Last data update: Jun 03, 2024. (Total: 46935 publications since 2009)
Records 1-25 (of 25 Records) |
Query Trace: Kurbatova EV [original query] |
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Pharmacokinetic-pharmacodynamic evidence from a phase 3 trial to support flat-dosing of rifampicin for tuberculosis
Ngo HX , Xu AY , Velásquez GE , Zhang N , Chang VK , Kurbatova EV , Whitworth WC , Sizemore E , Bryant K , Carr W , Weiner M , Dooley KE , Engle M , Dorman SE , Nahid P , Swindells S , Chaisson RE , Nsubuga P , Lourens M , Dawson R , Savic RM . Clin Infect Dis 2024 BACKGROUND: The optimal dosing strategy for rifampicin in treating drug-susceptible tuberculosis (TB) is still highly debated. In the Phase 3 clinical trial Study 31/ACTG 5349 (NCT02410772), all participants in the control regimen arm received 600 mg rifampicin daily as a flat dose. Here, we evaluated relationships between rifampicin exposure and efficacy and safety outcomes. METHODS: We analyzed rifampicin concentration time profiles using population nonlinear mixed-effects models. We compared simulated rifampicin exposure from flat- and weight-banded dosing. We evaluated the effect of rifampicin exposure on stable culture conversion at 6 months, TB-related unfavorable outcomes at 9, 12, and 18 months using Cox proportional hazard models, and all trial-defined safety outcomes using logistic regression. RESULTS: Our model derived rifampicin exposure ranged from 4.57 mg·h/L to 140.0 mg·h/L with a median of 41.8 mg·h/L. Pharmacokinetic simulations demonstrated that flat-dosed rifampicin provided exposure coverage similar to weight-banded dose. Exposure-efficacy analysis (N=680) showed that participants with rifampicin exposure below the median experienced similar hazards of stable culture conversion and TB-related unfavorable outcomes compared to those with exposure above the median. Exposure-safety analysis (N=722) showed that increased rifampicin exposure was not associated with increased grade 3 or higher adverse events, or serious adverse events. CONCLUSIONS: Flat-dosing of rifampicin at 600 mg daily may be a reasonable alternative to the incumbent weight-banded dosing strategy for the standard of care 6-month regimen. Future research should assess the optimal dosing strategy for rifampicin, at doses higher than the current recommendation. |
A standardized approach for collection of objective data to support outcome determination for late-phase TB trials
Kurbatova EV , Phillips PP , Dorman SE , Sizemore EE , Bryant KE , Purfield AE , Ricaldi J , Brown NE , Johnson JL , Wallis CL , Akol JP , Ocheretina O , Van Hung N , Mayanja-Kizza H , Lourens M , Dawson R , Nhung NV , Pierre S , Musodza Y , Shenje J , Badal-Faesen S , Vilbrun SC , Waja Z , Peddareddy L , Scott NA , Yuan Y , Vernon A , Goldberg SV , Swindells S , Chaisson RE , Nahid P . Am J Respir Crit Care Med 2023 207 (10) 1376-1382 INTRODUCTION: We developed a standardized method, "Possible poor treatment response" (PPTR), to help ascertain efficacy endpoints in Study S31/A5349 (NCT02410772), an open-label trial comparing two 4-month rifapentine-based regimens with a standard 6-month regimen for the treatment of pulmonary TB. We describe the use of the PPTR process and evaluate whether the goals of minimizing bias in efficacy endpoint assessment and attainment of relevant data to determine outcome for all participants were achieved. METHODS/DESIGN: A PPTR event was defined as the occurrence of one or more pre-specified triggers. Each PPTR required initiation of a standardized evaluation process that included obtaining multiple sputum samples for microbiology. RESULTS: Among 2,343 participants with culture-confirmed drug-susceptible TB, 454 individuals (19.4%) had a total of 534 individual PPTR events, of which 76.6% were microbiological (positive smear or culture at or after 17 weeks). At least one PPTR event was experienced by 92.4% (133 of 144) of participants with TB-related unfavorable outcome, and between 13.8 and 14.7% of participants with favorable and not assessable outcomes. 75% of participants with TB-related unfavorable outcomes had microbiological confirmation of failure to achieve disease-free cure. DISCUSSION: Standardized methodologies, such as our PPTR approach, could facilitate unbiased efficacy outcome determinations, improve discrimination between outcomes that are related and unrelated to regimen efficacy, and enhance the ability to conduct pooled analyses of contemporary trials. Clinical trial registration available at www. CLINICALTRIALS: gov, ID: NCT02410772. |
Four-Month Rifapentine Regimens with or without Moxifloxacin for Tuberculosis
Dorman SE , Nahid P , Kurbatova EV , Phillips PPJ , Bryant K , Dooley KE , Engle M , Goldberg SV , Phan HTT , Hakim J , Johnson JL , Lourens M , Martinson NA , Muzanyi G , Narunsky K , Nerette S , Nguyen NV , Pham TH , Pierre S , Purfield AE , Samaneka W , Savic RM , Sanne I , Scott NA , Shenje J , Sizemore E , Vernon A , Waja Z , Weiner M , Swindells S , Chaisson RE . N Engl J Med 2021 384 (18) 1705-1718 BACKGROUND: Rifapentine-based regimens have potent antimycobacterial activity that may allow for a shorter course in patients with drug-susceptible pulmonary tuberculosis. METHODS: In an open-label, phase 3, randomized, controlled trial involving persons with newly diagnosed pulmonary tuberculosis from 13 countries, we compared two 4-month rifapentine-based regimens with a standard 6-month regimen consisting of rifampin, isoniazid, pyrazinamide, and ethambutol (control) using a noninferiority margin of 6.6 percentage points. In one 4-month regimen, rifampin was replaced with rifapentine; in the other, rifampin was replaced with rifapentine and ethambutol with moxifloxacin. The primary efficacy outcome was survival free of tuberculosis at 12 months. RESULTS: Among 2516 participants who had undergone randomization, 2343 had a culture positive for Mycobacterium tuberculosis that was not resistant to isoniazid, rifampin, or fluoroquinolones (microbiologically eligible population; 768 in the control group, 791 in the rifapentine-moxifloxacin group, and 784 in the rifapentine group), of whom 