COLISTIN -NEWER METHODS IN DIAGNOSIS OF COLISITN RESSITANCE AND CLINICAL APPLICATIONS by Dr.T.V.Rao MD-

COLISTIN NEWER METHODS IN DIAGNOSIS OF COLISITN RESSITANCE AND CLINICAL APPLICATIONS by Dr.T.V.Rao MD-

As a Part of post graduate discussion in clinical Microbiology

Colistin, also known as polymyxin E, is an antibiotic used as a last-resort treatment for multidrug-resistant Gram-negative infections, including pneumonia. These infections may involve bacteria such as Pseudomonas aeruginosa, Klebsiella pneumoniae,

How Does Colistin Work?

Colistin belongs to the polymyxin class of antibiotics.

It is administered through intravenous (IV) or intramuscular (IM) injection.

Colistin binds to fatty molecules on the cell membranes of gram-negative bacteria.

This binding causes leakage of cell contents, ultimately leading to bacterial cell death.

Spectrum of Activity:

Colistin has a narrow spectrum of activity limited to a subset of gram-negative bacteria.

It is ineffective against gram-positive bacteria.

Gram-negative bacteria susceptible to colistin include:

Pseudomonas aeruginosa

Acinetobacter baumannii

Haemophilus influenzae

Bordetella pertussis

Legionella pneumophila

Salmonella species

Shigella species

Majority of Stenotrophomonas maltophilia strains

Carbapenem-resistant Enterobacteriaceae, including Escherichia coli and Klebsiella pneumoniae

Some Enterobacter species3 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 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 Currently, the available testing methods for colistin include: dilution methods [agar dilution (AD), broth microdilution (BMD), and broth microdilution], diffusion methods [disk diffusion and gradient diffusion] and automated systems. 6 - 8 The Clinical and Laboratory Standards Institute (CLSI), as well as the European Committee on Antimicrobial Susceptibility Testing (EUCAST) only validated the use of BMD for testing colistin susceptibility. MIC determination by Etest or broth dilution method. -

Dr.T.V.Rao MD