Chad Hartley II, PharmD candidate

Sepsis is a life-threatening infection that can quickly lead to tissue damage, organ failure, and even death. An estimated 18 to 31 million cases occur globally every year with 850,000 occurring in the United States.

 With the mortality rate of sepsis at up to 30%, it is the leading cause of death for patients in the ICU.

Sepsis can arise from any source of infection, with 2 of the most common sources being pneumonia and urinary tract infection.

The rapid progression of sepsis makes it imperative to diagnose and start goal-oriented treatments as soon as possible. It has been shown that patient survival rate decreases by 7.6% for every hour that antimicrobial therapy is delayed.

After sepsis is diagnosed, immediate care is indicated to prevent decompensation, organ damage, and death. A 5-step process called the 1-hour bundle was developed to facilitate rapid, goal-oriented treatment in sepsis situations. The 1-hour bundle presents a step-wise algorithm for the initial treatment of sepsis:

Start fluid resuscitation using crystalloid fluids at a dose of 20-30 mL/kg

The data show that proper recognition of sepsis indicators and adherence to goal-driven therapies decreases mortality and length of stay in the hospital. Pharmacists are ideally positioned to assist the health care team with achieving these goals and therefore improving patient outcomes.

Adherence to the 1-hour bundle has been shown to significantly reduce mortality from 20.4% without bundle adherence to 17.9% mortality with bundle adherence (p-value = 0.035).

 One study showed that patients who received antimicrobials within 1 hour of hypotension had a survival rate of 79.9%.

Furthermore, the choice of appropriate broad-spectrum antimicrobials is vital to patient survival. Results from another study investigating this topic showed that patients who received appropriate empiric therapy were 5 times as likely to survive compared to those who did not (52% versus 10.3%, p< 0.001).

Additionally, one 2-year study conducted at a teaching hospital showed that the management of patients admitted to the emergency department for sepsis decreases significantly when clinical pharmacists conduct consultations.

 During the 2-year study, 585 consultations were provided by pharmacists for patients with sepsis. These consultations included dosing recommendations (53%), addition of appropriate antibiotics (22%), and medication preparation (19%), with the main medication classes discussed being antibiotics (83%) and vasopressors (8%). In this way, pharmacists can impact the early management of patients with sepsis in multiple ways, especially in terms of the optimization of antibiotic selection and medication dosing.

Pharmacists have also proven to be valuable members of sepsis response teams and tend to improve adherence to early goal-driven therapy, leading to better patient outcomes. Several studies have shown that a pharmacist’s presence on a sepsis team has a statistically significant impact on the time to antimicrobial administration (0.61 hours versus 0.88 hours, p =0.001).

Additionally, pharmacists have been shown to have a significant impact on patients successfully receiving antimicrobials within 1 hour (100% versus 95%, p=0.025), patients receiving appropriate antimicrobials (97% versus 81%, p= 0.0008), and decreased mortality (4.8%, p=1.08).

Furthermore, one study showed that a pharmacist’s presence at bedside during initial sepsis treatment reduced the time from antimicrobial order to administration from 157 minutes to 54 minutes.

 In this way, the impact of the pharmacist extends beyond the bedside and clinical patient outcomes to other areas as well, including significantly reducing billing costs, extra drug charges, and extra laboratory charges, which helps to decrease the economic strain on hospitals and patients.

Sepsis is a serious disease that can culminate in organ damage and even death, if handled inappropriately, but there is clear evidence that with the right screening tools and policies, along with early goal-driven therapy, the risk of serious complications and mortality can be significantly reduced.

Currently, pharmacists take on several roles during patient management of sepsis. With such a rapidly progressing and deadly disease state, it is imperative to have proper strategies paired with interprofessional collaboration to increase positive patient outcomes when treating sepsis, with pharmacists playing a critical role on a sepsis response team.

Uffen JW, Oosterheert JJ, Schweitzer VA et al. Interventions for rapid recognition and treatment of sepsis in the emergency department: a narrative review. 

Cavanaugh JB, Sullivan JB, East N et al. Importance of Pharmacy Involvement in the Treatment of Sepsis. 

Milano PK, Desai SA, Eiting EA et al. Sepsis Bundle Adherence Is Associated with Improved Survival in Severe Sepsis or Septic Shock. 

The Western Journal of Emergency Medicine

Kumar A, Roberts D, Wood KE et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. 

Weant KA, Baker SN. Emergency Medicine Pharmacists and Sepsis Management. 

Moussavi K, Nikitenko V. Pharmacist impact on time to antibiotic administration in patients with sepsis in the ED. 

Sarani B, Brenner SR, Gabel B et al. Improving sepsis care through systems change: the impact of a medical emergency team. 

The Joint Commission Journal on Quality and Patient Safety

MacLaren R, Bond CA, Martin SJ et al. Clinical and economic outcomes of involving pharmacists in the direct care of critically ill patients with infections. 

Gawrys GW, Tun K, Jackson CB et al. The impact of rapid diagnostic testing, surveillance software, and clinical pharmacist staffing at a large community hospital in the management of Gram-negative bloodstream infections. 

