Last data update: May 06, 2024. (Total: 46732 publications since 2009)
Records 1-30 (of 32 Records) |
Query Trace: Mase S[original query] |
---|
Notes from the field: Supply interruptions of first- and second-line oral drugs to treat tuberculosis during the previous 12 months - California, January-March, 2023
Nabity SA , Agraz-Lara R , Bravo A , Benjamin R , Fong V , Lam CK , Keh C , Mase S , Flood J . MMWR Morb Mortal Wkly Rep 2024 72 (5253) 1390-1391 Tuberculosis (TB) drug supply disruptions are a recurring concern in the United States (1). Contributors to these disruptions include loss of manufacturers to the U.S. market, inefficient supply chains, and lack of active ingredients available for import.* The last severe U.S. TB drug shortage occurred in 2012, when isoniazid (INH) was temporarily unavailable for several months (2). INH and rifampin (RIF) are the cornerstones for treatment of drug-susceptible TB, and rifapentine (RPT), a long acting rifamycin, has been incorporated into shorter first-line regimens† to treat both latent TB infection (LTBI) (3) and TB disease§ (4). In recent years, the U.S. supply of several TB drugs has again been disrupted. The Food and Drug Administration has declared shortages of RPT (on March 25, 2020), RIF (on December 22, 2021), and INH (on May 17, 2023).¶ Approximately one fifth of all U.S. TB cases are reported from California (5). TB drug procurement is decentralized among the state’s 61 local TB programs,** mirroring the decentralization among U.S. states and territories. The California Department of Public Health and the California TB Controllers Association assessed the impact of the shortage on California’s TB programs. |
Outbreak of COVID-19 among vaccinated and unvaccinated homeless shelter residents - Sonoma County, California, July 2021 (preprint)
Bukatko A , Lobato MN , Mosites E , Stainken C , Reihl K , Deldari M , Bell JM , Morris MK , Wadford DA , Harriman K , Mase S . medRxiv 2021 08 In July 2021, the Sonoma County Health Department was alerted to three cases of COVID-19 among residents of a homeless shelter in Santa Rosa, California. Among 153 shelter residents, 83 (54%) were fully vaccinated; 71 (86%) vaccinated residents had received the Janssen COVID-19 vaccine and 12 (14%) received an mRNA (Pfizer BioNTech or Moderna) COVID-19 vaccine. Within 1 month, 116 shelter residents (76%) received positive SARS-CoV-2 test results, including 66 fully vaccinated residents and 50 not fully vaccinated. 9 fully vaccinated and 1 unvaccinated were hospitalized for COVID-19. All hospitalized cases had at least one underlying medical condition. Two deaths occurred, one in a vaccinated resident and one in a non-vaccinated resident. Specimens from 52 residents underwent whole genome sequencing; all were identified as SARS-CoV-2, Delta Variant AY.13 lineage. Additional mitigation measures are needed in medically vulnerable congregate setting where limited resources make individual quarantine and isolation not feasible. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
A Genomic Survey of SARS-CoV-2 Reveals Multiple Introductions into Northern California without a Predominant Lineage (preprint)
Deng X , Gu W , Federman S , du Plessis L , Pybus OG , Faria N , Wang C , Yu G , Pan CY , Guevara H , Sotomayor-Gonzalez A , Zorn K , Gopez A , Servellita V , Hsu E , Miller S , Bedford T , Greninger AL , Roychoudhury P , Starita LM , Famulare M , Chu HY , Shendure J , Jerome KR , Anderson C , Gangavarapu K , Zeller M , Spencer E , Andersen KG , MacCannell D , Paden CR , Li Y , Zhang J , Tong S , Armstrong G , Morrow S , Willis M , Matyas BT , Mase S , Kasirye O , Park M , Chan C , Yu AT , Chai SJ , Villarino E , Bonin B , Wadford DA , Chiu CY . medRxiv 2020 The COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2 has spread globally, resulting in >300,000 reported cases worldwide as of March 21st, 2020. Here we investigate the genetic diversity and genomic epidemiology of SARS-CoV-2 in Northern California using samples from returning travelers, cruise ship passengers, and cases of community transmission with unclear infection sources. Virus genomes were sampled from 29 patients diagnosed with COVID-19 infection from Feb 3rd through Mar 15th. Phylogenetic analyses revealed at least 8 different SARS-CoV-2 lineages, suggesting multiple independent introductions of the virus into the state. Virus genomes from passengers on two consecutive excursions of the Grand Princess cruise ship clustered with those from an established epidemic in Washington State, including the WA1 genome representing the first reported case in the United States on January 19th. We also detected evidence for presumptive transmission of SARS-CoV-2 lineages from one community to another. These findings suggest that cryptic transmission of SARS-CoV-2 in Northern California to date is characterized by multiple transmission chains that originate via distinct introductions from international and interstate travel, rather than widespread community transmission of a single predominant lineage. Rapid testing and contact tracing, social distancing, and travel restrictions are measures that will help to slow SARS-CoV-2 spread in California and other regions of the USA. |
Reply to Chang and Yew
Sotgiu G , Battista Migliori G , Menzies D , Mase S , Chorba T , Seaworth B , Nahid P . Am J Respir Crit Care Med 2020 202 (5) 778-779 We appreciate the letter by Drs. Chang and Yew commenting on the Official Guidelines of the American Thoracic Society (ATS)/CDC/European Respiratory Society (ERS)/Infectious Disease Society of America (IDSA) on the treatment of multidrug-resistant tuberculosis (MDR-TB) (1). Three issues are raised in the letter: first, the certainty of the evidence on the use of linezolid and bedaquiline in the management of fluoroquinolone-sensitive and -resistant MDR-TB; second, the risk of resistance to these two drugs with generalized use, suggesting focused use of these drugs in selected patients might limit this hazard and minimize acquisition of resistance and serious adverse events; and third, that with broadening availability of rapid drug susceptibility testing (DST), optimized longer and existing standardized shorter-course regimens still have value. |
Response to Correspondence: The impact of smoking on TB treatment outcomes includes recurrent TB
Wang EY , Ahluwalia IB , Mase SR . Int J Tuberc Lung Dis 2020 24 (11) 1225a-1225 Thank you for the opportunity to respond to the Correspondence by Drs. Chiang and Bam1 with regards to recurrent TB as a treatment outcome associated with smoking. We appreciate their interest in our article and their questions concerning the three manuscripts that were not included in our meta-analysis.2 The first, by Balian et al.2 was not identified in our updated search in August of 2017. The two other articles, by Masjedi et al.3 and Leung et al.,4 were excluded from our meta-analysis as they included former smokers in their smoking definitions and models. Our meta-analysis attempted to focus solely on current smokers and we excluded articles that specifically identified their exposure group as including former smokers. However, we agree that former smoking may be an important risk factor to consider in future research regarding smoking and TB treatment outcomes. | | We also concur with the conclusion that recurrent TB is an important treatment outcome that should be considered in the context of smoking behavior. This was not explored in our meta-analysis, but we encourage others to include this in future research and reviews of this topic. |
Genomic surveillance reveals multiple introductions of SARS-CoV-2 into Northern California.
