The legal implications of giving beta-lactam antibiotics to patients with a penicillin allergy are not widely understood by clinicians. In this interview a group of researchers with a recent publication on the topic discuss their work investigating the issue.
Interview with: Meghan Jeffres, Pharm.D., Elizabeth Hall-Lipsy, J.D., M.P.H, John Cleary, Pharm.D., FCCP, BCPS-AQ ID, and Travis King, Pharm.D., BCPS
Interview by: Timothy P. Gauthier, Pharm.D., BCPS-AQ ID
[Last updated: 8 May 2018]
Penicillin allergies are the most common drug allergy label for patients in the United States, with an estimated prevalence of around 10% of the population [1-4]. Interestingly, of all patients with a penicillin allergy label, only about 10% will have an allergic reaction if given penicillin [1-3]. The reason for the discrepancy between allergy labels and true allergies is influenced by factors such as inaccurate allergy histories and the fact that some true allergies can be lost over time. When a patient has a penicillin allergy label, clinicians infrequently have access to penicillin skin testing or other methods to help identify if the allergy label represents a true allergy or not.
The penicillin class of antibiotics is part of a larger group of antibiotics called beta-lactams, which includes the cephalosporin class and carbapenem class. Due to similar chemical structures, a true penicillin allergy may represent allergy to other beta-lactam drugs. In recent years cross-reactivity between beta-lactams has been increasingly attributed to common side-chains.
Beta-lactam drugs are amongst the most commonly employed antibiotics in clinical practice and frequently represent first-line drug options. If a penicillin allergy is present, it can block a clinician’s ability to provide the most safe and effective medication to their patient. With 90% of penicillin allergy labels being inaccurate, there are many instances when a clinician can reasonably prescribe a beta-lactam antibiotic despite the presence of a penicillin allergy label. However, there is a level of risk involved which varies greatly depending upon the particular clinical scenario.
As healthcare providers weigh the risks and benefits of using these front-line antibiotics in their patients with penicillin allergy labels, one question that may come up is about what legal risks exist. Published content for clinicians focusing on this topic is limited, but fortunately Dr. Meghan Jeffres and colleagues investigated the issue and have recently published their findings:
Given that this is a highly relevant topic in the field of antimicrobial stewardship, I reached out to the authors and requested an interview. They graciously accepted and the following was developed. Here are insights on the legal implications of giving beta-lactam antibiotics to patients with a penicillin allergy label…
1. What prompted your group to undertake an analysis of professional liability related to penicillin allergy labels?
I (M.J.) was frustrated by how many patients labeled as penicillin allergic were getting fluoroquinolones regardless of allergy history. When recommending cephalosporins or carbapenems both pharmacists and physicians often pushed back out of fear of legal action. I had no idea how to respond to their concerns.
[Note: fluoroquinolones are a class of antibiotics with multiple safety concerns]
A small group of Roseman pharmacy students did an initial search for cases using Google Scholar, which allows for case law searches. After reading only a few of the 350 cases identified, we quickly realized we were in over our heads. It turns out case law is its own language. We could not even figure out who won or lost a case. The stories about each case were fascinating, but there were so many cases to screen filled with legal jargon, the project progressed at an embarrassingly slow rate.
John Cleary reinvigorated the project while he was my mentor at American College of Clinical Pharmacy Focused Investigator Training. Our new goal was to find a lawyer willing to collaborate. It was a beautiful day when I received an email from Elizabeth Hall-Lipsy about an unrelated project and saw JD in her signature line. I waited approximately 5 seconds before tangenting to the penicillin allergy legal review project. She HAPPILY* accepted and brought a tremendous amount of clarity and organization to the project.
*Use of an all caps HAPPILY by E.H.L.
2. What is the major take home point for physicians and pharmacists when it comes to the legal implications of giving a beta-lactam antibiotic to a patient with a penicillin allergy label?
E.H.L.: Three take away points: DOCUMENT, DOCUMENT, DOCUMENT!
There is a really enormous difference between a mistake and professional negligence. No healthcare professional is going to be mistake-free, and we cannot expect anyone to be; we expect pharmacists to use their best judgment, and make a judgment call as to the best therapy for a patient in this situation under these circumstances. This is how and why documenting the decision-making process, the rationale for the selection of the best therapy out of several options, makes a difference in determining whether healthcare providers are negligent.
Concurrent notes describing the patient’s course of treatment are really helpful since most lawsuits are filed and litigated years after the actual event. Who can remember what they did and why they did it two years later? Accurate and thorough charting and notekeeping are the best tools for avoiding legal implications of decisions that might have negative consequences.
3. In your research did you unexpectedly come across anything that you found to be particularly surprising or interesting?
A favorite and most unexpected case did not make it into the systematic review, because the patient was Ferdinand the bull and not a human. In 1973, a veterinarian in Oklahoma performed minor surgery to correct a partial prolapse of the prepuce and gave Ferdinand 5 million units of penicillin post-operatively. He experienced an immediate allergic reaction and “gave up the ghost” even after administration of adrenalin and cortisol per court transcripts. The owner of the bull sued the veterinarian claiming that the veterinarian was negligent by not giving the bull a test dose to check for a penicillin allergy and failing to monitor the bull after administering penicillin.
