Positive Culture For Mycobacterium Tuberculosis Research Articles

BCG Infection after Bladder Cancer Treatment—3 Clinical Case Reports

Immunotherapy with Bacillus Calmette-Guerin (BCG) to treat non-muscle invasive bladder cancer has become an effective and superior alternative to chemotherapy. Intravesical treatment with BCG appears to be relatively safe; however, occasionally BCG infection complicates such treatment. In the present work we describe three patients in whom BCG infection occurred after intravesical BCG therapy. All patients had positive urine culture forMycobacterium tuberculosis complex, using AccuProbe culture identification and then Genotype Mycobacterium MTBC test identified Mycobacterium bovis BCG. The diagnosis is difficult and microbiologic study is usually negative, so high index of suspicion is essential.

Resistance to First-Line Antituberculosis Drugs in Spain, 2010–2011. RETUBES Study

IntroductionThe magnitude of current resistance to antituberculosis drugs in Spain is unknown. The objective of this study is to describe resistance to first-line antituberculosis drugs and determine the associated factors. MethodsProspective multicenter study of adult tuberculosis patients with positive Mycobacterium tuberculosis culture and antibiogram including first-line drugs in 32 hospitals and one out-patient center of the Spanish Health System between 2010 and 2011. ResultsA total of 519 patients, 342 Spanish nationals and 177 (34.1%) foreigners were studied. Drug resistance was found in 48 (9.2%), of which 35 (6.7%) were isoniazid-resistant. There were 10 (1.9%) multiresistant cases and no strain was extremely resistant. Initial isoniazid resistance was detected in 28 of the 487 (5.7%) antituberulosis-naïve patients, most of whom were foreigners (p<.01). Acquired resistance was seen in 7 (22.6%) previously treated cases. Multiresistance was initial in 6 cases (1.2%) and acquired in another 4 (12.9%). Factors associated with initial isoniazid resistance were immigrant status and group cohabitation (OR=2.3; 95% CI: 0.98–5.67 and OR=2.2; 95% CI: 1.05–7.07 respectively). The factor associated with acquired resistance to isoniazid was age below 50 years (p=.03). ConclusionsThe rate of initial isoniazid resistance is greater than estimated, probably due to the increase in immigration during recent years, suggesting that systematic national monitoring is required. Immigrants and those who cohabit in groups have a higher risk of isoniazid resistance.

Alarming levels of drug-resistant tuberculosis in HIV-infected patients in metropolitan Mumbai, India.

BackgroundDrug-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.MethodsA 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.ResultsBetween 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.ConclusionThe 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.

Rapid diagnosis of pyrazinamide-resistant multidrug-resistant tuberculosis using a molecular-based diagnostic algorithm

There is an urgent need for rapid and accurate diagnosis of pyrazinamide-resistant multidrug-resistant tuberculosis (MDR-TB). No diagnostic algorithm has been validated in this population. We hypothesized that pncA sequencing added to rpoB mutation analysis can accurately identify patients with pyrazinamide-resistant MDR-TB. We identified from the Dutch national database (2007-11) patients with a positive Mycobacterium tuberculosis culture containing a mutation in the rpoB gene. In these cases, we prospectively sequenced the pncA gene. Results from the rpoB and pncA mutation analysis (pncA added to rpoB) were compared with phenotypic susceptibility testing results to rifampicin, isoniazid and pyrazinamide (reference standard) using the Mycobacterial Growth Indicator Tube 960 system. We included 83 clinical M. tuberculosis isolates containing rpoB mutations in the primary analysis. Rifampicin resistance was seen in 72 isolates (87%), isoniazid resistance in 73 isolates (88%) and MDR-TB in 65 isolates (78%). Phenotypic reference testing identified pyrazinamide-resistant MDR-TB in 31 isolates (48%). Sensitivity of pncA sequencing added to rpoB mutation analysis for detecting pyrazinamide-resistant MDR-TB was 96.8%, the specificity was 94.2%, the positive predictive value was 90.9%, the negative predictive value was 98.0%, the positive likelihood was 16.8 and the negative likelihood was 0.03. In conclusion, pyrazinamide-resistant MDR-TB can be accurately detected using pncA sequencing added to rpoB mutation analysis. We propose to include pncA sequencing in every isolate with an rpoB mutation, allowing for stratification of MDR-TB treatment according to pyrazinamide susceptibility.

