Predictors of poor outcomes among patients treated for multidrug-resistant tuberculosis at DOTS-plus projects

The Objective of this analysis was to identify predictors of death, failure, and default among MDR-TB patients treated with second-line drugs in DOTS-plus projects in Estonia, Latvia, Philippines, Russia, and Peru, 2000-2004. Risk ratios (RR) with 95% confidence intervals (CI) were calculated using multivariable regression. Of 1768 patients, treatment outcomes were: cure/completed - 1156 (65%), died - 200 (11%), default - 241 (14%), failure - 118 (7%). Independent predictors of death included: age>45 years (RR?=?1.90 (95%CI 1.29-2.80), HIV infection (RR?=?4.22 (2.65-6.72)), extrapulmonary disease (RR?=?1.54 (1.04-2.26)), BMI<18.5 (RR?=?2.71 (1.91-3.85)), previous use of fluoroquinolones (RR?=?1.91 (1.31-2.78)), resistance to any thioamide (RR?=?1.59 (1.14-2.22)), baseline positive smear (RR?=?2.22 (1.60-3.10)), no culture conversion by 3rd month of treatment (RR?=?1.69 (1.19-2.41)); failure: cavitary disease (RR?=?1.73 (1.07-2.80)), resistance to any fluoroquinolone (RR?=?2.73 (1.71-4.37)) and any thioamide (RR?=?1.62 (1.12-2.34)), and no culture conversion by 3rd month (RR?=?5.84 (3.02-11.27)); default: unemployment (RR?=?1.50 (1.12-2.01)), homelessness (RR?=?1.52 (1.00-2.31)), imprisonment (RR?=?1.86 (1.42-2.45)), alcohol abuse (RR?=?1.60 (1.18-2.16)), and baseline positive smear (RR?=?1.35 (1.07-1.71)). Patients with biomedical risk factors for treatment failure or death should receive heightened medical attention. To prevent treatment default, management of patients who are unemployed, homeless, alcoholic, or have a prison history requires extra measures to insure treatment completion.     

Predictors of sputum culture conversion among patients with tuberculosis in the era of tuberculosis resurgence.

BACKGROUND: Sputum culture conversion among patients with tuberculosis (TB) is the most important indicator for the effectiveness of treatment and the infectivity of the disease. We sought to investigate predictors for documented sputum culture conversion among TB cases reported in the surveillance system. METHODS: This study included 780 patients with pulmonary TB who were initially sputum culture positive in New Jersey in 1994-1995. These patients were followed up for at least 1 week and up to 1 year. Kaplan-Meier curves and Cox proportional hazards models were performed to analyze the data. RESULTS: Overall, 469 (60.1%) of the 780 patients had documented sputum culture conversion. The elderly (36%) and non-Hispanic whites (41.3%) were the least likely to have documented sputum conversion. Patients who were initially given 4 or more drugs were 36% more likely to have documented sputum conversion than those who were initially given fewer than 4 drugs, after adjusting for other factors. Patients who were under the care of chest clinics and the model TB center were about 3 times more likely to have documented sputum conversion than those under care of private physicians. Sex, recurrent TB, foreign-born status, homelessness, injecting drug use, human immunodeficiency virus infection and drug-resistant TB were not significantly associated with the documentation of sputum culture conversion. CONCLUSIONS: A substantial proportion of sputum culture-positive TB patients have no documented sputum culture conversion. The type of care provider was the predominant determinant for the documentation of sputum culture conversion.     

Screening outcomes of household contacts of multidrug-resistant tuberculosis patients in Peshawar,Pakistan

Objective:To assess the profile of TB/multidrug-resistant TB(MDR-TB) among household contacts of MDR-TB patients.Methods:Close contacts of MDR-TB patients were traced in the cross-sectional study.Different clinical,radiological and bacteriological were performed to rule out the evidence of TB/MDR-TB.Results:Between January 2012 and December 2012,a total of 200 index MDR-TB patients were initiated on MDR-TB treatment,out of which home visit and contacts screening were conducted for 154 index cases.Of 610 contacts who could be studied,41(17.4%) were diagnosed with MDR-TB and 10(4.2%) had TB.The most common symptoms observed were cough,chest pain and fever.Conclusions:The high incidence of MDR-TB among close contacts emphasize the need for effective contact screening programme of index MDR-TB cases in order to cut the chain of transmission of this disease.     

