<< First  < Prev   1   2   3   4   5   ...   Next >  Last >> 
  • 14 Nov 2019 1:23 PM | MSHP Office (Administrator)

    Author: Cara Carter, PharmD

    As we delve deeper in to flu season, we are reminded of one of the greatest public health advances but also one of the biggest controversies of our time: immunizations. In the aftermath of Andrew Wakefield’s falsified article linking the MMR vaccine to autism as well as the support of the anti-vax movement from celebrities like Jenny McCarthy and Jim Carey, we are seeing a resurgence of diseases once deemed to be eradicated.1 As the winter season sets in and people spend more time indoors, they will be in close quarters with many people whose immunization and infection status may be unknown to them. It is important that we, as healthcare providers, are diligent in protecting our patients and doing our part to help prevent outbreaks. We can be actively involved in this effort by being prepared to mitigate vaccine hesitancy.

    Vaccine hesitancy is a delay in acceptance or refusal of vaccines despite availability of vaccination services.2 Though reasons for vaccine hesitancy are many, they fit in to 3 categories: confidence, complacency, and convenience. Confidence is the trust in the effectiveness and safety of vaccines, the system that delivers vaccines, competence of healthcare professionals, and the motives of those who establish policies on necessary vaccines.3 Being honest about vaccine side effects and reassuring parents of their safety can have an impact on confidence. This builds trust in the provider which is also shown to have a positive effect on vaccine compliance.4 In order to be successful in this endeavor, we, as health care providers, must be intentional in remaining current on vaccine information and providing reliable sources of information to patients and families who may be struggling with confidence.

    Complacency is the perception that risks of vaccine-preventable diseases are low and vaccines are not a necessary preventative action.3 Honest conversations about acute and chronic complications of vaccine preventable diseases and personal anecdotal evidence are appropriate measures for combatting complacency. Cases of measles have been reported in the state of Missouri just this year with outbreaks also being reported in El Paso, TX; Rockland County, NY; New York City, NY; Los Angeles County, CA; and multiple counties in the state of Washington.5 Anecdotal evidence that includes what the provider would do or has personally done for his or her children and prior experiences with vaccine safety have been shown to be effective according to a survey of primary care physicians in the United States.4

    Convenience is the extent to which vaccines are available, affordable, accessible, understood (language and health literacy), and appealing.3 Offering vaccine services at every clinic visit, before hospital discharge, and during prescription pick-up as well as informing patients of community resources such as immunization clinics and free or reduced cost immunization programs are a few ways that we can help overcome the issue of convenience. If additional issues related to convenience arise, such as lack of transportation, consider social work consultation to aid in resolution of the issues.

    From physicians to nurses, pharmacists to social workers, we all play a vital role in reducing vaccine hesitancy. Vaccine hesitancy is not an easy issue to combat, and may take more than one visit and assistance from more than one provider to put parents and patients at ease. We should not find this as a point of frustration or discouragement but, rather inspiration to keep growing and learning as practitioners. Did the patient have a question you could not answer? Was an issue brought up that you were unsure how to address? Use those as starting points of a literature search or questions to pose to colleagues for their insight. It is important for us to remember that the goal is to put parents and patients at ease while assuring them that they, too, are a part of the team. Our collective goal as a healthcare team is to do what is in the best interest of the patient because, as American author John C. Maxwell has taught us, “Teamwork makes the dream work.”

    References
    1. Centers for Disease Control and Prevention. Measles History. Available at: https://www.cdc.gov/measles/about/history.html. Accessed July 26, 2019.
    2. MacDonald NE, the SAGE Working Group on Vaccine Hesitancy. Vaccine hesitancy: Definition, scope and determinants. Vaccine 2015;33(34):4161-4.
    3. Strategic Advisory Group of Experts on Immunization, World Health Organization. Report of the SAGE Working Group on Vaccine Hesitancy. Available at: https://www.who.int/immunization/sage/meetings/2014/october/1_Report_WORKING_GROUP_vaccine_hesitancy_final.pdf. Accessed July 26, 2019
    4. Shen SC, Dubey V. Addressing vaccine hesitancy: Clinical guidance for primary care physicians working with parents. Le Medécin de famille canadien 2019;65:175-81.
    5. Centers for Disease Control and Prevention. Measles Cases and Outbreaks. Available at: https://www.cdc.gov/measles/cases-outbreaks.html. Accessed July 26, 2019.


  • 14 Nov 2019 1:08 PM | MSHP Office (Administrator)

    Authors: Colton Frazer, PharmD Candidate 2022 and Paul Juang, Pharm.D, BCPS, BCCCP, FASHP, FCCM

    2019 CDC Vaccine Schedule Changes

    Vaccines are an imperative part of the success of the modern health system. However, vaccines are only effective when utilized correctly. Due to the intricacies of the vaccination schedule, and the continually evolving contraindications, reviewing the Center for Disease Control’s vaccination schedule can be a valuable method of staying up to date from year to year. In this review of the CDC’s 2019 vaccination schedule, a few recent changes will be highlighted, Shingrix and Pneumococcal guidelines will be refreshed, and the new hexavalent vaccine, VaxelisTM, will be discussed. 

    Notable Changes as of February 2019:

    Influenza Vaccine:

    As of 2019 the Live Attenuated Influenza Vaccine (LAIV) has been listed separately from the Inactive Influenza Vaccine (IIV) and Recombinant Influenza Vaccine (RIV). Moreover, LAIV is suitable for ages 2 years through 49 years old. Absolute contraindications in adult and children patients for LAIV include immunocompromising conditions (including HIV infection), anatomical or functional asplenia, pregnancy, close contact with severely immunocompromised persons, received influenza antiviral medications in the previous 48 hours, cerebrospinal fluid leak, cochlear implant, asthma (5 years or older). Other problematic underlying medical conditions (e.g., chronic pulmonary, cardiovascular [except isolated hypertension], renal, hepatic, neurologic, hematologic, or metabolic disorders [including diabetes mellitus])


    If any of the above LAIV contraindications apply to the patient, then the CDC recommends the IIV or RIV as a safe alternative.

    Hepatitis A Vaccine:

    A new indication for HepA vaccine has been added, homelessness. This is because being homeless has been linked with a two to three times higher chance of contracting hepatitis A, as well as displaying more severe outcomes from the disease when compared to non-homeless. For this new indication there are 2 options: get a 2-dose series of single-antigen hepatitis A vaccine or a 3-dose series of hepatitis A and hepatitis B vaccine. Moreover, there is a new pediatric international travel recommendation for vaccination of patients age 6 - 11 months and for all travelers greater than 12 months of age.

    Hepatitis B Vaccine:

    The hepatitis B have been updated to a 2-dose Heplisav-B® given at least 4 weeks apart. As needed, it can be switched to 3-dose series of Engerix-B vaccine. The seroprotection of the two vaccine sets shows that the newer Heplisav-B® is the preferred method when possible. (65%-81% for Engerix-B vs. 90%-95% for Heplisav-B®)


    Common Vaccination Review

    Shingrix:

    The Shingrix vaccine is recommended by the CDC for immunocompetent people older than 50 years, and is to be given in a two shot series separated by 2 - 6 months. This is regardless of previous herpes zoster episodes, taking low-dose immunosuppressives/are anticipating immunosuppression, or have recovered from an immunocompromising disease.

    For patients who have had previous episodes of herpes zoster, there is no set time to wait to receive the Shingrix vaccine. However, Shingrix is not to be administered to patients with active herpes zoster infections. If the patient has recently received Zostavax®, it is recommended to wait at least 8 weeks before administering Shingrix.

    Contraindications include allergies to any component of Shingrix, seronegative to varicella, acute episode of herpes zoster, or women who are pregnant or breastfeeding

     

    PCV13 and PPSV23 in Children and Adults

    All infants should receive the PCV13 immunization at 2, 4, and 6 months old. Then, a booster should be administered at age 12 - 15 months. Furthermore, all adults 65 years and older are recommended to receive the pneumococcal vaccine. If the adult has never received a dose of PCV13 before, administer this first. One year later, the PPSV23 should be administered. If the adult has received their dose of PPSV23 already, then administer the PCV13 at least one year after. 


    Vaxelis

    In December 2018, the FDA approved VaxelisTM to vaccinate children between 6 weeks old and 4 years old. VaxelisTM is indicated to prevent diphtheria, tetanus, pertussis, hepatitis B, Haemophilus influenzae type b, and poliomyelitis. VaxelisTM is administered as a 3-shot series starting at the age of 6 weeks old, and ending before the child is 5 years old. This vaccine is a combo product, combining antigens for diphtheria, tetanus, pertussis, and poliomyelitis from drug company Sanofi, and antigens for H. influenzae type b and hepatitis B from drug company Merck. After receiving the 3-dose series of VaxelisTM, the child will still need to receive one additional pertussis shot to complete their immunizations to the agent. By using this combo-vaccine a child can receive their Hepatitis B series in 4 or 5 shots, compared to the normal 6 to 8 using conventional Hep. B vaccination series. Below is a chart illustrating the advantage of using the VaxelisTM vaccination series compared to alternative options.

    VaxelisTM is expected to be available for use by 2020.


    References:

    All information and pictures sourced from www.cdc.gov/vaccines.

