Isoniazid Mono-resistant Tuberculosis Research Articles

Clinical Profile and Treatment Outcome of H-mono/Polydrug-resistant Tuberculosis: A Single-center Retrospective Study

ABSTRACT Background: Isoniazid-monoresistant tuberculosis (Hr-TB) is the most prevalent drug-resistant TB. It often precedes multidrug-resistant TB (MDR-TB) and poses a major threat in the fight against TB control. The treatment outcome in Hr-TB and polydrug-resistant TB (PDR-TB) other than MDR still remains unclear. Aim: The aim of the study is to determine the clinical characteristics and treatment outcome in H-mono/PDR-TB under programmatic conditions. Materials and Methods: The study design was retrospective observational. It was conducted at the respiratory medicine department of a tertiary care institute in Mumbai. The medical records for bacteriologically confirmed TB patients diagnosed between July 2021 and December 2022 were reviewed. A total of 827 patients were enrolled and among them 46 patients with H-mono/PDR-TB were analyzed. The demographic data, clinical characteristics, and treatment outcomes were recorded. Results: Among 46 patients of isoniazid mono-resistant/PDR-TB analyzed from 827 bacteriologically confirmed TB, 24 were women with a mean age of 30.5 years. Twenty-five (54.34%) were resistant to isoniazid and the remaining 21 (45.66%) were PDR-TB. Primary Hr-TB was detected in 43 (93%) patients. The KatG mutation in 30 (65.2%) patients was the most common form of isoniazid (INH) mono resistance followed by inhA mutation 16 (34.8%). The fluoroquinolone (FQ)-based treatment regime as per national program guidelines had favorable outcomes in 42 (91.3%). However, unfavorable outcome with progression to MDR was observed in 3 (6.52%) and death in 1 (2.18%) patients. Conclusion: H-mono/PDR-TB is the most prevalent DRTB and most of them have primary resistance to isoniazid. Availability of first and SL LPA and limited DST with FQ-based regime under the national program has improved treatment outcomes in Hr-TB/PDR-TB.

Isoniazid monoresistant tuberculosis treatment outcomes in Puducherry, South India - A mixed methods study

SettingOn a programmatic basis, a new regimen was introduced in the National Tuberculosis Elimination Programme for isoniazid monoresistant tuberculosis in a few states in India. ObjectiveTo describe the clinical attributes and treatment outcomes of isoniazid mono-resistant tuberculosis patients on the new 6-month levofloxacin-containing regimen in Puducherry, India. DesignThe study is designed as a convergent parallel mixed-methods study: a retrospective cohort study and a descriptive qualitative study. A total of 180 Hr-TB patient health records were reviewed, and in-depth interviews with 35 participants were conducted. (20 Hr-TB patients and 15 HCWs). ResultsOf the total 180 Hr-TB patients included, we documented unfavourable outcomes in 26.1% of cases, and the KatG gene mutation was the most common mutation observed (63.9%). A significant risk of unfavourable outcomes was associated with low adherence and positive sputum at the third-month culture report. In interviewing the stakeholders, major challenges observed were the increased pill burden, delay in diagnosis, shortage of drugs, and lack of staff. ConclusionHr-TB patients have difficulty in adhering to the 6-month levofloxacin regimen, with the need for rigorous early 3-month follow-up and assessment.

A rare case of isoniazid mono-resistant tuberculosis presenting as cardiac tamponade along with an anterior mediastinal mass in a 15-year-old immunocompetent patient.

A 15-year-old boy presented with a sudden onset of breathlessness for 7 days, gradual loss of weight of 17.6 lbs over the last month and progressive hoarseness of voice for 7 months. The contrast-enhanced computed tomography (CECT) scan revealed a heterogeneously enhancing lesion in the anterior mediastinum with multiple discrete lymph nodes in the cervical and mediastinal locations. The GeneXpert MTB/RIF assay performed on the CT-guided biopsy of the mass was negative, but the culture for Mycobacterium tuberculosis was positive at 7 weeks of incubation. There was a suboptimal radiological response after 6 months of treatment. First-line drug susceptibility testing (DST) performed by line probe assay (LPA) on the positive culture detected high-level resistance to isoniazid. The treatment was modified as per DST results to which the patient responded well.

