Multicomponent antibiotic substances produced by fermentation: implications for regulatory authorities, critically ill patients and generics.
Teicoplanin and polymyxin E (colistin) are antibiotics consisting of multiple, closely related subcomponents, produced by fermentation. The principal components comprise a complex mixture of chemically related, active substances (teicoplanin A(2-1)-A(2-5) and polymyxin E(1-2), respectively), which might be required to be present in specific ratios to ensure optimal antibacterial and clinical efficacy. These subcomponents differ in their fatty acid and amino acid composition and, as such, the lipophilic and protein binding characteristics differ between components. This has therapeutic implications for critically ill patients, as the volume of distribution of the teicoplanin A2 and polymyxin E analogues at the onset of an intravenous infusion may impact on expected pharmacokinetics and influence outcome.
Department of Clinical Microbiology, Ampath National Laboratory Services, Suite 9C, Milpark Hospital, 9 Guild Road, Parktown West, 2193 Johannesburg, South Africa. Electronic address: brinka@ampath.co.za.
Adrian J
AJ
Brink
Department of Critical Care, Charlotte Maxeke Johannesburg Academic Hospital and Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Guy A
GA
Richards
Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy.
Gaia
G
Colombo
Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy.
Fabrizio
F
Bortolotti
Department of Pharmacy, University of Parma, Parma, Italy.
Paolo
P
Colombo
Bacteriology Laboratory, Faculty of Medicine, University Hospital Strasbourg, Strasbourg, France.
François
F
Jehl
D000596:Amino Acids / Q000032:analysis; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000302:isolation & purification / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001424:Bacterial Infections / Q000188:drug therapy; D003091:Colistin / Q000737:chemistry* / Q000302:isolation & purification / Q000493:pharmacokinetics / Q000627:therapeutic use*; D045424:Complex Mixtures / Q000737:chemistry / Q000302:isolation & purification / Q000493:pharmacokinetics / Q000627:therapeutic use; D016638:Critical Illness; D017277:Drug Approval; D005227:Fatty Acids / Q000032:analysis; D005285:Fermentation; D006801:Humans; D011485:Protein Binding; D012995:Solubility; D017334:Teicoplanin / Q000737:chemistry* / Q000302:isolation & purification / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome
D000596:Amino Acids; D000900:Anti-Bacterial Agents; D045424:Complex Mixtures; D005227:Fatty Acids; D017334:Teicoplanin; D003091:Colistin
Colistin; Generic; ICU; Pharmacokinetics; Polymyxin E(1–2); Subcomponent; Teicoplanin A(2-1)–A(2-5)