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.     

耐多药肺结核患者治疗6个月末痰培养阴转的影响因素分析

目的 了解耐多药肺结核(MDR-PTB)患者治疗6个月末痰培养阴转情况及其影响因素。方法 采用回顾性队列研究的方法,收集2011—2015年杭州市结核病定点医院确诊并开始抗结核药物治疗的365例MDR-PTB患者的人口学信息和实验室检测结果资料,分析研究对象治疗6个月末痰培养阴转情况,并采用Cox比例风险回归模型分析影响研究对象治疗6个月末痰培养阴转的因素。结果 365例研究对象中,332例在治疗6个月末痰培养阴性,阴转率为90.96%;287例(78.63%)治疗成功,78例(21.37%)治疗未成功。332例痰培养阴转的研究对象,阴转时间中位数(四分位数)为85.0(42.0,106.5)d,其中,治疗成功者占84.94%(282例)。33例痰培养未阴转者中,治疗成功者占15.15%(5例),两组比较差异有统计学意义(χ ²=87.00,P=0.000)。Cox回归分析结果显示,杭州户籍的MDR-PTB患者治疗6个月末痰培养易阴转[阴转率为4.09/100人年(149/36.41);调整风险比(aHR)(95%CI):1.37(1.10~1.71)];而对抗结核药物耐药的药品数量(简称“耐药数”)≥4种[阴转率为3.36/100人年(119/35.43);aHR(95%CI):0.76(0.61~0.96)]和年龄≥25岁[25~44岁组阴转率为3.69/100人年(143/38.80);aHR(95%CI):0.56(0.41~0.78)。45~64岁组阴转率为3.36/100人年(108/32.15);aHR(95%CI):0.52(0.37~0.73)。≥65岁组阴转率为3.33/100人年(27/8.10);aHR(95%CI):0.45(0.38~0.72)]的MDR-PTB患者治疗6个月末痰培养不易阴转。 结论 杭州地区MDR-PTB患者治疗成功率及治疗6个月末痰培养阴转率较高,但治疗6个月末痰培养阴转所需时间较长,应针对非杭州户籍者、耐药数多和年龄大的患者早期加强治疗和督导管理,以提高患者的治疗效果。     

Predictors of delayed sputum smear conversion among pulmonary tuberculosis patients in Kota Kinabalu,Malaysia: A retrospective cohort study

Smear-positive pulmonary tuberculosis (SPPTB) is the major contributor to the spread of tuberculosis (TB) infection, and it creates high morbidity and mortality worldwide. The objective of this study was to determine the predictors of delayed sputum smear conversion at the end of the intensive phase of TB treatment in Kota Kinabalu, Malaysia.This retrospective study was conducted utilising data of SPPTB patients treated in 5 TB treatment centres located in Kota Kinabalu, Malaysia from 2013 to 2018. Pulmonary TB (PTB) patients included in the study were those who had at least completed the intensive phase of anti-TB treatment with sputum smear results at the end of the 2nd month of treatment. The factors associated with delayed sputum smear conversion were analyzed using multiple logistic regression analysis. Predictors of sputum smear conversion at the end of intensive phase were evaluated.A total of 2641 patients from the 2013 to 2018 periods were included in this study. One hundred eighty nine (7.2%) patients were identified as having delayed sputum smear conversion at the end of the intensive phase treatment. Factors of moderate (advanced odd ratio [aOR]: 1.7) and advanced (aOR: 2.7) chest X-ray findings at diagnosis, age range of >60 (aOR: 2.1), year of enrolment 2016 (aOR: 2.8), 2017 (aOR: 3.9), and 2018 (aOR: 2.8), smokers (aOR: 1.5), no directly observed treatment short-course (DOTS) supervisor (aOR: 6.9), non-Malaysian citizens (aOR: 1.5), and suburban home locations (aOR: 1.6) were associated with delayed sputum smear conversion at the end of the intensive phase of the treatment.To improve sputum smear conversion success rate, the early detection of PTB cases has to be fine-tuned so as to reduce late or severe case presentation during diagnosis. Efforts must also be in place to encourage PTB patients to quit smoking. The percentage of patients assigned with DOTS supervisors should be increased while at the same time ensuring that vulnerable groups such as those residing in suburban localities, the elderly and migrant TB patients are provided with proper follow-up treatment and management.     

