Athena L. V. Hobbs

Implications of Augmented Renal Clearance on Drug Dosing in Critically Ill Patients: A Focus on Antibiotics.

Augmented renal clearance (ARC) has been reported in approximately 30–65% of patients in the intensive care unit (ICU) despite the presence of a normal serum creatinine concentration. In certain ICU patient populations (e.g., patients with sepsis or trauma), the incidence increases to roughly 50–85%. Risk factors for ARC include the following: age younger than 50–55 years, male sex, higher diastolic blood pressure, fewer comorbidities, and a lower Acute Physiology and Chronic Health Evaluation II (APACHE II) or modified Sequential Organ Failure Assessment (SOFA) score at ICU admission. In addition, patient populations with the highest reported incidence of ARC include those with major trauma, sepsis, traumatic brain injury, subarachnoid hemorrhage, and central nervous system infection. Due to the high incidence of ARC in patients with a normal serum creatinine concentration, clinicians should consider screening ICU patients deemed high risk by using the ARC scoring system or the identification and assessment algorithm provided in this review. In addition, an 8‐hour continuous urine collection should be considered to assess a measured creatinine clearance for evaluating the necessity of medication dosage adjustments. There is a clear association between ARC and subtherapeutic antibiotic concentrations as well as literature suggesting worse clinical outcomes; thus, the risk of underdosing antibiotics in a patient with ARC could increase the risk of treatment failure. This review examines strategies to overcome ARC and summarizes current pharmacokinetic and pharmacodynamic literature in patients with ARC in an effort to provide dosing guidance for this patient population.

Evaluating the Impact of the Addition of Cladribine to Standard Acute Myeloid Leukemia Induction Therapy

Background: Treatment for acute myeloid leukemia (AML) has remained relatively unchanged over the past few decades. Although recent drug approvals have provided an increase in the number of treatment options in AML, further optimization of standard induction therapy is still necessary. The most commonly utilized induction options have been well studied, but there is a paucity of literature comparing the combination of idarubicin with cytarabine and cladribine. Objective: To assess the clinical effectiveness of the addition of cladribine to idarubicin and cytarabine (7+3 IA) induction therapy in the treatment of AML. Methods: This retrospective, propensity score–matched cohort study evaluated 37 patients with previously untreated AML who received either 7+3 IA or idarubicin, cytarabine, and cladribine (7+3+5 IAC) as induction therapy. The primary end point of this study was complete response (CR), with secondary end points including hospital length of stay (LOS), and adverse event rates. Results: After propensity score matching, odds of reaching CR in the 7+3+5 IAC cohort were increased by 33% (95% CI = 1.09-1.55; P < 0.01) compared with the 7+3 IA cohort. Patients who received cladribine were also found to have a reduction in hospital LOS by 3.5 days (95% CI = 0.07-6.85; P = 0.045) without an increase in adverse event rates. Conclusion: The addition of cladribine to the 7+3 IA regimen may improve clinical outcomes when used as initial induction therapy, without increasing the incidence of adverse event rates.

Are first-generation cephalosporins obsolete? A retrospective, non-inferiority, cohort study comparing empirical therapy with cefazolin versus ceftriaxone for acute pyelonephritis in hospitalized patients

OBJECTIVES Literature is lacking regarding the utilization of first-generation cephalosporins for the treatment of acute pyelonephritis. The aim of this study was to determine whether cefazolin is non-inferior to ceftriaxone for the empirical treatment of acute pyelonephritis in hospitalized patients. The primary outcome included a composite of symptomatic resolution plus either defervescence at 72 h or normalization of serum white blood cell count at 72 h (non-inferiority margin 15%). Secondary outcomes included length of stay and 30 day readmission. A subgroup analysis of the composite outcome was also conducted for imaging-confirmed pyelonephritis. METHODS This was a retrospective, non-inferiority, multicentre, cohort study comparing cefazolin versus ceftriaxone for the empirical treatment of acute pyelonephritis in hospitalized patients. RESULTS Overall, 184 patients received one of the two treatments between July 2009 and March 2015. The composite outcome was achieved in 80/92 (87.0%) in the cefazolin group versus 79/92 (85.9%) in the ceftriaxone group (absolute difference 1.1%, 95% CI -11.1% to 8.9%, P = 0.83), meeting the pre-defined criteria for non-inferiority. The composite outcome for patients with imaging-confirmed pyelonephritis was achieved in 46/56 (82.1%) versus 42/50 (84.0%) for the cefazolin group and the ceftriaxone group, respectively (absolute difference 1.9%, 95% CI -12.8% to 16.5%, P = 0.80). Additionally, there were no statistically significant differences in length of stay or 30 day readmission for cystitis or pyelonephritis. CONCLUSIONS Cefazolin was non-inferior to ceftriaxone with regard to clinical response for the treatment of hospitalized patients with acute pyelonephritis in this study. No difference was observed for length of stay or 30 day readmission.

