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Title: Analysis of complex antibiotics
Author: Al-Lawati, Nabila J. M.
Awarding Body: University of Brighton
Current Institution: University of Brighton
Date of Award: 2012
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The emergence of multidrug resistant Gram-negative bacteria such as Pseudomonas aeruginosa and Acinetobacter baumannii has been recognized worldwide and some clinical isolates of these bacteria are now resistant to most of the antibiotics currently available. Unfortunately, there are at present not enough new antimicrobial drugs being produced by the pharmaceutical industry to keep pace with the continuing development of antibiotic resistance. Colistin is an old antibiotic and in the form of colistin methanesulphonate sodium (CMS) has re-emerged as a major treatment for burn patients colonised with Acinetobacter baumannii. However, this antibiotic can lead to profound toxicity and for this reason the blood levels of CMS should be carefully monitored. Unfortunately the methods available for measuring it in serum are not robust and are not able to differentiate between the two forms of colistin i.e. colistin sulphate (CLS) and CMS. In this study the chemical (Thin Layer Chromatography and High Performance Liquid Chromatography) and microbiological methods for CLS and CMS analysis were investigated to develop a methodology for reproducible quantification of CLS and CMS in water or serum. Since CMS in aqueous solution has the potential to hydrolyze to produce a complex mixture of colistin sulphomethylated derivatives as well as colistin base, the optimized chemical and microbiological methods were used to determine the degradation of CLS or CMS in aqueous solution and serum. The bacteriostatic and bactericidal activity of CLS and CMS were probed by calculations of minimum inhibitory concentrations and time survivor studies. Depending on their concentrations, both antibiotics were found to exhibit bacteriostatic and bactericidal properties against a range of Gram-negative bacteria. Membrane damage caused by both forms of colistin was investigated using Acinetobacter lwoffii R46383 anddetennining intracellular potassium leakage and 260nm absorbing materials leakage. CLS was shown to cause substantial membrane damage, indicated by rapid, gross potassium leakage, while the effect of CMS on the membrane appeared to be more subtle, with cells exhibiting a more concentration dependent loss of potassium. Adsorption isotherms ofCLS gave results that were indicative of high affmity isotherm (H- shape), while adsorption isotherms of CMS were indicative of co-operative sorption (S- shape). Investigations into CLS and CMS cytotoxicity were performed using normal rat kidney (NRK-52E) cell line; the investigations revealed that neither forms of colistin has a major adverse effect on the rat renal cells even at concentrations higher than the therapeutic doses.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: B000 Health Professions