Assessing febrile neutropenia outcomes in patients receiving primary versus secondary prophylactic G-CSF treatment therapy with intermediate neutropenic risk chemotherapy regimens.

BACKGROUND: Prophylaxis with granulocyte colony-stimulating factors (G-CSFs) reduce the severity and duration of chemotherapy-induced neutropenia. Currently, the use of G-CSF prophylactic treatment to prevent neutropenia and its complications varies widely in clinical practice with no standardization for intermediate-risk chemotherapy regimens. OBJECTIVE: The purpose of this study was to assess neutropenic outcomes in patients receiving intermediate-risk chemotherapy regimens who receive primary versus secondary prophylactic G-CSFs. METHODS: This is a retrospective, multicenter cohort study of patients who received intermediate risk chemotherapy regimens and at least one dose of G-CSF therapy. 121 patients were included and were divided into primary (n = 76) or secondary prophylaxis (n = 45) groups. The primary outcome for this study was the incidence of neutropenic episodes per course of treatment. The secondary outcomes included the percentage of patients who experienced delays in chemotherapy doses, the number of chemotherapy dose reductions, and the number of subsequent treatment delays. RESULTS: The incidence of neutropenic episodes over the course of therapy was 0.42 episodes in the primary group compared to 1.52 episodes in the secondary group (p < 0.05). 10.5% of patients in the primary group versus 54.3% of patients in the secondary group experienced chemotherapy dose delays (p < 0.05). There were no statistically significant differences in chemotherapy dose reductions or in the average number of FN risk factors between groups. CONCLUSION: This retrospective, cohort study determined that patients receiving intermediate risk chemotherapy regimens should receive primary prophylaxis, regardless of risk factors in order to decrease episodes of neutropenia and chemotherapy dose delays.

Combination therapy for disseminated strongyloidiasis with associated vancomycin-resistant, linezolid-intermediate Enterococcus faecium meningitis: A case report.

WHAT IS KNOWN AND OBJECTIVE: The rhabditid nematode Strongyloides stercoralis is the major causative agent of disseminated strongyloidiasis (DS). In rare cases, DS has caused enterococcal meningitis. If DS-associated vancomycin-resistant Enterococcus faecium (VRE) meningitis is suspected, combination antibiotic therapy should be considered. CASE SUMMARY: We present a case of a 61-year-old male who developed DS associated with vancomycin-resistant and linezolid-intermediate E. faecium meningitis after receiving corticosteroids. The VRE meningitis was treated with high-dose daptomycin 12 mg/kg, linezolid, tigecycline and quinupristin/dalfopristin. Despite negative cultures, the patient expired. WHAT IS NEW AND CONCLUSION: In patients with DS-associated VRE meningitis, early use of combination therapy may be warranted to improve patient outcomes.

Assessing mortality outcomes of beta-lactam-allergic patients presenting with sepsis.

OBJECTIVE: To determine the impact of reported beta-lactam allergies on in-hospital mortality and other clinical outcomes in patients who presented with severe sepsis or septic shock. METHODS: This single-center, retrospective cohort study was performed at a 35-bed emergency department in central Kentucky. Patients presenting with sepsis, aged 18years or older, were identified between October 2016 and June 2017. RESULTS: 438 patients with severe sepsis and/or septic shock were identified. Rates of the combined endpoint of in-hospital mortality or transfer to hospice were similar in patients with a beta-lactam allergy (7.2%) versus those with no reported beta-lactam allergy (10.4%) (p=0.41). Time to initiation of antibiotic therapy was slightly longer in the beta-lactam allergic group (2.2h) versus those with no reported beta-lactam allergy (2.15h), but the difference was not statistically significant (p=0.993). Patients were 20.9% more likely to receive an appropriate empiric antibiotic, based off of retrospective culture review, if they did not report a beta-lactam allergy (p=0.009). This led to a delay in effective therapy of 1.59h in the reported beta-lactam allergy arm (p=0.037). CONCLUSIONS: Adequate documentation of beta-lactam allergies is vital to ensure timely and appropriate treatment in patients presenting with severe sepsis and septic shock. Choosing alternative treatment options results in increased time to effective antibiotics, reduced likelihood of covering cultures with first antibiotic, and increased total hospital and variable direct cost.