    For any further information, or to check the most recent vaccination guidelines, please visit


  • 14 Nov 2019 12:48 PM | MSHP Office (Administrator)

    Authors: Mary Thorne, PharmD, PGY1 Pharmacy Resident and Kathryn Lincoln PharmD, BCPS, BCIDP, Clinical Pharmacist – Infectious Diseases, Olathe Medical Center

    Learning Objectives

    1. Provide background information on community acquired pneumonia (CAP)
    2. Explain the updated guidelines and the rationale behind the recommendations
    3. Compare the 2007 guideline to current guideline recommendations
    4. Summarize current recommendations for management of CAP

    Introduction

    The American Thoracic Society (ATS) and the Infectious Diseases Society of America (IDSA) developed updated guidelines for community-acquired pneumonia (CAP) and were released in October this year. The 2007 CAP guidelines were preceded by the 2005 ATS Guidelines for the Management of Adults with Hospital-acquired (HAP), Ventilator-associated (VAP), and Healthcare-associated Pneumonia (HCAP). In 2016, IDSA and ATS released Management of Adults with Hospital-acquired and Ventilator-associated Pneumonia, leaving out HCAP. Since their release, there has been controversy and much debate about how to manage patients that may have community-acquired pneumonia, but are more at risk than the general population for multi-drug resistant organisms (MDRO). More literature has become available for the management of CAP since the 2007 guidelines, including patients at risk for MDRO.

    Community-acquired pneumonia is defined as pneumonia that is acquired outside of the hospital setting. Common pathogens for CAP include Haemophilus influenza, Legionella species, Chlamydophila pneumoniae, Moraxella catarrhalis, Streptococcus pneumoniae, Staphylococcus aureus, and Mycoplasma pneumoniae.

    Recommendation #1

    In adults with CAP, recommend against obtaining sputum gram stain and culture routinely in adults with CAP managed in the outpatient setting (strong recommendation, very low quality of evidence).

    Pre-treatment gram stain and culture of respiratory secretions should be obtained for adult patients with CAP in the hospital setting who are classified as severe CAP. Severe CAP being patients who were empirically treated for MRSA or P. aeruginosa, previously infected with MRSA or P. aeruginosa, hospitalized and received parenteral antibiotics in the past 90 days.

    Studies did not show improved patient outcomes when evaluating sputum gram stain and culture either in combination or alone. Research is still needed for guidance on rapid, cost effective diagnostics to help identify organisms causing CAP and improve targeted therapy when there are risk factors for MRSA and P. aeruginosa.

    Recommendation #3

    In adults with CAP, recommend against routinely testing urine antigens in adults with CAP, except patients with severe CAP or in cases where indicated by epidemiological factors such as association with a Legionella outbreak or recent travel (conditional recommendation, low quality of evidence).

    Randomized trials have not shown benefit for urinary antigen testing for S. pneumoniae and Legionella. There is concern that narrowing therapy in response to positive urinary antigen tests could lead to increased risk of clinical relapse.

    Recommendation #4

    In adults with CAP, recommend during influenza season, test for influenza with a rapid influenza molecular assay (strong recommendation, moderate quality of evidence).

    During periods of high influenza activity, it is beneficial to utilize a rapid influenza test. Testing provides both therapeutic and infection control benefits.

    Recommendation #5

    In adults with CAP, recommend empiric antibiotic therapy initiated in adults with clinically suspected and radiographically confirmed CAP regardless of initial serum procalcitonin (strong recommendation, moderate quality of evidence).

    Procalcitonin is used to guide de-escalation, discontinuation and duration of antibiotics in patients with lower respiratory infections. The sensitivity of procalcitonin for detecting bacterial infection ranges from 38% to 91%. This test alone cannot be used to justify withholding antibiotics from patients with CAP.

    There is not an established procalcitonin threshold for determining viral versus bacterial pathogens in hospitalized patients with CAP. However, there is a strong correlation with a higher procalcitonin and the probability of a bacterial infection.

    Recommendation #6

    Clinicians should use a prediction rule for prognosis, preferentially the Pneumonia Severity Index (PSI) (strong recommendation, moderate quality of evidence).

    PSI should be used as a supplement to clinical judgment. There is evidence confirming the safety and effectiveness of using PSI in addition to clinical judgment as a prognostic tool. PSI is a prognostic model in immunocompetent patients with pneumonia using demographic and clinical variables from the time of diagnosis to predict 30-day mortality.


    Recommendation #8

    In the outpatient setting, antibiotics are recommended for empiric treatment of CAP in adults.  For healthy outpatient adults without comorbidities or risk factors for antibiotic resistant, the following is recommended: 

    • Amoxicillin 1g PO TID or
    • Doxycycline 100mg PO BID or
    • Macrolide: only in areas with pneumococcal resistance to macrolides < 25%
      • Azithromycin 500mg on first day then 250mg daily

    Outpatient adults with comorbidities such as chronic heart, lung, liver, or renal disease, diabetes mellitus, alcoholism, malignancy, or asplenia, the treatment options include monotherapy with a respiratory fluoroquinolone or combination therapy with a beta lactam plus a macrolide or a beta lactam plus doxycycline. There is limited evidence regarding the superiority or equivalency of antibiotic regimens for the treatment of CAP. 


    Recommendation #9

    For inpatient adults with non-severe CAP without risk factors for MRSA or P. aeruginosa, treatment options include monotherapy with a respiratory fluoroquinolone or combination therapy of a beta lactam plus a macrolide or combination of beta lactam plus doxycycline.

    For inpatient adults with severe CAP without risk factors for MRSA or P. aeruginosa, treatment recommendation includes a beta lactam plus a macrolide or a beta lactam plus a respiratory fluoroquinolone.

    In the absence of RCTs evaluating therapeutic alternatives in severe CAP, the evidence is from observational studies. The use of fluoroquinolones as monotherapy in severe CAP has not been well studied. There is also limited studies for the combination of a β-lactam and doxycycline in severe CAP patients. These treatment strategies are not recommended as empiric therapy for severe CAP.


    Recommendation #10

    In the inpatient setting, suggest not routinely adding anaerobic coverage for suspected aspiration pneumonia unless lung abscess or empyema is suspected (conditional recommendation very low quality of evidence).

    Older studies showed high rates of isolated anaerobic organisms in patients with aspiration pneumonia. However, more recent studies show that anaerobes are uncommon in hospitalized patients who are suspected to have aspiration pneumonia.

    Aspiration is a common occurrence and it is difficult to provide a true rate of aspiration pneumonia. Aspiration pneumonitis is when patients aspirate their gastric contents. More recent studies have suggested that anaerobes do not impact the causation and disease state of acute aspiration pneumonia.

    Recommendation #11

    Recommend abandoning use of the prior categorization of healthcare-associated pneumonia (HCAP) to guide selection of extended antibiotic coverage in adults with CAP (strong recommendation, moderate quality of evidence).

    If there are locally validated risk factors for the presence of MRSA or P. aeruginosa, clinicians should empirically cover for MRSA or P. aeruginosa in adults with CAP. HCAP was introduced due to studies showing a higher prevalence drug resistant pathogens. More recent studies have shown there is not a predicted higher prevalence of drug resistant pathogens when using the factors that define HCAP. The recommendation to abandon the category of HCAP is based on high-quality studies of patient outcomes.

    In most settings, studies have shown there is not a predicted higher prevalence of antibiotic-resistant pathogens, when using the factors that define HCAP. Patient outcomes have not improved despite a large increase in the use of broad spectrum antibiotics. Prior isolation of MRSA or P. aeruginosa is a strong risk factor when assessing a patient’s risk of having a respiratory infection with either MRSA or P. aeruginosa.  

    Recommendation #12

    Recommend not routinely using corticosteroids in adults with non-severe or severe CAP (strong recommendation, high quality of evidence).

    In patients with non-severe CAP, there is no evidence for mortality or organ failure benefit with the use of corticosteroids. There is limited data for the use of corticosteroids in patients with severe CAP. The risks of corticosteroids are hyperglycemia primarily, possibly increased rates of re-hospitalization and the potential for more complications.


    Recommendation #13

    Recommend anti-influenza treatment be prescribed for adults with CAP who test positive for influenza in the inpatient and outpatient setting, independent of duration of illness before diagnosis (strong recommendation, moderate quality of evidence).

    Clinical trials have not evaluated the effect of anti-influenza treatment in adult patients with influenza pneumonia. In the outpatient setting, it is unclear whether or not there is benefit to using anti-influenza treatment for patients who have tested positive for the influenza virus. 

    Recommendation #14

    Recommend that standard antibacterial treatment be initially prescribed for adults with clinical and radiographic evidence of CAP who test positive for influenza in the inpatient and outpatient settings (strong recommendation, low quality of evidence).

    A bacterial pneumonia infection can overlap with an active influenza viral infection. In patients recovering from a primary influenza infection, bacterial pneumonia may present later on, as worsening of symptoms. Patients are at risk for a concurrent infection of S. aureus bacterial pneumonia associated with influenza. The recommendation to treat patients with an antibacterial agent is based on the current evidence suggesting that bacterial co-infections with influenza can become complicated.

    Recommendation #15

    The duration of antibiotic therapy should be guided by a validated measure of clinical stability and antibiotic therapy should be continued until the patient achieves stability and for no less than a total of five days (strong recommendation, moderate quality of evidence).

    There are a few randomized trials addressing the appropriate duration for the treatment of patients with CAP. Despite limited data supporting a five-day treatment duration, it is recommended to treat patients for a minimum of five days even if a patient is clinically stable before five days. Clinical stability is the resolution of vital sign abnormalities such as, heart rate, respiratory rate, blood pressure, oxygen saturation, and temperature.

