Alternative Antibiotics After C-Section Linked to More Infections

Nancy A. Melville

September 20, 2018

The use of prophylactic antibiotics in cesarean-section delivery other than the standard recommendation of first-generation cephalosporins, such as cefazolin, is linked to an increased risk of adverse events, according to a new analysis of more than 6500 cesarean-section deliveries.

"Use of both standard alternative and inappropriate alternative antibiotics was associated with higher odds of surgical site infections compared with use of cefazolin for prophylaxis at the time of cesarean delivery," the authors report in their article published online September 7 in Obstetrics & Gynecology.

Although cephalosporins are recommended first-line for the prevention of wound infection with cesarean-section delivery, alternatives are necessary for women with significant beta-lactam allergies, they explain.

In such cases, the American College of Obstetricians and Gynecologists (ACOG) recommends alternative antibiotics, such as clindamycin combined with an aminoglycoside.

In comparing outcomes of the different antibiotics — including a third category of inappropriate antibiotics (women given neither standard antibiotics nor the recommended alternative), such as clindamycin only — Tetsuya Kawakita, MD, Department of Obstetrics and Gynecology, MedStar Washington Hospital Center, Washington, DC, and colleagues evaluated data of 6584 women who had cesarean-section delivery at the hospital between 2012 and 2017.

More Than 90% of Women Recommended Antibiotic Regimen

The vast majority of women, 6163 (93.6%), received standard cefazolin, while 274 (4.2%) received a standard alternative and 147 (2.2%) received inappropriate alternative antibiotics. Most who received inappropriate alternatives received a single agent — clindamycin or gentamicin.

Whereas use of recommended alternative antibiotics was not associated with an increased risk over cefazoline of the primary outcome — a composite of cellulitis, endometritis, deep wound infection, abdominopelvic abscess, and sepsis — alternative antibiotic use was shown in a subgroup analysis to be associated with an increased odds of cellulitis (adjusted odds ratio [OR], 1.93; 95% CI, 1.03 - 3.31).

Alternative antibiotic use was also linked with an increased odds of an emergency department visit resulting from a wound complication (adjusted OR, 2.34; 95% CI, 1.19 - 4.18) compared with cefazolin.

In addition, use of inappropriate antibiotics was associated with a significantly increased odds of the primary outcome compared with cefazolin (adjusted OR, 4.13; 95% CI, 2.59 - 6.36), as well as components of the composite outcome, including endometritis before discharge (adjusted OR, 6.68; 95% CI, 3.69 - 11.44) and cellulitis (adjusted OR, 3.23; 95% CI, 1.63 - 5.81).

The authors speculate that the increase in cellulitis seen with the use of recommended alternative antibiotics may reflect important differences between the drugs in response to skin flora.

"The increase in cellulitis may be explained by effectiveness of cefazolin in controlling skin flora such as Streptococcus species and Staphylococcus species compared with that of nonbeta-lactam agents," they suggest.

Standard Antibiotic Prophylaxis May Be Suitable for More Patients

Of the 274 women who received standard alternative antibiotics, 12 (4.4%) did not have a beta-lactam allergy, and of the 147 who received inappropriate alternative antibiotics, 24 (16.3%) did not report a beta-lactam allergy.

But a closer look at the allergies showed that only about 50% of women who received the standard antibiotic alternative and 39% who received inappropriate alternatives had what was considered "a significant history of beta-lactam reactions, such as anaphylaxis, angioedema, respiratory distress, or urticaria."

The others had either beta-lactam allergies with nonsignificant reactions or no specific documentation of an allergic reaction, suggesting that the standard treatment of cefazolin may in fact be appropriate — and more effective — in at least some of those women.

"Clinicians need to assess the validity of a patient-reported history of beta-lactam allergy because only 10–20% of patients reporting a beta-lactam allergy demonstrate a true allergy when assessed by skin testing," Kawakita and colleagues note.

Furthermore, "using cefazolin for women with a history of a nonsignificant beta-lactam allergy may lower the rate of post-cesarean wound complications," they stress.

Point-of-care testing for beta-lactam allergies, which has a negative predictive value of 97% in excluding a reaction to beta-lactam antibiotics, may be useful in better identifying the best candidates for alternative antibiotics, they suggest.

Meanwhile, they conclude, "further studies that examine alternatives to ACOG recommended alternative antibiotics would be useful."

The authors have reported no relevant financial relationships.

Obstet Gynecol. Published online September 7, 2018. Abstract

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