What is the safest antibiotic (abx) for a pregnant female with a severe penicillin (PCN) allergy?

Safest Antibiotic for Pregnant Women with Severe Penicillin Allergy

For pregnant women with severe penicillin allergy, vancomycin 1g IV every 12 hours is the safest choice when susceptibility testing is unavailable or shows resistance to clindamycin, while clindamycin 900 mg IV every 8 hours should be used if the organism is proven susceptible to both clindamycin and erythromycin. 1

Defining Severe Penicillin Allergy

Before selecting antibiotics, you must determine if the patient truly has a severe allergy. The CDC defines severe penicillin allergy as a history of any of the following after receiving penicillin or a cephalosporin: 2

• Anaphylaxis 2
• Angioedema 2
• Respiratory distress 2
• Urticaria 2

Critical caveat: Over 90% of patients reporting penicillin allergy are not truly allergic and would tolerate penicillins if administered. 3 This mislabeling often results from viral exanthems or drug intolerance rather than true IgE-mediated hypersensitivity. 3

Treatment Algorithm for Severe Penicillin Allergy in Pregnancy

Step 1: Obtain Antimicrobial Susceptibility Testing

The CDC mandates obtaining susceptibility testing for clindamycin and erythromycin on all GBS isolates from penicillin-allergic women at high risk for anaphylaxis. 2 This testing should be ordered at the time of prenatal GBS screening at 35-37 weeks gestation. 2

Step 2: Select Antibiotic Based on Susceptibility Results

If isolate is susceptible to both clindamycin and erythromycin:

• Use clindamycin 900 mg IV every 8 hours until delivery 1
• This is the preferred option when susceptibility is confirmed 1

If susceptibility testing is unavailable, pending, or shows resistance:

• Use vancomycin 1g IV every 12 hours until delivery 1
• Vancomycin should be reserved for cases where no other options exist due to concerns about promoting antimicrobial resistance 1

Step 3: What NOT to Use

Cefazolin is contraindicated in patients with severe penicillin allergy due to cross-reactivity risk, which occurs in approximately 10% of patients with true penicillin allergy. 1 While cross-reactivity between penicillins and structurally dissimilar cephalosporins like cefazolin is estimated at only 2-3% in verified penicillin allergy, 3 the CDC explicitly recommends against cefazolin use in severe reactions. 4

Erythromycin is no longer recommended for GBS infections due to increasing resistance patterns. 4

Special Considerations for Pregnancy

Safety Profile

Both clindamycin and vancomycin are considered safe during pregnancy when medically necessary: 5

• Penicillins remain first-line agents during pregnancy, but when contraindicated by severe allergy, alternative agents must be used 5
• No antibiotic can be described as absolutely safe, but proper use at appropriate doses does not cause serious harm to the unborn child 5

Testing for Inducible Clindamycin Resistance

The CDC recommends performing D-zone testing (double-disk diffusion method) on GBS isolates that are erythromycin-resistant but clindamycin-susceptible from penicillin-allergic women at high risk for anaphylaxis. 2 This detects inducible clindamycin resistance that could lead to treatment failure. 2

Common Pitfalls to Avoid

Pitfall #1: Accepting reported allergy without verification. Most reported penicillin allergies are not true allergies, and using alternative antibiotics unnecessarily increases risks of cesarean delivery, endometritis, wound complications, GBS sepsis in neonates, and antibiotic resistance. 3

Pitfall #2: Using vancomycin as first-line without attempting susceptibility testing. Always obtain cultures and susceptibility testing to allow for clindamycin use when possible, as vancomycin overuse promotes resistance. 1

Pitfall #3: Assuming all cephalosporins are contraindicated. While cefazolin should be avoided in severe penicillin allergy, the cross-reactivity risk is lower than historically believed. 3 However, CDC guidelines still recommend against cefazolin in severe reactions. 4

Consider Allergy Evaluation

Penicillin allergy evaluation using skin testing and oral challenge has been shown to be safe and effective in pregnancy. 6 In one study of 136 pregnant women who underwent penicillin allergy evaluation, 99% had negative skin tests and all 131 who proceeded to incremental drug challenge passed without adverse reactions or negative pregnancy outcomes. 6 Allergy evaluation should be considered as soon as possible during pregnancy to optimize antibiotic options. 3, 7