    Recommendation #16

    In adults with CAP whose symptoms have resolved within 5 to 7 days, we suggest not routinely obtaining follow-up chest imaging (conditional recommendation, low quality of evidence). 

    Data is limited when evaluating the utility of reimaging patients with pneumonia. More research may help to clarify any potential benefit to patients who need further radiology imaging after initial treatment.


    Summary

    Recommend abandoning use of HCAP to guide selection of extended antibiotic coverage in adults with CAP. Emphasis on local epidemiology and validated risk factors to determine need for MRSA or P. aeruginosa coverage. For standard empiric treatment of severe CAP, stronger evidence is in favor of β-lactam plus macrolide combination compared to β-lactam plus fluoroquinolone. 


    References

    1. Metlay JP, Waterer GW, Long AC, et al. Diagnosis and Treatment of Adults with Community-acquired Pneumonia. An Official Clinical Practice Guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med. 2019;200(7):e45-e67.
    2. Self WH, Balk RA, Grijalva CG, Williams DJ, Zhu Y, Anderson EJ, et al. Procalcitonin as a marker of etiology in adults hospitalized with community-acquired pneumonia. Clin Infect Dis 2017;65:183–190.
    3. El-Solh AA, Pietrantoni C, Bhat A, Aquilina AT, Okada M, Grover V, et al. Microbiology of severe aspiration pneumonia in institutionalized elderly. Am J Respir Crit Care Med 2003;167:1650–1654
    4. Marik PE, Careau P. The role of anaerobes in patients with ventilator associated pneumonia and aspiration pneumonia: a prospective study. Chest 1999;115:178–183 Intensive Care Med 1993;19:279–284.
    5. Kollef MH, Shorr A, Tabak YP, Gupta V, Liu LZ, Johannes RS. Epidemiology and outcomes of health-care-associated pneumonia: results from a large US database of culture-positive pneumonia. Chest 2005;128:3854–3862
    6. Attridge RT, Frei CR, Pugh MJ, Lawson KA, Ryan L, Anzueto A, et al. Health care-associated pneumonia in the intensive care unit: guideline-concordant antibiotics and outcomes. J Crit Care 2016; 36:265–271.
    7. Attridge RT, Frei CR, Restrepo MI, Lawson KA, Ryan L, Pugh MJ, et al. Guideline-concordant therapy and outcomes in healthcare associated pneumonia. Eur Respir J 2011;38:878–887.


  • 14 Nov 2019 12:38 PM | MSHP Office (Administrator)

    Authors: Harrison Yoon, PharmD Candidate 2020 and Julianne Yeary, Pharm.D.

    Introduction

    Vancomycin-resistant enterococcus (VRE) is an emerging drug-resistant organism responsible for increasing numbers of hospital-acquired infections. It readily colonizes the intestines without any symptoms, which can serve as an infection reservoir and spread quickly among hospitalized patients.1 In 2013, the Centers for Disease Control and Prevention (CDC) estimated 20,000 cases of nosocomial VRE infections in the United States with 1,300 cases resulting in death.2

    VRE bacteremia is associated with significant mortality rates and prolonged hospital stays.3,4 Limited treatment options are available for VRE bacteremia. IDSA Guidelines recommend both daptomycin and linezolid as first-line agents for the treatment of VRE bacteremia,5 but clear distinction of therapeutic outcomes between the two therapies is still lacking.

    Risk Factors for VRE Bacteremia

    Patient populations at risk for VRE bacteremia include those with previous VRE colonization, hematologic malignancy, hemodialysis, neutropenia, mucositis, recent surgery, indwelling catheters, previous antibiotic therapy, use of immunosuppressive agents, and organ transplantation.6

    Toxicity Profile of Linezolid and Daptomycin

    Linezolid is known to have a number of toxicities and drug interactions with its use. Notable toxicities include thrombocytopenia, neutropenia, lactic acidosis, peripheral and optic neuropathy, and increased liver enzymes.7 Serotonin syndrome can also be seen in patients receiving concomitant serotonergic agents because linezolid exhibits low monoamine oxidase (MAO) inhibition.

    Daptomycin is associated with increases in creatine kinase (CK) levels which can result in muscle pain/weakness and rhabdomyolysis. Cases of eosinophilic pneumonia have also been reported with prolonged daptomycin use.8

    Clinical Efficacy of Linezolid and Daptomycin

    A 2015 multicenter, retrospective cohort study by Britt and colleagues compared the effectiveness of linezolid vs. daptomycin in the Veteran Affairs healthcare system. The primary outcome was clinical failure defined as a composite of 30-day all-cause mortality, microbiologic failure, and 60-day recurrence of VRE bacteremia. Linezolid was associated with a higher risk of treatment failure (risk ratio: 1.37; 95% CI 1.13-1.67; p=0.011), higher 30-day mortality rates (42.9% vs. 33.5%; RR: 1.17; 95% CI: 1.02-1.30; p=0.026), and higher microbiologic failure rates (RR: 1.10; 95% CI: 1.02-1.18; p=0.011) compared to daptomycin. No difference in 60-day VRE bacteremia recurrence was observed between the two therapies. Standard daptomycin dosing of 6 mg/kg was used in the majority of patients. Duration of treatment differed between the groups, as the linezolid group received a median treatment duration of 7 days and daptomycin group received a median treatment duration of 11 days, but the results discussed above were controlled for treatment duration.9

    A single-center, retrospective cohort study by Narayanan and colleagues evaluated the clinical effectiveness of linezolid and daptomycin in 93 patients with VRE bacteremia between 2012 and 2016. The primary outcome was clinical failure defined as a composite of 14-day mortality, microbiologic failure, or relapse of VRE bacteremia. Overall, patients treated with daptomycin had a significantly higher rate of clinical failure compared to patients treated with linezolid (74.2% vs. 46.8%, p=0.01). Individual outcomes of 14-day mortality, microbiologic failure, and relapse of VRE bacteremia were worse in patients treated with daptomycin, but not statistically significant. Daptomycin dosing remained stable throughout the patient population at a standard dose of 6 mg/kg, and the treatment duration was undisclosed for both therapies.10

    A systematic review and meta-analysis of ten retrospective studies that does not include the studies discussed previously was published in 2014 by Balli and colleagues. A total of 967 patients were identified, and the primary outcome was 30-day all-cause mortality. Patients treated with daptomycin showed significantly higher 30-day all-cause mortality (OR: 1.61; 95% CI: 1.08-2.40) and overall mortality (OR: 1.41; 95% CI: 1.06-1.89) compared to linezolid patients. The median daptomycin dose was 6 mg/kg in six studies, 5.5 mg/kg in one study, and not reported in the remaining three studies.11

    High-Dose vs. Standard-Dose Daptomycin

    Therapeutic outcome differences between high-dose daptomycin and standard-dose daptomycin in VRE bacteremia should also be addressed. A 2016 prospective cohort study compared mortality rates of VRE bacteremia treated with high-dose daptomycin (>9 mg/kg) vs. standard dose daptomycin (6 mg/kg) vs. linezolid. Use of high-dose daptomycin correlated to a significantly lower all-cause 14-day mortality compared to standard dose daptomycin (OR: 0.76; 95% CI: 0.59-0.98; p=0.03). There were no significant differences in adverse events between the high-dose and the standard-dose daptomycin groups. The study also found had lower mortality rates in the linezolid group compared to the standard-dose daptomycin group (aOR: 0.34; 95% CI: 0.14-0.79; p=0.01) and compared to all patients receiving daptomycin regardless of dose (aOR: 0.39; 95% CI: 0.18-0.85; p=0.02). The linezolid group did not show a statistically significant difference in terms of mortality when compared with high-dose daptomycin patients alone (aOR: 0.98; 95% CI: 0.14-7.03; p=0.99).12

    Discussion

    In contrast to other literature discussed, Britt and colleagues found that linezolid use was associated with higher treatment failure compared to daptomycin. This may be due to a number of reasons. The linezolid group had a higher percentage of ICU admissions compared to the daptomycin group (83.5% vs. 70.5%), indicating that linezolid may have been used in more critically ill patients. Also, a higher percentage of linezolid patients were above the age of 65 compared to daptomycin group (54.9% vs. 46.2%),12 which likely contributed to the higher mortality and microbiologic failure rates seen. As stated, both retrospective cohort studies discussed utilized a standard daptomycin dose of 6 mg/kg for a majority of their patients.

    Optimal daptomycin dosing in VRE bacteremia is critical. Daptomycin exhibits dose-dependent bactericidal activity, so the standard daptomycin dose of 6 mg/kg may not be sufficient to induce sustained bactericidal activity to eradicate enterococcal bloodstream infections. Further studies to elucidate daptomycin dose-efficacy relationships may be an important step towards suggesting high-dose daptomycin as initial therapy for VRE bacteremia.

    Conclusion

    Linezolid and daptomycin are first-line options for VRE bacteremia. Although linezolid and daptomycin have notable differences in toxicities, literature regarding their comparative clinical efficacy is somewhat conflicting. A meta-analysis suggests slightly more favorable outcomes with linezolid compared to daptomycin, but definitive conclusions are difficult to make due to the insufficient daptomycin dosing in the majority of the studies included.

