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COLISTIN AND NEWER APPLICATIONS

Dr.T.V.Rao MD

Colistin an older compound modified for newer applications -Recent clinical studies

performed in a large number of patients showed that colistin “forgotten” for several decades

revived for the management of infections due to multidrug-resistant (MDR) Gram-negative bacteria

(GNB) and had acceptable effectiveness and considerably less toxicity than that reported in older

studies, belongs to the polymyxin group of antibiotics. It was first isolated in Japan in 1949 from

Bacillus polymyxa var. colistinus and became available for clinical use in 1959. Earlier Colistin was

given as an intramuscular injection for the treatment of Gram-negative infections, but fell out of 

favour after aminoglycosides became available because of its significant side effects. Today we are

challenged with many drug resistant gram-negative bacilli in particular Pseudomonas, It was

later used as topical therapy as part of selective digestive tract decontamination and is still used in

aerosolized form for patients with cystic fibrosis. Colistin is a bactericidal drug that binds to

lipopolysaccharides and phospholipids in the outer cell membrane of Gram-negative bacteria. It

competitively displaces divalent cations from the phosphate groups of membrane lipids, which leads

to disruption of the outer cell membrane, leakage of intracellular contents, and bacterial death. In

addition to its bactericidal effect, colistin can bind and neutralize lipopolysaccharide (LPS) and

prevent the pathophysiologic effects of endotoxin in the circulation, this property make it consider

in life threating conditions when the patients are diagnosed with septicaemias. The absence since

1995, of new substances active against resistant Gram-negative bacteria, has caused increasing

concern. Colistin has attracted more interest recently because of its significant activity against multi-

resistant P. aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae, and the low

resistance rates to it. However, there has been a significant recent increase in the data gathered on

colistin, focussing on its chemistry, antibacterial activity, mechanism of action and resistance,

pharmacokinetics, pharmacodynamics and new clinical application. Colistin sulfate is not effective

against Proteus, Providentia and Serratia. Susceptible organisms include P. aeruginosa, Legionella

spp, H. influenzae, Acinetobacter, V. cholera, Salmonella, Shigella and Pasteurella and to be tested

for Antibiogram as the situation warrants. It is one of the last resort antibiotics for multidrug

resistant Pseudomonas aeruginosa, and Acinetobacter. Microbiologists should avoid testing as first

line antibiotic for the routine specimens arise from various clinical departments. It has several

adverse reactions Super infection; renal damage; visual disturbances; GI disturbances, dizziness,nausea, vomiting; confusion, peripheral neuropathy; respiratory insufficiency and muscle weakness.

Potentially Fatal: Acute tubular necrosis, neurotoxicity; nephrotoxicity. The neuromuscular blockade

is potentially fatal, when associated with use of curariform muscle relaxants. When culture and

susceptibility information are available, they should be considered in selecting or modifying

antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns

may contribute to the empiric selection of therapy, in particular when physicians are not supported

by optimal Diagnostic methods. Many patients in Nephrology units may with renal compromise,

since colistimethate for injection is eliminated mainly by renal excretion, it should be used with

caution when the possibility of impaired renal function exists. The decline in renal function with

advanced age should be considered. Numerous recent clinical studies have confirmed that colistin is

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an efficient antimicrobial agent against nosocomial infections, including bacteraemia, ventilator-

associated pneumonia, urinary tract infection, and meningitis  due to MDR GNB, such as P.

aeruginosa, A. baumannii, and K. pneumonia, with an acceptable safety profile. Microbiologists

should be familiar with the zone sizes (CLSI) are lower for Colistin for several Enterobacteriaceae

when compared with other antibiotics, we must remember, the poor agar diffusion characteristics of 

colistin limit the predictive accuracy of the disk diffusion test and consequently values of 12-13 mm

should be confirmed with MIC determination by Etest or broth dilution method. - 

email; doctortvrao@gmail.com