Colistin

Some polymyxins are sold for second-line systemic therapy. Polymyxin B sulfate and colistimethate sodium can be used for intravenous, intramuscular, or intrathecal administration, especially for Pseudomonas aerupinosa mP QXiosis, 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. 

The antibacterial activity of five members (A to E) of the polymyxin group is of a similar nature. However, they are all nephrotoxic although this effect is much reduced with polymyxins B and E (colistin). Colistin sulphomethate sodium is the form of colistin used for parenteral administration. Sulphomyxin sodium, a mixture of sulphomethylated polymyxin B and sodium bisulphite, has the action and uses of polymyxin B sulphate, but is less toxic. 

To prevent development of resistance and promote synergy, inhaled tobramycin or colistin is usually added to an oral fluoroquinolone for P. aeruginosa coverage.1,3 Methicillin-sensitive S. aureus (MSSA) may be treated with oral amoxiciUin-clavulanic acid, dicloxacillin, first- or second-generation cephalosporins, trimethoprim-sulfamethoxazole, or clindamycin, depending on sensitivity. Likewise, methiciUin-resistant S. aureus (MRSA) may be treated with oral trimethoprim-sulfamethoxazole, clindamycin, minocycline, or linezolid. H. influenzae often produces... 

Nebulized colistin using the IV formulation may be an option in patients with tobramycin-resistant strains or intolerance to inhaled tobramycin. Due to an increased risk of bronchoconstriction after colistin inhalation, patients should pre-treat with albuterol and administer the first doses under medical observation.1,5... 

Polypeptides Bacitracin, colistin, and polymyxin B Eye, ear, or bladder infections... 

CiprofioxadnJ ampidllin-sulbadam, colistin, or tigecydine Baderoides tagilis (and others)... 

Cefepime,0 ceftazidime,0 piperadllin-tazobactam, or ticardllin-davulanate plus aminoglycoside Ciprofloxacin/ levofloxacin/ aztreonam/ imipenem," meropenem," or colistin... 

Pseudomonas aeruginosa Cefepime or ceftazidime (A-ll) tobramycin0,6 (A-lll) Ciprofloxacin (A-lll), meropenem (A-lll), piperacillin plus tobramycinP (A-lll), colistin 21 days... 

Colimycin, Colistin(not to be confused with Polymixin), Dextromycin,Flavomycin,Fradiomycin, Framycetin, Mycerin, Mycifradin, Neomix, Sofra-mycin, Streptothricin BI, BII. 

Erythromycin, a macrolide antibiotic, lacks a significant chromophore. Detection sensitivity was enhanced by using a wavelength of 200 nm and selecting an injection solvent of lower conductivity than the BGE. In order to facilitate the separation of erythromycin and its related substances, 35% (v/v) ethanol was incorporated into a 150 mM phosphate buffer pH 7.5. Resolution of all of the compounds was achieved in approximately 45 min. The method was employed as an assay method for erythromycin and for impurity determination. Peptide antibiotics, such as colistin and polymyxin, are mixtures of many closely related compounds. A validated CZE method for impurity analysis of polymyxin B was described, employing 130 mM triethanolamine-phosphate buffer at pH 2.5 to reduce the adsorption of analyte onto the capillary wall. Methyl-/l-cyclodextrin (M-/1-CD) and 2-propanol were found to be necessary for selectivity enhancement. Using similar buffer additives, the same group developed and validated a method for colistin analysis. ... 

Kang, J. W., Vankeirsbilck, T., Van Schepdael, A., Orwa, J., Roets, E., and Hoogmartens, J. (2000). Analysis of colistin sulfate by capillary zone electrophoresis with cyclodextrins as additive. 

Disruption of bacterial membrane structure Polymyxins Colistin Altered target Efflux... 

Patients suffering from cystic fibrosis often use various aerosolized drugs. To reduce the viscosity of the mucus in the airways, recombinant human deoxyribonuclease is used. This enzyme is the first recombinant protein that has been developed for specific delivery to the lungs via the airways. It has a local action on the mucus in the airways and its absorption is minimal. Another drug that decreases the viscosity of the mucus is acetylcysteine. Aerosolized antibiotics are a further group of therapeutics that is widely used by cystic fibrosis patients. Solutions of antibiotics like tobramycin or colistin are used in nebulizers to prevent exacerbation of the disease. Pentamidine has been used for the prophylaxis of Pneumocystis pneumonia in patients infected with HIV virus, while chronic rejection of lung transplants provided a reason to develop an aerosol formulation of cyclosporine A. 

Polymyxines Polymyxines are a gronp of related polypeptide antibiotics that are produced by sporo-forming soil bacteria Bacillus polymyxa and B. circulans, and they differ in amino acid content. Five different polymyxines have been identified—polymyxines A, B, C, D, and E, which differ in the amino acid content and are differentiated by additional letter notations and names— polymyxine B (aerosporin) and polymyxine E (colistin). It is known that in the process of development, some strains of B. polymyxa only form polymyxines A and C, and others synthesize polymyxines B and D. Polymyxine M was later isolated, a snlfomethyl derivative of polymyxine E. 

Incompatibilities Do not mix IV minocycline before or during administration with any solutions containing the following Adrenocorticotropic hormone (ACTH), aminophylline, amobarbital sodium, amphotericin B, bicarbonate infusion mixtures, calcium gluconate or chloride, carbenicillin, cephalothin sodium, cefazolin sodium, chloramphenicol succinate, colistin sulfate, heparin sodium, hydrocortisone sodium succinate, iodine sodium, methicillin sodium, novobiocin, penicillin, pentobarbital, phenytoin sodium, polymyxin, prochlorperazine, sodium ascorbate, sulfadiazine, sulfisoxazole, thiopental sodium, vitamin K (sodium bisulfate or sodium salt), whole blood. 

Avoid concurrent or sequential use of other neurotoxic and/or nephrotoxic drugs with streptomycin sulfate, including neomycin, kanamycin, gentamicin, cephaloridine, paromomycin, viomycin, polymyxin B, colistin, tobramycin, and cyclosporine. 

Treatment should be guided by the local or hospital resistance patterns. Extensive use of a quinolone for selective decontamination will increase the incidence of quinolone-resistant gram-negative pathogens. Alternative regimens for gut decontamination are oral colistin with an oral aminoglycoside such as neomycin. 

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