Later-generation fluoroquinolones more effective at reducing mortality risk in resistant TB

Later-generation fluoroquinolones significantly reduced the risk for mortality in patients with suspected drug-resistant tuberculosis compared with early-generation drugs of the same family, according to researchers.

The findings mean resistance to the older fluoroquinolones should not automatically steer clinicians away from using the newer ones, they wrote in Clinical Infectious Diseases.

“Use of later-generation fluoroquinolones significantly reduced patient mortality risk in our cohort, suggesting that removal of a later generation fluoroquinolone form a treatment regimen because of demonstrated resistance to an earlier generation fluoroquinolone might increase mortality risk,” they wrote.

Their prospective cohort study included 834 patients with positive sputum tests for TB. They were recruited at clinics in India, Moldova and South Africa in 2012 and 2013. The median patient age was 33 years, and 75% of participants said they had previously been treated for TB.

The researchers identified which drugs each patient had received at the start of treatment and again at 30 days after enrollment. The patients were followed for a mean of 190 days.

The sputum samples were tested for susceptibility to isoniazid, rifampicin, moxifloxacin, ofloxacin, kanamycin, Capastat (capreomycin, Akorn) and amikacin.

In all, 282 patients (34%) were susceptible to all the drugs tested, 52 (6%) were resistant to one drug, 153 (18%) had multidrug-resistant TB, 290 (34%) had pre-extensively drug-resistant TB (pre–XDR-TB) and 57 (7%) had XDR-TB. A total of 279 patients had TB resistant to ofloxacin, and of those, 272 (97%) were also resistant to moxifloxacin, the researchers wrote.

According to the researchers, 379 (45%) had taken a later-generation fluoroquinolone — either moxifloxacin or levofloxacin. Of those, 48% were phenotypically resistant to ofloxacin.

The overall mortality rate was 7.4%. However, when 39 patients without a recorded date of death were included, the mortality rose was 11.6% overall and 37.8% in those with XDR-TB.

Patients with XDR-TB had a 19.3% mortality rate, compared with 6.5% in those with MDR-TB (P = .02). Those with XDR-TB had nine times the risk for mortality than patients who had drug-susceptible TB, the researchers wrote.

Patients taking later-generation fluoroquinolones had less than half the mortality risk of those taking older or no fluoroquinolones (adjusted HR = 0.46; 95% CI, 0.26-0.8). But in the 57 patients with XDR-TB, the later-generation drugs were not associated with a significant decrease in mortality risk.

Among those who did not have XDR-TB, later-generation fluoroquinolones were associated with a risk reduction of nearly half (HR = 0.54; 95% CI, 0.29-0.98).

Patients with a BMI of less than 18.5 had almost twice the risk for mortality as those with a BMI of at least 18.5 (adjusted HR = 1.96; 95% CI, 1.15-3.35). Those data and the fluoroquinolone results led the researchers to conclude that more research is required.

“Further studies designed to assess the use of later-generation fluoroquinolones on mortality are needed,” they wrote. “In addition, individuals with higher levels of resistance or presenting with low BMI appear to be at significantly increased risk for mortality and should be monitored accordingly.”

Seifert M, et al. Clin Infect Dis. 2017; doi:10.1093/cid/cix422.

Source: Healio

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By Joe Green

Published: May 18, 2017, 5:51 p.m.

Last updated: May 18, 2017, 5:54 p.m.

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