    In summary, current literature favors linezolid over daptomycin in the treatment of VRE bacteremia, but clear evidence to support one agent over the other is lacking. High-dose daptomycin and linezolid have shown similar results, and both seem to be superior to standard-dose daptomycin. Choosing between high-dose daptomycin and linezolid should be individualized based on patient-specific factors such as severity of illness, concomitant infections, drug interactions, and tolerability to therapy.

    References

    1. O’Driscoll T, Crank CW. Vancomycin-resistant enterococcal infections: epidemiology, clinical manifestations, and optimal management. Infect Drug Resist. 2015; 8:217-30.
    2. Centers for Disease Control and Prevention. Antibiotic resistance threats in the United States. 2013; https://www.cdc.gov/drugresistance/pdf/ar-threats-2013-508.pdf. Accessed July 6th, 2019.
    3. Cheah AL, Spelman T, Liew D et al. Enterococcal bacteraemia: factors influencing mortality, length of stay and costs of hospitalization. Clin Microbiol Infect. 2013; 19(4):E181-9.
    4. Prematunge C. VRE and VSE bacteremia outcomes in the era of effective VRE therapy: A systematic review and meta-analysis. Infect Control Hosp Epidemiol. 2016; 37(1):26-35.
    5. Memel LA, Allon M, Bouza E et al. Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis. 2009; 49:1-45.
    6. Patel R. Clinical impact of vancomycin-resistant enterococci. J Antimicrob Chemother. 2003; 51:Suppl 3:iii13-21.
    7. Zyvox® [package insert]. New York, NY: Pfizer Company Inc.; 2008.
    8. Cubicin® [package insert]. Whitehouse Station, NJ: Merck & Co. Inc.; 2003.
    9. Britt NS, Potter EM, Patel N et al. Comparison of the effectiveness and safety of linezolid and daptomycin in vancomycin-resistant enterococcal bloodstream infection: A national cohort study of Veterans Affairs patients. Clin Infect Dis. 2015; 61(6):871-8.
    10. Narayanan N, Raj R, Vaidya P et al. Comparison of linezolid and daptomycin for the treatment of vancomycin-resistant enterococcal bacteremia. Ther Adv Infect Dis. 2019; 13(6):1-8.
    11. Balli EP, Venetis CA, Miyakis S. Systematic review and meta-analysis of linezolid versus daptomycin for treatment of vancomycin-resistant enterococcal bacteremia. Antimicrob Agents Chemother. 2014; 58(2):734-9.
    12. Chuang YC, Lin HY, Chen PY et al. Daptomycin versus linezolid for the treatment of vancomycin-resistant enterococcal bacteremia: implications of daptomycin dose. 2016; 22(10):890.


  • 14 Nov 2019 12:29 PM | MSHP Office (Administrator)

    Authors: Ellisa Zhang, PharmD Candidate 2020 and April Pottebaum, PharmD, BCPS

    Hepatitis B Risk

    Based on a national health survey, an estimated 850,000 people are living with hepatitis B in the United States.1 However, this number could be an underestimate since studies evaluating migration data and prevalence of hepatitis B in foreign countries estimate that this number could be as high as 2.2 million. 1 The hepatitis B virus (HBV) is a DNA virus that replicates in the liver and can progress to a chronic infection that leads to an increased risk of liver cirrhosis and hepatocellular carcinoma.1,2 HBV is transmitted through infected blood and body fluids via percutaneous or mucosal contact.1 It can also remain infectious on non-living surfaces in the environment for at least 7 days. Thus, patients on dialysis are especially at risk for acquiring HBV due to increased exposure to blood with frequent dialysis treatments as well as use of shared dialysis equipment.2

    Patients with end-stage renal disease (ESRD) are more susceptible to infection due to a weakening of the immune system secondary to uremia.3 Production of T-cells is decreased and alterations of costimulatory molecules CD80 and CD86 impair the activity of antigen-presenting cells in this patient population.This suppresses the adaptive immune response, leading to a higher rate of infection, a lower response rate to vaccinations, and a shorter duration of seroprotection against antigens.3 Fifty to seventy percent of dialysis patients respond to the hepatitis B vaccine, but only 40% will maintain protection against HBV three years after their vaccination series, as compared to initial response rates of > 90% in healthy adults aged < 40 years and 75% in adults aged 60 years.1,4 Studies evaluating causes of reduced seroconversion in ESRD patients show conflicting results, likely because these studies have small sample sizes and different methodologies for administering the hepatitis B vaccines.4-6 Since patients vaccinated in earlier stages of renal disease showed higher rates of seroconversion, it is advisable to start hepatitis B vaccinations before patients become dialysis dependent.7,8

    Current Hepatitis B Vaccine Recommendations

    Updated guidance on use of HBV vaccines in adults on hemodialysis was provided by ACIP in January 2018. Due to the increased risk of exposure to HBV, serological testing is recommended before vaccination for patients receiving hemodialysis.1 Testing includes the hepatitis B surface antigen (HBsAg), antibody to hepatitis B surface antigen (anti-HBs), and antibody to hepatitis B core antigen (anti-HBc). Anti-HBs levels >10 mIU/mL generally indicate seroprotection against HBV infection, but the cutoff values could differ based on the assay used. While testing is not required for vaccination, it can reduce costs by avoiding vaccination in persons who are already immune. In settings where testing is not feasible, vaccination should continue as administration of the vaccine to individuals who are immune due to acute or chronic HBV infection or previous vaccination does not increase the risk for adverse events.1

    For patients > 20 years old on dialysis, either high-dose Engerix-B® (40 mcg) or high-dose Recombivax HB® (40 mcg) given IM is recommended.1 Engerix-B® is a 4-dose series given at months 0, 1, 2, and 6 while Recombivax HB® is a 3-dose series given at months 0, 1, and 6. If the vaccination series is interrupted, it does not need to be restarted. If the second dose is delayed, it should be administered as soon as possible, and then the third dose must be separated from the second dose by at least 8 weeks. If the third dose is delayed, it should be administered as soon as possible.1 The series should be completed with vaccines from the same manufacturer when possible.9

    Although serologic testing for immunity is not routinely performed after vaccination of most individuals, anti-HBs levels should be assessed 1 to 2 months after completion of the vaccination series in dialysis patients.1 For most assays, if the level is >10 mIU/mL, then the patient is considered immune and does not need further vaccinations. However, if the level is <10 mIU/mL, then the patient should complete another full vaccination series, and another anti-HBs titer should be checked 1 to 2 months after this revaccination. If there is still no serologic response, then a test for HBsAg is recommended to determine infection status. A positive HBsAg indicates HBV infection, so the patient would need to be educated about strategies to prevent the spread of infection. If the HBsAg is negative, the patient is still susceptible to HBV infection, so he or she should be counseled on how to prevent infection and the importance of receiving hepatitis B immune globulin (HBIG) if exposed to infected blood.1

    Annual anti-HBs testing is recommended in dialysis patients to determine if a booster dose of hepatitis B vaccine is needed. Patients should receive a booster dose of hepatitis B vaccine if the anti-HBs level falls to <10 mIU/mL. Testing to assess the efficacy of the booster dose is not necessary.1 Figure 1 provides a summary of these recommendations.

    New Vaccine on the Market

    Heplisav-BTM by Dynavax is a newer HBV vaccine that was FDA-approved in November 2017 for adults 18 years and older. Heplisav-B™ is an attractive alternative to Engerix-B® or Recombivax HB® for hepatitis B vaccination due to a more convenient dosing schedule as well as better seroprotection.10 It is a 2-dose series, with doses administered IM at least one month apart. While the other HBV vaccines use aluminum hydroxide as an adjuvant, Heplisav-BTM uses a novel adjuvant cytosine phosphoguanine oligonucleotide (CpG1018). CpG1018 is synthesized from bacterial DNA and helps stimulate the immune system by activating the toll-like receptor 9 (TLR-9) pathway.10

    The clinical trials that led to approval of Heplisav-B™ were phase 3 noninferiority studies which compared response rates of Heplisav-BTM to Engerix-B®.11-13 In a study of healthy patients aged 18-55 years, Heplisav-B™ was shown to provide significantly higher rates of seroprotection as compared to Engerix-B® (97.9% vs 81.1%).11 Another study in healthy adults aged 40-70 years also found a significantly higher response to Heplisav-B™ as compared with Engerix-B® (94.8% vs 72.8%).12 Similar results were also observed in a study of patients with type 2 diabetes.13 While Heplisav-BTM did demonstrate increased efficacy as compared to Engerix-B® in each of these studies, it also caused more injection-site reactions.11-13 Despite these promising findings, the studies did not include patients on dialysis, so use of Heplisav-B™ cannot be routinely recommended in this patient population until more data is available.14 A study is currently enrolling patients on hemodialysis to assess the safety and efficacy of Heplisav-BTM with an estimated completion date of April 2021.15

    Even with the potential for improved immunogenicity with Heplisav-B™, ACIP still recommends testing for anti-HBs to determine vaccine response in hemodialysis patients and other populations at risk for HBV infection.14 Since there is limited data about switching between Heplisav-BTM and the other hepatitis B vaccines (i.e. Engerix-B® or Recombivax HB®), these vaccines should not be interchanged. If a patient receives one dose of Heplisav-BTM and one dose of another hepatitis B vaccine, then the vaccination series should be completed with a total of three vaccine doses.14

    Conclusion

    Patients on dialysis are at higher risk for HBV infection compared to the general population due to the nature of dialysis procedures requiring frequent vascular access and a suppressed immune system secondary to uremia. Furthermore, patients on dialysis have lower response rates to hepatitis B vaccines and decreased ability to maintain seroprotection against HBV. It is essential to ensure patients on dialysis are vaccinated appropriately and monitored annually for seroprotection to the hepatitis B virus. While alternative strategies for hepatitis B vaccination are needed to combat this problem and a newer HBV vaccine is showing promise for improved immunogenicity, further studies are needed to fully assess efficacy in this patient population. ACIP offers the most current evidence-based recommendations for vaccination to prevent HBV infection.

