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Oral Presentation Room C4 - 14:45-16:45 Monday, September 17th 2007 274. Drug-resistant and
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Clinical efficacy of once a day linezolid and azithromycin in the treatment
of multi-drug resistant tuberculosis
S.K. Agarwal. Chest Diseases, Institute of Medical Sciences, Varanasi, Uttar
Pradesh, India
Objective of the study was to see the clinical efficacy of a combination therapywith linezolid (L), azithromycin and other second-line anti-tuberculosis drugs inthe treatment of multi-drug resistant pulmonary tuberculosis (MDR-TB).
Forty-seven patients (study group), aged 18 years to 50 years having multi-drugresistant tuberculosis (MDR-TB) were given linezolid, azithromycin along withkanamycin, pyrazinamide, ethionamide and ethambutol under direct supervision.
Forty-five patients (control group) were given kanamycin, pyrazinamide, ethion-amide and ethambutol. All patients were HIV negative, smear-positive, non-pregnant and had been receiving anti-tuberculosis drugs for an average of 76weeks (32 to 132 weeks). All patients had isolates resistant to both isoniazid andrifampicin. Linezolid was given in the dose of 600mg once a day for 6 months.
Kanamycin was given in the dose of 25 mg/kg body weight on alternate days for24 weeks. Pyrazinamide was given for full course of therapy.
Forty-three cases in the study group and 42 in the control group completedthe treatment. The sputum negative conversion in the study group (81%) wassignificantly higher than in the control group (57%). The radiological improvementrate was 52% in the study group, significantly higher than that in the control group(27%) (P < 0.01). The closure rate of the lung cavities in the study group (69%)was higher than in the control group (45%) (P < 0.05). No significant differencewas found in the side-effects between the two groups.
Chemotherapy with linezolid, azithromycin, kanamycin, pyrazinamide, ethion-amide and ethambutol seems to be promising for Indian patients having MDR-TB.
2684
Nitric oxide, TNF-a and INF-g receptor in MDR-TB patients: a follow-up
study
A. Diwakar1, M. Sharma2, M. Bose2, S.N. Gaur1. 1Pulmonary Medicine,
Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India; 2Microbiology,
Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India
Nitric oxide (NO), a potent mycobactericidal molecule produced by macrophagesis regulated by TNF-a and INF-g.
We compared levels of NO, TNF-a and INF-g receptor response in MDR TBpatients with newly diagnosed cases of pulmonary TB.
Mononuclear cells from venous blood of 11 new and 21 MDR TB cases atthe start of first/second-line anti-tubercular drugs respectively were matured intomacrophages. One new and 9 MDR cases were lost in follow-up. The above-mentioned markers were measured and compared before and after 12 weeks oftreatment.
Abstract printing supported by Nonin Medical, Inc. Visit Nonin Medical, Inc. at stand B04:31 Oral Presentation Room C4 - 14:45-16:45 Monday, September 17th 2007 The NO and TNF-a levels were diminished in both new and MDR cases as conversion, rest of drugs continued for an average period of 20 months. Cure compared to normal controls; more severely in the new case group. With treatment, was defined when sputum culture was negative at end of 2-year treatment.
the levels of these markers showed an increase in both groups. INF-g receptor Result: All patients had resistance to atleast Isonizid and Rifampicin. Average
levels were initially increased and declined with treatment in both groups.
duration of pretreatment chemotherapy was 27 months. All patients were seroneg- The state of activation and immunologic parameters of ex-vivo matured ative for HIV. Out of 53 patients enrolled, 39 completed the treatment as planned, macrophages demonstrate differential response in new and MDR cases of tu- 3 patients died during treatment and 11 patients abandoned it or lost to follow up.
berculosis. Larger studies of longer duration are required to confirm whether Out of 39 who completed the treatment, 36 declared cured. Considering the best these markers can be used as an indicator to gauge the response to, and more scenario (excluding the lost and expired patients) cure rate was 92.3% (36/39) and importantly, failure of treatment.
in worst scenario (considering the lost and expired patients) cure rate was 67.9%(36/53). Out of 36 cured, 31(86.1%) came for follow-up for mean duration of45(3−66) months. 4 out of 31(12.9%) patients showed relapse. Significant side Levels at the start of treatment (Mean±SD) effects were experienced in 8 (20.5%) patients.