Predictors of mortality in multidrug-resistant tuberculosis patients from Brazilian reference centers, 2005 to 2012

Objectives

To determine the main predictors of death in multidrug-resistant (MDRTB) patients from Brazil.

Time to sputum culture conversion and its predictors among patients with multidrug-resistant tuberculosis in Hangzhou,China: A retrospective cohort study

The objective is to investigate the time to initial sputum culture conversion (SCC) and its predictors among multidrug-resistant tuberculosis (MDR-TB) patients in Hangzhou, China.A retrospective cohort study was conducted among patients who initiated MDR-TB treatment from 2011 to 2015 in Hangzhou, China. Successful achievement of initial SCC was defined as 2 consecutive negative cultures taken at least 30 days apart after initiation of treatment of MDR-TB. Successful treatment outcomes included being cured and completing treatment, while poor treatment outcomes included treatment failure, loss to follow-up, and death. Time to initial SCC was analyzed using the Kaplan–Meier method, and Cox proportional hazards regression was used to identify predictors of SCC.Among 384 patients enrolled with MDR-TB, 359 (93.5%) successfully achieved initial SCC after a median of 85 days (interquartile range, 40–112 days). A higher rate of SCC was observed in participants with successful treatment outcomes than those with poor treatment outcomes (P<.01). Multivariate analysis showed that age 25 to 64 years (compared with age<25; adjusted odds ratio [AOR], 0.7; 95% confidence interval [CI], 0.5–0.9; P < .01), age ≥65 years (compared with age < 25; AOR, 0.5; 95% CI, 0.3–0.8; P < .01), and household registration in Hangzhou (compared with non-Hangzhou registration; AOR, 1.3; 95% CI, 1.0–1.5; P < .05) were found to be associated with SCC.Although high SCC and treatment success rates were observed among MDR-TB patients in Hangzhou, the prolonged duration to initial SCC underscores the importance of emphasizing measures for infection control. A new policy of shifting outpatient treatment to inpatient treatment in China may reduce the risk of transmission from patients in the time window prior to SCC.     

Costs of patients hospitalized for multidrug-resistant tuberculosis.

SETTING: From 1993 through 1998, 1846 cases of multidrug-resistant tuberculosis (MDR-TB) were reported in the United States. Costs associated with MDR-TB are likely to be much higher than for drug-susceptible tuberculosis due to longer hospitalization, longer treatment with more expensive and toxic medications, greater productivity losses, and higher mortality. OBJECTIVE: To measure the societal costs of patients hospitalized for MDR-TB. DESIGN: We detailed in-patient costs for 13 multidrug-resistant patients enrolled in a national study. We estimated costs for physician care, out-patient treatment, and productivity losses for survivors and for deceased patients. RESULTS: In-patient costs averaged US$25,853 per person and $1036 per person-day of hospitalization. Outpatient costs per person ranged from $5744 to $41,821 (average $19028, or $44 a day). Direct medical costs averaged $44,881; indirect costs for those who survived averaged $32,964, and indirect costs for those who died averaged $686,381 per person. Total costs per person ranged from $28,217 to $181492 (average $89,594) for those who survived, and from $509490 to $1278066 (average $717555) for those who died. CONCLUSION: The societal costs of MDR-TB varied, mostly because of length of therapy (including in-patient), and deaths during treatment.     

Outcomes of patients with multidrug-resistant pulmonary tuberculosis treated with ofloxacin/levofloxacin-containing regimens

