Stability of 4 Intravenous Drug Formulations in Prefilled Syringes Stored Frozen for Up to 60 Days.

Purpose: Prefilled drug syringe use may reduce the cost of routine antibiotic drug delivery. Storage of prefilled syringes frozen (-20°C) or refrigerated (4°C-5°C), can optimize the use of robotic syringe filling systems if acceptable stability data is gathered per USP 797 standards. Methods: Four intravenous (IV) drug formulations were prepared from bulk standard solutions and filled into 10 mL syringes using an Intellifill© IV Robot. Formulations were Piperacillin (2.0 g) and Tazobactam (0.25 g) as 2.25 g in 10 mL; Piperacillin (3.0 g) and Tazobactam (0.375 g) as 3.375 g in 10 mL; Cefuroxime as 1.5 g in 11 mL; and Vancomycin as 1.0 g in 10 mL. Concentrations were assayed at "zero time," and after 21, 45, and 60 days frozen. Syringes were warmed to room temperature (RT) by gently rolling in hands. Three syringes of each formulation were assayed by stability-indicating HPLC per USP procedures. Assay results are the average of 5 injections of samples from each syringe upon return to RT and repeated for 3 separate syringes maintained at RT for 24 hours. Results: All formulations were stable out to 60 days frozen. Both of the piperacillin/tazobactam formulations were also stable when kept at refrigerated temperature for 9 days. Conclusion: Piperacillin/Tazobactam formulations can be stored frozen (-20°C) for up to 60 days with no appreciable loss. Cefuroxime and Vancomycin formulations can be stored frozen for up to 60 days. Both Piperacillin/Tazobactam formulations can be refrigerated for up to 9 days. Implementation of larger batch compounding coupled with frozen syringe storage and delivery could result in enhanced uniformity of composition and significant manpower savings.

Acute Kidney Injury in Patients Continued on Renin-Angiotensin System Blockers During Hospitalization.

BACKGROUND: Acute kidney injury (AKI) is common in hospitalized patients and is associated with adverse outcomes. This study aimed to evaluate patient characteristics and interventions during hospitalization associated with the development of AKI in patients continued on renin-angiotensin system (RAS) blockers during hospitalization. METHODS: A retrospective study of 184 adult patients admitted between January 2012 and September 2014 and continued on RAS blockers was conducted. Risk factors for AKI were compared between AKI (n = 92) and non-AKI (n = 92) groups. RESULTS: Patients who developed hospital-acquired AKI had a higher baseline serum creatinine (1.2 ± 0.4 versus 1 ± 0.3mg/dL, P < 0.001) and lower estimated glomerular filtration rate (54 ± 10 versus 57 ± 7mL/minute/1.73m2, P = 0.03) compared with patients who did not develop AKI. Patients who developed AKI were also more likely to be admitted to the intensive care unit, have surgical procedures, have hypotension and be prescribed loop diuretics. The presence of chronic kidney disease and hypotension were risk factors associated with AKI development. In addition, the AKI group had a significantly longer length of stay (14 days versus 8 days, P < 0.0001) and had a higher rate of all-cause hospital mortality (9% versus 1%, P = 0.03). CONCLUSIONS: Patients with chronic kidney disease, hypotension and those undergoing surgeries were more likely to develop AKI while receiving RAS blockers. During hospitalization, temporary discontinuation of these medications may be warranted in patients with these characteristics.

Impact of recommended weight-based dosing of granulocyte-colony stimulating factors in acute leukemia and stem cell transplant patients.