Diagnostic Microbiology and Infectious Disease

Tarabichi Y, Cheng A, Bar-Shain D et al. Improving Timeliness of Antibiotic Administration Using a Provider and Pharmacist Facing Sepsis Early Warning System in the Emergency Department Setting: A Randomized Controlled Quality Improvement Initiative. 

Articles

Several studies have shown that a pharmacist’s presence on a sepsis team has a statistically significant impact on patient outcomes, with pharmacists taking on several roles during patient management.

Sepsis Week: Pharmacists’ Have a Critical Impact on the Treatment of Sepsis

Influenza has been one of the most common viral infections for centuries. Perhaps the most destructive and well-remembered outbreak occurred in 1918 when approximately 500 million people world-wide were infected with what became known as the Spanish Flu.

The first influenza vaccine was developed in the 1933 for Influenza A, as Influenza B was not isolated until the 1940s. The first bivalent influenza vaccination was developed shortly thereafter in 1942.

Due to the rapidly evolving nature of influenza, an annual flu vaccination is developed to protect against infection from the most prevalent strains of the virus that experts anticipate will be circulating during the upcoming season, including 2 subtypes of Influenza A (H1N1 and H3N2) and 2 lineages of Influenza B (Victoria and Yamagata). A new vaccine is annually developed based on scientific modeling and testing to determine which strains will be most prevalent in the upcoming influenza season.

Vaccination timing depends on geographic location. The Northern Hemisphere’s flu season lasts from approximately October to March, but it is possible to contract influenza at any time. After vaccination, there is approximately a 2-week window where a vaccinated individual is still susceptible while the body forms an immune response due to the vaccine.

Because influenza has a long seasonal cycle, the question regarding whether multiple influenza vaccinations, spaced throughout the season, could provide added protection has arisen. There is validity to this question as previous studies have shown decreasing influenza vaccine protection with increasing time since vaccination.

 The vaccine’s efficacy (VE) against strains of H3N2 (VE 0% 111 days after vaccination) and Influenza B (VE 21.4% at season end) in particular decreased compared to its efficacy against H1N1 (VE 50.3% at season end).

A study by Ferdinands et al. showed a consistent rate of decline in vaccination effectiveness, about 7% decrease per month, in H3N2, H1N1, and Influenza B.

 Several studies agree that vaccination effectiveness declines significantly by 5 to 6 months after vaccination depending on the influenza strain.

Additionally, studies show that in some patient populations a 2-dose regimen of the seasonal influenza vaccination can induce greater seroprotection against influenza.

 A 2-dose regimen is given because a singular dose in these patients does not stimulate the immune system enough to produce a protective number of antibodies.

The first dose of the 2-dose regimen serves to prime the immune system by activating antigen-specific helper T-cells, while the second dose provides the immunity by causing the primed cells to differentiate into effector or memory cells that can mount a stronger response to the vaccine.

 While there is a large amount of consistent evidence for young, vaccine-naïve children receiving a 2-dose regimen, the data for a 2-dose regimen in other patient populations is conflicting. For example, some studies have shown benefit in patients with solid organ transplant,

while other studies did not indicate added benefit.

 However, in these studies the vaccinations were given as contiguous doses with only 2-4 weeks between the 2 doses.

In the past, it has been thought that older adults lost seroprotection associated with influenza vaccination more quickly than younger patients.

 However, recent studies have shown that there is not as much decrease in seroprotection as previously thought.

A study conducted by Skowronski et al. indicates that older adults who achieved seroprotection rates of 70-100% with initial vaccination maintained immunity for 5-6 months, which is comparable to other age demographics.

 A second dose of the influenza vaccine, given 4 weeks after the initial dose, does not significantly improve seroprotective rates overall in geriatrics in studies.

 However, it may have the potential to lengthen the duration of immunity.

A study by Matsushita et al. showed that when given a 2-dose regimen, with doses given 4 weeks apart, seroprotection rates against H3N2 (-4.9%) and Influenza B (-8.8%) did not decline between 4 and 22 weeks after vaccination in older adults; however protection against strain H1N1 (-19.3%) did decline significantly, which should be a consideration in years when H1N1 is the predominant strain circulating.

 Similarly, overall seroprotection rates did not decline significantly differently in adults > 75 years (-20.8%) when compared to adults < 75 years (-17.1%).

Considering the conflicting evidence of these studies, a multi-dose regimen of the yearly influenza vaccine is not recommended at this time except in influenza vaccine naïve children aged 6 months to 8 years old, and in select solid organ transplant patients. A 2-dose regimen for older adults has been explored, but additional data is needed before a conclusive recommendation can be made on whether or not a second dose is warranted. Other specialized patient populations may benefit from a multi-dose regimen, but as with older adults, more studies should be done to determine the efficacy before such a regimen is implemented into practice.

For now, optimizing influenza vaccine coverage is often best addressed with immunization timing. Patients should wait until the recommended time to be vaccinated to ensure immunity will last throughout influenza season.

inpatient pharmacist in Tuscaloosa, Alabama, and a faculty member with Auburn University in Arkansas.

 is a 2022 PharmD candidate at Auburn University, Harrison School of Pharmacy in Arkansas.

Because influenza has a long seasonal cycle, the question regarding whether multiple influenza vaccinations, spaced throughout the season, could provide added protection has arisen.