Deng X , Gu W , Federman S , du Plessis L , Pybus OG , Faria N , Wang C , Yu G , Bushnell B , Pan CY , Guevara H , Sotomayor-Gonzalez A , Zorn K , Gopez A , Servellita V , Hsu E , Miller S , Bedford T , Greninger AL , Roychoudhury P , Starita LM , Famulare M , Chu HY , Shendure J , Jerome KR , Anderson C , Gangavarapu K , Zeller M , Spencer E , Andersen KG , MacCannell D , Paden CR , Li Y , Zhang J , Tong S , Armstrong G , Morrow S , Willis M , Matyas BT , Mase S , Kasirye O , Park M , Masinde G , Chan C , Yu AT , Chai SJ , Villarino E , Bonin B , Wadford DA , Chiu CY . Science 2020 369 (6503) 582-587 The COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2 has spread globally, with >52,000 cases in California as of May 4, 2020. Here we investigate the genomic epidemiology of SARS-CoV-2 in Northern California from late January to mid-March 2020, using samples from 36 patients spanning 9 counties and the Grand Princess cruise ship. Phylogenetic analyses revealed the cryptic introduction of at least 7 different SARS-CoV-2 lineages into California, including epidemic WA1 strains associated with Washington State, with lack of a predominant lineage and limited transmission between communities. Lineages associated with outbreak clusters in 2 counties were defined by a single base substitution in the viral genome. These findings support contact tracing, social distancing, and travel restrictions to contain SARS-CoV-2 spread in California and other states. |
The impact of smoking on tuberculosis treatment outcomes: a meta-analysis
Wang EY , Arrazola RA , Mathema B , Ahluwalia IB , Mase SR . Int J Tuberc Lung Dis 2020 24 (2) 170-175 BACKGROUND: Cigarette smoking contributes to tuberculosis (TB) epidemiology. However, limited evidence exists on how smoking impacts TB treatment outcomes such as treatment loss to follow-up and culture conversion.METHODS: This meta-analysis assessed current evidence of the impact of active cigarette smoking on TB treatment outcomes. PubMed, Scopus, Embase, and the Cochrane Library were searched for English-language articles published from database inception through 2017. Articles addressing active pulmonary TB and cigarette smoking were identified and data abstracted. Smokers were defined as those who smoked every day or some days at the time of interview/diagnosis. Non-smokers did not smoke at the time of interview/diagnosis. Unfavorable outcomes included any outcome other than cure or completion of TB treatment. Three different data sets were examined: 8 articles addressing unfavorable treatment outcomes, 9 analyzing only treatment loss to follow-up, and 5 addressing delayed smear or culture conversion. Studies that had <20 subjects or that addressed only populations with comorbidities were excluded.RESULTS: We identified 1030 studies; 21 studies fulfilled the inclusion/exclusion criteria. Smokers had greater odds of unfavorable outcomes (pooled odds ratio [pOR] 1.23, 95%CI 1.14-1.33), delayed smear or culture conversion (pOR 1.55, 95%CI 1.04-2.07), and treatment loss to follow-up (pOR 1.35, 95%CI 1.21-1.50).CONCLUSION: Cigarette smoking is associated with negative treatment results and delayed conversion to negative smear or culture, suggesting smoking is an important factor for consideration in TB elimination efforts. |
Guidelines for the treatment of latent tuberculosis infection: Recommendations from the National Tuberculosis Controllers Association and CDC, 2020
Sterling TR , Njie G , Zenner D , Cohn DL , Reves R , Ahmed A , Menzies D , Horsburgh CRJr , Crane CM , Burgos M , LoBue P , Winston CA , Belknap R . MMWR Recomm Rep 2020 69 (1) 1-11 Comprehensive guidelines for treatment of latent tuberculosis infection (LTBI) among persons living in the United States were last published in 2000 (American Thoracic Society. CDC targeted tuberculin testing and treatment of latent tuberculosis infection. Am J Respir Crit Care Med 2000;161:S221-47). 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 (e.g., 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. |
Treatment of drug-resistant tuberculosis. An official ATS/CDC/ERS/IDSA Clinical Practice Guideline
Nahid P , Mase SR , Migliori GB , Sotgiu G , Bothamley GH , Brozek JL , Cattamanchi A , Cegielski JP , Chen L , Daley CL , Dalton TL , Duarte R , Fregonese F , Horsburgh CR Jr , Ahmad Khan F , Kheir F , Lan Z , Lardizabal A , Lauzardo M , Mangan JM , Marks SM , McKenna L , Menzies D , Mitnick CD , Nilsen DM , Parvez F , Peloquin CA , Raftery A , Schaaf HS , Shah NS , Starke JR , Wilson JW , Wortham JM , Chorba T , Seaworth B . Am J Respir Crit Care Med 2019 200 (10) e93-e142 Background: The American Thoracic Society, U.S. Centers for Disease Control and Prevention, European Respiratory Society, and Infectious Diseases Society of America jointly sponsored this new practice guideline on the treatment of drug-resistant tuberculosis (DR-TB). The document includes recommendations on the treatment of multidrug-resistant TB (MDR-TB) as well as isoniazid-resistant but rifampin-susceptible TB.Methods: Published systematic reviews, meta-analyses, and a new individual patient data meta-analysis from 12,030 patients, in 50 studies, across 25 countries with confirmed pulmonary rifampin-resistant TB were used for this guideline. Meta-analytic approaches included propensity score matching to reduce confounding. Each recommendation was discussed by an expert committee, screened for conflicts of interest, according to the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology.Results: Twenty-one Population, Intervention, Comparator, and Outcomes questions were addressed, generating 25 GRADE-based recommendations. Certainty in the evidence was judged to be very low, because the data came from observational studies with significant loss to follow-up and imbalance in background regimens between comparator groups. Good practices in the management of MDR-TB are described. On the basis of the evidence review, a clinical strategy tool for building a treatment regimen for MDR-TB is also provided.Conclusions: New recommendations are made for the choice and number of drugs in a regimen, the duration of intensive and continuation phases, and the role of injectable drugs for MDR-TB. On the basis of these recommendations, an effective all-oral regimen for MDR-TB can be assembled. Recommendations are also provided on the role of surgery in treatment of MDR-TB and for treatment of contacts exposed to MDR-TB and treatment of isoniazid-resistant TB. |
Treatment of drug-resistant tuberculosis
Mase SR , Chorba T . Clin Chest Med 2019 40 (4) 775-795 The treatment of drug-resistant tuberculosis (TB) is complicated and has evolved significantly in the past decade with the advent of rapid molecular tests and updated evidence-based guidelines of the World Health Organization and other organizations. The latest recommendations incorporate the use of new drugs and regimens that maximize efficacy and minimize toxicity to improve treatment outcomes for the patients. This article provides an overview of the latest published strategies for clinical and programmatic management of drug-resistant TB. |