194 were coinfected with human immunodeficiency virus and 1703 had cavitation on chest radiography. A total of 2234 participants could be assessed for the primary outcome (assessable population; 726 in the control group, 756 in the rifapentine-moxifloxacin group, and 752 in the rifapentine group). Rifapentine with moxifloxacin was noninferior to the control in the microbiologically eligible population (15.5% vs. 14.6% had an unfavorable outcome; difference, 1.0 percentage point; 95% confidence interval [CI], -2.6 to 4.5) and in the assessable population (11.6% vs. 9.6%; difference, 2.0 percentage points; 95% CI, -1.1 to 5.1). Noninferiority was shown in the secondary and sensitivity analyses. Rifapentine without moxifloxacin was not shown to be noninferior to the control in either population (17.7% vs. 14.6% with an unfavorable outcome in the microbiologically eligible population; difference, 3.0 percentage points [95% CI, -0.6 to 6.6]; and 14.2% vs. 9.6% in the assessable population; difference, 4.4 percentage points [95% CI, 1.2 to 7.7]). Adverse events of grade 3 or higher occurred during the on-treatment period in 19.3% of participants in the control group, 18.8% in the rifapentine-moxifloxacin group, and 14.3% in the rifapentine group. CONCLUSIONS: The efficacy of a 4-month rifapentine-based regimen containing moxifloxacin was noninferior to the standard 6-month regimen in the treatment of tuberculosis. (Funded by the Centers for Disease Control and Prevention and others; Study 31/A5349 ClinicalTrials.gov number, NCT02410772.). |
Central monitoring in a randomized, open-label, controlled phase 3 clinical trial for a treatment-shortening regimen for pulmonary tuberculosis
Bryant KE , Yuan Y , Engle M , Kurbatova EV , Allen-Blige C , Batra K , Brown NE , Chiu KW , Davis H , Elskamp M , Fagley M , Fedrick P , Hedges KNC , Narunsky K , Nassali J , Phan M , Phan H , Purfield AE , Ricaldi JN , Robergeau-Hunt K , Whitworth WC , Sizemore EE . Contemp Clin Trials 2021 104 106355 INTRODUCTION: With the growing use of online study management systems and rapid availability of data, timely data review and quality assessments are necessary to ensure proper clinical trial implementation. In this report we describe central monitoring used to ensure protocol compliance and accurate data reporting, implemented during a large phase 3 clinical trial. MATERIAL AND METHODS: The Tuberculosis Trials Consortium (TBTC) Study 31/AIDS Clinical Trials Group (ACTG) study A5349 (S31) is an international, multi-site, randomized, open-label, controlled, non-inferiority phase 3 clinical trial comparing two 4-month regimens to a standard 6 month regimen for treatment of drug-susceptible tuberculosis (TB) among adolescents and adults with a sample size of 2500 participants. RESULTS: Central monitoring utilized primary study data in a five-tiered approach, including (1) real-time data checks & topic-specific intervention reports, (2) missing forms reports, (3) quality assurance metrics, (4) critical data reports and (5) protocol deviation identification, aimed to detect and resolve quality challenges. Over the course of the study, 240 data checks and reports were programed across the five tiers used. DISCUSSION: This use of primary study data to identify issues rapidly allowed the study sponsor to focus quality assurance and data cleaning activities on prioritized data, related to protocol compliance and accurate reporting of study results. Our approach enabled us to become more efficient and effective as we informed sites about deviations, resolved missing or inconsistent data, provided targeted guidance, and gained a deeper understanding of challenges experienced at clinical trial sites. TRIAL REGISTRATION: This trial was registered with ClinicalTrials.gov (Identifier: NCT02410772) on April 8, 2015. |
COVID-19 in Americans aboard the Diamond Princess cruise ship.
Plucinski MM , Wallace M , Uehara A , Kurbatova EV , Tobolowsky FA , Schneider ZD , Ishizumi A , Bozio CH , Kobayashi M , Toda M , Stewart A , Wagner RL , Moriarty LF , Murray R , Queen K , Tao Y , Paden C , Mauldin MR , Zhang J , Li Y , Elkins CA , Lu X , Herzig CTA , Novak R , Bower W , Medley AM , Acosta AM , Knust B , Cantey PT , Pesik NT , Halsey ES , Cetron MS , Tong S , Marston BJ , Friedman CR . Clin Infect Dis 2020 72 (10) e448-e457 BACKGROUND: The Diamond Princess cruise ship was the site of a large outbreak of coronavirus disease 2019 (COVID-19). Of 437 Americans and their travel companions on the ship, 114 (26%) tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We interviewed 229 American passengers and crew after disembarkation following a ship-based quarantine to identify risk factors for infection and characterize transmission onboard the ship. RESULTS: The attack rate for passengers in single-person cabins or without infected cabinmates was 18% (58/329), compared with 63% (27/43) for those sharing a cabin with an asymptomatic infected cabinmate, and 81% (25/31) for those with a symptomatic infected cabinmate. Whole genome sequences from specimens from passengers who shared cabins clustered together. Of 66 SARS-CoV-2-positive American travelers with complete symptom information, 14 (21%) were asymptomatic while on the ship. Among SARS-CoV-2-positive Americans, 10 (9%) required intensive care, of whom 7 were ≥70 years. CONCLUSION: Our findings highlight the high risk of SARS-CoV-2 transmission on cruise ships. High rates of SARS-CoV-2 positivity in cabinmates of individuals with asymptomatic infections suggest that triage by symptom status in shared quarters is insufficient to halt transmission. A high rate of intensive care unit admission among older individuals complicates the prospect of future cruise travel during the pandemic, given typical cruise passenger demographics. The magnitude and severe outcomes of this outbreak were major factors contributing to the Centers for Disease Control and Prevention's decision to halt cruise ship travel in U.S. waters in March 2020. |
Impact of GeneXpert MTB/RIF® on treatment initiation and outcomes of RIF-resistant and RIF-susceptible TB patients in Vladimir TB dispensary, Russia.
