What are alternative IV antibiotics for group B streptococcus bacteremia when penicillin G (PCN G) is not an option?

Alternative IV Antibiotics for Group B Streptococcus Bacteremia

For patients who cannot receive penicillin G, ampicillin is the first alternative, followed by cefazolin for non-severe penicillin allergy, or vancomycin for severe penicillin allergy when clindamycin susceptibility is unknown or the isolate is resistant. 1, 2

First-Line Alternative: Ampicillin

• Ampicillin 2 g IV loading dose, then 1 g IV every 4 hours is an acceptable alternative to penicillin G for GBS bacteremia. 1, 2
• All GBS isolates worldwide remain universally susceptible to both penicillin and ampicillin, with no documented resistance to date. 3, 2, 4, 5, 6
• Ampicillin has a broader antimicrobial spectrum than penicillin G, which may increase selection pressure for resistant organisms, but remains highly effective against GBS. 3, 2

For Non-Severe Penicillin Allergy: Cefazolin

• Cefazolin 2 g IV loading dose, then 1 g IV every 8 hours is the preferred alternative for patients with non-severe penicillin allergy (no history of anaphylaxis, angioedema, urticaria, or respiratory compromise). 1, 2
• Cefazolin demonstrates excellent activity against GBS with minimum inhibitory concentrations <0.5 µg/mL among invasive U.S. isolates, and all isolates susceptible to penicillin are considered susceptible to cefazolin. 3
• Approximately 10% cross-reactivity risk exists between penicillin and cephalosporins, making careful allergy history assessment critical. 3, 1
• Only first-generation cephalosporins should be used, as resistance to second-generation cephalosporins (cefoxitin) has been documented. 3, 2

For Severe Penicillin Allergy: Risk-Stratified Approach

High-Risk Allergy Definition

• History of immediate hypersensitivity reactions including anaphylaxis, angioedema, urticaria, or respiratory distress to penicillin. 1
• Patients with asthma or other conditions that would make anaphylaxis more dangerous. 1

When Susceptibility Testing Available

• If the GBS isolate is susceptible to BOTH clindamycin AND erythromycin: clindamycin 900 mg IV every 8 hours. 1, 2
• Testing for both clindamycin and erythromycin susceptibility is mandatory, as erythromycin resistance frequently indicates inducible clindamycin resistance even when the isolate appears susceptible to clindamycin. 1, 2

When Susceptibility Unknown or Resistant

• Vancomycin 1 g IV every 12 hours is recommended when clindamycin/erythromycin susceptibility is unknown or the isolate is resistant. 1, 2, 7
• All GBS isolates remain universally susceptible to vancomycin. 4
• Vancomycin should be reserved for cases where no other options exist to minimize promoting antimicrobial resistance. 2

Critical Resistance Patterns to Consider

• Clindamycin and erythromycin resistance has increased dramatically since 2000, with clindamycin resistance exceeding 20% by 2010 in most serotypes. 6
• Resistance prevalence among invasive GBS isolates ranges from 7-25% for erythromycin and 3-17.5% for clindamycin in contemporary studies. 3, 8, 5, 6
• A 2023 study of 2017 invasive infant GBS isolates from 1970-2021 showed erythromycin resistance increased from 4.0% to 32.3% and clindamycin resistance from 1.5% to 17.5% when comparing pre-2000 to post-2000 isolates. 6
• Gentamicin shows universal high-level resistance and should not be used as monotherapy, though it may provide synergistic activity when combined with penicillin or ampicillin. 4, 5

Common Pitfalls to Avoid

• Never use clindamycin without confirming susceptibility to both clindamycin AND erythromycin, as erythromycin resistance often indicates inducible clindamycin resistance. 1, 2
• Many reported penicillin allergies are not true IgE-mediated reactions; detailed allergy history can identify patients who can safely receive beta-lactams rather than alternatives. 1
• Macrolides (erythromycin) should not be used empirically for GBS bacteremia in penicillin-allergic patients due to high resistance rates. 4, 6
• Do not use second-generation cephalosporins (cefoxitin) as cefoxitin resistance has been documented among invasive GBS isolates. 3, 2

Synergistic Combination Therapy

• The combination of vancomycin (or a beta-lactam) with an aminoglycoside acts synergistically in vitro against many GBS strains, though aminoglycosides alone are ineffective due to high-level resistance. 7, 4, 5
• Combination therapy with ampicillin plus gentamicin may be considered for severe invasive disease, though penicillin or ampicillin monotherapy remains standard for uncomplicated bacteremia. 2