    Figure 1.

    Current Recommendations on the Prevention of HBV Infection in Patients Undergoing Hemodialysis


    References

    1. Schillie S, Vellozzi C, Reingold A, et al. Prevention of hepatitis B virus infection in the United States: Recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2018;67(1):1–31.
    2. Yousaf F, Gandham S, Galler M, Spinowitz, Charytan C. Systematic review of the efficacy and safety of intradermal versus intramuscular hepatitis B vaccination in end-stage renal disease population unresponsive to primary vaccination series. Ren Fail. 2015;37(7):1080-88.
    3. Kato S, Chmielewski, Honda H, et al. Aspects of immune dysfunction in end-stage renal disease. CJASN. 2008;3(5):1526-33.
    4. Saco TV, Strauss AT, Ledford DK. Hepatitis B vaccine nonresponders: possible mechanisms and solutions. Ann Allergy Asthma Immunol. 2018;121:320-7.
    5. Asan A, Demirhan H, Sorkun HC, et al. Factors affecting responsiveness to hepatitis B immunization in dialysis patients. Int Urol Nephrol. 2017;49:1845-50.
    6. Eleftheriadis T, Pissas G, Antoniadi G, Liakopoulus V, Stefanidis I. Factors affecting effectiveness of vaccination against hepatitis B virus in hemodialysis patients. World J Gastroenterol. 2014;20(34):12018-25.
    7. Mast EE, Weinbaum CM, Fiore AE, et al. A comprehensive immunization strategy to eliminate transmission in the United States, recommendations of the Advisory Committee on Immunization Practices (ACIP) part II: immunization of adults. MMWR Recomm Rep. 2006;55(RR16):1-25.
    8. Daroza G, Loewen A, Djurdjev O, et al. Stage of chronic kidney disease predicts seroconversion after hepatitis B immunization: earlier is better. Am J Kidney Dis. 2003;42(6):1184-92.
    9. Ezeanolue E, Harriman K, Hunter P, Kroger A, Pellegrini C. General best practice guidelines for immunization. https://www.cdc.gov/vaccines/hcp/acip-recs/general-recs/downloads/general-recs.pdf. Accessed July 14, 2019.
    10. JAMA. A two-dose hepatitis B vaccine for adults (Heplisav-B) JAMA. 2018;319(8):822-23.
    11. Halperin SA, Ward B, Cooper C, et al. Comparison of safety and immunogenicity of two doses of investigational hepatitis B virus surface antigen co-administered with an immunostimulatory phosphorothioate oligodeoxyribonucleotide and three doses of a licensed hepatitis B vaccine in healthy adults 18-55 years of age. Vaccine. 2012;30(15):2556-63.
    12. Heyward WL, Kyle M, Blumenau J, et al. Immunogenicity and safety of an investigational hepatitis B vaccine with a Toll-like receptor 9 agonist adjuvant (HBsAg-1018) compared to a licensed hepatitis B vaccine in healthy adults 40-70 years of age. Vaccine. 2013; 31(46):5300-5.
    13. Jackson S, Lentino J, Kopp J, et al. Immunogenicity of a two-dose investigational hepatitis B vaccine, HBsAg-1018, using a toll-like receptor 9 agonist adjuvant compared with a licensed hepatitis B vaccine in adults. Vaccine. 2018;36(5):668-74.
    14. Schillie S, Harris A, Link-Gelles R, Romero J, Ward J, Nelson N. Recommendations of the advisory committee on immunization practices for use of a hepatitis B Vaccine with a novel adjuvant. MMWR Morb Mortal Wkly Rep. 2018;67:455–58.
    15. NIH. HEPLISAV-B® in adults with end-stage renal disease (ESRD) undergoing hemodialysis. ClinicalTrials website. https://clinicaltrials.gov/ct2/show/NCT03934736. May 2, 2019. Accessed June 28, 2019.  


  • 14 Nov 2019 12:14 PM | MSHP Office (Administrator)

    Author: Bert McClary

    In early April I saw a news segment titled “When Women Rule the World,” featuring Tina Brown discussing her 10th annual “Women in the World” conference.  Just a week before I had seen four women on the stage, and no men, taking the MSHP oath of office, administered to them by a fifth woman.  It was the first time that had occurred.

    We have had women active in MSHP since the beginning.  Today they outnumber the men and are a driving force in the organization, but it wasn’t always that way.  Even though there was no effort to exclude women from leadership or recognition, there was still an occasional unintended chauvinistic characteristic that came through. 

    Eleven of 54 registrants for the organizational meeting in 1970 were women, five of them members of religious orders, and one, Sister Jane McMenamy, had served on the original organizing committee from 1969.  Among women in hospital pharmacy during the early years, more were nuns because hospitals operated by religious orders funded pharmacy education for their staff.  Both the Metropolitan St. Louis Hospital Pharmacists Association and the Greater Kansas City Society of Hospital were formed by nuns.  A notable Missourian who participated in the preparation of the landmark 1964 Mirror to Hospital Pharmacy was Sister Mary Berenice, Director of Pharmacy at St. Mary’s Hospital, St. Louis.

    While gender was not called out as a specific issue in the early years, the first female elected MSHP officer was Secretary (of course) in 1973, and female membership was usually 10 to 20 percent.  There was also an MSHP BOP Advisory Committee memo that went out announcing a new BOP Executive Secretary, the managing staff employee of the Board (male, of course), “as well as a woman on the Board” (a Board member appointed by the Governor).  The memo did not include the name of either person, but the fact of a female appointee was notable.  Women as BOP appointees are frequent now.  The BOP has had five Executive Secretaries during the last 50 years, and the last two have been females.

    We have had many women serve in important positions of leadership as elected officers, members of the board of directors, and committee chair positions through the years, but it was 16 years before we elected our first woman MSHP president, Bonnie Grabowski, in 1986.  There have been 15 female presidents in 50 years; however we have done better recently, as 11 of our presidents in the last 20 years have been women, including five of the last seven. 

    WOW (Women of the World)!


  • 14 Nov 2019 11:55 AM | MSHP Office (Administrator)

    Authors: Caitlynn Tabaka, PharmD and

    Livia Allen, PharmD, BCCCP

    Learning Objectives

    1. Analyze the mechanism of action and pharmacokinetic properties of vasopressors to determine which vasopressor to use in specific scenarios.
    2. Identify the differences in dosing and preparation requirements for push-dose vasopressors.
    3. Evaluate current literature pertaining to the use of push-dose vasopressors outside of the operating room.
    4. Evaluate the safety concerns of utilizing push-dose vasopressors outside of the operating room.

    Introduction

    Vasopressors are excitatory and inhibitory agents utilized to increase a patient’s blood pressure through actions on the heart and/or vascular smooth muscle.1 They are traditionally administered through a central line as a continuous infusion for the management of fluid refractory systemic hypotension. Systemic hypotension is a medical emergency that can lead to end-organ ischemia if not managed properly.2 It is classified by a systolic blood pressure less than 90 mmHg, a diastolic blood pressure less than 60 mmHg or a mean arterial pressure less than 65 mmHg. The most common causes of hypotension include hypovolemic, cardiogenic, and distributive shock. Effective fluid resuscitation is crucial for stabilization of tissue hypoperfusion. The 2016 Surviving Sepsis Guidelines recommend that vasopressors be administered only once hypotension is found to be persistent despite adequate fluid challenges.3 

    Vasopressor agents are typically administered as continuous infusions. However, bolus doses of vasopressors have been used to optimize a patient’s hemodynamic status when rapid intervention is required. This method of intermittently administering bolus vasopressor doses can be referred to as push-dose vasopressors, neo-sticks, or phenyl-sticks.4,5 Utilizing push-dose vasopressors to treat hypotension and maintain adequate perfusion is a common evidence-based practice by anesthesiologists in the operating room (OR). Studies that used push-dose epinephrine, phenylephrine, and ephedrine in the OR for hemodynamic management, secondary to sedation and spinal anesthesia, had positive outcomes. Push-dose vasopressors were shown to be as efficacious and safe as continuous infusion vasopressors and patients who received them required less vasopressors overall.6-9 Due to the success in the OR, the use of push-dose vasopressors has transitioned to the emergency department (ED) and intensive care unit (ICU) in recent years as a practical strategy to urgently manage hemodynamically unstable patients.