Assessing Treatment Efficacy and Determinants of Outcome in Isoniazid Mono-resistant Tuberculosis Patients: A Prospective Observational Study in Gujarat

Introduction: There is a high number of isoniazid-resistant tuberculosis (TB) in India; estimates imply that over 25% of TB patients there are isoniazid-resistant. Hence, the study aimed to evaluate the effectiveness of therapy for patients with isoniazid-mono-resistant TB and the negative effects of the H-mono-resistant TB Regime. Materials and Methods: It was a hospital-based prospective observational study from September 2021 to August 2022. Hence, 100 patients diagnosed with isoniazid mono-resistance TB enrolled in this study. After obtaining the prior informed consent of all patients willing to approve the collection and publication of their data, including extensive clinical history and radiological, microbiological, and biochemical investigations, this study included all diagnosed cases of isoniazid mono-resistant TB. A descriptive statistical analysis was done for continuous and categorical variables. Differences in characteristics between participants were tested with logistic regression and cross-tabulation. P <0.05 was considered significant. Results: Among 100 patients participated, their mean age was 50.8 ± 3.2 years. About 72 (72%) participants have successful treatment outcomes (cure). Only about 25 (25%) patients had minor adverse drug reactions. Body mass index (16.6 [3.6–74]), substance addiction history (9.5 [3.3–26.9]), previous history of TB (9 [3.3–24.0]), type of lesion (5.3 [1.6–17]), and extent of the lesion (2.6 [1.03–6.07]) in chest X-ray were associated statistically with the treatment outcome. Conclusion: The findings suggest that the H-mono-resistance regime is generally well-tolerated, with only a small percentage of patients experiencing nonserious adverse drug reactions, and the overall successful treatment outcome in H-mono patients was 72%. The study also highlights the importance of monitoring drug resistance patterns, particularly for levofloxacin and moxifloxacin, and the need for effective treatment regimens for isoniazid mono-resistant pulmonary TB.

Delphi Survey on the Current and Future Korean Guidelines for Isoniazid-Monoresistant Tuberculosis.

Isoniazid-monoresistant tuberculosis (Hr-TB) has emerged as a global challenge, necessitating detailed guidelines for its diagnosis and treatment. We aim to consolidate the Korean guidelines for Hr-TB management by gathering expert opinions and reaching a consensus. A conventional Delphi method involving two rounds of surveys was conducted with 96 experts selected based on their clinical and research experience and involvement in nationwide tuberculosis studies and development of the Korean guidelines on tuberculosis. The survey consisted of three sections of questionnaires on diagnosis, treatment, and general opinions on Hr-TB. Among the 96 experts, 72 (75%) participated in the two rounds of the survey. A majority of experts (96%) strongly agreed on the necessity of molecular drug susceptibility testing (DST) for isoniazid and rifampin resistance in all tuberculosis patients and emphasized the importance of interpreting mutation types (inhA or katG) and additional molecular DST for fluoroquinolones for confirmed isoniazid-resistant cases. Over 95.8% of experts recommended treating Hr-TB with a combination of rifampin, ethambutol, pyrazinamide, and levofloxacin for six months, without exceeding 12 months unless necessary. They also acknowledged the drawbacks of long-term pyrazinamide use due to its side effects and agreed on shortening its duration by extending the duration of the rest of the treatment with a modified combination of choice. This Delphi survey enabled Korean tuberculosis experts to reach a consensus on diagnosing and treating Hr-TB. These findings will be valuable for developing the upcoming revised Korean guidelines for Hr-TB management.

Poor treatment outcome and associated risk factors among patients with isoniazid mono-resistant tuberculosis: A systematic review and meta-analysis.

