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Clinical Case for Discussion: You are attending to a healthy 72-year-old female for open reduction and internal fixation of a hip fracture. She is allergic to penicillin — she developed hives from a dose when she was a child. The orthopedic surgeon orders 1 gram of cefazolin IV before incision. What do you do?
Discussion: This is an important question for anesthesiologists. Many of us anesthetize up to 700 patients per year, and it’s common to administer pre-op cephalosporins for many of those cases. Numerous patients are allergic to penicillin. Let’s imagine two possible scenarios.
Scenario One: After the uneventful induction of general anesthesia, you mix 10 ml of normal saline with the powdered vial of 1 gram of cefazolin, and inject the antibiotic into your patient’s IV over two minutes time. One minute later, the oximeter tracing disappears, the blood pressure is unmeasurable, and frothing fluid bubbles up in the lumen of the endotracheal tube. You diagnose anaphylaxis.
Rewind and try again. Scenario Two: You choose to avoid cefazolin because of the previous penicillin allergy. Instead, you inject 1 gram of vancomycin over two minutes. The patient’s skin turns red, her blood pressure drops to 50/30, she develops ST elevation on her ECG, and she has a cardiac arrest.
In both scenarios, you wish you’d done something different. The key question is: How common is anaphylaxis to a cephalosporin in a patient with penicillin allergy?
First, let’s examine the incidence of penicillin allergy. Goodman & Gilman’s The Pharmacologic Basis of Therapeutics, 2006, Chapter 44, states that “Allergic reactions to penicillin occur in 0.7 – 10% of treatment courses. In approximate order of decreasing frequency, manifestations of allergy to penicillins include rashes, fever, bronchospasm, vasculitis, serum sickness, exfoliative dermatitis, Stevens–Johnson syndrome, and anaphylaxis. . . . About 0.001% of patients treated with penicillins die from anaphylaxis. . . . there are at least 300 deaths per year due to this complication of therapy. About 70% of these patients have had penicillin previously.”
Regarding cephalosporins, the same textbook states “Hypersensitivity reactions to the cephalosporins are the most common side effects, and there is no evidence that any single cephalosporin is more or less likely to cause such sensitization. The reactions appear to be identical to those caused by the penicillins, perhaps related to the shared beta-lactam structure of both groups of antibiotics. Immediate reactions such as anaphylaxis, bronchospasm, and urticaria are observed. . . . Because of the similar structures of the penicillins and cephalosporins, patients who are allergic to one class of agents may manifest cross-reactivity to a member of the other class. Immunological studies have demonstrated cross-reactivity in as many as 20% of patients who are allergic to penicillin, but clinical studies indicate a much lower frequency (about 1%) of such reactions.” The same textbook advises, “Patients with a history of a mild or a temporally distant reaction to penicillin appear to be at low risk of rash or other allergic reaction following the administration of a cephalosporin. However, patients who have had a recent severe, immediate reaction to a penicillin should be given a cephalosporin with great caution, if at all.”
A 2006 study (Apter AJ et al, Is There Cross-reactivity Between Penicillins and Cephalosporins? Am J Med. 2006 Apr;119(4):354.e11-9) presented a retrospective cohort study using the United Kingdom General Practice Research Database. A total of 3,375,162 patients received a penicillin; 506,679 (15%) received a subsequent cephalosporin. Among patients receiving a penicillin followed by a cephalosporin, absolute risk of anaphylaxis after the cephalosporin was less than 0.001%. The authors concluded that cephalosporins can be considered for patients with penicillin allergy.
A 2007 study (Pichichero ME, et al, Safe Use of Selected Cephalosporins in Penicillin-Allergic Patients: a Meta-Analysis. Otolaryngol Head Neck Surg. 2007 Mar;136(3):340-7) examined the Medline database for 40 years from 1965 to 2005, and found a significant increase in allergic reactions to cephalothin, cephaloridine, cephalexin, cefazolin, and cefamandole in penicillin-allergic patients; no increase was observed with cefprozil, cefuroxime, ceftazidime, or ceftriaxone. The authors concluded that first-generation cephalosporins have a modest cross-allergy with penicillins, but cross-allergy is negligible with 2nd- and 3rd-generation cephalosporins.