Variability in Emergency Medicine Provider Decisions on Hospital Admission and Antibiotic Treatment in a Survey Study for Acute Bacterial Skin and Skin Structure Infections: Opportunities for Antimicrobial Stewardship Education

Abstract Background Acute bacterial skin and skin structure infections (ABSSSIs) are a frequent cause of emergency department (ED) visits. Providers in the ED have many decisions to make during the initial treatment of ABSSSI. There are limited data on the patient factors that influence these provider decisions. Methods An anonymous survey was administered to providers at 6 EDs across the United States. The survey presented patient cases with ABSSSIs ≥75 cm2 and escalating clinical scenarios including relapse, controlled diabetes, and sepsis. For each case, participants were queried on their decision for admission vs discharge and antibiotic therapy (intravenous, oral, or both) and to rank the factors that influenced their antibiotic decision. Results The survey was completed by 130 providers. For simple ABSSSI, the majority of providers chose an oral antibiotic and discharged patients home. The presence of recurrence or controlled diabetes resulted in more variation in responses. Thirty-four (40%) and 51 (60%) providers chose intravenous followed by oral antibiotics and discharged the recurrence and diabetes cases, respectively. Presentation with sepsis resulted in initiation with intravenous antibiotics (122, 95.3%) and admission (125, 96.1%) in most responses. Conclusions Variability in responses to certain patient scenarios suggests opportunities for education of providers in the ED and the development of an ABSSSI clinical pathway to help guide treatment.

Effectiveness of a bundled approach to reduce urinary catheters and infection rates in trauma patients

HighlightsCAUTI prevention should include multifactorial efforts that work synergistically.Optimal technical aspects of urinary catheterization minimize risk for patient harm.Standardized urine culturing practices decrease risk for false‐positive cultures.Negative pyuria on urinalysis can rule out a CAUTI, but is not solely diagnostic.A multidisciplinary team can prospectively ensure accountability for processes. Background: Catheter‐associated urinary tract infections (CAUTIs) are common nosocomial infections. In 2015, the Centers for Medicare and Medicaid Services began imposing financial penalties for institutions where CAUTI rates are higher than predicted. However, the surveillance definition for CAUTI is not a clinical diagnosis and may represent asymptomatic bacteriuria. The objective of this study was to compare rates of urinary catheterization and CAUTI before and after the implementation of a bundled intervention. Methods: This retrospective review evaluated trauma patients from January 2013‐January 2015. The bundled intervention optimized the urinary catheterization process and culturing practices to reduce false positives. The CAUTI rate was defined as a positive surveillance CAUTI divided by total catheter days multiplied by 1,000 days. Results: A total of 6,236 patients were included (pre: n = 5,003; post: n = 1,233). Fewer patients in the post bundle group received a urinary catheter (pre: 25% vs post: 16%; P < .001). After bundle implementation, the CAUTI rate reduced over one third (pre: 4.07 vs post: 2.56; incidence rate ratio, 0.63; 95% confidence interval, 0.19‐2.07). Conclusions: Although the number of patients exposed to urinary catheters and catheter days was decreased, optimization of culturing practices was essential to prevent the CAUTI rate from increasing from a reduced denominator. Implementation of a CAUTI prevention bundle works synergistically to improve patient safety and hospital performance.

Impact of an antiretroviral stewardship strategy on medication error rates

PURPOSE The impact of an antiretroviral stewardship strategy on medication error rates was evaluated. METHODS This single-center, retrospective, comparative cohort study included patients at least 18 years of age infected with human immunodeficiency virus (HIV) who were receiving antiretrovirals and admitted to the hospital. A multicomponent approach was developed and implemented and included modifications to the order-entry and verification system, pharmacist education, and a pharmacist-led antiretroviral therapy checklist. Pharmacists performed prospective audits using the checklist at the time of order verification. To assess the impact of the intervention, a retrospective review was performed before and after implementation to assess antiretroviral errors. RESULTS Totals of 208 and 24 errors were identified before and after the intervention, respectively, resulting in a significant reduction in the overall error rate (p < 0.001). In the postintervention group, significantly lower medication error rates were found in both patient admissions containing at least 1 medication error (p < 0.001) and those with 2 or more errors (p < 0.001). Significant reductions were also identified in each error type, including incorrect/incomplete medication regimen, incorrect dosing regimen, incorrect renal dose adjustment, incorrect administration, and the presence of a major drug-drug interaction. A regression tree selected ritonavir as the only specific medication that best predicted more errors preintervention (p < 0.001); however, no antiretrovirals reliably predicted errors postintervention. CONCLUSION An antiretroviral stewardship strategy for hospitalized HIV patients including prospective audit by staff pharmacists through use of an antiretroviral medication therapy checklist at the time of order verification decreased error rates.

