Does the dose of beta-lactam (β-lactam) antibiotics need to be increased during pregnancy?

From the Guidelines

The dose of beta-lactam antibiotics generally needs to be increased during pregnancy to maintain therapeutic drug levels and ensure effective treatment of infections. Physiological changes in pregnancy, including increased blood volume, glomerular filtration rate, and altered drug metabolism, lead to faster drug clearance and lower serum concentrations of many antibiotics 1. For penicillins like ampicillin and amoxicillin, doses may need to be increased by 25-50% or given more frequently. Similarly, cephalosporins such as cefazolin, ceftriaxone, and cefepime often require higher doses or more frequent administration.

Key Considerations

• The key pharmacodynamics correlate to microbiologic and clinical response for β-lactams is the time that the plasma concentration of the drug is above the pathogen MIC relative to the dosing interval (T > MIC) 1.
• A minimum T > MIC of 60% is generally sufficient to allow a good clinical response in mild to moderate illness, but optimal response in severe infections, including sepsis, may be achieved with a T > MIC of 100% 1.
• The simplest way to increase T > MIC is to use increased frequency of dosing (given an identical total daily dose) or extended infusion of drug over several hours 1.

Dosing Adjustments

• Standard cefazolin prophylaxis for cesarean delivery is 2g rather than the 1g used in non-pregnant patients.
• The specific dose adjustment should be determined based on the particular beta-lactam, the infection being treated, and individual patient factors, with consultation of current treatment guidelines for the most accurate dosing recommendations.

Clinical Implications

• Without appropriate dose increases, pregnant women may experience treatment failures due to subtherapeutic antibiotic concentrations.
• It is essential to consider the unique physiological changes in pregnancy when determining antimicrobial dosing strategies to ensure optimal outcomes 1.

From the Research

Physiological Changes in Pregnancy

The dose of beta-lactam antibiotics may need to be increased in pregnancy due to physiological changes that occur during this period, including:

• Increased glomerular filtration rate
• Increased total body volume
• Enhanced cardiac output These changes can lead to pharmacokinetic alterations in antibiotics, requiring dose adjustment or careful monitoring and assessment 2.

Pharmacokinetics of Beta-Lactam Antibiotics

Studies have shown that the pharmacokinetics of beta-lactam antibiotics are altered during pregnancy, resulting in:

• Faster elimination of these antibiotics
• Lowered plasma concentrations These changes suggest that the dosage schedules of beta-lactam antibiotics may need to be adjusted during pregnancy to ensure adequate therapy 3.

Safety and Efficacy of Beta-Lactam Antibiotics

Beta-lactam antibiotics are generally considered safe and effective in pregnancy, with:

• Penicillins and cephalosporins being commonly used to treat infections such as group A and group B streptococci
• Limited spectrum cephalosporins being used as prophylactic agents
• Extended spectrum cephalosporins, penicillins, and carbapenems providing sufficient coverage against pathogenic organisms 4, 5.

Clinical Considerations

When using beta-lactam antibiotics in pregnancy, clinicians should consider:

• The potential for maternal allergy, particularly with penicillins
• The need for alternative agents, such as first-generation cephalosporins or macrolide antibiotics
• The importance of avoiding certain antibiotics, such as fluoroquinolones and tetracyclines, due to potential toxicity to the unborn child 4, 6.