Bedaquiline for the treatment of multidrug-resistant tuberculosis in the United States
Mase S , Chorba T , Parks S , Belanger A , Dworkin F , Seaworth B , Warkentin J , Barry P , Shah N . Clin Infect Dis 2019 71 (4) 1010-1016 BACKGROUND: In 2012, the Food and Drug Administration approved the use of bedaquiline fumarate as part of combination therapy for treatment of multidrug-resistant tuberculosis (MDR TB). We describe the treatment outcomes, safety, and tolerability of bedaquiline in our case series. METHODS: Data on patients started on bedaquiline for MDR TB between September 2012 and August 2016 were collected retrospectively through four TB programs using a standardized abstraction tool. Data were analyzed using univariate methods. Adverse events were graded using the Common Terminology Criteria for Adverse Events. RESULTS: Of 14 patients in this case series, 7/14 (50%) had MDR, 4/14 (29%) had pre-extensively-drug-resistant (XDR), and 3/14 (21%) had XDR. All had pulmonary TB, 5/14 (36%) had pulmonary and extrapulmonary TB, and 9/13 (69%) were smear-positive. One patient (7%) had HIV co-infection, 5/14 (36%) had diabetes mellitus, and 5 (36%) had been previously treated for TB. All patients were non-U.S.-born and 5 (36%) had private insurance. All patients achieved sputum culture conversion within a mean of 71 days (26-116); 6/14 after starting bedaquiline. Twelve (86%) completed treatment and 1/14 (7%) moved out of the country. One patient (7%) had QTc prolongation >500 milliseconds and died 20 months after discontinuing bedaquiline of a cause not attributable to the drug. The most common adverse events were peripheral neuropathy (50%), not customarily associated with bedaquiline use, and QTc prolongation (43%). CONCLUSIONS: Of 14 patients, one had an adverse event necessitating bedaquiline discontinuation. Safety, culture conversion, and treatment completion in this series support use of bedaquiline for the treatment of MDR/XDR TB. |
Tuberculosis Regional Training and Medical Consultation Centers in the United States: Characteristics, outcomes, and quality of medical consultations, June 1, 2010 - May 31, 2014
Mase SR , Samron R , Ashkin D , Castro KG , Ryan S , Seaworth B , Chen L , Lardizabal A , Tuckey D , Khan A , Posey DL , Chappelle C , Temesgen Z . J Clin Tuberc Other Mycobact Dis 2019 17 100114 Background: Tuberculosis (TB) Regional Training and Medical Consultation Centers (RTMCCs) were established in 2005 for TB medical consultation, training and education in the United States. A medical consultation database (MCD) captured all consultations provided by RTMCCs; we report on those provided from June 1, 2010 to May 31, 2014. Method(s): All MCD consultations during 2010-2014 were categorized into: provider type, setting, consultation topic, and patient age. We analyzed data frequencies and performed subgroup analyses by RTMCC, by TB incidence for the geographical area, and by year of consultation. End-user satisfaction was assessed by a 2016 telephone evaluation of RTMCC services. Result(s): A total of 11,074 consultations were delivered, with 10,754 (97.1%) in the U.S. and its current or former territories. Of these, 6018 (56%) were for high, 2443 (22.7%) for medium, and 2293 (21.3%) for low TB incidence settings. Most were for adults (81.3%) and answered within 24 h (96.2%). Nearly 2/3 consultations originated from health departments; providers included mostly physicians (44.3%) or nurses (37.6%). Common consult categories included TB disease (47.7%), case management (29.8%), latent TB infection (19.3%), diagnosis (16.1%), pharmacology (14.7%) and adverse side effects (14.3%). Among adverse side effects, hepatotoxicity was most common (39.6%). Volume and nature of consult requests remained relatively stable over the four-year period. Feedback from a 2016 CDC evaluation indicated overall satisfaction with RTMCC medical consultation services. Conclusion(s): RTMCCS were an important source of TB medical consultation over the time-frame of this assessment and provided quality expert consultation within 24 h. RMTCCs represent a reservoir of TB subject-matter expertise in the United States. |
Rifampin-resistant tuberculosis in the United States, 1998-2014
Sharling L , Marks SM , Goodman M , Chorba T , Mase S . Clin Infect Dis 2019 70 (8) 1596-1605 BACKGROUND: Monoresistance to rifamycins necessitates longer and more toxic regimens for tuberculosis (TB). We examined characteristics and mortality associated with rifampin-monoresistant (RMR) TB in the United States. METHODS: We analyzed Mycobacterium tuberculosis culture-positive cases reported to the National TB Surveillance System (excluding California because HIV infection was not reported to CDC during 2005-2010) between 1998 and 2014. We defined: (1) RMR TB found on initial drug susceptibility testing (DST), and (2) possible acquired rifampin-resistant (ARR) TB. We assessed temporal trends in RMR TB. For both classifications of rifampin resistance, we calculated adjusted risk ratios (adjRR) and 95% confidence intervals (CI) for social and clinical characteristics associated with mortality when compared to drug-susceptible TB in multivariable models using backwards selection. RESULTS: Of 180,329 TB cases, 126,431 (70%) cases were eligible for analysis, with 359 (0.28%) of eligible cases reported as RMR. The percentage of RMR TB cases with HIV declined 4% annually during 1998-2014. Persons with HIV and prior TB were more likely to have RMR TB (adjRR=25.9, CI=17.6-38.1), as were persons with HIV and no prior TB (adjRR=3.1, CI=2.4-4.1), versus those without either characteristic, controlling for other statistically significant variables. RMR cases had greater mortality (adjRR=1.4, CI=1.04-1.8), controlling for HIV and other variables. Persons with HIV had greater risk of ARR than persons without HIV (adjRR=9.6, CI=6.9-13.3) and ARR was also associated with increased mortality, controlling for HIV and other variables. CONCLUSIONS: All forms of rifampin resistance were positively associated with HIV infection and increased mortality. |
Tuberculosis in the United States: Medical consultation services provided by 5 Tuberculosis Regional Training and Medical Consultation Centers, 2013-2017
Goswami ND , Mase S , Griffith D , Bhavaraju R , Lardizabal A , Lauzardo M , Chen L , Wilson J , Chappelle C , Haley CA . Open Forum Infect Dis 2019 6 (6) ofz167 With only 9105 new US tuberculosis (TB) cases reported in 2017, expert consultation is essential for TB care. Data were captured 2013-2017 from consultations by 5 CDC-funded centers, now the TB Centers of Excellence (COEs). 14 586 consultations were provided to TB providers, most related to TB disease and treatment regimens. |
