Intestinal strictures linked to anaerobic antimicrobial therapy in infants with necrotizing enterocolitis

January 6, 2015 – The DCRI’s P. Brian Smith, MD, MPH, MHS, and other researchers conducted the study under the auspices of the Pediatric Trials Network.

Anaerobic antimicrobial therapy is associated with an increased risk of intestinal strictures in premature infants with necrotizing enterocolitis (NEC), although infants who underwent surgery for NEC have a slightly lower risk of death if they receive the therapy.

These findings, published recently in the journal Pediatrics, come from a study conducted by the DCRI’s Julie Autmizguine, MD, MHS; Christoph Hornik, MD, MPH; Daniel Benjamin Jr, MD, PhD, MPH; Michael Cohen-Wolkowiez, MD, PhD; P. Brian Smith, MD, MPH, MHS (pictured); and colleagues from other institutions. The study was conducted on behalf of the Best Pharmaceuticals for Children Act—Pediatric Trials Network Administrative Core Committee.

brian-smith-newsNEC, which occurs in approximately 10 percent of premature infants, is characterized by the inflammation and death of intestinal tissue. About 15 percent of infants with NEC will die of the condition, and for those who are treated with surgery, the rate rises to approximately 50 percent. NEC is typically treated with a variety of antibiotics and, in some cases, surgery. However, an earlier randomized trial suggested that anaerobic antimicrobial therapy was associated with increased risk of intestinal strictures. Strictures are intestinal obstructions resulting from wound healing, and are considered a marker of severity of NEC.

To determine the optimal antibiotic regimen for premature infants with NEC, the researchers identified 6,737 infants treated at 348 U.S. neonatal intensive-care units between 1997 and 2012. Of these infants, 3,358 (50 percent) were exposed to anaerobic antimicrobial therapy and 3,379 (50 percent) were not. Overall, 4,958 (74 percent) were treated medically, while 1,779 (26 percent) underwent surgery. The researchers then matched each infant who received the therapy with one who did not. Because infants with more severe cases of NEC are more likely to receive anaerobic antimicrobial therapy, the researchers used propensity score matching to ensure that similarly ill infants were compared. Out of the original cohort, 1,390 infants exposed to anaerobic antimicrobial therapy were matched with 1,390 infants not exposed.

The researchers found that infants who received anaerobic antimicrobial therapy were more likely to be on ventilation (2,152 [64 percent] vs 1,467 [45 percent]) and vasopressor therapy (839 [25 percent] vs 283 [8 percent]) compared with infants who did not receive anaerobic antimicrobial therapy. Among infants who received anaerobic antimicrobial therapy, clindamycin was the most frequently used anaerobic antibiotic (56 percent), followed by metronidazole (29 percent) and piperacillin–tazobactam (9 percent). Strictures as a single outcome were somewhat more common among infants who received anaerobic antimicrobial therapy. For infants who underwent surgery, death was less common with anaerobic antimicrobial therapy.

Because strictures are associated with more severe NEC, the lower rate of strictures in the nonanaerobic treatment group could be the result of infants dying before such strictures could develop, the researchers noted.