    Hypotension in the ED and ICU settings are often multifactorial. Depending on the severity and duration, hypotension has been associated with acute organ failure, need for ICU stay, and in-hospital mortality. Potential etiologies include septic shock, post intubation hypotension, traumatic brain injury, transient hypotension related to procedural sedation, or while crystalloid or blood product volume resuscitation is in progress.4,5 In these cases, push-dose vasopressors may be given rapidly through a peripheral line to serve as a temporary bridging measure. Push-dose vasopressors can provide adequate perfusion to vital organs until a central line is placed and a continuous vasopressor infusion is initiated.4,10

    Vasopressors

    The most commonly used vasopressors for bolus dosing are epinephrine and phenylephrine.4,5 Phenylephrine is preferred over epinephrine in patients who present with tachycardia or tachyarrhythmias.Similarly, push-dose norepinephrine has recently gained attention in the anesthesia literature due to its lower tendency to cause tachycardia. Norepinephrine also has the quickest onset and shortest duration of action. It can be utilized in a setting where quick on and offset of a vasopressor is desirable. Evidence supporting the use of push-dose norepinephrine outside the OR is lacking.11-14 Ephedrine is popular among the anesthesiologists due to its extended duration of action, however, using a product with an extended duration in the ED or ICU could lead to overcorrection of hypotension and bradycardia.4,16


    Literature

    The available literature consists of efficacy and safety evaluations of push-dose vasopressors for the management of hypotension. The evidence is currently limited to case series and retrospective studies conducted in the ED and ICU settings. Results from prospective, randomized controlled trials are not yet available. The two main push-dose vasopressors analyzed were epinephrine and phenylephrine with only one study evaluating the use of ephedrine and none evaluating norepinephrine. 10, 17-20 Push-dose vasopressors were used for a variety of indications including sepsis, respiratory distress/failure, cardiac arrest, trauma-induced hypotension, and post-intubation or procedural sedation induced hypotension.10, 17-20

     There was a wide range of doses and dosing frequencies between the studies. Only one study had a protocol in place with standard dosing regimens of push-dose vasopressors.20 Most of the patients included in the studies were transitioned to continuous infusion vasopressors. The three patient cases described by Gottlieb et al. required continuous norepinephrine to maintain hemodynamic control after receiving push-dose epinephrine.19 Schwartz et al. evaluated the need for continuous support within 30 minutes following push-dose vasopressors.18 They found that patients who were appropriately fluid challenged required less vasopressor boluses and had a lower rate of continuous vasopressor infusions compared to those inadequately fluid challenged. Only two other studies assessed patients that received adequate fluid resuscitation prior to the initiation of push-dose vasopressors.19,20 The most common adverse effects noted in the literature include bradycardia, hypertension, and tachycardia. Rotando et al. reported that 11% of the included patients had a dose related medication error.20 Overall, the studies concluded that further assessments of appropriateness, efficacy, and safety need to be conducted for the use of push-dose vasopressors outside of the OR.10,17-20


    Push-Dose Vasopressor Preparation

    Push-dose vasopressor concentrations are not available commercially and must be prepared at bedside prior to administration. The preparation generally involves diluting commercially available products with normal saline (NS) to achieve appropriate concentrations. It is recommended that organizations preparing and utilizing these products develop a standardized process for naming, dosing, ordering, preparing and administering push-dose vasopressors.4


    Safety Concerns

    Vasopressors are strong vasoconstrictors that can lead to tissue hypoperfusion and injury if extravasation occurs. The risk of extravasation is greater when administered peripherally versus centrally. Studies have shown the vast majority of vasopressor-induced tissue damage occurs in peripheral lines that are distal to the antecubital or popliteal fossa and when infused for greater than four hours.21 Peripheral administration of vasopressors should be monitored frequently and reserved for emergency situations as a temporizing measure until central venous access can be obtained. If dosed correctly, push-dose vasopressors can be a great way to prevent peripheral extravasation due to the administration of small intermittent doses at diluted concentrations. Additional adverse effects that can occur when push-dose vasopressors are dosed incorrectly include local skin and soft-tissue injury (necrosis), end-organ tissue ischemia, acute hypertension, cardiac ischemic events, and left ventricular dysfunction.22

    Ensuring patient safety in the ED setting can be challenging due to treatment of unfamiliar patients, crowding, high stress situation, reliance on verbal orders, and dispensing and administering medications without verification by a pharmacist.4 The risk of error increases when utilizing push-dose vasopressors because of required dose calculations, drug dilutions, and incremental push-dose administrations. Errors in preparation, drug selection, and administration have been frequently reported. Acquisto et al.describes patients receiving high doses of push-dose epinephrine and phenylephrine due to dosing errors.23 In one case, a post-surgical hypovolemic shock patient developed hypotension during transport. Once in the ICU, the physician ordered “phenylephrine 50” and the patient was given 50 mg instead of the intended 50 mcg push dose. Another case occurred when a post-surgical patient developed atrial fibrillation and was treated with diltiazem IV boluses. The patient developed asymptomatic hypotension and a phenylephrine push-dose was ordered. In this case, the entire 1000 mcg phenylephrine pre-mixed syringe was administered instead of the intended 100 mcg. In both cases, fluid resuscitation had not been implemented prior to the initiation of push-dose vasopressors.

    Another common push-dose vasopressor error includes physicians asking for epinephrine mixed to the 100 mcg/mL phenylephrine concentration instead of the 5-20 mcg/mL epinephrine concentration. Epinephrine is available in various doses and concentrations to be delivered by multiple routes depending on the indication. Four cases related to dosing errors of push-dose epinephrine resulted in cardiogenic shock, ST-elevation myocardial infarction, and ventricular tachycardia.22 Contribution to these errors were multifactorial and included inadequate physician knowledge about appropriate dose and route of epinephrine, complicated dose calculations involving decimals and ratios, and lack of adequate communication between physicians and nurses. The Institute for Safe Medication Practices (ISMP) has Safe Practice Guidelines for Adult IV Push Medications that states a lack of administrative policies/protocols/guidelines for IV injections is a risk factor for error.24 ISMP recommends guidelines for parenteral medications through IV push administration route should be simplified, standardized, and communicate safe practices associated with the IV medication.

    Conclusion

    Successful practice migration from the operating room to the ED and ICU has been a continuous process for ages. The use of succinylcholine and other neuromuscular blockers for rapid sequence intubation was reserved for the OR until rigorous clinical research evaluating the utilization of neuromuscular blockers for procedures in the ED demonstrated superior outcomes.25,26 Propofol for procedural sedation has a similar history. It was only being utilized in the OR until clinical trials demonstrated that it was safe and effective for procedural sedation in the ED and ICU settings.27,28 Both of these practices that were initially met with resistance are now mainstay practices in the ED and ICU.

    The resistance against the migration of push-dose vasopressors to the ED and ICU stems from the limited literature available evaluating efficacy and safety. The studies available are retrospective and have several notable limitations including significant variations in dosing and timing of administration, reduced utilization of crystalloid fluids, and small patient sample sizes. Overall there is a lack of clear systematic practice patterns concerning the use of vasopressors which lead to adverse effects and medical errors. Currently, there are no guidelines discussing the management of an unintentional push-dose vasopressor overdose. Tachycardia, hypertension, and reflexive bradycardia are the most likely adverse effects of these agents when utilizing bolus dosing. Due to the short half-lives of these agents the adverse effects should not last longer than 30 minutes. However, in extreme overdoses more severe adverse events may occur including arrhythmias, limb ischemia, hypertension leading cerebrovascular events, metabolic acidemia, and lactic acidosis.1,4

    Institutions that implement push-dose vasopressors should have clear protocols and procedures indicating appropriate patients, medications, doses, preparation, and administration for push-dose vasopressors. If used at all, push-dose vasopressors should only be utilized as a temporary bridging measure until a continuous vasopressor infusion can be initiated. Push-dose vasopressors should only be used in those patients who have received adequate fluid resuscitation.18,19 Further studies need to be conducted to evaluate the safety and efficacy of utilizing push-dose vasopressors outside of the OR.