Higher rates of tuberculosis among class B1 Filipino immigrants to Hawaii compared to nationwide, 2010-2014
Schmit KM , Brostrom R , Largen A , Pyan A , Wang Z , Mase S , Morris S . J Immigr Minor Health 2019 21 (6) 1300-1305 BACKGROUND: Immigrants to the United States from countries with a high burden of tuberculosis (TB) who have abnormal chest radiographs but negative sputum cultures during pre-immigration screening (TB Class B1) have a high risk of being diagnosed with TB disease within 1 year of arrival. METHODS: Using 2010-2014 national surveillance data, we compared proportions of Class B1 Filipino immigrants who received a diagnosis of TB disease within 1 year of arrival to Hawaii to proportions in other U.S. states (not including Hawaii) using chi-squared tests. RESULTS: In Hawaii, 40/1190 (3.4%) of Class B1 Filipino immigrants to Hawaii received a diagnosis of TB disease within 1 year of arrival compared with 220/16,035 (1.4%) nationwide (P < .01). CONCLUSIONS: During 2010-2014, the percentage of recent Class B1 Filipino immigrants in Hawaii with TB disease diagnosed within 1 year of arrival was over twice that as nationwide. |
Tuberculosis preventive treatment: the next chapter of tuberculosis elimination in India
Moonan PK , Nair SA , Agarwal R , Chadha VK , Dewan PK , Gupta UD , Ho CS , Holtz TH , Kumar AM , Kumar N , Kumar P , Maloney SA , Mase SR , Oeltmann JE , Paramasivan CN , Parmar MM , Rade KK , Ramachandran R , Rao R , Salhorta VS , Sarin R , Sarin S , Sachdeva KS , Selvaraju S , Singla R , Surie D , Tonsing J , Tripathy SP , Khaparde SD . BMJ Glob Health 2018 3 (5) e001135 The End TB Strategy envisions a world free of tuberculosis-zero deaths, disease and suffering due to tuberculosis by 2035. This requires reducing the global tuberculosis incidence from >1250 cases per million people to <100 cases per million people within the next two decades. Expanding testing and treatment of tuberculosis infection is critical to achieving this goal. In high-burden countries, like India, the implementation of tuberculosis preventive treatment (TPT) remains a low priority. In this analysis article, we explore potential challenges and solutions of implementing TPT in India. The next chapter in tuberculosis elimination in India will require cost-effective and sustainable interventions aimed at tuberculosis infection. This will require constant innovation, locally driven solutions to address the diverse and dynamic tuberculosis epidemiology and persistent programme monitoring and evaluation. As new tools, regimens and approaches emerge, midcourse adjustments to policy and practice must be adopted. The development and implementation of new tools and strategies will call for close collaboration between local, national and international partners-both public and private-national health authorities, non-governmental organisations, research community and the diagnostic and pharmaceutical industry. Leading by example, India can contribute to global knowledge through operational research and programmatic implementation for combating tuberculosis infection. |
Treatment correlates of successful outcomes in pulmonary multidrug-resistant tuberculosis: an individual patient data meta-analysis
Ahmad N , Ahuja SD , Akkerman OW , Alffenaar JC , Anderson LF , Baghaei P , Bang D , Barry PM , Bastos ML , Behera D , Benedetti A , Bisson GP , Boeree MJ , Bonnet M , Brode SK , Brust JCM , Cai Y , Caumes E , Cegielski JP , Centis R , Chan PC , Chan ED , Chang KC , Charles M , Cirule A , Dalcolmo MP , D'Ambrosio L , de Vries G , Dheda K , Esmail A , Flood J , Fox GJ , Frechet-Jachym M , Fregona G , Gayoso R , Gegia M , Gler MT , Gu S , Guglielmetti L , Holtz TH , Hughes J , Isaakidis P , Jarlsberg L , Kempker RR , Keshavjee S , Khan FA , Kipiani M , Koenig SP , Koh WJ , Kritski A , Kuksa L , Kvasnovsky CL , Kwak N , Lan Z , Lange C , Laniado-Laborin R , Lee M , Leimane V , Leung CC , Leung EC , Li PZ , Lowenthal P , Maciel EL , Marks SM , Mase S , Mbuagbaw L , Migliori GB , Milanov V , Miller AC , Mitnick CD , Modongo C , Mohr E , Monedero I , Nahid P , Ndjeka N , O'Donnell MR , Padayatchi N , Palmero D , Pape JW , Podewils LJ , Reynolds I , Riekstina V , Robert J , Rodriguez M , Seaworth B , Seung KJ , Schnippel K , Shim TS , Singla R , Smith SE , Sotgiu G , Sukhbaatar G , Tabarsi P , Tiberi S , Trajman A , Trieu L , Udwadia ZF , van der Werf TS , Veziris N , Viiklepp P , Vilbrun SC , Walsh K , Westenhouse J , Yew WW , Yim JJ , Zetola NM , Zignol M , Menzies D . Lancet 2018 392 (10150) 821-834 BACKGROUND: Treatment outcomes for multidrug-resistant tuberculosis remain poor. We aimed to estimate the association of treatment success and death with the use of individual drugs, and the optimal number and duration of treatment with those drugs in patients with multidrug-resistant tuberculosis. METHODS: In this individual patient data meta-analysis, we searched MEDLINE, Embase, and the Cochrane Library to identify potentially eligible observational and experimental studies published between Jan 1, 2009, and April 30, 2016. We also searched reference lists from all systematic reviews of treatment of multidrug-resistant tuberculosis published since 2009. To be eligible, studies had to report original results, with end of treatment outcomes (treatment completion [success], failure, or relapse) in cohorts of at least 25 adults (aged >18 years). We used anonymised individual patient data from eligible studies, provided by study investigators, regarding clinical characteristics, treatment, and outcomes. Using propensity score-matched generalised mixed effects logistic, or linear regression, we calculated adjusted odds ratios and adjusted risk differences for success or death during treatment, for specific drugs currently used to treat multidrug-resistant tuberculosis, as well as the number of drugs used and treatment duration. FINDINGS: Of 12 030 patients from 25 countries in 50 studies, 7346 (61%) had treatment success, 1017 (8%) had failure or relapse, and 1729 (14%) died. Compared with failure or relapse, treatment success was positively associated with the use of linezolid (adjusted risk difference 0.15, 95% CI 0.11 to 0.18), levofloxacin (0.15, 0.13 to 0.18), carbapenems (0.14, 0.06 to 0.21), moxifloxacin (0.11, 0.08 to 0.14), bedaquiline (0.10, 0.05 to 0.14), and clofazimine (0.06, 0.01 to 0.10). There was a significant association between reduced mortality and use of linezolid (-0.20, -0.23 to -0.16), levofloxacin (-0.06, -0.09 to -0.04), moxifloxacin (-0.07, -0.10 to -0.04), or bedaquiline (-0.14, -0.19 to -0.10). Compared with regimens without any injectable drug, amikacin