To date, isoniazid mono-resistant tuberculosis (TB) is becoming an emerging global public health problem. It is associated with poor treatment outcome. Different studies have assessed the treatment outcome of isoniazid mono-resistant TB cases, however, the findings are inconsistent and there is limited global comprehensive report. Thus, this study aimed to assess the poor treatment outcome and its associated risk factors among patients with isoniazid mono-resistant TB. Studies that reported the treatment outcomes and associated factors among isoniazid mono-resistant TB were searched from electronic databases and other sources. We used Joana Briggs Institute critical appraisal tool to assess the study's quality. We assessed publication bias through visual inspection of the funnel plot and confirmed by Egger's regression test. We used STATA version 17 for statistical analysis. Among 347 studies identified from the whole search, data were extracted from 25 studies reported from 47 countries. The pooled successful and poor treatment outcomes were 78% (95%CI; 74%-83%) and 22% (95%CI; 17%-26%), respectively. Specifically, complete, cure, treatment failure, mortality, loss to follow-up and relapse rates were 34%(95%CI; 17%-52%), 62% (95%CI; 50%-73%), 5% (95%CI; 3%-7%), 6% (95%CI; 4%-8%), 12% (95%CI; 8%-17%), and 1.7% (95%CI; 0.4%-3.1%), respectively. Higher prevalence of pooled poor treatment outcome was found in the South East Asian Region (estimate; 40%, 95%C; 34%-45%), and African Region (estimate; 33%, 95%CI; 24%-42%). Previous TB treatment (OR; 1.74, 95%CI; 1.15-2.33), having cancer (OR; 3.53, 95%CI; 1.43-5.62), and being initially smear positive (OR; 1.26, 95%CI; 1.08-1.43) were associated with poor treatment outcome. While those patients who took rifampicin in the continuation phase (OR; 0.22, 95%CI; 0.04-0.41), had extrapulmonary TB (OR; 0.70, 95%CI; 0.55-0.85), and took second-line injectable drugs (OR; 0.54, 95%CI; 0.33-0.75) had reduced risk of poor treatment outcome. Isoniazid mono-resistant TB patients had high poor treatment outcome. Thus, determination of isoniazid resistance pattern for all bacteriologically confirmed TB cases is critical for successful treatment outcome. PROSPERO registration number: CRD42022372367.

A Retrospective Analysis of Clinico-Demographic and Genetic Characteristics and Treatment Outcomes in Isoniazid Mono-Resistant Tuberculosis Patients: A Single-Center Study.

Treatment failure and relapse rates are more likely to occur when there is isoniazid (INH) resistance. So, we can no longer ignore the problem of isoniazid mono-resistance. It is pertinent to control the spread of primary INH resistance and prevent secondary resistance. This study aims to evaluate subjects' clinical, demographic, and genetic characteristics and exploretheir treatment outcomes. All data of isoniazid mono-resistant tuberculosis (TB) patients, which were maintained in the electronic database of mandatory notifications (NIKSHAY Portal) between 2017 and 2022, were reviewed. A total of 54 patients wereincluded after excluding five patients with ongoing treatment. Of 54 patients, 41 (75.9%) were cured, which was classified under favorable outcome, and the rest were classified under unfavorable outcome. Phenotypic, high-level mutation (katG) was found in 48 (88.9%) patients. Kaplan-Meier curves show that survival probabilities increase in weeks with regular intake of drugs. Our study found that those with younger ages and males were more affected. We found favorable outcomes in the majority of patients.

Pattern of InhA and KatG mutations in isoniazid mono resistant Mycobacterium tuberculosis isolates from Odisha

We conducted a retrospective analysis of the line probe assay (LPA) data during January to December 2019, from 8 districts of Odisha. The prevalence of Hr-TB (isoniazid resistance only) was 1.53% (50/3272) with a range of 0–3.4% in the 8 districts. Of the 50 Hr-TB strains, katG mutation and inhA mutations were seen in 74% (37/50) and 26% (13/50) strains respectively. S315T1 and C15T were common mutations in katG and inhA respectively. Since these mutations are closely related to high- or low degree resistance to INH, it has therapeutic implications.

Consequences of rpoB mutations missed by the GenoType MTBDRplus assay in a programmatic setting in South Africa.

