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Bacterial Infections
In an analysis of MDR MTB strains from patients in Germany during the past • Diseases caused by MDR and XDR strains of M. tuberculosis can be cured
10 years by the National Reference Centre for Mycobacteria in Borstel, a in half to two-thirds of cases by treatment strategies that are individually
more than five-fold increase of strains belonging to the Beijing phenotype tailored with respect to the resistance pattern of the bacterium, in
was found. Clusters were detected as the consequence of the virulent combination with surgical strategies, especially in cases limited to either
character of these TB strains and their infectiousness. one lobe of the lung or one lung. Intense monitoring of the adverse
effects of drugs along with monitoring and supporting adherence to
Eker et al.
9
will present data from between 2004 and 2006 including therapy is required.
184 MDR-TB patients, seven of them with XDR-TB, who were treated • About 20–25% of patients suffering from MDR and XDR will die from
in 27 different hospitals in Germany with complete susceptibility the disease. Another 15% will be ‘treatment failures’ with little chance
testing results. Fifty-three per cent and 86% of the MDR- and XDR-TB of cure. Some of these individuals will continue living in their community
cases, respectively, had prior treatment for TB. Ninety-eight per cent of with the risk of transmitting resistant strains.
the pre-treated patients were immigrants from countries belonging to • Currently, not even 20% of the estimated cases of MDR are adequately
the former Soviet Union. Five per cent were born in Germany. treated. If they are treated on the basis of standard or recommended
Resistance to all first-line drugs was found in 36% of the MDR cases, treatment regimes, including DOTS, without results of susceptibility
with resistance to FQ in 8% and to injectable drugs in 12.8%. In six of testing, amplification of drug resistance is to be expected.
the seven XDR-TB patients, MTB strains were resistant to all first-line • To achieve an overall reduction in TB incidence by 6–7% annually, 70%
drugs, and 59.3% of the MDR and 57.1% of the XDR cases were of all new sputum-smear-positive cases need to be identified and 85%
cured or completed treatment. Days in hospital were 123.3±81 in need to be successfully treated.
14,15
In Germany, cure rates in 2006 were
MDR and 202±130 in XDR. Linezolid, a drug rarely applied for TB only 81%.
16
The incidence of TB is continuing to increase and WHO
treatment in high-incidence countries, was applied in 39% of the MDR estimations expect an incidence for TB of 150 per 100,000 by 2015,
cases and 71.4% of XDR patients. The effectiveness of the drug representing more than 10 million cases a year.
cannot be evaluated from the data, as only patients with severe illness • The incidence of drug resistance will increase dramatically. More cases of
and susceptibility (usually to fewer than four drugs) were treated with MDR and XDR, through either an inadequate treatment regimen or the
linezolid. The drug has been applied in cases of resistant TB in untimely identification of cases with primary drug resistance, will be
Germany for more than 10 years, and linezolid-resistant strains have observed. There will be a continuous spread of drug-resistant MTB
already been detected. strains in HIV-seropositive individuals, especially in Africa with its huge
number of co-infections with HIV and MTB.
As early as 2001, Grimaldo et al.
10
reported the drug resistance of MTB • New drugs are being developed, but they need to be evaluated as
strains against ofloxacin and ciprofloxacin in the Philippines, a hyper- quickly and as thoroughly as possible, in controlled studies, to determine
endemic area for TB. A retrospective analysis between 1995 and 2000 their role as combination partners for the current second-line drugs for
revealed resistance of MTB strains against ciprofloxacin in 26.8% and resistant TB.
ofloxacin in 35.3%, with 17.2% showing MDR-TB. Among the MDR strains, • Diagnostic tools need to quickly identify drug resistance in smear-positive
51.4% were resistant to FQ. Resistance to FQ significantly increased TB cases in countries with a high incidence of MDR for an adequate and
compared with the data of 1989 and 1994. The importance of FQ as a individualised choice of treatment regimens.
combination partner drug in MDR- and XDR-TB is stressed by data from the • Development of resistance to key drugs in the treatment of MDR and
European ‘TBNET’ study.
11
In 425 MDR patients, 64 of whom were XDR, XDR such as fluoroquinolones must be minimised by prescribing these
therapeutic failure and death occurred in 19 and 20% of FQ-resistant MDR drugs only when indicated. The widespread use of theses drugs for the
and XDR strains, respectively. For FQ-sensitive strains the data showed a cure of other diseases should be abandoned.
9 and 12% failure rate, respectively. Susceptibility to capreomycin, the most • There is a continuous spread of pathogenic MTB strains strongly
effective injectable drug, is associated with an improved therapeutic associated with resistance, an example of which is the Beijing genotype.
outcome in MDR and XDR cases. Treatment failure and death was found in
28.1% of the 425 cases, in contrast to 60.9% in patients with proven Reduction of untreatable cases and deaths from MDR and XDR worldwide
resistance against capreomycin.
12
can be achieved by gaining control over the development of drug
resistance in high-incidence countries. Although the WHO has
Development of new drugs for TB treatment is a crucial issue and some drug implemented programmes against drug-resistant TB in high-prevalence
candidates have already entered phase II clinical trials using nitroimidazoles countries, there will hopefully be no issues related to economic depression
(i.e. PA-824 and OPC-67683), which have activity against both replicating in the developed countries. ■
and non-replicating anaerobic cells. Flouroquinolones such as moxifloxacin
and gatifloxacin are included in phase III clinical trials, but there is still no Acknowledgements
proof of shorter treatment courses or more effective treatment outcomes Many thanks to Dr Ruesch-Gerdes and Dr Niemann of the National Reference
compared with the standard regimen (except in animal models).
13
There are Centre for Mycobacteria in Borstel, Germany, for communicating data on
some important things to learn from the presented studies: linezolid resistance of MTB strains and MDR-TB strain genotyping in Germany.
1. MMWR Morb Mortal Wkly Rep, 2006;55:301–5. 7. Cox HS, et al., Clin Infect Dis, 2007;44:1421–7. 13. Young DB, et al., J Clin Invest, 2008;118:1255–65.
2. Gandhi NR, et al., Lancet, 2006;368:1575–80. 8. Cox HS, et al., Respir Res, 2005;6:134 14. Elzinger G, et al., Lancet, 2004;363:814–19.
3. WHO_HTM_TB_2007_387_eng.pdf 9. Eker B, et al., Emerg Infect Dis, 2008;14:1700–1706. 15. Dye C, et al., Intern J Tuberc Lung Dis, 2006;10:460–62.
4. Migliori GB, et al., Eur Respir J, 2007;30:623–6. 10. Grimaldo ER, et al., Int J Tuberc Lung Dis, 2001;5:546–50. 16.
www.rki.de/cln_048/nn_274324/DE/Content/InfAZ/T/
5. Cox HS, et al., PLos ONE, 2007;2(11):e1126. 11. Migliori GB, et al., Eur Respir J, 2007;30:323–6. Tuberkulose/Tuberkulose.htm
6. Mitnick CD, et al., N Engl J Med, 2008;359:563–74. 12. Migliori GB, et al., Eur Respir J, 2008;31:1155–9.
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