Download the Free Unbound MEDLINE PubMed App to your smartphone or tablet.
Available for iPhone, iPad, iPod touch, and Android.
Mycobacterium tuberculosis AND drug use and [keywords]
- The Usefulness of Serum Procalcitonin in Patients With Tuberculous Pleurisy. [JOURNAL ARTICLE]
- Chest 2014 Oct 1; 146(4_MeetingAbstracts):923A.
Respiratory Infections Posters IISESSION TYPE: Original Investigation PosterPRESENTED ON: Wednesday, October 29, 2014 at 01:30 PM - 02:30 PMPURPOSE: Procalcitonin (PCT) is a marker of the inflammatory response to infection. Despite limited research on PCT in pulmonary tuberculosis (PTB) patients, it is known as a poor prognostic marker in PTB patients, when serum PCT is above the normal cut-off point (0.05ng/ml). However, studies for the characteristics of tuberculous pleurisy (TP) patients, according to serum PCT level, have rarely been reported. Therefore, this study evaluated the difference between TP patients with the serum PCT levels below or above the normal cut-off point, to identify the clinical implication.METHODS: A retrospective analysis was performed in 73 patients (PCT < 0.05ng/ml, n=40 (54.8%) vs PCT ≥ 0.05ng/ml, n=33 (45.2%)) with TP diagnosis who had no isolated pathogens except for Mycobacterium tuberculosis in Kangbuk Samsung hospital, between January 2010 and December 2012RESULTS: There were 46 male and 27 female patients with a median age of 46 years. Pleural effusion was found unilateral sided in 60 (82.2%) and both sided in 13 (17.8%) at simple radiography. Radiographic active signs of PTB were found in 38 (52.8%) among 72 patients with chest CT scan. Additionally, mycobacterial identification was possible in 4 patients (2 with culture and 2 with nucleic acid amplification test for M.tubercuosis) with inactive signs on CT scan. So, 42 patients (57.5%) belonged to the pleuro-pulmonary group. The others had isolated pleurisy. Culture for spontaneous sputum or bronchial washing specimens were performed in all the patients. Culture was positive in 27 patients (37.0%). Out of 70 patients with effusion culture result, culture was positive in 17 (24.3%). In a multiple logistic regression analysis, the patients with above the normal cut-off point (0.05ng/ml) had significantly pleuro-pulmonary lesions (OR, 64.179; 95% CI, 1.945 - 2117.439, P=0.020), and positive result in culture for pleural fluid (OR, 27.703; 95%CI, 1.392 - 551.348, P=0.030).CONCLUSIONS: Serum PCT level above the normal cut-off point would suggest the presence of pleuro-pulmonary lesions and positive culture for pleural fluid in TP patients. So, it might aid physicians to decide whether to isolate initially, and to evaluate the effusion aggressively, for microbiological confirmation and drug sensitivity test.CLINICAL IMPLICATIONS: Clinical implication of serum PCT above the normal, demonstrated by these findings is the potential risk of M. tuberculosis transmission to contacts and help to diagnose TP by microbiological confirmation.DISCLOSURE: The following authors have nothing to disclose: Jae-Uk Song, Seong Yong Lim, Si young LIm, Hye Kyeong ParkNo Product/Research Disclosure Information.
- Cost Analysis: Delayed Diagnosis of a Case of INH-Resistant TB. [JOURNAL ARTICLE]
- Chest 2014 Oct 1; 146(4_MeetingAbstracts):917A.
