Anti-tubercular Treatment Regimen Research Articles

Ocular toxicity of daily anti-tubercular treatment regimen: A prospective observational study

Context: India carries a significant burden of TB which is the commonest cause of infectious disease-related mortality. Anti-tubercular drugs can cause serious ocular toxic effects. Optical coherence tomography (OCT) can be used as a valuable tool in the quantitative analysis of anti-tubercular treatment (ATT)-induced toxic optic neuropathy. Aims: To study the changes in visual parameters in patients on ATT and to analyze the OCT changes in patients by taking measurements once before initiation of treatment and once during ongoing treatment (between three and six months). Settings and Design: Tertiary care center, Prospective observational study. Methods and Material: A prospective observational study was conducted in 140 eyes of 70 subjects undergoing ATT as per the latest RNTCP guidelines where the following determinants were examined, and the corresponding values were taken once before initiation of treatment and once during ongoing treatment (between three and six months) and results were analyzed. Around 90% of the subjects were examined at the end fourth month. Visual acuity was taken using the Log Mar chart, color vision using Ishihara’s chart, and slit lamp examination and fundus evaluation using a 90 D lens. OCT was done and average nasal, temporal, superior, and inferior quadrant retinal nerve fiber layer (RNFL) measurements were taken. Perimetry was also done; however, findings were not included in this study. Statistical Analysis Used: Frequency and percentage were applied to study the changes in visual parameters in patients on ATT. A paired t-test was applied for numerical variables to analyze the OCT changes in patients undergoing ATT. A P value < 0.05 was considered statistically significant. Results: Despite a near-normal appearance of the fundus on ophthalmoscopy, OCT clearly demonstrated and quantified the loss of retinal nerve fibers. Statistically significant RNFL thinning (P value < 0.001) was noted in the superior, temporal, and inferior quadrants and least in the nasal quadrant (P = 0.005). Significant deterioration in visual acuity was observed following three months of ATT (P = 0.001). Red-green color vision abnormalities were detected in 14 out of 140 eyes (10%). Conclusions: RNFL thickness was reduced on OCT. RNFL thickness quantification and assessment of other visual parameters especially color vision help in the early diagnosis of ocular toxic effects of ATT. Hence, awareness and active screening are imperative in preventing visual impairment and blindness.

Identification of factors associated with non-adherence and discontinuation of antitubercular drugs in patients with tuberculosis

The effectiveness of the anti-tubercular treatment (ATT) depends on adherence to the proposed highly effective therapeutic scheme. When the patient starts ATT and fails to come to the healthcare facility for more than 30 consecutive days from the date scheduled for his return, it is considered abandonment. The objective was to identify the difficulties associated with non-adherence and abandonment of the ATT regimen and evaluate the regulation of anti-tuberculosis drugs in Kyrgyzstan. Patients with tuberculosis make the decision to abandon treatment because they are unaware of the time needed, the continuity of treatment, and for reasons of the disappearance of signs and symptoms. The use of alcohol and illicit drugs has a poor prognosis for the treatment, factors that predispose patients to abandon the treatment and prolong the drug therapy. The majority of the patients discontinue treatment because of adverse effects, contributing to the interruption of treatment, so patients should be assisted regularly. To strengthen the requirements for the quality of purchased anti-tuberculosis drugs, when drawing up the technical specification of the government decree of Kyrgyzstan, it is necessary to give preference to drugs that have been prequalified by World Health Organization or evaluated by strict regulatory authorities.

Evaluation of clinical profiles, imaging findings and antituberculosis treatment outcome in granulomatous mastitis: An Indian scenario

BackgroundThe management of choice for granulomatous mastitis (GM) has yet to be determined but few studies have demonstrated that anti-tubercular treatment (ATT) could be an effective alternative therapeutic option. Hence, the objective of the current study is to determine the clinical feature, radiological imaging findings, and histopathological examination results exhibited by GM and tuberculosis (TB)-proven GM as well as to evaluate the ATT clinical outcome in GM patients. MethodsThe study was performed on 68 GM patients who were referred to the department of pulmonology by the breast clinic (from January 2018 to August 2021). Study populations were categorized into two groups GM and TB-proven GM patients and all were prescribed with standard ATT regimen and were continuously followed up. SPSS version 25 was employed for statistical assessment. ResultsOur study showed that 6 patients from GM and 4 patients from the TB-proven GM group got relapsed. For patients who displayed partial remission, ATT treatment was started after assessing the side effects potential. 14.6% (n = 6) and 7.4% (n = 2) patients who initially demonstrated partial remission were also completely cured. ATT treatment curable rate was determined to be 90% (n = 37) and 81.5% (n = 22) for GM and TB-proven GM patients correspondingly. Therefore, the current study demonstrated nil significant differences between groups. ConclusionThe current study warrants that ATT therapy could be an effective and better treatment of choice for GM patients irrespective of their clinical condition.

