Determination of Residual Antibiotics in Cryopreserved Heart Valve Allografts

Abstract

Introduction: Cardiovascular allografts are systematically incubated in antibiotics for their decontamination, and the antibiotics are removed before allograft implantation. We studied the occurrence of antibiotic residues in allograft valves. Methods: 12 experimental allografts were analyzed in this study. The concentration of the residual antibiotics was determined by high-performance liquid chromatography and the results were expressed as microgram per gram of allograft tissue. Results: The initial analysis showed that only vancomycin HCl and lincomycin HCl were retained in the allograft, whereas no traces of polymyxin B sulfate were detected in the tissue samples. Furthermore, the values found for the antibiotic residues in the extracted solution from the allografts were similar to the initial results: Vancomycin and lincomycin were detected in very low concentrations and no polymyxin B residues were observed. According to the World Health Organization (WHO), the maximum daily doses for vancomycin, lincomycin and polymyxin B are 2.0, 1.8 and 0.4 g, respectively. The thresholds for reporting degradation products are 0.05% for vancomycin and lincomycin and 0.1% for polymyxin B. The residual values for the two detected antibiotics were largely below 0.05%. Conclusions: Antibiotic residues in the allograft valves do not present any risk for their recipients. Increased allograft resistance to infections is probably due to the retention of antibiotics in the tissue.

Residual Antibiotics in Decontaminated Human Cardiovascular Tissues Intended for Transplantation and Risk of Falsely Negative Microbiological Analyses

“…Tissue samples decontaminated with antibiotic cocktails are a specific type of microbiological sample that may present bacteriostatic and/or fungistatic properties [8] , [15] . The intrinsic properties of the tissues, such as enzymatic activity, immunologic events, and presence of antimicrobial peptides [16] , which are well described in the skin [17] , cornea [18] , and amniotic membrane [19] , may be exacerbated by the presence of residual antibiotics following tissue decontamination with antibiotic cocktails [7] , [8] , [20] . The European and US Pharmacopoeias indicate eliminating any factor that may interfere with microbial growth during sterility testing from samples [9] , [10] .…”

A sensitive HPLC-UV method for quantifying vancomycin in biological matrices: Application to pharmacokinetic and biodistribution studies in rat plasma, skin and lymph nodes

“…Biodistribution studies have shown VCN to be widely distributed into most body organs after administration via intravenous injection or infusion [3], including cerebrospinal fluid (CSF) [4], heart valves [5], lungs [6] and interstitial fluid (ISF) [7]. As a consequence, and for therapeutic drug monitoring purposes, it is important to develop a sensitive and selective method for analysing and quantifying VCN in a range of different biological samples.…”

Experimental procedures for decontamination and microbiological testing in cardiovascular tissue banks

“…31,70 Perhaps even worse, there is a risk that the antibiotics can cause severe allergic or toxic reactions in tissue recipients. 71,72 We were unable to find current studies that reported on this issue and its potential to cause serious clinical consequences. There is a risk that recipients who have an allergy to specific antibiotics could develop allergic reactions after transplantation as a result of extremely high concentrations of antibiotics in the tissues.…”