Respiratory Infections Posters IISESSION TYPE: Original Investigation PosterPRESENTED ON: Wednesday, October 29, 2014 at 01:30 PM - 02:30 PMPURPOSE: Despite a declining incidence of tuberculosis (TB) in the USA, TB control programs face significant challenges. Delayed diagnosis and drug resistant TB are two examples. We report the results of a contact investigation of a patient with a delay in diagnosis of isoniazid (INH) resistant TB and estimate the costs to the public health system.METHODS: The index case was an 82-year-old male with non-resolving pneumonia and 20 pound weight loss despite oral and intravenous antibiotics over a ten month period. Late in the course of his illness, multiple sputum and a bronchoalveolar lavage (BAL) fluid samples were acid-fast stain negative. The cultures of the specimens grew Mycobacterium tuberculosis that was later found to be INH resistant by DNA study. Despite standard therapy, the patient subsequently died of respiratory failure. Contact analysis was performed based on Tennessee state guidelines, a medical record review, an interview with the index patient, and a field investigation. Personnel at four health-care facilities and other individuals were included in the contact investigation. Total costs were estimated by the public health department.RESULTS: A total of 434 contacts were identified. Thirty contacts had history of significant reactions to purified protein derivative (PPD) skin testing in the past but asymptomatic. Two step PPD skin testing was non-reactive in 371 of the contacts. A gamma interferon test was negative in 7 contacts. Ten contacts were lost to follow up and four died prior to the investigation. Eight were initial reactors (3 started treatments). Three contacts were recent convertors, requiring rifampin preventive therapy. One pregnant female was advised to defer PPD until after delivery. Six out of eight contacts completed rifampin therapy for LTBI. The cost of preventative therapy and testing was approximately $20,000. The cost calculation will be broken down for review. The man hours involved in the contact investigation are not included in this expense.CONCLUSIONS: This investigation highlights the serious concern regarding delayed diagnosis of INH resistant TB and its impact on health care and costs to society. First, the delay in diagnosis likely resulted in the death of the index case. Second, the delay also resulted in 434 contacts resulting in significant cost expenditures.CLINICAL IMPLICATIONS: We hope that our report will educate clinicians on the impact of a delayed diagnosis of TB can have on individual patients and on the public health system.DISCLOSURE: The following authors have nothing to disclose: Saurabh Desai, Brijal Patel, Parthavkumar Patel, David Kirschke, Ryland Byrd, Thomas Roy, Jayantilal MehtaNo Product/Research Disclosure Information.
- Are Primary MDR and XDR Tuberculosis a New Version of Tuberculosis in Romania? [JOURNAL ARTICLE]
- Chest 2014 Oct 1; 146(4_MeetingAbstracts):914A.
Respiratory Infections Posters ISESSION TYPE: Original Investigation PosterPRESENTED ON: Wednesday, October 29, 2014 at 01:30 PM - 02:30 PMPURPOSE: To assess the impact of Primary Multiple Drug Resistant (MDR) and Extensively Drug Resistant (XDR) Tuberculosis (TB) on epidemiological trend of TB in Romania from January 2010 to December 2013.METHODS: An epidemiological survey on the prevalence of primary anti-tuberculosis drug resistance was conducted on Pulmonary TB cases annually diagnosed in Romania, from January 2010 to December 2013. Mycobacterial isolates were tested for sensitivity to first and second-line anti tuberculosis drugs and drug resistance profile was monitoring. Surveillance of computerized national data was collected from 42 counties and 6 sectors of Bucharest by TB Surveillance Unit of Pneumology «Marius Nasta» Institute, Bucharest, Romania. The case detection rate of primary and acquired drug resistance was determined.RESULTS: From 2010 to 2013, in Romania, the number of newly TB cases annually registered decreased from 21,078 to 16,817; TB prevalence decreased from 40,030 to 34,071 cases but the prevalence of MDR-TB increased from 3.88% to 4.23%; 1976 cases of Pumonary TB disease were identified with MDR strains of Mycobacterium tuberculosis, respectively 111 with XDR profile of resistance. Almost a half of notificated TB cases were investigated by drug sensitivity testing. The structure of MDR-TB reveals a progressive trend of Primary MDR TB strains from 20.20% (116/574) in 2010 to 22.82% (76/333) in 2013. Primary XDR-TB cases have the tendency to decreased from 7 to 1. The effectiveness of therapy in patients with Pulmonary MDR-TB was reported as treatment success rate of 59% to 75%, failure rate of 10% to 16%, abandon from 8% to 13% and death outcome from 7% to 13%.CONCLUSIONS: The prevalence of MDR is low but the progresive ascendent trend of primary MDR TB strains represents a red fleg for the burden of tuberculosis in Romania.CLINICAL IMPLICATIONS: Possible outbreaks of MDR and XDR-TB may represent a turning point in TB epidemics. Primary MDR-TB and the most severe XDR-TB are difficult or impossible to be treated and may lead the way to a broken barrier of the health frontier among human comunities.DISCLOSURE: The following authors have nothing to disclose: Oana Arghir, Gilda PopescuNo Product/Research Disclosure Information.