Assessing the impact of CKD on outcomes in septic shock patients receiving standard Vs reduced initial fluid volume.

OBJECTIVE: To determine if following fluid resuscitation recommendations in the Surviving Sepsis Campaign guidelines affects hospital length of stay (LOS) in chronic kidney disease (CKD) patients who present to the emergency department with sepsis-induced hypotension or septic shock. DESIGN: Retrospective, single center, cohort study. SETTING: 433-bed community hospital with a 35-bed emergency department in central Kentucky. PATIENTS: Adults (≥18 years of age) who presented to the emergency department with severe sepsis or septic shock, as defined by the Centers for Medicare and Medicaid Services (CMS), with documented CKD and at least one episode of hypotension within 6 h of presentation. A total of 106 patients were included in the study. MEASUREMENTS AND MAIN RESULTS: Patients were stratified into two groups based on the total volume of weight-based crystalloid fluid bolus initiated within the first three hours of hypotension onset (<27 mL/kg and ≥ 27 mL/kg). There was a statistically significant reduction in the primary outcome of median LOS among patients who received less than 27 mL/kg of a crystalloid fluid bolus (5.1 vs 7.7 days, p = .003). Likewise, there was a statistically significant reduction in the secondary outcome of total cost per case in the reduced fluid volume cohort (p = .019. No significant differences were found in other secondary outcomes, including vasopressor requirements, ICU admission rate, and normalization of MAP at 6 h. CONCLUSION: The results of this single-center, retrospective study indicate that CKD patients who receive guideline-directed fluid resuscitation (≥27 mL/kg) for sepsis-induced hypotension or septic shock experience a longer hospital LOS compared to those who receive a reduced initial fluid volume.

Implementation of an adult code sepsis protocol and its impact on SEP-1 core measure perfect score attainment in the ED.

INTRODUCTION: Timely management of sepsis has become an urgent concern among most hospitals. Institutions have been searching for unique ways to increase the quality of care and timely adherence to proven therapies. The objective of this study was to determine the impact of an Adult Code Sepsis Protocol on the rate of SEP-1 perfect score attainment (PSA) among patients who presented to the emergency department (ED) with severe sepsis or septic shock, as defined by the Centers for Medicare and Medicaid Services (CMS). METHODS: This was a retrospective, observational cohort study in a 35-bed tertiary care hospital ED from December 2016 to February 2018. Adults (≥18 years of age) who met the CMS-case definition of severe sepsis or septic shock presenting to the ED either prior to or after implementation of an Adult Code Sepsis Protocol were included. RESULTS: The primary outcome of SEP-1 PSA, which was abstracted in an all-or-none fashion, increased from 30.7% to 71.3% (p < 0.001). Inpatient mortality was reduced from 4% to 0% (p = 0.011) after protocol implementation. Protocol initiation also resulted in a significant reduction in both time to initiation of appropriate, empiric and effective antimicrobial therapy, based on culture results by 48 and 111 min, respectively (p < 0.001). There were no significant differences in other secondary outcomes including ICU length-of-stay, readmission, or economic outcome measures. CONCLUSIONS: The addition of an Adult Code Sepsis Protocol in the ED significantly increased the rate of SEP-1 PSA, reduced inpatient mortality, and improved the time to initiation of effective antimicrobial therapy.

Intraosseous administration of 4-factor prothrombin complex concentrate prior to emergent surgery after receiving apixaban.

WHAT IS KNOWN AND OBJECTIVE: The 4-factor prothrombin complex concentrate (4F-PCC) may be used to emergently achieve haemostasis in patients on anticoagulation prior to surgery. Limited data exist using the intraosseous route of administration of 4F-PCC in patients taking factor Xa inhibitors. CASE DESCRIPTION: We describe a case of a 69-year-old female receiving oral apixaban that was successfully administered 4F-PCC using intraosseous access prior to emergent surgery to obtain haemostasis intraoperatively. WHAT IS NEW AND CONCLUSION: Intraosseous access may be a viable route of administration for 4F-PCC in patients receiving factor Xa inhibitors to achieve haemostasis when necessary.

Comparison of Hemostatic Outcomes in Patients Receiving Fixed-Dose vs. Weight-Based 4-Factor Prothrombin Complex Concentrate.

