(P273) A Scoping Review of Linezolid Safety in Pregnancy

Background: Syphilis is a serious global health problem, with nearly one million cases among pregnant women resulting in over 350,000 adverse birth outcomes annual. Due to benzathine penicillin shortages and its high cost, alternative syphilis treatments are needed. Linezolid 600 mg daily or twice daily is clinically used for skin infections and drug-resistant tuberculosis. Linezolid has shown high efficacy against syphilis in animal models. Common side effects of prolonged use include neuropathy and thrombocytopenia. As a low-cost, widely available antibiotic, linezolid has the potential to be an alternative syphilis treatment.



Methods: We conducted a scoping review to investigate the safety of linezolid during pregnancy. We reviewed the publicly available FDA materials submitted for the New Drug Application 021130 Pfizer (Zyvox-linezolid) 2000-2021. We also searched PubMed and Embase for reports published between May 3, 1999, to June 10, 2022, using keywords “linezolid” and “pregnancy”. We reviewed linezolid dosage, duration of treatment, disease of interest, and animal, fetal and maternal toxicities to assess the safety of linezolid treatment.



Results: We identified 171 studies and included thirteen with data on animal or human outcomes. Of the six animal studies, no teratogenic effects from linezolid (at an equivalent dose for 60 kg adult) were observed in 311 mice, rats, or rabbits. Fetal and maternal toxicity in 56 animals occurred at human equivalent dosages of 486 to 2,187 mg daily (typical human dose 600 to 1200 mg daily) for 11-12 days, including increased litter loss and decreased survival and fertility of pups. Among 31 reported cases of linezolid exposure in pregnant women, linezolid was given to 30 with drug-resistant tuberculosis and one with Staphylococcus aureus infection. Thirty of 31 pregnant women experienced no fetal or maternal toxicity. Polyneuropathy was reported in one case after 5 months of long-term use.





Conclusion: Our scoping review found no teratogenic effects of linezolid. Adverse effects in animals appeared at dosages close to typical human dose, but no adverse events were reported in a small number of women. Further research may be needed to determine the safety of linezolid in pregnancy.