Pulmonary tuberculosis among political asylum seekers screened at Heathrow Airport, London, 1995-9

BACKGROUND: Over 50% of cases of tuberculosis (TB) in the UK occur in people born overseas, and new entrants to the country are screened for TB. A study was undertaken to determine the prevalence and disease characteristics of pulmonary TB in new entrants to the UK seeking political asylum. METHODS: A retrospective analysis of the results of screening 53 911 political asylum seekers arriving at Heathrow Airport between 1995 and 1999 was performed by studying Airport Health Control Unit records and hospital medical records. Outcome measures were chest radiograph abnormalities, sputum smear, culture, and drug resistance data for Mycobacterium tuberculosis. RESULTS: The overall prevalence of active TB in political asylum seekers was 241 per 100 000. There were large variations in prevalences of TB between asylum seekers from different regions, with low rates from the Middle East and high rates from the Indian subcontinent and sub-Saharan Africa. The frequency of drug resistance was high; 22.6% of culture positive cases were isoniazid resistant, 7.5% were multidrug resistant (resistant to both isoniazid and rifampicin), and 4% of cases diagnosed with active disease had multidrug resistant TB. CONCLUSIONS: The prevalence rate of TB in political asylum seekers entering the UK through Heathrow Airport is high and more M tuberculosis isolates from asylum seekers are drug resistant than in the UK population. Extrapolating these figures, it is estimated that 101 political asylum seekers with active pulmonary TB enter the UK every year, of whom about 25 would have smear positive disease.     

Characteristics of patients with drug resistant and drug sensitive tuberculosis in East London between 1984 and 1992.

BACKGROUND--The aim of this study was to investigate retrospectively factors associated with drug resistant tuberculosis at the London Chest Hospital. METHODS--The microbiology results for patients with tuberculosis at the hospital for the period 1984-92 were reviewed, together with case notes and chest radiographs of all patients with drug resistant tuberculosis and of 101 patients with drug sensitive tuberculosis notified during the same period as a control group. RESULTS--Culture positive pulmonary tuberculosis occurred in 292 patients. Drug resistant strains were isolated from 20 patients (6.8%). Ten of the 292 (3.4%) had strains resistant to a single drug and nine (3.1%) had resistance to more than one first line drug. One patient had strains resistant to isoniazid and capreomycin. Strains resistant to more than one drug were all resistant to isoniazid and rifampicin. In five patients these strains were also resistant to pyrazinamide and in two they were resistant to streptomycin. Single drug resistant strains were resistant to isoniazid (nine patients) or streptomycin (one patient). Among the risk factors studied previous treatment for tuberculosis was the most significant association with drug resistant tuberculosis (7/9) for patients with resistance to more than one drug; 5/11 for single drug resistance compared with 6/101 patients in the drug sensitive group (odds ratio 22.8). Other risk factors were bilateral disease at presentation (odds ratio 8.5), and disease at a young age (odds ratio 1.03). CONCLUSIONS--Previous treatment for tuberculosis and bilateral disease at presentation were found to be more commonly associated with cases of drug resistant than with drug sensitive tuberculosis.     

获得性免疫缺陷综合征合并结核病患者对结核分枝杆菌二线药物耐药特征分析

目的了解获得性免疫缺陷综合征（AIDS）合并结核病（TB）患者感染结核分枝杆菌二线药物耐药特点。 方法选取2010年4月至2012年10月于北京大学地坛医院教学医院住院的艾滋病合并结核病患者标本,由中国疾病预防控制中心培养鉴定。进行4种一线药物（异烟肼、利福平、链霉素、乙胺丁醇）和4种二线药物（卷曲霉素、卡那霉素、氧氟沙星、乙硫异烟胺）药敏试验监测,并对所有菌株在gyrA、gyrB、rrs、tlya、eis和ethA基因位点进行DNA测序以检测基因多态性。 结果经培养鉴定共得到31株结核分枝杆菌,其中12株耐卷曲霉素,8株耐氧氟沙星,4株耐卡那霉素,5株耐乙硫异烟胺,耐药率分别为38.71%、25.81%、12.90%和16.13%。7株菌为耐多药菌株,1株菌为广泛耐药菌株,耐药率分别为22.58%和3.23%。耐药菌株最常见的突变位点是rrs₁₄₀₁,gyrA₉₄和gyrA₉₀。一线敏感菌株中氧氟沙星的耐药率显著低于一线耐药菌株（P = 0.012）。性别与结核分枝杆菌耐药差异无统计学意义（P = 0.533）,年龄> 40岁组的氧氟沙星耐药率低于其余两组（P = 0.043）。结核初治组与复治组患者二线耐药率、CD4水平差异无统计学意义（P = 0.333、0.307）。 结论AIDS合并TB患者存在二线抗结核药物原发耐药,其中卷曲霉素耐药率最高,其次是氧氟沙星。     

