Surveillance of Mycobacterium tuberculosis drug resistance in Hong Kong, 1986-1999, after the implementation of directly observed treatment.

OBJECTIVE: To study changing trends in TB epidemiology with emphasis on drug resistance rates in various age groups from 1986-1999. DESIGN: Laboratory-based data on drug susceptibility testing against streptomycin (SM), isoniazid (NH), rifampicin (RMP) and ethambutol (EMB) had been collected continuously in a centralised TB laboratory in Hong Kong. Epidemiological parameters such as sex, age and drug resistance rates in new and retreatment cases were measured and analysed for longitudinal trends. RESULTS: Of 48 924 non-duplicate isolates from new TB cases, 7045 (14.4%) were resistant to one or more drugs, 5773 (11.8%) were resistant to SM and/or INH while 881 (1.8%) were multidrug-resistant (MDR-TB). Of 3857 isolates from retreatment patients, 1176 (30.5%) were resistant to one or more drugs, 616 (16.0%) were resistant to SM and/or [NH, and 467 (12.1%) were MDR-TB. For isolates from new cases, significant declines were observed in the resistance rates against any drug, SM alone, INH alone, SM+INH and INH+RMP. For retreatment isolates, significant declines were also observed in resistance to any drug and INH+RMP. In both new and retreatment cases, isolates from patients aged over 65 years showed significantly lower drug resistance (any drug and INH+RMP) compared with other age groups (16-34 years and 35-65 years). CONCLUSION: With successful implementation of DOTS over a 14-year period, laboratory-based surveillance data showed significant declines in drug resistance, including MDR-TB. This has occurred amidst demographic changes associated with a generally ageing population as well as highly mobile sectors that are in constant exchange with highly endemic areas.     

Pattern of mycobacterial resistance to four anti-tuberculosis drugs in pulmonary tuberculosis patients in the state of Qatar after the implementation of DOTS and a limited expatriate screening programme.

OBJECTIVE: To determine the resistance pattern of Mycobacterium tuberculosis to four anti-tuberculosis drugs in pulmonary tuberculosis patients in the State of Qatar after the implementation of DOTS and an expatriate screening programme on arrival. METHOD: A state-wide, population-based, retrospective analysis of all cases of pulmonary tuberculosis with positive M. tuberculosis culture reported to the Division of Public Health TB Unit from January 1996 to December 1998. M. tuberculosis sensitivity testing was done by the Bactec method for isoniazid (INH), rifampicin (RMP), streptomycin (SM) and ethambutol (EMB). The results were interpreted as a daily change of the growth index of test vials (with drug) compared with controls. RESULTS: There were 406 isolates with positive M. tuberculosis culture. Sixty-one (15%) were resistant to one or more of the four anti-tuberculosis drugs, of which 58 (95%) were from newly diagnosed cases (primary) and three (5%) were from previously treated cases (acquired). Primary resistance was as follows: any resistance 15%, INH 12.4%, RMP 2%, SM 5.2%, EMB 0.8% and multidrug resistance (MDR, resistance to INH and RMP at least) was found in 0.8%. Acquired resistance was as follows: any resistance 15%, INH 15%, RMP 5%, SM 5% and MDR 5%. CONCLUSION: The prevalence of resistance to four anti-tuberculosis drugs is strikingly low due to the limited expatriate screening programme (chest radiography) and implementation of DOTS. The four-drug regimen is recommended for the initial phase of therapy until the results of sensitivity testing are known.     

Prevalence of katG Ser315 substitution and rpoB mutations in isoniazid-resistant Mycobacterium tuberculosis isolates from Brazil.

