Systematic review of the evidence for rational dosing of colistin

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dc.contributor.authorVisser Kift, E
dc.contributor.authorMaaartens, G
dc.contributor.authorBamford, C
dc.date.accessioned2021-10-08T07:20:29Z
dc.date.available2021-10-08T07:20:29Z
dc.date.issued2014
dc.description.abstractBACKGROUND: There is an alarming global increase in the incidence of nosocomial infections with multidrug-resistant Gram-negative bacteria, which are often only susceptible to colistin. Colistin was developed prior to current methods of establishing dosing using pharmacokinetic-pharmacodynamic relationships. Dosing regimens differ in package inserts from different manufacturers and in different guidelines. It is imperative to avoid under-dosing with colistin in order to limit the development of resistance, as it is the last line of defence. METHODS: We conducted a systematic review of the literature to develop guidelines for rational dosing of intravenous colistin, with a particular focus on critically ill patients. RESULTS: Colistin is administered as the inactive pro-drug colistimethate sodium. Colistin demonstrates concentration-dependent bacterial killing, suggesting that higher doses should be administered less frequently to achieve higher peak concentrations. Dose-related nephrotoxicity occurs, making it impossible to safely achieve concentrations that prevent the selection of resistant mutants or the effective eradication of bacteria with higher minimum inhibitory concentrations. Theoretically, combination therapy should be used to reduce the risk of selection of resistant bacteria. In critically ill patients, a loading dose should be given to rapidly achieve therapeutic concentrations, followed by maintenance doses of 4.5 MU 12-hourly. Maintenance dose adjustment is necessary with renal impairment. CONCLUSION: Easier access to colistin is needed in South Africa, where it is not a registered medicine. Further research is needed to better characterise colistin's pharmacokinetic-pharmacodynamic relationships in humans and to establish whether combinations of colistin with other antimicrobials result in improved clinical outcomes or a reduction in selection of resistant bacteria.
dc.identifier.apacitationVisser Kift, E., Maaartens, G., & Bamford, C. (2014). Systematic review of the evidence for rational dosing of colistin. <i>South African Medical Journal</i>, 104(3), 183 - 177. http://hdl.handle.net/11427/34933en_ZA
dc.identifier.chicagocitationVisser Kift, E, G Maaartens, and C Bamford "Systematic review of the evidence for rational dosing of colistin." <i>South African Medical Journal</i> 104, 3. (2014): 183 - 177. http://hdl.handle.net/11427/34933en_ZA
dc.identifier.citationVisser Kift, E., Maaartens, G. & Bamford, C. 2014. Systematic review of the evidence for rational dosing of colistin. <i>South African Medical Journal.</i> 104(3):183 - 177. http://hdl.handle.net/11427/34933en_ZA
dc.identifier.issn0038-2469
dc.identifier.ris TY - Journal Article AU - Visser Kift, E AU - Maaartens, G AU - Bamford, C AB - BACKGROUND: There is an alarming global increase in the incidence of nosocomial infections with multidrug-resistant Gram-negative bacteria, which are often only susceptible to colistin. Colistin was developed prior to current methods of establishing dosing using pharmacokinetic-pharmacodynamic relationships. Dosing regimens differ in package inserts from different manufacturers and in different guidelines. It is imperative to avoid under-dosing with colistin in order to limit the development of resistance, as it is the last line of defence. METHODS: We conducted a systematic review of the literature to develop guidelines for rational dosing of intravenous colistin, with a particular focus on critically ill patients. RESULTS: Colistin is administered as the inactive pro-drug colistimethate sodium. Colistin demonstrates concentration-dependent bacterial killing, suggesting that higher doses should be administered less frequently to achieve higher peak concentrations. Dose-related nephrotoxicity occurs, making it impossible to safely achieve concentrations that prevent the selection of resistant mutants or the effective eradication of bacteria with higher minimum inhibitory concentrations. Theoretically, combination therapy should be used to reduce the risk of selection of resistant bacteria. In critically ill patients, a loading dose should be given to rapidly achieve therapeutic concentrations, followed by maintenance doses of 4.5 MU 12-hourly. Maintenance dose adjustment is necessary with renal impairment. CONCLUSION: Easier access to colistin is needed in South Africa, where it is not a registered medicine. Further research is needed to better characterise colistin's pharmacokinetic-pharmacodynamic relationships in humans and to establish whether combinations of colistin with other antimicrobials result in improved clinical outcomes or a reduction in selection of resistant bacteria. DA - 2014 DB - OpenUCT DP - University of Cape Town IS - 3 J1 - South African Medical Journal LK - https://open.uct.ac.za PY - 2014 SM - 0038-2469 T1 - Systematic review of the evidence for rational dosing of colistin TI - Systematic review of the evidence for rational dosing of colistin UR - http://hdl.handle.net/11427/34933 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/34933
dc.identifier.vancouvercitationVisser Kift E, Maaartens G, Bamford C. Systematic review of the evidence for rational dosing of colistin. South African Medical Journal. 2014;104(3):183 - 177. http://hdl.handle.net/11427/34933.en_ZA
dc.language.isoeng
dc.publisher.departmentDepartment of Medicine
dc.publisher.facultyFaculty of Health Sciences
dc.sourceSouth African Medical Journal
dc.source.journalissue3
dc.source.journalvolume104
dc.source.pagination183 - 177
dc.source.urihttps://dx.doi.org/10.7196/SAMJ.10727
dc.subject.otherCritical Illness
dc.subject.otherCross Infection
dc.subject.otherProdrugs
dc.subject.otherColistin
dc.subject.otherSodium
dc.subject.otherPharmacokinetics
dc.subject.otherTherapeutics
dc.subject.otherMicrobial Sensitivity Tests
dc.subject.otherRisk
dc.subject.otherIncidence
dc.subject.otherHomo sapiens
dc.titleSystematic review of the evidence for rational dosing of colistin
dc.typeJournal Article
uct.type.publicationResearch
uct.type.resourceJournal Article
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