provided modest benefits, but kanamycin and capreomycin were associated with worse outcomes. The remaining drugs were associated with slight or no improvements in outcomes. Treatment outcomes were significantly worse for most drugs if they were used despite in-vitro resistance. The optimal number of effective drugs seemed to be five in the initial phase, and four in the continuation phase. In these adjusted analyses, heterogeneity, based on a simulated I(2) method, was high for approximately half the estimates for specific drugs, although relatively low for number of drugs and durations analyses. INTERPRETATION: Although inferences are limited by the observational nature of these data, treatment outcomes were significantly better with use of linezolid, later generation fluoroquinolones, bedaquiline, clofazimine, and carbapenems for treatment of multidrug-resistant tuberculosis. These findings emphasise the need for trials to ascertain the optimal combination and duration of these drugs for treatment of this condition. FUNDING: American Thoracic Society, Canadian Institutes of Health Research, US Centers for Disease Control and Prevention, European Respiratory Society, Infectious Diseases Society of America. |
Pediatric tuberculosis consultations across 5 CDC regional tuberculosis training and medical consultation Centers
Mase A , Ryan S , Mader G , Alvarez A , Armitige L , Chen L , McSherry G , Wilson J , Mase S , Banerjee R . J Clin Tuberc Other Mycobact Dis 2018 11 23-27 Background: The U.S. Centers for Disease Control and Prevention (CDC) funds five Regional Tuberculosis Training and Medical Consultation Centers (RTMCCs) that provide training and consultation for tuberculosis (TB) control and management. RTMCC utilization for assistance with diagnosis and management of TB in children has not been described. We analyzed pediatric TB consultations performed across all RTMCCs in terms of question type, provider type, and setting. Methods: The CDC medical consultation database was queried for consultations regarding patients ≤ 18 years provided between 1/1/13–4/22/15 by all RTMCCs (Curry International TB Center, Heartland National TB Center, Mayo Clinic Center for TB, New Jersey Medical School Global TB Institute, Southeastern National TB Center). Each query was categorized into multiple subject areas based on provider type, setting, consultation topic, and patient age. Results: The 5 RTMCCs received 1164 pediatric consultation requests, representing approximately 20% of all consultations performed by the centers during the study period. Providers requesting consults were primarily physicians (46.3%) or nurses (45.0%). The majority of pediatric consult requests were from state and local public health departments (679, 58.3%) followed by hospital providers (199, 17.1%); fewer requests came from clinicians in private practice (84, 7.2%) or academic institutions (40, 3.4%). Consults addressed 14 different topics, most commonly management of children with TB disease (19.1%), latent TB infection (LTBI) (18.2%), diagnosis or laboratory testing (18.7%), and pharmacology (9.2%). Discussion: Pediatric consultations accounted for approximately 20% of all consultations performed by RTMCCs during the study period. RTMCCs were utilized primarily by public health departments regarding management of TB disease, LTBI, and diagnosis or laboratory testing. The relative underutilization of the RTMCCs by clinicians in non-public health settings, who often manage children with TB exposure or infection, warrants further study. As US TB case rates decline and providers become less experienced with childhood TB, medical consultation support may become increasingly important. |
The California Multidrug-Resistant Tuberculosis Consult Service: a partnership of state and local programs
Shah NS , Westenhouse J , Lowenthal P , Schecter G , True L , Mase S , Barry PM , Flood J . Public Health Action 2018 8 (1) 7-13 Background: The US Centers for Disease Control and Prevention recommend expert consultation for multi-drug-resistant tuberculosis (MDR-TB) cases. In 2002, the California MDR-TB Service was created to provide expert MDR-TB consultations. We describe the characteristics, treatment outcomes and management of patients referred to the Service. Methods: Surveillance data were used for descriptive analysis of cases, with consultation during July 2002-December 2012. Clinical consultation data and modified World Health Organization indicators were used to assess the care and management of cases, with consultation from January 2009 to December 2012. Results: Of 339 MDR-TB patients, 140 received a consultation. The proportion of patients receiving a consultation increased from 12% in 2002 to 63% in 2012. There were 24 pre-extensively drug-resistant TB and 5 patients with extensively drug-resistant TB. The majority (n = 123, 88%) completed treatment, 5 (4%) died, 7 (5%) moved before treatment completion, 4 (3%) stopped treatment due to an adverse event and 1 (1%) had an unknown outcome. Indicator data showed that 86% underwent rapid molecular drug susceptibility testing, 98% received at least four drugs to which they had known or presumed susceptibility, and 93% culture converted within 6 months. Conclusions: Consultations with the MDR-TB Service increased over time. Results highlight successful treatment and indicator outcomes. |
High rate of treatment completion in program settings with 12-dose weekly isoniazid and rifapentine (3HP) for latent Mycobacterium tuberculosis infection
Sandul AL , Nwana N , Holcombe JM , Lobato MN , Marks S , Webb R , Wang SH , Stewart B , Griffin P , Hunt G , Shah N , Marco A , Patil N , Mukasa L , Moro RN , Jereb J , Mase S , Chorba T , Bamrah-Morris S , Ho CS . Clin Infect Dis 2017 65 (7) 1085-1093 Background: RCTs demonstrated the newest LTBI regimen, 12 weekly doses of directly observed isoniazid and rifapentine (3HP), as efficacious as 9 months of isoniazid (9H) with a greater completion rate (82% versus 69%); however, 3HP has not been assessed in routine health care settings. Methods: Observational cohort of LTBI patients receiving 3HP through 16 US programs was used to assess treatment completion, adverse drug reactions (ADRs), and factors associated with treatment discontinuation. Results: Of 3288 patients eligible to complete 3HP, 2867 (87.2%) completed treatment. Children 2-17 years had the highest completion rate, 94.5% (155/164). Patients reporting homelessness had a completion rate of 81.2% (147/181). In univariable analyses, discontinuation was lowest among children (relative risk [RR], 0.44 [95% CI, 0.23-0.85]; P = .014), and highest in persons ≥65 years (RR, 1.72 [95% CI, 1.25-2.35] P = .001). In multivariable analyses, discontinuation was lowest among contacts of patients with TB disease (adjusted relative risk [ARR], 0.68 [95% CI, 0.52-0.89]; P = .005), and students (ARR, 0.45 [95% CI, 0.21-0.98]; P = .044); highest with incarceration (ARR, 1.43 [95% CI, 1.08-1.89]; P=.013) and homelessness (ARR, 1.72 [95% CI, 1.25-2.39]; P = .001). ADRs were reported by 1174 (35.7%) patients, of whom 891 (76.0%) completed treatment. Conclusions: Completion of 3HP in routine health care settings was greater overall than rates reported from clinical trials, and greater than historically observed using other regimens among reportedly nonadherent populations. Widespread use of 3HP for LTBI treatment could accelerate elimination of TB disease in the United States. |
