Katherine Shea

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.

Effect of a Health Care System Respiratory Fluoroquinolone Restriction Program To Alter Utilization and Impact Rates of Clostridium difficile Infection.

ABSTRACT Fluoroquinolones are one of the most commonly prescribed antibiotic classes in the United States despite their association with adverse consequences, including Clostridium difficile infection (CDI). We sought to evaluate the impact of a health care system antimicrobial stewardship-initiated respiratory fluoroquinolone restriction program on utilization, appropriateness of quinolone-based therapy based on institutional guidelines, and CDI rates. After implementation, respiratory fluoroquinolone utilization decreased from a monthly mean and standard deviation (SD) of 41.0 (SD = 4.4) days of therapy (DOT) per 1,000 patient days (PD) preintervention to 21.5 (SD = 6.4) DOT/1,000 PD and 4.8 (SD = 3.6) DOT/1,000 PD posteducation and postrestriction, respectively. Using segmented regression analysis, both education (14.5 DOT/1,000 PD per month decrease; P = 0.023) and restriction (24.5 DOT/1,000 PD per month decrease; P < 0.0001) were associated with decreased utilization. In addition, the CDI rates decreased significantly (P = 0.044) from preintervention using education (3.43 cases/10,000 PD) and restriction (2.2 cases/10,000 PD). Mean monthly CDI cases/10,000 PD decreased from 4.0 (SD = 2.1) preintervention to 2.2 (SD = 1.35) postrestriction. A significant increase in appropriate respiratory fluoroquinolone use occurred postrestriction versus preintervention in patients administered at least one dose (74/130 [57%] versus 74/232 [32%]; P < 0.001), as well as in those receiving two or more doses (47/65 [72%] versus 67/191 [35%]; P < 0.001). A significant reduction in the annual acquisition cost of moxifloxacin, the formulary respiratory fluoroquinolone, was observed postrestriction compared to preintervention within the health care system (

Operational and Clinical Strategies to Address Drug Cost Containment in the Acute Care Setting

123,882 versus

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

12,273; P = 0.002). Implementation of a stewardship-initiated respiratory fluoroquinolone restriction program can increase appropriate use while reducing overall utilization, acquisition cost, and CDI rates within a health care system.

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

To provide clinical and operational strategies to generate drug cost savings in the hospital setting.

Impact of an antiretroviral stewardship strategy on medication error rates

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.

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

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.

659: IMPACT OF A URINE CULTURE ORDERING PROCESS ON CATHETER-ASSOCIATED URINARY TRACT INFECTIONS IN AN ICU

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.

Antibiotic Utilization and Antimicrobial Stewardship in Community Hospitals

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.