The Multidrug-Resistant Gram-negative Superbugs Threat Require Intelligent Use of the Last Weapon.

The global emergence and dissemination of multidrug-resistant Gram-negative superbugs, particularly carbapenem-resistant Acinetobacter baumannii and Klebsiella pneumoniae, lead to the limited effectiveness of antibiotics for treating nosocomial infections. In most cases, polymyxins are the last resort therapy, and these antibiotics must be used intelligently to prolong their efficacy in clinical practice. Polymyxin B and colistin (polymyxin E) were introduced prior to modern drug regulation, and the majority of the 'old' drug information is unreliable. Recent pharmacokinetic data do not support the renal dose adjustment of intravenous (IV) polymyxin B as suggested by the manufacturer, and this drug must be scaled by the total body weight. Whereas IV colistin is formulated as an inactive prodrug, colistin methanesulfonate (CMS) has different pharmacokinetic profiles than polymyxin B. To achieve maximum efficacy, CMS should be administered as a loading dose scaled to body weight and a maintenance dose according to the renal profiles. Polymyxin combination therapy is suggested due to a sub-therapeutic plasma concentration in a significant proportion of patients and a high incidence of polymyxin hetero-resistance among Gram-negative superbugs. In conclusion, polymyxins must be reserved as a last resort and should be wisely used when truly indicated.