The unexpected and uncontrollable re-emergence of multidrug-resistant gram-negative bacterial infections demands the re-use of last-resort drugs like polymixin E (colistin). Serum creatinine values were implemented to identify both nephrotoxicity and steady-state levels of colistin in patients with normal renal function, and these values have a direct impact on the PK-parameters of colistin. Patients with normal renal function, as well as those who cannot achieve a plasma colistin concentration of 2 mg/L or whose infected microorganisms have a MIC (minimum inhibitory concentration) larger than 1 mg/L, will require combination therapy. Time-kill experiments were found to be a better method in synergistic research, with an emphasis on resistant strains., In Time kill tests, the usual threshold for proving synergy for combination therapy was that the combination caused a 2log10 CFU/ml reduction at 24 hours. Although checkerboard experiments are less expensive and faster, they allow for the examination of a greater number of strains. The proper dosing for colistin is not entirely known, international guidelines have been published to help clarify best practices. Since polymyxins were reintroduced into the clinic in the 1980s, there has been a lot of uncertainty about their use due to differences in formulations. CMS doses are specified in either international units (IU) or milligrammes of colistin base activity (CBA) in hospital guidelines and prescription orders, depending on the country's labelling system. To have a uniform strategy to specifying all doses in either numbers of IUs or milligrammes of CBA, international harmonisation is critically needed. The desired target average steady-state plasma concentration (Css,avg) of colistin must be considered when determining the initial daily maintenance dose. The Pharmacokinetics, Pharmacodynamics, PK-PD findings, in-vitro data from various research, were all discussed in this study.

Key words: Colistin, Pharmacokinetic, Pharmacodynamics, PK-PD.