Published Date: 2008-08-03 14:00:29
Subject: PRO/EDR> Tuberculosis, XDR - Austria ex Romania
Archive Number: 20080803.2373
TUBERCULOSIS, XDR - AUSTRIA ex ROMANIA
A ProMED-mail post
ProMED-mail is a program of the
International Society for Infectious Diseases
Date: Thu 31 Jul 2008
Source: Eurosurveillance [edited]
Extensively Drug-Resistant Tuberculosis - First Report Of A Case In
Austria, May 2008 A Indra1, M Rowhani2, R Rumetshofer2, B Robl1, M
Konrad1, L Meidlinger1, F Allerberger (<email@example.com>)1 1.
Austrian Agency for Health and Food Safety (AGES), Vienna, Austria 2.
Hospital Baumgartner Hohe, Vienna, Austria
We report on the 1st documented extensively drug-resistant tuberculosis
(XDR-TB) case in Austria, diagnosed this year . The term XDR-TB
was used for the 1st time in March2006, in a report jointly published
by the Centers for Disease Control and Prevention (CDC) and the World
Health Organization (WHO) to describe a disease caused by
_Mycobacterium tuberculosis_ that was resistant not only to isoniazid
and rifampicin (i.e. multi-drug resistant tuberculosis, MDR-TB) but
also to at least 3 of the 6 classes of 2nd-line anti-TB drugs -
aminoglycosides, polypeptides, fluoroquinolones, thioamides,
cycloserine, and para-aminosalycilic acid [1,2]. As this definition was
dependent on un-standardized drug susceptibility testing (DST)
methodologies and did not necessarily distinguish the most
difficult-to-treat cases using the current drug armamentarium, it was
eventually modified in October 2006 . XDR-TB is now defined as:
resistance to at least rifampicin and isoniazid, in addition to any
fluoroquinolone and to at least one of the 3 following injectable drugs
used in anti-TB treatment: capreomycin, kanamycin, and amikacin .
In May 2008, a 45-year old male Romanian presented to a pulmonology
centre in Vienna, Austria, complaining of fatigue, constitutional
symptoms and weight loss. The patient was afebrile (37.5 C) with an
oxygen saturation of 91.3 percent on air room, not associated with
haemoptysis or night sweats, but presenting with a productive cough
yielding large amounts of yellowish-greenish sputum. The patient
reported having been treated with an incomplete regimen of
anti-tuberculous drugs in Romania in 2002, following his 1st diagnosis
of tuberculosis. By 2003, while still on treatment, DST showed
1st-line anti-tuberculous drugs. No information is available on the
drug regimen employed during this 1st episode of MDR-TB.
In 2007, having felt no marked improvement, the patient travelled to
Sweden to continue treatment. DST of sputum showed resistance against
isoniazid, rifampicin, pyrazinamide, amikacin, ofloxacin and
sensitivity to ethambutol, linezolid, moxifloxacin and fusidic acid. He
was discharged on medication following 7 months of treatment (regimen
reportedly tailored to the DST) during which his condition improved and
sputum became negative. Upon return to his hometown, however, the
patient could not procure all the medication
prescribed, and his health deteriorated again. The patient therefore
travelled (by train) to Austria to seek further treatment.
On examination, the patient was 1.70 m tall but weighed only 53 kg.
Auscultation revealed bilateral crepitations. Chest X-ray examination
showed a reduced volume of the left lung with alveolar infiltrations,
and cavitatory lesions on the left side. Blood tests showed
leukocytosis (neutrophil count of 13.63 x 109/l) and an elevated
C-Reactive Protein (37 mg/l; local cut-off value 12 mg/l).
Ziehl-Neelsen staining of sputum smear showed abundant acid fast
bacilli (AFB 3+). Therapy with terizidon, ethambutol, linezolid,
moxifloxacin and capreomycin was re-established, based on the results
from the sputum cultures from Sweden. Under therapy, the patient's
condition improved, he gained 7 kg in weight and the load of AFB in
sputum smears fell to 1+. Isolates from sputum samples
taken in Austria yielded _M. tuberculosis_ of spoligotype T1
(1111111111111111111111111111111100001111111). On 18 Jul 2008, DST
showed in-vitro resistance against isoniazid, rifampicin, pyrazinamide,
amikacin, ofloxacin, capreomycin, rifabutin, cycloserine, and
protionamide, and susceptibility to streptomycin, ethambutol,
para-aminosalycilic acid and linezolid. Accordingly, capreomycin
therapy was terminated, and para-aminosalycilic acid and streptomycin
were added to the treatment regimen.