Ershova JV , Volchenkov GV , Somova TR , Kuznetsova TA , Kaunetis NV , Kaminski D , Demikhova OV , Chernousova LN , Vasilyeva IA , Kerr EM , Cegielski JP , Kurbatova EV . BMC Infect Dis 2020 20 (1) 543 BACKGROUND: The main advantage of GeneXpert MTB/RIF® (Xpert) molecular diagnostic technology is the rapid detection of M.tuberculosis DNA and mutations associated with rifampicin (RIF) resistance for timely initiation of appropriate treatment and, consequently, preventing further transmission of the disease. We assessed time to treatment initiation and treatment outcomes of RIF-resistant and RIF-susceptible TB patients diagnosed and treated in Vladimir TB Dispensary, Russia in 2012, before and after implementation of GeneXpert MTB/RIF® diagnostic technology. METHODS: All adult patients suspected of having TB during February-December 2012 underwent a clinical examination, chest x-ray, microscopy, culture, and phenotypic drug susceptibility testing (DST). Starting August 2012 Xpert diagnostic technology became available in the facility. We used logistic regression to compare treatment outcomes in pre-Xpert and post-Xpert periods. Kaplan-Meier curves and log-rank test were used to compare the time to treatment initiation between the groups. RESULTS: Of 402 patients screened for TB during February-December 2012, 338 were diagnosed with TB (280 RIF-susceptible, 58 RIF-resistant). RIF-resistant patients in the post-Xpert group started treatment with second-line drugs (SLD) earlier than those in pre-Xpert group (median 11 vs. 37 days, Log-rank p = 0.02). The hazard ratio for time to SLD treatment initiation was significantly higher in post-Xpert group (HR:2.06; 95%CI:1.09,3.89) compared to pre-Xpert group. Among the 53/58 RIF-resistant TB patients with available treatment outcome, 28 (53%) had successful outcomes (cured/completed treatment) including 15/26 (58%) in post-Xpert group versus 13/27 (48%) in pre-Xpert group. The observed difference, however, was not statistically significant (OR:0.69; 95%CI:0.23,2.06). Among RIF-susceptible TB cases time to treatment initiation was not significantly different between the groups (2 vs. 3 days, Log-rank p = 0.73). Of 252/280 RIF-susceptible TB cases with treatment outcome, 199 (79%) cases had successful outcome including 94/114 (82%) in post-Xpert group versus 105/138 (76%) in pre-Xpert group (OR:0.68; 95%CI:0.36,1.26). CONCLUSION: We observed that availability of Xpert for initial diagnosis significantly reduced the time to SLD treatment for RIF-resistant patients in the Vladimir TB Dispensary. Although implementation of rapid diagnostics did not improve treatment outcomes, early diagnosis of MDR-TB is important for selection of appropriate treatment regimen and prevention of transmission of drug-resistant strains of TB. |
Public Health Responses to COVID-19 Outbreaks on Cruise Ships - Worldwide, February-March 2020.
Moriarty LF , Plucinski MM , Marston BJ , Kurbatova EV , Knust B , Murray EL , Pesik N , Rose D , Fitter D , Kobayashi M , Toda M , Canty PT , Scheuer T , Halsey ES , Cohen NJ , Stockman L , Wadford DA , Medley AM , Green G , Regan JJ , Tardivel K , White S , Brown C , Morales C , Yen C , Wittry B , Freeland A , Naramore S , Novak RT , Daigle D , Weinberg M , Acosta A , Herzig C , Kapella BK , Jacobson KR , Lamba K , Ishizumi A , Sarisky J , Svendsen E , Blocher T , Wu C , Charles J , Wagner R , Stewart A , Mead PS , Kurylo E , Campbell S , Murray R , Weidle P , Cetron M , Friedman CR . MMWR Morb Mortal Wkly Rep 2020 69 (12) 347-352 An estimated 30 million passengers are transported on 272 cruise ships worldwide each year* (1). Cruise ships bring diverse populations into proximity for many days, facilitating transmission of respiratory illness (2). SARS-CoV-2, the virus that causes coronavirus disease (COVID-19) was first identified in Wuhan, China, in December 2019 and has since spread worldwide to at least 187 countries and territories. Widespread COVID-19 transmission on cruise ships has been reported as well (3). Passengers on certain cruise ship voyages might be aged >/=65 years, which places them at greater risk for severe consequences of SARS-CoV-2 infection (4). During February-March 2020, COVID-19 outbreaks associated with three cruise ship voyages have caused more than 800 laboratory-confirmed cases among passengers and crew, including 10 deaths. Transmission occurred across multiple voyages of several ships. This report describes public health responses to COVID-19 outbreaks on these ships. COVID-19 on cruise ships poses a risk for rapid spread of disease, causing outbreaks in a vulnerable population, and aggressive efforts are required to contain spread. All persons should defer all cruise travel worldwide during the COVID-19 pandemic. |
High-dose rifapentine with or without moxifloxacin for shortening treatment of pulmonary tuberculosis: Study protocol for TBTC study 31/ACTG A5349 phase 3 clinical trial
Dorman SE , Nahid P , Kurbatova EV , Goldberg SV , Bozeman L , Burman WJ , Chang KC , Chen M , Cotton M , Dooley KE , Engle M , Feng PJ , Fletcher CV , Ha P , Heilig CM , Johnson JL , Lessem E , Metchock B , Miro JM , Nhung NV , Pettit AC , Phillips PPJ , Podany AT , Purfield AE , Robergeau K , Samaneka W , Scott NA , Sizemore E , Vernon A , Weiner M , Swindells S , Chaisson RE . Contemp Clin Trials 2020 90 105938 INTRODUCTION: Phase 2 clinical trials of tuberculosis treatment have shown that once-daily regimens in which rifampin is replaced by high dose rifapentine have potent antimicrobial activity that may be sufficient to shorten overall treatment duration. Herein we describe the design of an ongoing phase 3 clinical trial testing the hypothesis that once-daily regimens containing high dose rifapentine in combination with other anti-tuberculosis drugs administered for four months can achieve cure rates not worse than the conventional six-month treatment regimen. METHODS/DESIGN: S31/A5349 is a multicenter randomized controlled phase 3 non-inferiority trial that compares two four-month regimens with the standard six-month regimen for treating drug-susceptible pulmonary tuberculosis in HIV-negative and HIV-positive patients. Both of the four-month regimens contain high-dose rifapentine instead of rifampin, with ethambutol replaced by moxifloxacin in one regimen. All drugs are administered seven days per week, and under direct observation at least five days per week. The primary outcome is tuberculosis disease-free survival at twelve months after study treatment assignment. A total of 2500 participants will be randomized; this gives 90% power to show non-inferiority with a 6.6% margin of non-inferiority. DISCUSSION: This phase 3 trial formally tests the hypothesis that augmentation of rifamycin exposures can shorten tuberculosis treatment to four months. Trial design and standardized implementation optimize the likelihood of obtaining valid results. Results of this trial may have important implications for clinical management of tuberculosis at both individual and programmatic levels. TRIAL REGISTRATION: NCT02410772. Registered 8 April 2015,https://www.clinicaltrials.gov/ct2/show/NCT02410772?term=02410772&rank=1. |
