Can I Prescribe a Cephalosporin If He Is Allergic to Penicillin?

Patient Presentation
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.

Discussion
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.

Learning Point
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?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: Antibiotics and Allergy.

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

  • Patient Care
    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.

  • Medical Knowledge
    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.

  • Practice Based Learning and Improvement
    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.

  • Professionalism
    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.

  • Systems Based Practice
    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.

    Author
    Donna M. D’Alessandro, MD
    Professor of Pediatrics, University of Iowa Children’s Hospital
    and

    Nancy Bonthius, PharmD.
    Clinical Assistant Professor of Pediatrics

  • What Causes Photophobia?

    Patient Presentation
    A 3-year-old female came to clinic with a 2 hour history of sudden onset of pain and photophobia. She was traveling in the car with the windows rolled down when she started to cry and said her left eye hurt. Her mother stopped the car and examined the eyes which she said appeared normal. Her mother had some saline eye drops with her and irrigated the left eye and then they returned home. Again her mother irrigated the eye, but the child continued to complain of pain and photophobia. The mother stated that she continued to rub the left eye intermittently, but less so since leaving to come to clinic.

    The past medical history showed visits for strep throat, otitis media and atopic dermatitis. The family history was positive for some visual acuity problems in both sides of the family as family members aged. There weres no neurological problem including migraine headache, but the mother said that she had intermittent musculoskeletal related headaches. The review of systems was negative.

    The pertinent physical exam showed a cooperative child with mild erythema of the left sclera who preferred the room to be dimmed, but would tolerate full illumination. Visual acuity was 20/20. There were no obvious visual field defects. There was some very minor erythema of the left lid compared to the right without obvious trauma such as an insect bite. The ophthalmological examination revealed all extra ocular movements to be intact. Pupils were 3 mm, equal, round and reactive to light and accomodation. The sclera was mildly injected. No obvious foreign body was seen or discharge noted on the sclera, palpebral conjunctiva and with eversion of the upper lid. Fluorescein dye and a Wood’s lamp revealed a corneal abrasion about 1 cm in length just lateral to the limbus and running in an 11 o’clock to 5 o’clock position. The right eye and neurological examination was normal as was the rest of her examination.

    The diagnosis of a corneal abrasion was made. A topical anesthetic was applied for patient comfort. A topical antibiotic ointment was also applied and the eye patched. The patient’s clinical course showed her going home and sleeping. She kept the patch on for an addition 2 hours and then took it off just before bed and was not complaining of pain or photophobia. Her ophthalmological examination was normal the next day including no evidence of corneal abrasion on fluorescein dye testing.

    Discussion
    Corneal abrasions are common problems in children that can be caused from a variety of trauma. Children’s fingernails and toys are frequent culprits along with dust particles particularly under windy circumstances. A review of treatment for corneal abrasions and a brief differential diagnosis of painful eyes can be found at: To Patch or Not to Patch, That is the Question

    Learning Point
    Photophobia is excessive light sensitivity and can be caused by a variety of entities. The differential diagnosis includes:

    • Ophthalmological problems
      • Glaucoma, congenital
      • Retinitis pigmentosa
    • Drugs
      • Atropine
      • Ethosuximide
      • Mercury
    • Infection
      • Amoebic meningoencephalitis
      • Aspergillosis
      • Botulism
      • Enrlichiosis
      • Lyme Disease
      • Lymphocytic Choriomeningitic Virus
      • Measles
      • Meningitis
      • Onchocerciasis
      • Parasites
      • Rociky Mountain Spotted Fever
      • Typhus – Rickettsia prowazekii
      • Viral and bacterial keratoconjunctivitis
    • Systemic disease
      • Acrodermatitis enteropathica
      • Albinism
      • Cyclic vomiting
      • Cystinosis
      • Juvenile Idiopathic Arthritis
      • Kawasaki Disease
      • Migraine
      • Sjogren-Larsson Syndrome
      • Vitamin A deficiency
      • Reiter syndrome
      • Lymphoproliferative disorders
    • Trauma
      • Burns
      • Corneal abrasion, irritation, ulceration
      • Retinal detachment

    Questions for Further Discussion
    1. What is the differential diagnosis of ptosis?
    2. What is the differential diagnosis of nystagmus?

    Related Cases

    To Learn More
    To view pediatric review articles on this topic from the past year check PubMed.

    Evidence-based medicine information on this topic can be found at SearchingPediatrics.com, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

    Information prescriptions for patients can be found at MedlinePlus for these topics: Eye Diseases and Visual Impairment and Blindness.

    To view current news articles on this topic check Google News.

    To view images related to this topic check Google Images.

    Medicine San Frontiers. Clinical Guidelines Diagnosis and Treatment Manual. Available from the Internet at http://www.refbooks.msf.org/msf_docs/en/Clinical_Guide/CG_en.pdf (rev. 2007, cited 5/11/09).

    Centers for Disease Control Yellow Book Chapter 4 – Rickettsial InfectionsAvailable from the Internet at wwwn.cdc.gov/travel/yellowbook/ch4/rickettsial.aspx (cited 5/11/09).

    eMedicine. Available from the Internet at http://emedicine.medscape.com/ (rev. 2009, cited 5/11/09).

