PMID- 23667572
OWN - NLM
STAT- MEDLINE
DCOM- 20131217
LR  - 20220321
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 5
DP  - 2013
TI  - Drug-associated adverse events and their relationship with outcomes in patients 
      receiving treatment for extensively drug-resistant tuberculosis in South Africa.
PG  - e63057
LID - 10.1371/journal.pone.0063057 [doi]
LID - e63057
AB  - 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.  approximately 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      withdrawn in 14/104(14%) patients, implicated in (14/34) 41% of the total drug 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.
FAU - Shean, Karen
AU  - Shean K
AD  - Lung Infection and Immunity Unit, Division of Pulmonology and UCT Lung Institute, 
      Department of Medicine, University of Cape Town, Cape Town, South Africa.
FAU - Streicher, Elizabeth
AU  - Streicher E
FAU - Pieterson, Elize
AU  - Pieterson E
FAU - Symons, Greg
AU  - Symons G
FAU - van Zyl Smit, Richard
AU  - van Zyl Smit R
FAU - Theron, Grant
AU  - Theron G
FAU - Lehloenya, Rannakoe
AU  - Lehloenya R
FAU - Padanilam, Xavier
AU  - Padanilam X
FAU - Wilcox, Paul
AU  - Wilcox P
FAU - Victor, Tommie C
AU  - Victor TC
FAU - van Helden, Paul
AU  - van Helden P
FAU - Grobusch, Martin P
AU  - Grobusch MP
FAU - Warren, Robin
AU  - Warren R
FAU - Badri, Motasim
AU  - Badri M
FAU - Dheda, Keertan
AU  - Dheda K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130507
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Antitubercular Agents)
SB  - IM
EIN - PLoS One. 2013;8(5). doi:10.1371/annotation/644591a8-8ae6-450e-974e-1cd1f08f52c7. 
      Groubusch, Martin [corrected to Grobusch, Martin P]
MH  - Antitubercular Agents/*adverse effects/*therapeutic use
MH  - Demography
MH  - Dose-Response Relationship, Drug
MH  - Extensively Drug-Resistant Tuberculosis/complications/*drug 
      therapy/microbiology/mortality
MH  - Female
MH  - HIV Infections/complications
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - Male
MH  - Multivariate Analysis
MH  - Mycobacterium tuberculosis
MH  - South Africa/epidemiology
MH  - Treatment Outcome
PMC - PMC3646906
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/05/15 06:00
MHDA- 2013/12/18 06:00
PMCR- 2013/05/07
CRDT- 2013/05/14 06:00
PHST- 2012/09/11 00:00 [received]
PHST- 2013/03/31 00:00 [accepted]
PHST- 2013/05/14 06:00 [entrez]
PHST- 2013/05/15 06:00 [pubmed]
PHST- 2013/12/18 06:00 [medline]
PHST- 2013/05/07 00:00 [pmc-release]
AID - PONE-D-12-28470 [pii]
AID - 10.1371/journal.pone.0063057 [doi]
PST - epublish
SO  - PLoS One. 2013 May 7;8(5):e63057. doi: 10.1371/journal.pone.0063057. Print 2013.