Mycobacterial infection in HIV seropositive and seronegative populations, 1987-93.

BACKGROUND--Although the causes of the worldwide resurgence of tuberculosis are multifactorial, the HIV epidemic is believed to have had a central role. Control is further threatened by the emergence of multidrug-resistant tuberculosis. METHODS--A retrospective evaluation was undertaken of trends in pulmonary and extrapulmonary culture positive mycobacterial pathology, and the prevalence of drug-resistant tuberculosis in both HIV seropositive and, presumptively, HIV seronegative patients receiving their clinical care at St Mary's Hospital, London. Five hundred and thirty eight patients (188 of whom were known to be HIV seropositive) with positive mycobacterial isolates between January 1987 and March 1993 were identified from laboratory records. These were cross referenced with drug surveillance records. RESULTS--Overall, between 1987 and 1992 there was a progressive 3.5 fold increase in positive mycobacterial isolates and a 2.5 fold increase in patients with proven mycobacterial infection. This increase was greater within the HIV seropositive population. A total of 663 positive mycobacterial isolates was evaluated; the major pathogen identified was Mycobacterium tuberculosis (379 isolates, 57%). Three hundred and fourteen patients were diagnosed as having M tuberculosis, 49 of whom were HIV seropositive. M tuberculosis was predominantly isolated from the lung. Of 358 positive cultures for M tuberculosis (68 HIV seropositive, 290 presumptively HIV seronegative), only 27 isolates (7.6%), almost exclusively derived from presumed HIV seronegative patients, were resistant to either isoniazid, rifampicin, or both drugs together. No increases in drug-resistant isolates were observed over this period. CONCLUSIONS--There has been a considerable increase in the incidence of tuberculosis in both HIV seronegative and seropositive populations during the study period. The emergence of drug-resistant tuberculosis was not observed.     

Drug-resistant pulmonary tuberculosis in a cohort of southern African goldminers with a high prevalence of HIV infection.

OBJECTIVES: To determine rates of drug resistance to Mycobacterium tuberculosis and associated risk factors, including HIV infection. DESIGN: Prospective cohort study of patients with pulmonary tuberculosis. SETTING: The study population comprised 28,522 men working on four goldmines in Westonaria, Gauteng. Health care is provided at a 240-bed mine hospital, Gold Fields West Hospital, and its primary health care facilities. SUBJECTS: All 425 patients with culture-positive pulmonary tuberculosis identified in 1995. OUTCOME MEASURES: Tuberculosis drug resistance on enrollment and after 6 months' treatment. RESULTS: There were 292 cases of new tuberculosis, 77 of recurrent disease and 56 prevalent cases in treatment failure. Two hundred and seven patients (48.7%) were HIV infected. Primary resistance to one or more drugs (9%) was similar to the 11% found in a previous study done on goldminers in 1989. Primary multidrug resistance (0.3%) was also similar (0.8%). Acquired multidrug resistance was 18.1%: 6.5% for recurrent disease and 33.9% in treatment failure cases. Neither HIV infection nor the degree of immunosuppression as assessed by CD4+ lymphocyte counts was associated with drug resistance at the start or end of treatment. New patterns of drug resistance were present in 9 of 52 patients in treatment failure at 6 months, 1 of whom was HIV-infected. CONCLUSION: Primary and acquired drug resistance rates are stable in this population and are not affected by the high prevalence of HIV infection.     

