• Second Generation Cephalosporins:  Cefuroxime

  • Cefuroxime:  Adverse Reactions^2,3

     

    • Gastrointestinal^2,12 

      • The most frequently reported adverse reactions to cefuroxime involve the gastrointestinal tract.

        • Nausea, vomiting, diarrhea, and abdominal pain occur in a dose-dependent manner, with oral formulations generating more GI upset than parenteral administration.

        • In clinical trials examining oral cefuroxime axetil for cystitis, 15.6% of patients reported adverse events, with diarrhea/loose motions being the most frequent gastrointestinal manifestation.

        • These reactions are typically mild and transient, often resolving spontaneously during continued therapy.

    • Hypersensitivity Reactions and IgE-Mediated Anaphylaxis^5,6,7

      • Although cefuroxime exhibits a overall favorable safety profile, IgE-mediated hypersensitivity reactions ranging from benign cutaneous reactions to life-threatening anaphylaxis can occur.

      • Anaphylaxis to cefuroxime is rare but well-documented, manifesting within seconds to minutes of drug exposure with symptoms including throat itching, tongue and angioedema, generalized urticaria, dyspnea, hypotension, and loss of consciousness.

      • Serum tryptase measurement provides objective documentation, with levels typically elevated above 13 µg/L during acute anaphylactic events, peaking within 1-2 hours and normalizing by 24 hours.

        • Anaphylaxis can occur even in patients with prior cefuroxime exposures that were tolerated without adverse events, indicating that sensitization may develop over time.

      • Diagnostic evaluation of cefuroxime anaphylaxis employs skin prick testing and specific IgE assays, though false-negative results occur and sensitivity/specificity remain imperfect.

      • Cross-reactivity to penicillins in patients developing cefuroxime anaphylaxis is minimal, as demonstrated by negative penicillin skin tests even in patients with documented cefuroxime-specific IgE.^6,7  

    • Cross-Reactivity with Penicillins and Other β-Lactams^8,9,10,11   

      • Contemporary meta-analyses of patients with reported penicillin allergy demonstrate that the risk of clinically significant cross-reactivity with second and third-generation cephalosporins such as cefuroxime is less than 2% (specifically 0.7-2.0%).

        • This low cross-reactivity rate reflects fundamental differences in the R1 and R3 side chains of cefuroxime compared to penicillin and amoxicillin, with the dissimilar side chains minimizing epitope recognition by penicillin-specific IgE antibodies.

        • Cefuroxime is considered a safe alternative for most patients with documented true penicillin allergy, provided that severe immediate-type reactions such as anaphylaxis, Stevens-Johnson syndrome, or toxic epidermal necrolysis have not previously occurred.

        • In patients with penicillin allergy reporting non-severe reactions (delayed rashes, oral tolerance), preoperative penicillin allergy testing has demonstrated that over 95% of patients test negative and can safely receive cephalosporin prophylaxis.

      • In patients with pre-existing beta-lactam sensitization, cefuroxime maintains a 6.3% hypersensitivity rate in sensitized populations, and 4.2% in those specifically sensitized to penicillin alone.

        • Even in penicillin-allergic patients, cefuroxime offers substantially reduced allergic risk compared to other beta-lactams.¹³

    • Severe Cutaneous Adverse Reactions: Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis

      • Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) represent rare but catastrophic complications of cefuroxime therapy, with mortality rates for TEN reaching 30-50%.

        • These severe cutaneous adverse reactions typically present with an initial prodromal period characterized by fever and constitutional symptoms, followed by the appearance of widespread blistering, erythema, and eventual epidermal detachment.

        • The latency period between cefuroxime exposure and SJS/TEN development varies from days to weeks, necessitating vigilant patient monitoring throughout therapy and in the weeks following treatment completion.

        • The European Medicines Agency has issued formal warnings emphasizing that any sign of serious cutaneous reaction mandates immediate drug discontinuation and emergency evaluation.¹⁴

      • Hematologic Manifestations^2,8,14

        • Reports of cefuroxime-associated hematologic abnormalities include decreased hemoglobin or hematocrit, eosinophilia, and prolonged prothrombin time.

          •  Mechanisms underlying these effects vary; eosinophilia likely represents a hypersensitivity phenomenon, while prothrombin time prolongation may reflect intestinal dysbiosis with reduced bacterial synthesis of vitamin K-dependent factors.

            • In patients with risk factors for coagulopathy (poor nutritional status, renal disease, prolonged antibiotic therapy, or concomitant anticoagulation), monitoring of prothrombin time or INR is advisable, with vitamin K supplementation administered when warranted.

      • Clostridioides difficile-Associated Disease

        • Cefuroxime use disrupts normal colonic flora, increasing susceptibility to Clostridioides difficile infection.

          • Prolonged or repeated courses substantially elevate risk.

            • C. difficile colitis presents with watery diarrhea, abdominal cramping, and systemic toxicity, potentially progressing to toxic megacolon and septic shock in severe cases.

            • Management requires prompt discontinuation of cefuroxime, assessment of disease severity, and initiation of anti-C. difficile therapy with oral vancomycin or fidaxomicin.

      • Neurologic Adverse Effects

        • A post-marketing surveillance study identified a statistically significant elevated risk of delirium in hospitalized patients receiving several antibiotics including cefuroxime.

          • While the exact mechanism remains unclear, high doses in patients with renal impairment create potential for neurotoxicity.

            •   Cefuroxime overdosage can induce cerebral irritation potentially resulting in seizures, particularly in patients with renal insufficiency or prior seizure history.

            • Patients requiring high doses should undergo appropriate dose reductions for renal impairment, and neurologic status should be monitored vigilantly.

February, 2026