Conclusion: MDR-TB can be cured successfully and requires much effort from
INF-g receptor (% of cells) both the patients and health care workers.
Concomitant MDR-TB and candidiasis
S. Iglikova1, A. Alenova2. 1Immunology, Nationaly TB-Centre, Almaty,Kazakhstan; 2Immunology, Nationaly TB-Centre, Almaty, Kazakhstan Target: to investigate the peculiarities of immunity among patients with duelinfection MDR-TB and candidiasis. Materials: 25 patients with both drug resistant Levels after 12 weeks of treatment pulmonary tuberculosis and candidiasis confirmed through bacteriological methodimplemented (Gr. I) and 15 patients with MDR-TB without candidiasis (Gr. II).
INF-g receptor (% of cells) There were investigated: level of anti-TB antibodies, IgM, IgG to Candida albicansin blood and bronchoalveolar lavage, non-specific antibodies IgM, IgG and IgA; CD3+, CD4+, CD8+, CD11b+, CD16+, CD19+, and NST-test. Results: In Group I titer of blood anti-TB antibodies (ATA) was 0.751±0.03, blood IgG titer to Candida albicans 0.215±0.01, IgM 0.105±0.1. Non-specific antibodies titer ofIgA, IgM, IgG – 1.5±0.01g/l, 2.2±0.2g/l, 15.9±6.5g/l correspondingly. Averagelymphocytes values: CD3+ 51.3±0.04%, CD4+ 17.8±0.2%, CD8+ 22.1±0.2%,CD11b+ 15.1±0.1%, CD+16 6.5±0.09%, CD19+ 5.1±0.1%; spontaneous and stimulate with BCG vaccine NST-test 11.1±0.8% and 15.9±0.9%. Group II: ATA RpoB and katG mutations as an epidemiologic markers of
0.899±0.06, blood IgG to C. albicans 0.101±0.02, IgM 0.090±0.03. Non-specific multi-drug-resistant M. tuberculosis strains isolated in Kyrgyz Republic
antibodies IgA, IgM and IgG: 1.7±0.01, 2.4±0.1, 16.9±7.1 correspondingly; J. Isakova1, Z. Goncharova2, A. Usupopova1, J. Kojomkulov2, A. Aldashev1.
CD3+ 53.9±0.06, CD4+ 19.1±0.2, CD8+ 21.8±0.3, CD11b+ 16.2±0.2, CD16+ 1 Laboratory of Molecular and Cell Aiology, Institute of Molecular Biology and 8.4±0.1, CD19+ 4.9±0.2%, NST-test: 12.5±0.6% and 21.4±0.8%. Thus, suppres- Medicine, Bishkek, Kyrgyzstan; 2Laboratory Diagnostics, National Centre of sive effect of C. albicans impacts on immunity when concomitance of MDR-TB Phthisiology, Bishkek, Kyrgyzstan and candidiasiss that leads to low treatment effectiveness.
The Kyrgyz Republic is one of countries with high levels of tuberculosis. The problem is becoming more critical with an appearance and spread of multiple- Current tuberculosis patterns in a changing European union
drug resistance of M. tuberculosis.
D. Falzon1, F. Ait-Belghiti1. 1Department of Infectious Diseases (EuroTB), Aim: To characterize the rpoB, katG, inhA and ahpC gene mutations in rifampicin
Institut de Veille Sanitaire, Saint-Maurice, France (RIF) and isoniazid (INH) resistant of M. tuberculosis strains.
Materials and Methods: A total 328 specimens were examined from patients
Background: the socio-economic status of states joining the European Union
with pulmonary and extra pulmonary tuberculosis. Mutations of rpoB, KatG, inhA (EU) since 2004 differs from that of the original ones and ahpC gene were detected by biological chip.