Pre‐Multidrug‐Resistant Mycobacterium tuberculosis Infection Causing Fatal Enteric Disease in a Dog from a Family with History of Human Tuberculosis

This report describes a fatal case of a pet dog with major enteric signs owned by a family that has experienced cases of pulmonary tuberculosis (TB) in the household. Clinical and epidemiological aspects, imaging data, microbiological, haematological and histopathological examinations were assessed to diagnosis of disease. gyrB‐RFLP, spoligotyping and MIRU‐VNTR allowed molecular detection of M. tuberculosis strain from S family. The resazurin microtiter assay indicated that all isolates were resistant to isoniazid, ethambutol, ciprofloxacin, ofloxacin, streptomycin and amikacin. The public health concerns related to canine tuberculosis and risk of the dissemination by pets of M. tuberculosis pre‐multidrug‐resistant (PMD) to isoniazid, ethambutol and other first‐line drugs used in human therapy of TB are discussed. We believe this to be the first report of PMD M. tuberculosis infection in a dog presenting mainly enteric manifestation, confirmed as S lineage by molecular methods, owned by a family in which TB has spread in the household for generations.     

Rates of drug resistance and risk factor analysis in civilian and prison patients with tuberculosis in Samara Region, Russia

BACKGROUND: Tuberculosis (TB) and HIV rates continue to escalate in Russia, but true rates for drug resistance, especially multidrug resistant tuberculosis (MDR TB), are unknown. A study was conducted with the aims of identifying first line drug resistance, both in the civilian and prison sectors, for new and previously treated cases; and risk factors for the development of drug resistance. METHODS: A cross sectional survey was undertaken of 600 patients (309 civilians, 291 prisoners) with bacteriologically confirmed pulmonary TB over a 1 year period during 2001-2 in Samara Oblast, Russia. RESULTS: The prevalence of isoniazid, rifampicin, streptomycin, ethambutol and pyrazinamide resistance in new TB cases (civilian and prison patients) was 38.0%, 25.2%, 34.6%, 14.7%, and 7.2%, respectively. The prevalence of MDR TB was 22.7%, 19.8%, and 37.3% in all new cases, new civilian cases, and new prison cases, respectively, with an overall prevalence of 45.5% and 55.3% in previously treated cases. Factors associated with resistance included previous TB treatment for more than 4 weeks, smoking (for isoniazid resistance), the presence of cavitations on the chest radiograph, and imprisonment. HIV was not associated with resistance in all patients. The rates of resistance were significantly higher in prisoners, with rate ratios (RR) of 1.9 (95% CI 1.1 to 3.2) for MDR TB, 1.9 (95% CI 1.1 to 3.2) for rifampicin, and 1.6 (95% CI 1.0 to 2.6) for isoniazid. CONCLUSIONS: Rates of first line drug resistance are high, particularly in prisoners and previously treated cases. TB control programmes should initially focus on standardised treatment to maximise cure, combined with measures to reduce institutional TB spread (particularly in prisons) coupled with early diagnosis of MDR TB to reduce the spread and development of resistance.     

结核分枝杆菌快速培养和常规药敏试验在脊柱结核治疗中的应用

目的 探讨BACT/ALERT 3D系统快速培养和绝对浓度法药敏试验对指导脊柱结核个体化化疗的应用价值,分析研究脊柱结核耐药情况.方法 根据临床表现、影像学表现、病理检查,50例患者诊断为脊柱结核,并接受手术治疗.收集术中所取脓液、干酪样组织.低温避光保存,8 h内送检,常规处理后接种液体培养基,使用BACT/ALERT 3D系统进行分枝杆菌快速培养.培养阳性者接种PNB和TCH培养基进行菌种鉴定,并将细菌接种至含药改良罗氏培养基,按绝对浓度法进行11种常用一线和二线抗结核药物药敏试验.结果 50例标本培养阳性21例(42%),人型结核杆菌19例,牛型结核杆菌2例.结核杆菌培养和药敏试验平均耗时41 d(28～58 d).其中耐药11例(52.4%),异烟肼耐药4例(19.0%),利福平和乙胺丁醇各1例(4.8%),链霉素3例(14.3%),力克肺疾2例(9.5%),左氧氟沙星8例(38.1%).结论 结核分枝杆菌快速培养和常规药敏试验准确度高,费用低,可检测常用一线和二线药物的敏感性,适用于指导脊柱结核个体化化疗方案的制定.异烟肼、利福平、吡嗪酰胺、乙胺丁醇或(和)链霉素联合用药方案对多数初治脊柱结核患者有效.     

