Microsoft powerpoint - iuatld2009_poster91149_drug_resistance_final.ppt

Drug resistance of Mycobacterium tuberculosis in patients with
new pulmonary tuberculosis in Lviv/UA
T. Bodmer1 , M. Pavljuk2, O. Zargaryan2, L. Rak2, U. Bischler3, and J.-P. Zellweger4
1University of Berne, Institute for Infectious Diseases, Berne, Switzerland; 2Lviv Regional Phtisio-Pulmonological Treatment and Diagnostic Centre, Sykhiv, Ukraine; 3Bear and Lion, Berne, Switzerland; 4Swiss Lung Association, Berne, Switzerland Revised abstract
Results, contd.
Background: Standardized drug therapy is one of the cornerstones of the current WHO strategy for the elimination of
Figure 2 delineates the Bactec® MGIT 960 DST patterns of four clinical Mtb tuberculosis (TB), however, the emergence and transmission of drug-resistant strains of Mycobacterium tuberculosis (Mtb) is increasingly jeopardizing the success of this strategy. The availability of local drug resistance surveillance data is patient isolates and the respective turn-around-times (TAT), i.e. the intervals therefore of the utmost importance for guiding TB control programs. The STOP TB LVIV Study Group has recently collected between the start of sample processing and the availability of the DST results. Mtb isolates from 24 consecutive patients with new pulmonary TB in Lviv, Ukraine (“pilot study”). The drug susceptibilities of these isolates were tested in order to estimate the rate of primary drug resistance in Lviv. Methods: Drug susceptibilities of Mtb isolates obtained from patients with new pulmonary TB were assessed by the Bactec
Figure 2. Bactec® MGIT 960 DST patterns
MGIT 960 method (Becton-Dickinson, Germany). The following drugs were tested at the critical concentrations (mg/L) indicated: isoniazid (0.1; 0.4), rifampicin (1.0), pyrazinamide (100), ethambutol (5.0; 7.5), streptomycin (1.0; 4.0), and levofloxacin (1.0). 2A. Susceptible M. tuberculosis
2B. INH-resistant M. tuberculosis
Results: To date, the drug susceptibility testing results of 24 isolates are available. Of these, 15 (63%) were susceptible to
all the drugs tested. Two (7%) showed mono-resistance to isoniazid, and three (13%) were resistant to both isoniazid and streptomycin. Four (17%) isolates were resistant to at least isoniazid and rifampicin, i.e. were MDR-TB. Conclusions: Our limited data set suggests that in Lviv approximately 80% of the patients with new pulmonary TB are
amenable to cure by WHO’s standard drug regimen or modifications thereof, whereas approx. 20% are not. Corroboration will require the study of a larger patient population. If these results are confirmed, upgrading the laboratory infrastructure and introducing assays for the rapid detection of MDR- and/or XDR-TB will be essential to effectively combat the current TB epidemic and to minimize the emergence of new drug-resistant strains. Background
2C. INH- and SM-resistant M. tuberculosis
2D. Multidrug-resistant M. tuberculosis
Standardized drug therapy is one of the cornerstones of the current WHO strategy for the elimination of tuberculosis (TB), however, the emergence and transmission of drug-resistant strains of Mycobacterium tuberculosis (Mtb) is increasingly jeopardizing the success of this strategy. The availability of local drug resistance surveillance data is therefore of the utmost importance for guiding TB control programs. The STOP TB LVIV Study Group has recently collected Mtb isolates from 24 consecutive patients with new pulmonary TB in Lviv, Ukraine (see abstract #91148). The drug susceptibilities of these isolates were tested in order to estimate the rate of drug resistance in new cases of pulmonary TB in Lviv/UA. Figure 3. Association of microscopy results and turn-around-time (TAT)
Figure 3 shows the distribution of TAT in Patients and procedures
Fifty consecutive patients with newly diagnosed pulmonary TB were enrolled days), respectively. In the latter, 90% of between 16.06.08 and 02.07.08 Three sputum specimens per patient were the DST results were available within 35 collected, split (see abstract #91148) and processed as outlined in figure 1: Figure 1. Specimen collection and processing scheme
Table 2 summarizes the Bactec® MGIT 960 DST results of the 24 Mtb patient isolates. One patient isolate was resistant to the fluoroquinolone tested. Storage at +4°C prior to processing: mean (±SD) 35.7 days (±4.2) Table 2. DST results and treatment options
Resistance N
Duration
Comments
H, isoniazid; E, ethambutol; R, rifampicin; S, streptomcin; Z, pyrazinamide; FQ, fluoroquinolone*for patients with extensive disease; **individualised treatment on the basis of individual DST results (adapted from Ref 2); ***XDR TB ? Conclusions
¾ Our results suggest that among HIV-negative patients with newly diagnosed Drug susceptibility testing (DST) of the following drugs at the concentrations o approx. 4 out of 5 patients were amenable to treatment with the standard drug (µg/ml) indicated was performed by Bactec® MGIT 960 (BD Diagnostics, Switzerland): isoniazid (0.1; 0.4), rifampicin (1.0), pyrazinamide (100), o approx. 1 out of 5 patients was infected by MDR TB and would thus require individually tailored treatment on the basis of personal DST results (2) ethambutol (5.0; 7.5), streptomycin (1.0; 4.0), and levofloxacin (1.0).
o XDR TB may be an issue, since one FQ-resistant MDR TB isolate was detected ¾ The availability of timely and reliable DST results can A total of 24 patient isolates were tested. Patients’ characteristics are shown 9 reduce the emergence of additional drug resistance 9 improve patient compliance (fewer drugs, less drug interactions/side effects) 9 reduce overall cost (better outcomes, fewer drugs) Table 1. Patients’ characteristics
¾ At this stage of the local TB epidemic implementation of the Bactec® MGIT Characteristic All
subjects
960 system for primary culture and DST will probably be most cost-effective for the diagnosis of new, sputum smear-positive patients, as here 50% and 90% of the DST results were available within 26 and 35 days, respectively References
Dye, C. Doomsday postponed? Preventing and reversing epidemics of drug-resistant tuberculosis. Nature Rev. Microbiol. 2009; 7: 81-87.
WHO emergency update 2008. Guidelines for the programmatic management of drug-resistant tuberculosis.
Acknowledgements
We wish to thank the clinical and laboratory staff from Sykhiv and Bern for excellent support and collaboration, and BD Diagnostics
Switzerland for supplying reagents.
Financial support
This study was supported by a grant of the Canton of Berne, Switzerland, to the NGO Bear and Lion, Berne, Switzerland.

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