Aims: to outline key differences in tuberculosis (TB) epidemiological patterns in
Results: 183 of 328 samples (56%) were found to be wild type MBT strains, while
145 (44%) samples contained mutations associated with RIF or INH resistance.
Methods: we use data reported to the European TB surveillance network.
The single primary drug resistance only to RIF was 3% (10/328), whereas to INH Results: In 2005, the 27 EU countries reported 91,845 TB cases – 36% by
it was 15.2% (50/328). Multidrug resistance to RIF+INH was found in 25.9% Bulgaria and Romania that joined the EU in 2007. Total notification rate in 12 (85/328). 15 types of mutations were found in RIF-resistant. The most common states joining the EU since 2004 was >4 times higher than in the original 15 point mutations in rpoB gene were in codon 531 (60%), 526 (19%), 516 (5.5%).
(48.7 vs 10.7/100,000). In 2001–2005, rates decreased more in new states (−2.6% The point mutation Ser531Leu was at the highest frequency (59%). Resistance yearly) than in the original (−1.8%), and among the latter increases were observed to INH was associated mostly with mutations found in katG gene – 91%, inhA in Sweden (8%) and United Kingdom (5%) related to fluxes in foreign-born cases.
gene – 7% and ahpC gene – 2%. In the katG gene five different mutations were Compared to new members, the original states had a larger proportion of TB cases detected: Ser315Thr – 94%, Ser315Asn – 3%, Ser315Arg – 1%, Ser315Gly – 1% of foreign-origin (1% vs 41% in 2005), and higher HIV prevalence in TB cases and Ile335Val – 1%. In the inhA region the only found mutation was inhA T15 in recent years (0.6% vs 4.9%, 20 countries) although HIV prevalence increased (7%). In the ahpC promoter region – AhpC_9 (1%) and AhpC_12 (1%) mutations in 2000–2005 in Estonia (6.4% in 2005) and Latvia (3.5%). In 2005, resistance to isoniazid and rifampicin (MDR) was 10 times higher in new EU members Estonia, Conclusion: The rifampicin and isoniasid resistance of M. Tb strains isolated
Latvia and Lithuania (combined MDR: 18.1%) than in 13 other countries (1.8%).
in Kyrgyzstan is associated mostly with Ser531Leu mutation of rpoB gene, In 9 original EU countries in 2004, treatment success was lower and death was Ser315Thr mutation of katG gene and InhT15 mutation.
higher (74%, 7% respectively) among new TB cases than in 11 new states (79%,5%).
Conclusion: In westernised countries, vulnerable groups including immigrants
Long-term treatment out comes in multi drug resistant tuberculosis
should be prioritized in TB control. Estonia, Latvia and Lithuania should target MDR and HIV. Central European countries – several bordering ex-USSR countries R. Prasad1, S.K. Verma2, S. Verma3, A. Jain4. 1Deptt. of Pulmonary Medicine, with large TB case-loads – should be vigilant to avoid a re-emergence of TB as K.G. Medical University, Lucknow, India; 2Deptt. of Pulmonary Medicine, seen in western Europe in the early 1990s.
K.G. Medical University, Lucknow, India; 3Deptt. of Pulmonary Medicine,K.G. Medical University, Lucknow, India; 4Deptt of Micrbiology, K.G. Medical University, Lucknow, India Identifying pulmonary tuberculosis in emergency rooms: a decision
instrument for rapid patient isolation
Aim: Our study analyzes the long term treatment outcome with second line drugs
A. Hamzaoui1, P. Lesprit2, B. Maitre1, L. Deforges3, S. Aberrane4, E. Girou2, in patients with Multi Drug Resistant Tuberculosis (MDR-TB).
