Formulation of a flush solution of heparin, vancomycin, and colistin for implantable access systems in oncology

Abstract

Introduction: Because of the increased use of im plantable access systems, the incidence of blood stream and catheter infections associated with these systems has concomitantly increased. Classically, he parin-lock flush solutions were used to prevent thrombosis; more recently, vancomycin was added to the solution to prevent infections caused by Gram- positive bacteria, particularly coagulase-negative Staphylococci. Disorders due to Gram-negative organ isms have now appeared in oncologic patients. We therefore tested the addition of colistin to heparin- vancomycin solutions. Colistin was chosen for its good activity against Gram-negative bacteria (98% susceptibility in our hospital), its good tolerance due to low systemic passage, and its low cost. Methods: We developed formulations contain ing heparin (100 IU/mL) and various concentrations of vancomycin (10-500 μg/mL) and colistin (10-100 μg/mL) in 0.9% NaCl. Each sterile solution was tested for physical and chemical compatibility (spectropho tometry, nuclear magnetic resonance, and pH mea surements) and its antibacterial activity (against ox acillin-resistant Staphylococcus aureus, Enterococcus faecium, Klebsiella pneumoniae exhibiting broad- spectrum betalactamase (BSBL), imipenem-resistant Pseudomonas aeruginosa) for 2 months at 4°C and at room temperature. Results: The most suitable combination of drugs is heparin (100 IU/mL), vancomycin (100 μg/mL), and colistin (100 μg/mL). This flush solution main tains activity when stored at 4°C for up to 1 month. Conclusions: We feel that the combination of heparin, vancomycin, and colistin can be used as a flush solution for indwelling catheters.

Stability and compatibility of antimicrobial lock solutions

“…58 When vancomycin 0.1 mg/ mL was combined with colistimethate sodium 0.1 mg/mL and heparin sodium 100 units/mL, the vancomycin concentration remained stable for 60 days at 4 °C and for 15 days at 25 °C. 63 Published reports on research into other combinations using vancomycin discuss solutions containing ceftazidime, amikacin, and rifampin, but these studies reported only on visual compatibility at varying concentrations. 19,46,64,65 These antibacterial lock solution combinations may be useful in patients with polymicrobial infections.…”

“…At day 30, a 25% decrease in vancomycin concentrations was found; however, colistimethate and heparin activity remained within 10% of the initial activity. 63 Rifamycins. Rifampin used synergistically with other antimicrobials for ALT displays potent elimination of biofilm and prevention of the occurrence of resistant organisms, but validated stability data are lacking.…”

Antibiotic lock therapy: review of technique and logistical challenges

“…Stability data for colistimethate and SMX/TMP are limited, but these may be potential options for treatment of CRBSI secondary to MDRO. 46 Clindamycin use in a lock solution is limited to a single published study. 26 Macrolides have been utilized in lock solutions in combination due to their potential impact on biofilms.…”