Polymyxin B Sulfate
Indications: Bacteremia; Conjunctivitis, infectious; Infection, urinary tract; Meningitis
WARNING:
When this drug is given intramuscularly and/or intrathecally, it should be given only to hospitalized patients, so as to provide constant supervision by a physician.
Renal function should be carefully determined and patients with renal damage and nitrogen retention should have reduced dosage. Patients with nephrotoxicity due to polymyxin B sulfate usually show albuminuria, cellular casts, and azotemia. Diminishing urine output and a rising BUN are indications for discontinuing therapy with this drug.
Neurotoxic reactions may be manifested by irritability, weakness, drowsiness, ataxia, perioral paresthesia, numbness of the extremities, and blurring of vision. These are usually associated with high serum levels found in patients with impaired renal function and/or nephrotoxicity. The concurrent use of other nephrotoxic and neurotoxic drugs, particularly kanamycin, streptomycin, cephaloridine, paromomycin, tobramycin, polymyxin E (colistin), neomycin, gentamicin, and viomycin, should be avoided.
The neurotoxicity of polymyxin B sulfate can result in respiratory paralysis from neuromuscular blockade, especially when the drug is given soon after anesthesia and/or muscle relaxants.
Usage in pregnancy: The safety of this drug in human pregnancy has not been established.
DESCRIPTION:
Polymyxin B sulfate is one of a group of basic polypeptide antibiotics derived from B polymyxa (B aerosporous) .
Polymyxin B sulfate is in powder form suitable for preparation of sterile solutions for intramuscular, intravenous drip, intrathecal, or ophthalmic use.
In the medical literature, dosages have frequently been given in terms of equivalent weight of pure polymyxin B base. Each milligram of pure polymyxin B base is equivalent to 10,000 units of polymyxin B and each microgram of pure polymyxin B base is equivalent to 10 units of polymyxin B.
Aqueous solutions of polymyxin B sulfate may be stored up to 12 months without significant loss of potency if kept under refrigeration. In the interest of safety, solutions for parenteral use should be stored under refrigeration and any unused portion should be discarded after 72 hours. Polymyxin B sulfate should not be stored in alkaline solutions since they are less stable.
CLINICAL PHARMACOLOGY:
Polymyxin B sulfate has a bactericidal action against almost all gram-negative bacilli except the Proteus group. Polymyxins increase the permeability of bacterial cell wall membranes. All gram-positive bacteria, fungi, and the gram-negative cocci, N gonorrhoeae and N meningitidis , are resistant.
Susceptibility plate testing: If the Kirby-Bauer method of disc susceptibility testing is used, a 300-unit polymyxin B disc should give a zone of over 11 mm when tested against a polymyxin B-susceptible bacterial strain.
Polymyxin B sulfate is not absorbed from the normal alimentary tract. Since the drug loses 50 percent of its activity in the presence of serum, active blood levels are low. Repeated injections may give a cumulative effect. Levels tend to be higher in infants and children. The drug is excreted slowly by the kidneys. Tissue diffusion is poor and the drug does not pass the blood brain barrier into the cerebrospinal fluid. In therapeutic dosage, polymyxin B sulfate causes some nephrotoxicity with tubule damage to a slight degree.
INDICATIONS AND USAGE:
Acute Infections Caused by Susceptible Strains of Pseudomonas aeruginosa . Polymyxin B sulfate is a drug of choice in the treatment of infections of the urinary tract, meninges, and bloodstream caused by susceptible strains of Ps aeruginosa . It may also be used topically and subconjunctivally in the treatment of infections of the eye caused by susceptible strains of Ps aeruginosa .
It may be indicated in serious infections caused by susceptible strains of the following organisms, when less potentially toxic drugs are ineffective or contraindicated:
H influenzae, specifically meningeal infections.
Escherichia coli, specifically urinary tract infections.
Aerobacter aerogenes, specifically bacteremia.
Klebsiella pneumoniae, specifically bacteremia.
Note: In Meningeal Infections, polymyxin B sulfate Should Be Administered Only by the Intrathecal Route.
CONTRAINDICATIONS:
This drug is contraindicated in persons with a prior history of hypersensitivity reactions to the polymyxins.
PRECAUTIONS:
See BOXED WARNING.
Baseline renal function should be done prior to therapy, with frequent monitoring of renal function and blood levels of the drug during parenteral therapy.
