Infection with HIV is a major risk factor
for the development of resistance to key second-line anti-tuberculosis (TB)
drugs, US investigators report in the online edition of Clinical Infectious Diseases.
“The present study provides the first
comprehensive assessment of predictors of acquired resistance to two key
classes of second-line antituberculosis drugs, fluoroquinolones and second-line
injectable agents,” write the authors. “The proportion of acquired resistance
was larger among MDR TB [multi-drug resistant TB] patients, patients with
positive HIV status, and those with SLD [second-line drugs] in the initial
Resistance to anti-TB drugs is a growing
public health problem. The World Health Organization (WHO) estimates that there
were 650,000 cases of multidrug-resistant TB (defined as resistance to the
first-line drugs isoniazid and rifampicin) in 2011.
There are also concerns around resistance to
second-line anti-TB drugs. Resistance to an injectable second-line therapy and
a drug in the fluoroquinolone class means that someone has extensively
drug-resistant TB (XDR-TB). Treatment outcomes for people with XDR-TB are
poor and mortality is high. XDR-TB has been reported in 77 countries, including
Investigators wanted to determine the
incidence and risk factors for the emergence of resistance to injectable drugs
and fluoroquinolone in people taking TB therapy in the US.
They therefore analysed data from the US
National TB Surveillance System between 1993 and 2008. People were eligible
for inclusion in the study if the results of drug susceptibility tests
conducted at the start and completion of TB therapy were available.
Of 2274 people without resistance to an
injectable second-line agent at baseline, 49 (2.2%) acquired
resistance during follow-up. Of the 1141 people who were initially
susceptible to a fluoroquinolone, 32 (2.8%)
developed resistance. A total of five people with MDR-TB at baseline acquired
resistance to both an injectable drug and a fluoroquinolone “and thus developed
Encouragingly, resistance became less frequent
after 1993. “The decrease in frequency of acquired resistance beginning in 1992
may be attributed to the public health response to the TB epidemic,” suggest
the investigators. This included “greatly improved TB control activities and
increased proportion of patients treated under directly observed therapy (DOT)
in the US from that time.” However, they caution, “acquisition of resistance to
SLD in the US continues to occur.”
Factors associated with the emergence of
resistance to injectable second-line drugs were: age between 25 and 44 years
(aOR = 2.7; 95% CI, 95% CI, 1.2-6.3); infection with HIV (aOR = 2.5; 95% CI,
1.3-4.7); treatment for MDR-TB at baseline (aOR = 5.5; 95% CI, 2.9-10.5); and
therapy that included any second-line drug (aOR = 2.4; 95% CI, 1.2-4.7).
The authors note that the people aged
between 25 and 44 who acquired resistance included a high proportion of people with HIV and injecting drug users.
Acquired resistance to fluoroquinolones was
associated with baseline MDR-TB (aOR = 6.5; 95% CI, 2.9-14.6). The small number
of people developing resistance to this type of drug limited the
investigators’ ability to find other associations.
They conclude that people in groups with
a high-risk of resistance “should be prioritized for fast-track DST [drug susceptibility
testing] and rapid molecular tests for drug resistance and strictly follow
supervised treatment based on the drug susceptibility test results. Earlier
identification of patients at risk of developing XDR TB enables more diligent
infection control measures, critical for preventing transmission of the