- Factors Associated With Mortality Among Tuberculosis Patients in Southeast Turkey. [JOURNAL ARTICLE]
- Chest 2014 Oct 1; 146(4_MeetingAbstracts):912A.
Respiratory Infections Posters ISESSION TYPE: Original Investigation PosterPRESENTED ON: Wednesday, October 29, 2014 at 01:30 PM - 02:30 PMPURPOSE: Tuberculosis (TB) is a disease caused by bacillus mycobacterium tuberculosis. Despite effective chemotherapy, it remains significant global health issue. We aimed to investigate the parameters affecting the mortality in patients receiving treatment for tuberculosis.From January 2005 to December 2011, 2450 tuberculosis patients who were followed in tuberculosis dispensaries in the city of Diyarbakir were reviewed retrospectively. Case definitions and treatment outcomes wereclassified according to WHO criteria. Human immunodeficiency virus (HIV) infection were not examined in our patients.Of the 2450 patients, 1339 were males (54.7%) and 1111 were females (45.3%), with mean age of 32,15±17,87 years. 62.5% of the patients had pulmonary tuberculosis and 37.5% of the patients had extrapulmonary tuberculosis (EPTB). Mortality was significantly increased in patients aged between 56-65 years (p<0,001), in category II (p=0,006), in patients having combination with pulmonary and extra-pulmonary TB (p=0,002), and EPTB alone (p=0,004). When patients compared according to TB location, mortality was significantly increased in gastrointestinal tuberculosis and meningitis (Figure 1). Males had higher mortality rates than females (2,4% vs 1,6%). Besides, relapse patients (5.1%) had a higher mortality rate according to case definitions (Table 1). Twenty-two patients had multi-drug resistant tuberculosis and none of them died.Mortality was increased in patients aged between 56-65 years, male gender, relapse, category II and EPTB patients.We suggest that tuberculosis control programs should pay more attention to high-risk groups, and if necessary retreatment regimen for this risk group should be revised.We identified factors independently associated with increased mortality following a diagnosis of tuberculosis. We suggest that mortality rate and excess mortality be routinely used as a monitoring tool for evaluating the efficiency of the national control programme.The following authors have nothing to disclose: Süreyya Yilmaz, Mahsuk Taylan, Hadice Selimoglu Sen, Özlem Abakay, Zülfükar Yilmaz, Ali ihsan Carkanat, Melike Demir, Fusun TopcuNo Product/Research Disclosure Information.
- Infected Lung Bullae With an Acid-Fast Organism. [JOURNAL ARTICLE]
- Chest 2014 Oct 1; 146(4_MeetingAbstracts):909A.
Respiratory Infections Posters ISESSION TYPE: Original Investigation PosterPRESENTED ON: Wednesday, October 29, 2014 at 01:30 PM - 02:30 PMPURPOSE: Mycobacterium kansasii, is the second most common respiratory Non-TB Mycobacterial isolate which is associated with pulmonary disease that is indistinguishable from Tuberculosis infection in immunocompetent persons. Symptomatic illness, clinical and radiologic evidence of infection have been found regardless of immune status.METHODS: 83 year old male with history of O2 dependent moderately severe restrictive airway disease who presented to the emergency department due to increased morning productive cough with yellow sputum production, weight loss of around 20lbs in past month. No history of occupational, environmental or chemical exposure. Objectively, decreased air entry on both lower lungs was noted. Initial evaluation revealed hypoxia on 4 liter of oxygen via nasal cannula. Plain radiograph was evident for cavitory lesion in the both posterior basal segments with air-fluid levels. Contrast CT chest confirmed above findings as possibility of infected bullae. Broad spectrum antibiotic coverage was initiated. Pertinent microbiology studies inludes three sputum samples were positive for Acid fast bacilli; thus Anti-TB treatment with four drug regimen was started. PPD and sputum PCR for TB was negative, so Anti-TB treatment was terminated & antibiotic treatment was adjusted. His hospital course was complicated by worsening of respiratory status. In spite of aggressive supportive measures, patient's condition continued to deteriorate and resulted into the patient's demise. 5 weeks later, identification of sputum culture tested positive for M. kansasii.RESULTS: M. kansasii is a nontuberculous, photochromogenic mycobacterium. Usually discovered from various water sources; rarely from animals (cattle, swine) or soil. Human-to-human transmission has not been documented. Annual rates of infection have been in the range of 0.5 to 1 per 100,000; It seems to predominate along the southeastern and southern coastal states and the central plains states. People at risk includes- pre-existing lung pathology, occupational groups including miners, sandblasters.CONCLUSIONS: For the best possible therapeutic & favorable outcome, M. kansasii should be actively investigated in certain high risk patients.An early identification of M. kansasii and sensitivity to antimicrobial agent is essential, as it has shown in vitro resistance to pyrazinamide & isoniazid. Relapse rate of 9% over a follow up period of five years after standard treatment combinations with rifampicin and ethambutol has been documented.DISCLOSURE: The following authors have nothing to disclose: Pragnesh PatelNo Product/Research Disclosure Information.