Effects of the Modified Antitubercular Treatment Regimen on Renal Function in Patients With Chronic Kidney Disease and Pulmonary Tuberculosis: An Observational Study.

Chronic kidney disease (CKD) increases an individual's vulnerability to infections like tuberculosis. Doses of pyrazinamide and ethambutol are modified to treat such individuals. Additionally, the renal function tends to decline with advancing age. Therefore, it is crucial to study the effect of antitubercular drugs on renal function in youngand elderly patients. The primary objective of this study was to determine the change in serum creatinine levels at six months from baseline in two study groups that included patients aged ≤50 and >50 years. The secondary objectivewas to determine changes in estimated glomerular filtration rate (eGFR) and BMI six months from baseline. We recruited 40 patients with CKD and pulmonary tuberculosis from Srirama Chandra Bhanja (SCB) Medical College and Hospital, India. Each participant received the modified doses of antitubercular drugs. Their serum creatinine, eGFR, and BMI were assessed at baseline, two and six months.Participants had a mean age of 50.93±9.83 years. The median changes in serum creatinine and eGFR values from baseline were -0.19 and -0.23 mg/dl and 4.16 and 3.93 ml/min/m2 for the two study groups, respectively. Furthermore, the differences in BMI from baseline were 1.91 and 2.14 kg/m2, respectively, for the two groups. The renal function was found to be improved after six months of treatment with modified antitubercular drugs. The intergroup comparisons were not statistically significant. We conclude that the modifiedregimen helps effectively cure pulmonary tuberculosis and significantly improves renal function in CKD patients. Further studies are required togeneralize these findings.

Knowledge on the risk factors of drug-resistant tuberculosis among newly diagnosed patients of tuberculosis with first-line antitubercular treatment regimen

Knowledge on the risk factors of drug-resistant tuberculosis among newly diagnosed patients of tuberculosis with first-line antitubercular treatment regimen

A retrospective observational study of presentation, diagnosis, and management of patients with genitourinary tuberculosis in a tertiary care hospital of India

Objectives: To study the clinical features, diagnostic methods, and management of genitourinary tuberculosis (GUTB). Methods: This retrospective study included 117 patients with GUTB admitted over a period of 10 years. The analysis of the patients was done in terms of presentation, organ involved, diagnostic methods, and management. The 6-month anti-tubercular treatment (ATT) was given to all patients, which included isoniazid, rifampicin, and ethambutol/pyrazinamide. Follow-up period was 1–10 years. Results: The mean age of the patients was 32.5 ± 6.4 years with a male: female ratio of 1:1.51. The majority of the patients presented with irritative voiding symptoms (66.47%) and hematuria (47.6%). The common infected organs were kidney (64.9%), ureter (27.35%), urinary bladder (17.09%), prostate (3.4%), and epididymis (5.19%). 25.6% of patients had positive chest X-ray, and 61.2% of the patients had positive Mantoux test. The diagnostic positivity rate for polymerase chain reaction, urine Mycobacteriumtuberculosis culture test, and urine acid-fast bacilli test was 67.7%, 35.4%, and 21.6%, respectively. 71 (60.13%) of the patients needed surgical intervention. After medical therapy, the adverse reactions noted were abnormal liver function in four cases, pruritus in three cases, and skin eruption in one case. Among the total of 117 patients followed over a period of 1 year to 10 years, none recurred. Conclusion: In a retrospective study of 117 patients with GUTB, majority had bladder symptoms, 60.13% needed surgery, and all were treated with 6-month course of ATT regimen consisting of isoniazid, rifampicin, and ethambutol/pyrazinamide, with none showing recurrence during the period of 1–10 years of follow-up.

