September 29, 2025
4 min read
More than 80% of pregnancy-related deaths in the United States are preventable. Infection is the second leading cause of pregnancy-related mortality behind bleeding causes.
Racial and ethnic disparities persist among maternal deaths, which were further highlighted during the COVID-19 pandemic. Diagnosis of antepartum infections (intraamniotic infection or chorioamnionitis) and post-partum infections (postpartum endometritis) often rely on clinical evaluation alone without defined pathologic or microbiologic evidence. As a result, empiric antibiotic therapy is a treatment mainstay. Antibiotics with more reliable spectra of activity and fewer adverse effects are available. Ever-evolving antimicrobial resistance, increasing concern for maternity care deserts, and ongoing health inequities prompt the need to rethink empiric antibiotic prescribing practices in pregnancy and post-partum infections.
Chorioamnionitis involves the amniotic fluid, fetal membranes and placenta, usually arising through ascending bacterial invasion from the genital tract after the rupture of membranes. Postpartum endometritis is most commonly encountered following cesarean section in which the endometrium and myometrium are infected. These infections tend to be polymicrobial with pathogens, such as group B Streptococcus, Escherichia coli (and other Enterobacterales), and anaerobes, stemming from the normal flora of the genital tract.
Recent, quality data examining the microbiological makeup of these infections is limited. Most published data come from the 1980s and 1990s, making interpretation of pathogen vs. contaminant more difficult.
Current state
Defined diagnostic criteria for antepartum and postpartum infections are imprecise, lending to a low threshold for empiric antibiotic therapy initiation. Additionally, chorioamnionitis and postpartum endometritis have overlapping clinical signs and symptoms with the obstetric timeline serving as a key distinguishing feature.
The American College of Obstetricians and Gynecologists (ACOG) 2017 committee opinion categorizes intraamniotic infection by:
- isolated maternal fever (isolated oral temperature of 102.2F or higher, or a persistent oral temperature of 100.4F to 102.02F);
- suspected intraamniotic infection (maternal intrapartum fever plus maternal leukocytosis, purulent cervical discharge and/or fetal tachycardia); and
- confirmed intraamniotic infection.
In comparison, diagnostic criteria for postpartum endometritis includes at least two signs or symptoms (for example, fever with a temperature higher than 100.4F, uterine or abdominal pain or tenderness, or purulent drainage from uterus) or organism isolation from endometrial fluid or tissue. The absence of fever does not preclude diagnosis of these infections when other associated signs and symptoms are present.
Antimicrobial therapy is an important adjunct to source control efforts for peripartum infections. Source control is obtained through delivery of the fetus and placenta in intraamniotic infection. Postpartum endometritis may require intervention with removal of retained products of conception for source control. The combination of ampicillin, gentamicin and clindamycin — also known as “triple I” therapy — has long been first line for peripartum infection treatment. Although this three-drug combination has been shown to be clinically effective, supportive studies are largely from the 1980s and based on in vitro cultures and susceptibilities.
ACOG recommends ampicillin with gentamicin first line for intraamniotic infections to be continued through delivery. A 2021 systematic review and meta-analysis investigating the optimal antibiotic regimen for chorioamnionitis found a lower composite morbidity (endometritis, pneumonia, sepsis, blood transfusion and ileus) with ampicillin/sulbactam vs. ampicillin plus gentamicin (0/43 patients vs. 6/49 patients; P = 0.03).
For postpartum endometritis, a 2015 Cochrane review compared different antibiotics with patients who received clindamycin plus gentamicin therapy. Less treatment failure was seen in the clindamycin plus gentamicin cohort than those treated with penicillin or cephalosporins. No difference was seen between clindamycin plus gentamicin vs. other antibiotic regimens, including beta-lactam/beta-lactamase inhibitor combinations. Coverage for more resistant anaerobes, namely Bacteroides fragilis group, was inadequate in the penicillin and early generation cephalosporin groups. A short antibiotic course for postpartum endometritis, stopping 24 to 48 hours following last febrile episode in conjunction with clinical improvement, is supported.