Neutrophil-associated central nervous system inflammation in tuberculous meningitis immune reconstitution inflammatory syndrome.

The immunopathogenesis of tuberculosis-associated immune reconstitution inflammatory syndrome (IRIS) remains incompletely understood, and we know of only 1 disease site-specific study of the underlying immunology; we recently showed that Mycobacterium tuberculosis culture positivity and increased neutrophils in the cerebrospinal fluid (CSF) of patients with tuberculous meningitis (TBM) are associated with TBM-IRIS. In this study we investigated inflammatory mediators at the disease site in patients with TBM-IRIS. We performed lumbar puncture at 3-5 time points in human immunodeficiency virus (HIV)-infected patients with TBM (n = 34), including at TBM diagnosis, at initiation of antiretroviral therapy (ART) (day 14), 14 days after ART initiation, at presentation of TBM-IRIS, and 14 days thereafter. We determined the concentrations of 40 mediators in CSF (33 paired with blood) with Luminex or enzyme-linked immunosorbent assays. Findings were compared between patients who developed TBM-IRIS (n = 16) and those who did not (TBM-non-IRIS; n = 18). At TBM diagnosis and 2 weeks after ART initiation, TBM-IRIS was associated with severe, compartmentalized inflammation in the CSF, with elevated concentrations of cytokines, chemokines, neutrophil-associated mediators, and matrix metalloproteinases, compared with TBM-non-IRIS. Patients with TBM-non-IRIS whose CSF cultures were positive for M. tuberculosis at TBM diagnosis (n = 6) showed inflammatory responses similar to those seen in patients with TBM-IRIS at both time points. However, at 2 weeks after ART initiation, S100A8/A9 was significantly increased in patients with TBM-IRIS, compared with patients with TBM-non-IRIS whose cultures were positive at baseline. A high baseline M. tuberculosis antigen load drives an inflammatory response that manifests clinically as TBM-IRIS in most, but not all, patients with TBM. Neutrophils and their mediators, especially S100A8/A9, are closely associated with the central nervous system inflammation that characterizes TBM-IRIS.

Treatment outcomes of childhood tuberculous meningitis: a systematic review and meta-analysis

Tuberculous meningitis disproportionately affects young children. We aimed to characterise treatment outcomes for this deadliest and most debilitating form of tuberculosis. We did a systematic review and meta-analysis of childhood tuberculous meningitis studies published up to Oct 12, 2012. We included study reports that applied predefined diagnostic criteria and described treatment regimens and outcomes. We pooled risks of death during treatment and neurological sequelae among survivors. As secondary objectives, we assessed study-level characteristics as sources of heterogeneity, and we pooled frequencies of presenting symptoms and diagnostic findings. For all meta-analyses we used random-effects models with the exact binomial likelihood method. 19 studies met our inclusion criteria, with reported treatment outcomes for 1636 children. Risk of death was 19·3% (95% CI 14·0-26·1) and probability of survival without neurological sequelae was 36·7% (27·9-46·4). Among survivors, risk of neurological sequelae was 53·9% (95% CI 42·6-64·9). Diagnosis in the most advanced disease stage (3) occurred in 307 (47%) of 657 patients and was associated with worse outcomes than was earlier diagnosis. The most common findings at presentation were cerebrospinal fluid (CSF) leucocytosis (frequency 99·9%, 95% CI 68·5-100·0), CSF lymphocytosis (97·9%, 51·9-100·0), fever (89·8%, 79·8-95·2), and hydrocephalus (86·1%, 68·6-94·6). Frequency of CSF acid-fast-bacilli smear positivity was 8·9% (95% CI 5·0-15·4), and frequency of CSF culture positivity for Mycobacterium tuberculosis was 35·1% (16·8-59·2). Despite treatment, childhood tuberculous meningitis has very poor outcomes. Poor prognosis and difficult early diagnosis emphasise the importance of preventive therapy for child contacts of patients with tuberculosis and low threshold for empirical treatment of tuberculous meningitis suspects. Implementation of consensus definitions, standardised reporting of data, and high-quality clinical trials are needed to clarify optimum therapy. None.

