related, peer-reviewed literature that detailed an "actionable" intervention among hospitalized populations during 2021. The top 13 publications were selected using a modified Delphi technique. These manuscripts were reviewed to highlight "actionable" interventions used by antimicrobial stewardship programs in hospitalized populations to capture potentially effective strategies for local implementation.
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