Antibiotics vs allergies. Penicillin and more
Antibiotics belong to the drugs that most commonly cause allergic reactions [1]. They play a significant role in so-called multi-drug hypersensitivity syndromes [8].
β-lactam antibiotics
The β-lactam antibiotics (and penicillins in particular) are at the forefront of these [2], due to their widespread use. This is the most numerous group of preparations used in the treatment of bacterial infections – including those that are severe and have a difficult location, such as endocarditis [3].
These antibiotics show activity against, for example, staphylococci (except penicillinase-producing strains), streptococci (except enterococci) or the pneumoniae bacillus [4]. They are used in the treatment of common diseases – both in adults and children. They are prescribed by doctors among others for infections of the upper and lower respiratory tract, paranasal sinuses, middle ear, oral cavity, genitourinary tract [4].
β-Lactam antibiotics are divided into penicillins, cephalosporins, carbapenems and monobactams. Penicillins include the popular broad-spectrum antibiotics ampicillin, amoxicillin and piperacillin [3]. Interestingly, they cause skin reactions in up to 80-90% of patients with infectious mononucleosis [5].
IgE-mediated hypersensitivity to penicillins is the best understood mechanism among all drug allergies [8]. Penicillin allergy accounts for between 6 and 25% of all reported drug reactions. For all β-lactam antibiotics, the declared proportion of allergic reactions is 15%. However, this prevalence is not confirmed by verification studies [14].
Macrolides and fluoroquinolones
The second group of antibiotics that can cause allergic reactions are macrolides (e.g. erythromycin, clarithromycin or azithromycin) [7]. Macrolides, however, sensitise much less frequently. On the other hand, they interact with other drugs. Therefore, in the treatment of respiratory tract infections, they are reserved for patients with an immediate allergy to β-lactams [6].
Recently, hypersensitivity to fluoroquinolones has also been reported with increasing frequency. This may be related to their increasing use in treatment [8]. Fluoroquinolones have shown great efficacy against drug-resistant strains of bacteria [9].
What does an antibiotic allergy look like? Symptoms
The reaction to an antibiotic can be immediate (within an hour) or delayed. It does not always occur after the first contact with the drug (in the case of an IgE-mediated reaction, symptoms manifest themselves with the following contact) [2]. It can be limited to skin lesions or develop into a systemic, fulminant reaction [12].
Symptoms of antibiotic allergy include:
- maculopapular erythema,
- acute urticaria,
- persistent erythema,
- angioedema,
- moderate to severe anaphylaxis (in about 8% of cases) [13],
- severe drug reaction, e.g. toxic epidermal necrolysis [8].
Immediate reactions are usually manifested by urticaria and/ or angioedema, wheezing, and rhinitis [10]. With these mechanisms, each further exposure to the allergen is associated with an increased risk of life-threatening anaphylaxis [10]. Delayed reactions, on the other hand, are more likely to manifest as maculopapularerythema than immediate reactions [2].
Is this really an allergy?
It is emphasised that penicillin allergy is over-recognised, generating not only cost but also health effects [8]. Other antibiotics are more expensive and more toxic from it. There is confusion between the term’s ‘hypersensitivity’, ‘sensitisation’ and ‘allergy’. And with allergy, the risk of cross-reactions must be considered , e.g. between penicillins and other β-lactam antibiotics, which have a similar structure [11].
As a result, not only penicillin, but also other β-lactams are commonly excluded from treatment [8]. This in turn has consequences such as the generation of antibiotic-resistant strains [14].
The problem arises from the fact that the diagnosis of antibiotic allergy is often based only on the medical history. Meanwhile, the medical history is not sufficient to make the diagnosis [8].
There is a lack of awareness among both patients and doctors that not all types of hypersensitivity are allergies. Among those diagnosed with an antibiotic allergy, approximately 1-3% of children and 10% of adults do not show allergic symptoms during an oral challenge test [11]. This indicates a misdiagnosis. Only in a small percentage of patients is antibiotic allergy confirmed by available diagnostic methods [14].
Diagnostic tests
In the diagnosis of antibiotic allergy, methods such as can be used:
- skin and patch tests,
- laboratory tests (determination of sIgE in blood),
- lymphocyte transformation test (LTT),
- provocation tests (in hospital settings) [8].
The main method is skin testing, which is performed 4-6 weeks after exposure to the drug [8]. In children with suspected allergy, the same procedure as in adults is recommended [8].
In the case of hypersensitivity to a drug from the β-lactam group, it is advisable to select an alternative antibiotic from the same group. Allergologists emphasise that all β-lactam antibiotics should not be rashly excluded [8,14]. In penicillin allergy, carbapenems and monobactams are usually well tolerated [10].
An allergy to an antibiotic in a child – what should you know?
Hypersensitivity reactions to antibiotics in children can be much more severe than in adults [10]. In a study that included paediatric patients (up to 12 years of age), 30 severe drug reactions were reported over 3 months. As many as 60% of these children were under 1 year of age. The majority of reactions (67%) occurred after an antibiotic [10]. The predominant symptoms were skin rash and urticaria (37%). Less common were:
- Fever,
- shivering,
- vomiting,
- anaphylaxis (fatal in one child).
There is a tendency to classify any unexpected reaction to drugs in children as an allergy. Meanwhile, skin symptoms during antibiotic use are often due to a concomitant virus infection. This is associated with an unclear antibiotic-virus interaction [11].
The results of a study conducted in a group of children admitted to the emergency department for a reaction to a β-lactam antibiotic have been published. A viral infection was detected in the majority. A diagnostic test for allergy was also performed, which gave rise to the classification of only 7% of these children as allergic to the antibiotic received [11].
Aleksandra Lipiec
translation: Julia Majsiak