Multidrug-resistant tuberculosis patients' views of interventions to reduce treatment loss to follow-up
Tupasi T , Garfin AMCG , Mangan JM , Orillaza-Chi R , Naval LC , Balane GI , Basilio R , Golubkov A , Joson ES , Lew WJ , Lofranco V , Mantala M , Pancho S , Sarol JN Jr , Blumberg A , Burt D , Kurbatova EV . Int J Tuberc Lung Dis 2017 21 (1) 23-31 SETTING: Patients who initiated treatment for multidrug-resistant tuberculosis (MDR-TB) at 15 Programmatic Management of Drug-resistant Tuberculosis (PMDT) health facilities in the Philippines between July and December 2012. OBJECTIVES: To describe patients' views of current interventions, and suggest changes likely to reduce MDR-TB loss to follow-up. METHODS: In-depth interviews were conducted between April and July 2014 with MDR-TB patients who were undergoing treatment, had finished treatment at the time of the interview (controls), or had been lost to follow-up (LTFU). Responses were thematically analyzed. RESULTS: Interviews were conducted with 182 patients who were undergoing or had completed treatment and 91 LTFU patients. Views and suggestions could be thematically categorized as approaches to facilitate adherence or address barriers to adherence. The top themes were the need for transportation assistance or improvements to the current transportation assistance program, food assistance, and difficulties patients encountered related to their medications. These themes were addressed by respectively 63%, 60%, and 32% of the participants. CONCLUSIONS: A more patient-centered approach is needed to improve MDR-TB treatment adherence. Programs should strive to provide assistance that considers patient preferences, is adequate to cover actual costs or needs, and is delivered in a timely, uninterrupted manner. |
Multidrug-resistant tuberculosis patients lost to follow-up: self-reported readiness to restart treatment
Mangan JM , Tupasi TE , Garfin AM , Lofranco V , Orillaza-Chi R , Basilio R , Naval LC , Balane GI , Joson ES , Burt D , Lew WJ , Mantala M , Pancho S , Sarol JN , Golubkov A , Kurbatova EV . Int J Tuberc Lung Dis 2016 20 (9) 1205-11 SETTING: Multidrug-resistant tuberculosis (MDR-TB) patients lost to follow-up (LTFU) from Programmatic Management of Drug-resistant Tuberculosis facilities in the Philippines. OBJECTIVES: To gain insight into patients' readiness to return to treatment. METHODS: MDR-TB patients who initiated treatment and were categorized as LTFU were identified using TB registers, contacted, and asked to consent to an interview and medical record review. At the conclusion of the interview, patients' readiness to restart treatment was assessed and examined in relation to demographic, clinical, and interview data. Odds ratios were calculated. RESULTS: When asked if they would consider restarting MDR-TB treatment, 3% of the 89 participating patients reported that they had already restarted, 34% indicated that they wanted to restart, 33% had not considered restarting, 28% were undecided, and 2% had decided against restarting. Patients who wanted to restart treatment were more likely to report having borrowed money for TB-related expenses (OR 5.97, 95%CI 1.27-28.18), and were less likely to report being self-employed (OR 0.08, 95%CI 0.01-0.67), or perceive themselves at low or no risk for TB relapse (OR 0.30, 95%CI 0.08-0.96) than patients who did not indicate an interest in restarting treatment. CONCLUSIONS: Efforts to re-engage LTFU patients in care should consider financial barriers, knowledge gaps, and personal adherence challenges in patients. |
Factors associated with loss to follow-up during treatment for multidrug-resistant tuberculosis, the Philippines, 2012-2014
Tupasi TE , Garfin AM , Kurbatova EV , Mangan JM , Orillaza-Chi R , Naval LC , Balane GI , Basilio R , Golubkov A , Joson ES , Lew WJ , Lofranco V , Mantala M , Pancho S , Sarol JN Jr . Emerg Infect Dis 2016 22 (3) 491-502 To identify factors associated with loss to follow-up during treatment for multidrug-resistant (MDR) tuberculosis (TB) in the Philippines, we conducted a case-control study of adult patients who began receiving treatment for rifampin-resistant TB during July 1-December 31, 2012. Among 91 case-patients (those lost to follow-up) and 182 control-patients (those who adhered to treatment), independent factors associated with loss to follow-up included patients' higher self-rating of the severity of vomiting as an adverse drug reaction and alcohol abuse. Protective factors included receiving any type of assistance from the TB program, better TB knowledge, and higher levels of trust in and support from physicians and nurses. These results provide insights for designing interventions aimed at reducing patient loss to follow-up during treatment for MDR TB. |
Association between regimen composition and treatment response in patients with multidrug-resistant tuberculosis: A prospective cohort study