A 2002 study (Hameed TK, Robinson JL. Review of the Use of Cephalosporins in Children With Anaphylactic Reactions From Penicillins, Can J Infect Dis. 2002 Jul;13(4):253-8), searched the PubMed database including the 35 years from 1966 to 2001, and identified 5 case reports of anaphylaxis to cephalosporins in patients who had previous anaphylaxis to penicillin. None were children. They found an additional 12 published cases of cephalosporin anaphylaxis in patients with a history of penicillin allergy but without penicillin anaphylaxis. The authors concluded that there was no evidence to support the avoidance of cephalosporins in children who had previous anaphylaxis to penicillin.
I surveyed the Stanford private practice community anesthesia faculty regarding their standard approach to this problem, and discovered the following: 1) None of the private anesthesiologists would administer IV cephalosporins to a patient whose past reaction to penicillin was life-threatening, e.g. bronchospasm, anaphylaxis or airway swelling. 2) In patients with a past history of a penicillin-induced urticaria, the private practitioners were split 50:50 on whether they would administer the requested cephalosporin. Half the practitioners considered penicillin-induced urticaria a contraindication to cephalosporin, and half did not. The importance of accurate history-taking was stressed, as many patients are not certain of the difference between a rash and hives. 3) None of the private anesthesiologists had a case of anaphylaxis to a cephalosporin in a patient with a penicillin allergy.
If an anesthesiologist decides not to administer a cephalosporin, the anesthesiologist will likely consult with the attending surgeon for his/her preference for an alternative broad-spectrum pre-op antibiotic of choice. Common alternatives to a cephalosporin are clindamycin, vancomycin, or ciprofloxacin. Alternative antibiotics have their own issues. Clindamycin carries the risk of pseudomembranous colitis. Rapid IV administration of vancomycin can result in marked vasodilation, the “red-man syndrome,” and an acute drop in blood pressure, as in Scenario Two above.
What will you do for the 72-year-old woman with the past history of penicillin-induced hives? Per Apter’s study, the risk of cephalosporin-induced anaphylaxis in the patient with a history of penicillin allergy is less that .001%. Comforted by this knowledge, you administer the cefazolin IV over twenty minutes. The patient has no adverse reaction.
Introducing …, THE DOCTOR AND MR. DYLAN, Dr. Novak’s debut novel, a legal mystery. Publication date September 9, 2014 by Pegasus Books.
The first four chapters are available for free at Amazon. Read them and you’ll be hooked! To reach the Amazon webpage, click on the book image below:
Stanford professor Dr. Nico Antone leaves the wife he hates and the job he loves to return to Hibbing, Minnesota where he spent his childhood. He believes his son’s best chance to get accepted into a prestigious college is to graduate at the top of his class in this remote Midwestern town. His son becomes a small town hero and academic star, while Dr. Antone befriends Bobby Dylan, a deranged anesthetist who renamed and reinvented himself as a younger version of the iconic rock legend who grew up in Hibbing. An operating room death rocks their world, and Dr. Antone’s family and his relationship to Mr. Dylan are forever changed.
Equal parts legal thriller and medical thriller, The Doctor and Mr. Dylan examines the dark side of relationships between a doctor and his wife, a father and his son, and a man and his best friend. Set in a rural Northern Minnesota world reminiscent of the Coen brothers’ Fargo, The Doctor and Mr. Dylan details scenes of family crises, operating room mishaps, and courtroom confrontation, and concludes in a final twist that will leave readers questioning what is of value in the world we live in.
Bang-Up Debut Novel, November 16, 2014
By Norm Goldman “Publisher & Editor of Bookpleasures”
This part legal and medical thriller is structured with a mixed bag of situations involving relationships, jealousy, evil, lies, courtroom drama, operating room mishaps as well as moments that engender conflicting and unexpected outcomes. Noteworthy is that as the suspense builds readers will become eager to uncover the truth involving a mishap concerning Nico and a surgical procedure that has unanticipated ramifications.
This is a bang-up debut from a writer who understands timing and is able to deliver hairpin turns, particularly involving the courtroom drama,that you would expect from a book of this genre.
