Author: Nathan Hanson, PharmD, MS, BCPS
Legislative Day is April 1st - will you be joining us? No, this isn’t a practical joke…advocacy is our job! Why? Because advocacy is leadership in action.
The playoffs are here, and what a year it’s been already! And like most years, this year we have been reminded how important the rules are. We see games decided and seasons completely changed because of one rule and one referee’s interpretation of that rule. Players can only do what they do best when they have the right rules, and when there is a clear understanding of those rules.
This brings us to pharmacy. Like the players, we are only able to use our skills and play the game within the rules that we have been given. Our patients need us to advocate for the best rules that allow pharmacists to provide the care that they need. Our patients need us to understand the rules so that we can safely and creatively serve their needs. Luckily, by joining MSHP you have already taken the first and most important step in the advocacy process. Over the next few MSHP newsletters we will we review the simple next steps that you can take to advocate for your patients.
We need to make up our minds that advocacy is indeed our job. Remember, advocacy just means that we work hard to
Understand the current rules so we follow them correctly
Improve the rules, using the systems that are in place.
When described this way, it makes it clear that advocacy is part of every pharmacy leader’s job.
Why is advocacy part of a pharmacy leader’s job? Pharmacists and technicians are committed to creative problem solving, quality assurance, and quality improvement. But we can only solve problems within the rules of the game, and we can’t assure quality unless we know what quality is, and we can make the biggest improvements to quality when we adjust the rules to allow innovative approaches. Every year our pharmacy schools train outstanding students, and every year our residencies provide even more training. But where to deploy all of that talent and passion? The potential can only be fully realized when we advocate for our patients.
I’ll leave you with a little light reading. First, the ASHP statement on advocacy as a professional obligation:
“ASHP believes that all pharmacists have a professional obligation to advocate on behalf of patients and the profession. Pharmacists should stay informed of issues that affect medication-related outcomes and advocate on behalf of patients, the profession, and the public. These issues may include legal, regulatory, financial, and other health policy issues, and this obligation extends beyond the individual practice site to their broader communities.”1
Next, a letter from Scott Knoer and Erin Fox that lays out some practical steps to take in our advocacy journey2 and an article3 showing the value of participating in a Legislative Day. Of course you can’t do everything, but it’s a new year for a fresh start! By attending Legislative Day or choosing to do one of these things in 2020 you can demonstrate Leadership in Action by advocating for our patients and our profession.
Advocacy is our job – let’s decide to do it well!
Author: Becca Nolen, Pharm.D., BCPS, BCIDP, AAHIVP Member, MSHP Research and Education Foundation
The local ASHP Clinical Skills Competition winners from both the St. Louis College of Pharmacy and the University of Missouri-Kansas City were recognized during the MSHP reception at Midyear. Congratulations to William Miller & Blake Robbins from STLCOP and Amelia Gooch & Garrett Matthews from UMKC! Thank you for representing Missouri!
MSHP R&E Foundation is currently accepting submissions and nominees for two awards. The deadline for all submissions and nominations will be Friday, January 31st.
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:
Each letter of nomination must include:
Tonnies Preceptor Award
MSHP R&E Foundation is pleased to honor a health system pharmacist for outstanding service to the profession as a preceptor to pharmacy students and/or residents. Below are the Criteria and Procedures to nominate a preceptor for the award.
The Tonnies Preceptor award was established in 2020, named after Fred Tonnies, Jr. for his long standing support of MSHP (past-president 1976-1978), Mid-Missouri Society of Hospital Pharmacists (MMSHP) (past-president 1988) and numerous professional and academic contributions to Pharmacy. He was one of the founding members of MSHP and MMSHP, and has over 35 years of precepting experience. The Tonnies Preceptor Award is presented each year to a deserving candidate who has been nominated in recognition of sustained contributions in multiple areas:
The award will be presented to a health system pharmacist that consistently exemplifies the core values (Professionalism, Desire to educate and share knowledge with students, Willingness to mentor, Willingness to commit the time necessary for precepting, Respect for others, Willingness to work with a diverse student population) and the following characteristics:
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.”
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:
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:
Common Vaccination Review
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
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.
All information and pictures sourced from www.cdc.gov/vaccines.
For any further information, or to check the most recent vaccination guidelines, please visit
Authors: Mary Thorne, PharmD, PGY1 Pharmacy Resident and Kathryn Lincoln PharmD, BCPS, BCIDP, Clinical Pharmacist – Infectious Diseases, Olathe Medical Center
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.
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.
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.
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.
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.
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.
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:
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Authors: Harrison Yoon, PharmD Candidate 2020 and Julianne Yeary, Pharm.D.
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
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.
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.
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
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.
Current Recommendations on the Prevention of HBV Infection in Patients Undergoing Hemodialysis
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)!
Authors: Caitlynn Tabaka, PharmD and
Livia Allen, PharmD, BCCCP
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
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
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
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.
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.
Submit for CE
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.
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:
To advocate for this legislation, go to ASHP’s online advocacy center, contact your representative, and ask them to co-sponsor S. 2723.