The first trial found the veterinarian negligent. The veterinarian appealed, lost, then appealed to the Supreme Court of Oklahoma and won. The court stated that the testimony showed that penicillin was the best post-operative antibiotic available, reaction to penicillin in large animals was rare, a large animal’s failure to respond to treatment was even more rare, and for this reason it was not the practice in the community to warn of possible reactions to penicillin. The court stated that the evidence was insufficient to support an inference that a reasonably prudent veterinarian in the exercise of reasonable care would have disclosed this risk to the owner. In addition, the court concluded that the veterinarian had no duty to warn the owner his bull might have had a reaction to the penicillin. The court held that the record was insufficient to support an inference a veterinarian employing the reasonable skill, diligence, and attention as may ordinarily be expected of careful, skillful and trustworthy persons in his profession would have conducted a pre-injection sensitivity test.
4. Would you consider cephalosporins and carbapenems to be contraindicated for any specific patient groups with a labeled penicillin allergy?
We believe carbapenems are safe for patients with penicillin allergies.
Penicillins and carbapenems are structurally different and do not have any side chain similarities. There are also two trials, each with over 200 patients, in which patients with proven allergies to penicillin tolerated both skin and IV challenges to imipenem-cilastatin, meropenem, and ertapenem.
- Patients with Immediate penicillin allergy (type I): Gaeta et al. J Allergy Clin Immunol 2015;135:972-976.
- Patients with delayed penicillin allergy (type II, III, IV): Romano et al. Allergy 2013;68:1618–1621.
Unlike carbapenems, several cephalosporins share side chains with penicillin, amoxicillin, or ampicillin. Due to the high rate of cross-reactivity between penicillin, amoxicillin, and ampicillin, we recommend avoiding any cephalosporin with similar side chains to any of the natural penicillins. The most commonly used cephalosporin that shares a side chain is cephalexin. Cephalexin and ampicillin have a side chain that is almost identical and have been shown to be cross-reactive in 20% of patients. There are three excellent reviews with cross-reactivity charts that explore the medicinal chemistry of cephalosporin and penicillin side chains.
- Side chain cross-reactivity: Romano et al. J Allergy Clin Immunol. 2016;138(1):179-186.
- Side chain revew: Trubiano et al. J Allergy Clin Immunol Pract 2017;5:1532-42.
- Side chain review: DePestel et al. J Am Pharm Assoc 2008;48:530–540.
5. What would you suggest is the greatest misconception that needs to be addressed when it comes to legal concerns and prescribing beta-lactam antibiotics to patients with a penicillin allergy label?
E.H.L.: The vast, vast majority of cases never make it to trial. Many providers worry about having a judgment against them, but it is very unlikely that a lawsuit will make it to trial.
Lawsuits make for good TV, but most cases take a long time in the discovery phase where all parties disclose their experts’ opinions and theories of the case and never is a new piece of evidence discovered the night before trial.
Generally, cases settle or are determined through motions where as a matter of law, parties or claims can be dismissed from the lawsuit.
6. What do you expect the future holds at the cross-roads of litigation and prescribing beta-lactams to patients with a labeled penicillin allergy?
In the future we think the prevalence of pharmacist defendants in malpractice suits is likely to increase.
Historically, as long as a pharmacists accurately filled a prescription they were generally protected against liability if a patient experienced an adverse outcome related to their medication. But, the role of the pharmacist as a member of the health care team is expanding to emphasize the cognitive services of a pharmacist rather than the product dispensed. As pharmacists advocate for greater patient care responsibilities and “provider” status, become a more visible member of the health care team, and more frequently provide cognitive services, they and their employers, will become named parties to malpractice suits with greater frequency.
The Klasch v. Walgreens is an excellent example of the changing legal opinion of a pharmacist’s responsibility. A pharmacist working for Walgreens was the target of a medical negligence case in which TMP/SMX was dispensed to a patient with a known sulfa allergy. The case involved a woman who had reported she might have a sulfa allergy to her physician in 2005 but was unsure. In 2006, she required an antibiotic for a urinary tract infection. Her physician prescribed TMP/SMX after questioning her allergy history, which Klasch downplayed as not being significant. A caregiver went to pick up the TMP/SMX prescription from Walgreens. The pharmacist asked the caregiver to call Klash in an effort to clarify the sulfa allergy notation in her profile. Klasch reported that she had taken TMP/SMX in the past and had not experienced a reaction. The pharmacist filled and dispensed the TMP/SMX prescription. Klasch ingested the TMP/SMX later the same day and developed a rash that progressed to toxic epidermal necrolysis and death. The original court granted summary judgment for Walgreen Co. that was appealed. Summary judgement means Walgreens won. The case was appealed by the Klasch Estate. The appellate court sided with the Klasch Estate and stated that a pharmacist has a duty to exercise reasonable care in warning the customer or notifying the prescribing doctor of this risk. Based on this ruling it is possible to conclude that the pharmacist needed to 1) call the prescribing physician to verify a TMP/SMX prescription in the setting of a sulfa allergy and 2) educate Klasch of the risk of an allergic reaction, how to identify symptoms of allergic reaction and what to do if symptoms occur.
