To Anti-tuberculosis Research Articles

Negative effects of undernutrition on sputum smear conversion and treatment success among retreatment cases in Uganda: A quasi-experimental study

RationaleThe causal relationship between undernutrition and response to anti-tuberculosis (TB) treatment and TB treatment outcomes among people with retreatment TB is understudied. ObjectiveTo evaluate the effect of undernutrition on treatment success and sputum smear conversion among people with retreatment drug-susceptible TB in Kampala, Uganda. MethodsWe conducted a quasi-experimental study utilizing propensity score weighting among people with retreatment drug-susceptible TB aged ≥ 15 years treated between 2012 and 2022 in Kampala. The primary exposure was undernutrition assessed using the mid-upper arm circumference at the time of TB diagnosis. The primary outcome was treatment success defined as cure or treatment completion at month 6. Sputum smear conversion was the secondary outcome and was measured as a change in sputum smear status from positive to negative at months 2, 5, and 6. We estimated the causal effect of undernutrition on the outcomes using a propensity-score weighted modified Poisson regression model with robust error variance. Measurements and main resultsOf the 605 participants, 432 (71.4 %) were male, 215 (35.5 %) were aged 25–34 years, 427 (70.6 %) had bacteriologically confirmed pulmonary TB, 133 (22.0 %) were undernourished and 398 (65.8 %) achieved treatment success. Of participants with bacteriologically confirmed pulmonary TB, 232 (59.0 %), 327 (59.3 %), and 360 (97.6 %) achieved sputum smear conversion at months 2, 5, and 6, respectively. Undernutrition reduced treatment success (RR 0.42, 95 % CI 0.32–0.55) as well as sputum smear conversion at months 2 (RR 0.45, 95 % CI 0.42–0.49) and 5 (RR 0.46, 95 % CI 0.43–0.51) but not month 6 (RR 0.99, 95 % CI 0.97–1.02). ConclusionUndernutrition negatively impacts treatment outcomes. Therefore, nutritional assessment should be an integral component of TB care, with nutritional counseling and support offered to those undernourished to optimize their TB treatment response and outcomes.

Quantifying non-adherence to anti-tuberculosis treatment due to early discontinuation: a systematic literature review of timings to loss to follow-up

BackgroundThe burden of non-adherence to anti-tuberculosis (TB) treatment is poorly understood. One type is early discontinuation, that is, stopping treatment early. Given the implications of early discontinuation for treatment outcomes,...

Usability of medication event reminder monitoring system and other determinants to improve the adherence to anti-tuberculosis drugs among patients of tertiary care hospital, Hyderabad

INTRODUCTION: Novel strategies to improve the adherence to anti-tuberculosis (TB) drugs include the digital adherence technology for monitoring these patients. The purpose of the study is to determine the acceptability and satisfaction of the medication event reminder monitoring system (MERMS) by the patients and to assess various determinants among adherent and nonadherent groups. MATERIALS AND METHODS: A facility-based cross-sectional study was undertaken among the drug-sensitive TB patients of a TB unit where the MERMS box was issued to them on a pilot basis under the national program. These were assessed on a validated scale of 11 questions graded on a 5-point Likert scale for the usability of MERMS box and various determinants among adherent and Nnonadherent groups were assessed. RESULTS: A total of 126 patients were included in our study with high satisfaction scores for the usage of the MERMS box. There was 89.7% adherence and 10.3% Nonadherence with this and the determinants found to be statistically significant were the large distance of the center from home, loss of daily wages, any of the family problems, Having insufficient money for performing regular investigations, fear of side effects of drugs, social stigma attached, travel cost, long waiting periods at DOTS center, and any toxicity of drugs being experienced. CONCLUSIONS: The usability of MERMS can be enhanced by bringing changes in the font of printed labels and operation instructions and the removal of social stigma can improve adherence.

Improved diagnosis of extrapulmonary tuberculosis in adults with and without HIV in Mbeya, Tanzania using the MPT64 antigen detection test.