Systematic review, meta-analysis, and cost effectiveness of treatment of latent tuberculosis infection to reduce progression to multidrug-resistant tuberculosis
Marks SM , Mase SR , Bamrah Morris S . Clin Infect Dis 2017 64 (12) 1670-1677 Background: Evidence-based recommendations for treating persons having presumed latent tuberculosis infection (LTBI) after contact to infectious multidrug-resistant tuberculosis (MDR TB) are lacking because published data consist of small observational studies. TB incidence in persons treated for latent multidrug-resistant-TB infection (MDR LTBI) is unknown. Methods: We conducted a systematic review of studies published (1/1/1994-12/31/2014) to analyze TB incidence, treatment completion and discontinuation, and cost effectiveness. We considered contacts with LTBI effectively treated if they were on ≥ one medication to which their MDR-TB strain was likely susceptible. We selected studies that compared treatment versus non-treatment outcomes and performed meta-analysis to estimate the relative risk of TB incidence and its 95% confidence interval. Results: We abstracted data from 21 articles that met inclusion criteria. Six articles presented outcomes for contacts who were treated compared with those not treated for MDR LTBI; 10 presented outcomes only for treated contacts, and five presented outcomes only for untreated contacts. The estimated MDR TB incidence reduction was 90% (9%-99%) using data from five comparison studies. We also found high treatment discontinuation rates due to adverse effects in persons taking pyrazinamide-containing regimens. Cost effectiveness was greatest using a fluoroquinolone/ethambutol combination regimen. Conclusions: Few studies met inclusion criteria, therefore results should be cautiously interpreted. We found a reduced risk of TB incidence with treatment for MDR LTBI, suggesting effectiveness in prevention of progression to MDR TB, and confirmed cost effectiveness. However, we found that pyrazinamide-containing MDR-LTBI regimens often resulted in treatment discontinuation due to adverse effects. |
Outcomes and costs of out-patient MDR-TB care in the USA
Marks SM , Hirsch-Moverman Y , Seaworth B , Salcedo K , Graviss EA , Armstrong L , Armitige L , Flood J , Mase S . Int J Tuberc Lung Dis 2017 21 (4) 477-478 We recently published an analysis of the characteristics and costs of in-patient care for multidrug-resistant tuberculosis (MDR-TB) in the United States, which extended previous analyses of a population-based sample of MDR-TB cases reported to the US Centers for Disease Control and Prevention from 2005 to 2007 and treated through 2012.1,2 These analyses did not focus on patients who were treated only in out-patient settings. Out-patient outcomes are important to document because the evidence behind the conditional recommendation by the World Health Organization to treat MDR-TB patients using mainly ambulatory care rather than hospitalization is of very low quality.3 The rationale for the recommendation was to reduce resource use and treatment delays, which contribute to transmission in facilities and the community. | We performed a secondary analysis of the population-based sample of 135 US MDR-TB patients to describe the characteristics, outcomes, and costs for 37 patients treated only in out-patient settings versus those with some in-patient care. Compared to patients receiving some in-patient care, patients aged 15–24 years (n = 24) had greater odds of out-patient-only treatment than patients aged ⩾25 years (n = 111) (odds ratio [OR] 2.8, 95% confidence interval [CI] 1.1–6.9). No patient with human immunodeficiency virus (HIV) infection, end-stage renal disease, or cancer, and one diabetic patient had out-patient-only care. Patients with acid-fast bacilli sputum smear-positive TB (OR 0.24, 95%CI 0.10–0.56), cavitary (OR 0.26, CI 0.11–0.64), multilobe (OR 0.19, 95%CI 0.08–0.46), or miliary (0%) disease had lower odds of out-patient-only treatment. |
Characteristics and costs of multidrug-resistant tuberculosis in-patient care in the United States, 2005-2007
Marks SM , Hirsch-Moverman Y , Salcedo K , Graviss EA , Oh P , Seaworth B , Flood J , Armstrong L , Armitige L , Mase S . Int J Tuberc Lung Dis 2016 20 (4) 435-41 OBJECTIVE: A population-based study of 135 multidrug-resistant tuberculosis (MDR-TB) patients reported to the Centers for Disease Control and Prevention (CDC) during 2005-2007 found 73% were hospitalized. We analyzed factors associated with hospitalization. METHODS: We assessed statistically significant multivariable associations with US in-patient TB diagnosis, frequency of hospitalization, length of hospital stay, and in-patient direct costs to the health care system. RESULTS: Of 98 hospitalized patients, 83 (85%) were foreign-born. Blacks, diabetics, or smokers were more likely, and patients with disseminated disease less likely, to receive their TB diagnosis while hospitalized. Patients aged 65 years, those with the acquired immune-deficiency syndrome (AIDS), or with private insurance, were hospitalized more frequently. Excluding deaths, length of stay was greater for patients aged 65 years, those with extensively drug-resistant TB (XDR-TB), those residing in Texas, those with AIDS, those who were unemployed, or those who had TB resistant to all first-line medications vs. others. Average hospitalization cost per XDR-TB patient (US$285 000) was 3.5 times that per MDR-TB patient (US$81 000), in 2010 dollars. Hospitalization episode costs for MDR-TB rank third highest and those for XDR-TB highest among the principal diagnoses. CONCLUSIONS: Hospitalization was common and remains a critical care component for patients who were older, had comorbidities, or required complex management due to XDR-TB. MDR-TB in-patient costs are among the highest for any disease. |
Pharmacokinetics and dosing of levofloxacin in children treated for active or latent multidrug-resistant tuberculosis, Federated States of Micronesia and Republic of the Marshall Islands