Yuen CM , Kurbatova EV , Tupasi T , Caoili JC , Van Der Walt M , Kvasnovsky C , Yagui M , Bayona J , Contreras C , Leimane V , Ershova J , Via LE , Kim H , Akksilp S , Kazennyy BY , Volchenkov GV , Jou R , Kliiman K , Demikhova OV , Vasilyeva IA , Dalton T , Cegielski JP . PLoS Med 2015 12 (12) e1001932 BACKGROUND: For treating multidrug-resistant tuberculosis (MDR TB), the World Health Organization (WHO) recommends a regimen of at least four second-line drugs that are likely to be effective as well as pyrazinamide. WHO guidelines indicate only marginal benefit for regimens based directly on drug susceptibility testing (DST) results. Recent evidence from isolated cohorts suggests that regimens containing more drugs may be beneficial, and that DST results are predictive of regimen effectiveness. The objective of our study was to gain insight into how regimen design affects treatment response by analyzing the association between time to sputum culture conversion and both the number of potentially effective drugs included in a regimen and the DST results of the drugs in the regimen. METHODS AND FINDINGS: We analyzed data from the Preserving Effective Tuberculosis Treatment Study (PETTS), a prospective observational study of 1,659 adults treated for MDR TB during 2005-2010 in nine countries: Estonia, Latvia, Peru, Philippines, Russian Federation, South Africa, South Korea, Thailand, and Taiwan. For all patients, monthly sputum samples were collected, and DST was performed on baseline isolates at the US Centers for Disease Control and Prevention. We included 1,137 patients in our analysis based on their having known baseline DST results for at least fluoroquinolones and second-line injectable drugs, and not having extensively drug-resistant TB. These patients were followed for a median of 20 mo (interquartile range 16-23 mo) after MDR TB treatment initiation. The primary outcome of interest was initial sputum culture conversion. We used Cox proportional hazards regression, stratifying by country to control for setting-associated confounders, and adjusting for the number of drugs to which patients' baseline isolates were resistant, baseline resistance pattern, previous treatment history, sputum smear result, and extent of disease on chest radiograph. In multivariable analysis, receiving an average of at least six potentially effective drugs (defined as drugs without a DST result indicating resistance) per day was associated with a 36% greater likelihood of sputum culture conversion than receiving an average of at least five but fewer than six potentially effective drugs per day (adjusted hazard ratio [aHR] 1.36, 95% CI 1.09-1.69). Inclusion of pyrazinamide (aHR 2.00, 95% CI 1.65-2.41) or more drugs to which baseline DST indicated susceptibility (aHR 1.65, 95% CI 1.48-1.84, per drug) in regimens was associated with greater increases in the likelihood of sputum culture conversion than including more drugs to which baseline DST indicated resistance (aHR 1.33, 95% CI 1.18-1.51, per drug). Including in the regimen more drugs for which DST was not performed was beneficial only if a minimum of three effective drugs was present in the regimen (aHR 1.39, 95% CI 1.09-1.76, per drug when three effective drugs present in regimen). The main limitation of this analysis is that it is based on observational data, not a randomized trial, and drug regimens varied across sites. However, PETTS was a uniquely large and rigorous observational study in terms of both the number of patients enrolled and the standardization of laboratory testing. Other limitations include the assumption of equivalent efficacy across drugs in a category, incomplete data on adherence, and the fact that the analysis considers only initial sputum culture conversion, not reversion or long-term relapse. CONCLUSIONS: MDR TB regimens including more potentially effective drugs than the minimum of five currently recommended by WHO may encourage improved response to treatment in patients with MDR TB. Rapid access to high-quality DST results could facilitate the design of more effective individualized regimens. Randomized controlled trials are necessary to confirm whether individualized regimens with more than five drugs can indeed achieve better cure rates than current recommended regimens. |
Epidemiology of primary multidrug-resistant tuberculosis, Vladimir Region, Russia
Ershova JV , Volchenkov GV , Kaminski DA , Somova TR , Kuznetsova TA , Kaunetis NV , Cegielski JP , Kurbatova EV . Emerg Infect Dis 2015 21 (11) 2048-51 We studied the epidemiology of drug-resistant tuberculosis (TB) in Vladimir Region, Russia, in 2012. Most cases of multidrug-resistant TB (MDR TB) were caused by transmission of drug-resistant strains, and >33% were in patients referred for testing after mass radiographic screening. Early diagnosis of drug resistance is essential for preventing transmission of MDR TB. |
Additional drug resistance of multidrug-resistant tuberculosis in patients in 9 countries
Kurbatova EV , Dalton T , Ershova J , Tupasi T , Caoili JC , Van Der Walt M , Kvasnovsky C , Yagui M , Bayona J , Contreras C , Leimane V , Via LE , Kim H , Akksilp S , Kazennyy BY , Volchenkov GV , Jou R , Kliiman K , Demikhova OV , Cegielski JP . Emerg Infect Dis 2015 21 (6) 977-83 Data from a large multicenter observational study of patients with multidrug-resistant tuberculosis (MDR TB) were analyzed to simulate the possible use of 2 new approaches to treatment of MDR TB: a short (9-month) regimen and a bedaquiline-containing regimen. Of 1,254 patients, 952 (75.9%) had no resistance to fluoroquinolones and second-line injectable drugs and thus would qualify as candidates for the 9-month regimen; 302 (24.1%) patients with resistance to a fluoroquinolone or second-line injectable drug would qualify as candidates for a bedaquiline-containing regimen in accordance with published guidelines. Among candidates for the 9-month regimen, standardized drug-susceptibility tests demonstrated susceptibility to a median of 5 (interquartile range 5-6) drugs. Among candidates for bedaquiline, drug-susceptibility tests demonstrated susceptibility to a median of 3 (interquartile range 2-4) drugs; 26% retained susceptibility to <2 drugs. These data may assist national TB programs in planning to implement new drugs and drug regimens. |
Sputum culture conversion as a prognostic marker for end-of-treatment outcome in patients with multidrug-resistant tuberculosis: a secondary analysis of data from two observational cohort studies