OBJECTIVE: To analyze outcomes of patients with multidrug-resistant tuberculosis (MDR-TB) treated with ofloxacin/levofloxacin-containing regimens. MATERIALS AND METHODS: From February 1990 through June 1997, 63 MDR-TB patients (with bacillary resistance to at least isoniazid and rifampin in vitro) were analyzed retrospectively. Twenty-two patients (34.9%) had had no previous antituberculosis chemotherapy. Each patient received either ofloxacin (53) or levofloxacin (10) even though 13 patients had bacilli resistant to ofloxacin in vitro. The other accompanying drugs mainly included aminoglycosides, cycloserine, ethionamide/prothionamide, and pyrazinamide. Sputum smear and culture examinations for acid-fast bacilli (AFB) were performed monthly for the initial 6 months and then at 2- to 3-month intervals until the end of treatment. Comparison was made between clinical successes and failures using univariate and multiple logistic regression analyses for the following variables: age, sex, presence of cavitation, extent of disease, sputum smear positivity, in vitro resistance to ofloxacin, in vitro resistance to streptomycin and/or ethambutol, treatment adherence, and the number of drugs per regimen. RESULTS: Fifty-one patients (81.0%) were cured, nine patients (14.3%) failed, and three patients (4.7%) died. For the entire group, the mean duration of treatment was 14.0 months, and the mean number of drugs was 4.7. Mean durations of chemotherapy in successful and failed patients were 14.5 and 14.2 months, respectively. Mean time for sputum smear and culture conversions were 1.7 and 2.1 months, respectively. Only cavitation, resistance to ofloxacin, and poor adherence were found to be variables independently associated with adverse outcomes (p < 0.05; odds ratios = 15.9, 13.5, 12.8, respectively). Negative sputum cultures after 2 and 3 months of therapy were 100% predictive of cure. Positive sputum cultures after 2 and 3 months were 52.3% and 84.6% predictive of failure, respectively. One patient (2.1%) relapsed after apparent cure. Twenty-five patients experienced adverse drug reactions, but only 12 of them needed drug modifications. CONCLUSION: Most MDR-TB patients can be treated effectively with ofloxacin/levofloxacin-containing regimens. Presence of cavitation, resistance to ofloxacin in vitro, and poor adherence to therapy portend treatment failure. Monitoring monthly sputum culture for AFB in the initial months of chemotherapy helps predict clinical outcomes.     

Hypokalemia among patients receiving treatment for multidrug-resistant tuberculosis

INTRODUCTION: Between January 1999 and December 2000, 125 patients in Lima, Peru were enrolled in individualized treatment for multidrug-resistant tuberculosis (MDR-TB). Hypokalemia was observed to be an important adverse effect encountered in this cohort. OBJECTIVE: To identify risk factors associated with the development and persistence of hypokalemia during MDR-TB therapy, and to review the incidence and management of hypokalemia in patients receiving MDR-TB therapy. METHODS: A retrospective case series of 125 patients who received individualized therapy for MDR-TB between January 1, 1999, and December 31, 2000. RESULTS: Among 115 patients who were screened for electrolyte abnormalities, 31.3% had hypokalemia, defined as a potassium level of < 3.5 mEq/L. Mean serum potassium at time of diagnosis was 2.85 mEq/L. Diagnosis of low serum potassium occurred, on average, after 5.1 months of individualized therapy. Multivariate analysis of risk factors for this adverse reaction identified two causes: administration of capreomycin, and low initial body weight. Normalization of potassium levels was achieved in 86% of patients. CONCLUSIONS: Electrolyte disturbance was frequently encountered in our cohort of patients with MDR-TB. Successful screening and management of hypokalemia was facilitated by training the health-care team in the use of a standardized algorithm. Morbidity from hypokalemia can be significant; however, effective management of this side effect is possible without sacrificing MDR-TB treatment efficacy.     

Use of therapeutic drug monitoring for multidrug-resistant tuberculosis patients

STUDY OBJECTIVES: Therapeutic drug monitoring (TDM) is the process of obtaining the serum concentration of a medication and modifying the dose based on the results. Little is known about the application of TDM in the treatment of patients with multidrug-resistant (MDR) tuberculosis (TB) in clinical practice. This study characterized how TDM was applied in the management of MDR TB patients, and examined the clinical indications for ordering TDM, the process for obtaining drug concentrations, and the clinician response to the drug concentrations. DESIGN: In a retrospective study, we compared the clinical and demographic characteristics of MDR TB patients who received TDM with those who did not. The clinical application of TDM also was described in patients who received TDM. SETTING: A municipal TB control program.Patients or participants: Patients in whom TB was diagnosed that was caused by an isolate resistant to at least isoniazid and rifampin, and who received treatment for TB in one of the health department chest clinics between July 1, 1993, and August 31, 1997, were studied. RESULTS: Forty-nine patients receiving TDM had a longer time to culture conversion and treatment duration, more pulmonary TB in combination with an extrapulmonary site, drug resistance, and visits to the health department clinics (p < 0.05) than the 60 patients without TDM. Of the 49 patients who had initial TDM, 73.5% of them had the reason for being tested specified. A total of 85.7% of initial TDM results were collected at the appropriate time of blood sampling. Clinician response to TDM results varied with the drug that was being tested. CONCLUSIONS: The use of TDM depended largely on the patient's clinical presentation. Site-specific guidelines on the use of TDM for managing TB patients may maximize the benefit of TDM.     

