Pseudomonas aeruginosa polymyxin

The mechanism of acquired resistance in Pseudomonas aeruginosa is different. Chromosomal mutations result in the increase of a specific outer membrane protein with a concomitant reduction in divalent cations. Polymyxins bind to the outer membrane at sites normally occupied by divalent cations, and therefore it is thought that a reduction in these sites will lead to decreased binding of the antibiotic with a consequent decreased susceptibility of the cell. 

Macfarlane, E.L., Kwasnicka, A., Ochs, M.M., Hancock, R.E. PhoP-PhoQ homologues in Pseudomonas aeruginosa regulate expression of the outer-membrane protein OprH and polymyxin B resistance. Mol Microbiol 34 (1999) 305-316. 

McPhee, J.B., Lewenza, S., Hancock, R.E. Cationic antimicrobial peptides activate a two-component regulatory system, PmrA-PmrB, that regulates resistance to polymyxin B and cationic antimicrobial peptides in Pseudomonas aeruginosa. Mol Microbiol 50 (2003) 205-217. 

Moskowitz, S.M., Bums, J.L., Nguyen, C.D., Hftiby, N., Ernst, R.K., Miller, S.I. Polymyxin resistance and lipid A structure of Pseudomonas aeruginosa isolated from colistin-treated and colistin-naive cystic fibrosis patients. Pediatr Pulmonol Suppl 20 (2000) 272. 

Polymyxin B is also active against Gram-negative organisms, particularly Pseudomonas aeruginosa. Its principal use now is topical application for skin, eye and external ear infections. 

Polymyxin E (colistin) is used in the treatment of serious Gram-negative bacterial infections, particularly those caused by Pseudomonas aeruginosa. It binds tightly to the lipid A component of LPS in the outer membrane of Gram-negative bacteria. The outer leaflet of the membrane structure is distorted, segments of which are released and the permeability barrier is destroyed. The polymyxin mole-... 

Some polymyxins are sold for second-line systemic therapy. Polymyxin B sulfate and colistimethate sodium can be used for intravenous, intramuscular, or intrathecal achninistration, especially for Pseudomonas aeruginosa infections, but also for most other gram-negative organisms, such as those resistant to first-line antibiotics. Nephrotoxicity and various neurotoxicities are common in parenteral, but not in topical, use. Resistance to polymyxins develops slowly, involves mutation and, at least in some bacteria, adaptation, a poorly understood type of resistance that is rapidly lost on transfer to a medium free of polymyxin. Resistance can involve changes in the proteins, the lipopolysaccharides, and lipids of the outer membrane of the cell (52). Polymyxin and colistin show complete cross-resistance. 

Polymyxin B, a polypeptide antibiotic (500,000 units in 300 to 500 mL of 5% dextrose in water for continuous IV drip), is used in acute infections caused by susceptible strains of Pseudomonas aeruginosa. It may be used topically and subconjunctivally in the treatment of infections of the eye caused by susceptible strains of P. aeruginosa. 

T. I. Nicas and R. E. W. Hancock, Outer membrane protein HI of Pseudomonas aeruginosa involvement in adaptive and mutational resistance to ethylenediaminetetraacetate, polymyxin B, and gentamicin, J. Bacterial, 143 (1980) 872-878. 

Alterations in the cell envelope of Pseudomonas aeruginosa resistant to polymyxin are associated with the alteration of the outer membrane through a... 

Valerius NH, Koeh C, Hoiby N. Prevention of chronie Pseudomonas aeruginosa eolonisation in eystie fibrosis by early treatment. Laneet 1991 338 725-726. Wilson FE. Aeute respiratory failure secondary to polymyxin inhalation. Chest 1981 79 237-239. 

Infections of the skin, mucous membranes, eye, and ear due to polymyxin B—sensitive microorganisms respond to local application of the antibiotic in solution or ointment. External otitis, frequently due to Pseudomonas, may be cured by the topical use of the drug. R aeruginosa is a common cause of infection of comeal ulcers local application or subconjunctival injection of polymyxin B often is curative. 

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