A Day Late and a Dollar Short: Managing Antimicrobial Drug Shortages

Little,Erica;Tucker,Natalie;

A Day Late and a Dollar Short: Managing Antimicrobial Drug Shortages

September 3, 2024

By Erica K. Little, PharmD, BCIDP
Natalie Tucker, PharmD, BCIDP

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ContagionContagion, Summer 2024 Digital Edition

Volume 09

Issue 02

With antimicrobial drug shortages expected to continue globally, developing mitigation strategies is essential to prevent complications, including antimicrobial resistance.

2024 is on track to have the highest number of new shortages per year in over a decade.

Drug shortages are nothing new in the world of pharmacy. As of March 31, 2024, 48 new drug shortages have already been reported per the American Society of Health-System Pharmacists. This puts 2024 on track to have the highest number of new shortages per year since 2012.¹ Unfortunately, antimicrobials are 42% more likely to be in shortage than the average medication² and are currently among the top 5 drug classes with active shortages (FIGURE).¹ One of the main factors that drives the increased risk of a drug shortage is price. The low prices of many commonly used generic antimicrobials can create a margin that is not sustainable for manufacturers to maintain an adequate supply chain.² On a global scale, there are only a small number of geographically concentrated manufacturers supplying the active pharmaceutical ingredients needed to maintain the supply chain, meaning there is decreased ability to absorb changes and a heightened risk of disruption due to environmental or other factors.³

Shortages of first-line antimicrobials can have devastating consequences from both a patient care and global health perspective. These shortages often lead to increased use of second- or third-line antimicrobials that have broader spectrums, higher risks of adverse effects, higher costs, and potentially less evidence for efficacy in definitive treatment of certain organisms. Increased use of broadspectrum agents can have a significant impact on antimicrobial resistance,^4,5 which is considered by the World Health Organization to be one of the top 10 global health threats facing humanity.²

During a piperacillin/tazobactam shortage that began in 2015,⁶ findings from one study at an academic medical center found that meropenem usage increased by 111% despite the center having an active antimicrobial stewardship program.⁷Another academic medical center saw their frequency of vancomycin-resistant enterococci and carbapenem-resistant Enterobacterales nearly double during the same shortage.⁸ Findings from a study of 88 US medical centers identified that risk of hospital-onset Clostridioides difficile infection increased significantly at institutions that shifted practice toward using broader-spectrum antibiotics.⁹From a global health perspective, lack of access to antimicrobials can be a driver of excess mortality, especially in lower-income countries.¹⁰ In addition to the negative impact on patient care, shortages can have a significant impact on healthcare organizations from an operational and cost perspective, which includes the increased workload needed to change pharmacy automation and electronic medical records (EMRs).¹ To address an antimicrobial shortage at an institution, various measures need to be implemented. These measures should involve members from purchasing, pharmacy, antimicrobial stewardship, and infectious diseases to create alternative treatment plans. Colleagues from informatics also need to be involved if changes in the EMR are needed to address the shortage. Changing how antimicrobials in shortage are ordered in the EMR can be a challenge. One option is to remove the medication from clinician order entry. This requires the clinician to contact the pharmacist to order the medication; therefore, the hospital must have 24-hour pharmacy services to prevent any delays in care. The benefit of this strategy is that it requires the pharmacist to serve as a double check that the medication is indicated for the patient; appropriate alternatives can also be provided as necessary in real time. Findings from 2 studies that reviewed the effects of a restriction-based approach through pharmacy for an antibiotic shortage demonstrated a significant decrease in use of the target antibiotic for the duration of the shortage period.^11,12 A second option is to build an alert in the EMR to direct providers to clinically appropriate alternatives when the antimicrobial agent in shortage is ordered. This option empowers the clinician to choose an appropriate alternative themself and does not require the pharmacist to be contacted in every case. However, the pharmacist should still carefully review the order in verification to ensure the most appropriate alternative is selected for the patient. An example of what this looks like can be seen in the TABLE.

A third option involves sequestering stock of the antimicrobial agent in shortage to the central inpatient pharmacy rather than storing it in automated dispensing cabinets throughout the hospital or in operating rooms. This helps maintain a more accurate count of available product and maintain tighter control over allocation of the drug to better conserve supply for patients with appropriate indications. With any of the previous options, ensuring timely communication to pharmacy staff and clinicians regarding the shortage and mitigation plans is critical. Even though there are significant challenges, there can also be opportunities that arise from antimicrobial shortages. When a specific agent can no longer be used, this allows the antimicrobial stewardship team to reevaluate its current use and place on formulary. Through this review, areas of improvement are often identified. One example from past experience is the intravenous azithromycin shortage during the start of the COVID-19 pandemic in 2020. This allowed for implementation of a 5-dose automatic duration on all azithromycin orders to prevent patients with respiratory tract infections from receiving unnecessary doses, based on guidelines for upper and lower respiratory tract infections available at the time.^13,14,15After the shortage resolved, the 5-dose limit was kept in place, paving the way for future EMR-based projects aimed at reducing antimicrobial durations of therapy.

Antimicrobial shortages can provide an opportunity to leverage supply conservation demands to gain support from information technology (IT) and health-system leadership for implementing long-term, evidence-based practice changes. During a previous experience with a cefazolin shortage concern,⁶ a review of inpatient cefazolin usage found that most administrations occurred in the perioperative setting. This prompted a review of surgical antibiotic prophylaxis guidelines and order sets, leading to the discovery that most surgeons were using cefazolin postoperatively for a full 24 hours.

An initiative was proposed to eliminate postoperative administration of antibiotic prophylaxis for most procedure types based on a review of clinical literature and national guidelines supporting single-dose, preoperative- only prophylaxis.¹⁶This initiative was approved by surgical group leaders without significant pushback due to the urgency of an impending shortage and the push to conserve cefazolin for patients with severe infections. Additionally, health-system IT teams often prioritize updates to the EMR due to drug shortages, so changes to several major perioperative order sets were ready to go live in significantly less time than an average IT resource-intensive project. Because of the updates to guidelines and order sets made possible by the shortage, the initiative was successfully implemented and remained the standard of care after the shortage period. With antimicrobial shortages expected to continue, it is important that pharmacy teams and antimicrobial stewardship programs in every health-system work together to proactively develop strategies to mitigate consequences of shortages. There should ideally be a consistent pharmacy-driven system in place to monitor and track impending shortages and determine the need to order additional stock or implement mitigation efforts. With proactive systems in place, it is more feasible to look for the opportunities created by shortages to review existing practices and implement changes that may benefit the health-system and patient care in the long run.