Browsing by Author "Theron, Danie"

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    Determination of kanamycin plasma levels using LC-MS and its pharmacokinetics in patients with multidrug-resistant tuberculosis with and without HIV-infection
    (OMICS, 2015) Mugabo, Pierre; Abaniwonda, Mercy, I.; Theron, Danie; Hassan, Shafick, M.; Stander, Marietjie; Van Zyl, Leonie; McIlleron, Helen; Madsen, Richard
    The objectives of the study were: (1) to determine kanamycin plasma concentrations using liquid chromatography coupled with mass spectrometry (LC-MS), (2) to investigate kanamycin pharmacokinetics (PK) in patients with multi-drug resistant tuberculosis (MDR-TB), (3) to find out whether HIV infection, kidney dysfunction and antiretroviral drugs influence kanamycin PK. The study was designed as a non-randomized study involving male and female HIV- positive and HIVnegative patients admitted for MDR-TB treatment. Blood samples were collected before (baseline) and ½, 1, 2, 4, 8 and 24 hours after intramuscular injection of kanamycin. LC-MS was used to quantify kanamycin plasma concentrations. Thirty one patients including 13 HIV (+) participated in the study. The lower limit of detection and lower limit of quantification of kanamycin were 0.06 μg/ml and 0.15 μg/ml respectively. Kanamycin PK parameters were described and there was no significant difference between HIV-positive and HIV-negative patients. A statistical significant difference (p=0.0126) was found in the renal function in HIV - positive and HIV - negative patients. However, this difference did not affect kanamycin elimination. No interactions have been identified between antiretroviral drugs and kanamycin. Conclusion: LC-MS analysis method is highly specific and highly sensitive in the detection and quantification of kanamycin plasma concentrations. Kanamycin PK in patients with MDR-TB was described. Due to a limited number of patients, we cannot rule out any influence of HIV - infection, renal impairment and antiretroviral drugs on kanamycin pharmacokinetics. The relationship between the area under the curve of kanamycin free plasma concentrations (fAUC) and its minimum inhibitory concentrations (MIC) on M.tuberculosis isolated from the sputum of each patient should be assessed. Therefore, kanamycin free plasma concentrations and MIC should be determined.
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    Do HIV infection and antiretroviral therapy influence multidrug-resistant tuberculosis treatment outcomes?
    (Academic Journals, 2015) Mugabo, Pierre; Adewumi, A.O.; Theron, Danie; Burger, Andries; Van, Zyl L.
    The aim of this study was to find out whether human immunodeficiency virus (HIV)-infection and antiretroviral drugs influence multidrug-resistant (MDR)-tuberculosis (TB) treatment outcomes. The study compares MDR-TB treatment outcomes between HIV-positive and HIV-negative patients. It involved patients admitted for treatment of MDR-TB between 1 January 2004 and 31 December 2006. From 363 patients selected, 268 (177 males and 91 females) had MDR-TB and 95 patients (59 males and 36 females) were co-infected with HIV. Children in the HIV-negative group were 41 and 7 in the HIV-positive group. The HIV-infection was treated with Stavudine, Lamivudine and Efavirenz in 54 patients. Kanamycin, Ethionamide, Ofloxacin, Terizidone, Pyrazinamide and Ethambutol were used for MDR-TB treatment. In HIV-negative and HIV-positive patients MDR-TB treatment outcomes were, respectively as follows: 37 and 35% cure, 9 and 5% treatment failure, 20 and 25% lost to follow up, 11 and 17% mortality, 19 and 13% treatment completed, 6 and 5% transfer-out. The cure rate was 100% in children. In HIV-positive patients, MDR-TB cure rate was 35% in patients on ARVs and 34% in patients not receiving ARVs. The difference between these cure rates is not statistically significant (p-value = 0.79). The median (range) duration of ART before the start of MDR-TB treatment was 10.5 (1 to 60) months and did not influence MDR-TB treatment outcomes. In children, the full treatment was supervised in hospital. This could explain the 100% cure rate. Adults' treatment was supervised in hospital only during the intensive phase then followed up as out patients over 18 months. According to the results of this study, HIV-infection and antiretroviral therapy did not influence MDR-TB treatment outcomes.