SETTING: Four hundred and sixty-eight isoniazid (INH) resistant Mycobacterium tuberculosis isolates recovered from a selected Brazilian population. OBJECTIVE: To check for susceptibility to other chemotherapeutic drugs used in TB treatment, and to ascertain mutations involved in INH and rifampicin (RMP) resistance. DESIGN: Antimicrobial susceptibility to RMP, streptomycin and ethambutol (EMB) was evaluated by the resistance ratio method and pyrazinamide (PZA) by activity assay. Single strand conformation polymorphism (SSCP) and sequence analysis were performed in samples from this panel to confirm mutations in codon 315 of the katG and in a 69-bp region of the rpoB gene. RESULTS: Combined resistance to INH+RMP, INH+ PZA, INH+EMB, and INH+RMP+PZA was shown in respectively 272 (58.1%), 126 (26.9%), 47 (10%), 116 (24.8%) isolates. No katG mutation was found in 19 (39.6%) of 48 strains tested. Ser315Thr substitution was found in 29 (60.4%). All RMP-resistant strains tested (n = 25) showed rpoB mutations. S531L substitution was found in 15 (60%). CONCLUSION: INH-resistant strains isolated from selected Brazilian populations frequently show resistance to other first-line anti-tuberculosis drugs. rpoB mutation was responsible for RMP resistance in all strains. Among INHr strains, katG mutations were shown in only 60.4%. Genetic approaches targeting the rpoB gene but not the katG gene have a high sensitivity to detect resistance among Brazilian M. tuberculosis strains.     

Tuberculosis treatment today

In West and East Germany the incidence of tuberculosis is declining. However, with an incidence of 22 per 100,000 inhabitants in West Germany and 17 new diseases per 100,000 inhabitants in East Germany it is not a rare disease. In the chemotherapy of pulmonary tuberculosis, isoniazid (INH), rifampicin (RMP), ethambutol (EMB), streptomycin (SM), pyrazinamide (PZA) and prothionamide (PTH) are the most relevant drugs. The chemotherapy of tuberculosis is always carried out as a combination therapy of at least three drugs. A rapid cultural conversion of the sputum as well as low rates of failures and relapses are regarded as parameters of quality. Therefore six-month-regimens with initially four drugs (INH + RMP + PZA + SM or EMB) or nine-(twelve-) month-regimens with initially three medicaments (INH + RMP + PZA, or INH + RMP + EMB or INH + RMP + SM) may be recommended. Peculiarities of the therapy in patients with AIDS, with drug resistance, with relapses.     

Blood agar for susceptibility testing of Mycobacterium tuberculosis against first-line drugs.

OBJECTIVE: To evaluate the performance of blood agar for the susceptibility testing of 50 Mycobacterium tuberculosis clinical isolates against isoniazid (INH), rifampicin (RMP), streptomycin (SM) and ethambutol (EMB). DESIGN: The activity of the drugs was determined by the proportion method on blood agar instead of Middlebrook 7H10 agar according to Clinical Laboratory Standard Institute recommendations. The final concentrations of INH, RMP, SM and EMB were 0.2 microg/ml, 1 microg/ ml, 2 microg/ml and 5 microg/ml, respectively. RESULTS: The results were compared with the radiometric proportion method as the reference, and the agreements were determined as 100% for INH and RMP, 92% for SM and 96% for EMB. The specificity, sensitivity, positive predictive value and negative predictive value were 90.4% and 97.5%, 100% and 90%, 66.6% and 90% and 100% and 97.5% for SM and EMB, respectively, while these values were 100% for INH and RMP. The results of susceptibility testing were obtained on the 14th day of incubation. CONCLUSION: According to this preliminary study, our results suggest that blood agar can be used as an alternative medium for the susceptibility testing of M. tuberculosis strains against INH, RMP, SM and EMB in resource-limited countries. However, further studies are needed before implementating the method in diagnostic laboratories.     

Multicenter study of MTT and resazurin assays for testing susceptibility to first-line anti-tuberculosis drugs.