PURPOSE: Febrile neutropenia (FN) is a major risk factor for infection-related morbidity and mortality. The National Comprehensive Cancer Network recommends the prophylactic use of granulocyte-colony stimulating factors (G-CSF), dosed at 5 mcg/kg and rounded to the nearest vial size. A previous medication use evaluation conducted within a multi-hospital healthcare system demonstrated that only 67% of patients were started on appropriate weight-based dosing. The purpose of this study was to evaluate the effect of appropriate weight-based G-CSF dosing in patients on clinical outcomes. METHODS: A retrospective chart review of patients with acute leukemia or stem cell transplant recipients who received G-CSF from May 2009 to September 2015 was conducted. Patient admissions were reviewed in regards to neutropenia length, incidence of FN, length of stay, and final disposition (alive or deceased). Admissions were divided into one of three weight-based dosing groups of under 5 mcg/kg, recommended 5 mcg/kg within a 10% range, and over 5 mcg/kg which were named under, recommended, and over, respectively. RESULTS: Ninety-four admissions were included. Average age of this patient population was 58 years old, and the majority of patients were male (53%) and Caucasian (55%). Majority of patients had been diagnosed with acute myeloid leukemia (91%). Data showed average duration of neutropenia was around 10 days regardless if the patient received under 5 mcg/kg, the recommended 5 mcg/kg or over 5 mcg/kg G-CSF (10.1 ± 6.7 days, 8.9 ± 9.2 days, 10.1 ± 9.1 days, respectively). Length of stay was similar for patients regardless of initial G-CSF dose (29.6 ± 16.0 days, 29.1 ± 18.4 days, and 24.5 ± 17.0, respectively). However, the incidence of FN was significantly greater for those who received under 5 mcg/kg of G-CSF (87% for under, 68% for recommended, and 54% for over). CONCLUSIONS: In this retrospective analysis, variations from the recommended 5 mcg/kg G-CSF dose did not significantly impact length of neutropenia, length of stay, nor mortality. However, patients who received under the 5 mcg/kg of G-CSF dose may be at a greater risk of FN.

Impact of a discharge medication therapy management program in an extended care hospital.

OBJECTIVES: To study the feasibility and effectiveness of a discharge medication therapy management program. DESIGN: Quasi-experimental pre-post study design. SETTING: Thirty-six-bed hospital within an extended care hospital. PARTICIPANTS: All patients admitted to facility from January 2009 to December 2009 (control) and February 2010 to January 2011 (program). INTERVENTION: Pharmacist review of anticipated discharge following 18-20 days of stay, with suggested medication changes communicated to physicians via patient chart. Agreed changes were implemented on the next day. MEASUREMENTS: Patient readmissions within 30, 60, and 90 days into the hospital system. Medication interventions were quantified as to type. RESULTS: During the control period, 432 patients were followed, and during the intervention period, 369 patients were followed, with similar lengths of stay. In the intervention period, 565 medication interventions were attempted on 216 patients, with an 85.3% acceptance rate. The major intervention was discontinuation of medications. Mean maintenance medications per patient decreased from 10.57 to 9.46 in the intervention group, and daily medication doses per patient decreased from 17.95 to 15.73 (P < 0.001). Readmission rates were lower at 30 and 60 days in the intervention group, with a 90-day overall decrease in system readmission rate from 51% to 39% (P < 0.001). CONCLUSION: The discharge medication management program was successful in decreasing both number and type of discharge medications via pharmacist intervention. Overall, patient system readmission rates were also significantly decreased in the intervention period.

Evaluation of vancomycin and gentamicin dialysis clearance using in vivo and in vitro systems.

Advances in hemodialysis (HD) techniques have increased the potential for drug removal. Quantifying drug clearance in clinical studies for all possible dialysis conditions is impractical, given the variability in dialysis conditions. The purpose of this study was to determine the dialysis clearance (CL(D)) of vancomycin and gentamicin using in vitro and in vivo methods and evaluate the applicability of in vitro data. In vitro dialysis was used to determine the CL(D) of vancomycin and gentamicin under conditions of intermittent HD (IHD) and sustained low-efficiency dialysis (SLED). Two Fresenius polysulfone dialyzers were studied: F180NR for IHD and F50 for SLED. Data were compared with in vivo CL(D) determined in patients with end-stage renal disease receiving IHD and from the literature for SLED. Under IHD conditions, in vitro CL(D) of vancomycin and gentamicin was 131 ± 3 and 154 ± 3 mL/min, respectively, and under SLED condition it was 72 ± 9 and 84 ± 11 mL/min, respectively. These values were 11-27% higher than in vivo CL(D) for IHD (103 ± 15 mL/min for vancomycin and 132 ± 25 mL/min for gentamicin) and SLED (63 mL/min for vancomycin and 76 ± 38 mL/min for gentamicin). There was a statistically significant difference in vancomycin clearance by IHD for the in vitro study compared with in vivo data (p = 0.012), but not for gentamicin (p = 0.18). In vitro methods overestimated in vivo CL(D), but are reasonable to assist with drug regimen design if one considers the limitations.

Vancomycin-resistant Enterococcus bacteremia: an evaluation of treatment with linezolid or daptomycin.

