Discussion

This retrospective cohort study of patients with suspected or confirmed chorioamnionitis at a multi-site health system demonstrated that patients were more likely to receive recommended antibiotics for IAI in an optimal time frame when cefoxitin was utilized compared to combination antibiotics. There were no differences observed in any of the additional secondary outcomes, including 30-day infection-related readmission, need for further surgical or procedural interventions, or overall mortality. This study highlights the advantages of cefoxitin in terms of timeliness of antibiotic therapy, compared to the current first-line regimen of ampicillin and gentamicin, in a setting where ACOG recommends ‘immediate’ administration of antibiotics. ²

The current ACOG guidelines for the management of IAI recommend ampicillin and gentamicin as first-line agents, based on historical studies. These recommendations have not been revisited in recent years, despite growing concerns about the adverse effects associated with aminoglycosides, which are increasingly falling out of favor in clinical practice for non-pregnant patients, and improved safety profile for other antimicrobials such as cephalosporins like cefoxitin. ^{Reference Pek, Heil and Wilson13} Notably, the use of aminoglycosides in IAI remains one of the few areas where they are still recommended as part of the first-line therapy options. Historically, few studies have explored cefoxitin as a potential treatment for chorioamnionitis.

Several studies from the 1980s demonstrated comparable efficacy between cefoxitin and other antimicrobial regimens for obstetric and gynecologic infections. ^{Reference Sweet, Gall and Gibbs14–Reference Faro, Phillips, Baker, Goodrich, Turner and Riddle17} However, many of the comparator agents like moxalactam and mezlocillin are no longer available for therapeutic use, these studies were not specific for chorioamnionitis, and the data are outdated by newer literature. A 2024 study analyzed the use of cefoxitin for chorioamnionitis in the context of evolving institutional practices and recent clinical data. ^{Reference Bailey, Schacht and Pazienza8} The review highlights a large retrospective cohort study in which a healthcare system transitioned to first-line cefoxitin monotherapy for IAIs, including chorioamnionitis. This change was associated with noninferior rates of serious maternal clinical events postdelivery compared to traditional regimens such as ampicillin plus gentamicin, after adjusting for baseline differences between groups. The study emphasizes the importance of local resistance patterns and institutional protocols in guiding antibiotic selection but supports the adoption of cefoxitin as an evidence-based treatment option for the management of chorioamnionitis.

ACOG identifies several single-agent alternatives to ampicillin plus gentamicin that vary in antimicrobial spectrum and operational practicality. Ampicillin–sulbactam and piperacillin–tazobactam provide broad coverage of the polymicrobial pathogens involved, including anaerobes; however, the expanded gram-negative coverage of piperacillin–tazobactam is generally unnecessary for routine chorioamnionitis and may raise stewardship concerns. Although recent literature compared combination therapy to piperacillin–tazobactam, including a retrospective study that demonstrated piperacillin–tazobactam was noninferior to ampicillin plus gentamicin for IAI, with no significant differences in composite maternal or neonatal morbidity after propensity-score matching. ^{Reference Anderson, Scarpaci and Hardy18} Ertapenem provides the most convenient once-daily dosing and broad-spectrum activity but may be limited by cost, antimicrobial stewardship considerations, and reduced reliability in critically ill or hypoalbuminemic patients. All single-agent regimens simplify care by eliminating the need for adjunctive clindamycin after cesarean delivery. Additionally, most of these alternatives can be administered as an IV push, improving timeliness and preserving IV access.

Cefoxitin, along with the other alternative regimens, may represent a more efficient and operationally streamlined alternative to ampicillin and gentamicin regimens for chorioamnionitis, offering both clinical effectiveness and workflow advantages. Many patients admitted to labor and delivery units often have only a single peripheral IV line available, which may complicate the administration of combination therapy and introduce potential for medication delays and errors. Additionally, gentamicin introduces further logistical complexity due to weight-based dosing requirements and the need for dose calculations that may depend on pharmacist availability, posing challenges in settings without 24-hour pharmacy support.

This study has several limitations that should be considered when interpreting the findings. First, the lack of standardized clinical documentation across patient records introduced variability, which may have led to inconsistencies in data interpretation and limited the ability to precisely identify the timing and rationale for clinical decisions. The primary outcome measure has not been validated and differs from Surviving Sepsis Campaign recommendations, which are based on time from sepsis recognition to antibiotic initiation. In this study, antibiotic order entry was used as “time zero,” and time to completion was measured, reflecting EHR limitations, as the exact time of clinical recognition is not reliably recorded. Thus, order time served as a pragmatic surrogate that may not fully capture the onset of clinical suspicion, and the 60- to 90-minute time frame was inferred.

Variability in gentamicin dosing protocols within the study site is another limitation which may limit comparisons across patients and healthcare settings. Importantly, the absence of neonatal outcome data limits the ability to comprehensively evaluate the overall efficacy of cefoxitin. Additionally, AKI was evaluated only among patients receiving gentamicin, given its known risk of nephrotoxicity, which limits our ability to directly compare this safety outcome with cefoxitin. Lastly, this study is subject to potential unmeasured confounding variables, including but not limited to factors such as staffing variability, patient census and workload, and delays or inconsistencies in clinical documentation.

The use of cefoxitin for the treatment of chorioamnionitis was associated with a reduced time to recommended antibiotic administration, demonstrating improved efficiency in initiating appropriate therapy. Although no significant differences were observed in secondary clinical outcomes, these findings contribute to the growing body of evidence supporting the efficacy and clinical utility of cefoxitin in the management of chorioamnionitis.