Patient Preferences in the Emergency Department (ED) Before Treatment for Acute Bacterial Skin and Skin Structure Infection (ABSSSI)

Abstract Background Reducing hospital admission and improving transitions of care can lessen the burden of ABSSSIs in EDs and hospitals. Limited research to date has assessed the patient’s preference for ABSSSI treatment. Understanding patient preferences may provide insights that encourage optimal treatment plans and improve satisfaction with their care. Methods A patient survey was conducted across 5 hospital EDs in the US. After providing informed consent, patients with ABSSSI completed a baseline survey assessing their ABSSSI history and preferences for antibiotic (ABX) therapy [intravenous (IV) vs. oral] and treatment location. Patient characteristics and ensuing treatment details were collected from the medical record after the ED or hospitalization was completed. Descriptive statistics were used for analyses. Results Seventy-one patients were enrolled and completed the baseline survey. The mean ± SD age was 50 ± 17 years, 22 (31%) had diabetes, and 47 (66.2%) had a previous ABSSSI. The median (25th-75th quartile) lesion size was 190 (53-613) cm2; 51 (71.8%) presented with cellulitis, an abscess, or both. Fifty-four (76.1%) were admitted to the hospital with a median (25th-75thquartile) length of stay of 4.5 (2-9) days. In the ED, vancomycin (39.4%) and β-lactams (36.6%) were the most common ABX; IV was prescribed in 58/63 (92.1%) patients. Once admitted, 37 (68.5%) and 34 (63%) patients received vancomycin and β-lactams, respectively. When surveyed, 26 (36.6%) patients preferred to receive ABX at home, while 22 (31.0%) chose hospital stay for one or more nights. The most common ABX preference was a single IV dose to complete treatment, selected by 29 (40.8%) patients. The most important ABX factors were efficacy and their doctor’s opinion, then convenience and route of administration; least important were treatment location, adverse events, and cost. Conclusion In these patients presenting to the ED with ABSSSI, the majority were admitted to the hospital and received IV ABX. Patient preferences for treatment location varied, but many valued therapies that could prevent admission. These data suggest opportunities for improving ABSSSI care by engaging the patient and offering treatment alternatives they may not be aware of. Disclosures K. R. Keyloun, Allergan: Employee, Salary. D. P. Nicolau, Allergan: Grant Investigator, Scientific Advisor and Speaker’s Bureau, Consulting fee, Research grant and Speaker honorarium. J. L. Kuti, Allergan: Grant Investigator, Investigator, Scientific Advisor and Speaker’s Bureau, Consulting fee, Research grant and Speaker honorarium

Is More Always Better? Effect of a Combination Pseudomonas Antibiogram on Levofloxacin Use and Patient Outcomes for Pneumonia in a Large Community Hospital

Abstract Background Evidence suggests that combination therapy for Pseudomonas pneumonia only provides mortality benefit in critically ill patients. In November 2015, the Antimicrobial Stewardship Subcommittee at Baptist Memorial Hospital-Memphis (BMH-Memphis) developed a combination Pseudomonasantibiogram and guideline, based on local susceptibilities, for critically ill patients with Hospital Acquired Pneumonia (HAP), Health Care Associated Pneumonia (HCAP), or Ventilator Associated Pneumonia (VAP). Methods This is a single center, retrospective study evaluating patients admitted to the BMH-Memphis medical intensive care unit (MICU) and surgical intensive care unit (SICU) with a diagnosis-related group (DRG) code for HAP, HCAP, or VAP.The primary objective of this study was to compare levofloxacin days of therapy per 1000 patient-days (DOT/1000 patient-days) before and after implementation of the combination Pseudomonas antibiogram guideline at BMH-Memphis. Secondary objectives included a comparison of individual levofloxacin orders, 30-day mortality, hospital length of stay (LOS), ICU LOS, 90-day incidence of extended spectrum β-lactamases (ESBLs), and 30-day readmission rates and incidence of Clostridium difficile. Adverse events including acute kidney injury and QTc prolongation were also evaluated pre- and post-implementation of the guideline. Results A total 150 patients were included in this study to meet power for the primary objective. Levofloxacin DOT/1000 patient-days was reduced by 3.4 days in the post-implementation period (P < 0.001) with a 63% reduction in individual levofloxacin orders (P < 0.001). Furthermore, there were significantly lower 30-day mortality rates in the post-implementation period, which persisted in a multivariate logistic regression analysis (P = 0.01). There was no difference in hospital or ICU LOS, 30 day readmission rates or incidence of Clostridium difficile,or 90-day incidence of ESBLs. There was also no difference in adverse events between the two study periods. Conclusion This study demonstrates that the implementation of a combination anti-pseudomonal guideline can decrease levofloxacin use while reducing 30-day mortality rates without increasing hospital or ICU LOS. Disclosures All authors: No reported disclosures.