BACKGROUND: Four-factor prothrombin complex concentrate (4F-PCC) is a blood coagulation product indicated for urgent reversal of warfarin. Currently there are no studies using 4F-PCC as a fixed dose to achieve hemostasis with warfarin as well as direct factor Xa inhibitors. OBJECTIVES: The objective of this study was to evaluate the efficacy and safety of 4F-PCC administration using a fixed dose of approximately 2000 factor IX units to achieve hemostasis in anticoagulated patients, compared with weight-based therapy. METHODS: This single-center, retrospective cohort study was performed at a 433-bed tertiary care hospital in central Kentucky. Patients from January 1, 2014 to December 31, 2018 were included if they were 18 years or older and received 4F-PCC for hemostasis of oral anticoagulation. Efficacy was assessed by determining if clinically effective hemostasis was achieved after receiving a fixed-dose vs. a weight-based dose of 4F-PCC. RESULTS: Seventy-two patients were included in the study. Thirty-eight received weight-based dosing, compared with 34 receiving a fixed dose. Results yielded no statistical difference in clinically effective hemostasis using a fixed-dose vs. weight-based dosing, 91.2% and 78.9%, respectively (p = 0.150). There was no significant difference in adverse events, length of stay, or in-hospital mortality between groups; however, significant acquisition cost savings was realized. CONCLUSIONS: A fixed-dose regimen of approximately 2000 factor IX units of 4F-PCC may be a reasonable approach to achieve hemostasis in patients receiving warfarin or factor Xa inhibitors. Additionally, utilization of a fixed-dose regimen may lead to significant acquisition cost savings for facilities.

Pharmacy-Driven Dexmedetomidine Stewardship and Appropriate Use Guidelines in a Community Hospital Setting.

BACKGROUND: Dexmedetomidine is a widely utilized agent in the intensive care unit (ICU) because it does not suppress respiratory drive and may be associated with less delirium than midazolam or propofol. Cost of dexmedetomidine therapy and debate as to the proper duration of use has brought its use to the forefront of discussion. OBJECTIVE: To validate the efficacy and cost savings associated with pharmacy-driven dexmedetomidine appropriate use guidelines and stewardship in mechanically ventilated patients. METHODS: This was a retrospective cohort study of adult patients who received dexmedetomidine for ICU sedation while on mechanical ventilation at a 433-bed not-for-profit community hospital. Included patients were divided into pre-enactment (PRE) and postenactment (POST) of dexmedetomidine guideline groups. RESULTS: A total of 100 patients (50 PRE and 50 POST) were included in the analysis. A significant difference in duration of mechanical ventilation (11.1 vs 6.2 days, P = 0.006) and incidence of reintubation (36% vs 18% of patients, P = 0.043) was seen in the POST group. Aggregate use of dexmedetomidine 200-µg vials (37.1 vs 18.4 vials, P = 0.010) and infusion days (5.4 vs 2.5 days, P = 0.006) were significantly lower in the POST group. Dexmedetomidine acquisition cost savings were calculated at $374 456.15 in the POST group. There was no difference between the PRE and POST groups with regard to ICU length of stay, expected mortality, and observed mortality. CONCLUSIONS: Pharmacy-driven dexmedetomidine appropriate use guidelines decreased the use of dexmedetomidine and increased cost savings at a community hospital without adversely affecting clinical outcomes.

Evaluating Outcomes of a Pharmacist-Driven Pain Management Consult Service.

The opioid crisis continues to place a significant burden on American families and the healthcare system. To date, there is an evolving body of evidence demonstrating that pharmacists can positively impact patient care in the pain management specialty. The purpose of this study is to evaluate 24-hour average pain scores before and after a clinical pharmacist completes a physician-ordered pain consult in a community hospital setting. For the primary outcome, there was a statistically significant reduction in pain scores 48 hours post consult (6.5 vs. 5.2; p < 0.001; Table 3) and 24 hours prior to discharge (6.1 vs. 4.5; p < 0.001; Table 3) when compared to pain scores 24 hours prior to consult. Additionally, there was a statistically significant reduction in the number of morphine milligram equivalents (MMEs) at 48 hours post consult (149.4 vs. 133.8; p < 0.001; Table 4) and 24 hours prior to discharge (136.5 vs. 100.6; p < 0.001; Table 4) when compared to 24 hours prior to consult. This pharmacist-driven pain consult service demonstrated a statistically significant reduction in pain scores while simultaneously reducing MME utilization and the number of opioids ordered, using a multimodal evidence-driven approach to pain management in a community hospital.

