Can an intravenous amoxicillin/clavulanate preparation be used for skin testing to document a suspected allergic reaction to oral amoxicillin/clavulanate?

Skin Testing for Co-Amoxiclav Allergy: IV vs Oral Preparation

Yes, you can use intravenous amoxicillin/clavulanate preparation for skin testing to evaluate a suspected reaction to oral co-amoxiclav, as the route of administration does not alter the antigenic determinants relevant for skin testing. 1

Key Principles for Beta-Lactam Skin Testing

Testing Methodology

• Skin testing requires testing with the actual culprit drug, not just generic penicillin determinants, as selective reactions to specific beta-lactam components are common 2, 3
• For amoxicillin-clavulanate reactions, you must test with both amoxicillin AND the amoxicillin-clavulanate combination, as clavulanate itself causes 32.7% of immediate reactions to this combination 4
• The formulation (IV vs oral) does not matter for skin testing purposes—what matters is testing the specific drug components (amoxicillin and clavulanate) 5, 2

Critical Testing Components

• Standard penicillin skin testing alone is insufficient for amoxicillin-clavulanate allergy evaluation 2, 3
• In one study, 54.8% of patients with amoxicillin allergy had positive reactions only to amoxicillin or amoxicillin-clavulanate determinants, not to standard penicillin reagents (PPL/minor determinants) 2
• Selective clavulanate reactions account for approximately one-third of confirmed immediate reactions to amoxicillin-clavulanate, with skin test sensitivity below 50% for this component 4

Practical Testing Algorithm

Skin Test Protocol

• Perform skin prick testing first, followed by intradermal testing if negative 1
• Test with: benzylpenicilloyl-polylysine (PPL), minor determinants, penicillin G, amoxicillin, AND amoxicillin-clavulanate combination 2
• Maximum testing concentrations: 1-3 mg/mL for amoxicillin and amoxicillin-clavulanate 1
• Read results at 15-20 minutes for immediate reactions and at 24-48 hours for delayed reactions 5

Important Caveats

• Skin testing has only ~60% predictive value for clinical hypersensitivity to beta-lactam antibiotics 1
• Negative skin tests do not guarantee the absence of allergy—they must be followed by supervised drug challenge for definitive diagnosis 1
• Delayed reactions (maculopapular rashes occurring days after starting therapy) cannot be reliably diagnosed with skin testing and require direct oral challenge instead 6, 7

When Skin Testing Should NOT Be Performed

Absolute Contraindications

• History of Stevens-Johnson syndrome, toxic epidermal necrolysis, DRESS syndrome, severe hepatitis, interstitial nephritis, or hemolytic anemia 8
• These severe reactions mandate permanent avoidance without testing 8

Low-Risk Scenarios Where Direct Challenge Is Preferred

• Benign maculopapular rash occurring >1 year ago without systemic symptoms 6, 7
• Non-severe delayed reactions in children, where direct oral challenge without skin testing is the recommended approach 7
• Over 90% of children with reported amoxicillin rashes tolerate the drug on re-exposure 6, 7

Clinical Context: Route of Administration

Why IV Preparation Works for Skin Testing

• The antigenic determinants (beta-lactam ring, side chains, and clavulanate moiety) are identical regardless of formulation 1
• Skin testing evaluates IgE-mediated sensitization to drug epitopes, which are present in both IV and oral preparations 1, 4
• Excipients differ between formulations but are rarely the cause of true allergic reactions 5

Limitations of Skin Testing

• Skin testing has limited utility for non-IgE-mediated reactions such as delayed maculopapular rashes 6, 7
• The positive predictive value is less than 50%, meaning many patients with positive skin tests would actually tolerate the drug 7
• Sensitivity decreases over time—the longer the interval since the reaction, the less reliable skin testing becomes 7

Recommended Approach Based on Reaction Type

For Immediate Reactions (Within 1 Hour)

• Perform comprehensive skin testing with PPL, minor determinants, amoxicillin, and amoxicillin-clavulanate 4, 2
• If skin tests are negative, proceed with supervised oral challenge to confirm tolerance 1, 8
• Use IV preparation for skin testing if oral preparation is unavailable 1

For Delayed Reactions (Days After Starting)

• Skip skin testing entirely and proceed directly to supervised oral challenge when antibiotics are next needed 6, 7
• Skin testing has poor sensitivity/specificity for delayed, non-IgE-mediated reactions 6, 7

For Severe Reactions

• Avoid all testing and permanently avoid the drug if history suggests Stevens-Johnson syndrome, TEN, DRESS, or anaphylaxis with cardiovascular compromise 8