Adverse drug reactions from - antibiotics

Reaction types

Spans hypersensitivity (immediate and delayed), direct organ toxicity, and microbiome disruption
Penicillin/beta-lactam allergy - the commonest reported drug allergy, but most labels are inaccurate (only ~10% of self-reported "penicillin allergic" patients are truly allergic on testing)
Key organ-specific patterns: aminoglycosides (oto/nephrotoxic), vancomycin (nephrotoxic, red man syndrome), fluoroquinolones (tendinopathy, QT, dysglycaemia), macrolides (QT, GI), Clostridioides difficile (any antibiotic, esp. clindamycin/fluoroquinolones/cephalosporins)

C. difficile infection - inc with age, hospitalisation, PPI use, broad-spectrum antibiotic exposure
Penicillin allergy de-labelling programs now standard - most labelled patients can safely tolerate penicillins after testing/graded challenge

IgE-mediated (Type I): immediate urticaria/angioedema/anaphylaxis - beta-lactams, less commonly others
Delayed T-cell mediated: maculopapular rash (commonest), SJS/TEN, DRESS - esp. with aminopenicillins, sulfonamides, anticonvulsant cross-reactivity
Direct toxicity: aminoglycosides -> hair cell/renal tubular damage (dose- and duration-dependent, exacerbated by dehydration); vancomycin -> histamine release (red man syndrome, rate-related, not true allergy) and nephrotoxicity
Microbiome disruption: broad-spectrum agents -> loss of colonisation resistance -> C. difficile overgrowth and toxin production
Fluoroquinolones: collagen effects -> tendinopathy/rupture (esp. Achilles, elderly, concurrent corticosteroids)

Clinical pattern recognition: immediate (mins-hours) vs delayed (days) reaction timing is the key branch point
Red man syndrome vs anaphylaxis: red man syndrome is rate-related flushing/pruritus without hypotension/bronchospasm - slow the infusion, it is not a contraindication to future vancomycin
Penicillin allergy assessment: detailed history +/- skin testing +/- graded oral challenge for low-risk histories
C. difficile - stool toxin/PCR testing in antibiotic-associated diarrhoea

True IgE-mediated allergy: avoid the culprit and cross-reactive agents; refer for allergy testing/de-labelling if history is vague or low-risk
SJS/TEN/DRESS: stop the drug immediately, supportive care +/- specialist burns/dermatology unit, do not rechallenge
Aminoglycoside/vancomycin toxicity: therapeutic drug monitoring, dose adjustment for renal function, limit duration
Red man syndrome: slow the vancomycin infusion rate, antihistamine premedication if recurrent
**C. difficile: stop the causative antibiotic if possible**, oral vancomycin or fidaxomicin per severity
Fluoroquinolone tendinopathy: stop the drug, rest the tendon, avoid in patients on concurrent corticosteroids where possible

Penicillin allergy label (even if inaccurate) associated with worse outcomes - more broad-spectrum antibiotic use, higher rates of resistant infection and C. difficile
QT prolongation risk compounds with macrolides + fluoroquinolones + antiarrhythmics/antipsychotics

Most delayed maculopapular rashes resolve on stopping the drug without sequelae
SJS/TEN/DRESS carry significant morbidity/mortality and require lifelong avoidance
C. difficile - recurrence risk ~20% after first episode, higher with each subsequent episode

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