Drug resistance patterns in 111 cases of drug-resistant tuberculosis spine

Purpose

We report the largest study conducted till date of drug resistant tuberculosis in spine analyzing the drug susceptibility patterns in 111 cases of proven drug resistance.

Methods

An observed cross-sectional study was conducted. Six-hundred and eighty-six patients with positive cultures underwent sensitivity testing to 13 commonly used anti-tubercular drugs using BACTEC MGIT-960 system.

Results

Females (60.3%) outnumbered males (39.6%). Only three patients (2.7%) were found HIV positive, and none of these had AIDS. Forty-four (39.6%) patients had taken AKT in the past for some form of tuberculosis. Eight (7.2%) patients had history of treatment default. The drug sensitivity testing revealed 87 (78.3%) cases of multi drug resistance (resistance to both isoniazid and rifampicin) and 3 (2.7%) cases of XDR-TB spine. Of the individual drugs, widespread resistance was present to both isoniazid (92.7%) and rifampicin (81.9%), followed by streptomycin (69.3%). Least resistance was found to kanamycin, amikacin and capreomycin.

Conclusion

It is recommended to do routine biopsy, culture and drug sensitivity testing in all patients of tuberculosis spine to guide selection of appropriate second-line drugs when required. In cases of non availability of drug susceptibility testing despite repeated attempts, it is suggested to use data from large series such as this to plan best empirical chemotherapy protocol.

     

Mechanism of drug resistance,characterization of plasmid-borne determinants and transformation study in P. aeruginosa from burn and ICU units-its susceptibility pattern

The transfer of drug resistance between hospital pathogens has led to alarming increase of multidrug resistant strains imposing therapeutic challenges. These resistant isolates harbor various mechanisms to counteract the drugs administered and have been reported to deliver these factors to sensitive strains in hostile environment. The present study aimed to screen for multidrug resistant Pseudomonas aeruginosa strains for the production of extended-spectrum β-lactamases, metallo-β-lactamases, AmpC β-lactamase, drug efflux phenotypes and co-transfer the resistance for cephalosporin and other non-beta lactam antibiotics in CaCl₂ treated drug sensitive E. coli strains. From the 87 samples processed about 23 isolates of P. aeruginosa were ESBL and MBL positive, 5 (20%) were found to be AmpC β-lactamase producers, efflux mechanism was observed in 8 isolates, 15 isolates had MIC of 16 μg/ml. A putative efflux mechanism was observed in 8 out of 23 isolates that showed decrease in the MIC of meropenem with reserpine. The plasmid profile was characterized for all the common isolates obtained from burn and ICU units. About 69.66% of E. coli recombinants scored positive for both beta lactam and non-beta lactam antibiotics is due to co transfer of resistant plasmid obtained from P. aeruginosa.     

Antibiotikaresistenz und deren Bedeutung bei urogenitalen Infektionen

Urinary tract infections (UTI) are among the most frequent bacterial infections and therefore make a significant contribution to the widespread use and extensive misuse of antibacterial drugs. The amount of antibiotics used directly correlates with the emergence of antibiotic resistance. The World Health Organization (WHO) has recently issued a fact sheet highlighting the worldwide increase in antibiotic resistance. The spectrum of urological diseases affected by antibiotic resistance ranges from benign uncomplicated cystitis to severe life-threatening urosepsis and from urethritis to multidrug resistant tuberculosis. The European Section of Infections in Urology (ESIU) performs an annual surveillance study to evaluate antibiotic resistance in urology which revealed excessively high resistance rates, similar to other surveillance studies. In the light of these developments the World Alliance against Antibiotic Resistance (WAAAR) has advocated a 10-point action plan to combat the rapid rise of worldwide antibiotic resistance.     

