A 4-year-old male came to clinic with a 5-day history of upper respiratory infection symptoms and a 1 day history of sudden onset of left ear pain. He had runny nose and occasional coughing without fever, but the evening before became febrile to 101.0 degrees Fahrenheit and had left ear pain that kept awakening him from sleep. Acetaminophen was given with some relief of pain and his temperature also returned to normal.
The past medical history showed that he had otitis media as an infant and toddler. A rash was reported after receiving amoxicillin for an otitis episode but this was not seen by a health care provider. He had been treated with a macrolide for strep throat per parent preference. The family history was positive for a grandparent that reportedly was penicillin allergic. The father was allergic to “some antibiotic but I don’t remember which one and it was a long time ago.” He also did not remember what symptoms occurred at the time. The review of systems was negative.
The pertinent physical exam showed an afrebile preschooler with copious clear rhinorrhea and normal growth and vital signs. His left tympanic membrane was red, bulging, and without a light reflex or movement. His right tympanic membrane was opaque with a splayed light reflex and decreased mobility. His throat showed copious rhinorrhea posteriorly, with 2+/4+ tonsils and no exudates. He had shoddy anterior cervical lymphadenopathy. His nasal turbinates were boggy. Lungs were clear, and the rest of his examination was normal.
The diagnosis of left otitis media was made. As this appeared consistent with a secondary infection of the left ear after the initial upper respiratory infection, the physician choose to treat him with an antibiotic. His mother was very concerned and did not want to use a penicillin or a cephalosporin as she had read about cross-reactivity of cephalosporins in some patients. The physician agreed that although this did not sound like a significant reaction to a penicillin, she decided to use another antibiotic class, and as he had successfully used a macrolide this was again prescribed. Later after the visit, the physician did a PubMed search and found a recent review of antibiotic cross-reactivity. She decided that the next time the child needed an antibiotic and the parent was unwilling to use a penicillin that a cephalosporin probably could be appropriately prescribed. She placed a note in his electronic medical record with this information and also had the article filed in the office for review as needed.
Otitis media is a common problem in pediatrics. As approximately 50% of all otitis media is viral in etiology, antibiotics in many cases are unnecessary and potentially harmful to patients. Overprescribing of antibiotics can lead to bacterial resistance in the community and potentially to allergic reactions in patients. Allergic reactions to antibiotics can be difficult to diagnose as some initial reactions may present solely as a rash. Unfortunately, many viral infections may also cause rashes. These rashes may mistakenly be associated with the antibiotic. Thus, the patient may erroneously be labeled as antibiotic allergic. On the other hand, patients who truly are antibiotic allergic may have minor symptoms the second or third time they are exposed, but then have symptoms that progress with further exposure. It can be difficult for the healthcare provider to know what is the right thing to do.
Adverse drug reactions (ADRs) were classically classified as immunologic (Types I-IV, Type I is immediate hypersensitivity reaction due to an IgE mediated response) and non-immunologic which includes predictable adverse effects and toxicity states. Idiosyncratic reactions are usually non-immunologic. Today ADRs are also classified as Type A or B. Type A reactions are more common, frequent and predictable and are non-immunologic reactions. Type B reactions are less common, more serious and less predictable. Type B includes the immunologic and idiosyncratic reactions. Approximately 75% of ADRs are Type A.
The cross-reactivity of cephalosporin in a penicillin-allergic patient ranges from 7-18%. The problem, as noted, is that many nonallergic ADRs (Type A) are reported as a true drug allergy. Recent data supports a lower incidence of true cross-reactivity. The relative risk of an anaphylactic reaction to a cephalosporin ranges from 1:1000 to 1:1,000,000. In patients who are penicillin allergic this risk increases by 4 fold. Because of the improved manufacturing process today though, there is more cross-reactivity within the cephalosporins than between cephalosporins and penicillins.
The structural composition of the cephalosporins and penicillins is similar. It is mainly the side-chains at the Penicillin 6-position and Cephalosporin 7-position that give the antibiotics their potency and are the main contributor to allergic reactions. The 3-position side chain for cephalosporins mainly affects pharmacokinetic properties of the drug but may to a lesser degree also contribute to allergic reactions.
