Colistin past and future: a bibliographic analysis

Objective: Colistin is a venerable drug that has found renewed interest because of multidrug resistance (MDR) and the shortfall of effective antibiotics. We present a synthesis of publication trends on MDR infection, colistin, and its adverse events, as a measure of the medical-academic community's interest, to inform current redevelopment strategies.

Design: This was a multidatabase electronic search over 50 years with back- and forward-referencing through Web of Knowledge. Studies were grouped into MDR, colistin, and adverse events and were plotted in 5-year clusters.

Results: Three periods could be mapped with distinct literature trends: A, 1940 to 1975; B, 1975 to 2000; and C, post-2000. Period A was characterized by increasing publications, soon followed by adverse-effect-themed publications. Period B reported a sharp publication decline; and period C reported a sharp increase in interest, mirroring the exponential increase in MDR literature. Period B predated standardized modern pharmacologic requirements. Period C coincided with novel drug development techniques.

Discussion: Two current trends (period C) were identified. Optimization of the current formulation may have been influenced by period B. Current research efforts within this trend include pharmacokinetic/pharmacodynamic analysis, purification, formulation, and resistance surveillance. The second trend involved colistin's redevelopment by tailored chemical reengineering to produce novel and patentable chemical entities, with an interdisciplinary approach emphasis. It is hoped that an analysis of the interplay between historical trends and current redevelopment strategies of this colistin case study may highlight strategies to stoke the drying antibiotic pipeline.