Evidence that rifampicin can be used safely for non-tuberculous diseases

The incidence of primary resistance to rifampicin in Mycobacterium tuberculosis has been analysed in countries where rifampicin is restricted to use for treating tuberculosis and in countries where its use is not restricted. There is no evidence that rifampicin-resistant M tuberculosis strains are more common where the use of the drug is unrestricted. Resistance to rifampicin is less common than is resistance to streptomycin or to isoniazid. We can thus see no danger of producing resistant strains of M tuberculosis if rifampicin therapy is used for short periods for non-tuberculosis infections. The problem of resistance mutants arising in the non-tuberculous species being treated is overcome by combining rifampicin with trimethoprim.     

Tuberculosis in England and Wales in 1993: results of a national survey. Public Health Laboratory Service/British Thoracic Society/Department of Health Collaborative Group

BACKGROUND: A national survey of tuberculosis notifications in England and Wales was carried out in 1993 to determine the notification rate of tuberculosis and the trends in the occurrence of disease by ethnic group in comparison with the findings of similar surveys in 1978/79, 1983, and 1988. The prevalence of HIV infection in adults notified with tuberculosis in the survey period was also estimated. METHODS: Clinical, bacteriological, and sociodemographic information was obtained on all newly notified cases of tuberculosis in England and Wales during the six months from 2 January to 2 July 1993. The prevalence of HIV infection in 16-54 year old patients with tuberculosis notified throughout 1993 was assessed using "unlinked anonymous" testing supplemented by matching of the register of patients with tuberculosis with that of patients with AIDS reported to the PHLS AIDS centre. Annual notification rates were calculated using population estimates from the 1993 Labour Force Survey. RESULTS: A total of 2706 newly notified patients was eligible for inclusion in the survey of whom 2458 were previously untreated the comparable figures for 1988 were 2408 and 2163. The number of patients of white ethnic origin decreased from 1142 (53%) in 1988 to 1088 (44%) in 1993 whereas those of patients of Indian, Pakistani, or Bangladeshi (Indian subcontinent (ISC)) ethnic origin increased from 843 (39%) in 1988 to 1014 (41%) and those of "other" (non-white, non-ISC) ethnic origins increased from 178 (8%) to 356 (14%). The largest increase was seen in the black African ethnic group from 37 in 1988 to 171 in 1993. Forty nine per cent of patients had been born abroad and the highest rates were seen in those who had recently arrived in this country. The overall annual notification rate for previously untreated tuberculosis in England and Wales increased between 1988 and 1993 from 8.4 to 9.2 per 100,000 population. The rate declined in the white, Indian, and black Caribbean ethnic groups and increased in all other groups. In the white group the rate of decline has slowed since the last survey: in several age groups the rates were higher in 1993 than 1988 but the numbers in these groups were small. Thirty six (4.1%) of the 882 previously untreated respiratory cases were resistant to isoniazid and three (0.3%) to isoniazid and rifampicin. Sixty two (2.3%) adults aged 16-54 years were estimated to be HIV-infected. Evidence of under-reporting of HIV positive tuberculosis patients was found. CONCLUSIONS: The number of cases and annual notification rate for previously untreated tuberculosis increased between 1988 and 1993. Although the decline in rates in the white population has continued, the rate of decline has slowed. The high rates in the ISC ethnic group population have continued to decline since 1988 whereas rates in the black African group have increased. An increased proportion of cases were found among people born abroad, particularly those recently arrived in this country. In previously untreated cases the level of drug resistance remains low and multi-drug resistance is rare. A small proportion of adults with tuberculosis were infected with HIV but there may be selective undernotification of tuberculosis in these patients.