Mase SR , Jereb JA , Gonzalez D , Martin F , Daley CL , Fred D , Loeffler A , Menon L , Morris SB , Brostrom R , Chorba T , Peloquin CA . Pediatr Infect Dis J 2015 35 (4) 414-21 BACKGROUND: In the Federated States of Micronesia (FSM) and then the Republic of the Marshall Islands (RMI), levofloxacin pharmacokinetics (PK) were studied in children receiving directly observed once-daily regimens (10 mg/kg, age <5 years; 15 20 mg/kg, age ≤5 years) for either multidrug-resistant tuberculosis (MDR TB) disease or latent infection after MDR TB exposure, to inform future dosing strategies. METHODS: Blood samples were collected at 0 (RMI only), 1, 2, and 6 hours (50 children, aged 6 months to 15 years) after oral levofloxacin at >6 weeks of treatment. Clinical characteristics and levofloxacin Cmax, elimination half-life (t1/2), and area under the curve from 0 to 24 hours (AUC0-24 hours * microg/mL) were correlated to determine optimal dosage and to examine associations. Population PK and target attainment were modeled. With results from FSM, dosages were increased in RMI toward the target maximal drug concentration (Cmax) for Mycobacterium tuberculosis, 8-12 microg/ml. RESULTS: Cmax correlated linearly with per-weight dosage. Neither Cmax nor t1/2 was associated with gender, age, body mass index, concurrent medications, or pre-dose meals. At levofloxacin dosage of 15-20 mg/kg, Cmax ≥ 8 microg/ml was observed, and modeling corroborated a high target attainment across the ratio of the area under the free-concentration-versus-time curve to minimum inhibitory concentration (fAUCss,0-24/MIC) values. CONCLUSIONS: Levofloxacin dosage should be 15-20 mg/kg for Cmax ≥ 8 microg/ml and a high target attainment across fAUCss,0-24/MIC values in children ≥2 years of age. |
Tuberculosis and diabetes mellitus in the Republic of Kiribati: a case-control study
Viney K , Cavanaugh J , Kienene T , Harley D , Kelly PM , Sleigh A , O'Connor J , Mase S . Trop Med Int Health 2015 20 (5) 650-657 OBJECTIVES: To better inform local management of TB-diabetes collaborative activities, we aimed to determine the prevalence of diabetes among persons with and without TB and to determine the association between TB and diabetes in Kiribati, a Pacific Island nation. METHODS: We compared consecutively enrolled TB cases to a group of randomly selected community controls without evidence of TB. Diabetes was diagnosed by HbA1c, and clinical and demographic data were collected. A tuberculin skin test was administered to controls. The chi-square test was used to assess significance in differences between cases and controls. We also calculated an odds ratio, with 95% confidence intervals, for the odds of diabetes among cases relative to controls. Unweighted multivariate logistic regression was performed to adjust for the effects of age and sex. RESULTS: A total of 275 TB cases and 499 controls were enrolled. The diabetes prevalence in cases (101, 37%) was significantly greater than in controls (94, 19%) (adjusted odds ratio: 2.8; 95% CI 2.0-4.1). Fifty-five percent (108) of all diabetic diagnoses were new; this proportion was higher among controls (64.8%) than cases (46.5%). Five patients with TB were screened to detect one patient with diabetes. CONCLUSIONS: There is a strong association between TB and diabetes in Kiribati and bidirectional screening should be conducted in this setting. |
Effect of diabetes on tuberculosis presentation and outcomes in Kiribati
Cavanaugh J , Viney K , Kienene T , Harley D , Kelly PM , Sleigh A , O'Connor J , Mase S . Trop Med Int Health 2015 20 (5) 643-649 OBJECTIVES: To determine the association between diabetes and the clinical features and treatment outcomes of TB in Kiribati. METHODS: We enrolled consecutive TB patients who presented from August 2010 to February 2012 and compared clinical features and TB treatment outcomes for patients with and without diabetes, as measured by hemoglobin A1c assay. Poor outcome was defined as death, default or treatment failure, and good outcome as treatment success or cure. RESULTS: 275 eligible persons with TB disease were enrolled; 101 (37%) had diabetes. TB patients with diabetes were more likely to have acid-fast bacilli (AFB) seen on sputum-smear microscopy (RR: 1.3; 95% CI: 1.03-1.62). The risk of poor outcome did not differ between patients with or without diabetes (RR: 1.1; 95% CI: 0.5-2.7). CONCLUSION: TB patients with diabetes are more likely than those without to have sputum with AFB on microscopy. This could increase transmission in the community. Early detection of TB by screening patients with diabetes, and the converse, could be important public health interventions where diabetes and TB are prevalent. |
Treatment for LTBI in contacts of MDR-TB patients, Federated States of Micronesia, 2009-2012
Bamrah S , Brostrom R , Dorina F , Setik L , Song R , Kawamura LM , Heetderks A , Mase S . Int J Tuberc Lung Dis 2014 18 (8) 912-918 SETTING: Few studies have shown the operational feasibility, safety, tolerability, or outcomes of multi-drug-resistant latent tuberculous infection (MDR LTBI) treatment. After two simultaneous multidrug-resistant tuberculosis (MDR-TB) outbreaks in Chuuk, Federated States of Micronesia, infected contacts were offered a 12-month fluoroquinolone (FQ) based MDR LTBI treatment regimen. DESIGN: Between January 2009 and February 2012, 119 contacts of MDR-TB patients were followed using a prospective observational study design. After MDR-TB disease was excluded, 12 months of daily FQ-based preventive treatment of MDR LTBI was provided by directly observed therapy. RESULTS: Among the 119 infected contacts, 15 refused, while 104 began treatment for MDR LTBI. Of the 104 who initiated treatment, 93 (89%) completed treatment, while 4 contacts discontinued due to adverse effects. None of the 104 contacts who undertook MDR LTBI treatment of any duration developed MDR-TB disease; however, 3 of 15 contacts who refused and 15 unidentified contacts developed MDR-TB disease. CONCLUSION: Providing treatment for MDR LTBI can be accomplished in a resource-limited setting, and contributed to preventing MDR-TB disease. The Chuuk TB program implemented treatment of MDR LTBI with an 89% completion rate. The MDR LTBI regimens were safe and well tolerated, and no TB cases occurred among persons treated for MDR LTBI. |
Treatment practices, outcomes, and costs of multidrug-resistant and extensively drug-resistant tuberculosis, United States, 2005-2007