Resistencia a fármacos antituberculosos de primera línea en España durante 2010-2011. Estudio RETUBES

IntroductionThe magnitude of current resistance to antituberculosis drugs in Spain is unknown. The objective of this study is to describe resistance to first-line antituberculosis drugs and determine the associated factors. MethodsProspective multicenter study of adult tuberculosis patients with positive Mycobacterium tuberculosis culture and antibiogram including first-line drugs in 32 hospitals and one out-patient center of the Spanish Health System between 2010 and 2011. ResultsA total of 519 patients, 342 Spanish nationals and 177 (34.1%) foreigners were studied. Drug resistance was found in 48 (9.2%), of which 35 (6.7%) were isoniazid-resistant. There were 10 (1.9%) multiresistant cases and no strain was extremely resistant. Initial isoniazid resistance was detected in 28 of the 487 (5.7%) antituberulosis-naïve patients, most of whom were foreigners (P<.01). Acquired resistance was seen in 7 (22.6%) previously treated cases. Multiresistance was initial in 6 cases (1.2%) and acquired in another 4 (12.9%). Factors associated with initial isoniazid resistance were immigrant status and group cohabitation OR=2.3; 95%CI: .98-5.67 and OR=2.2; 95%CI: 1.05-7.07 respectively). The factor associated with acquired resistance to isoniazid was age below 50 years (P=.03). ConclusionsThe rate of initial isoniazid resistance is greater than estimated, probably due to the increase in immigration during recent years, suggesting that systematic national monitoring is required. Immigrants and those who cohabit in groups have a higher risk of isoniazid resistance.

Drug resistance pattern of Mycobacterium tuberculosis isolates from patients of five provinces of Iran

ObjectiveTo determine the patterns of resistance to first line anti-tuberculosis (TB) drugs among a collection of Mycobacterium tuberculosis (MTB) isolates from 5 provinces of Iran. MethodsA total of the 6 426 clinical specimens from patients suspected of active TB were collected from March 2010 to June 2012. All specimens were subjected for microscopy and culture tests in the TB centers of studies provinces. Drug susceptibility testing to the first line anti-TB drugs for culture positive MTB was performed on Löwenstein-Jensen (LJ) medium using proportion method. ResultsOf 6 426 clinical specimens, 261 were culture positive for mycobacteria, of which 252 were MTB and 9 were MOTT (mycobacteria other than tuberculosis). Of 252 MTB isolates, 211 (83.7%) were pan-susceptible and 41 (16.3%) were resistant to at least one drug. Resistance was most common to streptomycin, 30 isolates (12.0%), followed by isoniazid, 20 isolates (8.0%), rifampin, 15 isolates (6.0%) and ethambutol, 14 isolates (5.5%). Sixteen (6.3%) MTB isolates were MDR. A clear evidence of heterogeneity amongst the 5 provinces in the proportions with resistance to one or more drugs was observed [χ2; = 12.209 (4 degrees of freedom), P values = 0.015 9]. ConclusionsThe prevalence of drug resistance in this study area underscoring the need for further enforcement of TB control strategies in the Iran. Drug susceptibility testing for all TB cases to provide optimal treatment, establishing advanced diagnostic facilities for rapid detection of MDR-TB and continuous monitoring of drug resistance are recommended for prevention and control of drug-resistant TB.