Diagnosis and Treatment of Tuberculous Meningoencephalitis and Toxoplasma Encephalitis in Positive HIV Patient: Case Report

Background Tuberculous meningoencephalitis (TBME) and toxoplasma encephalitis (TE) are the most frequent cerebral opportunistic infections in positive HIV patients in developed countries. This study aims to determine a presumptive diagnosis of TBME and TE based only on clinical, CD4-count, and radiology features and to attend suitable early treatment for better patient outcomes. Case Description A 40-year-old presented to the emergency unit of dr. Mintohardjo Naval Hospital with decreased consciousness. History of positive HIV status, pulmonary tuberculosis for six months and anti-tubercular-treatment (ATT) drop-out. The GCS was E2M5V2, lung crackles, nuchal rigidity, positive Babinski reflex, and duplex hemiparesis. CD4-count: 4 cells/mm3. Multiple hypodense lesions, “finger-like-oedema”, featured on non-contrast head CT-scan. A lumbar puncture was not performed. Treatment of TBME included an ATT regimen, pyridoxine, cotrimoxazole, anti-oedema, and TE treatment included clindamycin and pyrimethamine. Based on the clinical and radiological diagnosis of TBME (nuchal rigidity, history of ATT drop-out, multiple hypodense lesions on CT-scan) and TE (altered mental status, duplex hemiparesis, CD4-count, “finger-like-oedema” projections on CT-scan), ATT and TE treatment were given for ten days. There were significant clinical improvements by GCS E4M6V3, negative nuchal rigidity after being treated early by ATT and TE treatment. Conclusions Presumptive Diagnosis of TBME and TE in HIV patients can be determined only based on clinical, CD4-count, and radiology examination. However, there are significant clinical improvements in giving ATT along with TE treatment immediately in positive HIV patients.

A Case Series on GeneXpert Negative Tuberculous Mastitis and the Effect of Anti-tuberculous Treatment

Background: Breast tuberculosis is significant due to its rare occurrence and dilemma in prospective treatment and differentiation from neoplastic lesions. Tuberculosis of the breast usually affects women from Asia, most commonly, the Indian subcontinent and Africa. Tuberculous mastitis has a wide range of clinical presentation, radiological features, and even microbiological presentation. Materials and Method: A prospective study was conducted over 6 months. 40 female patients with varied presentations correlating to tuberculous mastitis with a lump in the breast for a particular period of time were included in the study. Results: The patients’ ages varied from 20 to 45 years. After routine investigations, the patients went in for incision and drainage or incisional biopsy or both and postoperatively their histopathological reports revealed granulomatous breast disease (tuberculous mastitis) with negative GeneXpert (CB-NAAT). Patients were started on an anti-tubercular treatment regimen and showed a progressive decrease in symptomatology. Conclusion: Granulomatous breast abscess/ tuberculous breast abscess has a varied presentation and no fixed treatment regime. Anti-tuberculous drugs in such patients proved to be efficacious in symptomatic relief with prevention of recurrence/ fistula formation.

Standard versus sequential anti-tubercular treatment in patients with tuberculous meningitis: a randomized controlled trial.

To compare the safety and efficacy of sequential anti-tubercular treatment (ATT) regimen with the standard regimen in tuberculous meningitis (TBM). This single-centre, open-label, parallel group randomized controlled trial was conducted from May 2017 to June 2019 in India. Treatment-naïve patients with TBM fulfilling the inclusion criteria were randomized to four drug ATT regimens (rifampicin, isoniazid, ethambutol and pyrazinamide) administered either simultaneously (standard arm) or one after another (sequential arm) in a 1 : 1 ratio. The primary endpoint was drug-induced hepatitis (DIH) and the secondary endpoints were in-hospital death and disability at 3 and 6months using a modified Rankin Scale. A total of 97 patients with TBM were recruited; 15 did not meet the inclusion criteria and 2 refused to participate. The median age of the patients was 26y (range 15-75) and 37 (46.2%) were males. The patients in the sequential arm had fewer cases of DIH (20% vs 42.5%; p=0.03). The patients in the sequential arm had lower in-hospital mortality (2.5% vs 17.5%; p=0.025) and better 6-month outcomes (25.0% vs 50.0%; p=0.02) compared with the standard arm. Sequential ATT was associated with a lower frequency of DIH, lower in-hospital mortality and better 6-month outcome. Clinical Trials Registry of India (ctri.nic.in) identifier: REF/2016/09/012214/CTRI/2017/10/010072.

