Multidrug-Resistant Tuberculosis Treatment Outcomes in Relation to Treatment and Initial Versus Acquired Second-Line Drug Resistance.
BACKGROUND
Resistance to second-line drugs develops during treatment of multidrug-resistant (MDR) tuberculosis, but the impact on treatment outcome has not been determined.


METHODS
Patients with MDR tuberculosis starting second-line drug treatment were enrolled in a prospective cohort study. Sputum cultures were analyzed at a central reference laboratory. We compared subjects with successful and poor treatment outcomes in terms of (1) initial and acquired resistance to fluoroquinolones and second-line injectable drugs (SLIs) and (2) treatment regimens.


RESULTS
Of 1244 patients with MDR tuberculosis, 973 (78.2%) had known outcomes and 232 (18.6%) were lost to follow-up. Among those with known outcomes, treatment succeeded in 85.8% with plain MDR tuberculosis, 69.7% with initial resistance to either a fluoroquinolone or an SLI, 37.5% with acquired resistance to a fluoroquinolone or SLI, 29.3% with initial and 13.0% with acquired extensively drug-resistant tuberculosis (P < .001 for trend). In contrast, among those with known outcomes, treatment success increased stepwise from 41.6% to 92.3% as the number of drugs proven effective increased from ≤1 to ≥5 (P < .001 for trend), while acquired drug resistance decreased from 12% to 16% range, depending on the drug, down to 0%-2% (P < .001 for trend). In multivariable analysis, the adjusted odds of treatment success decreased 0.62-fold (95% confidence interval, .56-.69) for each increment in drug resistance and increased 2.1-fold (1.40-3.18) for each additional effective drug, controlling for differences between programs and patients. Specific treatment, patient, and program variables were also associated with treatment outcome.


CONCLUSIONS
Increasing drug resistance was associated in a logical stepwise manner with poor treatment outcomes. Acquired resistance was worse than initial resistance to the same drugs. Increasing numbers of effective drugs, specific drugs, and specific program characteristics were associated with better outcomes and less acquired resistance.
US Centers for Disease Control and Prevention, Atlanta, Georgia.
J Peter
JP
Cegielski
US Centers for Disease Control and Prevention, Atlanta, Georgia.
Ekaterina
E
Kurbatova
Medical Research Council, Pretoria, Republic of South Africa.
Martie
M
van der Walt
Medical Research Council, Pretoria, Republic of South Africa.
Jeannette
J
Brand
US Centers for Disease Control and Prevention, Atlanta, Georgia.
Julia
J
Ershova
Tropical Disease Foundation, Manila, Philippines.
Thelma
T
Tupasi
Tropical Disease Foundation, Manila, Philippines.
Janice Campos
JC
Caoili
US Centers for Disease Control and Prevention, Atlanta, Georgia.
Tracy
T
Dalton
Socios en Salud Sucursal.
Carmen
C
Contreras
National Institute of Health, Lima, Peru.
Martin
M
Yagui
Socios en Salud Sucursal.
Jaime
J
Bayona
US Centers for Disease Control and Prevention, Atlanta, Georgia.
Charlotte
C
Kvasnovsky
Riga East University Hospital Centre of Tuberculosis and Lung Diseases, Latvia.
Vaira
V
Leimane
Riga East University Hospital Centre of Tuberculosis and Lung Diseases, Latvia.
Liga
L
Kuksa
US Centers for Disease Control and Prevention, Atlanta, Georgia.
Michael P
MP
Chen
National Institute for Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland.
Laura E
LE
Via
National Masan Hospital, Changwon.
Soo Hee
SH
Hwang
US Centers for Disease Control and Prevention, Atlanta, Georgia.
Melanie
M
Wolfgang
Vladimir Oblast Tuberculosis Dispensary.
Grigory V
GV
Volchenkov
Vladimir Oblast Tuberculosis Dispensary.
Tatiana
T
Somova
US Centers for Disease Control and Prevention, Atlanta, Georgia.
Sarah E
SE
Smith
Ministry of Health, Bangkok.
Somsak
S
Akksilp
Office of Disease Prevention and Control Region 7, Ubon Ratchathani, Thailand.
Wanpen
W
Wattanaamornkiet
Korean Institute of Tuberculosis, Seoul, Republic of Korea.
Hee Jin
HJ
Kim
Korean Institute of Tuberculosis, Seoul, Republic of Korea.
Chang-Ki
CK
Kim
Orel Oblast Tuberculosis Dispensary.
Boris Y
BY
Kazennyy
Orel Oblast Tuberculosis Dispensary.
Tatiana
T
Khorosheva
Tartu University Hospital.
Kai
K
Kliiman
National Tuberculosis Registry, National Institute for Health Development,Tallinn, Estonia.
Piret
P
Viiklepp
Taiwan Centers for Disease Control, Taipei.
Ruwen
R
Jou
Taiwan Centers for Disease Control, Taipei.
Angela Song-En
AS
Huang
Central Tuberculosis Research Institute, Russian Academy of Medical Sciences, Moscow, Russian Federation.
Irina A
IA
Vasilyeva
Central Tuberculosis Research Institute, Russian Academy of Medical Sciences, Moscow, Russian Federation.
Olga V
OV
Demikhova
Joey
J
Lancaster
Ronel
R
Odendaal
Lois
L
Diem
Therese C
TC
Perez
Tarcela
T
Gler
Kathrine
K
Tan
Cesar
C
Bonilla
Oswaldo
O
Jave
Luis
L
Asencios
Gloria
G
Yale
Carmen
C
Suarez
Allison Taylor
AT
Walker
Inga
I
Norvaisha
Girts
G
Skenders
Ingrida
I
Sture
Vija
V
Riekstina
Andra
A
Cirule
Erika
E
Sigman
Sang-Nae
SN
Cho
Ying
Y
Cai
Seokyong
S
Eum
Jongseok
J
Lee
Seungkyu
S
Park
Doosoo
D
Jeon
Isdore C
IC
Shamputa
Beverly
B
Metchock
Tatiana
T
Kuznetsova
Rattanawadee
R
Akksilp
Wanlaya
W
Sitti
Jirapan
J
Inyapong
Elena V
EV
Kiryanova
Irina
I
Degtyareva
Evgenia S
ES
Nemtsova
Klavdia
K
Levina
Manfred
M
Danilovits
Tiina
T
Kummik
Yung-Chao
YC
Lei
Wei-Lun
WL
Huang
Vladislav V
VV
Erokhin
Larisa N
LN
Chernousova
Sofia N
SN
Andreevskaya
Elena E
EE
Larionova
Tatyana G
TG
Smirnova
D000293:Adolescent; D000328:Adult; D000368:Aged; D000995:Antitubercular Agents / Q000627:therapeutic use*; D024901:Drug Resistance, Multiple, Bacterial; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000302:isolation & purification; D011446:Prospective Studies; D013183:Sputum / Q000382:microbiology; D016896:Treatment Outcome; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy*; D055815:Young Adult
D000995:Antitubercular Agents
acquired drug resistance; extensively drug-resistant tuberculosis; multidrug-resistant tuberculosis; second-line drugs; treatment outcome