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A delicate balance

Friday, April 6, 2018
By Marla Broadfoot
Rachel Greenberg, Michael Cotten

Should she change the dose of steroids? Administer a diuretic? Remove the feeding tube? Rachel Greenberg makes hundreds of crucial decisions while shuffling through the dimly lit bays of the neonatal intensive care unit (NICU) at Duke University Medical Center in Durham, North Carolina. As she checks on the little ones entrusted to her care, some babies fuss in open cribs beneath mobiles emitting soothing tones; the smallest, weighing less than half a kilogram, slumber in cases of clear plastic. In the corners, computer monitors silently shout messages such as “Wash your hands!”

Near the end of Greenberg's rounds, the young neonatologist visits one of the newest arrivals, a baby girl with mahogany skin and wisps of black hair, recently transferred from a community hospital. She was born 4 weeks too early, and though she's faring better than most in the NICU, a note in her chart concerns Greenberg. Doctors at the community hospital had given the baby antibiotics without testing for an infection. Greenberg wonders whether the drugs were necessary. She had run a blood culture herself and found no bacteria. Maybe the baby never had an infection. Or maybe she had, and the antibiotics were working. With no way to know, Greenberg continues the medication.

Routinely giving antibiotics to premature babies may do more harm than good.

Like that baby, the vast majority of the nearly half-million infants born prematurely in the United States are given antibiotics, even without evidence of infection. Many preemies are kept on the drugs after blood tests say they are not sick. Yet that practice, once considered the best way to protect a hospital's most vulnerable patients, is now being challenged. “We're beginning to recognize that the risk of giving that antibiotic may actually outweigh the benefit,” says Josef Neu, a neonatologist at the University of Florida in Gainesville.

Some studies suggest that even while helping fight certain infections, those drugs may encourage others by wiping out an infant's developing gut microbiome—those trillions of resident microbes with functions as diverse as synthesizing vitamins and bolstering our immune systems. By disrupting that microbial ecosystem, blanket antibiotic dosing of babies, particularly preemies, may promote a host of problems later in life, such as asthma and obesity. And recent research indicates that long after preemies leave the NICU, they can harbor many antibiotic-resistant microorganisms, potentially endangering not only themselves, but also the wider population.

In all corners of medicine, doctors are waking up to the dangers of antibiotic overuse. But change is coming slowly to the NICU. Another message that pops up on the monitors at Duke is: “Antibiotics are not always the answer!” Yet many neonatologists hesitate to alter their habits, unable to shake the fear that a baby may die on their watch. “We are working to change our perception … to fight the belief that antibiotics are always the safe thing to do,” Greenberg says.

Neu hopes to provide hard evidence with a small clinical trial: A random selection of premature infants who would have been given antibiotics automatically will instead be placed in a nontreatment control group. For 2 years, his team will track the microbiomes and health of the preemies. Some of Neu's colleagues feel uneasy about withholding antibiotics, but he says answers are needed. “What can we do to use these antibiotics more intelligently? This is, I think, one of our biggest conundrums in neonatal intensive care right now.”

Today, babies born as early as 28 weeks routinely survive, as do more than half of those born at 24 weeks (although often with significant disabilities). Much of the credit goes to antibiotics, which have thwarted infections such as sepsis and group B strep that a preemie's immature immune system could not have fought on its own. Those successes spurred a steady increase in routine antibiotic use in the NICU. At last count, three of the top four drugs prescribed in the NICU were antibiotics.

Over time, however, scientists began noticing that antibiotics can increase babies' risk of the very afflictions the drugs aim to protect against—such as fungal infections, late-onset sepsis, and a deadly intestinal disorder called necrotizing enterocolitis. In a seminal 2009 study in Pediatrics, for example, Greenberg's colleague Michael Cotten showed that each additional day of antibiotics significantly increased the odds that a preemie would develop necrotizing enterocolitis or die.

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