Safety of Antimicrobials During Pregnancy: A Systematic Review of Antimicrobials Considered for Treatment and Postexposure Prophylaxis of Plague

Abstract

Background 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. Methods 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. Results 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. Conclusions 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.

Antimicrobial Treatment and Prophylaxis of Plague: Recommendations for Naturally Acquired Infections and Bioterrorism Response

“…To contribute to the evidence base on treatment of plague, epidemiologists from CDC’s Division of Vector-Borne Diseases analyzed treatment and outcomes among 533 reported U.S. cases of plague ( 16 ). To inform specific recommendations for pregnant women, the Plague Clinical Guidelines Team and other contributors conducted systematic literature reviews of plague among pregnant women ( 21 ) and of existing published safety data regarding antimicrobials suggested for the treatment and prophylaxis of plague among pregnant women ( 48 ).…”

“…A review of the safety of fluoroquinolones during pregnancy did not find evidence of an association between maternal fluoroquinolone exposure and pregnancy loss or birth defects ( 93 ). A separate systematic review examined the safety of nonfluoroquinolone antimicrobials used for the treatment of plague and found that several were potentially associated with adverse maternal or fetal outcomes ( 48 ). Consequently, although the risks for plague underscore the need for antimicrobial treatment of pregnant women to approximate recommendations for the nonpregnant population, several modifications are warranted in settings where there are no antimicrobial shortages.…”

“…Some studies have identified an association between trimethoprim-sulfamethoxazole exposure in the first trimester among pregnant women not taking folic acid supplements and the development of fetal neural tube defects ( 48 ). However, this drug is used regularly during pregnancy.…”

Does the Fetus Limit Antibiotic Treatment in Pregnant Patients with COVID-19?

“…Reports indicate that approximately 80% of prescriptions during pregnancy are antibiotics, and it is assumed that between 20–39% of women will receive antibiotics during pregnancy [ 30 , 31 , 32 ]. During pregnancy, different antibacterial regimens are used in clinical practice, including cephalosporins, ẞ-lactams, macrolides, fluoroquinolones, glycopeptides, and lincosamides [ 30 , 31 , 32 ].…”

Prevalência De Infecção Urinária Em Gestantes Atendidas Por Unidade Básica De Saúde Em Jaraguá Do Sul, Sc - Brasil / Prevalence of Urinary Infection in Pregnant Women Attended by a Basic Health Unit in Jaraguá Do Sul, Sc - Brazil

“…Sulfonamides or the association between sulfamethoxazole and trimethoprim (cotrimoxazole) should be avoided in the first trimester due to the teratogenic potential oftrimethoprim and in the third trimester because it can cause Kernicterus in the baby, especiallyin premature infants, as well as increased risk of miscarriage (Yu et al, 2020).Other common antibiotics, such as quinolones and tetracyclines, should not be prescribed in pregnancy due to toxic effects on the fetus. Therefore, treatment in pregnancy is limited in terms of potentially usable drugs (Brasil, 2012;Yu et al, 2020) due to MDR bacteria fosfomycin treatment against MDR pathogens causing UTI (Babiker et al, 2019).…”