Sulbactam Pregnancy Category
Ampicillin-sulbactam does not have an FDA pregnancy category because the old letter system (A, B, C, D, X) was discontinued in 2015, but based on available data, it can be used during pregnancy when clearly needed as animal studies show no fetal harm and it is considered compatible for use. 1, 2
FDA Labeling Information
The FDA drug labels for ampicillin-sulbactam explicitly state: "Reproduction studies have been performed in mice, rats, and rabbits at doses up to ten (10) times the human dose and have revealed no evidence of impaired fertility or harm to the fetus due to ampicillin and sulbactam for injection." 1, 2
However, the labels also note: "There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed." 1, 2
Clinical Guidelines Classification
According to the 2020 ERS/TSANZ respiratory guidelines, amoxicillin (which is in the same penicillin class) is classified as TGA Category A and FDA Category [B], and amoxicillin+clavulanic acid (a similar beta-lactam/beta-lactamase inhibitor combination) is classified as TGA Category B1 and FDA Category [B], both listed as "Compatible" for use during pregnancy. 3
The same guidelines note a concern that amoxicillin+clavulanic acid is "not recommended in women at risk of pre-term delivery (very low risk of necrotising enterocolitis in the fetus)." 3
Pharmacokinetic Considerations
Pregnancy significantly alters the pharmacokinetics of ampicillin-sulbactam, increasing elimination and decreasing drug exposure. A 1993 pharmacokinetic study demonstrated that pregnancy significantly increased the elimination rate constant, decreased the area under the drug-versus-time curve, shortened the serum half-life, and increased total body clearance for ampicillin compared to the postpartum state. 4
This means pregnant women may require shorter dosing intervals or higher doses to maintain therapeutic concentrations, though the standard dosing regimen (ampicillin-sulbactam every 6 hours) typically remains adequate for most infections. 4
Safety During Different Trimesters
Ampicillin-sulbactam can be used throughout all trimesters of pregnancy when bacterial infection requires treatment. 5 The 2011 review on antibiotic use in pregnancy confirms that "penicillins are a first-line antibiotic treatment during pregnancy, with the exception of cases in which there is a maternal allergy to penicillin." 5
Cephalosporins (which share similar safety profiles with penicillins) are also considered first-line agents during pregnancy. 5
Labor and Delivery Considerations
Studies in guinea pigs showed that intravenous ampicillin decreased uterine tone, frequency of contractions, height of contractions, and duration of contractions. 1, 2
However, "it is not known whether the use of ampicillin and sulbactam for injection in humans during labor or delivery has immediate or delayed adverse effects on the fetus, prolongs the duration of labor, or increases the likelihood that forceps delivery or other obstetrical intervention or resuscitation of the newborn will be necessary." 1, 2
Breastfeeding
Low concentrations of ampicillin and sulbactam are excreted in breast milk; therefore, caution should be exercised when administered to a nursing woman. 1, 2
Clinical Context
The 2025 North American HS guidelines support the use of amoxicillin/clavulanic acid (a similar combination) during pregnancy based on expert opinion, noting that evidence from non-HS patients suggests cephalexin, azithromycin, and clindamycin are safe with no adverse effects reported. 6
For surgical prophylaxis, the 2024 WHO guidelines note that ampicillin+sulbactam showed no better outcomes than cefazolin for cesarean section, but both are considered acceptable options. 7
Practical Recommendation
Use ampicillin-sulbactam during pregnancy when there is a clear bacterial infection requiring treatment, as the maternal benefit of treating serious infections outweighs theoretical fetal risks. 1, 2, 5 The drug should not be withheld in cases of serious maternal infection, as untreated bacterial infections pose greater risks to both mother and fetus than the medication itself. 5