- Black Lungs in a Crack Enthusiast. [JOURNAL ARTICLE]
- Chest 2014 Oct 1; 146(4_MeetingAbstracts):193A.
Miscellaneous Student/Resident Case Report Posters IISESSION TYPE: Medical Student/Resident Case ReportPRESENTED ON: Tuesday, October 28, 2014 at 01:30 PM - 02:30 PMINTRODUCTION: Cocaine use is widespread in the United States, with 5 to 8 million current abusers. The principal method of intoxication is smoked cocaine, often referred to as "crack". It is the most commonly used illicit drug among patients seen in the emergency department, and the most frequent cause of drug-related deaths. Pulmonary sequelae include respiratory symptoms, such as persistent cough, wheeze, dyspnea and hemoptysis, deterioration in lung function, and pulmonary infiltrates or interstitial pneumonitis. We present a case of an inhaled cocaine abuser who developed respiratory compromise thought initially to be secondary to miliary mycobacterium tuberculosis based on initial work up and imaging, but was later discovered to have a grossly black lung as a result of deposition of carbonaceous material from the inhaled drug. Such findings are usually isolated to those with coal-worker pneumoconiosis.CASE PRESENTATION: A 52 year-old black female crack addict presented with a 4-month history of dyspnea. She denied other respiratory and constitutional symptoms. She was in moderate respiratory distress with oxygen saturation of 92% on 3 L supplemental oxygen. Exam was significant for diffuse rales on auscultation, but was otherwise unremarkable. Chest x-ray and subsequent CT scan revealed a military nodular pattern. A diagnosis of TB was entertained and bronchoscopy was performed when induced sputum failed to reveal any acid-fast bacilli (AFB). The tracheobronchial tree was grossly unremarkable, but black fluid was obtained on bronchoalveolar lavage (Figure 1). Cytology revealed numerous alveolar macrophages with pigmented granules that stained negative with hemosiderin. However, neither bronchoscopy nor a bone marrow aspirate performed subsequently revealed evidence of AFB. Video-assisted thoracic surgery was performed and the entire surface of the lung was found to be black (Figure 2). On subsequent questioning, she denied exposure to coal, woodsmoke or being in a fire.DISCUSSION: This case highlights a unique pulmonary presentation of crack cocaine abuse. The rate of adverse respiratory effects secondary to cocaine has paralleled the increased trend of smoking the drug. Cocaine abusers may typically develop pulmonary infiltrates, but it's rare to present with a diffuse, miliary infiltrative pattern, which is more common with MTB, sarcoidosis or pneumoconiosis. Furthermore, such widespread deposition of particulate matter is more often observed in those with chronic exposure to coal dust.CONCLUSIONS: Though the impact of inhaled cocaine may be under-estimated, this report emphasizes the need to expand the differential beyond infectious etiologies when a patient presents with a miliary infiltrative pattern on imaging in the setting of cocaine abuse, especially when BAL return yields black fluid.Reference #1: Janxes R. Klingen; Eric Bensadoun M. Pulmonary complications from alveolar accumulation of carbonaceous material in a cocaine smoker. Chest. 1992;101(4)DISCLOSURE: The following authors have nothing to disclose: Bashar Mourad, Hammad Bhatti, James Cury, Adil ShujaatNo Product/Research Disclosure Information.
- INH Resistance on Effective Antituberculous Therapy. When Do We Need Molecular Testing? [JOURNAL ARTICLE]
- Chest 2014 Oct 1; 146(4_MeetingAbstracts):173A.
