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TORONTO -- Three broad-spectrum antibiotic combinations commonly used to treat complicated intra-abdominal infections (cIAIs) in premature infants are equally safe, a researcher said here.
In a partly randomized multi-center trial, the three combinations were well tolerated with no unexpected safety signals, according to , of Duke University in Durham, N.C.
They also had much the same efficacy, Smith reported at the annual meeting of the
"These data do not support one regimen over another," Smith concluded.
That outcome was "initially kind of disappointing, because I wanted to see if one was better than the other," commented of Cincinnati Children's Hospital Medical Center, who was not part of the study but who co-moderated the session at which it was presented.
But what the study does, he told ľֱ, is "validate" the choices that clinicians have been making and give them some reassurance. "They're all going to be safe," he said, and that's a key consideration in the pediatric setting.
Complicated intra-abdominal infections -- such as necrotizing enterocolitis (NEC) or spontaneous intestinal perforation -- are a leading cause of morbidity and mortality in premature infants, Smith noted.
But the best antimicrobial regimen is not known, there have been safety concerns with some of the medications, and the most commonly used drugs are not labeled by the FDA for premature babies, he noted.
To help fill the gap, he and colleagues designed a partly randomized trial of the three combinations: ampicillin, gentamicin, and metronidazole; ampicillin, gentamicin, and clindamycin; or piperacillin-tazobactam and gentamicin.
Infants with a cIAI were randomly assigned to one of the three combinations within 48 hours of diagnosis, he said. Participating centers were also allowed to contribute safety data from infants who were on one of the study combinations outside of the trial protocol.
All told, 127 infants were randomized and an additional 49 babies were entered on a non-randomized basis. Some 62 babies (45 randomized) got ampicillin, gentamicin, and metronidazole; 46 (40 randomized) got ampicillin, gentamicin, and clindamycin; and 70 (42 randomized) got piperacillin-tazobactam and gentamicin.
The most common diagnosis was NEC, in 53%-66% of patients depending on the group.
Safety, defined as death within 30 days, was the primary endpoint. But the investigators also had a long list of "outcomes of special interest" that they were following, including gastrointestinal surgeries, progression to a higher stage of NEC, intestinal stricture or perforation, positive blood culture, short bowel syndrome, seizures, death, intraventricular hemorrhage (grade 3 or 4), and feeding intolerance.
Efficacy, a secondary outcome, was assessed at 30 days, with overall therapeutic success being defined as the baby being alive, with negative blood cultures, and a clinical cure score of more than 4.
Mortality on the three regimens was similar, Smith reported: 8.1% for ampicillin, gentamicin, and metronidazole; 11% for ampicillin, gentamicin, and clindamycin; and 10% for piperacillin-tazobactam and gentamicin.
In each group, about half of the infants had at least one adverse event, but the proportion of serious events was lower, ranging from 16% to 23% over the three groups. Events considered related to the study drugs were rarer still, occurring in 1.4%-2.2% of the infants.
Most of the babies had at least one of the outcomes of special interest, Smith said, with rates ranging from 59% to 73%, but none of the events was significantly more or less common in any group.
Overall therapeutic success was high -- 81% for ampicillin, gentamicin, and metronidazole; 87% for ampicillin, gentamicin, and clindamycin; and 80% for piperacillin-tazobactam and gentamicin.