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Antibiotic inhibition of bacterially induced fetal membrane weakening
J A McGregor1, J N Schoonmaker, B D Lunt
1Department of Obstetrics and Gynecology, University of Colorado Health Sciences Center, Denver.
Abstract:
A fetal membrane model was used to evaluate in vitro the efficacy of two antibiotics, erythromycin and clindamycin, in preventing bacterial protease-induced weakening of amniochorion. Standardized inocula of protease-producing bacteria (10(9) colony-forming units [cfu]/mL Staphylococcus aureus, incubated at 37C for 20 hours) reliably reduced fetal membrane structural integrity as reflected by bursting tension and work to rupture. Supraminimal inhibitory concentrations (supra-MICs) (erythromycin 0.23 microgram/mL; clindamycin 0.56 microgram/mL) and subminimal inhibitory concentrations (sub-MICs) (erythromycin 0.13 microgram/mL; clindamycin 0.06 microgram/mL) of both antibiotics prevented fetal membrane impairment due to test bacteria. Supra-MICs of both antibiotics prevented bacterial cell growth and release of protease. Sub-MICs of both antibiotics allowed bacterial cell growth of test microorganisms but inhibited protease release and subsequent fetal membrane damage. These findings suggest that inhibitory and even subinhibitory doses of antibiotics such as erythromycin and clindamycin may be effective in reducing the occurrence of premature rupture of membranes and subsequent preterm birth mediated by susceptible microorganisms.
Insights
Erythromycin and clindamycin, even at sub-MIC levels, prevent bacterial protease damage to fetal membranes. This suggests antibiotics may reduce premature rupture of membranes and preterm birth.
Area of Science:
- Obstetrics and Gynecology
- Infectious Diseases
- Pharmacology
Background:
- Bacterial protease production can weaken fetal membranes, leading to premature rupture of membranes (PROM) and preterm birth.
- Staphylococcus aureus protease is a key factor in amniochorion degradation.
Purpose of the Study:
- To evaluate the in vitro efficacy of erythromycin and clindamycin in preventing bacterial protease-induced fetal membrane weakening.
- To determine if sub-MICs of these antibiotics can inhibit protease activity and protect fetal membrane integrity.
Main Methods:
- A fetal membrane model was used to assess structural integrity (bursting tension, work to rupture).
- Standardized Staphylococcus aureus inocula were used to induce membrane damage.
- Antibiotic concentrations tested included supra-MICs and sub-MICs for erythromycin and clindamycin.
Main Results:
- Both supra-MICs and sub-MICs of erythromycin and clindamycin prevented fetal membrane impairment.
- Supra-MICs inhibited bacterial growth and protease release.
- Sub-MICs allowed bacterial growth but inhibited protease release, preventing membrane damage.
Conclusions:
- Inhibitory and sub-MIC doses of erythromycin and clindamycin are effective in preventing bacterial protease-induced fetal membrane damage.
- These findings suggest a potential therapeutic role for these antibiotics in reducing PROM and associated preterm birth.