EFFICACY AND SAFETY OF POLYMYXIN B IN CRITICALLY ILL PATIENTS WITH DRUG-RESISTANT GRAM-NEGATIVE BACTERIAL INFECTIONS
DOI:
https://doi.org/10.69598/tbps.21.2.165-189Keywords:
polymyxin b, drug-resistant bacteria, critically ill patients, treatment, pharmacokinetics, pharmacodynamics, adverse effectsAbstract
Polymyxin B has been reintroduced as an important therapeutic option for multidrug-resistant
Gram-negative bacterial infections which the global incidence continues to rise. Polymyxin B is administered in its active form, allowing plasma concentrations to reach pharmacokinetic targets more rapidly. Antibacterial efficacy is associated with a steady-state area under the concentration-time curve over 24 hours (AUCss,24h) of 50–100 mg·h/L, representing the therapeutic window that balances efficacy and nephrotoxicity. For intravenous administration, a loading dose of 2.0–2.5 mg/kg is recommended, followed by 1.25–1.50 mg/kg every 12 hours. Optimal dosing remains controversial, particularly regarding adjustments based on renal function, body weight, and renal replacement therapy. Furthermore, for infections in the lungs or central nervous system, adjunctive local administration including inhalation and intrathecal or intraventricular injection might be considered in case of suboptimal response to intravenous antibiotics. Compared with colistin, the efficacy of polymyxin B for drug-resistant Gram-negative infections in most studies is generally comparable, but polymyxin B is associated with a lower rate of nephrotoxicity. Neurotoxicity and skin hyperpigmentation are reported more frequently than with colistin. Therefore, the use of polymyxin B in critically ill patients requires individualized dosing decisions based on the minimum inhibitory concentration of the causative pathogen, the site of infection, disease severity, and organ function, with close monitoring of renal function and adverse effects throughout the course of treatment.
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