New study reveals cefoxitin as effective first-line treatment for intraamniotic infections

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recent Clinical Infectious Diseases The study evaluated the efficacy of cefoxitin in the treatment of endometritis and intraamniotic infection (IAI).

This follows the June 2023 update of local order sets and guidelines recommending first-line cefoxitin monotherapy for the treatment of IAI and endometritis.

Study: Cefoxitin for intraamniotic infections and endometritis: a retrospective comparison with traditional antimicrobial therapy regimens in a health setting.  Image credit: Ground Pictures/Shutterstock.comStudy: Cefoxitin for intraamniotic infection and endometritis: a retrospective comparison with traditional antimicrobial therapy regimens in a health setting.. Image credit: Ground Pictures/Shutterstock.com

Background

IAI is a polymicrobial infection of the placenta, amniotic fluid, fetal membranes, fetus, or decidua. These can seriously endanger the life of the fetus or the pregnant person if not recognized and treated promptly using intrapartum antibiotics and delivery.

IAIs have also been shown to be associated with a higher likelihood of cesarean delivery 2.3 . Post-partum endometritis reflects infection of the endometrium, decidua, or myometrium after delivery of the fetus.

The American College of Obstetricians and Gynecologists (ACOG) recommends gentamicin and ampicillin as first-line antibiotic treatment for IAI.

It also calls for consideration of penicillin allergy to clindamycin, cefazolin, and vancomycin, depending on the severity of the allergy.

A local review of prescription patterns was conducted in June 2023 due to shortages of intravenous clindamycin in the United States.

This review recommended cefoxitin monotherapy as first-line antimicrobial therapy for the treatment of endometritis and IAI, replacing gentamicin and ampicillin with or without clindamycin.

About the study

This study was retrospective and observational and conducted in South Carolina. Adult hospitalized patients diagnosed with endometritis or chorioamnionitis were enrolled.

Patient outcome and treatment data were extracted from the electronic medical record (EMR) system. Individuals were excluded if they lacked EMR relevant data.

Patients were divided into two groups. The first (n=122) were treated between June 23, 2023 and August 31, 2023, the period in which the guidelines were in place.

The second group (n=350) included those treated between April 1, 2016, and June 22, 2023, when standard antimicrobial therapy was in place.

The primary composite study outcome was serious clinical events at 30 days postpartum. Serious clinical events may result in hospital readmission, ICU admission, death, or deep surgical site infection.

The individual components of the composite result constitute the secondary result. Secondary outcomes also included length of hospital stay.

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Guidelines recommending cefoxitin monotherapy were non-inferior to traditional guidelines involving ampicillin and gentamicin for serious clinical events after delivery.

Reducing the likelihood of readmission for endometritis and IAI was the main driver of the results documented here.

In the post-cefoxitin group, a 63% reduction in the likelihood of experiencing a serious clinical event and a 69% reduction in hospitalization was observed. Comparable length of hospital stay was observed across the two groups.

Additional considerations with cefoxitin include improved patient experience, reduced nursing workload, lower healthcare costs, and reduced risk of medication errors. Cefoxitin is time-effective compared to ampicillin/gentamicin/clindamycin “triple therapy”.

Multiple administration increases the potential for regimen errors and common adverse reactions. Other disadvantages of gentamicin include weight-based dosing that delays prescription and the need for drug monitoring to ensure safety.

Strengths and limitations

Strengths of this study include a large healthcare system spanning multiple campuses and a modern patient cohort, analysis of antimicrobial resistance and current pathogens.

A key limitation of the study centered on its observational and retrospective design, meaning patients received different antimicrobials across different groups.

Fewer events post-cefoxitin may lead to fewer events and fewer secondary infections.

The lack of microbiology data for medical infections was an additional limitation of this study. This leads to an incomplete understanding of the potential pathogenic organisms involved in these infections.

Moreover, clinical diagnosis of endometritis and chorioamnionitis is an additional limitation. These conditions are usually identified and managed by those who care for labor patients.

Recent studies have shown that clinical signs for the diagnosis of chorioamnionitis do not accurately identify patients with proven intra-amniotic infection. In 61% of patients with clinical IAI, microorganisms were identified in the amniotic fluid.

Of these individuals, about a quarter showed intra-amniotic inflammation without detectable microorganisms. Here, an attempt was made to standardize the cohort based on ICD-10 codes. However, it must be noted that diagnosis and ICD-10 codes depend on the treating physician.

Conclusion

In summary, this study showed that local transition to first-line antimicrobial therapy using cefoxitin monotherapy was effective and current practice is expected to continue.

The treatment of endometritis and IAI with cefoxitin requires a much less complex administration procedure than conventional methods.

Preliminary findings suggest that cefoxitin may be a promising avenue for modernizing the treatment of endometritis and IAI.



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