The value of serum lipoarabinomannan in the diagnosis of pulmonary tuberculosis

Objective The aim of this study was to assess the value of serum lipoarabinomannan (LAM) in the diagnosis of pulmonary tuberculosis (TB). Background The accurate diagnosis of TB is difficult. Recent studies indicate that a LAM assay (ELISA) may have some utility in the diagnosis of TB. Material and methods Sera from 40 individuals with confirmed pulmonary TB and 20 healthy individuals were tested for the presence of LAM by means of ELISA assay. Culture positivity for Mycobacterium tuberculosis was used as the reference standard for TB diagnosis. Results The serum LAM ELISA test showed high positivity in confirmed TB patients; sputum smear combined with LAM diagnosed 95% of the confirmed cases; tuberculin skin test, elevated erythrocyte sedimentation rate, immunocompetent state, and radiological tests have shown significant differences from qualitative and quantitative serum LAM. Serum LAM sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 90, 100, 93.3, 100, and 83.3%, respectively. Conclusion The LAM test is a simple and reliable test for the diagnosis of pulmonary TB.

Comprehensive cardiovascular magnetic resonance for monitoring the response to therapy in pericardial tuberculosis

A Caucasian 25-year-old man with cardiac tamponade underwent urgent pericardiocentesis with the removal of 100 ml of siero-ematic essudative fluid. Smear microscopy detected acid-fast bacilli, and pericardial tuberculosis was confirmed by positive culture for Mycobacterium tuberculosis. One-week after pericardiocentesis, cardiovascular magnetic resonance (CMR) was performed (upper panel). Short-axis cine steady-state free precession ( Panel A ), black-blood T 1-weighted ( Panel B ), and …

Vitamin D deficiency in patients with tuberculosis.

To determine the frequency and association of Vitamin D deficiency in patients with tuberculosis. Case control study. Medical Department, Combined Military Hospital, Kharian, from July 2010 to June 2012. One hundred and five outdoor patients of tuberculosis were selected with 255 gender matched controls. Tuberculosis was diagnosed by presence of acid fast bacilli in sputum smears, positive culture for Mycobacterium tuberculosis or demonstration of chronic caseating granulomatous inflammation in tissue specimens. Controls were drawn randomly from general population. Serum 25 hydroxyvitamin D [25 (OH) D3] levels < 25 ng/ml was considered Vitamin D deficiency. The results were analyzed on SPSS version 17. Mean Vitamin D levels were 23.23 ± 6.81 ng/ml in cases, 29.27 ± 8.89 ng/ml in controls (p < 0.0001). Vitamin D deficiency was found in 57% of cases and 33% controls (p < 0.0001). Mean Vitamin D levels were significantly lower in females with tuberculosis (20.84 ng/ml) as compared to males (25.03 ng/ml, p = 0.002). Mean BMI in patients of tuberculosis with Vitamin D deficiency were 19.51 ± 1.77 kg/m2 and in patients with normal Vitamin D were 21.65 ± 1.79 kg/m2 (p < 0.0001). Mean Vitamin D levels in patients with multi-drug resistant tuberculosis was lower to a mean of 15.41 ± 4.67 ng/ml (p < 0.0001). There is significant deficiency of Vitamin D in patients with tuberculosis as compared to controls. This deficiency is more pronounced in females, individuals with low BMI, extra pulmonary and MDR tuberculosis.

Immunocytochemical detection of mycobacterial antigen in extrapulmonary tuberculosis

The aim of the study is to determine whether immunostaining for mycobacterial antigen can contribute to the cytological diagnosis of extrapulmonary tuberculosis (EPTB). The study was carried out on aspirated material of lymph nodes, and other accessible sites, from 65 patients with clinical diagnosis of tuberculosis (TB). Twenty patients, diagnosed by fine-needle aspiration, with non-tuberculous granulomas served as controls. The diagnosis of TB was based on the demonstration of acid-fast bacilli (AFB), culture positivity for Mycobacterium tuberculosis (M. tuberculosis), or response to treatment with standard anti-tubercular therapy. Immunostaining was done using polyclonal antibody to mycobacteria. AFB positivity by Ziehl Neelsen (ZN) staining was 21%, 65.38%, and 68% respectively in Pattern 1 (granulomas alone), in Pattern 2 (granulomas with necrosis), and in Pattern 3 (necrosis alone). Overall AFB positivity was 56.92%. Twenty-eight of 65 cases were negative for AFB on direct smear. Culture was positive in 46% (13/28). Sensitivity and specificity of immunostaining were 96.92% (63/65) and 95%, respectively. Immunoreactivity was seen in 26 (92.8%) of 28 cases which were negative by ZN staining. Except in the case of leprosy, in which cross reactivity was seen, there was no immunoreactivity in the control group. Immunocytochemistry (ICC) had high sensitivity (96.2%) and specificity (95%) in the diagnosis of EPTB. ICC may be a useful adjunct to evaluation of cytomorphology and ZN staining.