     

Intrinsic resistance to chemotherapeutic agents in murine osteosarcoma cells

BACKGROUND: There are two general categories of drug resistance: acquired and intrinsic. The mechanisms involved in acquired drug resistance have been extensively studied, and several mechanisms have been described. However, the mechanisms responsible for intrinsic drug resistance have not been elucidated, to our knowledge. The purpose of the present study was to investigate the cytological and biochemical differences between acquired and intrinsic drug resistance in osteosarcoma cells. METHODS: We previously isolated a clonal cell line (MOS/ADR1) to study acquired resistance in osteosarcoma by exposure of parental murine osteosarcoma cells (MOS) to doxorubicin. In the present study, we cloned a new, intrinsically resistant cell line (MOS/IR1) by single-cell culture of MOS cells and we investigated the differences in cell phenotype and the mechanisms of resistance in both of these resistant clones. RESULTS: The MOS/ADR1 and MOS/IR1 cells were sevenfold and fivefold more resistant to doxorubicin than the parental murine osteosarcoma cells. Morphologically, the MOS/ADR1 cell line was composed of polygonal cells, whereas the MOS/IR1 cell line consisted of plump spindle cells with long cytoplasmic processes. The MOS/IR1 cells showed a much lower level of alkaline phosphatase activity than did the MOS/ ADR1 and MOS cells. There were no substantial differences in the cellular DNA content or the doubling time among these three lines. Overexpression of the P-glycoprotein involved in the function of an energy-dependent drug-efflux pump was detected in the MOS/ADR1 cells but not in the MOS/ IR1 cells. After the cells were incubated with doxorubicin for one hour, the two resistant lines had less accumulation of the drug than did the parent line (p < 0.05). The addition of a P-glycoprotein antagonist, verapamil, or the depletion of cellular adenosine triphosphate resulted in a marked increase in the accumulation of doxorubicin in the MOS/ADR1 cells (p < 0.05) but not in the MOS/ IR1 cells. The MOS/ADR1 cells were found to exhibit cross-resistance only to substrates for P-glycoprotein (such as doxorubicin, vincristine, and etoposide), whereas the MOS/IR1 cells were resistant to all of the drugs studied (including cisplatin and methotrexate). The degree of drug resistance in the MOS/IR1 cells was found to be associated with the molecular weight of the drugs (p < 0.05). Permeabilization of the plasma membrane by saponin increased both the accumulation of doxorubicin (p < 0.05) and the cytotoxic activity of this drug in all lines, but the effects were most pronounced in the MOS/IR1 cells. CONCLUSIONS: Taken together, this data suggests that reduced drug accumulation in the MOS/IR1 cells may be due to the effect of decreased permeability of the plasma membrane on the transport of drugs from the extracellular environment into the cytosol of the cell and that this may be the mechanism responsible for intrinsic resistance to multiple drugs in the MOS/IR1 cell line. CLINICAL RELEVANCE: Current drug treatment for human osteosarcoma may include multiple chemotherapeutic agents, such as doxorubicin, cisplatin, and methotrexate. These drugs exhibit different cytotoxic actions and, thus, the mechanisms of resistance to individual drugs vary. Clinical resistance to multidrug chemotherapy may be observed in tumors that recur after repetitive chemotherapy and in previously untreated tumors. In the former group, a tumor cell may express multidrug resistance by combining several different mechanisms due to its exposure to various drugs. In the latter group, however, this is not likely. Decreased intracellular drug accumulation due to reduced permeability of the plasma membrane, found in the MOS/IR1 cells, is one possible mechanism and may explain the intrinsic resistance to multidrug chemotherapy for the treatment of osteosarcoma. Further study regarding the resistance mechanism in the MOS/IR1 cells may help to overcome the intrinsic drug resistance in oste     

Risk factors for multidrug‐resistant tuberculosis in northwest Ethiopia: A case–control study