Infectious Disease Student/Resident Case Report Posters IISESSION TYPE: Medical Student/Resident Case ReportPRESENTED ON: Tuesday, October 28, 2014 at 01:30 PM - 02:30 PMINTRODUCTION: There is 7% prevalence of INH resistant MTB strains in US population, mostly in immigrant population. We rarely question the efficacy of the 4 anti-tuberculous regimen for the treatment of pansensitive strains.CASE PRESENTATION: A 53 years old white homeless male was admitted with dyspnea of few days duration, associated with subjective fever. He had yellowish bloody sputum for the past two years. He travelled by bus over the past two months prior to admission, during which time he noticed progressive leg swelling. Imaging revealed bilateral upper lobes pulmonary cavitations, pulmonary embolism ( as in chest CT image) and DVT of the extremities. The interferon immunoassay test and HIV serology were negative. High amount of AFB in the sputum were identified as M. tuberculosis. The conventional four drug antituberculous therapy was initiated then narrowed down to INH and RIF after 2 months, when the initial isolate came back pansensitive. Surprisingly, 10 weeks later, a repeated culture of the sputum showed the MTB to be resistant to INH despite therapeutic blood levels of INH and rifampin. CDC confirmed INH resistance but the molecular testing did not detect any of the mutations associated with INH resistance. Further sensitivity testing showed sensitivity to all other drugs, including second line drugs. On PZA, ETB, levafloxacin, rifampin, patient had negative sputum cultures.DISCUSSION: The development of INH resistance on effective therapy is rare. We describe the possible mechanisms of resistance leading to this event. Resistance to INH in Mycobacterium tuberculosis is mediated by at least two genes, katG and inhA (see drug pathway figure). Mutations in other genes are considered compensatory mutations that may be a marker for INH resistance but do not appear to confer INH resistance. Host factors (malnutrition, low CD4 count, immunocompromised status) may be more important than pathogen related factors in determining clinical manifestations of disease and clinical outcomes. Compared to current drug sensitivity testing method, that are reporting isolates as either drug susceptible or drug resistant, rapid molecular methods may provide information concerning both the level of resistance and cross-resistance to other anti-TB drugs.CONCLUSIONS: The development of resistance on effective therapy, as it was the case in our patient, is rare. Our case raises questions regarding the appropriate use of molecular techniques to detect and identify mycobacterial resistance mechanisms and the clinical impact of lack of detectable genetic mutations. Reference #1: World Health Organization (2010) Multidrug and extensively drug-resistant TB (M/XDR-TB)- 2010 Global Report on Surveillance and Response. Geneva, Switzerland: World Health Organization PressReference #2: •Dantes R, et al. (2012) Impact of Isoniazid Resistance-Conferring Mutations on the Clinical Presentation of Isoniazid Monoresistant Tuberculosis. PLoS ONE 7(5): e37956DISCLOSURE: The following authors have nothing to disclose: Ahmed Abuzaid, Cezarina MindruNo Product/Research Disclosure Information.
- A Rare Case of Pulmonary Nocardiosis Presenting as Pyopneumothorax in an HIV Patient. [JOURNAL ARTICLE]
- Chest 2014 Oct 1; 146(4_MeetingAbstracts):158A.
Infectious Disease Global Case ReportsSESSION TYPE: Global Case ReportPRESENTED ON: Tuesday, October 28, 2014 at 01:30 PM - 02:30 PMINTRODUCTION: Nocardiosis is bacterial infection caused by gram positive filamentous rods called Nocardia which tend to strike the lungs, brain and skin. The risk of nocardial infection is increased in immunocompromised patients, particularly those with defects in cell-mediated immunity. Nocardia was first reported as a complication of HIV infection in 1985. It is an uncommon opportunistic pathogen in HIV and is usually associated with advanced immunosuppression and high mortality. Pulmonary Nocardia presents as localized or diffuse pneumonias, which may be accompanied by cavitation, abscess formation, pleural effusion or