Evaluation of the 2007 WHO guideline to diagnose smear negative tuberculosis in an urban hospital in Ethiopia

BackgroundThe 2007 World Health Organization (WHO) guideline to diagnose smear-negative tuberculosis (TB) in HIV-prevalent settings was mainly based on expert advice and therefore requires evaluation in real life situations.MethodsIn 2009, this guideline was introduced at the ALERT hospital in Ethiopia. From October 2009 to January 2011, the accuracy of the guideline was evaluated using Mycobacterium tuberculosis culture positivity as reference standard in HIV positive TB suspects.ResultsA total of 459 TB suspects were enrolled during the study period; 336 (73.2%) were HIV positive. Acid fast bacilli sputum smear microscopy was done for 74.7% (251/336) HIV positive TB suspects; 94.4% (237/251) were smear negative. A chest X-ray was performed in 92.8% (220/237) and a Mycobacterium tuberculosis culture in 63.7% (151/237). The median TB diagnostic delay for smear negative cases was 3 days (interquartile range 3–4 days). Of the 75 patients diagnosed with smear negative pulmonary TB, 89. 4% (67/75) were diagnosed by chest X-ray, 9.4% (7/75) by culture and 1.3% (1/75) by clinical suspicion only. In 147 smear negative TB suspects Mycobacterium tuberculosis culture and chest X-ray results were available. Among these 147 patients, the sensitivity of the chest X-ray to diagnose smear negative TB in HIV-positive TB suspects was 53.3% (95% CI: 26.7-78.7); the specificity 67.4% (95% CI: 58.7-75.3).ConclusionThe 2007 WHO diagnostic algorithm for the diagnosis of smear negative TB is likely to reduce the diagnostic delay and therefore decrease morbidity and mortality of TB in a HIV prevalent settings like Ethiopia.

Recognizing Laboratory Cross-Contamination

Mycobacterium tuberculosis (MTB) isolation from clinical specimens is the standard for TB diagnosis. Positive MTB cultures are rarely questioned, but false-positive culture rates range from 2% to 4%. In December 2011, two smear-negative, culture-positive TB cases were reported to the Oklahoma State Department of Health (OSDH) in people without TB signs or symptoms. OSDH TB control officers interviewed physicians and laboratory personnel, reviewed patient charts, traced epidemiologic links, and performed microbiologic studies to determine if these were true TB cases. Both specimens were found to have been processed on the same day, at the same laboratory, under the same hood, and by the same technician sequentially after a strongly smear-positive TB specimen. No epidemiologic links were identified among the three patients. Spoligotyping and 24-locus mycobacterial interspersed repetitive unit typing of the three specimens were identical. Only liquid media grew MTB in the two questionable specimens. A laboratory splash incident was suspected, whereby all three liquid media sample lids were open during inoculation rather than being opened one at a time, causing cross-contamination. Also, the two specimens were incubated for 2-3 weeks longer than standard protocol before MTB growth was observed. Patient 1 was not treated for TB because her physician doubted the culture result. Patient 2, an organ transplant recipient, began four-drug anti-TB therapy, and an investigation was initiated for transplant-associated TB. Adherence to strict laboratory techniques and recognizing the possibility of false-positive MTB cultures, especially when inconsistent with clinical data, are essential in preventing erroneous TB diagnoses.

AB0651 Preventive antituberculosis treatment before biologic agents initiating: frequency of prescription and tolerance in a sample of tunisian rheumatologic population

BackgroundTreatment of latent tuberculosis (TB) is mandatory before biologic agents’ instauration to prevent the risk of reactivation.ObjectivesTo assess frequency and reasons of TB chemoprophylaxis prescription in rheumatologic population and its...