Rifampicin resistance missed by commercial rapid molecular assays but detected by phenotypic assays may lead to discordant susceptibility results and affect patient management. This study was conducted to evaluate the causes of rifampicin resistance missed by the GenoType MTBDRplus and its impact on the programmatic management of tuberculosis in KwaZulu-Natal, South Africa. We analysed routine tuberculosis programme data from January 2014 to December 2014 on isolates showing rifampicin susceptibility on the GenoType MTBDRplus assay but resistance on the phenotypic agar proportion method. Whole-genome sequencing was performed on a subset of these isolates. Out of 505 patients with isoniazid mono-resistant tuberculosis on the MTBDRplus, 145 (28.7%) isolates showed both isoniazid and rifampicin resistance on the phenotypic assay. The mean time from MTBDRplus results to initiation of drug-resistant tuberculosis therapy was 93.7 days. 65.7% of the patients had received previous tuberculosis treatment. The most common mutations detected in the 36 sequenced isolates were I491F (16; 44.4%) and L452P (12; 33.3%). Among the 36 isolates, resistance to other anti-tuberculosis drugs was 69.4% for pyrazinamide, 83.3% for ethambutol, 69.4% for streptomycin, and 50% for ethionamide. Missed rifampicin resistance was mostly due to the I491F mutation located outside the MTBDRplus detection area and the L452P mutation, which was not included in the initial version 2 of the MTBDRplus. This led to substantial delays in the initiation of appropriate therapy. The previous tuberculosis treatment history and the high level of resistance to other anti-tuberculosis drugs suggest an accumulation of resistance.

Comparison of different regimens with or without fluoroquinolone in isoniazid-resistant tuberculosis: A multicenter cohort study

In 2018, the World Health Organization recommended a 6-month four-drug regimen (rifampicin, ethambutol, pyrazinamide, and levofloxacin) for the treatment of isoniazid-monoresistant tuberculosis. However, the regimen had very low certainty. This cohort study assessed the impact of fluoroquinolone use and initial baseline regimen on treatment effectiveness in isoniazid-monoresistant tuberculosis. This multicenter retrospective cohort study included 318 patients with isoniazid-monoresistant tuberculosis notified between 2011 and 2018 in Korea. Baseline regimens were classified into two groups, namely 6-9-month rifampicin, ethambutol, and pyrazinamide (6-9REZ) and a combination regimen of 2-month rifampicin, ethambutol, pyrazinamide and 7-10-month rifampicin and ethambutol (2REZ/7-10RE). Multivariable logistic regression was performed to assess factors associated with positive treatment outcomes. Of 318 enrolled patients, 234 (73.6%) were treated with the 6-9REZ and 103 (32.4%) with additional fluoroquinolone. In a multivariable logistic regression model comparing the 6-9REZ and 2REZ/7-10RE groups, there was no difference in the odds of positive outcomes (adjusted odds ratio = 1.08, 95% confidence interval = 0.65-1.82). Addition use of fluoroquinolone was not associated with positive treatment outcomes in the whole cohort (adjusted odds ratio = 1.41, 95% confidence interval = 0.87-2.27); however, its additional use was beneficial in the 2REZ/7-10RE subgroup (adjusted odds ratio = 3.58, 95% confidence interval = 1.32-9.75). Both initial baseline regimens, 6-9REZ and 2REZ/7-10RE, were similarly effective. Shortening of the pyrazinamide administration duration with additional fluoroquinolone use could be a safe alternative for patients with potential hepatotoxicity related to pyrazinamide.

Molecular detection of isoniazid monoresistance improves tuberculosis treatment: A retrospective cohort in France

Isoniazid-monoresistant tuberculosis (HR-TB) requires early diagnosis and adapted treatment to achieve optimal outcomes. The primary aim of the study was to assess the impact of the implementation of rapid diagnostic tests on HR-TB treatment in France. We designed a retrospective multicentre study including consecutive HR-TB patients diagnosed in 2016 and 2017. Implementation of a molecular assay detecting isoniazid resistance directly on a clinical sample was recorded. The association between early implementation of such assays and adequate treatment was assessed by a multivariable Cox proportional hazards model. Overall, 99 HR-TB patients were included from 20 University Hospitals. Among all smear-positive HR-TB patients, only 26% beneficiated from early molecular HR detection. This detection was independently associated with shorter time to adequate treatment (HR=2.0 [1.1-3.8], p=0.03). In our study, molecular detection of HR on an initial sample was independently associated with earlier treatment adaptation.