empyema. Here we report an unusual presentation of pulmonary nocardia as pyopneumothorax and diagnosis of the same in resource limited setting.CASE PRESENTATION: 41 year old male with no significant past medical history presented with shortness of breath and cough for 15 days. Review of systems was positive for low grade fever, significant weight loss and decreased appetite for 3 months. Patient is weaver by occupation with a smoking history of 12.5 pack years. He is sexually active with one female partner and denied any drug abuse. On examination, he was pale, dehydrated and cachectic. Vital signs showed tachycardia, tachypnea and oxygen saturation of 91% on room air. Breath sounds were diminished on the left side of chest. Other systems were unremarkable. Laboratory testing revealed hemoglobin 6.2 g/dl, WBC 8600/μL, platelet 150,000/μL, BUN 103 mg/dl and serum creatinine 1.8 mg/dl. Serum electrolytes and hepatic function panel were normal except for low albumin of 3 g/dl. Chest x-ray showed pyopneumothorax on the left side without mediastinal shift. Chest tube was placed emergently which drained 100 cc of purulent material. Further workup confirmed HIV infection with a CD4 count of 26 cells /μL. Pleural fluid analysis showed acid fast filamentous rods by Kinyoun procedure. Aerobic culture grew Nocardia, however further speciation was not done. Screening and diagnostic testing for mycobacterium tuberculosis were negative. After the pesumptive diagnosis of Nocardia with staining, treatment was initiated with high dose intravenous trimethoprim-sulfamethoxazole and amikacin. Clinical improvement was seen in 1 week and antibiotic therapy was switched to oral trimethoprim-sulfamethoxazole. Anti-retroviral therapy was started and patient's CD4 count improved to 206 cells /μL in 6 months.DISCUSSION: Nocardia are branching, beaded, filamentous bacteria, ubiquitous in soil. Important characteristics of nocardial infection are its ability to disseminate to any organ and tendency to progress or relapse despite appropriate therapy which makes early diagnosis and treatment crucial. It usually appears in advanced immunodeficiency with CD4 cell count less than 50 cells/μL in approximately 50% to 85% cases. It is also more common in patients not on active treatment for HIV, and in one case series report 37% of patients with Nocardia infection had undiagnosed HIV infection. It is often complicated by coinfections like Mycobacterium tuberculosis, Mycobacterium Avium Complex, Pseudomonas aeruginosa and Pneumocystis jiroveci making diagnosis difficult. Diagnosis is established by isolation and identification of the organism from a clinical specimen. First line of treatment is trimethoprim-sulfamethoxazole. However combination therapy with Amikacin, imipenem or third generation cephalosporins is warranted in patients with severe infection and also prolonged course of antibiotics is recommended because of the relapsing nature of the disease.CONCLUSIONS: This case highlights the unusual presentation of nocardia as pyopneumothorax. Often there is delay in diagnosis due to its low incidence, nonspecific clinical presentation and relatively difficult culture. In a resource limited country like India, diagnosis can be made with acid fast staining and aerobic culture. Prompt initiation of treatment is life-saving and can prevent dissemination of the disease.Reference #1: AS King, PhD, JG Castro, MD and GCK Dow, MD. Nocardia farcinica lung abscess presenting in the context of advanced HIV infection: Spontaneous resolution in response to highly active antiretroviral therapy alone. Can J Infect Dis Med Microbiol. 2009 Autumn; 20(3): e103-e106. Reference #2: Uttamchandani RB, Daikos GL, Reyes RR, et al. Nocardiosis in 30 patients with advanced human immunodeficiency virus infection: clinical features and outcome. Clin Infect Dis 1994; 18:348.DISCLOSURE: The following authors have nothing to disclose: Aswini Kumar, Aswanth Reddy, Kumar SatagopanNo Product/Research Disclosure Information.
- Compassionate Use of Bedaquiline in the Treatment of Extensively Drug-Resistant Pulmonary Tuberculosis. [JOURNAL ARTICLE]
- Chest 2014 Oct 1; 146(4_MeetingAbstracts):132A.