Extrapulmonary tuberculosis (EPTB) in People Living with HIV (PLWHIV) is a diagnostic challenge. Our immunochemistry based MPT64 antigen detection test has shown improved sensitivity compared to current laboratory tests in the resource limited diagnostic setting. The aim of this study was to validate the implementability and diagnostic performance of the test in PLWHIV and HIV negative adults in a HIV endemic Tanzanian setting. Adult (>18 y) presumptive EPTB patients were prospectively enrolled at Mbeya Zonal Referral Hospital and followed to the end of treatment or until an alternative diagnosis was reached. Suspected sites of infection were sampled and were subject to routine diagnostics, GeneXpert MTB/RIF assay and the MPT64 test. The performance of the diagnostics tests was assessed using a composite reference standard that included clinical suspicion, mycobacterial culture, response to anti-tuberculosis (TB) therapy, cytological and radiological findings. Patients (N = 168) were categorized as 21 confirmed TB, 23 probable TB and 44 possible TB cases, 69 patients were categorized as non-TB cases and 11 were uncategorized. In the TB group, the three most common infections were adenitis (41%), peritonitis (19%) and pleuritis (14%). The TB and non-TB groups did not differ in HIV seropositivity (46% vs 42%) Among HIV negative and PLWHIV, the MPT64 test had a sensitivity of (91% vs 78%), specificity (75% vs 86%), positive predictive value (80% vs 88%), negative predictive value (89% vs 74%), and accuracy (84% vs 81%), respectively. Performance was not significantly reduced in PLWHIV, and sensitivity was higher than in the currently used tests, including the GeneXpert MTB/RIF assay. The MPT64 test improved the diagnosis of EPTB, irrespective of HIV status. The test performed better than currently used diagnostic test. The test was implementable in a tertiary level hospital with basic pathology services in a HIV endemic Tanzanian setting.

IMB-BZ as an Inhibitor Targeting ESX-1 Secretion System to Control Mycobacterial Infection.

Resistance to anti-tuberculosis (TB) drugs is a major issue in TB control, and demands the discovery of new drugs targeting the virulence factor ESX-1. We first established a high-throughput screen (HTS) assay for the discovery of ESX-1 secretion inhibitors. The positive hits were then evaluated for the potency of diminishing the survival of virulent mycobacteria and reducing bacterial virulence. We further investigated the probability of inducing drug resistance and the underlying mechanism using mycobacterial protein fragment complementation. A robust HTS assay was developed to identify small molecules that inhibit ESX-1 secretion without impairing bacterial growth in vitro. A hit named IMB-BZ specifically inhibits the secretion of CFP-10 and reduces virulence in an ESX-1-dependent manner, therefore resulting in significant reduction in intracellular and in vivo survival of mycobacteria. Blocking the CFP-10-EccCb1 interaction directly or indirectly underlies the inhibitory effect of IMB-BZ on the secretion of CFP-10. Importantly, our finding shows that the ESX-1 inhibitors pose low risk of drug resistance development by mycobacteria in vitro as compared with traditional anti-TB drugs, and exhibit high potency against chronic mycobacterial infection. Targeting ESX-1 may lead to the development of novel therapeutics for tuberculosis. IMB-BZ holds the potential for future development into a new anti-TB drug.

Hypersensitivity reactions to multiple anti-tuberculosis drugs.

This study aimed to evaluate hypersensitivity reactions to anti-tuberculosis (TB) drugs. We retrospectively compared the clinical manifestations and treatment outcomes of single and multiple drug hypersensitivity reactions (DHRs). Twenty-eight patients were diagnosed with anti-TB DHRs using oral drug provocation tests. Of these 28 patients, 17 patients (60.7%) had DHRs to a single drug and 11 (39.3%) had multiple DHRs. The median age of patients was 57.5 years (interquartile range [IQR], 39.2-73.2). Of the total patients, 18 patients (64.3%) were men. The median number of anti-TB drugs causing multiple DHRs was 2.0 (IQR 2.0-3.0). Rifampin was the most common drug that caused DHRs in both the single and multiple DHR groups (n = 8 [47.1%] and n = 9 [52.9%], respectively). The treatment success rate was lower in the multiple DHR group than in the single DHR group; however, the difference was not statistically significant (81.8% vs. 94.1%; P = 0.543). Multiple anti-TB DHRs were common in all patients who experienced DHRs, and rifampin was the most common causative drug. The treatment outcomes appeared to be poorer in patients with multiple DHRs than in those with single DHRs.

