What are the side effects of Cephalosporin (Cephalosporins)?

From the Guidelines

Cephalosporins can cause several side effects, with allergic reactions being the most concerning, and patients with a history of penicillin allergy should be cautious, although cross-reactivity is estimated to be around 2-4.8% according to recent studies 1.

Common Side Effects

• Gastrointestinal issues like diarrhea, nausea, and vomiting, which occur in 1-10% of patients
• Approximately 1-3% of patients may develop a rash
• Rare but serious side effects include Clostridium difficile-associated diarrhea, blood disorders like neutropenia or thrombocytopenia, and nephrotoxicity (particularly with cephalosporins like cefepime)

Allergic Reactions

• Patients with a history of anaphylaxis to cephalosporins should undergo penicillin skin testing and drug challenge prior to administration of a penicillin therapy, as suggested by a 2022 practice parameter update 1
• Cross-reactivity with penicillin allergies is estimated to be around 2-4.8%, which is lower than previously thought, and most penicillin-allergic patients can tolerate cephalosporins 1

Monitoring and Precautions

• Patients should be monitored for allergic reactions, especially during the first dose, and should report severe diarrhea, unusual bleeding, or signs of kidney problems
• First-generation cephalosporins like cefazolin have fewer side effects than broader-spectrum later generations
• For patients with any immediate penicillin allergy history, a non–cross-reactive cephalosporin can be administered by full dose or drug challenge, as suggested by recent guidelines 1

From the Research

Cephalosporin Side Effects

• Cephalosporins are generally well-tolerated antibiotics, but they can cause adverse effects, including allergic reactions, which occur in 0.9 to 3.2% of patients 2.
• Other common side effects include localized gastrointestinal disturbances, hepatotoxicity, nephrotoxicity, and mild central nervous system effects 2, 3.
• Haematological toxicity is rare, but specific agents have been associated with neutropenia, hypoprothrombinaemia, haemolytic anaemia, and problems with platelet production and function 2.
• The route of administration may result in minor adverse reactions, including thrombophlebitis and pain 2.
• Cephalosporins with a 3-methyl thiotetrazole side-chain can confer a risk of reduced synthesis of prothrombin and disulfiram-like reactions in patients consuming alcohol 3.
• Some cephalosporins, such as ceftriaxone and cefoperazone, are excreted via the bile, leading to high biliary concentrations and an increased risk of diarrhoea 3.

Hypersensitivity Reactions

• Hypersensitivity reactions to cephalosporins are becoming increasingly common, with a wide range of immunopathologic mechanisms 4.
• Patients allergic to cephalosporins may react to other beta-lactams with common R1 side chains, but tend to tolerate cephalosporins with disparate R1 side chains 4.
• Skin testing for cephalosporins has not been well validated, but appears to have a good negative predictive value for cephalosporins with disparate R1 side chains 4.
• Rapid drug desensitization procedures are safe and effective for immediate and some nonimmediate cephalosporin reactions 4.

Population-Based Studies

• A retrospective population-based analysis found that new reports of cephalosporin-associated allergy were more frequent among women than among men 5.
• The most frequent serious cephalosporin-associated adverse drug reactions were Clostridium difficile infection, nephropathy, and all-cause death 5.
• Physician-documented cephalosporin-associated anaphylaxis and serious cutaneous adverse reactions are rare compared to other adverse drug reactions 5.