Balance resistance fears with infection prevention

Vancomycin solution reduces infections in NICU

Though controversial due to fears of rising antibiotic resistance, it appears that minute amounts of vancomycin in heparin lock solutions can dramatically reduce deadly bloodstream infections (BSIs) in neonates under intensive care, a leading researcher has found.

"If you look at all bloodstream infections that occurred in the study population, there was a very substantial reduction — a 60% reduction — in bloodstream infections with the use of a vancomycin heparin lock solution," said Dennis Maki, MD, the chief of infectious diseases at the University of Wisconsin Hospital and Clinics in Madison. He presented the study’s results recently in San Diego at the Interscience Conference on Antimicrobial Agents and Chemotherapy.

The issue is controversial because there is a perception regarding previous studies that "this is irresponsible use of anti-infectives for prophylaxis — that this would lead to wide-scale antibiotic resistance," Maki said. Vancomycin is fading in efficacy against resistant strains of both enterococci and Staphylococcus aureus. But the question has not been adequately addressed for heparin lock solutions — used with devices like peripherally inserted central catheters (PICCs) — because some studies have not prospectively screened patients for colonization by vancomycin-resistant organisms. Maki did and found none.

"Colonization by vancomycin-resistant bacteria was not seen in any children, and we did careful susceptibility testing of every single isolate obtained from devices, the skin, the blood cultures. We saw absolutely no evidence of MIC [minimum inhibitory concentration] shift suggesting that they might be selecting for resistance," he said.

One of the leading experts in health care epidemiology in catheter-related infections, Maki looked at the risk and reward in undertaking the study in a neonatal intensive care unit (NICU). "The pathogenesis of device-related infection with long-term devices — which we define as cuffed and tunneled catheters, PICCs, ports, perhaps cuffed hemodialysis catheters — appears to be mainly interluminal contaminants," he said. "We think that this would suggest that anti-infective lock solutions ought to beneficial with these long-term types of devices. And we know that hospitalized neonates, who require prolonged IV access, are at very high risk of catheter-related BSIs, particularly with CNS [coagulase negative staph]."

In the study, 82 neonates in a Level III NICU with a PICC randomly were assigned to have the catheter lock solution containing vancomycin (25µ/mL) or saline (control). Peripheral and PICC-drawn blood cultures and a PICC hub culture were obtained when sepsis was suspected, and catheter and hub cultures were obtained at PICC removal. Surveillance cultures were done to detect colonization by vancomycin-resistant enterococci (VRE), and blood vancomycin levels were measured. A "definite" catheter-related BSI was defined as a positive peripheral blood culture with a clonally concordant colonized catheter or hub. Subjects in the two groups had similar patient profiles and length of PICC duration.

"That were eight definite catheter-related bloodstream infections in the control group; none in the heparin lock solution group," Maki said. "There were five probable’ catheter related [infections] in the control group; two in the treatment group."

Of particular interest was the finding that vancomycin could not be detected in the blood of any infants receiving the antibiotic in the heparin lock solution. "The reason I think this is the case — and why I think that anti-infective lock solutions probably will have no impact on the patient’s microflora — is that the total amount of vancomycin in the lumen of that catheter is less than 5 mcg," Maki said. "You couldn’t begin to measure it in blood or urine. If it is so infinitesimal — even if you flushed it all in — its hard to see how its going to have an impact on antibiotic resistance."

Larger clinical trials are needed, but the study provides "proof in principle" that prophylactic use of a vancomycin-laced lock solution can markedly reduce the incidence of PICC-related BSI, Maki said. Still, the hope is that an agent other than vancomycin can be found to have the same effect. "I would much rather find something that there is not even the slightest question of impact on resistance," he said.