TwinCities.com PIONEER PRESS Entertainment
by Mary Ann Grossman, Entertainment Editor, St. Paul Pioneer Press email@example.com, January 4, 2015
“The Doctor & Mr. Dylan” by Rick Novak (Pegasus Books, $17.50)
Dr. Nico Antone doesn’t hide the fact he hates his wife, but he says he didn’t kill her during an operation. The authorities think otherwise and his trial is the riveting suspense in this novel that is part medical thriller, part legal thriller, part exploration of family relationships.
Nico is an anesthesiologist (as is the author) who leaves his wife, their plush life in California and his job at Stanford to move to his hometown of Hibbing so their son, Johnny, has a better chance of getting into a prestigious college. Johnny hates the idea of moving to a small, cold town, but he’s popular from the first day in school. Nico doesn’t do so well. He’s envied by Bobby, an anesthetist who’s jealous of the better-educated Nico. But it’s hard to take Bobby seriously, since he thinks he’s the young Bob Dylan and lives in the house where Bobby Zimmerman grew up. To complicate matters, Nico is attracted to the mother of the young woman his son is dating. When the two teens get in trouble, Nico’s furious, rich wife comes to Minnesota and needs an emergency operation that puts her on Nico’s operating table.
Novak grew up in Hibbing, where he worked in the iron ore mines and played on the U.S. Junior Men’s Curling championship teams of 1974 and ’75. After graduating from Carleton College, he earned a medical degree at the University of Chicago and spent 30-plus years at Stanford Hospital, where he was an associate professor of anesthesia and Deputy Chief of the Anesthesia Department. His courtroom scenes are based on his experiences as an expert witness.
The Physician’s Late-Night Reading List
Two Pritzker alums pen captivating tales
By Brooke E. O’Neill, University of Chicago Pritzker School of Medicine, editir, Medicine on the Midway Magazine
For most physicians, writing — patient notes, case histories, perhaps journal articles — is part of the job. But for anesthesiologist-novelist Rick Novak, MD’80, and neurosurgeon-memoirist Moris Senegor, MD’82, it’s a second career that consumes early morning hours long before they step into the OR.
Fans of John Grisham will find a kindred spirit in Novak, whose fast-paced medical thriller, The Doctor & Mr. Dylan (Pegasus Books, 2014), transports readers to rural Northern Minnesota, where an accomplished physician and a deranged anesthetist who thinks he’s rock legend Bob Dylan see their worlds collide in the most unexpected ways.
Delivering real-life twists and turns — and a love letter to the Bay Area — is Senegor’s Dogmeat: A Memoir of Love and Neurosurgery in San Francisco (Xlibris, 2014), a coming-of-age tale chronicling the author’s away rotation with renowned neurosurgeon Charles Wilson, MD, at the University of California, San Francisco. Brutally honest, it spares no details of a time Senegor, who also served as a resident under the University of Chicago’s famed neurosurgery chair Sean Mullan, MD, describes as “one of the biggest failures of my life.”
One a vividly imagined nail-biter, the other an intimate peek into the surgical suite, both books deliver an ample dose of intensity and drama.
The Doctor and Mr. Dylan (Pegasus Books, 2014) by Rick Novak, MD’80
“I thought it was a novel way of killing someone,” said Rick Novak, deputy chief of anesthesiology at Stanford University, describing the imagined hospital death that was the genesis of his dark thriller The Doctor & Mr. Dylan. A huge Bob Dylan fan — the rock icon was born in Novak’s hometown of Hibbing, Minnesota, where the story takes place — he then dreamed up a possible culprit: a psychotic anesthetist who thinks he’s Dylan.
From there, the words flowed. “I would write whenever I was with my laptop and had a free moment: in mornings, in evenings, in gaps between cases,” said Novak, who also blogs about anesthesia topics. “I don’t sleep much.”
After finishing the manuscript — one year to write, another to edit — came the challenge of finding a publisher. “In anesthesia, I’m an expert,” Novak said. “In the literary world, I’m an unknown.” After 207 responses of “no, thanks” or no answer at all, he landed an agent. Two months later, she informed him that Pegasus Books had bought his debut novel.
“I started crying,” Novak admits. “I have a third grader and at the time the big word the class was learning was ‘perseverance.’ That was it exactly.”