Prevalence and outcome of isoniazid-monoresistant tuberculosis at a university hospital in Saudi Arabia.

Objectives:To determine the prevalence and outcome in patients with isoniazid-monoresistant Mycobacterium tuberculosis complex and compare them to those in patients with non-isoniazid-monoresistant Mycobacterium tuberculosis.Methods:This cross-sectional analytical study was conducted at King Khalid University Hospital, Riyadh, Saudi Arabia. The data were retrospectively collected from the electronic medical records of patients who tested positive for Mycobacterium tuberculosis between May 2015 and April 2019.Results:We identified 105 patients infected with Mycobacterium tuberculosis. The prevalence proportion of isoniazid-monoresistant tuberculosis was 8.6% (n=9). Five patients with isoniazid-monoresistant tuberculosis (55.6%) were successfully treated, while one patient died. In the nonresistant population, 51 (53.1%) patients were successfully treated. However, 12 (12.5%) patients with no isoniazid resistance had an unsuccessful treatment outcome. The resistant group had a longer treatment duration with a mean of 12 months compared to the non-isoniazid-resistant group, with a mean treatment duration of 9.5 months. Twenty-eight patients (26.7%) had adverse events, with the majority of them being in the non-isoniazid-resistant group.Conclusion:Isoniazid monoresistance is the most common form of drug resistance found in our population. Our study has not shown any significance in the outcome of isoniazid-resistant cases compared to non-isoniazid-resistant cases. This may be due to the low number of isoniazid-monoresistant cases in our population.

Isoniazid-monoresistant tuberculosis in France: Risk factors, treatment outcomes and adverse events

ObjectivesIsoniazid-monoresistant tuberculosis (HR-TB) is the most prevalent form of drug-resistant TB worldwide and in France and is associated with poorer treatment outcomes compared with drug-susceptible TB (DS-TB). The objective of this study was to determine the characteristics of HR-TB patients in France and to compare outcomes and safety of treatment for HR-TB and DS-TB. MethodsWe performed a case-control multicenter study to identify risk factors associated with HR-TB and compare treatment outcomes and safety between HR-TB patients and DS-TB patients. ResultsCharacteristics of 99 HR-TB patients diagnosed and treated in the university hospitals of Paris, Lille, Caen and Strasbourg were compared with 99 DS-TB patients. Female sex (OR = 2.2; 1.0–4.7), birth in the West-Pacific World Health Organization region (OR = 4.6; 1.1–18.7) and resistance to streptomycin (OR = 77.5; 10.1–594.4) were found to be independently associated with HR-TB. Rates of treatment success did not differ significantly between HR-TB and DS-TB. ConclusionsFactors associated with HR-TB are not significant enough to efficiently screen TB patients at risk of HR-TB. The systematic implementation of rapid molecular testing on clinical samples remains the only effective way to make the early diagnosis of HR-TB and adapt treatment.

Tuberculosis Drug Susceptibility, Treatment, and Outcomes for Belarusian HIV-Positive Patients with Tuberculosis: Results from a National and International Laboratory.