Kurbatova EV , Cegielski JP , Lienhardt C , Akksilp R , Bayona J , Becerra MC , Caoili J , Contreras C , Dalton T , Danilovits M , Demikhova OV , Ershova J , Gammino VM , Gelmanova I , Heilig CM , Jou R , Kazennyy B , Keshavjee S , Kim HJ , Kliiman K , Kvasnovsky C , Leimane V , Mitnick CD , Quelapio I , Riekstina V , Smith SE , Tupasi T , van der Walt M , Vasilyeva IA , Via LE , Viiklepp P , Volchenkov G , Walker AT , Wolfgang M , Yagui M , Zignol M . Lancet Respir Med 2015 3 (3) 201-9 BACKGROUND: Sputum culture conversion is often used as an early microbiological endpoint in phase 2 clinical trials of tuberculosis treatment on the basis of its assumed predictive value for end-of-treatment outcome, particularly in patients with drug-susceptible tuberculosis. We aimed to assess the validity of sputum culture conversion on solid media at varying timepoints, and the time to conversion, as prognostic markers for end-of-treatment outcome in patients with multidrug-resistant (MDR) tuberculosis. METHODS: We analysed data from two large cohort studies of patients with MDR tuberculosis. We defined sputum culture conversion as two or more consecutive negative cultures from sputum samples obtained at least 30 days apart. To estimate the association of 2 month and 6 month conversion with successful treatment outcome, we calculated odds ratios (ORs) and 95% CIs with random-effects multivariable logistic regression. We calculated predictive values with bivariate random-effects generalised linear mixed modelling. FINDINGS: We assessed data for 1712 patients who had treatment success, treatment failure, or who died. Among patients with treatment success, median time to sputum culture conversion was significantly shorter than in those who had poor outcomes (2 months [IQR 1-3] vs 7 months [3 to ≥24]; log-rank p<0.0001). Furthermore, conversion status at 6 months (adjusted OR 14.07 [95% CI 10.05-19.71]) was significantly associated with treatment success compared with failure or death. Sputum culture conversion status at 2 months was significantly associated with treatment success only in patients who were HIV negative (adjusted OR 4.12 [95% CI 2.25-7.54]) or who had unknown HIV infection (3.59 [1.96-6.58]), but not in those who were HIV positive (0.38 [0.12-1.18]). Thus, the overall association of sputum culture conversion with a successful outcome was substantially greater at 6 months than at 2 months. 2 month conversion had low sensitivity (27.3% [95% confidence limit 16.6-41.4]) and high specificity (89.8% [82.3-94.4]) for prediction of treatment success. Conversely, 6 month sputum culture conversion status had high sensitivity (91.8% [85.9-95.4]), but moderate specificity (57.8% [42.5-71.6]). The maximum combined sensitivity and specificity for sputum culture conversion was reached between month 6 and month 10 of treatment. INTERPRETATION: Time to sputum culture conversion, conversion status at 6 months, and conversion status at 2 months in patients without known HIV infection can be considered as proxy markers of end-of-treatment outcome in patients with MDR tuberculosis, although the overall association with treatment success is substantially stronger for 6 month than for 2 month conversion status. Investigators should consider these results regarding the validity of sputum culture conversion at various timepoints as an early predictor of treatment efficacy when designing phase 2 studies before investing substantial resources in large, long-term, phase 3 trials of new treatments for MDR tuberculosis. FUNDING: US Agency for International Development, US Centers for Disease Control and Prevention, Division of Intramural Research of the US National Institute of Allergy and Infectious Diseases, Korea Centers for Disease Control and Prevention. |
Mortality among tuberculosis patients with acquired resistance to second-line anti-tuberculosis drugs - United States, 1993-2008
Ershova JV , Kurbatova EV , Moonan PK , Cegielski JP . Clin Infect Dis 2014 59 (4) 465-72 BACKGROUND: Resistance to second-line anti-tuberculosis drugs (SLD) severely compromises treatment options of drug-resistant tuberculosis (TB). We assessed the association between acquisition of resistance (AR) to second-line injectable drugs (SLI) or fluoroquinolones (FQ) and mortality among TB cases confirmed by positive culture results with available initial and final drug susceptibility test (DST) results. METHODS: We analyzed data from U.S. National TB Surveillance System, 1993-2008. Acquired resistance was defined as drug susceptibility at initial DST but resistance to the same drug at final DST. We compared survival with Kaplan-Meier curves and analyzed the association between AR and mortality using a univariate extended Cox proportional hazards model adjusted for age. RESULTS: Of 2,329 cases with both initial and final DST to SLI, 49 (2.1%) acquired resistance; 13/49 (26.5%) had treatment terminated by death versus 222 (10.0%) of those without AR to SLI (P<0.001). Of 1,187 cases with both initial and final DST to FQ, 32 (2.8%) acquired resistance; 12/32 (37.5%) had treatment terminated by death versus 121 (10.9%) of those without AR to FQ (P=0.001). Controlling for age, mortality was significantly greater among cases with AR to SLD than among cases without AR (adjusted hazard ratio (aHR)[SLI], 2.8; 95% confidence interval (CI),1.4-5.4; aHR[FQ], 1.9; 95% CI,1.0-3.5). MDR TB at treatment initiation, positive HIV status, and extrapulmonary disease were also significantly associated with mortality. CONCLUSION: Mortality was significantly greater among TB cases with AR to SLD. Providers should consider AR to SLD early in treatment, monitor DST results, and avoid premature deaths. |
Association between Mycobacterium tuberculosis complex phylogenetic lineage and acquired drug resistance
Yuen CM , Kurbatova EV , Click ES , Cavanaugh JS , Cegielski JP . PLoS One 2013 8 (12) e83006 BACKGROUND: Development of resistance to antituberculosis drugs during treatment (i.e., acquired resistance) can lead to emergence of resistant strains and consequent poor clinical outcomes. However, it is unknown whether Mycobacterium tuberculosis complex species and lineage affects the likelihood of acquired resistance. METHODS: We analyzed data from the U.S. National Tuberculosis Surveillance System and National Tuberculosis Genotyping Service for tuberculosis cases during 2004-2011 with assigned species and lineage and both initial and final drug susceptibility test results. We determined univariate associations between species and lineage of Mycobacterium tuberculosis complex bacteria and acquired resistance to isoniazid, rifamycins, fluoroquinolones, and second-line injectables. We used Poisson regression with backward elimination to generate multivariable models for acquired resistance to isoniazid and rifamycins. RESULTS: M. bovis was independently associated with acquired resistance to isoniazid (adjusted prevalence ratio = 8.46, 95% CI 2.96-24.14) adjusting for HIV status, and with acquired resistance to rifamycins (adjusted prevalence ratio = 4.53, 95% CI 1.29-15.90) adjusting for homelessness, HIV status, initial resistance to isoniazid, site of disease, and administration of therapy. East Asian lineage was associated with acquired resistance to fluoroquinolones (prevalence ratio = 6.10, 95% CI 1.56-23.83). CONCLUSIONS: We found an association between mycobacterial species and lineage and acquired drug resistance using U.S. surveillance data. Prospective clinical studies are needed to determine the clinical significance of these findings, including whether rapid genotyping of isolates at the outset of treatment may benefit patient management. |
