Part III: Guidelines for Selected Antimicrobial Use
3.5 Polymyxin B and Colistin
Polymyxin B and colistin (polymyxin E) have resurged as salvage therapy for Gram-negative infections, most notably multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of Pseudomonas aeruginosa, Acinetobacter baumannii, and Enterobacterales. [208–210]
Burkholderia cepacia, Morganella species, Proteus species, Providencia species, and Serratia species are intrinsically resistant to polymyxin B and colistin.
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Plasmid-mediated mobile colistin resistance (mcr) gene family conferring resistance to polymyxin B and colistin has been described since 2016. The mcr genes are geographically widely distributed. [211]
Polymyxin B
Polymyxin B is preferred over colistin for routine systemic use in invasive infections, due to its superior pharmacokinetic (PK) characteristics in humans and decreased potential to cause nephrotoxicity. [210]
Adults with normal renal function:
Loading dose: 20,000–25,000 units/kg, based on total body weight (equivalent to 2–2.5 mg/kg) over 1 hour [210]
Initial daily maintenance dose for patients with severe infections: 12,500–15,000 units/kg (equivalent to 1.25–1.5 mg/kg) every 12 hours, infused over 1 hour. [210]
There is limited data on dosing in obese patients. Consider adjusted body weight. For tailored dosing guidance, please consult a clinical microbiologist or infectious disease physician. [213–215]
No dosage adjustment for renal insufficiency. [135,210,212] While the manufacturer labelling for polymyxin B recommends dose reduction in patients with renal impairment, clinical data suggests that polymyxin B clearance is not significantly altered in kidney dysfunction. [212,216–218] Reducing the polymyxin B dose in patients with renal impairment may result in suboptimal drug exposure, treatment failure, or development of antibiotic resistance. [210,212,218–220]
Adverse reactions (non-exhaustive)
Neurotoxicity: neuromuscular blockade; circumoral paresthesias, extremity numbness, blurred vision, drowsy, irritable, ataxia; can manifest as respiratory arrest. [135,223]
Skin hyperpigmentation [224]
- Colistin
Appears as colistin sulphate for oral and topical uses, and as colistimethate sodium for parenteral and inhalational uses.
Because of its renal clearance with presence of active colistin in the urinary tract, and less favourable PK characteristics for systemic infection, colistin is preferred for the treatment of lower urinary tract infections. [210]
Dosing
Adults with normal renal function:
Loading dose: I.V. ~9 million units, infused over 1 hour, and to administer the first maintenance dose 12–24 hours later. [210]
Initial daily maintenance dose: I.V. ~4.5 million units, infused over 1 hour, at 12-hour intervals. [210]
Monitor renal function and adjust the daily dose accordingly. [210]
There is limited data on dosing in obese patients. Consider ideal body weight and avoid total body weight. For tailored dosing guidance, please consult a clinical microbiologist or infectious disease physician. [215,225–228]
Adverse reactions (non-exhaustive)
Neurotoxicity: Vertigo, facial circumoral paresthesias, abnormal vision, confusion, ataxia; neuromuscular blockade results in respiratory failure; may unmask myasthenia gravis. [135]
Pseudo-Bartter syndrome including metabolic alkalosis and electrolyte abnormalities. [230]
Please closely monitor renal function in patients receiving polymyxin B or colistin.
Wherever possible, concomitant nephrotoxic agents should be avoided in patients receiving polymyxin B or colistin. [210]
Please consult a clinical microbiologist or infectious disease physician for the use of polymyxin B or colistin.
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