Retrospective review of ceftriaxone versus levofloxacin for treatment of E. coli urinary tract infections.

Background Urinary tract infections (UTIs) are among the most common bacterial infections. Options for initial treatment of pyelonephritis or UTI requiring hospitalization include levofloxacin (LVF) or extended-spectrum cephalosporins. Globally, uropathogenic Escherichia coli resistance rates to fluoroquinolones have increased in recent years. Objective To compare clinical outcomes of patients receiving ceftriaxone (CTX) to those who received LVF empirically for the treatment of E. coli UTI. Setting 433-bed community hospital in Lexington, KY. Methods Retrospective, single center, cohort study of adults with a urine culture positive for E. coli who received either IV LVF or CTX empirically for the treatment of UTI. Main outcome measure The primary outcome was hospital length of stay. Secondary outcomes include time to susceptible therapy (TsT), hospital cost, and susceptibility to empiric therapy. Results There was no statistically significant difference in LOS or hospital cost. Subgroup analysis compared patients that received concordant CTX treatment and patients that received discordant LVF treatment. Patients that received concordant CTX treatment had a nonsignificant shorter median LOS (4.16 vs. 6.34 days). Median hospital cost was lower ($4345 vs. $8462, p = 0.004) and median TsT was shorter (5.83 vs. 64.46 h, p < 0.001) in the concordant CTX group. Conclusion Choice of empiric antibiotic therapy should be based on local antibiogram data. For patients with UTI requiring hospitalization, CTX seems to be an effective empiric therapy for most patients. More data is required to examine the effectiveness of local and source specific antibiograms on clinical outcomes when guiding treatment of patients with UTI.

Impact of real-time notification of Clostridium difficile test results and early initiation of effective antimicrobial therapy.

BACKGROUND: Clostridium difficile is a prominent nosocomial pathogen and is the most common causative organism of health care-associated diarrhea. To our knowledge, no studies have investigated the impact of real-time notification of culture results with rapid antimicrobial stewardship program (ASP) intervention in the setting of C difficile infection (CDI). The purpose of this study was to assess the impact of real-time notification of detection of toxigenic C difficile by DNA amplification results in patients with confirmed CDI. METHODS: This is a single-center, retrospective cohort study at a 433-bed tertiary medical center in central Kentucky. The study consisted of 2 arms: patients treated for CDI prior to implementation of real-time provider notification and patients postimplementation. The primary outcome was time to initiation of effective antimicrobial therapy. RESULTS: The median time to initiation of effective antimicrobial therapy decreased from 5.75 hours in the preimplementation cohort to 2.05 hours in the postimplementation cohort (P = .001). ASP intervention also resulted in a shorter time from detection of CDI to order entry of effective antimicrobial therapy in the patient's electronic medical record (3.0 vs 0.6 hours; P = .001). CONCLUSIONS: The implementation of a real-time notification system to alert a pharmacist-led ASP of toxigenic CDI resulted in statistically significant shorter times to order entry and subsequent initiation of effective antimicrobial therapy and contact precautions.

Clinical and economic impact of meropenem resistance in Pseudomonas aeruginosa-infected patients.

BACKGROUND: The emergence of carbapenem resistance has had a significant impact on both clinical and economic outcomes. METHODS: A retrospective, observational cohort study was performed in a 433-bed tertiary care medical center. The cohort was established from all inpatients with Pseudomonas aeruginosa-positive cultures over a 3-year period. Two multivariate models were developed: a logistic regression model to evaluate the primary outcome of in-hospital mortality and a linear regression model to evaluate the secondary outcome of total hospital cost. RESULTS: The adjusted odds ratio for in-hospital mortality among patients with meropenem-resistant isolates was 2.89 (95% confidence interval [CI], 1.15-7.28). There were significantly more deaths in the meropenem-resistant group (28.1% vs 8.9%, P = .003). Patients with meropenem-resistant P aeruginosa experienced a 4-day increase in median length of stay versus those in the meropenem-susceptible group (14 vs 9 days, P = .004). Likewise, the percentage of patients who required intensive care unit (ICU) admission increased from 42% to 81.3% (P <.001). Meropenem resistance was also associated with a significant increase in total hospital cost by a factor of 1.42 among patients who were not admitted to the ICU (95% CI, 1.03-1.95). CONCLUSIONS: Our results demonstrate that meropenem resistance was a significant predictor of in-hospital mortality. Carbapenem resistance also resulted in a significant increase in hospital cost, but only among patients who were not admitted to the ICU.