Performance of Cepheid (R) Xpert MTB/RIF (R) and TB-Biochip (R) MDR in two regions of Russia with a high prevalence of drug-resistant tuberculosis
Kurbatova EV , Kaminski DA , Erokhin VV , Volchenkov GV , Andreevskaya SN , Chernousova LN , Demikhova OV , Ershova JV , Kaunetis NV , Kuznetsova TA , Larionova EE , Smirnova TG , Somova TR , Vasilieva IA , Vorobieva AV , Zolkina SS , Cegielski JP . Eur J Clin Microbiol Infect Dis 2013 32 (6) 735-43 The purpose of this study was to assess the performance of Cepheid(R) Xpert MTB/RIF(R) ("Xpert") and TB-Biochip(R) MDR ("TB-Biochip"). Sputum specimens from adults with presumptive tuberculosis (TB) were homogenized and split for: (1) direct Xpert and microscopy, and (2) concentration for Xpert, microscopy, culture [Lowenstein-Jensen (LJ) solid media and Mycobacteria Growth Indicator Tube(R) (MGIT)], indirect drug susceptibility testing (DST) using the absolute concentration method and MGIT, and TB-Biochip. In total, 109 of 238 (45.8 %) specimens were culture-positive for Mycobacterium tuberculosis complex (MTBC), and, of these, 67 isolates were rifampicin resistant (RIF-R) by phenotypic DST and 64/67 (95.5 %) were isoniazid resistant (INH-R). Compared to culture of the same specimen, a single direct Xpert was more sensitive for detecting MTBC [95.3 %, 95 % confidence interval (CI), 90.0-98.3 %] than direct (59.6 %, 95 % CI, 50.2-68.5 %) or concentrated smear (85.3 %, 95 % CI, 77.7-91.1 %) or LJ culture (80.8 %, 95 % CI, 72.4-87.5 %); the specificity was 86.0 % (95 % CI, 78.9-91.3 %). Compared with MGIT DST, Xpert correctly identified 98.2 % (95 % CI, 91.5-99.9 %) of RIF-R and 95.5 % (95 % CI, 85.8-99.2 %) of RIF-susceptible (RIF-S) specimens. In a subset of 104 specimens, the sensitivity of TB-Biochip for MTBC detection compared to culture was 97.3 % (95 % CI, 91.0-99.5 %); the specificity was 78.1 % (95 % CI, 61.5-89.9 %). TB-Biochip correctly identified 100 % (95 % CI, 94.2-100 %) of RIF-R, 94.7 % (95 % CI, 76.7-99.7 %) of RIF-S, 98.2 % (95 % CI, 91.4-99.9 %) of INH-R, and 78.6 % (95 % CI, 52.1-94.2 %) of INH-S specimens compared to MGIT DST. Xpert and Biochip were similar in accuracy for detecting MTBC and RIF resistance compared to conventional culture methods. |
Epidemiology of pyrazinamide-resistant tuberculosis in the United States, 1999-2009
Kurbatova EV , Cavanaugh JS , Dalton T , Click E , Cegielski JP . Clin Infect Dis 2013 57 (8) 1081-93 BACKGROUND: Pyrazinamide (PZA) is essential in tuberculosis (TB) treatment. We describe the prevalence, trends and predictors of PZA resistance in Mycobacterium tuberculosis complex (MTBC) in the U.S. METHODS: We analyzed culture-positive MTBC cases with reported drug susceptibility tests (DST) for PZA in 38 jurisdictions routinely testing for PZA susceptibility from 1999-2009. National TB Genotyping Service data for 2004-2009 were used to distinguish Mycobacterium tuberculosis from Mycobacterium bovis and determine phylogenetic lineage. RESULTS: Overall 2.7% (2,167/79,321) of MTBC cases had PZA resistance, increasing annually from 2.0% to 3.3% during 1999-2009 (P<0.001), largely due to an increase in PZA monoresistance. PZA-monoresistant MTBC (versus drug-susceptible) was associated with age 0-24 years (adjusted prevalence ratio [aPR]=1.50, 95% CI 1.31-1.71), Hispanic ethnicity (aPR=3.52, 2.96-4.18), HIV infection (aPR=1.43, 1.15-1.77), extrapulmonary disease (aPR=3.02, 2.60-3.52), and normal chest radiograph (aPR=1.88, 1.63-2.16), and inversely associated with Asian (aPR=0.59, 0.47-0.73) and Black (aPR=0.37, 0.29-0.49) race. Among multidrug-resistant (MDR) cases 38.0% were PZA-resistant; PZA resistance in MDR MTBC was associated with female sex (aPR=1.25, 1.08-1.46) and previous TB diagnosis (aPR=1.37, 1.16-1.62). Of 28,080 cases with genotyping data, 925 (3.3%) had PZA resistance; 465/925 (50.3%) were M. bovis. In non-MDR M. tuberculosis cases, PZA resistance was higher in the Indo-Oceanic than the East Asian lineage (2.2% versus 0.9%; respectively; aPR=2.26, 1.53-3.36), but in MDR cases it was lower in the Indo-Oceanic lineage (22.0% versus 43.4%, respectively; aPR=0.54, 0.32-0.90). CONCLUSIONS: Specific human and mycobacterial characteristics were associated with pyrazinamide-resistant MTBC, reflecting both specific subgroups of the population and phylogenetic lineages of the mycobacteria. |
Prevalence of anti-tuberculosis drug resistance in foreign-born tuberculosis cases in the U.S. and in their countries of origin
Taylor AB , Kurbatova EV , Cegielski JP . PLoS One 2012 7 (11) e49355 BACKGROUND: Foreign-born individuals comprise >50% of tuberculosis (TB) cases in the U.S. Since anti-TB drug resistance is more common in most other countries, when evaluating a foreign-born individual for TB, one must consider the risk of drug resistance. Naturally, clinicians query The Global Project on Anti-tuberculosis Drug Resistance Surveillance (Global DRS) which provides population-based data on the prevalence of anti-TB drug resistance in 127 countries starting in 1994. However, foreign-born persons in the U.S. are a biased sample of the population of their countries of origin, and Global DRS data may not accurately predict their risk of drug resistance. Since implementing drug resistance surveillance in 1993, the U.S. National TB Surveillance System (NTSS) has accumulated systematic data on over 130,000 foreign-born TB cases from more than 200 countries and territories. Our objective was to determine whether the prevalence of drug resistance among foreign-born TB cases correlates better with data from the Global DRS or with data on foreign-born TB cases in the NTSS. METHODS AND FINDINGS: We compared the prevalence of resistance to isoniazid and rifampin among foreign-born TB cases in the U.S., 2007-2009, with US NTSS data from 1993 to 2006 and with Global DRS data from 1994-2007 visually with scatterplots and statistically with correlation and linear regression analyses. Among foreign-born TB cases in the U.S., 2007-2009, the prevalence of isoniazid resistance and multidrug resistance (MDR, i.e. resistance to isoniazid and rifampin), correlated much better with 1993-2006 US surveillance data (isoniazid: r = 0.95, P<.001, MDR: r = 0.75, P<.001) than with Global DRS data, 1994-2007 (isoniazid: r = 0.55, P = .001; MDR: r = 0.50, P<.001). CONCLUSION: Since 1993, the US NTSS has accumulated sufficient data on foreign-born TB cases to estimate the risk of drug resistance among such individuals better than data from the Global DRS. |