Avoid concurrent use of a curariform muscle relaxant and other neurotoxic drugs (ether, tubocurarine, succinylcholine, gallamine, decamethonium and sodium citrate) which may precipitate respiratory depression. If signs of respiratory paralysis appear, respiration should be assisted as required, and the drug discontinued.
As with other antibiotics, use of this drug may result in overgrowth of nonsusceptible organisms, including fungi. If superinfection occurs, appropriate therapy should be instituted.
ADVERSE REACTIONS:
See BOXED WARNING.
Nephrotoxic Reactions: Albuminuria, cylinduria, azotemia, and rising blood levels without any increase in dosage.
Neurotoxic Reactions: Facial flushing, dizziness progressing to ataxia, drowsiness, peripheral paresthesias (circumoral and stocking-glove), apnea due to concurrent use of curariform muscle relaxants and other neurotoxic drugs or inadvertent overdosage, and signs of meningeal irritation with intrathecal administration; e.g., fever, headache, stiff neck, and increased cell count and protein cerebrospinal fluid.
Other Reactions Occasionally Reported: Drug fever, urticarial rash, pain (severe) at intramuscular injection sites, and thrombophlebitis at intravenous injection sites.
DOSAGE AND ADMINISTRATION:
Parenteral
Intravenous: Dissolve 500,000 units polymyxin B sulfate in 300-500 cc of 5 percent dextrose in water for continuous intravenous drip.
Adults and Children: 15,000-25,000 units/kg body weight/day in individuals with normal kidney function. This amount should be reduced from 15,000 units/kg downward for individuals with kidney impairment. Infusions may be given every 12 hours; however, the total daily dose must not exceed 25,000 units/kg/day.
Infants: Infants with normal kidney function may receive up to 40,000 units/kg/day without adverse effects.
Intramuscular. Not recommended routinely because of severe pain at injection sites, particularly in infants and children. Dissolve 500,000 units polymyxin B sulfate in 2 cc sterile distilled water (Water for Injection, U.S.P.) or sterile physiologic saline (Sodium Chloride Injection, U.S.P.) or 1 percent procaine hydrochloride solution.
Adults and Children: 25,000-30,000 units/kg/day. This should be reduced in the presence of renal impairment. The dosage may be divided and given at either 4-or 6-hour intervals.
Infants: Infants with normal kidney function may receive up to 40,000 units/kg/day without adverse effects.
Note: Doses as high as 45,000 units/kg/day have been used in limited clinical studies in treating prematures and newborn infants for sepsis caused by Ps aeruginosa .
Intrathecal: A treatment of choice for Ps aeruginosa meningitis. Dissolve 500,000 units polymyxin B sulfate in 10 cc of sterile physiologic saline (Sodium Chloride Injection, U.S.P.) for 50,000 units per ml dosage unit.
Adults and Children Over 2 Years of Age: Dosage is 50,000 units once daily intrathecally for 3-4 days, then 50,000 units once every other day for at least 2 weeks after cultures of the cerebrospinal fluid are negative and sugar content has returned to normal.
Children Under 2 Years of Age: 20,000 units once daily, intrathecally for 3-4 days or 25,000 units once every other day. Continue with a dose of 25,000 units once every other day for at least 2 weeks after cultures of the cerebrospinal fluid are negative and sugar content has returned to normal.
IN THE INTEREST OF SAFETY, SOLUTIONS FOR PARENTERAL USE SHOULD BE STORED UNDER REFRIGERATION, AND ANY UNUSED PORTIONS SHOULD BE DISCARDED AFTER 72 HOURS.
Topical
Ophthalmic: Dissolve 500,000 units polymyxin B sulfate in 20-50 cc sterile distilled water (Water for Injection, U.S.P.) or sterile physiologic saline (Sodium Chloride Injection, U.S.P.) for a 10,000-25,000 units per cc concentration.
For the treatment of Ps aeruginosa infections of the eye, a concentration of 0.1 percent to 0.25 percent (10,000 units to 25,000 units per cc) is administered 1-3 drops every hour, increasing the intervals as response indicates.
Subconjunctival injection of up to 10,000 units/day may be used for the treatment of Ps aeruginosa infections of the cornea and conjunctiva.
Note: Avoid total systemic and ophthalmic instillation over 25,000 units/kg/day.