Infectious Disease Case Report PostersSESSION TYPE: Affiliate Case Report PosterPRESENTED ON: Tuesday, October 28, 2014 at 01:30 PM - 02:30 PMINTRODUCTION: Extensively Drug Resistant Tuberculosis (XDR-TB), is uncommon in developed countries with only 63 cases reported in the US between 1993-2011. Treatment is tailored to culture sensitivities with second line anti-tuberculosis (anti-TB) drugs. We report the first case in United States of compassionate use of bedaquiline for the treatment of pulmonary XDR-TB.A 30 year-old man, former smoker, with diabetes, presented with fevers and hemoptysis one month after immigrating to New York from a high incidence country. His chest x-ray revealed bilateral cavitary upper lobe infiltrates (Figure 1). Sputum smears for acid-fast bacilli were positive as were cultures for Mycobacterium Tuberculosis. He was empirically started on first-line anti-TB drugs, and his regimen was modified as results from susceptibility testing became available eventually revealing XDR-TB. He was ultimately treated with pyrazinamide, ethionamide, paraminosalycilic acid, cycloserine, capreomycin, amoxicillin/clavulanic, meropenem and linezolid. As a result of multiple adverse effects from his XDR-TB treatment, especially linezolid induced demyelinating peripheral neuropathy, bedaquiline was obtained through a compassionate use program in order to maintain an effective treatment regimen for XDR-TB after the discontinuation of linezolid. He tolerated bedaquiline well experiencing only mild transaminitis and successfully completed his XDR-TB treatment.DISCUSSION: Three cases in the literature pertain to the compassionate use of bedaquiline. In each of these cases, bedaquiline was added in place of a fourth agent in a treatment regimen when there were no additional options remaining. QTC prolongation and increased risk of death have been noted in patients receiving bedaquiline. High incidences of nausea (35.3% vs. 25.7%) and hepatotoxicity (8.8% vs. 1.9%) have also been reported with bedaquiline when compared to placebo.Bedaquiline is a novel agent for the treatment of Pre-XDR or XDR Tuberculosis. In our patient bedaquiline was added to an effective XDR regimen to ameliorate the side effect profile in order to allow for the successful completion of therapy. Reference #1: CDC, Trends in Tuberculosis - United States, 2011. MMWR, 2012. 61(11): p. 181-185. Reference #2: Tiberi, S., et al., Bedaquiline in MDR/XDR-TB cases: first experience on compassionate use. Eur Respir J, 2014. 43(1): p. 289-92. Reference #3: Diacon, A.H., et al., The diarylquinoline TMC207 for multidrug-resistant tuberculosis. N Engl J Med, 2009. 360(23): p. 2397-405.The following authors have nothing to disclose: Melissa Lesko, Mauricio Danckers Degregori, Rosemary Adamson, Eric LeibertNo Product/Research Disclosure Information.
- Alarming Levels of Drug-Resistant Tuberculosis in HIV-Infected Patients in Metropolitan Mumbai, India. [JOURNAL ARTICLE]
- PLoS One 2014; 9(10):e110461.
Drug-resistant tuberculosis (DR-TB) is a looming threat to tuberculosis control in India. However, no countrywide prevalence data are available. The burden of DR-TB in HIV-co-infected patients is likewise unknown. Undiagnosed and untreated DR-TB among HIV-infected patients is a major cause of mortality and morbidity. We aimed to assess the prevalence of DR-TB (defined as resistance to any anti-TB drug) in patients attending public antiretroviral treatment (ART) centers in greater metropolitan Mumbai, India.A cross-sectional survey was conducted among adults and children ART-center attendees. Smear microscopy, culture and drug-susceptibility-testing (DST) against all first and second-line TB-drugs using phenotypic liquid culture (MGIT) were conducted on all presumptive tuberculosis patients. Analyses were performed to determine DR-TB prevalence and resistance patterns separately for new and previously treated, culture-positive TB-cases.Between March 2013 and January 2014, ART-center attendees were screened during 14135 visits, of whom 1724 had presumptive TB. Of 1724 attendees, 72 (4%) were smear-positive and 202 (12%) had a positive culture for Mycobacterium tuberculosis. Overall DR-TB was diagnosed in 68 (34%, 95% CI: 27%-40%) TB-patients. The proportions of DR-TB were 25% (29/114) and 44% (39/88) among new and previously treated cases respectively. The patterns of DR-TB were: 21% mono-resistant, 12% poly-resistant, 38% multidrug-resistant (MDR-TB), 21% pre-extensively-drug-resistant (MDR-TB plus resistance to either a fluoroquinolone or second-line injectable), 6% extensively drug-resistant (XDR-TB) and 2% extremely drug-resistant TB (XDR-TB plus resistance to any group-IV/V drug). Only previous history of TB was significantly associated with the diagnosis of DR-TB in multivariate models.The burden of DR-TB among HIV-infected patients attending public ART-centers in Mumbai was alarmingly high, likely representing ongoing transmission in the community and health facilities. These data highlight the need to promptly diagnose drug-resistance among all HIV-infected patients by systematically offering access to first and second-line DST to all patients with 'presumptive TB' rather than 'presumptive DR-TB' and tailor the treatment regimen based on the resistance patterns.