High rate of rifampicin resistance of Mycobacterium tuberculosis in the Taif region of Saudi Arabia.

This retrospective study was undertaken to determine the prevalence and pattern of resistance to antituberculosis drugs among patients with sputum-proven pulmonary tuberculosis who were seen in Taif Chest Hospital over 24 months (between June 1986 and May 1988). The overall prevalence was 22.6% and the majority (53%) were resistant to two drugs. Resistance to streptomycin was most frequent (16%) followed by rifampicin (15%). Resistance to isoniazid was surprisingly low (6.5%). 23.3% of the resistant group had previously received antituberculosis drugs as against 15.4% in the sensitive group. There was a significant association between previous therapy and resistance to antituberculosis drugs. Recommendations to reduce the problem of resistance and to improve compliance are discussed.     

Resistance to antituberculosis drugs in Japan

Setting: Five years after the last survey of drug-resistant tuberculosis in Japan, a serious new phenomenon has gradually begun to appear. A nationwide survey was conducted by the Tuberculosis Research Committee.Objective: To determine resistance patterns to five anti-tuberculosis drugs and risk factors.Design: Cultures were obtained from patients hospitalized at 38 hospitals in various districts of Japan throughout 6 months, from 1 June through 30 November in 1992. Drug susceptibility testing was carried out in the national reference laboratory.Results and Conclusion: Resistance to one or more drugs was found in 5.6% of new cases and 27.8% of recurrent cases (P < 0.001). About 88% of drug resistant isolates from the new cases were resistant to one drug, while 50.8% of the drug resistant isolates from the recurrent cases had resistance to two or more drugs (P < 0.001). Resistance rates to both isoniazid and rifampin in new cases was very low (only 0.14%). Primary drug resistance rates were higher in age groups less than 60 years old, compared to those of 60 years and over (P = 0.05). Compared with the rate in Japanese patients, foreign-born individuals had a higher resistance rate in the recurrent cases (P = 0.034). This survey indicated a similar trend in resistance rates to five antituberculosis drugs to those of the last survey in 1987.     

Medical therapy of Mycobacterium avium-intracellulare pulmonary disease

Fifty-four patients meeting strict criteria for invasive pulmonary disease caused by Mycobacterium avium-intracellulare complex have been treated and followed at San Antonio State Chest Hospital during the past 15 yr. Chemotherapy with standard antituberculosis drugs was successful in effecting sputum conversion in 32 (59%) of the 54 patients. Regimens containing 2 drugs were successful in only 1 of 10 patients. If 3 or more drugs were given, 91% of those with moderately advanced cavitary disease and 64% of those with far advanced disease responded. There was no correlation between sputum conversion and use of a drug to which the organism exhibited susceptibility in vitro. No particular drug or combination of drugs was uniquely effective.     

Antituberculosis drug resistance and anonymous HIV surveillance in tuberculosis patients in Botswana, 2002

Two surveys undertaken in Botswana in the 1990s have recorded low rates of antituberculosis drug resistance, despite a three-fold rise in tuberculosis since 1989. We undertook a third survey to determine both trends since 1995 and HIV prevalence in tuberculosis patients in Botswana. Sputum specimens were obtained from patients nationwide in 2002 who also underwent anonymous, rapid HIV testing by use of Oraquick. Of 2200 sputum smear-positive patients and 219 previously treated patients with suspected recurrent tuberculosis, 1457 (60%) were infected with HIV. Resistance to at least one drug in new patients rose from 16 (3.7%) isolates in 1995 to 123 (10.4%; p<0.0001) in 2002. Interventions for tuberculosis control are urgently needed in Botswana to prevent further emergence of drug resistance.     

耐多药空洞肺结核的介入治疗

目的　探讨耐多药空洞肺结核介入治疗的意义。方法 采用 36例临床培养的耐药菌株作耐药结核菌抑制试验、临床对照观察的方法。 1 80例耐多药空洞肺结核住院患者随机分成两组,均用 3DLOZA/1 8DLOZ化疗方案治疗,治疗组 86例配合抗结核药物凝胶介入治疗并完成疗程。结果 提高抗结核药物浓度,可有效控制耐药结核菌生长,而所需浓度远远低于药物凝胶的含药浓度。临床观察治疗组比对照组痰菌阴转率高 (88.4%),痰菌阴转速度也快,空洞闭合率高 (43.0%),空洞闭合速度快,疗效较好。单发空洞、干酪空洞的疗效比多发空洞、纤维空洞的疗效较好。未发现与介入药物凝胶有关的不良反应。结论 经纤支镜引导灌注抗结核药物凝胶,是治疗耐多药空洞肺结核的有效方法,其有净化空洞,促使痰菌转阴,空洞闭合的作用。并且有安全无创,无明显不良反应,并发症少的优点,值得临床推广使用。     

