What is the recommended injectable Polymyxin B dosage for an adult with a serious Gram‑negative infection, including the dose range per kilogram per day, maximum single dose, adjustments for severe infection, renal function, neuromuscular disease, and the dosing regimen for pediatric patients aged one month or older?

Injectable Polymyxin B Dosing

For adults with serious Gram-negative infections, administer polymyxin B with a loading dose of 2-2.5 mg/kg followed by maintenance dosing of 1.5-3 mg/kg/day divided into two daily intravenous doses (every 12 hours), with no dose reduction required for renal impairment. 1, 2

Standard Adult Dosing Regimen

Loading Dose (Critical First Step)

• Always initiate therapy with a loading dose of 2-2.5 mg/kg to rapidly achieve therapeutic plasma concentrations on the first day 1, 2, 3
• The loading dose must be given to all patients, including those with severe renal dysfunction or on continuous renal replacement therapy (CRRT) 1, 2
• For a 70 kg patient, this translates to 140-175 mg as the loading dose 1

Maintenance Dosing

• Standard maintenance: 1.5-3 mg/kg/day divided into 2 doses (every 12 hours) 1, 2, 3
• For severe infections, use the higher end of the dosing range (2.5-3.0 mg/kg/day) 3
• For a 70 kg patient, maintenance dose is 105-210 mg/day divided into two doses 1, 2

Renal Function Adjustments

Critical Distinction from Older Recommendations

Do not reduce doses in patients with renal impairment - this is the most important distinction from colistin and contradicts older FDA labeling 1, 2, 3. The standard dosing regimen should be maintained regardless of creatinine clearance 1.

Evidence Supporting No Renal Adjustment

• Polymyxin B clearance is not influenced by renal function, with comparable exposures in patients with normal versus impaired renal function 4, 5
• Total body clearance shows no relationship with creatinine clearance (r² = 0.008) 5
• Urinary recovery is only 3.7-8.1%, indicating predominantly non-renal clearance 5, 6
• Polymyxin B has significantly lower nephrotoxicity compared to colistin (11.8% vs 39.3%) 2, 3

Renal Replacement Therapy

• No dose adjustment necessary for patients on CRRT - use standard dosing of 1.5-3 mg/kg/day 1, 2

Neuromuscular Disease Considerations

• Exercise extreme caution in patients with myasthenia gravis or other neuromuscular disorders 7
• Neurotoxicity manifests as perioral paresthesia, dizziness, and numbness of extremities, typically resolving within 23 hours without treatment 6
• Consider avoiding polymyxin B entirely in patients with severe neuromuscular disease if alternative agents are available 7

Pediatric Dosing (≥1 Month of Age)

• Colistin (not polymyxin B) is more commonly used in pediatrics: 2.5-5 mg CBA/kg/day IV in 2 or 4 divided doses 8
• Maximum pediatric dose: 100 mg CBA/dose 8
• Note: The guideline evidence primarily addresses colistin for pediatric multidrug-resistant infections rather than polymyxin B 8

Therapeutic Drug Monitoring

• Target steady-state average concentration: approximately 3.35 mg/L 1, 2
• Optimal AUCss,24h target: 50-100 mg·h/L 2, 3
• Therapeutic drug monitoring is encouraged to optimize dosing and minimize toxicity 1, 2

Combination Therapy Requirements

Polymyxin B should be used in combination therapy rather than monotherapy for carbapenem-resistant infections 2, 3. Specific combinations include:

• For ventilator-associated pneumonia (VAP) or hospital-acquired pneumonia (HAP): combine IV polymyxin B with adjunctive inhaled colistin (not inhaled polymyxin B) 2
• For carbapenem-resistant Enterobacterales bloodstream infections: consider combination with tigecycline or meropenem (extended infusion) 2
• When treating VAP with suspected multidrug-resistant gram-negative pathogens: combine with an antipseudomonal β-lactam agent (piperacillin-tazobactam, cefepime, or meropenem) 3

Nephrotoxicity Risk Management

• Avoid concurrent nephrotoxic agents: aminoglycosides, NSAIDs, diuretics, ACE inhibitors/ARBs 1, 3
• Less frequent dosing (every 12 hours) is less nephrotoxic than more frequent administration due to lower kidney tissue drug concentrations 9
• Monitor serum creatinine daily during therapy 9

Duration of Therapy

• HAP/VAP: 7-day course 2
• Carbapenem-resistant Enterobacterales bloodstream infections: 7-14 days 2

Common Pitfalls to Avoid

• Do not omit the loading dose - failure to load results in subtherapeutic levels for the first 24-48 hours 2, 3
• Do not confuse polymyxin B with colistin dosing - they have different unit conversions (polymyxin B in mg vs colistin in mg CBA) and dosing requirements 2, 3
• Do not reduce doses based on renal function - this outdated practice contradicts current pharmacokinetic evidence 1, 2, 4, 5
• Do not use as monotherapy for carbapenem-resistant infections when combination therapy is feasible 2, 3

Special Route: Intrathecal Administration

For patients >2 years with CNS infections requiring intrathecal therapy:

• Administer 50,000 units (≈5 mg) intrathecally once daily for 3-4 days, then every other day for at least 2 weeks after cerebrospinal fluid cultures become negative 2