The patient is presently isolated in a TB ward at a pulmonology centre
in Vienna. We have no information on results of contact tracing
performed for this patient.
While this is the 1st published report of a case of XDR-TB in Austria,
it does not preclude the possibility that other cases had occurred or
transited the country previously. This study illustrates some key
public health concerns very pertinent to TB in the world today,
including disease chronicity, its association with low-resource
settings, the mobility of infectious patients and the role of improper
medication in the aetiology of drug-resistant disease.
By June 2008, 18 countries in the European Union (EU) and Western
Europe -- including Romania -- and 6 in the former Soviet Union had
officially reported XDR-TB cases . Four of these countries (Czech
Republic, Germany, Italy, and Slovenia) share a border with Austria. A
large part of the drug-resistant TB caseload in Europe occurs in the
countries of the former Soviet Union . The XDR-TB case in Austria
originated from Romania, a resource-constrained country at the eastern
border of the EU. Our case shows
only too well that XDR-TB is not confined by state borders. Schmid et
al. have recently also described an outbreak of MDR-TB among
HIV-seronegative refugees in Austria . As the reporters of the 1st
XDR-TB case in Ireland concluded in a recent article, we expect to have
further cases from amongst nationals of countries with a high burden of
drug-resistant TB .
The available evidence shows that XDR-TB results mainly from poor
clinical practice . Poor adherence to treatment, inappropriate
prescription, irregular drug supply, and poor drug quality are the main
reasons for acquiring resistance in TB . Once XDR-TB is acquired,
the prospects of successful chemotherapy remain low. In one series from
Western European countries, the mortality among non-HIV patients was
reportedly 36 percent . This makes the implementation of appropriate
public health measures to prevent further spread all the more crucial.
The occurrence of XDR-TB in Austria should serve as a wake-up call to
strengthen the national TB control programme by implementing
evidence-based measures to regulate the monitoring of TB treatment and
1. Migliori GB, Loddenkemper R, Blasi F, Raviglione MC. 125 years after
discovery of the tubercle bacillus: the new XDR-TB threat. Is "science"
enough to tackle
the epidemic? Eur Respir J. 2007;29:423-7.
2. Centers for Disease Control and Prevention: Emergence of
with extensive resistance to second-line drugs worldwide. MMWR Morb
Mortal Wkly Rep.
3. World Health Organization. Extensively drug-resistant tuberculosis
Recommendations for prevention and control. Weekly Epidemiological
Record. 2006;81: 430-2.
4. World Health Organization, Stop TB Department. Global map and
information on XDR-TB.
(last accessed 29 Jul 2008).
5. The WHO/IUATLD Global Project on Anti-tuberculosis Drug Resistance
Anti-tuberculosis drug resistance in the world, 2002-2007. 4th Global Report
(WHO/HTM/TB/2008.394). WHO, Geneva, Switzerland. 2008.
6. Schmid D, Fretz R, Kuo HW, Rumetshofer R, Meusburger S, Magnet E, et
al. An outbreak
of multi-drug resistant tuberculosis in refugees in Austria in
2005/2006. Int J Tuberc
Lung Dis 2008; in press.
7. Kennedy B, Lyons O, McLoughlin A, Gibbons N, O'Flanagan D, Keane J.
drug-resistant tuberculosis: First report of a case in Ireland. Euro Surveill.
2008;13(30):pii=18935. Available from:
8. Coker RJ, Bell A, Pitman R, Hayward A, Watson J. Screening
programmes for tuberculosis
in new entrants across Europe. Int J Tuberc Lung Dis. 2004;8(8):1022-6.
9. Migliori GB, Ortmann J, Girardi E, Besozzi G, Lange C, Cirillo DM,
et al. Extensively
drug-resistant tuberculosis, Italy and Germany. Emerg Infect Dis.
[This patient could possibly have had primary MDR or XDR-TB (the report
does not say whether drug susceptibility testing (DST) to 1st and
2nd-line drugs was done initially or done to 2nd-line drugs one year
later when he was diagnosed with MDR-TB in Romania), or he had
emergence of MDR and XDR-TB as a result of the inappropriate use of
anti-TB drugs, e.g., his possibly being treated with only a single drug
at a time to which his organism was susceptible. Contributory factors
were likely limited access to a TB diagnostic laboratory that was
capable of doing DST for 2nd-line anti-TB drugs as well as 1st-line
drugs and inconsistent use of DST to guide anti-TB drug therapy in a
resource-poor country. Additional contributory factors in this patient
were poor adherence to the treatment regimen and irregular drug supply.