Comparison of various antimicrobial agents as catheter lock solutions: preference for ethanol in eradication of coagulase-negative staphylococcal biofilms.

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.

[1]  M. Allon Prophylaxis against dialysis catheter-related bacteremia with a novel antimicrobial lock solution. , 2003, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[2]  K. Ko,et al.  In vitro evaluation of the antibiotic lock technique (ALT) for the treatment of catheter-related infections caused by staphylococci. , 2006, The Journal of antimicrobial chemotherapy.

[3]  I. Raad,et al.  Optimal Antimicrobial Catheter Lock Solution, Using Different Combinations of Minocycline, EDTA, and 25-Percent Ethanol, Rapidly Eradicates Organisms Embedded in Biofilm , 2006, Antimicrobial Agents and Chemotherapy.

[4]  H. Ceri,et al.  The Calgary Biofilm Device: New Technology for Rapid Determination of Antibiotic Susceptibilities of Bacterial Biofilms , 1999, Journal of Clinical Microbiology.

[5]  D. Qu,et al.  Formation and properties of in vitro biofilms of ica-negative Staphylococcus epidermidis clinical isolates. , 2007, Journal of medical microbiology.

[6]  W. Poole,et al.  Late-onset sepsis in very low birth weight neonates: the experience of the NICHD Neonatal Research Network. , 2002, Pediatrics.

[7]  D. K. Benjamin,et al.  Bacteremia, central catheters, and neonates: when to pull the line. , 2001, Pediatrics.

[8]  S. Percival,et al.  Use of In Vivo-Generated Biofilms from Hemodialysis Catheters To Test the Efficacy of a Novel Antimicrobial Catheter Lock for Biofilm Eradication In Vitro , 2004, Journal of Clinical Microbiology.

[9]  I. Chopra,et al.  Comparison of assays for detection of agents causing membrane damage in Staphylococcus aureus. , 2004, The Journal of antimicrobial chemotherapy.

[10]  W. Dunne,et al.  Diffusion of rifampin and vancomycin through a Staphylococcus epidermidis biofilm , 1993, Antimicrobial Agents and Chemotherapy.

[11]  S. Patole,et al.  Intravenous rifampicin in neonates with persistent staphylococcal bacteraemia , 2002, Acta paediatrica.

[12]  M. Edmond,et al.  Use of ethanol lock therapy to reduce the incidence of catheter-related bloodstream infections in home parenteral nutrition patients. , 2007, JPEN. Journal of parenteral and enteral nutrition.

[13]  J. Cheesbrough,et al.  Antimicrobial lock therapy for catheter-related bacteraemia among patients on maintenance haemodialysis. , 2002, The Journal of antimicrobial chemotherapy.

[14]  R. Donlan Role of Biofilms in Antimicrobial Resistance , 2000, ASAIO journal.

[15]  R. Soutar,et al.  Complications of the ethanol-lock technique in the treatment of central venous catheter sepsis. , 2005, The Journal of infection.

[16]  F. K. Gould,et al.  Use of antibiotic locks to treat colonized central venous catheters. , 2001, The Journal of antimicrobial chemotherapy.

[17]  K. Lewis Persister cells and the riddle of biofilm survival , 2005, Biochemistry (Moscow).

[18]  M. Deighton,et al.  Methods for studying biofilms produced by Staphylococcus epidermidis. , 2001, Methods in enzymology.

[19]  C. Edmiston,et al.  Impact of selective antimicrobial agents on staphylococcal adherence to biomedical devices. , 2006, American journal of surgery.

[20]  Frederik Hammes,et al.  Assessment and Interpretation of Bacterial Viability by Using the LIVE/DEAD BacLight Kit in Combination with Flow Cytometry , 2007, Applied and Environmental Microbiology.

[21]  S. Aaron,et al.  Multiple Combination Bactericidal Testing of Staphylococcal Biofilms from Implant-Associated Infections , 2006, Antimicrobial Agents and Chemotherapy.

[22]  L. Baddour,et al.  Adherence of coagulase-negative staphylococci to plastic tissue culture plates: a quantitative model for the adherence of staphylococci to medical devices , 1985, Journal of clinical microbiology.

[23]  E. Castagnola,et al.  Catheter Lock and Systemic Infusion of Linezolid for Treatment of Persistent Broviac Catheter-Related Staphylococcal Bacteremia , 2006, Antimicrobial Agents and Chemotherapy.

[24]  B. Almirante,et al.  Antibiotic-lock therapy for long-term intravascular catheter-related bacteraemia: results of an open, non-comparative study. , 2006, The Journal of antimicrobial chemotherapy.

[25]  A. Rønnestad,et al.  Coagulase-Negative Staphylococcal Sepsis in Neonates: Association Between Antibiotic Resistance, Biofilm Formation and the Host Inflammatory Response , 2005, The Pediatric infectious disease journal.

