logging in or signing up Colistin in Multi Drug Resistant Bacteria doctorrao Download Post to : URL : Related Presentations : Share Add to Flag Embed Email Send to Blogs and Networks Add to Channel Uploaded from authorPOINT lite Insert YouTube videos in PowerPont slides with aS Desktop Copy embed code: Embed: Flash iPad Copy Does not support media & animations WordPress Embed Customize Embed URL: Copy Thumbnail: Copy The presentation is successfully added In Your Favorites. Views: 535 Category: Education License: All Rights Reserved Like it (0) Dislike it (0) Added: January 03, 2012 This Presentation is Public Favorites: 0 Presentation Description Colistin in Multi Drug Resistant Bacteria Comments Posting comment... Premium member Presentation Transcript Colistinin Multidrug Resistant Bacteria : Colistinin Multidrug Resistant Bacteria Dr.T.V.Rao MD POLYMYXINS : Polymyxins are antibiotics, with a general structure consisting of a cyclic peptide with a long hydrophobic tail. They disrupt the structure of the bacterial cell membrane by interacting with its phospholipids. They are produced by the Gram-positive bacterium Bacillus polymyxa and are selectively toxic for Gram-negative bacteria due to their specificity for the lipopolysaccharide molecule that exists within many Gram-negative outer membranes. POLYMYXINS Introduction : Introduction Polymyxin E First isolated in Japan 1949 & available for clinical use in 1959 IM for gram (-) infection Fell out of favor after aminoglycosides usage Aerosolized form for cystic fibrosis IV for pan resistant nosocomial infections (Pseudomonas & Acinetobacter spp.) Colistin – A Polymyxin : Colistin is a cationic polypeptide antibiotic from the polymyxin family that was first introduced in 1962 but abandoned in the early 1970s because of initial reports of severe toxicities. However, a recent increase in the prevalence of multidrug resistant (MDR) Pseudomonas aeruginosa and the lack of novel agents in development calls for a need to re-examine the role of colistin therapy in patients with cystic fibrosis. Colistin – A Polymyxin What is Colistin : Colistin (also called polymyxin E) 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 . Colistin was given as an intramuscular injection for the treatment of gram-negative infections, but fell out of favor after aminoglycosides became available because of its significant side effects. 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. What is Colistin Structure of Polymyxins : Structure of Polymyxins Polymyxin B Sulfate is one of a group of basic polypeptide antibiotics derived from B polymyxa (B aero porous). Polymyxin B sulfate is the sulfate salt of Polymyxins B1 and B2, which are produced by the growth of Bacillus polymyxa (Prazmowski) Migula (Fam. Bacillacea) Colistin : 7 Colistin The target of antimicrobial activity of colistin is the bacterial cell membrane Colistin has also potent anti-endotoxin activity The endotoxin of G-N bacteria is the lipid A portion of LPS molecules, and colistin binds and neutralizes LPS Mechanism of Action : Mechanism of Action Bactericidal Bind to lipopolysaccharides(LPS) & phospholipids in the outer cell membrane of G(-) bacteria Neutralize LPS & prevent pathophysiologic effects of endotoxin Resistance is uncommon Disk diffusion method cannot be used Spectrum of Activity : Spectrum of Activity Pseudomonas & A. baumannii E. coli, Enterobacter H. influenza Bordetella pertussis Legionella, Klebsiella spp. Salmonella spp., Shigella spp. Stenotrophomonas maltophilia Pharmacokinetics : Pharmacokinetics Colistin sulfate, colistin methanesulfonate Not absorbed from GI tract Hydrolized after IV administration to colistin Half life 251 minutes Excreted in the urine, no biliary excretion Mechanism of action : After binding to lipopolysaccharide (LPS) in the outer membrane of Gram-negative bacteria, polymyxins disrupt both the outer and inner membranes. The hydrophobic tail is important in causing membrane damage, suggesting a detergent-like mode of action. Removal of the hydrophobic tail of polymyxin B yields polymyxin nonapeptide, which still binds to LPS but no longer kills the bacterial cell. However, it still detectably increases the permeability of the bacterial cell wall to other antibiotics, indicating that it still causes some degree of membrane disorganization Mechanism of action Clinical Uses of Polymyxins : Only polymyxins B and E are used clinically; the others damage the kidneys. Polymyxin B can also cause kidney damage and therefore can only be applied topically to treat infections such as those of the eye, ear, skin, and urinary bladder. Polymyxin E, also known as colistin, is used frequently for diarrhea in children. The chief therapeutic use of the polymyxins is treating infections of gram-negative bacteria that are resistant to penicillin and other