Stability and in vitro efficacy of antibiotic-heparin lock solutions potentially useful for treatment of central venous catheter-related sepsis

Objectives: Increasing numbers of patients for whom infection is a major risk are dependent on central venous catheters. Antibiotic-anticoagulant locks may have a role in preventing or treating catheter-related infections. The aim of this study was to determine the in vitro stability and efficacy of anti biotic-heparin lock solutions. Methods: Candidate antibiotics (amikacin, ciprofloxacin, flucloxacillin, gentamicin, linezolid, teicoplanin) were investigated in vitro, either individually or in combination, in solution with heparin. The solutions were initially tested for visual precipitation. The efficacy of stable solutions and taurolidine was then tested in a catheter model bioassay system against microorganisms commonly encountered in catheter-related septicaemia. Results: In general, lower concentrations of heparin (less than or equal to1000 U/mL) combined with antibiotics resulted in precipitation, whereas high concentrations (3500-10000 U/mL) were compatible with a broader range of antibiotic concentrations. The stability of each anti biotic-heparin combination required individual assessment. Bioassays identified the following promising antibiotic-anticoagulant solutions: for broad-spectrum empirical cover, a teicoplanin-ciprofloxacin-heparin solution; for directed use, flucloxacillin-heparin for methicillin-susceptible Staphylococcus aureus (MSSA), high dose teicoplanin-heparin for methicillin-resistant S. aureus (MRSA), high-dose linezolid-heparin for vancomycin-resistant enterococci (VRE) and ciprofloxacin-heparin for (susceptible) Pseudomonas aeruginosa; for prophylactic use, taurolidine. Conclusion: These solutions now warrant clinical trials to investigate their role in the management of catheter-related septicaemia.