OBJECTIVE: A multicentre evaluation was performed to assess two rapid low-cost methods, MTT (3-[4.5-dimethylthiazol-2-yl]-2.5-diphenyltetrazolium bromide) and resazurin assays, for testing the susceptibility of Mycobacterium tuberculosis to the first-line anti-tuberculosis drugs rifampicin (RMP), isoniazid (INH), ethambutol (EMB) and streptomycin (SM). METHODS: Thirty coded M. tuberculosis strains were sent to seven laboratories located in Latin America, representing six countries. Each site performed the colorimetric assays, MTT and resazurin, blind for the first-line drugs RMP, INH, EMB and SM. The minimum inhibitory concentration results obtained were compared to the conventional proportion method on Lowenstein-Jensen medium. RESULTS: After establishing the breakpoint concentrations, excellent results were obtained for RMP, INH and EMB, with levels of specificity and sensitivity of between 96% and 99%. CONCLUSION: MTT and resazurin assays are promising, accessible new alternative methods for middle- and low-resource countries that need low-cost methods to perform rapid susceptibility testing of M. tuberculosis to key anti-tuberculosis drugs.     

Anti-drug pattern of drug-resistant Mycobacterium tuberculosis and analysis of mutation in drug-target genes

The antimycobacterial susceptibility test was performed and minimal inhibitory concentration (MIC) to drugs was determined in 98 strains of Mycobacteium tuberculosis (MTB) isolated in Tokyo from 2000 to 2003, to find which were resistant to any of the four main anti-MTB drugs, isoniazid (INH), rifampicin (RFP), streptomycin (SM), and ethambutol (EMB). 27strains of them were resistant only to SM, and 16 strains were resistant only to INH. 51 strains of them were resistant to not only INH but also other drugs. 38 strains were resistant to both INH and RFP. 19 strains were resistant to all four drugs, including 7 strains resistant to new quinolon anti-biotics also. Nucleotide or amino-acid mutations in drug resistant MTB genome were determined by DNA sequencing method. Mutation of codon 516, 526, or 531 of rpoB gene was detected in 98% of MTBs resistant to RFP. Deletion or insertion of katG gene or nucleotide mutation at regulatory region of ahpC gene was detected in MTBs highly resistant to INH. Amino acid mutation of katG gene, especially at codon 315, was detected in MTBs resistant to INH intermediate. Nucleotide mutations at regulatory region of inhA gene were detected in MTBs resistant to INH at low level. Amino acid mutation at codon 43 or 88 of rpsL gene was detected in MTBs highly resistant to SM, and nucleotide mutation at 512, 513, or 516 of rrs gene was detected in MTBs resistant to SM at low level. Amino acid mutation at codon 306 of embB gene was detected in 87% of MTBs resistant to EMB.     

Anti-tuberculosis drug susceptibility testing of Mycobacterium bovis BCG Tokyo strain.

SETTING: The Mycobacterium bovis bacille Calmette-Guérin (BCG) vaccine is the only vaccine against tuberculosis (TB), owing to its valuable protective effects and low virulence. However, it can occasionally cause systemic infection in immunocompromised hosts. Isoniazid (INH), rifampicin (RMP), streptomycin (SM) and ethambutol (EMB) are known to be effective anti-tuberculosis drugs and are used for the treatment of BCG infections. Unfortunately, there are few studies of the susceptibility of BCG vaccine strains to these drugs. OBJECTIVE: To measure the minimum inhibitory concentrations (MICs) of BCG Tokyo vaccine products for anti-tuberculosis drugs and assess vaccine safety in terms of drug susceptibility. DESIGN: We measured the MIC for one seed and five product lots of BCG Tokyo strain for INH, RMP, SM and EMB using Middlebrook 7H11 agar plates. RESULTS: The MIC results for INH were 0.06 and 0.125 mg/ml for the product and seed lots, respectively. The MIC results for RMP, SM and EMB were 0.25-0.5, 0.25 and 2-4 microg/ml, respectively. CONCLUSION: Our results indicate that the BCG Tokyo strain was susceptible to the major anti-tuberculosis drugs and treatable even in cases of severe adverse events, including systemic infection.     

