Antimicrobial stewardship programs (ASPs) are critical tools for promoting the safe and effective use of antimicrobial drugs. ASPs are not developed directly for reducing healthcare costs, but good stewardship leads to more cost-effective care. This includes impacting drug expenditures as well as other costs.

Pharmacy expertise is one of the CDC Core Elements of ASPs in hospitals. Regulatory bodies such as The Joint Commission and The Centers for Medicaid and Medicare Services endorse the critical role of pharmacy expertise in ASPs. However, activities of antimicrobial stewardship pharmacists can vary significantly between organizations. Combine this with a general lack of understanding of what ASP pharmacists do and there is no surprise a gap can often be observed between what pharmacy team members think ASP pharmacists should do versus what ASP pharmacists actually can do. Further complicating the issue, variability is a major commonality across ASPs, since each organization has its own specific patient populations, epidemiology, drug use patterns, physical resources, medical services, staff strengths/weaknesses, technology, administrative structure, and organizational priorities.

Even though ASPs are complex, there are many instances where common ground can be observed across sites. For example, programs often need to focus resources on appropriate management of urinary tract infections, respiratory tract infections, and skin and soft tissue infections since they are all common infectious processes. As programs aim to address high-priority items there are also financial targets that may be at play for the department or organization. For the antimicrobial stewardship pharmacist this commonly involves engaging in measures to control drug-related costs while ensuring optimal care. 

Each year the American Journal of Health-System Pharmacy publishes an article about national trends in prescription drug expenditures, including projections for the next year. This is an excellent resource for identifying which drugs should be on your radar for high economic impact potential. In the July 2023 edition of the publication which displays 2022 data with predictions for 2023, HIV medication bictegravir/ emtricitabine/ tenofovir (Biktarvy) ranked 8 in the top 25 drugs by expenditures overall, pneumococcal conjugate vaccine ranked 17 in the top 25 drug expenditures in clinics, and remdesivir (Veklury) was the top drug expenditure in hospitals (for the second year running). By drug category, antivirals ranked third, systemic antiinfectives ranked eighth, and antifungal agents ranked twenty-fourth. It’s likely 2024 will have some of the same high-cost drugs as 2023.

In light of the above information, it may be helpful to discuss antimicrobial drug costs in the context of what antimicrobial stewardship pharmacists can do. That will be the focus of this article. Here I will discuss my top 5 high-cost antimicrobials for hospitals to watch in 2024 and how your antimicrobial stewardship pharmacist can have an impact. Please note that cost-savings/avoidance opportunities can vary by practice setting, some drugs will be discussed by category, and this is by no means an all-inclusive list of high-cost antimicrobials to look out for in 2024.

1. COVID-19 medications: Remdesivir (Veklury^®) and nirmatrelvir/ritonavir (Paxlovid^®)

Although the pandemic is over, COVID-19 is here to stay. With the musical chairs of prevalent SARS-CoV-2 variants and different types of immunity in the community, the rate of severe/critical COVID-19 has thankfully become less frequent while mild-moderate COVID-19 has become relatively more common. There is of course no way to predict the future, but it is highly likely COVID-19 will come in waves as respiratory viruses tend to do each year.

For severe/critical COVID-19, intravenous remdesivir will most likely continue to be a mainstay of therapy. Exceeding $550 per vial, a 5 day course of remdesivir is over $3,300. ASP pharmacists can impact remdesivir use practices by implementing and overseeing criteria for use which are enforced by electronic medical systems and/or pharmacy staff verifying orders. Activities can include ensuring reasonable use as well as avoiding excessively long durations of treatment or delay to discharge. ASP pharmacists can be a critical resource for bridging prescriber awareness to local guidelines, based upon institutional data and trends.

For mild-moderate COVID-19, commercially available oral nirmatrelvir/ ritonavir is the preferred option (except when issues such as drug-drug interactions are a problem). At just under $1500 for a 5 day course, nirmatrelvir/ ritonavir is less expensive than remdesivir, but it is still high cost compared to most antimicrobial drugs on the market. ASP pharmacists can help promote using nirmatrelvir/ ritonavir over remdesivir when both are an option for a hospitalized patient, which supports better treatment and reduced expenditures. Monitoring data, engaging prescriber stakeholders, and providing targeted education may serve to promote optimal use of nirmatrelvir/ ritonavir.

Molnupiravir (Lagevrio^®) approved under an Emergency Use Authorization is another COVID-19 medication to be aware of, but it’s much less likely to be used in the hospital than remdesivir or nirmatrelvir/ ritonavir, since it is third-line for mild-moderate COVID-19 and clinical data supporting it’s efficacy are much less favorable as compared to nirmatrelvir/ ritonavir.

2. Beta-Lactams for drug-resistant gram-negative bacteria

Some of the highest-cost antibacterial drugs fall into this category, and include:

• Sulbactam-durlobactam (Xacduro^®)
• Meropenem-vaborbactam (Vabomere^®)
• Imipenem-cilastatin-relebactam (Recarbrio^®)
• Ceftolozane-tazobactam (Zerbaxa^®)
• Ceftazidime-avibactam (Avycaz^®)
• Cefepime-enmetazobactam (Exblifep^®, not priced yet but expected to be expensive)
• Cefiderocol (Fetroja^®)

Most of these antibiotics fall into the $750-$1300 per day range, but it does depend on renal function, dosing, and contracting. The mix of use on these antibiotics will vary depending on local epidemiology and prescriber preferences. Caring for immunocompromised patients or those from a local nursing facility may be a big driver of drug use for multi-drug resistant organisms, which is where these antibiotics are most commonly employed.

