Coagulase-negative staphylococci (CoNS) are the main causative agents of bacteraemia in infants managed in neonatal intensive care units (NICUs). Intraluminal colonization of long-term central venous catheters by these bacteria and subsequent biofilm formation are the prerequisites of the bloodstream infections acquired in NICUs. The catheter lock technique has been used to treat catheter colonization; however, the optimum choice of antimicrobial agents and their corresponding concentrations and exposure times have not been determined. The effectiveness of catheter lock solutions (CLSs) was assessed by determining the minimal biofilm eradication concentration of antimicrobial agents against CoNS biofilms. Five conventional antibiotics (oxacillin, gentamicin, vancomycin, ciprofloxacin and rifampicin) alone or in combination, as well as ethanol, were evaluated. Ethanol was found to be superior to all of these conventional antibiotics when used as a CLS. A time-kill study and confocal laser scanning microscopy revealed that exposure to 40 % ethanol for 1 h was sufficient to kill CoNS biofilm cells. To our knowledge, this is the first in vitro study to provide solid evidence to support the rationale of using ethanol at low concentrations for a short time as a CLS, instead of using conventional antibiotics at high concentrations for a long period to treat catheter-related bloodstream infections.
INTRODUCTIONCoagulase-negative staphylococci (CoNS), predominantly Staphylococcus epidermidis, are the most common causative agents of bloodstream infections in neonatal intensive care units (NICUs) (Stoll et al., 2002;Villari et al., 2000). These bacteria are relatively avirulent compared with Staphylococcus aureus and other organisms that also cause bloodstream infections. The pathogenesis of CoNS infection depends mainly on their ability to form biofilms on the surfaces of various polymers (Klingenberg et al., 2005;von Eiff et al., 2002). Long-term catheters are used in both ambulant and hospitalized patients in areas such as intensive care and oncology to provide central venous access for various therapies (Ackoundou-N'guessan et al., 2006;Onland et al., 2006;Opilla et al., 2007;van de Wetering & van Woensel, 2007). Major adverse effects of long-term catheterization are catheter-related bloodstream infections (CRBSIs), due to intraluminal colonization of catheters by CoNS, and subsequent biofilm formation on the surface of the catheter lumen.Systemic antibiotics have been widely used to treat CRBSIs, but failures have been reported frequently (Allon, 2004;Benjamin et al., 2001;Berrington & Gould, 2001;Gagnon et al., 1993) due to the inability of most conventional antibiotic therapies to eradicate biofilm-grown bacteria (Donlan, 2000;Klingenberg et al., 2005) or to poor access of antibiotics to the surface of the catheter lumen (Bastani et al., 2000). These deficits can be overcome by the catheter lock technique (CLT), which involves filling the lumen of the catheter with an antimicrobial agent at high concentration (100-...