Drug resistance of Mycobacterium tuberculosis in the Sunamganj District of Bangladesh

Spread of drug-resistant tuberculosis (TB) threatens TB-control programmes, and all countries need to monitor the patterns and trends of anti-TB drug resistance. Such data assess the quality of control programmes and help forecast future trends of drug resistance. It will also help to establish guidelines for TB therapy. The aim of the current study was to describe the rate of drug-resistant Mycobacterium tuberculosis in the Sunamganj District of Bangladesh. Bacterial isolates were collected from sputum smear positive (ss+) patients who attended the National TB Programme from November 2003 to December 2004. A total of 95 isolates was tested for susceptibility to streptomycin (SM), isoniazid (INH), rifampicin (RMP) and ethambutol (EMB) at the National Reference Laboratory for Mycobacteria at the Norwegian Institute of Public Health (NIPH), Oslo. The total resistance among new cases to any drug was 31%. For SM it was 18%, INH 23%, RMP 2%, EMB 10% and 2% were multidrug-resistant (MDR). The National Tuberculosis Programme (NTP) in Sunamganj is still effective, although the high resistance to INH is alarming. An increased risk of treatment failure has been demonstrated in areas with high levels of INH resistance, and a high proportion of INH resistant cases may develop resistance to RMP during treatment.     

Characterization of clinical isolates of Mycobacterium tuberculosis resistant to drugs and detection of RpoB mutation in multidrug-resistant tuberculosis in the Philippines.

SETTING: Retrospective study of Mycobacterium tuberculosis isolates at the STD/AIDS Cooperative Central Laboratory, Philippines. OBJECTIVE: To describe patterns of M. tuberculosis resistance against first-line anti-tuberculosis drugs, and to analyze the rpoB gene codon mutation of rifampicin (RMP) resistant isolates and correlate genotypic and phenotypic patterns. DESIGN: One hundred and sixty-four M. tuberculosis complex isolates were retrieved for phenotypic analysis; 89 were resistant to any anti-tuberculosis drug and 50 were RMP-resistant, whereas 48 were multidrug-resistant (MDR). Of these 48, only 33 were available for genotypic analysis of the rpoB gene. RESULTS: Most drug-resistant isolates were phenotypically resistant to isoniazid (INH) (93%), and the probability of an RMP-resistant isolate becoming MDR was 96%. In 33 MDR isolates, 13 types of mutations in nine independent codons were identified; the most frequently mutated codons were S531L (61%) and G510H (15%), which were present in 76% (25/33) of the isolates. S531L was noted in 85.7% of the RMP + INH + SM resistant isolates, while only 80% of the isolates with INH + RMP, EMB + SM resistance showed this mutation. CONCLUSION: The high probability of RMP isolates being MDR suggests that genetic analysis of RMP resistance is useful in detecting MDR-TB. Worldwide accumulation of findings on circulating MDR-TB strains provides indispensable information about the re-emergence of TB.     

Surveillance of Mycobacterium tuberculosis drug resistance in France, 1995-1997. AZAY Mycobacteria Study Group.

OBJECTIVE: To measure the rate of primary and secondary drug resistance of Mycobacterium tuberculosis on an ongoing basis. DESIGN: Data on all culture-positive tuberculosis were collected prospectively from 1995 through 1997 from a microbiological laboratory network of 19 university hospitals throughout France, and submitted quarterly to the National Reference Centre for Surveillance of Mycobacterial Diseases. RESULTS: A total of 2998 patients were included in the study. Among the 2333 (78%) previously untreated patients, 8.6% had isolates resistant to any drug, 4.8% to streptomycin (SM) alone, 1.2% to isoniazid (INH) alone, 1.8% to SM + INH, and 0.3% to INH + rifampicin (RMP) or multidrug resistance (MDR). Foreign birth was independently associated with a higher risk of primary resistance to any drug (odds ratio [OR] 1.5). Among the 268 (9%) previously treated patients, 20.9% had isolates resistant to any drug, 6.3% to SM alone, 3.4% to INH alone, 4.1% to SM + INH, and 3.7% to INH + RMP. Foreign birth (OR = 2.3), and human immunodeficiency virus positive status (OR = 4.4) were independently associated with a higher risk of secondary resistance to any drug. CONCLUSION: During the last 30 years there has been no increase in resistance to any drug among previously untreated patients. As expected, secondary resistance was highly associated with foreign birth. MDR-TB remains a rare event in France.     

