NEODOSE

INDICATIONS

Optimal dosing for colistin is unknown. However, a review of adult data suggest higher colistin concentrations, which may not be achieved with the manufacturer recommended dosing, and a regimen of colistin combined with other antibiotics may be necessary. The safety of higher doses is unknown.

• Gram-negative infections, multi-drug resistant:ul>style=”margin-left:7px;”>
• Intermittent IV Infusion: Intermittent IV colistin in combination with at least one other antibiotic, used for the treatment of multi-drug resistant infections, mostly Acinetobacter baumannii and Klebsiella pneumoniae, resulted in a 76% favorable clinical outcome in a retrospective study (n=21 treatment courses in 18 neonates). Microbiological clearance was documented in 17 of the 21 courses. During therapy with colisin, 5 patients with severe sepsis and multi-organ dysfunction died. The dose of colistimethate sodium ranged from 50,000 to 75,000 IU/kg/day in 3 divided doses [1.7 to 2.5 mg/kg/day of colistin base]. Renal impairment developed in 2 neonates, both subsequently died of multi-organ dysfunction. No significant difference in clinical and microbiological outcomes were observed between very low birthweight infants (VLBW, less than 1500 g) and non-VLBW infants with multi-drug resistant gram-negative bacilli infections treated with colistin 5 mg/kg/day IV in 3 divided doses in a retrospective study (n=66). Efficacy (microbiological clearance and survival) was 89.3% for the VLBW group and 86.8% for the non-VLBW group (p greater than 0.99). Serum magnesium and potassium concentrations were lower (p less than 0.001 for both events), as well as the need for magnesium and potassium supplementation were higher (p less than 0.001 for both events) in the VLBW group compared with non-VLBW group. There was no difference in the rate of acute kidney injury (14.3% vs 2.6%, respectively). Klebsiella pneumoniae was the most commonly treated infection, occurring in 60.7% and 63.2% of the VLBW and non-VLBW groups
• Aerosolized/nebulization: Aerosolized colistin either as monotherapy or in combination with other IV antibiotics demonstrated potential for treating full-term and pre-term neonates with Acinetobacter baumannii (13 of the 16 neonates had multidrug-resistant isolates) ventilator-associated pneumonia in 2 retrospective studies. Neither clinical nor laboratory adverse events were reported. The dosage of colistin base was 4 mg/kg/dose aerosolized with an ultrasonic nebulizer for 15 minutes every 12 hours for a median of 9 days (4 to 14 days) in neonates on a ventilator while receiving concurrent IV antibiotics. All of the 16 neonates who received nebulized colistin cleared the A baumannii infection. Another regimen was colistimethate sodium 1 million international units (33.4 mg colistin base) monotherapy twice daily for an average of 9.1 days (4 to 22 days)

CONTRAINDICATIONS/PRECAUTIONS

• Acute respiratory failure may result when reconstituted colistimethate solution for inhalation is not used promptly. After reconstitution, colistimethate is hydrolyzed to form active components, including polymyxin E1, which has shown to cause localized inflammation of the airway epithelia and eosinophilic infiltration when administered by inhalation.
• Bronchospasms may occur with inhalation of colistin; consider premedication with a bronchodilator.
• Clostridium difficile-associated diarrhea (CDAD), including mild diarrhea to fatal colitis, has been reported and may occur more than 2 months after administration. If CDAD is suspected or confirmed, discontinue any ongoing antibiotic therapy.
• Concomitant use of sodium cephalothin should be avoided.
• Increased risk of neuromuscular blockade leading to apnea in patients with renal impairment. Dosage adjustment should be reduced in proportion to the extent of the impairment.
• Respiratory arrest has been reported after IM administration.
• Reversible and dose-dependent nephrotoxicity may occur.
• Transient neurological disturbances (eg, circumoral paresthesia or numbness, tingling or formication of the extremities, generalized pruritus, vertigo, dizziness, and slurring of speech), may occur and dosage adjustments may be necessary.

ADVERSE EFFECTS

The most commonly reported adverse effects are gastrointestinal upset, slurred speech, dizziness, tingling of the extremities or tongue, itching, urticaria, rash, fever, respiratory distress, apnea, and nephrotoxicity. Serum creatinine increased more than 0.5 mg/dL above baseline in 2 out of 18 neonates administered IV colistin. Neither clinical nor laboratory adverse events were reported with aerosolized colistin in 8 neonates. Serum creatinine and blood urea nitrogen remained within normal limits 72 hours after completion of colistin therapy.

ADMINISTRATION

• Intramuscular Route: Administer by deep IM injection into large muscle mass (eg, gluteal muscles or lateral portion of thigh). The concentration of colistin base is 75 mg/mL
• Intravenous Route:
  • Continuous Infusion: Slowly inject one-half the total daily dose over 3 to 5 minutes at a concentration of 75 mg/mL of colistin base. Add the remaining half of the total daily dose to a compatible solution. Administer by slow IV infusion, starting 1 to 2 hours after the initial dose, over the next 22 to 23 hours. The choice of IV solution and the volume used are dictated by the requirements of fluid and electrolyte management.
  • Intermittent Administration: Infuse one-half of the total daily dose slowly over 3 to 5 minutes at a concentration of 75 mg/mL colistin base every 12 hours. Doses were added to 5 mL of normal saline and infused over 30 minutes in an observational study of 18 neonates

MONITORING

Closely monitor for toxicity in pediatric patients. Monitor urine output, BUN, and serum creatinine.