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Study: High-Dose Vancomycin Increases Risk of Kidney Damage in Children

Each 5-mg/kg rise in dose boosts risk by 16%

The results of a small study conducted at the Johns Hopkins Children’s Center show that hospitalized children given high-dose intravenous (IV) infusions of the antibiotic vancomycin to treat drug-resistant bacterial infections face an increased risk of kidney damage –– an often-reversible but sometimes serious complication.

The findings, published in the December issue of the Annals of Pharmacotherapy, highlight the importance of prescribing the medication cautiously, the investigators say, and also underscore the need for newer, safer drugs to treat resistant infections.

“Our results bear out the difficult balancing act between ensuring the dose is high enough to successfully treat these serious and, at times, life-threatening infections against the small but real risk for kidney damage,” said senior investigator Carlton Lee, PharmD, MPH. “Ultimately, what we really need are new drugs that achieve the same therapeutic effect without taking a toll on the kidneys and other organs.”

Vancomycin, the researchers note, is a drug reserved for the treatment of bacterial infections that don’t respond to other medications, and it has been used safely for decades. But the spread of drug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), prompted new dosing guidelines in 2009, which called for treatment with higher doses of the drug when a resistant infection is suspected.

Although the new high-dose guidelines were written with adult patients in mind, many pediatric hospitals have applied the high-dose approach to the treatment of children to ensure that the drug reaches high-enough levels in the blood to successfully knock out the resistant germs and to stave off the serious complications associated with such pernicious bacteria. The researchers also emphasize that this 30-year-old antibiotic can be a lifesaver for many patients with serious bacterial disease and that kidney damage is generally reversible when treatment stops.

The study, based on an analysis of the records of 175 children treated with vancomycin at Johns Hopkins between 2009 and 2010, found that 14% developed kidney damage.

Tellingly, Lee says, the higher the dose was, the greater the risk, with each 5-mg/kg increase boosting the risk of kidney failure by 16%. In other words, a 20-kg (44-lb) child receiving 1,600 mg of vancomycin per day has a 16% higher risk for kidney damage compared with a child of the same age and weight receiving 1,200 mg of the drug daily. Other factors driving risk included prolonged therapy –– each additional day of treatment increased the risk by 11% –– and simultaneous use of other drugs that can tax the kidneys, the researchers found. Children who received more than one such medication showed a five-times-higher risk of kidney damage.

The average length of treatment with vancomycin was 8 days among children who experienced kidney injury compared with 4 days among those who didn’t. The average daily dose among children who developed kidney damage was 10 mg/kg higher than the average daily dose among kids who didn’t develop kidney damage.

 The researchers noted that each child receiving vancomycin underwent periodic blood tests to measure the kidney filtration rate. Children receiving vancomycin were being treated for invasive, serious infections of the skin, bone, heart, lung, and brain, or for bloodstream infections caused by MRSA.

Despite the small number of patients involved in the study, the researchers said they believe their results apply to patients at pediatric hospitals nationwide, highlighting the urgent need to develop newer, safer therapies for drug-resistant bacterial infections in children, something the Johns Hopkins Children’s Center is actively pursuing in several clinical trials.

The researchers said that calls for high-dose IV vancomycin should be made after factoring in a child’s overall health and the use of any other medications. In any case, they said, vancomycin therapy should include careful and frequent monitoring of kidney function in those receiving high doses.

Source: EurekAlert; December 22, 2014.

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