ASP pharmacists and infectious diseases physicians should arguably be involved with every case in which one of these antibiotics is prescribed. ASP pharmacists should work with local stakeholders to steer reasonable selection for initiation, streamlining after 48-72 hours, safety monitoring, and local protocol development with formulary decisions. In addition, ASP pharmacists can work with pharmacy buyers and patient assistance program contacts to control inventories, ensuring the antibiotics that are expected to be needed are available, but while also ensuring excessive stock is avoided and vial replacement programs are leveraged.

3. Intravenous vancomycin

In most hospitals intravenous vancomycin remains the mainstay for empiric treatment of severe infections suspected to involve gram-positive bacteria such as methicillin-resistant Staphylococcus aureus (MRSA). While vancomycin drug acquisition costs are not near what is seen with the newer beta-lactam/ beta-lactamase inhibitors, the whole price of vancomycin is considerable and may even contribute to longer than necessary lengths of stay. Vancomycin takes up a lot of time for pharmacists, nurses, and labs. Using it smarter or avoiding it all together can yield economic benefits which impact multiple departments and reduce the risk for acute kidney injury.

ASP pharmacists can help promote use of vancomycin alternatives, de-escalation, and discharge facilitation. There are a long list of ways ASP pharmacists can engage with this, which includes but is not limited to:

• Engaging lab on workflows to leverage MRSA nares PCR to de-escalate therapy
• Working with emergency department prescribers to selectively avoid unnecessary initiations for indications such as non-purulent skin infection or urosepsis
• Promoting oral antibiotics (including now inexpensive oral linezolid) to help facilitate discharge
• Early switch to daptomycin for discharge or in patients at high risk for acute kidney injury
• Employing a vancomycin monitor to engage stakeholders in improving practices
• Teaching pharmacy staff how to individualize vancomycin care to optimize workflows which reduce burdens on pharmacists, nurses, and lab staff

A programmatic approach to optimizing vancomycin practices is recommended, rather than attempting to assign the ASP pharmacist to serve as the daily front-line vancomycin dosing and monitoring point-person.

4. Vaccines

Use of vaccinations within the hospital are impacted by patient populations, regulatory requirements, and organizational priorities. Vaccines for influenza, pneumococcus, tetanus, diptheria, hepatitis B, and rabies (including rabies immune globulin) may be of particular note due to volume of use and acquisition cost. Vaccines such as those for RSV, varicella, and SARS-CoV-2 may be less relevant to the hospital setting if more encouraged for outpatient use, but may also be relevant in the hospital. Hospitals should consider their individual historical and expected vaccine use.

ASP pharmacists can assist with developing as well as evolving standardized processes for patient identification and delivery of vaccinations, working with medical, nursing, informatics, and other staff. ASP pharmacists may also lead medication use evaluations while overseeing pharmacy learners (e.g., student interns, residents), which support identifying opportunities to enhance local practices.

Vaccine-related work is not something an ASP pharmacist needs to be deeply engaged in, but they should be involved in the programmatic monitoring of routine practices and engagement for workflow improvements. ASP pharmacists may also be good team players for vaccine inventory control, especially when shortages are expected (e.g., the tetanus vaccine supply issue of 2024).

5. HIV medications

Bictegravir/ emtricitabine/ tenofovir (Biktarvy^®) costs around $140 per pill. It is one of the most important HIV medications today as a well-tolerated single pill regimen recommended by HIV.gov guidelines. Other guideline-recommended antiretrovirals such as rilpivirine (Edurant^®), and emtricitabine/ tenofovir alafenamide (Descovy^®) also carry significant acquisition costs at approximately $50, $75 per pill, respectively.

ASP pharmacists can assist with developing programs focused on antiretroviral stewardship and  formulary management. They can also support inventory control measures, which includes consideration for working with some medications that have short-date expirations after opening. Since many hospitals do not deal with a high volume of patients with HIV, ASP pharmacists can serve as a critical resource to ensure complete regimens, avoiding missed doses, and proper monitoring.

Closing Comments

Institutions can choose to employ their ASP pharmacist as programmatic workflow coordinators, front-line infectious diseases clinical pharmacists, or a mix of the two. How ASP pharmacists are empowered has a great impact on their ability to mitigate costs related to antimicrobial agents such as those discussed here. There can be a great benefit to having ASP pharmacists engaged in pharmacy operations (including inventory control), clinical pharmacy workflow management (including staff interventions), and front-line services (including guiding the use of high-cost beta-lactams).

Several other items of interest not discussed here may include antifungal drugs (e.g., posaconazole [Noxafil^®], isavuconazole [Cresemba^®]), C. difficile therapies for treatment (e.g., fidaxomicin [Fidaxomicin^®]) or prophylaxis (e.g., Vowst^®, Rebyota^®), and long-acting agents primed for outpatient infusion (e.g., dalbavancin [Dalvance^®], oritavancin [Orbactiv, Kimyrsa], rezafungin [Rezzayo^®]).

Find Timothy Gauthier, Pharm.D, BCPS, BCIDP as @IDstewardship on X and Instagram.

The views and opinions expressed in this article are those of the author and do not necessarily reflect the policy or position of any previous, current, or potential future employer.