Tuberculosis in Korea. The relationship between prior therapy and drug resistance

A review of 121 culture-positive cases of pulmonary tuberculosis from 1979 to 1984, including both Korean and American patients, at the major US military hospital in Korea indicated that most antituberculosis drug resistance occurred in patients with a history of previous antituberculosis therapy. The 98 patients without previous therapy who were not household contacts of a known resistant case had low rates of drug resistance (7 percent to isoniazid, 5 percent to streptomycin, 2 percent to p-aminosalicylic acid, and none to rifampin or ethambutol). All were sensitive to at least two of the drugs in the commonly prescribed regimen of isoniazid, rifampin, and ethambutol. In contrast, both patients who were household contacts of a known resistant case and 11 (52 percent) of the 21 patients with previous therapy had drug-resistant organisms. Our data support the use of isoniazid as preventive therapy for those who develop tuberculin reactivity while in Korea, in the absence of close contact with a known resistant case. Our data also suggest that the regimen of isoniazid, rifampin, and ethambutol is appropriate initial therapy for active disease acquired in Korea, provided that an adequate history excluding these risk factors can be obtained.     

Surveillance of antituberculosis drug resistance in Switzerland 1995-1997: the central link.

The purpose of the present paper is to investigate the usefulness of routine notification of antituberculosis drug susceptibilities. In Switzerland, laboratories have to report susceptibilities to isoniazid, rifampicin, ethambutol, and pyrazinamide to the Federal Office of Public Health. All clinical and laboratory information on every single tuberculosis case is routinely linked. Proportions of drug resistance were calculated and logistic regression was applied to evaluate the role of potential risk factors. Eighty percent (1056) of all culture-positive tuberculosis cases reported between October 1995 and December 1997 were analysed. The strains of 66 (6.3%) patients had resistances to at least one drug. Risk factors identified were previous antituberculosis treatment (adjusted odds ratio 7.3, 95% confidence interval 3.9-13.6), male sex (1.4, 1.1-2.0), and age <65 yrs (1.5, 1.0-2.3). Fourteen cases (1.3%), 13 of them foreign-born, were resistant to at least isoniazid and rifampicin. Reporting of drug susceptibilities allows routine assessment of the proportion of drug resistant tuberculosis and populations at risk. This proportion was found to be small in Switzerland. Risk factors were previous treatment for tuberculosis, male sex, and age <65 yrs. Resistance to at least isoniazid and rifampicin was predominantly found in foreign-born patients.     

Resistance to antituberculosis drugs in Riyadh, Saudi Arabia

The prevalence of resistance to antituberculosis drugs in Riyadh was found to be 21.3%, while the rate of primary drug resistance was 11.5%. Resistance to isoniazid was the most common (19.4%) followed by rifampicin and streptomycin. The prevalence of primary and acquired rifampicin resistance was 3 and 33.7% respectively. The majority of isolates from patients with acquired resistance to rifampicin were resistant also to isoniazid.     

The influence of epidemiologic factors on drug resistance rates in tuberculosis

We evaluated the relationship between drug resistance rates and various epidemiologic factors in 376 hospitalized adults with culture-proved tuberculosis, studying 356 cases prospectively, 20 retrospectively. The patient was interviewed in 332 cases. Patients born in the United States, Canada, or Europe were considered to belong to Group I. Group II consisted of patients born in Latin America, Asia, or Africa and was subdivided into II(a), immigrants living in the United States for more than 10 yr, and II(b), those living here less than 10 yr. Of the 70 patients who had received antituberculosis therapy in the past, resistance rates in Group II (n = 31) to isoniazid (INH), streptomycin (SM), and rifampin (RIF) were extremely high: 39, 29, and 19%, respectively. Nineteen percent showed resistance to both INH and RIF. In Group I (n = 39), INH, SM, and RIF resistance rates were 8, 5, and 8%, respectively. Of 283 patients who gave no history of prior antituberculosis therapy, those in Groups I and II(a) (n = 170) rarely showed INH or RIF resistance. Among recent immigrants from Latin America or Asia [Group II(b), n = 113], 11.5% showed INH or RIF resistance and 14% harbored organisms resistant to SM. Thus, the 3 variables that are most helpful in estimating the likelihood of drug resistance are a history of prior antituberculosis therapy, country of origin, and duration of residence in the United States.     