Marks SM , Flood J , Seaworth B , Hirsch-Moverman Y , Armstrong L , Mase S , Salcedo K , Oh P , Graviss EA , Colson PW , Armitige L , Revuelta M , Sheeran K . Emerg Infect Dis 2014 20 (5) 812-21 To describe factors associated with multidrug-resistant (MDR), including extensively-drug-resistant (XDR), tuberculosis (TB) in the United States, we abstracted inpatient, laboratory, and public health clinic records of a sample of MDR TB patients reported to the Centers for Disease Control and Prevention from California, New York City, and Texas during 2005-2007. At initial diagnosis, MDR TB was detected in 94% of 130 MDR TB patients and XDR TB in 80% of 5 XDR TB patients. Mutually exclusive resistance was 4% XDR, 17% pre-XDR, 24% total first-line resistance, 43% isoniazid/rifampin/rifabutin-plus-other resistance, and 13% isoniazid/rifampin/rifabutin-only resistance. Nearly three-quarters of patients were hospitalized, 78% completed treatment, and 9% died during treatment. Direct costs, mostly covered by the public sector, averaged $134,000 per MDR TB and $430,000 per XDR TB patient; in comparison, estimated cost per non-MDR TB patient is $17,000. Drug resistance was extensive, care was complex, treatment completion rates were high, and treatment was expensive. |
Provisional CDC guidelines for the use and safety monitoring of bedaquiline fumarate (Sirturo) for the treatment of multidrug-resistant tuberculosis
Mase S , Chorba T , Lobue P , Castro K . MMWR Recomm Rep 2013 62 1-12 Multidrug-resistant tuberculosis (MDR TB) is caused by Mycobacterium tuberculosis that is resistant to at least isoniazid and rifampin, the two most effective of the four first-line TB drugs (the other two drugs being ethambutol and pyrazinamide). MDR TB includes the subcategory of extensively drug-resistant TB (XDR TB), which is MDR TB with additional resistance to any fluoroquinolone and to at least one of three injectable anti-TB drugs (i.e., kanamycin, capreomycin, or amikacin). MDR TB is difficult to cure, requiring 18-24 months of treatment after sputum culture conversion with a regimen that consists of four to six medications with toxic side effects, and carries a mortality risk greater than that of drug-susceptible TB. Bedaquiline fumarate (Sirturo or bedaquiline) is an oral diarylquinoline. On December 28, 2012, on the basis of data from two Phase IIb trials (i.e., well-controlled trials to evaluate the efficacy and safety of drugs in patients with a disease or condition to be treated, diagnosed, or prevented), the Food and Drug Administration (FDA) approved use of bedaquiline under the provisions of the accelerated approval regulations for "serious or life-threatening illnesses" (21CFR314.500) (Cox EM. FDA accelerated approval letter to Janssen Research and Development. Available at http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2012/204384Orig1s000ltr.pdf). This report provides provisional CDC guidelines for FDA-approved and unapproved, or off-label, uses of bedaquiline in certain populations, such as children, pregnant women, or persons with extrapulmonary MDR TB who were not included in the clinical trials for the drug. CDC's Division of TB Elimination developed these guidelines on the basis of expert opinion informed by data from systematic reviews and literature searches. This approach is different from the statutory standards that FDA uses when approving drugs and drug labeling. These guidelines are intended for health-care professionals who might use bedaquiline for the treatment of MDR TB for indicated and off-label uses. Aspects of these guidelines are not identical to current FDA-approved labeling for bedaquiline. Bedaquiline should be used with clinical expert consultation as part of combination therapy (minimum four-drug treatment regimen) and administered by direct observation to adults aged ≥18 years with a diagnosis of pulmonary MDR TB (Food and Drug Administration. SIRTURO [bedaquiline] tablets label. Available at http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/204384s000lbl.pdf). Use of the drug also can be considered for individual patients in other categories (e.g., persons with extrapulmonary TB, children, pregnant women, or persons with HIV or other comorbid conditions) when treatment options are limited. However, further study is required before routine use of bedaquiline can be recommended in these populations. A registry for persons treated with bedaquiline is being implemented by Janssen Therapeutics to track patient outcomes, adverse reactions, laboratory testing results (e.g., diagnosis, drug susceptibility, and development of drug resistance), use of concomitant medications, and presence of other comorbid conditions. Suspected adverse reactions (i.e., any adverse event for which there is a reasonable possibility that the drug caused the adverse event) and serious adverse events (i.e., any adverse event that results in an outcome such as death, hospitalization, permanent disability, or a life-threatening situation) should be reported to Janssen Therapeutics at telephone 1-800-526-7736, to FDA at telephone 1-800-332-1088 or at http://www.fda.gov/medwatch, and to CDC's Emergency Operations Center at telephone 1-770-488-7100. |
Surgical interventions for drug-resistant tuberculosis: a systematic review and meta-analysis
Marrone MT , Venkataramanan V , Goodman M , Hill AC , Jereb JA , Mase SR . Int J Tuberc Lung Dis 2013 17 (1) 6-16 BACKGROUND: With the emergence of multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB), surgery, which had been replaced by short-course chemotherapy, is again being considered a viable treatment option. OBJECTIVE: To assess the literature on the effectiveness of surgical interventions in the treatment of drug-resistant TB. METHODS: Medline, EMBASE, and PubMed were searched from 1975 to April 2012 in addition to hand searching reference lists, and the International Journal of Tuberculosis and Lung Disease. Potentially relevant studies were assessed according to pre-defined eligibility criteria: MDR- and XDR-TB patients undergoing surgical and non-surgical treatment. Treatment outcomes were extracted according to internationally accepted definitions and included in meta-analyses using random effects models. RESULTS: Summary meta-analysis of 24 comparison studies revealed a significant association between surgery and successful treatment compared to non-surgical interventions (OR 2.24, 95%CI 1.68-2.97). A meta-analysis from 23 single-arm studies demonstrated that respectively 92% (95%CI 88.1-95) and 87% (95%CI 83-91) of surgical patients achieved successful short- and long-term outcomes. Subgroup analyses showed that favorable surgical outcomes were associated with increased drug resistance in studies reporting surgical and non-surgical treatment outcomes. CONCLUSIONS: While the results suggest that surgical intervention is associated with successful treatment outcomes in patients with drug-resistant TB, there is insufficient evidence to recommend surgery plus chemotherapy over chemotherapy alone, to evaluate the potential harm from surgery and to determine the optimal conditions for surgery. Controlled studies are needed to better assess the effectiveness of surgery and to investigate other contextual issues. |
- Page last reviewed:Feb 1, 2024
- Page last updated:May 06, 2024
- Content source:
- Powered by CDC PHGKB Infrastructure