Performance of the MeltPro MTB Assays in the Diagnosis of Drug-Resistant Tuberculosis Using Formalin-Fixed, Paraffin-Embedded Tissues.

The MeltPro MTB assays for detection of resistance to antituberculosis (TB) drugs perform well in genotypic drug susceptibility testing (DST) of clinical samples, but their effectiveness with formalin-fixed, paraffin-embedded (FFPE) tissues is unknown. FFPE tissues were obtained from 334 patients with TB. Susceptibility to rifampicin (RIF), isoniazid (INH), and fluoroquinolones was examined using the MeltPro MTB assays, with Xpert MTB/RIF (Xpert) and/or phenotypic DST (pDST) results as references. Samples with discordant results were analyzed by multiplex polymerase chain reaction-targeted amplicon sequencing (MTA-seq). With pDST as the reference, the MeltPro MTB assays sensitivity for RIF, INH, levofloxacin (LVX), and moxifloxacin (MXF) was 95.00%, 96.00%, 100%, and 100%, respectively, and the specificity was 95.15%, 95.92%, 94.69%, and 89.92%, respectively. Concordance was 99.08% between the MeltPro MTB and Xpert (κ = 0.956) for RIF and 95.12% (κ = 0.834), 95.93% (κ = 0.880), 95.12% (κ = 0.744), and 90.24% (κ = 0.367) between the MeltPro MTB and pDST for RIF, INH, LVX, and MXF, respectively. MTA-seq confirmed the discordancy between the MeltPro MTB and pDST for 26 (89.66%) of 29 samples. The MeltPro MTB assays rapidly and efficiently predict Mycobacterium tuberculosis resistance to the main first- and second-line anti-TB drugs in FFPE tissues.

Targeting ESX-1 Secretion System to Control Mycobacterial Infection

Resistance to anti-tuberculosis (TB) drug is a major public health problem threatening the progress that has been made in TB care and control worldwide. The rise of mycobacterium resistance to traditional antibiotics has motivated recent efforts to discover new drug candidates that target virulence factors. In this work, we have developed a robust high-throughput screen (HTS) assay that directly measures the activity of ESX-1 secretion. This screen identifies small molecules that inhibit ESX-1 secretion and thereby bacterial virulence without impairing bacterial growth in vitro. A hit named IMB-BZ specifically inhibits the secretion of CFP-10 and reduces virulence in an ESX-1 dependent manner, therefore resulting in significant reduction in intracellular and in vivo survival of mycobacterial. Importantly, our data illuminate the great advantage of the ESX-1 inhibitors in the low risk of mycobacterium developing resistance in vitro as compared with traditional anti-TB drug as well as in the strong potency against latent mycobacterial infection. Thus targeting ESX-1 may lead to the development of therapeutics to drug resistant-tuberculosis.

Laboratory diagnosis of immuno-mediated reactions of hypersensitivity to drugs in patients with pulmonary tuberculosis

To date, there are no unified and standardized laboratory methods for diagnosis allergic reactions to anti-TB drugs.Objective — to optimize the methods of laboratory diagnostics of hypersensitivity reactions to anti-tuberculosis (TB) drugs in patients with pulmonary tuberculosis and to find out their immunological mechanisms.Materials and methods. Clinical and immunological examination was carried out in 39 patients with pulmonary tuberculosis, which were divided into two groups: 1st — with the presence of clinical manifestations of hypersensitivity to anti-TB drugs; 2rd — without visible clinical sings of hypersensitivity. The tests were performed to detect intolerance to first-line anti-TB drugs in vitro: activation of basophiles, determination of serum tryptase, total (IgE) and specific (IgEsp ) immunoglobulin E levels, and erythrocyte sedimentation rate (ESR).Results and discussion. Patients of the 1st group showed increase levels of tryptase, total IgE, specific IgEsp for rifampicin and ethambutol in the blood. Frequency of positive values of ESR for isoniazid was significantly higher in group 1. Correlation between ESR and number of activated basophils and its activated receptors, levels of tryptase and total IgE was observed.Conclusions. The most informative tests in vitro to determine the causative drug in TB patients with clinical manifestations of allergy are: the level of specific IgEsp for rifampicin and ethambutol; erythrocyte sedimentation reaction for isoniazid. The use of basophil activation test is limited in the diagnosis of immuno-mediated allergic reactions to first-line anti-TB drugs

Isoniazid and Rifampin-Resistance Mutations Associated With Resistance to Second-Line Drugs and With Sputum Culture Conversion.