Drug-resistant tuberculosis in Yangon, Myanmar

The extent of drug resistant tuberculosis (TB) in the capital city of Myanmar, Yangon has not yet been reported. This study aimed to determine the proportion and pattern of drug resistance to first-line anti-TB drugs, among Mycobacterium tuberculosis complex isolates from sputum smear positive TB patients who attended National TB Programme Yangon centres in April-August and October-December 2002. Drug susceptibility was determined by the Mycobacteria Growth Indicator Tube manual system (Becton Dickinson, MD, USA). Of the 567 patients, sputum specimens from 447 (79%) had a positive culture. Of these, 357 isolates (80%) had a susceptibility test result. Isolates from 76 of 259 (29.3%) new patients and from 45 of 98 (45.9%) previously treated patients were resistant to at least 1 of the anti-TB drugs. Resistance to isoniazid (INH) (22.0% vs 40.8%: new vs previously treated patients) and to > or =2 drugs (17.8% vs 29.6%: new vs previously treated patients) was common. Multidrug- resistant TB (MDR-TB) among new and previously treated patients was 4.2% and 18.4%, respectively. INH-resistant (adjusted OR: 2.0, 95% CI 1.1-3.6) and MDR-TB (adjusted OR: 3.4, 95% CI 1.4-8.3) cases were more likely to have taken anti-TB drugs > or =1 month previously. Collectively, prevalence of MDR-TB and TB resistance to > or =2 drugs are not rare in Yangon.     

Drug resistance of Mycobacterium tuberculosis isolated from treated patients in Pakistan

An investigation was carried out to establish the extent of drug resistance among treated patients. A sample population of patients living in Lahore, Pakistan, which is a high prevalence area for tuberculosis, was studied. The total of 256 culture-positive cases in this study were divided into three groups according to the length of previous treatment. There was no significant difference in the antituberculosis treatment regimens or the drug resistance pattern among the three groups. All the patients had had at least three drugs for more than 6 months, and streptomycin and isoniazid were always included in the regimen. About one-third of the patients showed resistance to one or more drug, with the highest resistance being to streptomycin and INH. Resistance to rifampicin, which was introduced fairly recently in this area, was a little more than 5%, which is an increase from the last report.     

上海市首次复治肺结核患者的耐药性分析

目的 了解上海市首次复治肺结核患者的耐药情况,为制定复治化疗方案提供科学依据.方法 回顾性分析2002年1月至2004年12月上海市疾病预防控制中心登记的痰结核杆菌培养阳性的上海市首次复治肺结核病例,全部培养阳性菌株进行菌种鉴定及5种抗结核药物（异烟肼、利福平、链霉素、乙胺丁醇、对氨水杨酸钠）的耐药性测试.结果 首次复治肺结核患者的总耐药率为39.6%,男、女患者的耐药率分别为38.5%和44.4%,青年组、中年组和老年组的耐药率分别为50.0%、41.6%和34.6%.标准初治失败组和标准初治复发组的总耐药率（70.0%和47.5%）、耐药≥3种的发生率（70.0%和18.3%）均显著高于非标准初治复发组（28.2%和6.4%）.标准初治失败组的耐多药率（70.0%）显著高于标准初治复发组（16.7%）和非标准初治复发组（7.3%）.非标准初治复发组中初治用药1～5个月者的耐药率（13.0%）显著低于用药≥12个月者（55.0%）,初治用药≤2种的耐药率（24.4%）略低于用药≥3种者（30.8%）.结论 不同复治类型的首次复治肺结核病例的耐药率因用药史不同而各异,提示现行的标准复治化疗方案对其中部分患者可能无效.     

Anti-tuberculosis drug resistance in two clinics in Ecuador.

SETTING: Two private hospitals, one in the capital city and one in the eastern rainforest of Ecuador. OBJECTIVE: To document the prevalence of anti-tuberculosis drug resistance in Ecuador in patients who had not received prior treatment and in those who had. DESIGN: Drug resistance was determined using the proportion method with solid medium on the first isolate of Mycobacterium tuberculosis from all patients who attended the two hospitals between 1989 and 1996. Documentation of prior treatment was obtained by patient interview. RESULTS: Resistance was identified in 39 of 161 patients (24%) who had had no prior treatment. Resistance was 14.2% to isoniazid, 11.8% to rifampin and 8.7% to both (multidrug-resistant tuberculosis). Among 60 patients who had received prior treatment, 18 (30%) were resistant to isoniazid, and 14 (23.3%) to rifampin, while multidrug resistance was seen in 10 (16.7%). CONCLUSION: In these populations the prevalence of resistance both in patients with no prior treatment and in patients with prior treatment was ominously high. The initial treatment regimens and patient management in Ecuador should be re-evaluated in an effort to prevent further increases in drug resistance.     

