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Drug-associated adverse events and their relationship with outcomes in patients receiving treatment for extensively drug-resistant tuberculosis in South Africa.

Shean K, Streicher E, Pieterson E, Symons G, van Zyl Smit R, Theron G, Lehloenya R, Padanilam X, Wilcox P, Victor TC, van Helden P, Grobusch MP, Groubusch M, Warren R, Badri M, Dheda K - PLoS ONE (2013)

Bottom Line: Sputum culture-conversion was less likely in those with severe (grade 3-5) vs. grade 0-2 AEs [2/27(7%) vs. 24/88(27%); p = 0.02].The type, frequency and severity of AEs was similar in HIV-infected and uninfected patients.Capreomycin, which was empirically administered in most cases, was withdrawn in 14/104(14%) patients, implicated in (14/34) 41% of the total drug withdrawals, and was associated with all 6 deaths in the severe AE group (renal failure in five patients and hypokalemia in one patient).

View Article: PubMed Central - PubMed

Affiliation: Lung Infection and Immunity Unit, Division of Pulmonology and UCT Lung Institute, Department of Medicine, University of Cape Town, Cape Town, South Africa.

ABSTRACT

Background: Treatment-related outcomes in patients with extensively drug-resistant tuberculosis (XDR-TB) are poor. However, data about the type, frequency and severity of presumed drug-associated adverse events (AEs) and their association with treatment-related outcomes in patients with XDR-TB are scarce.

Methods: Case records of 115 South-African XDR-TB patients were retrospectively reviewed by a trained researcher. AEs were estimated and graded according to severity [grade 0 = none; grade 1-2 = mild to moderate; and grade 3-5 = severe (drug stopped, life-threatening or death)].

Findings: 161 AEs were experienced by 67/115(58%) patients: 23/67(34%) required modification of treatment, the offending drug was discontinued in 19/67(28%), reactions were life-threatening in 2/67(3.0%), and 6/67(9.0%) died. ∼50% of the patients were still on treatment at the time of data capture. Sputum culture-conversion was less likely in those with severe (grade 3-5) vs. grade 0-2 AEs [2/27(7%) vs. 24/88(27%); p = 0.02]. The type, frequency and severity of AEs was similar in HIV-infected and uninfected patients. Capreomycin, which was empirically administered in most cases, was withdrawn in 14/104(14%) patients, implicated in (14/34) 41% of the total drug withdrawals, and was associated with all 6 deaths in the severe AE group (renal failure in five patients and hypokalemia in one patient).

Conclusion: Drug-associated AEs occur commonly with XDR-TB treatment, are often severe, frequently interrupt therapy, and negatively impact on culture conversion outcomes. These preliminary data inform on the need for standardised strategies (including pre-treatment counselling, early detection, monitoring, and follow-up) and less toxic drugs to optimally manage patients with XDR-TB.

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Related in: MedlinePlus

Study plan stratified according to treatment site, HIV status and severity of adverse drug reactions.
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pone-0063057-g001: Study plan stratified according to treatment site, HIV status and severity of adverse drug reactions.

Mentions: We retrospectively reviewed the case records of 115 consecutive laboratory-confirmed XDR-TB patients diagnosed between August 2002 and February 2008 at three designated XDR-TB treatment centres in South Africa (see Figure 1 for the study outline). Patients were admitted to the facilities for the duration of their treatment and thus adherence was assumed to be excellent unless the patients self discharged (designated as default from treatment). Case records were comprehensively reviewed by a trained researcher for AEs listed in Table 1 (including duration, type and severity), drug regimen used (dose, indication, route of administration), culture conversion and mortality outcomes, and HIV status. Associated demographic and clinical information were also transcribed into a case record form, and the information captured by double data entry.


Drug-associated adverse events and their relationship with outcomes in patients receiving treatment for extensively drug-resistant tuberculosis in South Africa.

Shean K, Streicher E, Pieterson E, Symons G, van Zyl Smit R, Theron G, Lehloenya R, Padanilam X, Wilcox P, Victor TC, van Helden P, Grobusch MP, Groubusch M, Warren R, Badri M, Dheda K - PLoS ONE (2013)

Study plan stratified according to treatment site, HIV status and severity of adverse drug reactions.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3646906&req=5

pone-0063057-g001: Study plan stratified according to treatment site, HIV status and severity of adverse drug reactions.
Mentions: We retrospectively reviewed the case records of 115 consecutive laboratory-confirmed XDR-TB patients diagnosed between August 2002 and February 2008 at three designated XDR-TB treatment centres in South Africa (see Figure 1 for the study outline). Patients were admitted to the facilities for the duration of their treatment and thus adherence was assumed to be excellent unless the patients self discharged (designated as default from treatment). Case records were comprehensively reviewed by a trained researcher for AEs listed in Table 1 (including duration, type and severity), drug regimen used (dose, indication, route of administration), culture conversion and mortality outcomes, and HIV status. Associated demographic and clinical information were also transcribed into a case record form, and the information captured by double data entry.

Bottom Line: Sputum culture-conversion was less likely in those with severe (grade 3-5) vs. grade 0-2 AEs [2/27(7%) vs. 24/88(27%); p = 0.02].The type, frequency and severity of AEs was similar in HIV-infected and uninfected patients.Capreomycin, which was empirically administered in most cases, was withdrawn in 14/104(14%) patients, implicated in (14/34) 41% of the total drug withdrawals, and was associated with all 6 deaths in the severe AE group (renal failure in five patients and hypokalemia in one patient).

View Article: PubMed Central - PubMed

Affiliation: Lung Infection and Immunity Unit, Division of Pulmonology and UCT Lung Institute, Department of Medicine, University of Cape Town, Cape Town, South Africa.

ABSTRACT

Background: Treatment-related outcomes in patients with extensively drug-resistant tuberculosis (XDR-TB) are poor. However, data about the type, frequency and severity of presumed drug-associated adverse events (AEs) and their association with treatment-related outcomes in patients with XDR-TB are scarce.

Methods: Case records of 115 South-African XDR-TB patients were retrospectively reviewed by a trained researcher. AEs were estimated and graded according to severity [grade 0 = none; grade 1-2 = mild to moderate; and grade 3-5 = severe (drug stopped, life-threatening or death)].

Findings: 161 AEs were experienced by 67/115(58%) patients: 23/67(34%) required modification of treatment, the offending drug was discontinued in 19/67(28%), reactions were life-threatening in 2/67(3.0%), and 6/67(9.0%) died. ∼50% of the patients were still on treatment at the time of data capture. Sputum culture-conversion was less likely in those with severe (grade 3-5) vs. grade 0-2 AEs [2/27(7%) vs. 24/88(27%); p = 0.02]. The type, frequency and severity of AEs was similar in HIV-infected and uninfected patients. Capreomycin, which was empirically administered in most cases, was withdrawn in 14/104(14%) patients, implicated in (14/34) 41% of the total drug withdrawals, and was associated with all 6 deaths in the severe AE group (renal failure in five patients and hypokalemia in one patient).

Conclusion: Drug-associated AEs occur commonly with XDR-TB treatment, are often severe, frequently interrupt therapy, and negatively impact on culture conversion outcomes. These preliminary data inform on the need for standardised strategies (including pre-treatment counselling, early detection, monitoring, and follow-up) and less toxic drugs to optimally manage patients with XDR-TB.

Show MeSH
Related in: MedlinePlus