This case is an excellent teaching case that tests the learned intermediary doctrine and will likely be cited in future cases in which a pharmacist is the defendant. The American Bar Association wrote a great article explaining how the ruling of the Nevada Supreme Court interacts with the learned intermediary doctrine, available here. You can even listen to discussion between lawyers and the Nevada Supreme Court here.
REFERENCES
DISCLAIMER
The contents of this interview are for informational purposes only and not for the purpose of providing legal advice. The opinions expressed are the opinions of the authors and may not reflect the opinions of other clinicians or attorneys. Anyone seeking medical-legal guidance should consult with a licensed legal professional.
I would like to express my utmost appreciation to Dr. Jeffres, Prof. Hall-Lipsy, Dr. Cleary, and Dr. King for taking the time to complete this interview and share their perspectives on this important topic.
ABOUT THE INTERVIEWEES
Dr. Jeffres obtained her doctor of pharmacy degree from the University of Wyoming School of Pharmacy (Laramie, WY). After graduation she completed a pharmacy practice residency with Intermountain Healthcare (Lake City, UT), followed by a pharmacy specialty residency in infectious diseases at Barnes-Jewish Hospital (St. Louis, MO). Dr. Jeffres is currently at the University of Colorado Skaggs School of Pharmacy (Aurora, CO) where she teaches infectious diseases, global health, and clinical decision making. Her practice site is the University of Colorado Hospital (Aurora, CO) where she precepts pharmacy students and pharmacy residents on an internal medication rotation.
Dr. Jeffres areas of research include: infectious diseases patient outcomes, antibiotic stewardship, antibiotic adverse reactions and allergies, and active learning.
You can find her on Twitter @PharmerMeg.
Elizabeth A. Hall-Lipsy, JD, MPH
Professor Hall-Lipsy received a Masters of Public Health in 2002 and a Doctor of Jurisprudence degree in 2005, both from the University of Arizona.
She coordinates The University of Arizona of Arizona College of Pharmacy’s Professional Certificate in Health Disparities and focuses her scholarship on health disparities as well as laws and policies that influence health.
John Cleary, Pharm.D., FCCP, BCPS-AQ ID
Dr. Cleary is a pharmacotherapist at a metropolitan Catholic hospital and faculty at the University of Mississippi Schools of Pharmacy and Medicine. He has been a pharmacotherapist at Saint Dominic – Jackson Memorial Hospital since 1992 where he has been practicing infectious diseases in addition to general pharmacotherapy. He joined the University of Mississippi, School of Pharmacy in 1986, reached the rank of Professor in 2000 and in 2012 became an emeritus professor. In August of 1990 he received an appointment at the University of Mississippi School of Medicine and is a founding director of the Mycotic Research Center. During his nearly 30 years at the University, he has established and directed an ASHP accredited residency in Infectious Disease and an ACCP accredited Fellowship in Infectious Diseases. He is BPS board certified and has added qualifications in Infectious Diseases. Prior to this faculty appointment, he earned a B.S. degree in pharmacy from the University of Missouri – Kansas City in 1983, a Doctor of Pharmacy (Pharm.D.) degree from the University of Iowa in 1985 and finally, completed infectious disease training at the University of Minnesota in 1986.
He has published more than 100 peer reviewed manuscripts and book chapters in the area of infectious diseases, many specifically focused on improving antifungal pharmacotherapy. He is a manuscript reviewer for several prestigious pharmacy and medical journals and is currently serving on the Editorial Board of The Annals of Pharmacotherapy and Current Fungal Infection Reports. In recognition of his contributions to the profession, he received multiple awards, the most prestigious includes a Fulbright Scholarship.
Travis King, Pharm.D.
Dr. King earned his Doctor of Pharmacy degree from the University of Mississippi, School of Pharmacy. He completed his PGY1 Pharmacy Practice residency at Methodist University Hospital in Memphis, TN and went on to complete a PGY2 Infectious Diseases residency at the University of Mississippi Medical Center in Jackson, MS.
Dr. King currently works at Ochsner Medical Center – New Orleanrs, where he specializes in the management of complex infectious diseases, antimicrobial stewardship strategies, and clinical microbiology. He is an active member of the Infectious Diseases Society of America, Society of Infectious Diseases Pharmacists, American Society of Microbiology, Clinical & Laboratory Standards Institute, and American College of Clinical Pharmacy. His practice and research interests include antifungal stewardship, molecular detection of antimicrobial resistance, antimicrobial stewardship practice improvement, and antimicrobial toxicology.
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