    ACGME Competencies Highlighted by Case

  • Patient Care
    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.
    5. Patients and their families are counseled and educated.
    7. All medical and invasive procedures considered essential for the area of practice are competently performed.
    8. Health care services aimed at preventing health problems or maintaining health are provided.

  • Medical Knowledge
    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.

    Author

    Donna M. D’Alessandro, MD
    Professor of Pediatrics, University of Iowa Children’s Hospital

  • He Just Makes a Mess!

    Patient Presentation
    An almost 4-year-old male came to his well child visit. His mother complained that he “just makes a mess” every time he urinates into the toilet since he was toilet trained at age 3. She says that she and her husband have tried to work with him, but he seems to spray urine all over the back of the toilet. They have tried to assist him and to be able to urinate into the toilet bowl he needs to position his penis almost totally downward, otherwise in a semi-horizontal position his urinary stream to points upward. She denies that he has a splayed urinary stream. He denies any urgency, frequency, pain, pruritis, nor diurnal or nocturnal enuresis. She states that he urinates every 3-5 hours, and has soft bowel movements every day to every other day. His mother reported that he seemed to take a long time urinating and that if he was outside “he could hit a tree or rock several feet away.”

    The past medical history is unremarkable.
    The family history is negative for any genitourinary problems except for a great grandfather with benign prostatic hypertrophy and difficulty voiding in later life. There were no hearing problems. The review of systems was negative.

    The pertinent physical exam showed a happy child who was growing and developing normally. He also had normal blood pressure readings during this and previous visits. The penile meatus was located at the tip of the penis and showed a small amount of extra tissue ventrally at the tip of the meatus (resembling a ski-ramp). The meatal diameter was small. His penis and testes were normal and he had a normal cremasteric reflex. The diagnosis of meatal stenosis was confirmed when the physician watched the child urinate as he had an upwardly-deflected, non-splayed urinary stream. The patient was referred to a urologist and the patient’s clinical course showed that he had a meatotomy without complications. At his 5 year well child examination, he reported no urinary problems or “making a mess.”

    Discussion
    Meatal stenosis is a common problem. It can occur in up to 10% of circumcised boys. It is also more common in circumcised boys. This may be due to chronic irritation of the delicate tissues of the meatus caused by exposure to urine in the diaper and mechanical irritation of the diaper itself. Families may not notice the problem until the child is toilet training or afterwards because they do not witness the urinary stream and its deflection. Another potential mechanism is frenular artery damage during circumcision which results in ischemia and subsequent stenosis.

    The history usually includes symptoms that the urinary stream is defected upwards and is high-velocity (= long distance). There may be pain or burning with urination, blood spotted underwear, and urgency, frequency or emptying of the bladder may be prolonged. Some children will sit during urination to alleviate the symptoms or need to move farther away from the toilet to aim the stream into the toilet. Depending on the tissues involved, some families may also report a splayed urinary stream.

    Treatment includes possible dilatation with lubricated feeding tubes and followup lubrication of the site, or meatotomy which is curative and rarely has recurrence of the stenosis.

    Learning Point
    Ventral or dorsal displacement of the urinary stream can be caused by meatal stenosis, epispadias, and hypospadias. Splaying of the urinary stream can be seen in patients with meatal stenosis and congenital urethral polyps

    Questions for Further Discussion
    1. At what ag are most females or male children toilet trained for daytime urine?
    2. What are indications for medical circumcision?

    Related Cases

      Symptom/Presentation
      Urine

    To Learn More
    To view pediatric review articles on this topic from the past year check PubMed.

    Evidence-based medicine information on this topic can be found at SearchingPediatrics.com, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

    Information prescriptions for patients can be found at MedlinePlus for this topic: Penis Disorders.

    To view current news articles on this topic check Google News.

    To view images related to this topic check Google Images.

    Angel CA. Meatal Stenosis. eMedicine.
    Available from the Internet at http://emedicine.medscape.com/article/1016016-overview (rev. 06/12/2006, cited 5/7/09).

    Cooper C, Nepple KG, Hellerstein S. Voiding Dysfunction. eMedicine.
    Available from the Internet at http://emedicine.medscape.com/article/1016198-overview (rev. 06/24/2008, cited 5/7/09).

    ACGME Competencies Highlighted by Case

  • Patient Care
    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.
    7. All medical and invasive procedures considered essential for the area of practice are competently performed.
    8. Health care services aimed at preventing health problems or maintaining health are provided.
    9. Patient-focused care is provided by working with health care professionals, including those from other disciplines.

  • Medical Knowledge
    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.

  • Interpersonal and Communication Skills
    19. The health professional works effectively with others as a member or leader of a health care team or other professional group.

  • Systems Based Practice
    23. Differing types of medical practice and delivery systems including methods of controlling health care costs and allocating resources are known.
    24. Cost-effective health care and resource allocation that does not compromise quality of care is practiced.

    Author
    Donna M. D’Alessandro, MD
    Professor of Pediatrics, University of Iowa Children’s Hospital