Pregnancy-related pharmacokinetics and antimicrobial prophylaxis during fetal surgery, cefazolin and clindamycin as examples

Prenat Diagn. 2020 Aug;40(9):1178-1184. doi: 10.1002/pd.5753. Epub 2020 Jun 14.

Abstract

Antimicrobial prophylaxis during surgery aims to prevent post-operative site infections. For fetal surgery, this includes the fetal and amniotic compartments. Both are deep compartments as drug equilibrium with maternal blood is achieved relatively late. Despite prophylaxis, chorio-amnionitis or endometritis following ex utero intrapartum treatment or fetoscopy occur in 4.13% and 1.45% respectively of the interventions. This review summarizes the observations on two commonly administered antimicrobials (cefazolin, clindamycin) for surgical prophylaxis during pregnancy, with emphasis on the deep compartments. For both compounds, antimicrobial exposure is on target when we consider the maternal and fetal plasma compartment. In contrast, amniotic fluid concentrations-time profiles display a delayed and much more blunted pattern, behaving as deep compartment. For cefazolin, there are data that document further dilution in the setting of polyhydramnios. Along this deep compartment concept, there is some accumulation during repeated administration, modeled for cefazolin and observed for clindamycin. The relative underexposure to antimicrobials in amniotic fluid may be reflected in the pattern of maternal-fetal complications after fetal surgery, and suggest that antimicrobial prophylaxis practices for fetal surgery should be reconsidered. Further studies should be designed by a multidisciplinary team (fetal surgeons, clinical pharmacologists and microbiologists) to facilitate efficient evaluation of antimicrobial prophylaxis.

Publication types

  • Review

MeSH terms

  • Amniotic Fluid / drug effects
  • Amniotic Fluid / metabolism
  • Anti-Bacterial Agents / blood
  • Anti-Bacterial Agents / pharmacokinetics*
  • Anti-Bacterial Agents / therapeutic use
  • Antibiotic Prophylaxis / methods
  • Cefazolin / blood
  • Cefazolin / pharmacokinetics
  • Cefazolin / therapeutic use
  • Clindamycin / blood
  • Clindamycin / pharmacokinetics
  • Clindamycin / therapeutic use
  • Female
  • Fetoscopy* / methods
  • Fetus / blood supply
  • Fetus / drug effects
  • Fetus / metabolism
  • Humans
  • Infant, Newborn
  • Male
  • Placental Circulation / drug effects
  • Pregnancy / blood
  • Pregnancy / metabolism*

Substances

  • Anti-Bacterial Agents
  • Clindamycin
  • Cefazolin