2015-denmark-figure-129.html
DANMAP 2015 3D
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danmap 2015 130 textbox 8.5 increasing rates of drug-
resistance
in mycobacterium
tuberculosis
isolates in denmark background: in recent years, the global incidence of
tuberculosis
(tb) has declined. however, the emergence of drug-resistant mycobacterium
tuberculosis
(mtb) strains challenges tb control in many parts of the world, especially eastern europe, asia and southern africa (https://extranet.who.int/sree/reports?op=vs&path=/who_hq_reports/g2/prod/ext/mdrtb_indicators_map). multidrug-resistant (mdr) tb is caused by mtb resistant to at least rifampin and isoniazid, the two most important drugs for tb treatment. extensively-drug-resistant (xdr) tb is a form of mdr-tb with additional
resistance
to any of the fluoroquino- lones (e.g. moxifloxacin) and to at least one of three injectable second-line drugs (amikacin, capreomycin or kanamycin). by now, xdr-tb has been reported in 105 countries worldwide [1]. mtb drug
resistance
is caused by spontaneous mutations in genes during the bacterial multiplication, which confer
resistance
to the drugs at different frequencies. exposure to a single drug, or suboptimal drug concentrations, provides a selective environment favouring drug-resistant bacteria and the develop- ment of mdr/xdr-tb [2]. previously, mdr-tb has only been identified in approx.0.5% of all culture-verified tb-
cases
in den- mark, corresponding to approx. two
cases
per year, and until recently in 2013, xdr-tb had not been seen. in comparison, in the who european region, the prevalence of mdr-tb among 88,732 new pulmonary tb
cases
tested was 18.4% in 2014 [3]. methods: in denmark, all clinical samples from suspected tb patients have been cultured at the international reference labo- ratory of mycobacteriology, statens serum institut (ssi). at first, stained using auramine-rhodamine followed by fluorescence microscopy. then, cultured in liquid medium (bactec mgit 960 system, bd) and solid medium (löwenstein-jensen). if culture positive, mtb has been identified by mtbc tbc id (bd) and genotype mtbc (hain lifescience) and phenotypic susceptibility tests have been performed by the modified proportion method on liquid media in mgit 320/960 systems (bd) supplemented by genotypic susceptibility tests with genotype mtbdr plus and genotype mtbdr sl (hain lifescience). results: five mdr-tb
cases
and 1 xdr-tb case were detected in denmark in 2015 among approx. 358 notified
cases
, corre- sponding to 1.7% mdr/xdr-tb in total. the xdr-tb case was russian-born and found to be resistant to 13 out of 15 tested antibiotics (!) in addition, 1 somalian-born mdr-tb case was resistant to all fluoroquinolones, and 1 syrian-born mdr-tb case was resistant to 2 out of 3 tested injectable second-line drugs. thus, these two
cases
were ?pre-xdr?. two of the 3 other mdr-tb
cases
were from somalia whereas one was from denmark. additionally 13
cases
(3.6%) were isoniazid mono-resis- tant. discussion: the 2015 drug-
resistance
figures for mtb are the highest ever registered in denmark with 5 mdr-tb-
cases
plus the only second xdr-tb case in the country; the first was registered in 2014. in addition, two of the mdr-tb
cases
were ?pre- xdr? with additional problematic
resistance
. although the total figures are small, we have to be prepared for an increasing number of mdr/xdr-tb
cases
in denmark in the future. it is important to remind clinicians to be aware of drug-resistant tu- berculosis and remember to send all specimens for culturing, among others, to secure sensitive, fast and correct susceptibility testing, performed through a combination of phenotypic- and genotypic test methods. the sensitivity of genotypic tests only is low [4] as well as the positive predictive value [5] and genotypic tests are only available for a limited number of drugs [2]. troels lillebaek and erik svensson, international reference laboratory of mycobacteriology, ssi. for furher information: troels lillebaek tll@ssi.dk [1] http://who.int/mediacentre/factsheets/fs104/en/ [2] domínguez j, boettger e, cirillo d, cobelens f, eisenach k, gagneux s, hillemann d, horsburgh r, molina-moya b, niemann s, tortoli e, whitelaw a, lange c, tbnet and resist-tb networks. clinical implications of molecular drug
resistance
testing for mycobacterium
tuberculosis
: a tbnet/resist-tb consensus statement. int j tuberc lung dis 2016;20(1):24-42. [3] european centre for disease prevention and control/who regional office for europe.
tuberculosis
surveillance and monitoring in europe 2016. stockholm: european centre for disease prevention and control, 2016. [4] arentz m, sorensen b, horne dj, walson jl. systematic review of the performance of rapid rifampicin
resistance
testing for drug-resistant
tuberculosis
. plos one 2013; 8(10): e76533 [5] tomasicchio m, theron g, pietersen e, streicher e, stanley-josephs d, van helden p, warren r, dheda k. the diagnostic accuracy of the mtbdrplus and mtbdrsl assays for drug-resistant tb detection when performed on sputum and culture isolates. scientific reports 2016. 6:doi:10.1038/srep17850
methods-materials-2015-131.html