Dr. Joseph Andresen, Editor, Santa Clara County Medical Association Medical Bulletin, from the January/February 2015 issue:
BOOK REVIEW “THE DOCTOR AND MR. DYLAN”
This past month, Dr. Rick Novak handed me a hardbound copy of his debut novel The Doctor and Mr. Dylan. Rick and I go way back. It was my first week of residency at Stanford when we first met. A newcomer to the operating room, all the smells and sounds were foreign to me despite my previous three years in the hospital as an internal medicine resident. Rick, a soft spoken Minnesotan at heart, in his second year of residency, took me under his wing and guided me through those first few bewildering months, sharing his experience and wisdom freely.
Fast-forward 30 years later. Dr. Rick Novak, a novel and mystery author? This was new to me as I sat down and opened the first page of The Doctor and Mr. Dylan. I have to admit that I didn’t know what to expect. Few books highlight a physician/anesthesiologist as a protagonist, and few books feature a SCCMA member as a physician/author. However, a medical-mystery theme novel wasn’t at the top of my must read list. With my 50-hour workweek, living and breathing medicine, imagining more emotional stress and drama was the furthest thing from my mind. However, three days later, as I turned the last page, and read the last few words. “life is a series of choices. I stuck my forefinger into the crook of the steering wheel, spun it hard to the left and …” This completed my 72-hour journey of and free moments I had, completely immersed in this story of life’s disappointments, human imperfections, and simple joys.
Rick, I can’t wait for your next book. Bravo!
Hibbingite writes twisted medical tale
HIBBING — Readers who are looking for a whodunit that will keep them up all night are in for a treat.
Hibbing native Rick Novak recently released his first book “The Doctor and Mr. Dylan,” a fiction set in Hibbing that merges anesthesia complications, a tumultuous marriage and the legend of Bob Dylan.
“The dialogue is sometimes funny, and there are lots of plot twists,” he said.
Novak said the book will not only entertain readers, but teach them about anesthesiology, Dylanology, the stressful race for elite college admission, and life on the Iron Range.
“The book is very conversational and streamlined,” he said. “I try to write as one would tell a story out loud.”
Novak said “The Doctor and Mr. Dylan” took him three years to perfect. He is currently working on his second book.
This review is from: The Doctor and Mr. Dylan (Kindle Edition)
Just finished Dr. Novak’s delightful novel. I sincerely enjoyed his honest take about the pressures and values that exist within California’s Silicon Valley. He also brought the North Country of Minnesota to life with memorable characters and a twisting, addictive plot. Buried beneath the fun and funny story is a deeper message about how to best care for your kids, your relationships and yourself. Very well written and highly recommended.
Learn more about Rick Novak’s fiction writing at rick novak.com by clicking on the picture below:
6 thoughts on “SHOULD YOU INJECT A CEPHALOSPORIN INTO A PATIENT WHO IS ALLERGIC TO PENICILLIN?”
Wonderful. I agree.
Let me first say I love this blog! You have some great practical advise for common situations in everyday practice. Keep the posts coming!
Regarding this post, I recently read a literature review of this topic (as I was looking for some answers myself) that appeared in the May issue of The Journal of Emergency Medicine that you might find interesting.
Based on recent laboratory tests conducted in the mid-late 90s and early 2000s , Campagna et al report that cross-sensitivity is due to similar R1 side chains and not the Beta-lactam ring itself. Their recommendation is if a patient reports an allergy to investigate further (as your colleagues do already) avoid 1st and 2nd generation cephalosporins with a similar R1 side chain to the specific penicillin the patient is allergic to, and administer a 1st or 2nd generation cephalosporin if the side-chain is different. They provide a nice figure with 2 common pencillins, Amoxicillin and Ampicillin, and list which cephalosporins have similar R1 side chains. Cefazolin is not one of them. Finally, they recommend that 3rd and 4th generation cephalosporins can be given safely has they have little to no risk of cross-reactivity.
I am curious, in your practice do you ever give your patients a test-dose of an antibiotic, or do you not find that to be beneficial?
I’m very early in my nurse anesthesia training, I’ll be interested to see what is done in practice at my clinical sites.
Joseph, RN, SRNA
We don’t usually give a test dose of antibiotic. We give the dose slowly, however, and are vigilant of the vital signs during administration.
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