Polymyxin B

Indications

Polymyxin B is used for: Susceptible infections, Meningitis

Adult Dose

Intravenous Susceptible infections Adult: 15,000-25,000 U/kg daily by continuous IV drip or intermittent infusion 12 hrly at 60-120 min duration. Max: 2,000,000 U/day. Intramuscular Susceptible infections Adult: 25,000-30,000 U/kg daily in divided doses 4-6 hrly. Max: 2,000,000 U/day. Intrathecal Meningitis Adult: 50,000 U once daily for 3-4 days, then on alternate days for at least 2 wk after CSF cultures are negative and CSF glucose content is normal. Max: 2,000,000 U/day.

Child Dose

Intravenous Susceptible infections Adult: 15,000-25,000 U/kg daily by continuous IV drip or intermittent infusion 12 hrly at 60-120 min duration. Max: 2,000,000 U/day. Child: <2 yr 40,000 U/kg daily in divided doses 12 hrly; ?2 yr Same as adult dose. Intramuscular Susceptible infections Child: <2 yr 40,000 U/kg daily in divided doses 6 hrly (not routinely recommended due to pain at injection sites); >2 yr Same as adult dose but not routinely recommended due to pain at injection sites. Intrathecal Meningitis Child: <2 yr 20,000 U once daily for 3-4 days or 25,000 U on alternate days, followed by the latter dose for at least 2 wk after CSF cultures are negative and CSF glucose content is normal; >2 yr Same as adult dose.

Renal Dose

Renal Impairment CrCl >20 mL/minute: give 75-100% usual dose/day divided q12hr CrCl 5-20 mL/minute: give 50% usual dose/day divided q12hr CrCl <5 mL/minute: give 15% usual dose/day q12hr

Administration

IV/IM/IT Preparation IV: dilute 500,000 U in 300-500 mL D5W IM: reconstitute vial with 2 mL SWI , NS, or procaine HCl 1% solution Intrathecal (IT): reconstitute vial with10 mL NS; DO NOT use procaine HCl for IT IV/IM Administration IV: infuse over 60-90 min IM: give deep into upper outer quadrant of gluteal muscles

Contra Indications

Hypersensitivity to polymyxins; Concurrent use w/ nephrotoxic and/or neurotoxic drugs and neuromuscular blockers.

Precautions

Oliguria, myasthenia gravis, pregnancy, renal disease Potential risk of nephrotoxicity and neurotoxicity May inhibit neuromuscular transmission Inactivated by strong acidic or alkaline solution Discontinue if diminished urine output, rise in SCr or BUN, or signs of respiratory paralysis appear Do not use IM routinely, particularly in peds, because of severe inj site pain

Pregnancy-Lactation

Pregnancy Category: B: use when benefits outweigh risks Lactation: use caution; no data

Interactions

Potentially Fatal: Additive neurotoxic or nephrotoxic effect w/ bacitracin, streptomycin, neomycin, kanamycin, gentamicin, tobramycin, amikacin, cephaloridine, paromomycin, viomycin, colistin. Increased risk of resp paralysis w/ neuromuscular blockers (e.g. anaesthetics, muscle relaxants).

Adverse Effects

Side effects of Polymyxin B : Frequency Not Defined Anaphylactoid reactions with dyspnea and tachycardia Eosinophilia Fever Nephrotoxicity Neurotoxicity Skin exanthemata Urticaria

Mechanism of Action

Polymyxin B binds to phospholipids, alters permeability and disrupts the bacterial cytoplasmic membrane of mostly gm-ve organisms allowing leakage of intracellular constituents by binding to membrane phospholipids.