Evaluation of an alternative extended-infusion piperacillin-tazobactam dosing strategy for the treatment of gram-negative infections.

Introduction To enhance the probability of pharmacodynamic target attainment, piperacillin-tazobactam can be administered as either a continuous or extended-infusion dosage regimen for the treatment of gram-negative infections. Four hour extended-infusions of piperacillin-tazobactam 3.375 g administered intravenously (IV) every 8 h have been widely studied as an alternative to conventional, intermittent dosage regimens with largely favorable outcomes. Objective To assess the clinical and economic impact of a novel 3-h extended-infusion piperacillin-tazobactam dosing strategy for the treatment of gram-negative infections. Setting 433-bed community hospital in Lexington, KY. Methods Retrospective cohort study before and after the implementation of an alternative dosing protocol using a 3-h infusion of piperacillin-tazobactam 3.375 g IV every 6 h. Main outcome measures The primary outcome was in-hospital mortality. Secondary outcomes include length of stay, ICU length of stay, 30-day all-cause hospital readmissions, total cost per admission, complications, and a composite of in-hospital mortality and readmission within 30 days of discharge. Results Readmission within 30 days of hospital discharge was significantly reduced in the extended-infusion arm (1.2 vs. 13.7 %, P = 0.002). A composite endpoint of death or readmission was lower among patients who received the extended-infusion dosing regimen [ORadj 0.20; 95 % CI (0.07-0.57)]. However this was likely driven by reductions in readmission. Conclusion An alternative regimen of extended-infusion piperacillin-tazobactam resulted in a significant reduction in 30-day all-cause hospital readmission. These results indicate that 3-h infusions of piperacillin-tazobactam 3.375 g IV every 6 h may represent a clinically effective alternative to other commonly used regimens and results in fewer readmissions within 30 days.

Carfilzomib-associated tumor lysis syndrome.

Multiple myeloma is the second most common type of hematologic malignancy. It is a B-cell malignancy that affects the bone marrow and often results in thrombocytopenia as well as renal dysfunction. Treatment options range from oral and intravenous chemotherapy to bone marrow transplantation and supportive care. Carfilzomib was approved by the U.S. Food and Drug Administration in 2012 as a treatment option for patients with refractory multiple myeloma who have received at least two previous therapies and have demonstrated recent disease progression. According to the product labeling, the frequency of tumor lysis syndrome (TLS) is less than 1% in patients treated with carfilzomib. To our knowledge, no postmarketing events of TLS have been reported or published. We describe a 55-year-old man with relapsed multiple myeloma who developed a case of TLS that occurred after he received his first two doses of carfilzomib therapy on days 1 and 2; he also had chronic kidney disease secondary to his neoplastic disease. Beginning on day 4, his uric acid levels spiked to critical levels, prompting the use of rasburicase, which returned the levels to within normal limits. His phosphorus and creatinine levels increased during days 5 and 6. On day 8, the patient died, likely due to a combination of disease progression and the adverse effects of treatment. Use of the Naranjo adverse drug reaction probability scale indicated a probable relationship (score of 6) between the patient's development of TLS and carfilzomib therapy. The Hill criteria were used as a secondary measure to ensure causality, which also suggested a link between the patient's development of TLS and the administration of carfilzomib. This case report shows that even the most unlikely of adverse events may occur with medications, especially in the case of a new or recently approved medication. Caution must be taken when deciding to treat and when choosing hydration and premedications with regard to biologic and chemotherapeutic medications. In this case, additional hydration may have been considered. Although given the extent of the adverse reaction combined with the patient's underlying renal dysfunction, extra fluid may or may not have proven beneficial. The use of prophylactic rasburicase or allopurinol could have been considered, but these measures are not typically used with multiple myeloma due to the low incidence of TLS. All things considered, this unlikely adverse reaction may occur in certain patients. If other cases such as this occur, it may be advisable to use TLS prophylaxis in the future in certain patient populations, including those with renal dysfunction or worsening disease states.