Division of Preparedness and Emerging Infections, National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Centers for Disease Control and Prevention (CDC), Atlanta, Georgia, USA.
Division of Birth Defects and Infant Disorders, National Center on Birth Defects and Developmental Disabilities, CDC, Atlanta, Georgia, USA.
Clin Infect Dis. 2020 May 21;70(70 Suppl 1):S37-S50. doi: 10.1093/cid/ciz1231.
The safety profile of antimicrobials used during pregnancy is one important consideration in the decision on how to treat and provide postexposure prophylaxis (PEP) for plague during pregnancy.
We searched 5 scientific literature databases for primary sources on the safety of 9 antimicrobials considered for plague during pregnancy (amikacin, gentamicin, plazomicin, streptomycin, tobramycin, chloramphenicol, doxycycline, sulfadiazine, and trimethoprim-sulfamethoxazole [TMP-SMX]) and abstracted data on maternal, pregnancy, and fetal/neonatal outcomes.
Of 13 052 articles identified, 66 studies (case-control, case series, cohort, and randomized studies) and 96 case reports were included, totaling 27 751 prenatal exposures to amikacin (n = 9), gentamicin (n = 345), plazomicin (n = 0), streptomycin (n = 285), tobramycin (n = 43), chloramphenicol (n = 246), doxycycline (n = 2351), sulfadiazine (n = 870), and TMP-SMX (n = 23 602). Hearing or vestibular deficits were reported in 18/121 (15%) children and 17/109 (16%) pregnant women following prenatal streptomycin exposure. First trimester chloramphenicol exposure was associated with an elevated risk of an undescended testis (odds ratio [OR] 5.9, 95% confidence interval [CI] 1.2-28.7). Doxycycline was associated with cardiovascular malformations (OR 2.4, 95% CI 1.2-4.7) in 1 study and spontaneous abortion (OR 2.8, 95% CI 1.9-4.1) in a separate study. First trimester exposure to TMP-SMX was associated with increased risk of neural tube defects (pooled OR 2.5, 95% CI 1.4-4.3), spontaneous abortion (OR 3.5, 95% CI 2.3-5.6), preterm birth (OR 1.5, 95% CI 1.1-2.1), and small for gestational age (OR 1.6, 95% CI 1.2-2.2). No other statistically significant associations were reported.
For most antimicrobials reviewed, adverse maternal/fetal/neonatal outcomes were not observed consistently. Prenatal exposure to streptomycin and TMP-SMX was associated with select birth defects in some studies. Based on limited data, chloramphenicol and doxycycline may be associated with adverse pregnancy or neonatal outcomes; however, more data are needed to confirm these associations. Antimicrobials should be used for treatment and PEP of plague during pregnancy; the choice of antimicrobials may be influenced by these data as well as information about the risks of plague during pregnancy.
在决定如何治疗和提供孕妇感染鼠疫后的接触后预防（PEP）时，使用的抗菌药物的安全性是一个重要考虑因素。
我们在 5 个科学文献数据库中搜索了 9 种用于治疗孕妇鼠疫的抗菌药物（阿米卡星、庆大霉素、普拉佐米星、链霉素、妥布霉素、氯霉素、多西环素、磺胺嘧啶和甲氧苄啶-磺胺甲恶唑[TMP-SMX]）的安全性的原始资料，并提取了母婴、妊娠和胎儿/新生儿结局的数据。
在确定的 13052 篇文章中，有 66 项研究（病例对照、病例系列、队列和随机研究）和 96 份病例报告被纳入，共涉及 27751 例产前阿米卡星（n=9）、庆大霉素（n=345）、普拉佐米星（n=0）、链霉素（n=285）、妥布霉素（n=43）、氯霉素（n=246）、多西环素（n=2351）、磺胺嘧啶（n=870）和 TMP-SMX（n=23602）的暴露。在产前链霉素暴露的 18/121（15%）儿童和 17/109（16%）孕妇中报告了听力或前庭缺陷。在一项研究中，第一孕期氯霉素暴露与未降睾丸的风险升高相关（比值比[OR] 5.9，95%置信区间[CI] 1.2-28.7）。在一项研究中，多西环素与心血管畸形（OR 2.4，95%CI 1.2-4.7）有关，在另一项研究中与自然流产（OR 2.8，95%CI 1.9-4.1）有关。在第一孕期接触 TMP-SMX 与神经管缺陷的风险增加相关（汇总 OR 2.5，95%CI 1.4-4.3）、自然流产（OR 3.5，95%CI 2.3-5.6）、早产（OR 1.5，95%CI 1.1-2.1）和胎儿生长受限（OR 1.6，95%CI 1.2-2.2）。没有报告其他具有统计学意义的关联。
对于大多数审查的抗菌药物，不良的母婴/胎儿/新生儿结局并未一致观察到。在一些研究中，产前链霉素和 TMP-SMX 暴露与特定的出生缺陷有关。基于有限的数据，氯霉素和多西环素可能与不良的妊娠或新生儿结局有关；然而，需要更多的数据来证实这些关联。抗菌药物应在孕妇鼠疫的治疗和 PEP 中使用；抗菌药物的选择可能受到这些数据以及孕妇感染鼠疫风险的信息的影响。
