Antimicrobial Shortages: Opportunity to Improve Use?

2016 - 2 April - SCCM’s Quality Improvement Initiatives
Anthony Gerlach, BCPS, PharmD, FCCM; Karri Bauer, PharmD, BCPS AQ-ID
In this article, two experts discuss antimicrobial shortages.

 


The number of drug shortages has dramatically increased in recent years, with antimicrobials accounting for 15% of all shortages.(1) Antimicrobials represent life-saving medications, particularly for hospitalized patients, and present significant challenges in the arena of drug shortages. Between 2001 and 2013, the average number of antimicrobial shortages was 14.2, with a median duration of 188 days.(1) Of significant concern for hospitalized patients, injectable antimicrobials had a trend toward longer shortages compared to noninjectable antimicrobial shortages (median 250 days vs. 129 days, p = 0.06).(1)

There are many reasons for shortages. The most commonly cited reason is unavailability of raw materials or bulk items.(2) Noncompliance with current good manufacturing practices or other regulations may result in U.S. Food and Drug Administration (FDA) enforcement actions and temporary discontinuation of manufacturing. In addition, product contamination due to impurities or manufacturing delays may also lead to shortages. Importantly, many antimicrobials are sterile injectable products, which are at higher risk of contamination than oral medications. 

For hospitalized patients with infections, an antimicrobial may represent an irreplacable therapeutic option. In the event of a drug shortage, a nonpreferred or ineffective alternative antimicrobial may be selected if clinicians with expertise are not involved in the selection of the most appropriate substitute.(3) In addition, timely antimicrobial therapy is critical for the successful management of infectious diseases. If a particular antimicrobial is not readily available, time to active therapy may also be delayed.Complicating the issue further is the dramatic reduction in the approval of new antimicrobials by the FDA and the problem of escalating antimicrobial resistance. These factors are particularly worrisome because approximately half of antimicrobial shortages involved agents used in the treatment of resistant organisms.(1)

An example of a critical antimicrobial shortage is the ongoing issue with carbapenems. The current imipenem/cilastatin backorder has led to increased demand for the other antipseudomonal carbapenems, including meropenem and doripenem. For many patients, carbapenems represent the last-line class of antimicrobials for the treatment of multidrug-resistant organisms, including extended-spectrum beta-lactamase-producing organisms. In addition, the carbapenem shortage may also have partly caused disruptions in the distribution of other antipseudomonal beta-lactams, including piperacillin/tazobactam.(4) The shortage of these antimicrobials may lead to the use of inappropriate or more toxic agents, resulting in suboptimal patient outcomes. 

Clinicians must be aware of antimicrobial shortages and collaborate with interested parties, such as the institution’s antimicrobial stewardship program, to develop plans in their respective areas. The websites of both the FDA and the American Society of Health-System Pharmacists provide real-time useful information on antimicrobial shortages that clinicians should consult. Communication about shortages and multidisciplinary management is critical to prevent patient harm.(5) A variety of stewardship principles may assist in the management of shortages, including antimicrobial de-escalation and intravenous (IV) to oral switch. Appropriate de-escalation from broad-spectrum therapy can assist in preserving a limited supply. In addition, IV to oral switch is an important stewardship strategy, especially during a shortage, since the majority of antimicrobial shortages are injectable formulations. Although the majority of these data are from medical ICU patients, Elofson and colleagues demonstrated that switching to enteral antibiotics for the treatment of bacterial pneumonia within four days of initiation produced similar outcomes to the use of IV antibiotics in a surgical population.(6)

Conclusions
Antimicrobial shortages continue to present significant challenges for clinicians, particularly in the critical care setting. Clinicians must continue to collaborate with antimicrobial stewardship programs to ensure appropriate antimicrobial use during shortages. Antimicrobial stewardship principles, including de-escalation and IV to oral switch are imperative in conserving limited-supply antimicrobials, and represent options in critically ill patients. A multidisciplinary, comprehensive strategy and subsequent education of healthcare providers are key factors in the successful management of antimicrobial shortages.

References:

1.  Quadri F, Mazer-Amirshahi M, Fox ER, et al. Antibacterial drug shortages from 2001 to 2013: implications for clinical practice. Clin Infect Dis. 2015 Jun 15;60(12):1737-1742.
2.  Griffith MM, Gross AE, Sutton SH, et al. The impact of anti-infective drug shortages on hospitals in the United States: trends and causes. Clin Infect Dis. 2012 Mar 1;54(5):684-691.
3.   Leviton I. Commentary on “The impact of anti-infective drug shortages on hospitals in the United States: trends and causes.” Clin Infect Dis. 2012 Mar 1;54(5):692-693.
4. American Society of Health-System Pharmacists. Current Drug Shortage Bulletins. http://www.ashp.org/DrugShortages/Current/. Accessed January26, 2016.
5.  Griffith MM, Pentoney Z, Scheetz MH. Antimicrobial drug shortages: a crisis amidst the epidemic and the need for antimicrobial stewardship efforts to lessen the effects. Pharmacotherapy. 2012 Aug;32(8):665-667.
6.  Elofson KA, Forbes RC, Gerlach AT. Can enteral antibiotics be used to treat pneumonia in the surgical intensive care unit? A clinical outcomes and cost comparison. Int J Crit Illn Inj Sci. 2015 Jul-Sep;5(3):149-154.