[26]  L. Wong,et al.  Inhibition by ethanol of the growth of biofilm and dispersed microcosm dental plaques. , 1996, Archives of oral biology.

[27]  S. Chambers,et al.  Use of ethanol locks to prevent recurrent central line sepsis. , 2004, The Journal of infection.

[28]  J. Minton,et al.  Insufficient penetration of systemic vancomycin into the PermCath lumen. , 2000, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[29]  B. Souweine,et al.  Ethanol lock solution as an adjunct treatment for preventing recurrent catheter-related sepsis--first case report in dialysis setting. , 2006, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[30]  A. Widmer,et al.  Microbiological tests to predict treatment outcome in experimental device-related infections due to Staphylococcus aureus. , 1994, The Journal of antimicrobial chemotherapy.

[31]  É. Lerebours,et al.  Efficacy of antibiotic-lock technique with teicoplanin in staphylococcus epidermidis catheter-related sepsis during long-term parenteral nutrition. , 2002, JPEN. Journal of parenteral and enteral nutrition.

[32]  W. Onland,et al.  Ethanol-lock technique for persistent bacteremia of long-term intravascular devices in pediatric patients. , 2006, Archives of pediatrics & adolescent medicine.

[33]  B. Messing,et al.  Antibiotic-lock technique: a new approach to optimal therapy for catheter-related sepsis in home-parenteral nutrition patients. , 1988, JPEN. Journal of parenteral and enteral nutrition.

[34]  I. Raad,et al.  Comparative In Vitro Efficacies of Various Catheter Lock Solutions , 2006, Antimicrobial Agents and Chemotherapy.

[35]  J. Rotschafer,et al.  Elimination of quinolone antibiotic carryover through use of antibiotic-removal beads , 1993, Antimicrobial Agents and Chemotherapy.

[36]  D. Grando,et al.  Coagulase-negative staphylococci in very-low-birth-weight infants: inability of genetic markers to distinguish invasive strains from blood culture contaminants , 2006, European Journal of Clinical Microbiology and Infectious Diseases.

[37]  S. Stocks Mechanism and use of the commercially available viability stain, BacLight , 2004, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[38]  G. Peters,et al.  Pathogenesis of infections due to coagulase-negative staphylococci. , 2002, The Lancet. Infectious diseases.

[39]  G. Pugliese,et al.  Biofilms and Planktonic Cells of Pseudomonas aeruginosa Have Similar Resistance to Killing by Antimicrobials , 2002, Infection Control & Hospital Epidemiology.

[40]  Jerome J. Schentag,et al.  Pharmacokinetic and pharmacodynamic activities of ciprofloxacin against strains of Streptococcus pneumoniae, Staphylococcus aureus, and Pseudomonas aeruginosa for which MICs are similar , 1994, Antimicrobial Agents and Chemotherapy.

[41]  H. Caron,et al.  Prophylactic antibiotics for preventing early Gram-positive central venous catheter infections in oncology patients, a Cochrane systematic review. , 2005, Cancer treatment reviews.

[42]  R. Colwell,et al.  Viable but nonculturable Vibrio cholerae O1 in biofilms in the aquatic environment and their role in cholera transmission , 2007, Proceedings of the National Academy of Sciences.

[43]  P. Villari,et al.  Molecular Epidemiology of Staphylococcus epidermidis in a Neonatal Intensive Care Unit over a Three-Year Period , 2000, Journal of Clinical Microbiology.

[44]  M. Allon Dialysis catheter-related bacteremia: treatment and prophylaxis. , 2004, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[45]  J. V. van Woensel,et al.  Prophylactic antibiotics for preventing early central venous catheter Gram positive infections in oncology patients. , 2007, The Cochrane database of systematic reviews.

[46]  J. Costerton,et al.  Antimicrobial Activity of a Novel Catheter Lock Solution , 2002, Antimicrobial Agents and Chemotherapy.

[47]  L. Mermel,et al.  Guidelines for the management of intravascular catheter-related infections. , 2001, Infection control and hospital epidemiology.

[48]  M. Cormican,et al.  Linezolid Compared with Eperezolid, Vancomycin, and Gentamicin in an In Vitro Model of Antimicrobial Lock Therapy for Staphylococcus epidermidis Central Venous Catheter-Related Biofilm Infections , 2003, Antimicrobial Agents and Chemotherapy.

[49]  J. Leiva,et al.  Synergy of different antibiotic combinations in biofilms of Staphylococcus epidermidis. , 2001, The Journal of antimicrobial chemotherapy.

[50]  Hualiang Jiang,et al.  Antimicrobial activities of YycG histidine kinase inhibitors against Staphylococcus epidermidis biofilms. , 2007, FEMS microbiology letters.