Background To cure drug-resistant (DR) tuberculosis (TB), the antituberculous treatment should be guided by Mycobacterium tuberculosis drug-susceptibility testing (DST). In this study, we compared conventional DST performed in Minsk, Belarus, a TB DR high-burden country, with extensive geno- and phenotypic analyses performed at the WHO TB Supranational Reference Laboratory in Copenhagen, Denmark, for TB/HIV coinfected patients. Subsequently, DST results were related to treatment regimen and outcome. Methods Thirty TB/HIV coinfected patients from Minsk were included and descriptive statistics applied. Results Based on results from Minsk, 10 (33%) TB/HIV patients had drug-sensitive TB. Two (7%) had isoniazid monoresistant TB, 8 (27%) had multidrug-resistant (MDR) TB, 5 (17%) preextensive drug-resistant (preXDR) TB, and 5 (17%) had extensive drug-resistant (XDR) TB. For the first-line drugs rifampicin and isoniazid, there was DST agreement between Minsk and Copenhagen for 90% patients. For the second-line anti-TB drugs, discrepancies were more pronounced. For 14 (47%) patients, there were disagreements for at least one drug, and 4 (13%) patients were classified as having MDR-TB in Minsk but were classified as having preXDR-TB based on DST results in Copenhagen. Initially, all patients received standard anti-TB treatment with rifampicin, isoniazid, pyrazinamide, and ethambutol. However, this was only suitable for 40% of the patients based on DST. On average, DR-TB patients were changed to 4 (IQR 3-5) active drugs after 1.5 months (IQR 1-2). After treatment adjustment, the treatment duration was 8 months (IQR 2-11). Four (22%) patients with DR-TB received treatment for >18 months. In total, sixteen (53%) patients died during 24 months of follow-up. Conclusions We found high concordance for rifampicin and isoniazid DST between the Minsk and Copenhagen laboratories, whereas discrepancies for second-line drugs were more pronounced. For patients with DR-TB, treatment was often insufficient and relevant adjustments delayed. This example from Minsk, Belarus, underlines two crucial points in the management of DR-TB: the urgent need for implementation of rapid molecular DSTs and availability of second-line drugs in all DR-TB high-burden settings. Carefully designed individualized treatment regimens in accordance with DST patterns will likely improve patients' outcome and reduce transmission with drug-resistant Mycobacterium tuberculosis strains.

Management of isoniazid-monoresistant tuberculosis (Hr-TB) in Queensland, Australia: a retrospective case series

ObjectivesDrug-resistance represents a major threat in the fight against tuberculosis. Globally, isoniazid-monoresistant tuberculosis (Hr-TB) is twice as common as multidrug/rifampicin-resistant (MDR/RR)-TB. Recently updated WHO guidelines now recommend treatment of Hr-TB with rifampicin, ethambutol, pyrazinamide and levofloxacin for at least six months. Our primary objective was to define the frequency, treatment and outcomes for Hr-TB in Queensland, Australia. We also sought to determine the frequency of fluoroquinolone use and whether its inclusion improved outcomes. MethodsRetrospective case series of tuberculosis notifications in Queensland between 2000 and 2017 with at least low-level isoniazid resistance and preserved susceptibility to other first-line oral agents. ResultsHr-TB was identified in 7.2% of all notifications. Where outcomes were assessable (163/198), 76.1% were treated with first-line agents only and 11.0% received at least six months of a fluoroquinolone-containing regimen (consistent with recent WHO guidelines). Favourable outcomes were achieved in 95.7%, comparable to fully susceptible disease (94.9%). Inclusion of a fluoroquinolone did not significantly improve outcomes compared with a regimen containing first-line agents only, although these cases were more likely to have high-level resistance. Previous treatment made an unfavourable outcome more likely. ConclusionsHr-TB is prevalent in Queensland. Treatment outcomes in our cohort were comparable to fully susceptible disease. The current WHO-recommended regimen did not confer advantage over an appropriately constructed regimen containing first-line agents only. Our findings suggest that, in a well-resourced setting with good programmatic management, the addition of a fluoroquinolone may not substantially improve outcomes – potentially allowing these agents to be reserved for more extensively resistant disease.

Re-evaluating the role of isoniazid in treatment of pulmonary tuberculosis

Re-evaluating the role of isoniazid in treatment of pulmonary tuberculosis

Incidence, treatment, and outcomes of isoniazid mono-resistant Mycobacterium tuberculosis infections in Alberta, Canada from 2007-2017.