Mutations in the genes inhA, katG, and rpoB confer resistance to anti-tuberculosis (TB) drugs isoniazid and rifampin. We questioned whether specific mutations in these genes were associated with different clinical and microbiological characteristics. In a multicountry prospective cohort study of multidrug-resistant TB, we identified inhA, katG, and rpoB mutations in sputum isolates using the Hain MTBDRplus line probe assay. For specific mutations, we performed bivariate analysis to determine relative risk of baseline or acquired resistance to other TB drugs. We compared time to sputum culture conversion (TSCC) using Kaplan-Meier curves and stratified Cox regression. In total, 447 participants enrolled from January 2005 to December 2008 from 7 countries were included. Relative to rpoB S531L, isolates with rpoB D516V had less cross-resistance to rifabutin, increased baseline resistance to other drugs, and increased acquired fluoroquinolone resistance. Relative to mutation of katG only, mutation of inhA promoter and katG was associated with baseline extensively drug resistant (XDR) TB, increased acquired fluoroquinolone resistance, and slower TSCC (125.5 vs 89.0 days). Specific mutations in inhA and katG are associated with differences in resistance to other drugs and TSCC. Molecular testing may make it possible to tailor treatment and assess additional drug resistance risk according to specific mutation profile.

The molecular patterns of resistance to anti-tuberculosis drugs: an analysis from Istanbul, Turkey

Resistances to anti-tuberculosis (TB) drugs are related to the mutations in the genome of the Mycobacterium tuberculosis complex (MTBC). To expose the genomic mutations that cause anti-TB drug resistance. The GenoType MTBDRplus and MTBDRsl assays were used to detect genetic mutations. In this study of 1329 MTBC isolates, the sensitivities and specificities of genotypic methods for the detection of isoniazid (INH), rifampicin (RIF), ethambutol (EMB), and multi-drug resistance were 0.77, 0.84, 0.65, 0.89 and 0.99, 0.98, 0.67, 0.94, respectively. MUT3 mutations (S531L) of the rpoB gene for RIF resistance and MUT1 mutations (S315T1 and C15T) of the katG and inhA genes for INH resistance were dominant. The most frequently observed mutations that created resistance to fluoroquinolones (FLQ) were MUT3C (D94G) of the gyrA gene. The predominant mutations of EMB resistance were MUT1B (M306V) of the embB gene. Aminoglycosides/cyclic peptides (AG/CP) resistance was rare. The molecular mechanisms of anti-TB drugs resistance in MTBC strains found in Istanbul are similar to those in the literature.

Causality assessment of adverse drug reactions reported with antitubercular drugs in a tertiary care hospital - An observational study

Background: Adverse drug reactions (ADRs) are regarded as one of the major causes of non-adherence to anti-tuberculosis (TB) treatment. Identify ADRs and Establish a causal relationship between Suspected drug and Adverse Event is very important step from Pharmacovigilance point of view. Aim and Objective: This study aims to monitor the adverse effects of the drugs in the patients on treatment for TB and do the causality assessment. Materials and Methods: A prospective, single-centric, observational, and open-labeled study was carried out in a tertiary care hospital of Mumbai. Patients presenting with ADRs were monitored, analyzed and causality assessment was carried out using World Health Organization-Uppsala Monitoring Centre (WHO-UMC) and Naranjo’s assessment scale. Results: A total of 459 patients presenting with ADRs were enrolled in the study, their mean age was 34.60±14.21 years while male patients outnumbered female patients. About 363 patients presented with at least any one type of ADR followed by 96 patients presented with combination of any two ADRs, so study population (n = 459) presented with total 555 ADRs. Gastrointestinal and hepatobiliary system were the most affected sites of body. Majority of ADRs showed possible relation to the suspected drug during causality assessment using both the WHO-UMC and Naranjo’s scale. Conclusion: Majority of ADRs were mild to moderate in nature with no occurrence of severe ADR. It is important to establish information management systems to detect and report adverse drug events in chronic infective respiratory disease like TB. Focus should be given on assessment and prevention of medication errors resulting in ADRs.