BACKGROUND: Due to high rates of resistance and a limited number of efficacious antimicrobials for vancomycin-resistant Enterococcus (VRE), appropriate antibiotic selection is vital to treatment success. The purpose of this study was to assess clinical and microbiologic outcomes associated with the use of linezolid or daptomycin in the treatment of VRE bacteremia. METHODS: A retrospective analysis of adult patients with VRE bacteremia between January 2004 and July 2009 was conducted at a tertiary care hospital in the United States. Clinical and microbiologic outcomes for both therapies were evaluated using multiple criteria. RESULTS: Of the 361 patients with VRE bacteremia identified, 201 were included in the study (linezolid group, n = 138; daptomycin group, n = 63). More patients in the daptomycin group had hematologic malignancies (33% vs 14%) or received liver transplants (13% vs 4%). There was no difference in clinical or microbiologic cure between the linezolid and daptomycin groups (74% vs 75% and 94% vs 94%, respectively). Recurrence was documented in 3% of linezolid patients vs 12% of daptomycin patients (P = 0.0321). Reinfection was noted in 1% of patients in the linezolid group vs 6% of patients in the daptomycin group (P not significant). The average length of stay (LOS) was 37 days for the linezolid group vs 40 days for the daptomycin group (P not significant). Overall mortality was 20%, occurring in 25/138 linezolid patients vs 15/63 daptomycin patients (P not significant). CONCLUSIONS: No differences in clinical or microbiologic cure rates, LOS, or mortality were identified between the groups. Various factors may have contributed to the significantly higher recurrence of VRE bacteremia in daptomycin patients. This study suggests that linezolid and daptomycin appear equally efficacious in the treatment of VRE bacteremia.

Early vs delayed enteral nutrition in critically ill medical patients.

This study was conducted to identify current practice in provision of enteral nutrition (EN) and to determine effects of early enteral nutrition (EEN) on length of stay in the medical intensive care unit (ICU). In this prospective, observational study, medical ICU patients were evaluated to determine their candidacy for EEN. If patients were candidates for EN and expected to remain nothing-by-mouth for 48 hours, they were classified as receiving EEN (within 24 hours of admission) or delayed EN. Thirty-six patients were candidates for EEN. Eighteen received EEN and 18 received delayed EN. In the delayed group, the median time to start of EN was 2.1 +/- 4.8 days. Median ICU length of stay was 4.7 +/- 3.5 days in the EEN group compared with 8.5 +/- 8.3 days in the delayed group. Although hospital length of stay was shorter in the EEN group, this was not statistically significant (10.4 +/- 6.9 vs 16.9 +/- 11.5 days). Time on the ventilator was significantly shorter in the EEN group vs delayed (n = 30, 3.0 +/- 4.2 vs 6.0 +/- 9.2 days). The incidence of new pneumonia was lower in the EEN group (5.5% vs 44%), but no difference was found in the incidence of bacteremia. Hospital mortality was lower in the EEN group (1 vs 7 deaths). Given its association with numerous benefits, EEN within 24 hours of admission should be encouraged and implemented by clinicians in medical ICU patients, but additional research is needed.

Evaluation of glycemic control following discontinuation of an intensive insulin protocol.

BACKGROUND: Intensive insulin protocols (IIPs) have been demonstrated to reduce morbidity and mortality in critically ill patients. Currently, there are no published studies evaluating glycemic control after discontinuation of an IIP. OBJECTIVE: The purpose of this study was to compare blood glucose (BG) control during an IIP and for 5 days following its discontinuation (follow-up period). METHODS: The study was a retrospective review of intensive care unit patients who received an IIP for >or=24 hours. Data were collected during the last 12 hours of the IIP and subsequent follow-up period. RESULTS: For all 65 included patients, the mean +/- standard deviation for BG on the IIP was 123 +/- 26 mg/dL versus 168 +/- 50 mg/dL following discontinuation of the IIP (P < 0.001). The median (interquartile range) insulin that was administered decreased from 40 (22-65) units on the IIP to 8 (0-18) units after the IIP was stopped (P < 0.001). The mean daily BG during the follow-up period was significantly higher than that during the IIP (P < 0.001). Additionally, an insulin requirement of >20 units during the last 12 hours of the IIP was identified as a risk factor for poor glycemic control during the follow-up period (odds ratio: 4.62; 95% confidence interval: 1.17-18.17). CONCLUSIONS: This study demonstrates a significant increase in BG following discontinuation of an IIP. Higher insulin requirements during the last 12 hours of an IIP were identified as an independent risk factor for poor glycemic control following the IIP. A standardized insulin transition protocol may help better control BG after discontinuation of an IIP.