Ethiopia is one of 30‐high burden multidrug‐resistant tuberculosis (MDR‐TB) countries globally. The aim of this study was to describe the characteristics of patients with MDR‐TB and to investigate risk factors for MDR‐TB relative to having drug‐susceptible tuberculosis (TB), in northwest Ethiopia. A hospital‐based, unmatched case–control study was conducted. Cases were all MDR‐TB patients (i.e., resistant to at least rifampicin and isoniazid) who were confirmed by culture and drug‐susceptibility testing whilst enrolled on treatment at Gondar University Hospital. Controls were all drug‐susceptible tuberculosis (DS‐TB) patients who were confirmed by Gene Xpert MTB/RIF at Gondar University Hospital. Univariable and multivariable logistic regression models were used for comparisons, and odds ratios with 95% confidence intervals (CI) were computed to measure the strength of association between the dependent and independent variables. A total of 452 patients (242 MDR‐TB and 210 DS‐TB) were included in this study. The mean age of the study participants was 33 years (SD ± 14 years). Approximately one‐fifth (78, 17%) of all study participants were human immunodeficiency virus (HIV) positive; 21% (51) of cases and 13% (27) of controls. Risk factors associated with MDR‐TB were a history of previous TB treatment (Adjusted Odds Ratio (AOR): 83.8; 95% CI: 40.7, 172.5), low educational status (AOR: 5.32; 95% CI: 1.43, 19.81); and ages less than 20 years (AOR: 9.01; 95% CI: 2.30, 35.25) and 21–30 years (AOR: 2.61; 95% CI: 1.02, 6.64). HIV infection was also significantly associated with MDR‐TB among new TB patients (AOR: 5.55; 95% CI: 1.17, 26.20). This study shows that clinical and demographic features can be used to indicate higher risks of drug resistance in this setting.     

Surgery increased the chance of cure in multi-drug resistant pulmonary tuberculosis.

BACKGROUND: Medical treatment of multiple drug resistant (MDR) pulmonary tuberculosis is generally quite unsuccessful. Recently, surgical management is increasing and shows promise. We analyzed our experience to identify the benefits and complications of pulmonary resection in MDR pulmonary tuberculosis. METHODS: A retrospective review was performed in 27 patients undergoing pulmonary resection for MDR pulmonary tuberculosis between January 1994 and March 1998. Their average ages were 40 years and were diagnosed a median of 15 months before surgery. All patients had resistance to an average of 4.4 drugs including isoniazid and rifampin, and had received second line drugs selected according to drug sensitivity test preoperatively. Most patients (92.6%) had cavitary lesions. Bilateral lesions were also identified in 19 patients (70.4%), but the main focus was recognized in one side of the lung. Most patients were indicated to operation for those who could not achieve negative sputum despite adequate medical treatment (n = 16, 59.3%); or for negative patients who had significant pulmonary parenchymal lesion (n = 11, 40.7%) which would have had a high probability of recurrence. Pneumonectomy was done in nine patients, lobectomy in 16 and segmentectomy in two. RESULTS: There was no operative mortality. Morbidity occurred in seven patients (25.9%); prolonged air leakage in three patients, reoperation due to bleeding in two, bronchopleural fistula in one, and reversible blindness in one. The median follow up period was 15 months (range 3-45). Sputum negative conversion was achieved in 22 patients (81.5%) initially. However, continued postoperative chemotherapy could convert to negative in another four patients (14.8%). Only one pneumonectomy patient (3.7%) failed because of considerable contralateral cavity. CONCLUSION: For patients with MDR pulmonary tuberculosis which is localized, and with adequate pulmonary reserve function, surgical pulmonary resection combined with appropriate pre and postoperative anti-tuberculosis chemotherapy can achieve high success rate with acceptable morbidity.     

脊柱结核耐药性检测及耐药基因PCR-SSCP分析的应用价值

目的了解临床脊柱结核耐药情况,探讨耐药基因PCR-SSCP分析的临床应用价值。方法31例脊柱结核病灶应用BACTECMGIT960培养,所得临床分离株行药敏试验,对耐药基因rpsL、katG、rpoB行PCR-SS-CP分析。结果31例样本中27例培养阳性,其中18株存在不同程度耐药,总耐药率为66.67%。药物耐药率由高至低为链霉素10株(55.56%)、异烟肼8株(44.44%)、利福平7株(38.89%)、PZA3株(16.67%)。耐链霉素株rpsL突变率为70%,耐异烟肼株katG突变率为50%,耐利福平株rpoB突变率为71.43%。高浓度水平耐药株耐药基因突变率明显高于低浓度水平耐药株。结论常规药敏试验与耐药基因分析相结合可能更能准确地反应MTB的耐药情况。     

Development of multidrug resistance in a primitive neuroectodermal tumor cell line.