广东省肇庆地区结核病初始耐药发展趋势

目的　本文对肇庆地区1 996～2 0 0 4年新发初治菌阳肺结核病人1 2 4 2例的初始耐药情况进行分析。结果　发现初始耐药率由2 8.4%下降至1 9.4%。耐多药率有上升趋势,由8.9% ,上升为1 2 .7%。结论　提示初治病人需开展药敏试验,以制定最佳的化疗方案,避免耐多药菌的产生和传播。     

Prevalence of resistance to anti-tuberculosis drugs: results of the 1998/99 national survey in Italy.

OBJECTIVE: To determine the prevalence of resistance to the main anti-tuberculosis drugs in newly and previously treated tuberculosis patients in Italy and to evaluate the contribution of foreign-born and human immunodeficiency virus (HIV) positive cases to drug resistance. METHODS: Methods and definitions were derived from the WHO/IUATLD Global Project on Anti-tuberculosis Drug Resistance Surveillance. Univariate and multivariate analysis was used to study prevalence rates of drug resistance in risk groups. RESULTS: In a national survey in Italy, 810 initial isolates of Mycobacterium tuberculosis (683 from new cases, 115 from retreatment cases and 12 from patients whose treatment history was unknown/dubious) were analysed. Low prevalence of drug and multidrug resistance was found in the new cases (isoniazid 2.9%; rifampicin 0.8%; multidrug resistance 1.2%; any drug resistance 12.3%). The prevalence of resistance to isoniazid and rifampicin was significantly higher in immigrants and HIV-positive subjects, respectively. A high prevalence of drug resistance was found in cases with previous treatment failure or default (isoniazid 5.2%; rifampicin 4.3%; multidrug resistance 36.5%; any drug resistance 61.7%). RECOMMENDATIONS: Special efforts are necessary to monitor trends in drug resistance and to ensure favourable treatment outcomes among immigrants and HIV-positive tuberculosis cases.     

The nationwide tuberculosis drug resistance survey in Mongolia, 1999.

SETTING: Mongolia, a country in the Western Pacific Region burdened with many cases of tuberculosis, with rapid expansion of DOTS over the last several years. OBJECTIVE: To determine the prevalence of resistance to major anti-tuberculosis drugs among tuberculosis patients who have never been treated previously. DESIGN: Sputum specimens were collected from all smear-positive tuberculosis patients identified from 1 November 1998 to 1 May 1999. RESULTS: Resistance to any of the four major drugs (streptomycin, isoniazid, rifampicin, and ethambutol) was as high as 28.9% (95%CI 24.7-33.5), primarily due to high streptomycin resistance of 24.2% (95%CI 20.3-28.6). Isoniazid resistance was also high, at 15.3% (95%CI 12.1-19.1). Resistance levels to ethambutol and rifampicin were relatively low, at 1.7% (95%CI 0.8-3.5) and 1.2% (95%CI 0.5-2.9), presumably because these drugs were only recently introduced into Mongolia. Multidrug resistance was also rare, at 1.0% (95%CI 0.1-1.8). Drug resistance rates were higher in middle-aged patients than in younger and older age groups combined (P = 0.006). Males tended to have higher resistance than females, although this was of statistically marginal significance (P = 0.08). No significant regional differences in drug resistance were found. CONCLUSION: While multidrug resistance was rare, isoniazid resistance was very common, which necessitates closer monitoring of the treatment outcomes of individual patients as well as long-term follow-up for drug resistance on a nationwide scale.     

The epidemiologic patterns of drug-resistant Mycobacterium tuberculosis infections: a community-based study

A community-based study of tuberculosis in Santa Clara County, California was conducted in order to identify community-specific determinants of drug-resistant Mycobacterium tuberculosis infections. From January 1984 through December 1986, 517 verified cases of tuberculosis were reported from the county. Drug susceptibility test results to isoniazid, streptomycin, ethambutol, and rifampin were available for 256 of the 517 cases. The frequency of resistance of M. tuberculosis isolates to one or more drugs was 27% for all cases and 25% for those who had had no previous antituberculosis treatment. Isolates from Asian immigrants had the highest frequencies of resistance (33 to 45%), and the Southeast Asian immigrants had a drug-resistant tuberculosis case rate greater than 30/100,000 population per year. In patients who had cavitary lung disease and who had a previous history of tuberculosis, drug-resistant tuberculosis was 3.5 times as likely to occur than in persons who had neither of these characteristics (p less than 0.001). For such patients, the positive predictive value of isolating resistant M. tuberculosis approached 90%. We believe these community-based findings will guide clinical and public health interventions specifically appropriate for the community.     