Drug sensitivity patterns in Xpert-positive spinal tuberculosis: an observational study of 252 patients.

To evaluate the sensitivity patterns of anti-tubercular drugs in Xpert MTB-positive spinal tuberculosis (TB) patients and to formulate the guidelines for early start of empiric anti-tubercular treatment (ATT) in MDR-TB spine based on resistance pattern in this large series. It was a cross-sectional observational study of 252 consecutive patients who were Xpert MTB-proven spinal TB cases with retrospective analysis of prospective data. The Xpert MTB/RIF (Mycobacterium tuberculosis/rifampicin) assay was used to diagnose spinal TB and RIF resistance. All patients underwent drug sensitivity testing (DST) to 13 commonly used anti-tubercular drugs using BACTEC MGIT-960 system. The drug sensitivity pattern of primary and secondary anti-tubercular drugs was recorded and compared. The DST study revealed 110 (43.6%) cases of multi-drug resistant (MDR-resistance to both isoniazid and rifampicin) and 24 (9.5%) cases of non-MDR-TB spine. The widespread resistance was found for both isoniazid (91%) and rifampicin (85%), followed by streptomycin (61.9%). The least resistance was found for kanamycin, amikacin and capreomycin and no resistance found for clofazimine. The Xpert MTB/RIF assay is an efficient technique for the rapid diagnosis of spinal TB and suspected MDR-TB; however, it is recommended to do culture and DST in all patients with spinal TB to guide the selection of appropriate second-line drugs when required. In cases of non-availability of culture and DST, it is suggested to use data from large series such as this to plan the best empirical ATT regimen. These slides can be retrieved under Electronic Supplementary Material.

Assessment of adverse drug reactions to antituberculosis regimen in a tertiary care hospital

Background: Adverse drug reactions are common with multidrug therapy in tuberculosis, if detected early can improve patient compliance and prevent emergence of resistance.Methods: A prospective observational study as a part of Pharmacovigilance Program under Central Drugs Standard Control Organisation was conducted in Kasturba hospital, Manipal to collect adverse drug reactions (ADR). Data of patients reported with antitubercular treatment (ATT) related ADRs from September 2012 to August 2013 was evaluated for patient demography, type of tuberculosis, ATT regimen, organ/ system affected and time of onset of ADR. ADRs were then subjected to causality assessment as per WHO scale.Results: A total of 65 ADRs were reported in 60 patients during the study period, of which 46.7% were in males and 53.3% in females. 85% of ADRs were reported in patients with pulmonary tuberculosis. 77% of ADRs were observed with daily regimen. Common ADRs were hepatitis (40%), gastritis (15%), skin reactions (15%), peripheral neuropathy (14%), gout (6%) and nephritis (3%). Median duration for the onset of ADR was 31 days each for hepatitis, gout, nephritis and 20, 11, 9 days for gastritis, peripheral neuropathy and skin reactions respectively. As per causality assessment, 80% of ADRs were assigned “possible”, 11% “probable” and 9% “certain”. As per severity scale 27.7% of ADR were severe, 36.9% were moderate.Conclusions: Early detection and management of ADRs is vital for the success of ATT and patient adherence.

Congenital tuberculosis with multisystem involvement

Congenital tuberculosis is an uncommon condition, but in a country like India, where largest tuberculosis burden is found, there should be an eye on early diagnosis and management of this condition so as to prevent the devastating consequences of this disease considering the absence of specific pathogenic signs and symptoms. Here, we present a case of congenital tuberculosis in a newborn who was admitted on the 17th day after birth with the complaint of difficulty in breathing and lethargy for 3 days. On observing the antenatal history, it was found that mother after conception was diagnosed with pulmonary tuberculosis and was inadequately treated. The clinical indexes included no increase in body weight, hepatosplenomegaly, lethargy, and emaciated appearance. The treatment was initiated with antibiotics in intravenous form along with 4-drug antitubercular treatment (ATT). The 4-drug ATT was stopped after 1 week due to negative outcome in the tubercular screening, which leads to respiratory complications. The 4-drug ATT regimen was started again after a week on clinical basis which resulted in significant improvement within a few days. Hence, the present case presents a perspective that congenital tuberculosis can be considered in a newborn when mother has a history of tuberculosis before or during pregnancy.