    References

    1. Overgaard C, Dzˇavík V. Inotropes and vasopressors: review of physiology and clinical use in cardiovascular disease. Circulation. 2008; 118:1047-1056.
    2. Kellum J, Pinsky M. Use of Vasopressor Agents in Critically Ill Patients. Curr Opin Crit Care. 2002 June;8(3):236-41.
    3. Rhodes A, Evans L, Alhazzani W, et al. Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-377.
    4. Holden D, Ramich J, Timm E, et al. Safety Considerations and Guideline-Based Safe Use Recommendations for “Bolus-Dose” Vasopressors in the Emergency Department. Ann Emerg Med. 2018;71(1): 83-92.
    5. Tilton L, Eginger K, Gastonia N. Utility of Push-Dose Vasopressors for Temporary Treatment of Hypotension in the Emergency Department. J Emerg Nurs. 2016;42(3):279-81.
    6. Siddik-Sayyid S, Taha S, Kanazi G, et al. A randomized controlled trial of variable rate phenylephrine infusion with rescue phenylephrine boluses versus rescue boluses alone on physician interventions during spinal anesthesia for elective cesarean delivery. Anesth Analg. 2014; 118:611-618.
    7. Doherty A, Ohashi Y, Downey K, et al. Phenylephrine infusion versus bolus regimens during cesarean delivery under spinal anesthesia: a double-blind randomized clinical trial to assess hemodynamic changes. Anesth Analg. 2012; 115:1343-1350.
    8. Mohta M, Harisinghani P, Sethi AK, et al. Effect of different phenylephrine bolus doses for treatment of hypotension during spinal anesthesia in patients undergoing elective caesarean section. Anaesth Intensive Care. 2015; 43:74-80.
    9. Heesen M, Stewart A, Fernando R. Vasopressors for the treatment of maternal hypotension following spinal anaesthesia for elective caesarean section: past, present and future. Anesthesia. 2015;70: 252-257.
    10. Swenson K, Rankin S, Daconti L, et al. Safety of bolus-dose phenylephrine for hypotensive emergency department patients. Am J Emerg Med. 2018 Oct;36(10):1802-1806.
    11. Wang X, Mao M, Liu S, et al. A Comparative Study of Bolus Norepinephrine, Phenylephrine, and Ephedrine for the Treatment of Maternal Hypotension in Parturients with Preeclampsia During Cesarean Delivery Under Spinal Anesthesia. Med Sci Monit. 2019; 25:1093-1101.
    12. Wang X, Shen X, Liu S, et al. The Efficacy and Safety of Norepinephrine and Its Feasibility as a Replacement for Phenylephrine to Manage Maternal Hypotension during Elective Cesarean Delivery under Spinal Anesthesia. Biomed Res Int. 2018; 2018:1869189.
    13. Hassani V, Movaseghi G, Safaeeyan R, et al. Comparison of Ephedrine vs. Norepinephrine in Treating Anesthesia-Induced Hypotension in Hypertensive Patients: Randomized Double-Blinded Study. Anesth Pain Med. 2018;8(4):e79626.
    14. Levy B, Clere-Jehl R, Legras A, et al. Epinephrine Versus Norepinephrine for Cardiogenic Shock After Acute Myocardial Infarction. J Am Coll Cardiol 2018;72(2):173-182.
    15. Vazculep (phenylephrine hydrochloride) label - FDA package insert. Chesterfield MO: Eclat Pharmaceuticals; June 2014.
    16. Bangash M, Kong M, Pearse R. Use of inotropes and vasopressor agents in critically ill patients. Br J Pharmacol. 2012 Apr; 165(7);2015-33.
    17. Panchal A, Satyanarayan A, Bahadir J, et al. Efficacy of Bolus-dose Phenylephrine for Peri-intubation Hypotension. J Emerg Med. 2015;49(4):488-94.
    18. Schwartz M, Ferreira J, Aaronson P. The impact of push-dose phenylephrine use on subsequent preload expansion in the ED setting. American Journal of Emergency Medicine. 2016; 34:2419-2422.
    19. Gottlieb M. Bolus dose of epinephrine for refractory post-arrest hypotension. CJEM. 2018; 20(S2):S9-13.
    20. Rotando A, Picard L, Delibert S, et al. Push dose pressors: Experience in critically ill patients outside of the operating room. Am J Emerg Med. 2019;37(3):494-498.
    21. Loubani O, Green R. A systematic review of extravasation and local tissue injury from administration of vasopressors through peripheral intravenous catheters and central venous catheters. J Crit Care. 2015; 30:653.e9-e17. 
    22. Anwar M, Irvin C, Frank J, et al. Confusion about epinephrine dosing leading to iatrogenic overdose: a life-threatening problem with a potential solution. Ann Emerg Med. 2010; 55:341-4.
    23. Acquisto N, Bodkin R. Medication Errors with Push Dose Pressors in the ED and ICU. Am J Emerg Med. 2018 Mar;36(3):520-521.
    24. Institute for Safe Medication Practices. ISMP safe medication practice guidelines for adult IV push medications. Available at: http://www.ismp.org/Tools/guidelines/ivsummitpush/ivpushmedguidelines.pdf. Accessed, September 20th, 2019.
    25. Roberts D, Clinton J, Ruiz E. Neuromuscular Blockade for Critical Patients in the Emergency Department. Ann Emerg Med. 1986; 15:152-156.
    26. Tayal V, Riggs R, Marx J, et al. Rapid-sequence intubation at an emergency medicine residency: success rate and adverse events during a two-year period. Acad Emerg Med. 1999; 6:31-37.
    27. Burton J, Miner J, Shipley E, et al. Propofol for emergency department procedural sedation and analgesia: a tale of three centers. Acad Emerg Med. 2006; 13:24-30.
    28. Godwin S, Burton J, Gerardo C, et al. Clinical policy: procedural sedation and analgesia in the emergency department. Ann Emerg Med. 2014; 63:247-258.

    Submit for CE

  • 13 Nov 2019 1:27 PM | MSHP Office (Administrator)

    Author: Sarah Cox, PharmD, MS

    Impact of Drug Shortages:

    The number of drugs impacted by shortages nearly tripled over a five-year period (2007-2012).1

    Today, drug shortages continue to pose a threat to health-systems and patients. A survey conducted in collaboration with ASHP and sent to 1300 directors of pharmacy nationwide, indicated that 99% of health-systems had experienced at least one shortage in the past 6 months and about a third or respondents stated having shortages with over 30 different drugs. Costs were estimated to be near $216 million from labor resources allocated to preventing or preparing for shortages.2 Another survey of directors of pharmacy estimated that drug shortages account for one to five percent of medication errors.3

    Resources for Your Health-System to Manage Drug Shortages:

    While drug shortages are not new and health-systems already have put processes in place in attempt to prevent and address shortages, there are many resources available to aide in this process.

    1. ASHP Drug Shortages List: Includes a master list of current drug shortages and the date the shortage was updated. This list is very user friendly and allows browsing or searching for a specific drug. Clicking on the drug of choice will bring up a new web page with details about the products impacted (including NDC), reason for the shortage, available products, and estimated resupply dates
    2. ASHP Guidelines on Managing Drug Product Shortages: This resource provides strategies health-systems can take to preventing, planning for, and responding to drug shortages.
    3. ASHP Drug Shortages Roundtable Report: This document describes some background on drug shortages including common causes and potential remedies.
    4. ASHP Additional Resources: Webpage includes additional links to best practices, guidelines, tools, and publications on drug shortages including links to the FDA Drug Shortage site and CDC Vaccine Shortage site.

    Legislative Efforts:

    The FDA Safety and Innovation Act (FDASIA) was enacted in 2012 and included a requirement that drug manufacturers notify the Food and Drug Administration (FDA) “of any change in production that is reasonably likely to lead to reduction in supply.” While this legislation did lead to a reduction in the number of drug shortages, additional legislation may help reduce shortages even further.

    The Mitigating Emergency Drug Shortages Act was introduced by Senator Susan Collins (R-ME) and Senator Tina Smith (D-MN) on October 29, 2019. ASHP played a role in developing the objectives for this piece of legislation including:

    • “Requiring manufacturers to disclose the root causes and expected duration shortages
    • Extending reporting requirements to include contract manufacturers and active pharmaceutical ingredients
    • Requiring manufacturers to develop contingency plans to ensure an ongoing supply
    • Developing recommendations to incentivize manufacturers to enter the market for drugs in shortage; and
    • Examining the national security risks of shortages.”4

    Take Action:

    To advocate for this legislation, go to ASHP’s online advocacy center, contact your representative, and ask them to co-sponsor S. 2723.

    References:

    1. Public Health Threat Continues Despite Efforts to Help Ensure Product Availability. United States Government Accountability Office, Washington DC. 2014;pp14-194.
    2. Kaakeh R, Sweet BV, Reilly C, et al. Impact of Drug Shortages on National Survey Reveals High Level of Fristration, Low Level of Safety. Am J Health Syst Pharm. 2011;68(19):1811-1819.
    3. Caulder CR, Mehta B, Bookstaver PB, et al. Impact of Drug Shortages on Health-System Pharmacies in the Southeaster United States. Hosp Pharm. 2015;50(4):279-286.
    4. Issue Update: ASHP Influencing the National Conversation on Drug Shortages. https://ashsp.ac360.aristotleactioncenter.com/#/alertId/03de88de-d2d9-4f57-bf2d-b37fe4bc57b5/ October 24, 2019. 
  • 13 Nov 2019 1:14 PM | MSHP Office (Administrator)

    Author: Jackie Harris, Pharm.D, BCPS, Executive Director, MSHP Research and Education Foundation

    MSHP R&E Foundation is currently accepting submissions and nominees for several awards. 

    MSHP R&E Best Practice Award

    The Best Practice Award program recognizes innovation and outstanding performance in a pharmacy directed initiative. The theme for the 2020 award focuses on Innovative Stewardship Roles.  Submission deadline is December 30th, 2019.

    A poster of the program will be highlighted during the Spring Meeting Poster Session. The award recipient will be honored at a Reception during the Spring Meeting and have the opportunity to provide a brief podium presentation detailing the implementation and impact of the project to the attendees.

    Applicants will be judged on their descriptions of programs and practices currently employed in their health system based on the following criteria:

    ·    Inventiveness of the program

    ·    Significance of the program to the health system

    ·    Demonstration of benefit to patient care as supported by program evaluation data

    ·    Significance of the program to pharmacy practice

    ·    Quality of submitted program report

    ·    Relevance to other institutions

    Applicants must be active MSHP members practicing in a health-system setting such as a large or small hospital, home health, ambulatory clinic or other health care system. More than one successful program from a health system may be submitted for consideration.

    Award recipient will receive half off their meeting registration, a plaque and a $250 honorarium.

    Submission Instructions: A program summary not to exceed 400 words must be submitted with the application and include the following information.

    ·    Background – description of need for program

    ·    Goals and specific aims of the program

    ·    Program description/methods – description of development process, role(s) of the pharmacist, timeline

    ·    Results - when results are not yet available, include a description of how impact of the program will be measured

    ·    Conclusion – established and/or expected clinical impact of the program

    ·    Submissions may also include any pictures, graphs, figures or data tables that support the summary. Each of these must be clearly labeled and described. Such information will not count against the 400 word limit.