Minimal inhibitory concentrations of isoniazid, rifampin, ethambutol, and streptomycin against Mycobacterium tuberculosis strains isolated before treatment of patients in Taiwan

Minimal inhibitory concentrations (MICs) of isoniazid (INH), rifampin (RMP), ethambutol (EMB), and streptomycin (SM) for susceptible "wild" M. tuberculosis strains isolated from Taiwanese patients were within the limits previously reported for strains isolated in the United States. The highest agar-determined MICs (in 7H10 and 7H11 agar) corresponded well with the critical concentrations established for these media. The highest MICs found radiometrically in 7H12 broth were significantly lower than the critical concentrations proposed for this medium. On the basis of an evaluation of the highest broth-determined MICs found in this and in the previous study (1), we suggest that the following MICs, when determined radiometrically, should be used as breakpoints to classify the strain as "susceptible": for INH, 0.1 microgram/ml or less; for RMP, 0.5 microgram/ml or less; for EMB, 4.0 micrograms/ml or less; for SM, 2.0 micrograms/ml or less.     

Quality assurance programme for drug susceptibility testing of Mycobacterium tuberculosis in the WHO/IUATLD Supranational Reference Laboratory Network: five rounds of proficiency testing, 1994-1998.

SETTING: Quality assurance for the WHO/IUATLD Global Tuberculosis Drug Resistance Surveillance Programme. OBJECTIVE: To implement an ongoing proficiency-testing programme for drug susceptibility testing (DST) of Mycobacterium tuberculosis within the WHO/IUATLD Supranational Reference Laboratories Network (SRLN). DESIGN: Five culture panels, each consisting of 10 duplicate drug-susceptible and drug-resistant clinical isolates (100 strains) of M. tuberculosis were tested for resistance to streptomycin (SM), isoniazid (INH), rifampicin (RMP) and ethambutol (EMB). DST procedures included the proportion, absolute concentration and resistance ratio methods, as well as the radiometric BACTEC 460 method. RESULTS: The efficiency, sensitivity and specificity of M. tuberculosis DST as well as the intra-laboratory reproducibility showed that the laboratories tested susceptibility to RMP and to INH very reliably, with values ranging from 97% to 99%. The testing of SM and EMB was less dependable, with values ranging from 90% to 95%. The sensitivity of testing of EMB increased from 60% in Round 1 to 98% in Round 5, without a concomitant decrease in specificity. CONCLUSIONS: This study has shown that regular proficiency testing can significantly improve the quality of DST, even in the most sophisticated TB laboratories. Mean DST efficiency levels of 92% for both SM and EMB and 97% and 99% for INH and RMP, respectively, are proposed as reasonable performance goals for the SRL network. Efficiency, consistently lower than these values, would require remedial action. Efficiency levels lower than mean -1 standard error, i.e., 80% for SM and EMB, 89% for INH and 95% for RMP, should always be considered as sub-standard performance for DST.     

The resistance to major antituberculous drugs of Mycobacterium tuberculosis strains isolated from the respiratory system specimens of tuberculosis patients in Duzce, Turkey

Through generally curable, tuberculosis (TB) is becoming increasingly resistant to commonly used antibiotics. Drug-resistant and multidrug-resistant (MDR)-TB is a consequence of monotherapy, insufficient drug therapy and national TB control programs. The present study was designed to reveal the resistance to major antimicrobial drugs (isoniazid [INH], streptomycin [SM], ethambutol [EMB], and rifampicin [RIF]) of Mycobacterium tuberculosis isolated from the respiratory specimens of TB patients in Duzce, Turkey. A total of 62 TB patients (46 male, 16 female; age: 17 - 75 mean: 42 +/- 15.9) were included in the study; 52 (83.8%) were new cases and susceptible to all anti-TB drugs, while 10 (16.2%) were previously treated cases. Antimicrobial susceptibility tests were performed by the proportion method in L?wenstein-Jensen medium. Fifty-two of the 62 (83.8%) isolated M. tuberculosis strains were found to be susceptible to all drugs, and 7 (11.3%), 5 (8%), and 3 (4.8%) were resistant to SM, INH, and RIF, respectively; 3 (4.8%) were MDR. There were no EMB-resistant strains. The results of this study show the presence of drug-resistant and MDR strains of TB at Duzce in the northwest part of Turkey.     