Rare images of tuberculous pericarditis causing constrictive pericarditis

A 30-year old woman presented with complaints of chest pain, palpitation and echocardiographic findings of a constrictive cardiac haemodynamic pattern with calcification and thickening of the pericardium (Fig. 1). She underwent successful pericardiectomy. An intraoperative image of a typical caseification necrosis surrounding the whole pericardium, with a positive culture of mycobacterium tuberculosis is shown in Fig. 2 .

Prevalence of multidrug resistance in Mycobacterium tuberculosis isolates from HIV seropositive and seronegative patients with pulmonary tuberculosis in north India

BackgroundMultidrug resistant (MDR) and extensively-drug resistant (XDR) tuberculosis (TB) are a serious threat to the national TB control programs of developing countries, and the situation is further worsened by the human immunodeficiency virus (HIV) pandemic. The literature regarding MDR/XDR-TB is, however, scanty from most parts of India. We carried out this study to assess the prevalence of MDR/XDR-TB in new and previously treated cases of pulmonary TB and in HIV seropositive and seronegative patients.MethodsSputum and blood specimens were obtained from 2100 patients suspected of pulmonary tuberculosis and subjected to sputum microscopy and culture for TB, and HIV serology at our tertiary care centre in north India. The culture positive Mycobacterium tuberculosis isolates were subjected to drug susceptibility testing (DST) for first line anti-tuberculosis drugs, and the MDR isolates were further subjected to second line DST. Various parameters of the patients’ were analyzed viz. clinical presentation, radiology, previous treatment history, demographic and socioeconomic data and microbiology results.ResultsOf the 2100 patients, sputum specimens of 256 were smear positive for acid-fast bacilli (AFB), 271 (12.9%) grew Mycobacterium spp., and M. tuberculosis was isolated in 219 (10.42%). Of the 219 patients infected with M. tuberculosis, 20.1% (44/219) were found to be seropositive for HIV. Overall, MDR-TB was observed in 17.4% (39/219) isolates. There were 121 newly diagnosed and 98 previously treated patients, of which MDR-TB was found to be associated with 9.9% (12/121) and 27.6% (27/98) cases respectively. There was significantly higher association of MDR-TB (12/44, 27.3%) with HIV seropositive patients as compared to HIV seronegative patients (27/175, 15.4%) after controlling previous treatment status, age, and sex (odd’s ratio, 2.3 [95% CI, 1.000-5.350]; p-value, 0.05). No XDR-TB was found among the MDR-TB isolates.ConclusionThe present study demonstrated a high prevalence of drug resistance amongst pulmonary TB isolates of M. tuberculosis from north India as compared to the WHO estimates for India in 2010, though this could possibly be attributed to the clustering of more serious or referred cases at our tertiary care centre. The prevalence of MDR-TB in HIV seropositive patients was significantly higher than seronegative individuals. The study emphasizes the need to monitor the trends of drug resistance in TB in various populations in order to timely implement appropriate interventions to curb the menace of MDR-TB.

Treatment Response and Adverse Reactions in Older Tuberculosis Patients with Immunocompromising Comorbidities

PurposeThe aim of this study was to elucidate the effects of immunocompromising comorbidities on treatment response and adverse reactions in older tuberculosis (TB) patients.Materials and MethodsThe medical records of 182 patients older than 65 years with proven TB by positive culture of Mycobacterium tuberculosis and with available drug susceptibility tests were reviewed retrospectively. These patients were subsequently assigned to either the comorbidity group (n=78) or non-comorbidity group (n=104) depending on whether they had immunocompromising comorbidities.ResultsThe mean durations of treatment were 9.9±3.3 months in the comorbidity group and 9.3±3.2 months in the non-comorbidity group (p=0.21). M. tuberculosis culture results converted to negative in most patients with available follow-up cultures at two months after treatment. The successful treatment rates were 94.9% and 98.9% in the comorbidity and non-comorbidity groups, respectively (p=0.30). The most common side effects of anti-TB treatment were skin rash/pruritus (13% in the comorbidity group vs. 11% in the non-comorbidity group, p=0.79), gastro-intestinal problems (14% vs. 9%, p=0.25) and hepatotoxicity (14% vs. 7%, p=0.09).ConclusionThe present study shows that the successful treatment rate for TB is high and that immunocompromising comorbidities have no effect on the response to treatment and adverse effects in older TB patients.

