A randomized, controlled trial of parenteral clindamycin in neonatal necrotizing enterocolitis. Treatment of intra-abdominal infections is appropriate with single-agent or combination antibiotic therapy.
For an assessment of the efficacy of clindamycin in preventing bowel necrosis (intestinal gangrene or perforation), 42 premature infants with radiographically confirmed necrotizing enterocolitis (NEC) (pneumatosis, intraportal gas, or both) were randomly assigned to receive parenterally either ampicillin and gentamicin (control group, n = 22) or ampicillin, gentamicin, and clindamycin (n = 20), 20 mg/kg/d at 8-hour intervals for 10 to 14 days. Infants who had received antibiotics for greater than 24 hours before randomization and those developing intestinal gangrene or perforation less than 12 hours after randomization were excluded. Intestinal gangrene or perforation developed in four infants in the control group and six in the clindamycin group. Four in each group died of NEC. In the control group, one of 18 survivors developed a late stricture requiring surgical resection, whereas six of 15 survivors in the clindamycin group developed such strictures (P = 0.022). Routine inclusion of clindamycin in medical treatment of NEC does not reduce the frequency of intestinal gangrene or perforation and may be associated with an increase in late stricture formation. In a prospective, randomized, single-blind trial, we studied 112 adults with intra-abdominal infections and compared antibiotic therapy with cefoxitin plus placebo to therapy with tobramycin plus clindamycin. Seventy-five percent of patients receiving tobramycin-clindamycin and 71% of those receiving cefoxitin-placebo had either shock, bacteremia, malnutrition, alcoholism, rapidly or ultimately fatal underlying disease, infection originating from the distal small bowel or colon, or had had failed therapy before treatment ("high-risk" group). One third of the patients in both groups grew bacteria in the initial culture resistant to the antibiotic regimen used. Ten patients receiving cefoxitin-placebo (17%) and 11 receiving tobramycin-clindamycin (21%) had recurrence of infection or died of infection (clinical failures). Nineteen failures occurred in high-risk patients (p less than 0.05) and 17 were in patients that had antibiotic-resistant bacteria in the initial culture (p less than 0.01). Adverse effects were rare and remitted after antibiotics were stopped. Our results suggest that both cefoxitin and tobramycin-clindamycin are appropriate antibiotic regimens to treat intra-abdominal infections. Clinical failure is more common in high-risk patients and when antibiotic-resistant organisms are isolated from initial cultures.
There was insufficient evidence to recommend a particular antibiotic regimen for the treatment of NEC. There were concerns about adverse effects following the usage of clindamycin, related to the development of strictures. To address this issue a large randomised controlled trial needs to be performed.