B. Housset1. 1Respiratory Diseases, Hopital Intercommunal, Creteil, France;2 Method: A prospective uncontrolled study of 53 patients with MDR-TB attending
CEPI, Hopital Henri Mondor, Creteil, France; 3Microbiology, Hopital Henri the Department of Pulmonary Medicine, K G M U, Lucknow, India from June Mondor, Creteil, France; 4Microbiology, Hopital Intercommunal, Creteil, France 1998 to April 2004 with follow-up till June 2006. All patients were admitted foraverage duration of 64 (15–136) days and received an individually tailored regimen Respiratory isolation has been recommended for all patients with suspected based on previous treatment history, chosen from Kanamycin, PAS, Ethionamide, tuberculosis (TB) but adhesion to these guidelines is difficult to follow in the Cycloserine, Flouroquinolone, Clofazimine and Pyrazinamide. Kanamycin was context of low availability of hospital isolation rooms and significantly increasing used only for an average period of 4.2 (2.5−6) months till sputum smear Abstract printing supported by Nonin Medical, Inc. Visit Nonin Medical, Inc. at stand B04:31 Oral Presentation Room C4 - 14:45-16:45 Monday, September 17th 2007 Objective: We examined usefulness of routinely available data to improve isolation
decisions for suspected tuberculosis in emergency rooms.
To identify simple potential predictors of isolation need 46 smear positive patients
were retrospectively compared to 37 smear negative culture positive patients, and
37 culture negative controls who were isolated on admission due to TB clinical
suspicion. Demographic, epidemiological, symptoms and radiographic variables
were determined by chart review.
In multivariate analysis presence of TB risk factors, smoking, fever lasting more
than 2 weeks, weight loss and lung cavities on chest radiography were associated
with an increased risk of positive smear. A simple scoring system was developed
using these variables. This score was integrated as a palm/pocket PC software,
easy and simple to use in emergency room. A patient' s total score of 3 or higher
indicated the need of isolation accurately predicting a positive smear with high
sensitivity (0.98). A score of 2 or less was a strong predictor of smear negativity.
Specificity was 0.405: using this score, 40% of the smear-negative patients might
not have been isolated.
The score will now be prospectively tested in emergency rooms to evaluate its
performance in every day practice.
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Resistance to second-line anti-tuberculosis drugs: new drug resistant TB
treatment problem
A.L. Khanin1, I.B. Viktorova1,2, S.A. Dolgikh1,2, T.A. Jasukevitch2, L.A. Malyk2,
A.I. Gordon2. 1Phthysiopulmonary, State Medical Institute for Postgraduate
Training, Novokuznetsk, Russian Federation; 2Phthysiopulmonary, Novokuznetsk
TB Hospital, Novokuznetsk, Russian Federation
TB incidence in Novokuznetsk in 2005 was 111.3/100 with level of primary MDRTB as 18.75%. MDR TB management programme was started in 2003. Treatmentfailure in drug resistant TB was established in 10.6% of patients. In 93.3% of suchcases the resistance to II line anti-TB drugs was found to be the main cause offailure.
The aim of the study was to estimate the level drug resistance to second-line drugsin a big industrial city of Western Siberia.
In 2006 drug susceptibility tests (DST) to II line drugs were made in 141patients with drug resistant and multidrug resistant TB. DST was performedon L¨owenstein-Jensen media using absolute concentrations in a laboratory withcontrolled quality. Concentrations of second-line anti-TB drugs were the next:K – 30 mcg/ml, Eth – 30 mcg/ml, Cyc – 30 mcg/ml, Cap – 30 mcg/ml, Ofl – 2mcg/ml, PAS – 1 mcg/ml.
Drug resistance to at least one second-line drug was detected in 49 cases (34.8%),monoresistance was found in 28 cases (19.9%), resistance to 2 drugs – in 13 cases(9.2%), resistance to 3 drugs – in 8 (5.7%). High level of resistance to injectabledrugs (K, Cap) and ethionamide was found. Table.
Drug resistance to second-line anti-TB drugs is a potential problem of MDR TBtreatment. Every third patient with resistance to first-line drugs in Novokuznetskhas resistance to at least one II line drug.
Drug resistance to II line anti-TB drugs Resistance to 2nd line anti-TB drugs Resistance to at least 1 drug Any resistance with K Any resistance with Cap Any resistance with Eth Any resistance with Ofl Any resistance with PAS Abstract printing supported by Nonin Medical, Inc. Visit Nonin Medical, Inc. at stand B04:31

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