Penicillin Allergies: Adverse reactions to the world’s first antibiotic.
A look into allergic reactions to Penicillin, “the wonder drug”.
Written by Rijuta Mitra
Accidentally discovered by Sir Alexander Fleming, Penicillin is hailed was the miracle drug during the second world war and also marked the beginning of the era of antibiotics. All forms of natural and semisynthetic penicillins, or drugs with a similar structure such as cephalosporins or carbapenems, can cause allergy. Cephalosporins are a large group of antibiotics derived from the mold Acremonium (previously called Cephalosporium). Cephalosporins are bactericidal (kill bacteria) and work in a similar way to penicillins. They bind to and block the activity of enzymes responsible for making peptidoglycan, an important component of the bacterial cell wall. They are called broad-spectrum antibiotics because they are effective against a wide range of bacteria. These drugs, which have a beta-lactam ring, are recognized as one of the most frequent causes of immediate and non-immediate drug reactions. Adverse reactions to penicillin have been reported in 0.2% per course of treatment in a large unselected cohort, and between 3.3–5% in a large drug surveillance programme.
The key difference between penicillin and cephalosporin is that penicillin is more susceptible to β-lactamases, whereas cephalosporin is less susceptible to β-lactamases. Both penicillin and cephalosporin are antibacterial drugs. Furthermore, these compounds act by inhibiting transpeptidases (the enzyme that catalyzes the synthesis of peptidoglycan).
However, a significant number of patients labelled as ‘penicillin allergic’ are not truly allergic to the drug. As a result, these antibiotics can be withheld unnecessarily, which may subsequently affect their clinical outcomes, increase healthcare costs and contribute to the development of drug resistant bacteria. Some of the statistics of penicillin allergy include:
- Penicillin allergy is the most commonly reported drug allergy.
- It is estimated that between <10% and up to 20% of those reporting penicillin allergy are truly allergic.
- Prescription of a penicillin to patients with a previous allergy-like event after penicillin treatment is common and could result in serious harm or death.
The prevalence of penicillin hypersensitivity in the general population is unknown as no prospective studies evaluating sensitization rates during treatment have been undertaken to date. However, from data extracted from the electronic health medical records of patients who had at least one outpatient visit, the prevalence of ‘allergy’ in the general population appears to be around 9% for penicillins and 1.3% for cephalosporins.
Penicillin allergy signs and symptoms may include:
- Skin rash.
- Hives.
- Itching.
- Fever.
- Swelling.
- Shortness of breath.
- Wheezing.
- Runny nose.
- Itchy, watery eyes.
- Anaphylaxis.
The incidence of true penicillin allergy (a type I reaction which is immunoglobulin E [IgE] mediated) is <0.05% of the general population. True penicillin allergy can be fatal, with a risk of anaphylaxis estimated in around 0.002% of treated patients. A UK study of drug-induced fatal anaphylaxis between 1992 and 1997 reported 12 deaths due to antibiotics. Up to 20% of drug-related anaphylaxis deaths in Europe and up to 75% of deaths for all drug-related anaphylaxis in the USA are caused by penicillin.
Risk factors
Patients aged between 20–49 years are at increased risk of anaphylaxis, although the reasons remain unknown. There is no evidence to suggest a hereditary link to anaphylaxis and therefore family history is irrelevant. The latest data suggest there is no link between atopic disease (e.g. patients with asthma, eczema or hay fever) and increased risk of penicillin allergy , although patients with atopic disease may experience more severe reactions.
As many as 85% of patients who previously reacted to penicillin may not react upon second exposure if the time interval from the last exposure is prolonged.
Clinical history of penicillin allergy in the more distant past (>15 years) is associated with only a very low risk (0.4%) of reactions, and only 20–30% of patients positive on a penicillin skin test remain positive after ten years.
An allergic reaction is most commonly seen after parenteral administration. Less commonly, penicillin allergy reactions can occur days or weeks after exposure and may persist after treatment has stopped. Other conditions associated with penicillin allergy include serum sickness, drug-induced anaemia, drug reaction with eosinophilia and systemic symptoms (DRESS) and nephritis.
Treatment options
The following interventions may be used to treat the symptoms of an allergic reaction to penicillin:
- Withdrawal of the drug. If your doctor determines that you have a penicillin allergy — or likely allergy — discontinuing the drug is the first step in treatment.
- Antihistamines. Your doctor may prescribe an antihistamine or recommend an over-the-counter antihistamine such as diphenhydramine (Benadryl) that can block immune system chemicals activated during an allergic reaction.
- Corticosteroids. Either oral or injected corticosteroids may be used to treat inflammation associated with more-serious reactions.
Treatment of anaphylaxis. Anaphylaxis requires an immediate epinephrine injection as well as hospital care to maintain blood pressure and support breathing
Patients who have experienced a type I allergic reaction with penicillins (e.g. urticaria, laryngeal oedema, bronchospasm, hypotension) should not be prescribed beta-lactam agents including penicillins, cephalosporins, carbapenems or monobactams.
Cephalosporins and carbapenems can be used with caution in patients that do not have a history of a type I mediated allergic reaction. However, at the time of these early studies, cephalosporin formulations contained trace amounts of penicillin , so this figure is thought to be an overestimate. The true incidence of cross-sensitivity is unknown but there are data to suggest that it is much lower]. Second and third generation cephalosporins (e.g. cefuroxime, ceftriaxone, ceftazidime) have a lower propensity for cross reactivity, as they have different side chains to penicillin, which contribute to the decreased immunogenicity. However, alternatives should be used wherever possible.
Carbapenems (e.g. meropenem, imipenem, ertapenem, doripenem ) have a cross reaction rate of 1–6% in patients who have previously suffered IgE-mediated reactions to penicillins. A thorough clinical history should be taken before prescribing this class of drugs to a patient with known or suspected penicillin allergy. Aztreonam is a monobactam that does not contain a bicyclic-ring structure similar to penicillins, cephalosporins and carbapenems. It can therefore be used safely in patients with a history of penicillin allergy, unless the patient is known to be allergic to ceftazidime, which has an identical side chain to aztreonam.
Tetracyclines (e.g. doxycycline), macrolides (e.g. clarithromycin), aminoglycosides (e.g. gentamicin), metronidazole, quinolones (e.g. ciprofloxacin) and glycopeptides (e.g. vancomycin) are all unrelated to penicillins and are safe to use in patients with penicillin allergy. However, patients with penicillin allergy are more likely to react to any class of drug .
Prevention
If you have a penicillin allergy, the simplest prevention is to avoid the drug. Steps you can take to protect yourself include the following:
Inform health care workers. Be sure that your penicillin allergy or other antibiotic allergy is clearly identified in your medical records. Inform other health care professionals, such as your dentist or any medical specialist.
SOURCES: GOOGLE.scholar, Wikipedia, www.ndorms.ox.ac.uk, drugs.com, mayoclinic.org