Nationwide study of drug resistance among acid-fast bacilli positive pulmonary tuberculosis cases in Lebanon.

OBJECTIVE: To assess the prevalence of drug resistance among smear-positive sputum specimens from pulmonary tuberculosis (TB) cases in Lebanon. DESIGN: Between July 2002 and April 2004, 224 newly diagnosed TB cases and 21 previously treated TB cases were collected nationwide. Mycobacterium tuberculosis isolates were tested against isoniazid (INH), rifampicin (RMP), streptomycin (SM) and ethambutol (EMB) using the BACTEC-TB system. RESULTS: M. tuberculosis and non-tuberculous mycobacteria (NTM) isolates were recovered from 190 and 15 new cases, respectively, and from 16 and 1 previously treated cases, respectively. Overall drug resistance among new TB vs. previously treated TB cases was 19.5% and 75%, and for single drugs it was INH (12% vs. 63%), RMP (3% vs. 56%), SM (12% vs. 44%) and EMB (3% vs. 44%). The overall rate of multidrug resistance (MDR) was 5.8% (1% vs. 62.5%). The male:female ratio was 1.3:1; most were young adults. CONCLUSION: Relatively moderate single drug resistance and very low MDR rates were found among new TB cases, while among previously treated TB cases very high resistance and MDR resistance rates were detected. Such findings underline the need for ongoing stringent control measures to curb the spread of M. tuberculosis and its deleterious effects.     

Antimicrobial resistance of Mycobacterium tuberculosis isolates from children in Greece, 1994-2004.

OBJECTIVE: To document the prevalence of resistance to various agents of Mycobacterium tuberculosis strains derived from children over 1994-2004. DESIGN: We prospectively studied the susceptibility patterns of 77 strains of M. tuberculosis isolated from the same number of children, which provided 112 positive samples. RESULTS: Most children were boys (53.2%), native Greeks (87%) and aged under 2 years (41.5%). Sample origin was mainly gastric fluid (97 cases, 86.6%). Sixty-one isolates (79.2%) were susceptible to all anti-tuberculosis agents and 16 (20.8%) were resistant to > or =1 drug. Multidrug resistance (MDR), resistance to at least isoniazid (INH) and rifampicin (RMP), was seen in three cases (3.9%). On comparing resistance to INH, RMP and streptomycin (SM) and MDR in children and adults diagnosed with tuberculosis in our centre during the same time period, SM resistance was significantly more common in children (P < 0.001), while a trend for increased resistance to INH was also observed in children (P = 0.079). CONCLUSION: Resistance of M. tuberculosis isolates to the first line anti-tuberculosis drugs appears to be comparable in children and adults in Greece, while SM resistance appears to be more common in children. Tracing the sources of these children is important for the effective surveillance and treatment of tuberculosis.     

The national tuberculosis drug resistance survey in Cambodia, 2000-2001.