Isoniazid resistant Mycobacterium tuberculosis (Hr-TB) is the most frequently encountered TB resistance phenotype in North America but limited data exist on the effectiveness of current therapeutic regimens. Ineffective treatment of Hr-TB increases patient relapse and anti-mycobacterial resistance, specifically MDR-TB. We undertook a multi-centre, retrospective review of culture-positive Hr-TB patients in Alberta, Canada (2007–2017). We assessed incidence and treatment outcomes, with a focus on fluoroquinolone (FQ)-containing regimens, to understand the risk of unsuccessful outcomes. Rates of Hr-TB were determined using the mid-year provincial population and odds of unsuccessful treatment was calculated using a Fisher’s Exact test. One hundred eight patients of median age 37 years (IQR: 26–50) were identified with Hr-TB (6.3%), 98 of whom were able to be analyzed. Seven percent reported prior treatment. Rate of foreign birth was high (95%), but continent of origin did not predict Hr-TB (p = 0.47). Mean compliance was 95% with no difference between FQ and non-FQ regimens (p = 1.00). Treatment success was high (91.8%). FQ-containing regimens were frequently initiated (70%), with no difference in unsuccessful outcomes compared to non-FQ-containing regimens (5.8% vs. 13.8%, OR 0.4, 95% CI 0.1–2.3, p = 0.23). Only one patient (1%) utilizing a less common non-FQ-based regimen including two months of pyrazinamide developed secondary multidrug resistance. Unsuccessful treatment was low (<10%) relative to comparable literature (~15%) and showed similar outcomes for FQ and non-FQ-based regimens and no deficit to those using intermittent fluoroquinolones in the continuation phase of treatment. Our findings are similar to recent data, however prospective, randomized trials of adequate power are needed to determine the optimal treatment for Hr-TB.

Characteristics and Treatment Outcomes of Isoniazid Mono-Resistant Tuberculosis: A Retrospective Study.

PurposeIsoniazid (INH) mono-resistant tuberculosis (Hr-TB) is a highly prevalent type of drug-resistant TB, possibly associated with unfavorable treatment outcomes. However, definitive guidelines on an optimal treatment regimen and duration for Hr-TB are currently under discussion. We evaluated the characteristics and treatment outcomes of Hr-TB patients.Materials and MethodsWe retrospectively reviewed the medical records of Hr-TB patients treated at a South Korean tertiary referral hospital from January 2005 to December 2018.ResultsWe included 195 Hr-TB patients. 113 (57.9%) were male, and the median age was 56.6 [interquartile range, 40.2–68.6] years. Mutations in katG were the most frequent [54 (56.3%)], followed by those in the inhA [34 (35.4%)]. Favorable and unfavorable outcomes were noted in 164 (84.1%) and 31 (15.9%) patients, respectively. Smoking history [odds ratio (OR)=5.606, 95% confidence interval (CI): 1.695–18.543, p=0.005], low albumin level (OR=0.246, 95% CI: 0.104–0.578, p=0.001), and positive acid-fast bacilli culture at 2 months (OR=7.853, 95% CI: 1.246–49.506, p=0.028) were associated with unfavorable outcomes.ConclusionA tailored strategy targeting high-risk patients is imperative for improved treatment outcomes. Further research on the rapid and accurate detection of resistance to INH and other companion drugs is warranted.

Factors associated with isoniazid resistant tuberculosis among human immunodeficiency virus positive patients in Swaziland: a case-control study

BackgroundIsoniazid resistant tuberculosis is the most prevalent type of resistance in Swaziland and over two-thirds of the isoniazid resistant tuberculosis patients are tuberculosis and human immunodeficiency virus co-infected. The study aimed to determine risk factors associated with isoniazid resistant tuberculosis among human immunodeficiency virus positive patients in Swaziland.MethodsThis was a case-control study conducted in nine healthcare facilities across Swaziland. Cases were patients with isoniazid resistant tuberculosis (including 78 patients with isoniazid mono-resistant tuberculosis, 42 with polydrug-resistant tuberculosis, and 77 with multidrug-resistant tuberculosis). Controls were presumed drug-susceptible tuberculosis patients (n = 203). Multinomial logistic regression was used to determine related factors.ResultsThe median time lag from diagnosis to tuberculosis treatment initiation was 50 days for isoniazid mono or poly drug-resistant tuberculosis, 17 days for multidrug-resistant tuberculosis compared to 1 day for drug-susceptible tuberculosis patients. History of previous tuberculosis treatment was positively associated with either isoniazid mono or poly drug-resistant tuberculosis (OR = 7.91, 95% CI: 4.14–15.11) and multidrug-resistant tuberculosis (OR = 12.20, 95% CI: 6.07–24.54). Isoniazid mono or poly resistant tuberculosis patients were more likely to be from rural areas (OR = 2.05, 95% CI: 1.23–3.32) and current heavy alcohol drinkers compared to the drug-susceptible tuberculosis group. Multi drug-resistant tuberculosis patients were more likely to be non-adherent to tuberculosis treatment compared to drug-susceptible tuberculosis group (OR = 3.01, 95% CI: 1.56–5.82).ConclusionTo prevent and control isoniazid resistant tuberculosis among HIV-positive patients in Swaziland, the tuberculosis program should strengthen the use of rapid diagnostic tests, detect resistance early, promptly initiate supervised tuberculosis treatment and decentralize quality tuberculosis services to the rural areas. Adherence to tuberculosis treatment should be improved.