Prevalência de resistência primária em pacientes com tuberculose pulmonar sem fatores de risco conhecidos para resistência primária

To estimate the prevalence of primary resistance to the drugs in the basic treatment regimen for tuberculosis in treatment-naïve patients with pulmonary tuberculosis and no known risk factors for such resistance, as well as to identify factors potentially associated with drug resistance. This was an exploratory cross-sectional study. We analyzed the medical records of the subjects enrolled in two clinical trials of treatments for drug-susceptible tuberculosis between November 1, 2004 and March 31, 2011 at the Prof. Newton Bethlem Outpatient Clinic of the Federal University of Rio de Janeiro Thoracic Diseases Institute, located in the city of Rio de Janeiro, Brazil. The inclusion criteria were being > 18 years of age, testing positive for AFB in the first sputum sample, having a positive culture for Mycobacterium tuberculosis, having undergone drug susceptibility testing, and being treatment-naïve. Patients with a history of imprisonment or hospitalization were excluded, as were those who had been in contact with drug-resistant tuberculosis patients. We included 209 patients. The overall prevalence of primary drug resistance was 16.3%. The overall prevalence of resistance to isoniazid and streptomycin was, respectively, 9.6% and 9.1%, compared with 5.8% and 6.8% for single-drug resistance to isoniazid and streptomycin, respectively. The prevalence of resistance to two or more drugs was 3.8%, and the prevalence of multidrug resistance was 0.5%. No statistically significant associations were found between the variables studied and drug susceptibility testing results. In this sample, the prevalence of primary drug resistance was high despite the absence of known risk factors.

Frequency, Severity, and Prediction of Tuberculous Meningitis Immune Reconstitution Inflammatory Syndrome

Tuberculosis immune reconstitution inflammatory syndrome (IRIS) is a common cause of deterioration in human immunodeficiency virus (HIV)-infected patients receiving tuberculosis treatment after starting antiretroviral therapy (ART). Potentially life-threatening neurological involvement occurs frequently and has been suggested as a reason to defer ART. We conducted a prospective study of HIV-infected, ART-naive patients with tuberculous meningitis (TBM). At presentation, patients started tuberculosis treatment and prednisone; ART was initiated 2 weeks later. Clinical and laboratory findings were compared between patients who developed TBM-IRIS (TBM-IRIS patients) and those who did not (non-TBM-IRIS patients). A logistic regression model was developed to predict TBM-IRIS. Forty-seven percent (16/34) of TBM patients developed TBM-IRIS, which manifested with severe features of inflammation. At TBM diagnosis, TBM-IRIS patients had higher cerebrospinal fluid (CSF) neutrophil counts compared with non-TBM-IRIS patients (median, 50 vs 3 cells ×10(6)/L, P = .02). Mycobacterium tuberculosis was cultured from CSF of 15 TBM-IRIS patients (94%) compared with 6 non-TBM-IRIS patients (33%) at time of TBM diagnosis; relative risk of developing TBM-IRIS if CSF was Mycobacterium tuberculosis culture positive = 9.3 (95% confidence interval [CI], 1.4-62.2). The combination of high CSF tumor necrosis factor (TNF)-α and low interferon (IFN)-γ at TBM diagnosis predicted TBM-IRIS (area under the curve = 0.91 [95% CI, .53-.99]). TBM-IRIS is a frequent, severe complication of ART in HIV-associated TBM and is characterized by high CSF neutrophil counts and Mycobacterium tuberculosis culture positivity at TBM presentation. The combination of CSF IFN-γ and TNF-α concentrations may predict TBM-IRIS and thereby be a means to individualize patients to early or deferred ART.