Drug resistance remains a formidable obstacle to the successful treatment of pediatric primitive neuroectodermal tumors. Resistance to chemotherapeutic agents may be related, in part, to expression of the multidrug resistance gene 1 (MDR1). The protein product of this gene, P-glycoprotein, confers resistance to multiple unrelated antineoplastic drugs. The cell line DAOY, derived from a primitive neuroectodermal tumor, was used as an in vitro model to examine the development of drug resistance. Cell lines resistant to actinomycin D were developed by the growth of DAOY in increasing concentrations of the drug. The IC50 (concentration of drug needed to induce a 50% reduction in cell growth) of the resultant lines to actinomycin D was more than 10 times that of the parental line. The resistant lines were cross-resistant to VP-16 (etoposide), despite lack of previous exposure to this drug. The resistance to actinomycin D was attenuated in the presence of verapamil, a known inhibitor of P-glycoprotein. The MDR1 gene was not expressed by the parental DAOY line at the messenger ribonucleic acid (RNA) and protein level. Expression of the MDR1 gene was documented in the resistant lines by RNA blot and immunoblot techniques. These results suggest that exposure to chemotherapeutic drugs can induce classical multidrug resistance in primitive neuroectodermal tumors.     

Guidelines for the treatment of latent tuberculosis infection: Recommendations from the National Tuberculosis Controllers Association and CDC, 2020

Comprehensive guidelines for treatment of latent tuberculosis infection (LTBI) among persons living in the United States were last published in 2000 (American Thoracic Society. Am J Respir Crit Care Med 161:S221‐S247, 2000). Since then, several new regimens have been evaluated in clinical trials. To update previous guidelines, the National Tuberculosis Controllers Association (NTCA) and CDC convened a committee to conduct a systematic literature review and make new recommendations for the most effective and least toxic regimens for treatment of LTBI among persons who live in the United States. The systematic literature review included clinical trials of regimens to treat LTBI. Quality of evidence (high, moderate, low, or very low) from clinical trial comparisons was appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. In addition, a network meta‐analysis evaluated regimens that had not been compared directly in clinical trials. The effectiveness outcome was tuberculosis disease; the toxicity outcome was hepatotoxicity. Strong GRADE recommendations required at least moderate evidence of effectiveness and that the desirable consequences outweighed the undesirable consequences in the majority of patients. Conditional GRADE recommendations were made when determination of whether desirable consequences outweighed undesirable consequences was uncertain (eg with low‐quality evidence). These updated 2020 LTBI treatment guidelines include the NTCA‐ and CDC‐recommended treatment regimens that comprise three preferred rifamycin‐based regimens and two alternative monotherapy regimens with daily isoniazid. All recommended treatment regimens are intended for persons infected with Mycobacterium tuberculosis that is presumed to be susceptible to isoniazid or rifampin. These updated guidelines do not apply when evidence is available that the infecting M tuberculosis strain is resistant to both isoniazid and rifampin; recommendations for treating contacts exposed to multidrug‐resistant tuberculosis were published in 2019 (Nahid P, Mase SR Migliori GB, et al Treatment of drug‐resistant tuberculosis. An official ATS/CDC/ERS/IDSA clinical practice guideline. Am J Respir Crit Care Med 2019;200:e93‐e142). The three rifamycin‐based preferred regimens are 3 months of once‐weekly isoniazid plus rifapentine, 4 months of daily rifampin, or 3 months of daily isoniazid plus rifampin. Prescribing providers or pharmacists who are unfamiliar with rifampin and rifapentine might confuse the two drugs. They are not interchangeable, and caution should be taken to ensure that patients receive the correct medication for the intended regimen. Preference for these rifamycin‐based regimens was made on the basis of effectiveness, safety, and high treatment completion rates. The two alternative treatment regimens are daily isoniazid for 6 or 9 months; isoniazid monotherapy is efficacious but has higher toxicity risk and lower treatment completion rates than shorter rifamycin‐based regimens. In summary, short‐course (3‐ to 4‐month) rifamycin‐based treatment regimens are preferred over longer‐course (6‐9 month) isoniazid monotherapy for treatment of LTBI. These updated guidelines can be used by clinicians, public health officials, policymakers, health care organizations, and other state and local stakeholders who might need to adapt them to fit individual clinical circumstances.