Acquired resistance to second-line drugs among persons with tuberculosis in the United States
Ershova JV , Kurbatova EV , Moonan PK , Cegielski JP . Clin Infect Dis 2012 55 (12) 1600-7 BACKGROUND: Acquired resistance to second-line drugs (SLD) is a problem in treating patients with drug-resistant tuberculosis (TB) worldwide. The objectives of this study were to identify risk factors for acquired resistance (AR) to injectable SLD and fluoroquinolones in the US National TB Surveillance System, 1993-2008. METHODS: We selected cases with initial and final drug susceptibility test (DST) results reported. We defined AR as resistance at the final DST but susceptibility to the same drug at the initial DST. We analyzed AR using 2-way frequency tables and multivariable logistic regression. RESULTS: Baseline prevalence of multidrug-resistant (MDR) and extensively drug-resistant (XDR)TB was 12.6% (1864/14,770) and 0.38% (56/14,770), respectively. Of 2,274 individuals without initial resistance to injectable SLD, 49 (2.2%) acquired resistance. Of 1,141 initially susceptible to fluoroquinolones, 32 (2.8%) acquired resistance. AR to injectable SLD was associated with age group 25-44 years (adjusted Odds Ratio [aOR], 2.7; 95% confidence interval [CI], 1.2-6.3), positive HIV status (aOR, 2.5; 95% CI, 1.3-4.7), MDR at treatment initiation (aOR, 5.5; 95% CI, 2.9-10.5), and treatment with any SLD (aOR, 2.4; 95% CI,1.2-4.7). AR to fluoroquinolones was associated with MDR TB at treatment initiation (aOR, 6.5; 95% CI, 2.9-14.6). CONCLUSION: Among patients with initial and final DST reported, risk factors for AR to injectable SLD included age, positive HIV status, MDR TB and initial treatment with any SLD, while the only predictor for AR to fluoroquinolones was MDR TB at treatment initiation. Providers should consider monitoring SLD DST for MDR TB patients in the indicated subgroups. |
Predictors of poor outcomes among patients treated for multidrug-resistant tuberculosis at DOTS-plus projects
Kurbatova EV , Taylor A , Gammino VM , Bayona J , Becerra M , Danilovitz M , Falzon D , Gelmanova I , Keshavjee S , Leimane V , Mitnick CD , Quelapio MI , Riekstina V , Viiklepp P , Zignol M , Cegielski JP . Tuberculosis (Edinb) 2012 92 (5) 397-403 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. |
Rifampicin-resistant Mycobacterium tuberculosis: susceptibility to isoniazid and other anti-tuberculosis drugs
Kurbatova EV , Cavanaugh JS , Shah NS , Wright A , Kim H , Metchock B , Van Deun A , Barrera L , Boulahbal F , Richter E , Martin-Casabona N , Arias F , Zemanova I , Drobniewski F , Santos Silva A , Coulter C , Lumb R , Cegielski JP . Int J Tuberc Lung Dis 2012 16 (3) 355-357 Based on data from 14 Supranational Tuberculosis (TB) Reference Laboratories worldwide, the proportion of rifampicin (RMP) resistant isolates that were isoniazid (INH) susceptible by phenotypic drug susceptibility testing varied widely (0.5-11.6%). RMP-resistant isolates that were INH-susceptible had significantly lower rates of resistance to other first- and second-line anti-tuberculosis drugs (except rifabutin) compared to multidrug-resistant isolates. RMP resistance is not a lways a good proxy for a presumptive diagnosis of multidrug-resistant TB, which has implications for use of molecular assays that identify only RMP resistanceassociated DNA mutations. (2012 The Union.) |
Global isoniazid resistance patterns in rifampin-resistant and rifampin-susceptible tuberculosis
Smith SE , Kurbatova EV , Cavanaugh JS , Cegielski JP . Int J Tuberc Lung Dis 2012 16 (2) 203-205 Following the World Health Organization's endorsement of the Xpert((R)) MTB/RIF assay, which rapidly and simultaneously diagnoses tuberculosis (TB) and detects resistance to rifampin (RMP), the question arises to what extent RMP resistance is an adequate marker for multidrug-resistant TB (MDR-TB). A retrospective analysis of data from >81 countries and subnational settings demonstrated that >40% of RMP-resistant isolates from new TB cases did not display resistance to isoniazid (INH) in settings with relatively low MDR-TB prevalence (one third of all countries and subnational settings). Results indicated the need for INH susceptibility testing in addition to RMP susceptibility testing. |
Frequency and type of microbiological monitoring of multidrug-resistant tuberculosis treatment
Kurbatova EV , Gammino VM , Bayona J , Becerra M , Danilovitz M , Falzon D , Gelmanova I , Keshavjee S , Leimane V , Mitnick CD , Quelapio MI , Riekstina V , Taylor A , Viiklepp P , Zignol M , Cegielski JP . Int J Tuberc Lung Dis 2011 15 (11) 1553-6 Monthly culture is usually recommended to monitor treatment of multidrug-resistant tuberculosis (MDR-TB). As mycobacterial laboratory capacity is limited in many settings, TB programs need evidence to decide whether monthly cultures are necessary compared to other approaches. We simulated three alternative monitoring strategies (culture every 2 or 3 months, and monthly smears alone) in a cohort of MDR-TB patients in Estonia, Latvia, Philippines, Russia and Peru from 2000 to 2004. This retrospective analysis illustrated that less frequent testing delays confirmation of bacteriological conversion. This would prolong intensive treatment, hospitalization and respiratory isolation, increasing cost and toxicity. After conversion, less frequent testing could delay diagnosis of possible treatment failure. |
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