    • Email your submission to mshp@qabs.com with Best Practice Award Submission in the subject line.

    MSHP R&E Best Residency Project Award

    The Best Residency Project Award recognizes innovation and outstanding performance in a pharmacy residency project.   A poster of the program will be highlighted during the Spring Meeting Poster Session. The award recipient will be honored at a Reception during the Spring Meeting and have the opportunity to provide a brief podium presentation detailing the implementation and impact of the project to the attendees. Submission deadline is December 30th, 2019.

    Applicants will be judged based on the following criteria:

    ·    Inventiveness of the project

    ·    Significance of the project to the health system

    ·    Demonstration of benefit to patient care as supported by project evaluation data

    ·    Significance of the project to pharmacy practice

    ·    Quality of submitted project report

    ·    Relevance to other institutions

    Applicants must be active MSHP members completing a residency in a health-system setting such as a large or small hospital, home health, ambulatory clinic or other health care system.

    Award recipient will receive half off their meeting registration, a plaque and a $250 honorarium.

    Submission Instructions: A program summary not to exceed 400 words must be submitted with the application and include the following information.

    ·    Background – description of need for project

    ·    Goals and specific aims of the project

    ·    Results - when results are not yet available, include a description of how impact of the project will be measured

    ·    Conclusion – established and/or expected clinical impact of the project

    Email your submission to mshp@qabs.com with Best Residency Project Award Submission in the subject line.

    Garrison Award

    The Garrison award was established in 1985, named after Thomas Garrison for his long standing support of MSHP (past-president 1974-1976), ASHP (past-president 1984) and numerous professional and academic contributions to Pharmacy. The Garrison Award is presented each year to a deserving candidate who has been nominated in recognition of sustained contributions in multiple areas:

    ·    Outstanding accomplishment in practice in health-system pharmacy;

    ·    Outstanding poster or spoken presentation at a state or national meeting;

    ·    Publication in a nationally recognized pharmacy or medical journal;

    ·    Demonstrated activity with pharmacy students from St. Louis or the UMKC Schools of Pharmacy;

    ·    Development of an innovative service in a health-system pharmacy in either education, administration, clinical service, or distribution;

    ·    Contributions to the profession through service to ASHP, MSHP and/or local affiliates.

    Each letter of nomination must include:

    ·    Name, work address, and telephone number of nominee;

    ·    Name, work address, and telephone number of nominator;

    ·    Sufficient explanation and documentation of the nominee’s accomplishment(s) to allow a proper decision by the selection committee;

    ·    and Curriculum Vitae of the Nominee.

    ·    To be considered for the Garrison Award, the nominee must be a current active member of the Missouri Society of Health-System Pharmacists. The winner will be selected by the Board of Directors of the MSHP Research and Education Foundation.  Email your nomination to mshp@qabs.com with Garrison Award Submission in the subject line.

    Submission Deadline for Garrison Award is January 31, 2020.

  • 26 Sep 2019 2:06 PM | Mandy Garion (Administrator)

    Authors: Shu-wen Tran, B.S., UMKC PharmD Candidate 2020 and Diana Tamer, B.S., Pharm.D., BCOP

    How is it possible that patients with certain metastatic cancers are still treated with traditional chemotherapy when targeted precision medicine is available for them as first line agents? While sequencing the whole genome led to having technologies today to sequence each patient’s tumor DNA, and finding targeted therapies for tumorigenesis driving mutations; these therapies are costly and not affordable to most patients—even those with insurance coverage. Is there any way to drive down the cost of oncolytic agents? Let’s explore some avenues.

    Targeted therapy, otherwise known as precision medicine, are medications designed to specifically target driving mutation(s) that is/are causing the cancer type. Targeted therapy differs from traditional therapy in that they act on a specific pathway or gene mutation related to the cancer type instead of acting systemically, affecting all normal and abnormal cells. Over the past 10 years, the FDA has approved more than 80 targeted oncolytic therapies, with more than half of them approved for oral administration.1 It is important to understand that traditional chemotherapies remain the standard of care in early stages of cancer, while targeted drug therapies are options for patients with metastatic disease—if they harbor a particular mutation.  That is also partly because as new drugs are studied in clinical trials for cancer patients, they start testing them in patients that have no other options and are at more advanced stages of their disease. That being said, as these drugs gain approval, clinical trials in earlier stages of the disease are underway; which will lead to maybe more use of these agents at all stages of cancer.

    Disparities in insurance plan coverage for cancer treatment is one of the most challenging aspects patients are facing. Patients are faced with a financial burden when their plan coverage diverges (medical versus pharmacy benefit), and their oral cancer drug therapy treatment is submitted through their pharmacy benefit, instead of their medical benefit. Often times a set-back in cancer treatment occurs because they are unable to afford therapy. So why is this happening?

    “Medical benefits often require patients to pay a flat copayment (perhaps $20 to $50 per visit) for care in an outpatient setting, which can include administration of intravenous medications. Pharmacy benefits, by contrast, often have a tiered copayment structure and other provisions that increase cost sharing for more expensive medications. Pharmacy benefits may include coinsurance (in which patients are responsible for a percentage of the medication cost), high overall deductibles, and caps on annual drug benefits.”2 Most insurance plans place oral cancer agents into a “specialty tier” or “fourth tier,” which may require a cost-sharing responsibility for the patient of anywhere from 25 to 33 percent of the cost of the drug, leading to copays which can range from$150-$7,000 per month. And these medications are taken chronically, typically on a daily basis, until disease progression, unacceptable toxicity, or death. And a common question that patient ask in clinic is: “What would I do when I can no longer afford this treatment?”

    In 2013, the Cancer Drug Parity Act3 was first introduced to Congress. The purpose of this bill is to help ensure that patients will not pay more for oral chemotherapy agents under their pharmacy benefit than they would for an intravenous chemotherapy agent under their medical benefit. One might wonder, don’t we have something like this in effect? Well, yes—in 43 states. Since 2007, many states have passed their own oral parity law, but it only applies to state health plans, leaving out patients under self-funded and fully insured health plans. If Congress approves this bill, the new federal legislation will require all health plans, including the remaining seven states to adopt this cancer drug parity act. Currently, seven states have yet to adopt this cancer drug parity act: Alabama, Idaho, Michigan, Montana, North Carolina, South Carolina, and Tennessee4.

    In a retrospective claims analysis published by Dr. Dusetzina and colleagues5, authors found that oral chemotherapy parity laws showed only “modest” financial benefit for patients. Their analysis encompassed 63,780 patients from three nationwide insurers (Aetna, Humana, and UnitedHealthcare), comparing effects before and after oral chemotherapy parity laws. Patients that were studied lived in one of 16 states that had implemented oral chemotherapy parity laws from July 2008 to July 2012, and who were receiving chemotherapy treatment. Results showed an increase in patient out-of-pocket (OOP) spend of more than $100 per month in plans subject to parity versus a slight decline in plans not subject to parity (8.4% to 11.1% vs. 12.0% to 11.7%, p=0.004). Monthly patient OOP spend on oral chemotherapy agents showed a decline in plans subject to parity in the 25th-, 50th-, and 75th percentile ($19.44, $32.13, $10.83, p<0.001), but saw an increase at the 90th- and 95th percentile ($37.19, $143.25, p<0.001). Dr. Dusetzina and colleagues conclude that “these laws alone may be insufficient to ensure that patients are protected from high out-of-pocket costs.”

    So what should we do? As more and more precision, targeted therapies are being pumped into the market, cancer patients should not have to pay any less for their oral cancer drug treatment under their pharmacy benefit than they would under their medical benefit. It is currently unclear exactly how many patients will benefit from this bill. This federal act is a start to help patients gain access to precision medicine. The underlying issue may be the price of the agents themselves. But that’s another article for another time.

    References:

    1. Abramson, R. “Overview of Targeted Therapies for Cancer”. My Cancer Genome 2018. Available from: https://www.mycancergenome.org/content/molecular-medicine/overview-of-targeted-therapies-for-cancer/ (Updated May 25).
    2. Wang B, Joffe S, Kesselheim AS et al. Chemotherapy parity laws: a remedy for high drug costs?. JAMA Internal Medicine 2014. 174(11):1721-1722. Available from: https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/1907003
    3. Cancer Drug Parity Act of 2019, H.R. 1730, 116th Cong. (2019). Available from: https://www.congress.gov/bill/116th-congress/house-bill/1730/text
    4. “Oral anti-cancer therapy access legislative landscape-2018”. Patients Equal Access Coalition, 2018. Available from: http://peac.myeloma.org/oral-chemo-access-map/
    5. Dusetzina SB, Huskamp HA, Winn AN et al. Out-of-pocket and healthcare spending changes for patients using orally administered anti-cancer therapy after adoption of state parity laws. JAMA Oncology 2018. 4(6):e173598. Available from: https://jamanetwork.com/journals/jamaoncology/article-abstract/2661763


<< First  < Prev   1   2   3   4   5   ...   Next >  Last >> 

Upcoming events


Copyright 2019, Missouri Society of Health-System Pharmacists
501(c)6 non-profit organization. 2650 S. Hanley Rd., Suite 100, St. Louis, MO 63144
p: 314-416-2246, f: 314-845-1891, www.moshp.org
Powered by Wild Apricot Membership Software