Variability in Emergency Medicine (EM) Provider Decisions on Hospital Admission and Antibiotic (ABX) Treatment for Acute Bacterial Skin and Skin Structure Infections (ABSSSI)

Abstract Background ABSSSI are a frequent cause of emergency room visits. Physicians (PHY) and Advanced Practice Providers (APP) have many decisions to make during the initial treatment of ABSSSI, including intravenous (IV) vs. oral (PO) ABX, and hospital admission vs. discharge home. There are limited data, however, on factors that influence the provider’s decision for the treatment of ABSSSI. Methods An anonymous survey was offered to EM providers at 5 hospitals across the US. The survey presented patient cases with ABSSSI ≥ 75cm2 and escalating clinical scenarios including relapse, controlled diabetes (DM), and SIRS. For each case, participants were queried on their decision for admission vs. discharge, ABX therapy (IV, PO, or both), and to rank factors that influenced their ABX decision. Descriptive and inferential statistics were used for analyses. Results Across the 5 hospitals, 104 providers completed the survey; 59 (56.7%) were PHY and 45 (43.3%) were APP. Experience was evenly represented with 50 (48.1%) providers practicing for ≥5 years and 54 (51.9%) less than 5 years. For the first case with no relapse, DM, or SIRS, most providers selected PO ABX [95 (91.4%)] and discharge [100 (96.2%)]. In case 2, the presence of relapse resulted in PO ABX for 50 (48.1%) and discharge in 54 (51.9%) of responses. In case 3, the presence of controlled DM resulted in PO ABX for 55 (53.4%) and discharge home in 65 (63.1%) of responses. Four (3.8%) and 13 (12.5%) providers chose to give 1–2 IV doses followed by PO and discharge the relapsed and DM cases, respectively. Compared with APP, PHY more frequently prescribed PO ABX for the DM case (62.7% vs. 40.9%, P = 0.046) and incorporated PO ABX into the treatment of the SIRS case (48.3% vs. 22.7%, P = 0.015). The addition of SIRS criteria in case 4 resulted in initiation with IV ABX [97 (95.1%)] and admission [100 (96.2%)]. The highest ranked factors influencing ABX selection were infection severity and co-morbidities; the lowest were patient convenience, adverse events, and cost. Conclusion These data highlight factors influencing EM provider decisions in the treatment of ABSSSI. Variability in responses to patient cases suggests opportunities for education and the development of an ABSSSI clinical pathway to guide treatment. Disclosures K. R. Keyloun, Allergan: Employee, Salary. D. P. Nicolau, Allergan: Grant Investigator, Scientific Advisor and Speaker’s Bureau, Consulting fee, Research grant and Speaker honorarium. J. L. Kuti, Allergan: Grant Investigator, Investigator, Scientific Advisor and Speaker’s Bureau, Consulting fee, Research grant and Speaker honorarium

Clostridium difficile Infection Rates Reduced at a Health Care System after Restriction of Respiratory Fluoroquinolones

Fluoroquinolones are one of the most commonly prescribed antibiotic classes in the United States and up to 81% of inpatient utilization has been deemed inappropriate. Our study, recently published in Antimicrobial Agents of Chemotherapy, aimed to determine the impact of respiratory fluoroquinolone education and restriction on utilization, appropriateness of quinolone-based therapy, and CDI rates within a health care system. Both phases of implementation were successful at significantly reducing respiratory fluoroquinolone utilization as well as CDI rates. Utilization was reduced by 48% after clinician education and 88% following implementation of restriction criteria. Mean monthly CDI cases also decreased by approximately 50% from pre-intervention to post-restriction.