SETTING: Cambodia has a high incidence of tuberculosis (TB). Hospital-based DOTS was predominant throughout the country from 1994 to 2002. OBJECTIVES: To determine the prevalence of resistance to four major anti-tuberculosis drugs, isoniazid (INH), rifampicin (RMP), ethambutol (EMB) and streptomycin (SM), among new cases as a baseline before a new National Tuberculosis Programme strategy with decentralised ambulatory DOTS was widely implemented. DESIGN: A cluster sampling of TB diagnostic centres with probability proportional to the number of new cases in a diagnostic centre in 1999 was used. Intake of cases took place from October 2000 to April 2001. RESULTS: From 734 isolates collected, drug susceptibility test results were obtained for 638 new cases. The prevalence of resistance to any of four drugs was 10.1% (95%CI 7.7-13). Resistance to INH was 6.1% (95%CI 4.3-8.4) and resistance to RMP 0.6% (95%CI 0.2-1.6). No multidrug-resistant (MDR) case was found among the new cases (95%CI 0.0-0.6). Three of 96 previously treated cases had MDR (3.1%, 95%CI 1.0-9.0). CONCLUSION: The first survey indicates that the current prevalence of MDR is low. It is necessary to track resistance trends when restructuring a DOTS-based programme.     

Low serum concentrations of anti-tuberculosis drugs and determinants of their serum levels.

SETTING: Low serum concentrations of anti-tuberculosis drugs have occasionally been associated with treatment failure. OBJECTIVE: To determine the prevalence of low serum concentrations of anti-tuberculosis drugs and to identify the determinants of drug concentrations. DESIGN: Venous blood was obtained 2 h after drug ingestion, and serum levels of isoniazid (INH), rifampicin (RMP), ethambutol (EMB), pyrazinamide (PZA), acetyl INH and 25-desacetyl RMP were analysed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Patients with human immunodeficiency virus co-infection and gastrointestinal disease or diarrhoea were excluded. RESULTS: Among 69 enrolled TB patients, the prevalence of a low 2 h serum concentration of at least one anti-tuberculosis drug was 46.4%. Prevalences of a low concentration of INH, RMP, EMB or PZA were 15.2%, 23.5%, 22.4% and 4.5%, respectively. By multivariate linear regression analysis, the serum concentrations of INH, RMP and PZA were positively associated with dose per kg of body weight (P < 0.05). Moreover, INH concentration was associated with acetyl INH/INH ratio (beta = -8.588, P < 0.001) and EMB concentration was associated with calculated creatinine clearance (beta = -0.025, P < 0.001). CONCLUSION: Low concentrations of anti-tuberculosis drugs are common, and although the clinical significance of low concentrations remains uncertain, it may be necessary to optimise drug doses by therapeutic drug monitoring, especially in patients with an inadequate clinical response to chemotherapy.     

194例住院结核病人的耐药分析

目的对194例住院结核病患者的痰标本获得的结核杆菌做耐药性检测,为临床制定抗痨方案提供一定的参考依据。方法对2007年至2010年的194例患者痰培养结核菌阳性患者的痰标本,分别做抗结核一线药物：异烟肼（INH）,利福平（RFP,）,乙胺丁醇（EMB）,链霉素（SM）的药敏试验,了解各药在初治和复治患者中的耐药情况。结果118例初治患者和76例复治患者对INH的耐药例数分别15和39例,耐药率分别15．25％和51．31％;对RFP的耐药例数分别lO和29例,耐药率分别8．47％和38．16％;对EMB的耐药例数分别8和20例,耐药率分别6．78％和26．32％;对SM的耐药例数分别6和28例,耐药率分别5．08％和36．84％。结论初治和复治患者均对INH的耐药率最高,其次为RFP及EMB,SM。复治患者的耐药率明显增高。耐两种或以上结核药的例数明显高于初治患者。     

难治性肺结核分支杆菌耐药性和药物依赖性的实验观察

目的探讨难治性肺结核分支杆菌耐药性和药物依赖性。方法对难冶性肺结核病人痰标本培养分离的分枝杆菌65株（例），进行低浓度、高浓度抗结核药物的耐药性和依赖性实验观察。结果65株分枝杆菌对SM、INH和RFP三种药物均耐药，EMB耐药率也较高（75．4％和69．2％）。分枝杆菌对sM依赖率分别为38．5％，INH为26．2％，RFP为18．5％，EMB为10．8％；同时依赖两种药物者为15．4％，三种药物为12．3％，四种药物为4．6％。结论难治性肺结核具有很高的耐药性和较高的依赖性。