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 upto 40,000 units/kg/day without adverse effects.

Intramuscular: Not recommended routinely because of severe pain at injection sites, particulary in infants and children. Dissolve 5,00,000 polymyxin B units in 0.9% sodium chloride injection.

Adults and Children: 25,000 to 30,000 units/kg/day. This should in the presence of renal impairment. The dosage may be divided and given at either 4 or 6 hours intervals. Infants: Infants with normal kidney function may receive upto 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 premature and newborn infants for sepsis caused by Pseudomonas aeruginosa.

Intrathecal: A treatment of choice for Pseudomonas aeruginosa meningitis. Dissolve 5,00,000 polymixin B units in 10 ml 0.9% sodium chloride injection 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 to 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 to 4 days or 25,000 units once every other day. Continue with a dose of 25,000 units once every other day for atleast 2 weeks after cultures of the cerebrospinal fluid are negative and sugar content has returned to normal.

IN THE INTEREST OF SAFETY, SOLUTIONS OF PARENTERAL USE SHOULD BE STORED UNDER REFRIGERATION AND ANY UNUSED PORTIONS SHOULD BE DISCARDED AFTER 72 HOURS.

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 paraesthesia, 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 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. Clostridium difficle associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Polymyxin B for injection and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile. C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents. If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management protein supplementation, antibiotic treatment of C. difficile and surgical evaluation should be instituted as clinically indicated.

Precautions
Prescribing polymyxin B in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increase the risk of the development of drug resistant bacteria. 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 non susceptible organisms, including fungi. If superinfection occurs, appropriate therapy should be instituted.

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.

Polymyxin B has bactericidal action against almost all Gram – negative bacilli except the Proteus group. Polymyxins increase the permeability of the bacterial cell membrane leading to death of the cell. All Gram-positive bacteria, fungi and Gram-negative cocci are resistant to polymyxin B. Appropriate methods should be used when performing in vitro susceptibility testing of polymyxin B. The following in vitro susceptibility test criteria should only be used for interpreting the results of polymyxin B susceptibility testing when the indicated quality control parameters are met during testing. In vitro susceptibility test interpretive criteria for pol7ymyxin B sulfate against pseudomonas aeruginosa.

Pharmacokinetics
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.