Surveillance of adverse events in the treatment of drug-resistant tuberculosis: first global report.

The World Health Organization (WHO) recommends that countries implement pharmacovigilance and collect information on active drug safety monitoring (aDSM) and management of adverse events.The aim of this prospective study was to evaluate the frequency and severity of adverse events to anti-tuberculosis (TB) drugs in a cohort of consecutive TB patients treated with new (i.e. bedaquiline, delamanid) and repurposed (i.e. clofazimine, linezolid) drugs, based on the WHO aDSM project. Adverse events were collected prospectively after attribution to a specific drug together with demographic, bacteriological, radiological and clinical information at diagnosis and during therapy. This interim analysis included patients who completed or were still on treatment at time of data collection.Globally, 45 centres from 26 countries/regions reported 658 patients (68.7% male, 4.4% HIV co-infected) treated as follows: 87.7% with bedaquiline, 18.4% with delamanid (6.1% with both), 81.5% with linezolid and 32.4% with clofazimine. Overall, 504 adverse event episodes were reported: 447 (88.7%) were classified as minor (grade 1-2) and 57 (11.3%) as serious (grade 3-5). The majority of the 57 serious adverse events reported by 55 patients (51 out of 57, 89.5%) ultimately resolved. Among patients reporting serious adverse events, some drugs held responsible were discontinued: bedaquiline in 0.35% (two out of 577), delamanid in 0.8% (one out of 121), linezolid in 1.9% (10 out of 536) and clofazimine in 1.4% (three out of 213) of patients. Serious adverse events were reported in 6.9% (nine out of 131) of patients treated with amikacin, 0.4% (one out of 221) with ethionamide/prothionamide, 2.8% (15 out of 536) with linezolid and 1.8% (eight out of 498) with cycloserine/terizidone.The aDSM study provided valuable information, but implementation needs scaling-up to support patient-centred care.

Understand the Burden of MDR TB in DHQ/Teaching Hospital Gujranwala

Resistance to anti-tuberculosis (TB) medicines is a major public health threat in most countries of the World. As small no. of representative and quality-assured information on the magnitude of this problem existed in Pakistan, a survey was conducted in the DHQ/Teaching Hospital Gujranwala.Between January 2017 and January 2018, 212 consecutively diagnosed new culture-positive TB patients residing in District Gujranwala were enrolled in the survey. Mycobacterium tuberculosis isolates were obtained from each patient and tested for susceptibility to Rifampin Resistant. Multidrug-resistant (MDR)-TB was found in 19.2% of new patients. Overall, nearly one in 8 patients enrolled had MDR-TB. Patients with less than 25 yrs of age have shown a higher odds ratio of multi-drug resistant TB than those aged >55 yrs.The findings of this survey in Gujranwala District are alarming and represent the high proportions of MDR-TB . This study greatly contributes to the understanding of the burden of drug-resistant TB in urban areas of Gujranwala.

Serious Adverse Reactions From Anti-tuberculosis Drugs Among 599 Children Hospitalized for Tuberculosis.