Treatment for multidrug-resistant tuberculosis in Japan

INTRODUCTION: Multidrug-resistant (MDR) tuberculosis is now refractory against standard chemotherapy for tuberculosis. The curability of medical treatments for it has been up to 50-75%. In Japan several hundreds new MDR tuberculosis cases are supposed to occur every year. This review is the outline of Japanese preliminary guideline of treatment for MDR tuberculosis. DRUG SUSCEPTIBILITY TEST: One of the most important points to manage MDR tuberculosis is the drug usages according to drug susceptibility. Recently some susceptibility tests with liquid media were introduced in our country, but Japanese new standard test of Ogawa method (using absolute concentration with proportion method) is still important from point of true evaluation of susceptibility. MEDICAL CHEMOTHERAPY: In MDR tuberculosis one-half of two-third cases are cured by suitable resume of anti-tuberculosis chemotherapy. If patients would prove to be suffered from MDR tuberculosis, chemotherapy resume must be changed from standard resume to special one, that are made from effective and stronger four or five (at least three) anti-tuberculosis drugs including new quinolons. Those drugs should be changed at the same time, not one by one. Although CPM and Tb1 cannot be available in Japan, but sometimes we have to try administrations of those drugs, beta-lactam antibiotics, interferon. The duration of treatment will be 18-24 months usually. If decreasing of tuberculosis bacilli in sputa is failed under new effective resume through four months treatment, surgical treatment may be indicated. SURGICAL TREATMENT: (1) In Fukujuji Hospital, Japan Anti-Tuberculosis Association, surgical treatments for seventy four cases of MDR tuberculosis were undergone from 1983 to 2001 March. 85 surgical interventions for them were performed in 71 pulmonary resections (pneumonectomy in 20, lobectomy in 44, segmentectomy in 7) for 64 cases, 8 thoracoplasties alone for 8 cases, 5 cavernostomies for 5 cases, 1 phrenic nerve avulsion for 1. The result of pulmonary resections was as follows; early negative conversion rate of tuberculosis expectorations was 97.2%, reexpectoration rate of sputa tuberculosis bacilli was 13.8%, final success rate of pulmonary resections was 91.7%. The factors significantly correlated to reexpectoration of tuberculosis bacilli were preoperative positive bacilli in sputa, few sensitive drugs, other cavitary lesions remained, postoperative prolonged bronchopleural fistula. The result of thoracoplasty alone revealed 75% success rate. In postoperative complications of 85 interventions, there was no operative death, prolonged bronchopleural fistula in 17.6%, respiratory failure in 8.7%, pyothorax in 5.9%. (2) Recently results of surgical treatment for MDR tuberculosis were reported in several literatures. Those success rates were almost same 85-95% as our result. They seemed to be very excellent for refractory cases against vigorous medical treatments. So any surgical treatment for MDR tuberculosis should be indicated more constructively in its earlier course. (3) Indication of surgical treatment is as follows; Main target lesions that should be removed are cavitary ones in pulmonary or pleural foci. And any capsulated localized tuberculosis foci more than 2 cm in diameter is better to be resected because of the possibility of later cavitation. Surgically it is the best that all tuberculosis foci are within a resected lobe, effective drugs remained as many as possible and no cardiopulmonary risks. But even if patient's state are over those criteria, resections of more extended pulmonary foci including in opposite sides can be tried within tolerable cardiopulmonary function. OTHER COMMENTS: Treatment for HIV-positive MDR tuberculosis and protection for nosocomial transmission of MDR tuberculosis are discussed briefly in this article. Preventive therapy for newly infected persons with MDR tuberculosis is controversial. At this time just in MDR tuberculosis cases no preventive therapy, careful following up, and drastic treatment with remained effective drugs after developping of disease will be recommended.