Isoniazid mono-resistant tuberculosis: Time to take it seriously

Background/AimsIn drug resistant tuberculosis (DRTB) suspects, rifampicin resistance has always been prioritized, hence Cartridge Based Nucleic Acid Amplification Test (CBNAAT) is recommended under Revised National Tuberculosis Control Programme (RNTCP), India. However, since it doesn't detect isoniazid resistance, rifampicin sensitive patients with unknown isoniazid status may be erroneously treated as drug sensitive TB, leading to poor treatment outcomes and emergence of multidrug resistant (MDR) TB. Hence isoniazid mono-resistance should be specifically looked for and treated as per recommendations.The objective of the present study, almost the first of its kind in India, was to evaluate the burden of isoniazid mono-resistance amongst patients diagnosed with DRTB and to study the association of different patient and disease related factors with treatment outcomes under the treatment regimen specific for isoniazid mono-resistance, started from January 1, 2017 in our state, under RNTCP. MethodsIt was a retrospective study which scrutinized medical records of 52 isoniazid mono-resistant TB patients started on treatment under RNTCP between January 1 to December 31, 2017. Necessary information on possible patient and disease related predicting factors like gender, age, type of mutation (katG/inhA), weight band (26–45 kg/46-70 kg), total serum protein/albumin levels, previous history of anti-tubercular treatment (ATT), history of smoking, HIV status, presence of diabetes mellitus (DM), presence of anemia, occurrence of adverse drug reactions (ADR) during treatment and duration of intensive phase (IP), was retrieved. These factors were analyzed for their possible association with treatment outcomes. ResultsOut of 103 DRTB patients enrolled, 50.5% (52/103) patients were diagnosed with isoniazid mono-resistance. 50/103 were MDR-TB and 1/103 were extensively-drug resistant TB (XDR-TB). Further analysis of these 52 isoniazid mono-resistant patients revealed:35 (67.3%) were males and 17 (32.7%) females. 27 (51.9%) patients were <30 years, 25 (48.1%) being ≥30 years of age. All patients were negative for HIV. 34/52 (65.4%) patients were declared cured, 15/52 were lost to follow up (LTFU) and 3/52 died (1 male, 2 females). Excluding these 3 patients who died, cure rates were significantly better in females (14/15 = 93.3%), with only 1/15 LTFU, than males (20/34 = 58.8% cure, 14/34 = 41.2% LTFU), (p = 0.019). Patients who were <30 years of age had significantly better cure rates (21/25 = 84%) with lesser LTFU's (4/25 = 16%), than those ≥30years of age (13/24 = 54.2% cure, 11/24 = 45.8% LTFU), (p = 0.032). Review of previous history of ATT revealed that 33 patients had primary isoniazid mono-resistance, 4 patients had previous history of being LTFU, 9 had recurrent TB and 3 were labeled as failure. Cure rates were significantly better in primary isoniazid mono-resistant patients (26/33 = 78.8%), than those with previous history of being LTFU(0/4), (p = 0.04).Type of mutation, weight band, total serum protein/albumin, history of smoking, presence of DM, presence of anemia, occurrence of ADR and duration of IP did not affect treatment outcomes. ConclusionIsoniazid mono-resistance formed a major chunk of DRTB, with majority of the patients detected with primary mono-resistance. Strategically framed treatment regimens for isoniazid mono-resistance under RNTCP in India are effective in a wide range of population. Still, there are high chances of LTFU/default, which needs to be addressed on priority. Male gender, age ≥30 years and being LTFU in the past are associated with poorer cure rates, hence should be paid special attention.