What is the recommended dose of colistin (polymyxin E) for a 3 kg neonate in the Neonatal Intensive Care Unit (NICU)?

Colistin Dosing for a 3 kg Neonate in the NICU

For a 3 kg neonate in the NICU, administer colistin (colistimethate sodium) at 2.5-5 mg colistin base activity (CBA)/kg/day intravenously, divided into 2 or 4 doses, which translates to 7.5-15 mg total daily dose for this patient. 1

Specific Dosing Calculation for This Patient

• Total daily dose range: 7.5 mg to 15 mg CBA per day 1
• Divided dosing options:
  • Every 12 hours: 3.75-7.5 mg per dose (twice daily) 1
  • Every 6 hours: 1.875-3.75 mg per dose (four times daily) 1
• Maximum dose: Do not exceed 100 mg CBA per dose (not applicable to this 3 kg patient) 1

Critical Dosing Considerations Based on Gestational and Postnatal Age

The guideline provides general neonatal dosing but does not stratify by gestational age for colistin specifically, unlike other antibiotics in the same table. 1 However, you must know the infant's:

• Gestational age (weeks)
• Postnatal age (days)
• Current renal function (creatinine clearance if available)

These factors significantly impact colistin clearance and should guide whether to use the lower (2.5 mg/kg/day) or higher (5 mg/kg/day) end of the dosing range. 2

Evidence Supporting Higher Doses in Select Cases

Recent pharmacokinetic data suggest that the FDA/EMA-recommended doses (2.5-5 mg CBA/kg/day) may be inadequate when:

• The pathogen MIC is ≥1 mg/L 1
• The patient has augmented renal clearance 1
• The patient has good renal function for age 1

However, for initial empiric therapy in a 3 kg neonate, start with the guideline-recommended range of 2.5-5 mg CBA/kg/day. 1 A recent study in critically ill pediatric patients used doses up to 11.6 mg CBA/kg/day with good tolerability, but this was in older children (median age 3.3 years), not neonates. 2

Route of Administration

• Intravenous route is standard for systemic infections 1, 3
• Inhalation route (4 mg CBA/kg/dose every 12 hours) is reserved for respiratory tract colonization or adjunctive therapy, not monotherapy 1
• Intrathecal/intraventricular route must be added for CNS infections, as IV dosing alone does not achieve adequate CSF concentrations 4

Administration Technique

Per FDA labeling: 3

• Reconstitution: 150 mg vial reconstituted with 2 mL sterile water = 75 mg/mL concentration 3
• Direct intermittent IV: Inject one-half of total daily dose over 3-5 minutes every 12 hours 3
• Continuous infusion: Inject first half over 3-5 minutes, then infuse remaining half over 22-23 hours 3

For a 3 kg neonate receiving 10 mg CBA/day (mid-range dosing):

• Give 5 mg over 3-5 minutes, then infuse remaining 5 mg over next 22-23 hours 3

Mandatory Monitoring During Therapy

Renal function must be monitored closely throughout colistin therapy. 1, 4

• Nephrotoxicity risk: 5.8-19% in neonatal/pediatric studies 5, 6, 7
• Electrolyte disturbances: Monitor and replace magnesium, as hypomagnesemia occurs frequently (24% required supplementation in one study) 6
• Avoid concomitant nephrotoxic agents (e.g., aminoglycosides, vancomycin) when possible, as combined use significantly increases nephrotoxicity risk 5, 6

One study reported that all three cases of nephrotoxicity occurred in patients receiving concomitant nephrotoxic agents with colistin. 5

Combination Therapy

Colistin should be used in combination with one or more additional agents to which the pathogen displays in vitro susceptibility. 1 In the reviewed studies, colistin was co-administered with other antimicrobials in 18 of 19 courses. 8 Monotherapy is not recommended for serious infections. 1

Expected Outcomes

Based on neonatal/infant data: 7

• Microbiologic cure: 94.2%
• Survival: 76.6%
• Nephrotoxicity: 5.8%
• Apnea: 3.9%

Common Pitfalls to Avoid

• Do not use colistin monotherapy for serious infections 1
• Do not co-administer with aminoglycosides unless absolutely necessary, as this dramatically increases nephrotoxicity 5, 6
• Do not rely on IV colistin alone for CNS infections—intrathecal administration is required 4
• Do not continue therapy without monitoring renal function at least every 2-3 days 1
• Do not forget to monitor and replace magnesium, as hypomagnesemia is common and reversible 6

Duration of Therapy

Average treatment duration in pediatric studies was 19.8 ± 10.3 days, with a range of 1-133 days depending on infection site and response. 5, 8 Duration should be individualized based on infection site, source control, and clinical response. 1