broad-spectrum antibiotics. Clinical Uses of Polymyxins Clinical uses : Polymyxins antibiotics are relatively neurotoxic and nephrotoxic and are usually only used as a last resort if modern antibiotics are ineffective or are contraindicated. Typical uses are for infections caused by strains of multi-drug resistant Pseudomonas aeruginosa or carbapenemase-producing Enterobacteriaceae. Clinical uses NEWER APPLICATIONS : NEWER APPLICATIONS Polymyxins B and E (also known as colistin) are used in the treatment of Gram-negative bacterial infections. The global problem of advancing antimicrobial resistance has led to a renewed interest in their use recently. Colistin: Re-emerging antibiotic for multidrug-resistant Gram-negative bacterial infections. : Colistin: Re-emerging antibiotic for multidrug-resistant Gram-negative bacterial infections. Increasing multidrug resistance in Gram-negative bacteria, in particular Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae, presents a critical problem. Limited therapeutic options have forced infectious disease clinicians and microbiologists to reappraise the clinical application of colistin, a polymyxin antibiotic discovered more than 50 years ago Colistin of Active …. : 16 Colistin of Active …. Active: Acinetobacter species, Pseudomonas aeruginosa, Enterobacteriaceae Emerging Problem MDR-Acinetobacter : MDR Acinetobacter (definition per Johns Hopkins) MDR Acinetobacter = an isolate that is susceptible to no more than one class of Antibiotic (excluding Colistin). In reality, MDR is typically resistant to commonly prescribed antibiotics or are susceptible to only the Aminoglycoside class. Emerging Problem MDR-Acinetobacter MDR-Acinetobacter –Treatment : Carbapenems (Meropenam& Imipenem) Colistin PolymyxinB Amikacin Rifampin Minocycline Tigecycline MDR-Acinetobacter –Treatment How Colistin Works : How Colistin Works 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 Experimental uses of Polymyxins : Polymyxins are used to neutralize or absorb LPS contaminating samples that are intended for use in e.g. immunological experiments. Minimization of LPS contamination can be important because LPS can evoke strong reactions from immune cells and therefore distort experimental results. By increasing permeability of the bacterial membrane system, polymyxin is also used to experimentally increase release of secreted toxins, such as Shiga toxin from Escherichia coli. Experimental uses of Polymyxins Colistin can Neutralize Endotoxins : Colistin can Neutralize Endotoxins In addition to its bactericidal effect, colistin can bind and neutralize lipopolysaccharide (LPS) and prevent the pathophysiologic effects of endotoxin in the circulation . Adverse Reaction : Adverse Reaction Nephrotoxicity Acute tubular necrosis 27% Normal renal function patient (mean inc. 0.9 mg/dL serum creatine) 58% impaired renal function patient (mean inc. 1.5 mg/dL serum creatine) Minimal data on long term use Adverse Reaction : Neurotoxicity 7% Facial & peripheral paresthesia Dizziness, weakness, vertigo, visual disturbance, confusion, ataxia, neuromuscular blockade Benign & reversible Adverse Reaction Caution with Polymyxins : Caution: when this drug is given intramuscularly, intravenously 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. . Caution with Polymyxins Polymyxin Can Cause Toxicity : Polymyxin Can Cause Toxicity 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. Colistin continues to be option MDR gram –ve bacteria : Because few, if any, new antibiotics with activity against multidrug-resistant Gram-negative bacteria will be available within the next several years, it is essential that Colistin is used in ways that maximize its antibacterial efficacy and minimize toxicity and development of resistance. Recent developments have improved use of Colistin in the 21st century. Colistin continues to be option MDR gram –ve bacteria Polymyxins too Develop Resistance : Polymyxins too Develop Resistance The gram-negative bacteria can develop resistance to polymyxins through various modifications of the LPS structure that inhibit the binding of polymyxins to LPS Colistin too becoming resistant … : The Colistin-resistant bacteria, A. baumanii is the most common, followed by K. pneumonia and P. aeruginosa. Resistance to Colistin can occur through mechanisms of mutation or adaptation , leading to bacterial cell membrane changes such as a decrease in the content of lipopolysaccharides, specific outer membrane proteins and Mg 2+ and Ca 2+ content Use the drug with caution and clinical adjustment Colistin too becoming resistant … Slide 29: Created by Dr.T.V.Rao MD for “e-learning” resources for Medical and Paramedical Students in Developing world Email email@example.com You do not have the permission to view this presentation. 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