The purpose of the study was to summarize the clinical characteristics of serious adverse reactions (ARs) related to anti-tuberculosis (TB) drugs in children hospitalized for TB. A comprehensive understanding of these drug-related ARs may serve to improve patient prognosis. Inpatients diagnosed with TB from 2008 to 2013 were enrolled retrospectively. The patients' demographics, diagnosis and ARs were recorded and analyzed for comprehensive evaluation. Of the 599 enrolled patients, 3.51% (21 of 599) developed serious ARs related to anti-TB drugs. Hepatotoxicity was the most common reaction (1.84%, 11 of 599). The incidence of rash with or without fever was 1% (6 of 599), and that of auditory impairments and renal injury was 0.33% (2 of 599) and 0.17% (1 of 599), respectively. One patient experienced hepatotoxicity, rash and fever. Hospital stay of inpatients with serious ARs was significantly longer (median: 24 days; range: 8-62 days) than that of those without reactions (median: 11 days; range: 1-83 days), though no distinctions were observed between the 2 groups with regard to average age, gender or involved organs. Hepatotoxicity occurred 6-30 days after the start of anti-TB treatment (median: 6 days) and 75% of the inpatients remained asymptomatic. Hepatotoxicity was traced to the drugs isoniazid, rifampin and pyrazinamide, while fever was mainly linked to pyrazinamide. In addition, streptomycin and amikacin led to auditory impairments and renal injury, respectively. Serious ARs of all inpatients were controlled and managed successfully. The incidence of serious ARs from anti-TB drugs among children inpatients was 3.5% and mainly consisted of hepatotoxicity. Inpatients with serious ARs tended to have longer hospital stays.

Genetic Determinants of the Pharmacokinetic Variability of Rifampin in Malawian Adults with Pulmonary Tuberculosis

ABSTRACTVariable exposure to antituberculosis (TB) drugs, partially driven by genetic factors, may be associated with poor clinical outcomes. Previous studies have suggested an influence of the SLCO1B1 locus on the plasma area under the concentration-time curve (AUC) of rifampin. We evaluated the contribution of single nucleotide polymorphisms (SNPs) in SLCO1B1 and other candidate genes (AADAC and CES-1) to interindividual pharmacokinetic variability in Malawi. A total of 174 adults with pulmonary TB underwent sampling of plasma rifampin concentrations at 2 and 6 h postdose. Data from a prior cohort of 47 intensively sampled, similar patients from the same setting were available to support population pharmacokinetic model development in NONMEM v7.2, using a two-stage strategy to improve information during the absorption phase. In contrast to recent studies in South Africa and Uganda, SNPs in SLCO1B1 did not explain variability in AUC0–∞ of rifampin. No pharmacokinetic associations were identified with AADAC or CES-1 SNPs, which were rare in the Malawian population. Pharmacogenetic determinants of rifampin exposure may vary between African populations. SLCO1B1 and other novel candidate genes, as well as nongenetic sources of interindividual variability, should be further explored in geographically diverse, adequately powered cohorts.

Association between TXNRD1 polymorphisms and anti-tuberculosis drug-induced hepatotoxicity in a prospective study.

Anti-tuberculosis drug-induced hepatotoxicity (ATDH) is a serious adverse reaction to anti-tuberculosis (TB) treatment. Thioredoxin reductase 1 (TXNRD1), encoded by the TXNRD1 gene, is an important enzyme involved in oxidant challenge. TXNRD1 plays a key role in regulating cell growth and transformation, and protects cells against oxidative damage. We investigated the association between TXNRD1 polymorphisms and ATDH susceptibility. In this prospective study, 280 newly diagnosed TB patients were followed-up for 3 months after beginning anti-TB therapy. Tag single-nucleotide polymorphisms (tag-SNPs) of TXNRD1 were selected using Haploview 4.2 based on the HapMap database of the Chinese Han in Beijing (CHB) panel. Genotyping was performed using the MassARRAY platform. Of the 280 patients enrolled in this study, 33 were lost to follow-up, 24 had ATDH, and 223 were free from ATDH. After adjusting for sex, age, smoking status, and body mass index, there were no significant differences in the allele and genotype frequency distributions of TXNRD1 SNPs between the ATDH and non-ATDH groups (all P > 0.05). The haplotype analysis showed that haplotype TCAGCC was associated with an increased risk of ATDH susceptibility [P = 0.024, OR (95%CI) = 6.273 (1.023-38.485)]. Further stratified analyses showed that the haplotype TCAGCC was associated with ATDH susceptibility in female subjects [P = 0.036, OR (95%CI) = 5.711 (0.917-35.560)] and non-smokers [P = 0.029, OR (95%CI) = 6.008 (0.971-37.158)]. Our results suggest that TXNRD1 variants may favor ATDH susceptibility in females and non-smokers. Further studies are required to verify this association.

