Page 20 - HA Convention 2016 [Abstracts (Day 1)]

HOSPITAL AUTHORITY CONVENTION 2016 Special Topics

T5.4 Latest Development of Tuberculosis Management 14:30 Theatre 2

Diagnosis and Management of Tuberculosis in Adults
Mok T
Department of Respiratory Medicine, Kwong Wah Hospital, Hong Kong

Tuesday, 3 May Diagnosis of Tuberculosis (TB)

To control TB we must improve its detection rate and detect cases early. In many settings, chest X-ray is an entry point
for TB diagnostic evaluation. Suspected patient should send sputum specimens for smear microscopy and culture. The
WHO-endorsed Xpert MTB/RIF assay and LPA Genotype MTBDRplus are invaluable tools for quick diagnosis of TB and
drug resistance. Treatment should be started in patients with compatible clinical picture (pulmonary and extrapulmonary
TB) despite negative smear and/or Xpert MTB/RIF test while waiting for culture. All patients diagnosed and started on TB
treatment should be checked for HIV status, if not already known.

Treatment of TB

The problems of anti-TB treatment are its long treatment duration (six months for drug susceptible TB and at least 20 months
of MDR TB) and the suboptimal treatment success rate for MDR (50%) and XDR-TB (26%) using second-line regimens
in programmatic settings. New drugs and new regimens are both needed to shorten duration of treatment and improve
successful treatment of resistant TB. Two of the novel drugs, bedaquiline and delamanid, have been conditionally approved
to treat MDR and XDR TB

Bedaquiline is a diarylquinoline which inhibits mycobacterial ATPase leading to intracellular ATP depletion. Phase two
studies demonstrated bedaquiline use with OBR could improve culture and cure rate for MDR- and XDR TB. As it prolongs
QT interval, caution should be exercised when bedaquiline is used with other QT lengthening-drugs, e.g., clofazimine and
moxifloxacin. The increased risk of death reported in one study was not confirmed in subsequent trials.

Delamanid is a new agent derived from nitro-dihydro-imidazooxazole which inhibits mycolic acid synthesis. Treatment with
this drug for six months combined with OBR can improve outcomes and reduce mortality among patients with both MDR-
and XDR-TB. Results from a completed Phase three trial are awaited. The drug also prolongs QT interval.

Oxazolidinone inhibits mycobacterial protein synthesis. Linezolid is considered the most effective Group five drug which can
achieve a cure rate of 70% when added to OBR for MDR/XDR patients. Side effects of linezolid include peripheral neuropathy
and myelosuppression and are common with long term use. Another member of oxazolidinone, sutezolid, has better
antimycobacterial activity and is less toxic than linezolid in mouse model of TB. It is in Phase two development. Pretomanid is
a nitroimidazole which decreases intracellular ATP and inhibit cell wall synthesis. In a phase 2b trial, pretomanid, moxifloxacin
and PZA in combination has higher mycobacteriocidal activity than HRZE during eight weeks of intensive phase of treatment.

Trials of Novel Regimens of Shorter Duration

REMoxTB trial which compared two four-month moxifloxacin-containing regimens with standard six-month regimen showed
the formers were associated with a higher relapse rate. Substituting RIF with high dose rifapentine in standard eight week
treatment increased culture negative rate. There are and will be many Phase two and three trials testing potential duration
shortening regimens (consisting of existing and new drugs) for both sensitive and resistant TB.

It is hoped that with the availability of novel drugs and new regimens, duration of TB treatment can be shortened and
treatment outcomes of MDR and XDR TB can be improved.

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