What is the protocol for administering a bedside intravenous test dose of piperacillin-tazobactam (antibiotic) to a patient with a history of penicillin allergies?

Protocol for Administering a Bedside Intravenous Test Dose of Piperacillin-Tazobactam to a Patient with Penicillin Allergies

For patients with a history of penicillin allergies who require piperacillin-tazobactam, skin testing should be performed first, followed by desensitization or graded challenge depending on skin test results and reaction history. 1, 2

Initial Assessment of Penicillin Allergy History

• Evaluate the nature and severity of the previous penicillin reaction to guide the testing approach 1
• Determine if the reaction was likely IgE-mediated (anaphylaxis, angioedema, bronchospasm, or urticaria) or non-IgE-mediated 3
• For patients with histories of severe non-IgE-mediated reactions such as Stevens-Johnson syndrome or toxic epidermal necrolysis, skin testing should not be performed 1
• If the reaction history is inconsistent with allergy (headache, isolated gastrointestinal symptoms), testing may not be required 3

Skin Testing Protocol

Preparation and Personnel Requirements

• Skin testing should only be performed by personnel trained in application and interpretation, with preparedness to treat rare anaphylaxis 1, 3
• Ensure emergency medications and equipment for treating anaphylaxis are readily available 3
• Patients should not have taken antihistamines prior to testing (specific timeframes depend on the antihistamine) 3

Testing Materials

• Major determinant: Benzylpenicilloyl poly-L-lysine (Pre-Pen) at 6 × 10⁻⁵ mol/L 3, 1
• Minor determinant: Penicillin G at 10,000 units/mL 3, 1
• Positive control: Histamine 1
• Negative control: Saline or diluent 1
• If available, piperacillin-tazobactam at non-irritating concentration 1

Testing Procedure

1. For high-risk patients (history of anaphylaxis, asthma, or beta-blocker use): Dilute reagents 100-fold for preliminary testing 3

2. For other patients: Dilute reagents 10-fold if the reaction occurred within the preceding year 3

3. Epicutaneous (prick) testing:

   • Place duplicate drops on volar forearm and pierce epidermis with 26-gauge needle without drawing blood 3
   • A positive test is defined as a wheal ≥4 mm larger than negative control after 15 minutes 3
   • Ensure histamine control is positive to validate results 3

4. Intradermal testing (if prick tests are negative):

   • Inject 0.02 mL of solutions intradermally using 26-27 gauge needle 3
   • Mark margins of wheals with pen 3
   • A positive test is defined as a wheal >2 mm larger than initial wheal size and >2 mm larger than negative control after 15 minutes 3 or a wheal ≥3 mm larger than negative control with ≥5 mm flare 3, 1

Management Based on Skin Test Results

If Skin Test Positive

• Desensitization is required before administering piperacillin-tazobactam 3
• Desensitization should be performed in a hospital setting due to risk of serious IgE-mediated reactions 3
• Can be performed orally or IV, with oral route considered safer and easier 3
• Desensitization typically takes 4-12 hours to complete 3
• After desensitization, patient must be maintained on penicillin continuously for the duration of therapy 3

If Skin Test Negative

• Patient can receive piperacillin-tazobactam with low risk (negative predictive value >95%) 3, 1
• Consider a graded challenge approach for added safety:
  • For patients with recent or severe reaction history, use a 2-step challenge 1
  • For others, a single-step challenge may be appropriate 1
  • Monitor for at least 30 minutes after administration 2

Special Considerations

• If full battery of skin test reagents (including minor determinants) is not available, patients with negative tests using only major determinant and penicillin G may still be considered at low risk 3
• If Pre-Pen (major determinant) is not available, all patients with history of IgE-mediated reactions should be desensitized in a hospital setting 3
• For patients with reactions not likely to be IgE-mediated, outpatient-monitored test doses can be considered 3
• Piperacillin-tazobactam is contraindicated in patients with a history of allergic reactions to penicillins, cephalosporins, or beta-lactamase inhibitors unless desensitization is performed 2
• Some patients may be selectively allergic to the tazobactam component rather than the piperacillin component 4

Administration of Piperacillin-Tazobactam

• Reconstitute and dilute according to manufacturer's instructions 2
• Administer over at least 30 minutes (using programmable syringe or infusion pump) 2
• Monitor patient closely during and after administration for signs of hypersensitivity reactions 2
• Be prepared to discontinue infusion and treat allergic reactions immediately if they occur 2