Predictors of Non-adherence to Anti-Tuberculosis Medication in Tuberculosis Patients in Thailand

The study aimed to assess the prevalence of and correlates the non-adherence to anti-tuberculosis (TB) medication in tuberculosis patients in Thailand. In 2014, a cross-sectional interview survey w...

Low isoniazid and rifampicin concentrations in TB/HIV co-infected patients in Uganda.

Introduction There is limited data available on exposure to anti-tuberculosis (TB) drugs in this region. Peloquin has described reference ranges [1] however some studies have demonstrated that patients actually achieve concentrations below these ranges [2]. There is limited data about exposure to anti-TB drugs in the HIV/TB co-infected population in Sub-Saharan Africa. Our objective is to describe the concentration of anti-TB drug levels in a well characterized prospective cohort of adult patients starting treatment for pulmonary TB.Methods This study is an ongoing study carried out in the TB/HIV integrated clinic at the Infectious Diseases Institute in Kampala, Uganda. Sputum culture and microscopy was done for all patients. We performed pharmacokinetic blood sampling of anti-TB drugs for 1 hour, 2 hours and 4 hours post dose at 2 weeks, 8 weeks and 24 weeks after initiation of anti-TB treatment using ultraviolet high-performance liquid chromatography (UV-HPLC). We described the maximum concentration (Cmax) of isoniazid (H), rifampicin (R), ethambutol (E) and pyrazinamide (Z) and compare them with the values observed by Peloquin et al. referenced in other studies.Results We started 113 HIV infected adults on a fixed dose combination of HREZ. The median age of our population was 33 years, of which 52% were male with a median BMI of 19 kg/m2 and a median CD4 cell count of 142 cells/µL. In 90% of the participants, the diagnosis of TB was based on microscopy and or cultures. The boxplot graph shows the median Cmax and IQR of H and R.Levels of H were found to be below the reference ranges (3–6 µg/mL) in 54/77(70.1%), 38/59(64.4%) and 15/24(62.5%) participants at weeks 2, 8 and 24. Rif levels were also found to be below the reference ranges (8–24 µg/mL) in 41/66(62.1%), 26/48(54.2%) and 8/10(8%) participants at weeks 2, 8 and 24, respectively. The mean Cmax of E and Z were within the reference range at week 2 and 8; mean Cmax of 3.2±SD2.1 µg/mL and 4.0±SD3.1 µg/mL for E and 41.6±SD13.1 µg/mL and 42.6±SD16.4 µg/mL for Z.Conclusion We observed lower concentrations of isoniazid and rifampicin in our study population of HIV/TB co-infected patients. The implications of these findings are not yet clear. We therefore need to correlate our findings with the response to TB treatment.

Evaluation of a modified direct agar proportion method for testing susceptibility of Mycobacterium tuberculosis from MGIT samples

The emergence of resistance to anti-tuberculosis (TB) drugs has become an obstacle to effective TB control. Thus, there is an urgent need to identify patients and initiate adequate treatment for drug-resistant cases in a timely manner. The BACTEC MGIT 960 system is well known for its rapid culturing time, and is in widespread use in Taiwan. In this study, we evaluated the possibility of replacing the traditional indirect agar proportion method with a modified direct agar proportion method (MDAPM), as a technique for rapid testing the drug susceptibility of Mycobacterium tuberculosis without additional cost. In this study, 432 positive MGIT 960 samples that were identified as M. tuberculosis complex using the MeDiPro M. tuberculosis Antigen Rapid Test or the Cobas Amplicor MTB test were evaluated. Each sample was tested separately by the MDAPM and indirect agar proportion method, between July 2008 and December 2008, to compare the consistency and total turnaround time. Four first-line anti-TB drugs-rifampin, isoniazid, ethambutol, and streptomycin-were tested. For the MDAPM and indirect agar proportion method, the respective consistencies for each drug were 99.31%, 98.38%, 98.38%, and 97.22%. Our results also indicated that the MDAPM leads to an average saving in working time of 2 weeks, compared with the traditional indirect agar proportion method. In addition to having the potential to shorten turnaround time without compromising diagnostic quality, the MDAPM also provides a more efficient and cost-effective procedure. This modified procedure presents potential benefits for TB diagnosis in laboratories already equipped with the MGIT 960 system.