Towards Improved Management of Tuberculous Bloodstream Infections: Pharmacokinetic Considerations with Suggestions for Better Treatment Outcomes

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dc.contributor.authorOkot Odongo, Charles
dc.contributor.authorNakiyingi, Lydia
dc.contributor.authorGatete Nkeramihigo, Clovis
dc.contributor.authorSeifu, Daniel
dc.contributor.authorBisaso Kuteesa, Ronald
dc.date.accessioned2022-12-04T20:01:24Z
dc.date.available2022-12-04T20:01:24Z
dc.date.issued2022
dc.description.abstractMycobacterium tuberculosis is the leading cause of sepsis among HIV-infected adults, yet effective treatment remains a challenge. Efficacy of antituberculous drugs is optimized by high Area Under Curve to Minimum Inhibitory Concentration (AUC/MIC) ratios, suggesting that both the drug concentration at the disease site and time above MIC are critical to treatment outcomes. We elaborate on sepsis pathophysiology and show how it adversely affects antituberculous drug kinetics. Expanding distribution volumes secondary to an increased vascular permeability prevents the attainment of target Cmax concentrations for nearly all drugs. Furthermore, sepsis-induced metabolic acidosis promotes protonation, which increases renal clearance of basic drugs such as isoniazid and ethambutol, and hence AUCs are substantially reduced. Compared with the treatment of non-sepsis TB disease, these distorted kinetics underlie the poor treatment outcomes observed with bloodstream infections. In addition to aggressive hemodynamic management, an increase in both the dose and frequency of drug administration are warranted, at least in the early phase of treatment.en_US
dc.identifier.citationOdongo, C. O., Nakiyingi, L., Nkeramihigo, C. G., Seifu, D., & Bisaso, K. R. (2022). Towards Improved Management of Tuberculous Bloodstream Infections: Pharmacokinetic Considerations with Suggestions for Better Treatment Outcomes. Antibiotics, 11(7), 895.en_US
dc.identifier.urihttps://www.mdpi.com/1711630
dc.identifier.urihttps://nru.uncst.go.ug/handle/123456789/5836
dc.language.isoenen_US
dc.publisherAntibioticsen_US
dc.subjecttuberculosisen_US
dc.subjectsepsisen_US
dc.subjecttreatmenten_US
dc.subjectpharmacokineticsen_US
dc.subjectCmaxen_US
dc.titleTowards Improved Management of Tuberculous Bloodstream Infections: Pharmacokinetic Considerations with Suggestions for Better Treatment Outcomesen_US
dc.typeArticleen_US
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