Antituberculosis drug resistance and associated risk factors in the European section of Turkey

BACKGROUND: We carried out this study in order to establish the prevalence of antituberculosis drug resistance in Mycobacterium tuberculosis strains and to determine risk factors for the development of resistance in Trakya region of Turkey. METHODS: Pattern of drug resistance in 214 M. tuberculosis isolates from patients with tuberculosis treated at the regional tuberculosis dispensaries were included in the study. RESULTS: Isolates of 105 (49.1%) were resistant to only one drug, and 62 (29.0%) were resistant to more than one drug. The total resistance rates to streptomycin, isoniazid, rifampicin, ethambutol and isoniazid + rifampicin were 29.0%, 27.1%, 21.5%, 10.3% and 11.6%, respectively. The secondary resistance rates in all drugs and combinations were higher than primary resistance rates (p<0.001). Step wise logistic regression revealed that (i) non-compliance with treatment increases the chances of development of resistance by 15 times [p<0.00001, 95% confidence intervals (95% CI) : 4.16 to 56.70], and (ii) a regimen of inadequate treatment increases the chance of development of drug resistance by 10.5 times (p<0.01, 95% CI=2.66 to 49.80). CONCLUSIONS: We propose that specially trained physicians should institute antituberculosis therapy and medication should be practiced under direct observation in this region.     

Study of drug resistance in previously treated tuberculosis patients in Gujarat, India.

SETTING: Department of Tuberculosis and Chest Diseases and State Tuberculosis Diagnosis and Training Centre (STDTC), a DOTS centre in Ahmedabad, Gujarat State, India. The study was carried out by retrospectively reviewing patient data between January 2000 and August 2001. OBJECTIVE: To evaluate the pattern of drug resistance among previously treated tuberculosis patients who remained symptomatic or smear-positive despite receiving anti-tuberculosis drugs under DOTS for a minimum of 5 months. DESIGN: A total of 1472 pulmonary tuberculosis patients who had taken anti-tuberculosis treatment were evaluated retrospectively with respect to their drug resistance pattern by sputum culture for acid-fast bacilli (AFB) and sensitivity testing with isoniazid, rifampicin, streptomycin and ethambutol (E). RESULT: Of the 1472 patients evaluated, 804 (54.6%) were treatment failure cases and 668 (45.4%) were relapse cases; 822 patients (373 failure and 449 relapse) were culture-positive. Of these 822 patients, 482 (58.64%, 261 failure and 221 relapse) were resistant to one or more drugs. Resistance to one drug was observed in 86 patients (10.46%), to two drugs in 149 (18.13%), to three drugs in 122 (14.84%) and to four drugs in 125 (15.21%). Single drug resistance was most commonly seen with isoniazid (62 patients, 7.5%), followed by streptomycin (12 patients, 1.4%), rifampicin (eight patients, 0.97%) and ethambutol (four patients, 0.4%). Resistance to isoniazid plus rifampicin alone was seen in 76 patients (9.2%). CONCLUSION: Drug resistance is a major problem in the treatment of pulmonary tuberculosis. Detection of drug resistance patterns and treatment with second-line anti-tuberculosis drugs in appropriate regimens are necessary in the treatment of failure and relapse cases in order to reduce the emergence of multidrug-resistant tuberculosis.     

High levels of resistance to second-line anti-tuberculosis drugs among prisoners with pulmonary tuberculosis in Georgia.

SETTING: Penitentiary system of Georgia. OBJECTIVE: To determine the prevalence of resistance to second-line drugs among prisoners with pulmonary tuberculosis (PTB). DESIGN: Retrospective evaluation of resistance to second-line drugs in tuberculosis (TB) patients treated from 2001 to 2003. RESULTS: The overall observed prevalence of multidrug-resistant TB (MDR-TB) was 14.4% (39/270). The lowest resistance was found for ofloxacin (OFX), which was 2.2% (6/270) overall and 5.1% (2/39) among MDR patients. Isolates from four non-MDR patients who had never received anti-tuberculosis treatment were found to be resistant to OFX. Resistance to kanamycin and capreomycin occurred simultaneously only among MDR patients and was observed in 17/39 cases (43.6%). High rates of resistance to > or =2 second-line drugs (18/39, 46.2%) and > or =3 second-line drugs (10/39, 25.6%) were observed among all MDR-TB patients, reaching respectively 59.3% and 29.6% among previously treated MDR-TB cases. Only one patient was found to be resistant to four second-line drugs. No extensively drug-resistant TB (XDR-TB) according to the latest definition was detected. CONCLUSION: Our findings reveal a serious threat to the TB control efforts in the study population.