Therefore, different cephalosporins with similar 7-position side chains are likely to act similarly in a patient. If one cephalosporin causes an allergic reaction then another with the same or similar side chain, is likely to produce an allergic reaction as well. Similarly, if the 6-position side chain of a pencillin produces an allergic reaction, a cephalosporin with the same or similar 7-position side chain is likely produce an allergic reaction in that patient as well. However, if the 7-position side chain is different then the patient is not likely to have an allergic reaction. For example, because amoxicillin and cefaclor have similar 6- and 7-position side chains, a patient who has an allergic reaction to amoxicillin is likely to have a similar reaction to the cefaclor. However, in the case of amoxicillin and cefdinir the 6- and 7-position side chains are different. Thus a patient who has an allergic reaction to amoxicillin is not likely to have a similar reaction to the cefdinir. This is not to say that a clinician does not have to be careful when prescribing any drug. Prudence and caution are always warranted.
Cross-reactivity between cephalosporins and penicillins is not necessarily a class effect. Therefore careful prescribing is important. Patients with any Type 1 allergic response to a penicillin or any non-Type 1 response that is life-threatening should not be prescribed a cephalosporin. There may be some instances where desensitization may be attempted because it is felt to be in the best interest of the patient after consultation with an allergist and infectious disease specialist. Desensitization should not be attempted with non-Type 1 life-threatening reactions such as Stevens-Johnson syndrome or toxic epidermal necrolysis. Patients with what appear to be a non-immunologic reactions, that are not life-threatening, may be considered for treatment with certain cephalosporins. Tables of side-chain similarities of the penicillins and cephalosporins are available (see De Pestel DD, Benninger MS, Danziger L et al. in To Learn More below) and the consultation of a pharmacist may also be needed depending on the clinical context.
Questions for Further Discussion
1. When should a child be prescribed a medic-alert bracelet?
2. How common are side effects from sulfonamide medications?
3. Where can I find the guidelines for treatment of otitis media?
To Learn More
To view pediatric review articles on this topic from the past year check PubMed.
To view current news articles on this topic check Google News.
To view images related to this topic check Google Images.
Atanaskovic-Markovic M, Velickovic TC, Gavrovic-Jankulovic M, Vuckovic O, Nestorovic B. Immediate Allergic Reactions to Cephalosporins and Penicillins and Their Cross-Reactivity in Children. Pediatr Allergy Immunol. 2005;16:341-347.
Segal AR, Doherty KM, Leggott J, Zlotoff B. Cutaneous reactions to drugs in children. Pediatrics. 2007 Oct;120(4):e1082-96.
De Pestel DD, Benninger MS, Danziger L et al. Cephalosporin Use in Treatment of Patients with Penicillin Allergies. J Am Pharm Assoc. 2008;48:530-40.
Huang F, Nowak-Wegrzyn A. Drug Allergy Claims in Children: From Self-reporting to Confirmed Diagnosis. Pediatrics. 2008;122;S194.
ACGME Competencies Highlighted by Case
1. When interacting with patients and their families, the health care professional communicates effectively and demonstrates caring and respectful behaviors.
2. Essential and accurate information about the patients’ is gathered.
3. Informed decisions about diagnostic and therapeutic interventions based on patient information and preferences, up-to-date scientific evidence, and clinical judgment is made.
4. Patient management plans are developed and carried out.
5. Patients and their families are counseled and educated.
6. Information technology to support patient care decisions and patient education is used.
8. Health care services aimed at preventing health problems or maintaining health are provided.
10. An investigatory and analytic thinking approach to the clinical situation is demonstrated.
11. Basic and clinically supportive sciences appropriate to their discipline are known and applied.
12. Evidence from scientific studies related to the patients’ health problems is located, appraised and assimilated.
13. Information about other populations of patients, especially the larger population from which this patient is drawn, is obtained and used.
14. Knowledge of study designs and statistical methods to appraisal clinical studies and other information on diagnostic and therapeutic effectiveness is applied.
15. Information technology to manage information, access on-line medical information and support the healthcare professional’s own education is used.
20. Respect, compassion, and integrity; a responsiveness to the needs of patients and society that supercedes self-interest; accountability to patients, society, and the profession; and a commitment to excellence and on-going professional development are demonstrated.
26. Partnering with health care managers and health care providers to assess, coordinate, and improve health care and how these activities can affect system performance are known.
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa Children’s Hospital
Nancy Bonthius, PharmD.
Clinical Assistant Professor of Pediatrics