Looking into the future
Pek and colleagues evaluated historical standard empiric antibiotic regimens used in peripartum infections and proposed modernized treatment regimens. Microbiological and outcome data for optimal empiric regimens for intraamniotic infections and postpartum endometritis is tough to generalize today with many studies published over 30 to 40 years ago.
Antimicrobial resistance continues to emerge. Gentamicin resistance rates among Enterobacterales along clindamycin among Streptococcus species and anaerobes is concerning. Both agents are accompanied by several toxicities. Aminoglycosides pose dosing challenges when faced with rapid volume of distribution changes, such as in the postpartum period, given their hydrophilic nature. Their narrow therapeutic index enhances potential for nephrotoxicity and ototoxicity. In intraamniotic infections, aminoglycosides readily cross the placenta, posing risks to the fetus. Clindamycin is a well-known risk for antibiotic-associated Clostridioides difficile infection.
Regimens that are safe in pregnancy and breastfeeding are essential. Proposed alternative antibiotics include piperacillin/tazobactam, ceftriaxone or cefepime plus metronidazole, or ertapenem (if concerned for extended-spectrum beta-lactamase-producing organisms). All of these provide reliable coverage of gram-negative, gram-positive and anaerobic pathogens.
Ampicillin/sulbactam and amoxicillin/clavulanate are options in areas where E. coli susceptibilities are greater than 80%. Beta-lactam monotherapy will also ease nursing and pharmacy operational burdens as these agents are often stored in automated dispensing machines for quick access. Weight-based gentamicin doses tend to require compounding in the pharmacy with subsequent transport to a care unit. Fluoroquinolone-based therapy is an alternative in patients with a history of IgE-mediated beta-lactam reactions. However, fluoroquinolones may carry some risks in pregnancy and breastfeeding, though not contraindicated.
ACOG encourages providers to consult with local microbiology laboratory and infectious diseases experts to determine whether there are alternative recommended regimens based on site resistance patterns.
Breaking old habits is hard. Efficacy data supporting alternative empiric regimens in peripartum infections are limited. In the same way, empiric gentamicin, ampicillin and clindamycin data are outdated. Formal comparison studies with beta-lactam monotherapy to standard empiric regimens are anticipated to be challenging to complete.
Greater attention to local susceptibility patterns and collaboration with microbiological and infectious disease experts combined with a fresh understanding of the usual offending pathogens will optimize empiric antibiotic therapy in peripartum infections.
For more information:
Jennifer Ross, PharmD, BCIDP, is an infectious diseases clinical pharmacist at M Health Fairview – University of Minnesota Medical Center. Ross can be reached at jross13@fairview.org.
Sources/Disclosures
Source:
Expert Submission
References:
- Alrowaily N, et al. Acta Obstet Gynecol Scand. 2021;doi:10.1111/aogs.14044.
- Chen Y, et al. JAMA Netw Open. 2025;doi:10.1001/jamanetworkopen.2025.4325.
- Committee Opinion No. 712: Intrapartum Management of Intraamniotic Infection. Obstet Gynecol. 2017;doi:10.1097/AOG.0000000000002236.
- Eugene Declercq, et al. Maternal Mortality in the United States, 2025. Commonwealth Fund. July 29, 2025. https://www.commonwealthfund.org/publications/issue-briefs/2025/jul/maternal-mortality-united-states-2025. Accessed Sept. 9, 2025.
- Mackeen AD, et al. Cochrane Database Syst Rev. 2015;doi:10.1002/14651858.CD001067.pub3.
- Pek Z, et al. Open Forum Infect Dis. 2022;doi:10.1093/ofid/ofac460.
- Samiee-Zafarghandy, S, et al. Journal of Pediatric and Neonatal Individualized Medicine. 2013;doi:10.7363/020227.
Disclosures:
Ross reports no relevant financial disclosures.