Spinal TB: Impact of Research Evidence on Clinical Practice

The evidence generated while treating the patients is the key for growth of science. Finding answers to series of research questions spread over many years may change the clinical practice. This presentation is based on 25 research questions, 44 publications while treating 3300 patients over last 28 years ( 1990-2017) which has substantially changed the objective of treatment in spinal tuberculosis (TB) from healing of lesion with sequelae of spinal deformity and paraplegia to achieving healed status with near normal spine. Three cases of late-onset paraplegia were evaluated (1990) by newly introduced MRI. The syringohydromyelia and severe cord atrophy were attributed as the cause of paraplegia. We conducted a series of prospective studies to define and correlate MRI observations on spinal cord in paraplegia and followed the treatment outcomes. The cord edema, myelomalacia, cord atrophy and syringomyelia were observed in cases with neural complications. The patients with cord edema and liquid compression are predictor for neural recovery, while dry lesions and myelomalacia for poor neural recovery. The mild cord atrophy was consistent with neural recovery while severe cord atrophy with sequalae of neural deficit. Upto 76% canal encroachment was found compatible with intact neural state. Spinal deformity in TB spine is better prevented than treated. The contagious vertebral body disease with intact disc spaces, subperiosteal and paravertebral, septate abscesses, intra-osseous and intraspinal abscesses are considered features of spinal TB and resolution of abscess and fatty replacement is characteristic of healing. The clinicoradiological predictors for diagnosing spinal TB in predestructive disease were defined. Only 35% patients achieved healed status on MRI by DOTS regimen at 8 months, Hence, it is unscientific to stop antitubercular treatment (ATT) at fixed time schedule. The criteria to suspect multi-drug resistant (MDR)-TB and guide to treatment were defined. Residual Kyphotic deformity in spine TB produces severe proximal/distal degeneration of spine and/or late-onset paraplegia. We correlated the final kyphosis with initial vertebral body (VB) loss, where 1.5 VB height loss will produce 600 spinal deformity or more, hence surgical correction of spinal deformity is indicated. The surgical steps of kyphotic deformity correction are: anterior corpectomy, posterior column shortening, instrumented stabilization, anterior gap grafting and posterior fusion in a single stage and sequentially. The surgical incision of costo-transversectomy was modified so that kyphosis correction and posterior Hartshill instrumentation can be performed simultaneously. The retroperitoneal extrapleural approach for dorsolumbar spine was described. Meta-analysis of spinal instrumentation in TB spine established the lack of defined indication of instrumented stabilisation. Panvertebral/ long segment disease, kyphotic deformity correction are listed as indications of instrumented stabilisation in TB spine. The end point of treatment in spinal TB still eludes us to resolve the optimum duration of ATT regimen. The PET scan may be used to define it. We believe if a clinician works slow and steady on a series of research questions and by sustained focused efforts can change the clinical practice. We after this sustained research work could contribute in framing Bone and Joint TB guidelines and publish as monograph.

Applied multiplex allele specific PCR to detect second-line drug resistance among multidrug-resistant tuberculosis in China

Rapid detection of resistance to the second-line drugs is essential for early initiation of appropriate anti-tubercular treatment regimen among multi-drug tuberculosis (MDR-TB). In this study, we applied a multiplex allele-specific PCR (MAS-PCR) to identify the mutations on codons 90 and 94 of gyrA and nucleotide 1401 of rrs for detecting ofloxacin (OFX) and kanamycin (KAN) resistance in 139 MDR-TB isolates from China. Using the traditional phenotypic method as the reference, MAS-PCR detected resistance to OFX and KAN with sensitivities of 67.3% and 76.5%, respectively, and specificities of 100.0%. Therefore, MAS-PCR assays can be used for rapid detection of second-line drug resistance among MDR-TB in China, enabling early administration of appropriate treatment regimens to the affected MDR-TB patients.

APPLICATION OF REALTIME PCR FOR DETECTING M.TUBERCULOSIS RESISTANT TO RIFAMPICIN AND ISONIAZID

Introduction: Conventional culture methods for antibiotic susceptibility testing for M. tuberculosis may take days to several weeks. Use of realtime PCR for rapid detection of drug and multidrug resistant tuberculosis could facilitate early initiation of appropriate anti-tubercular treatment regimen thereby interrupting transmission. Objectives: 1. Determine prevalence of rifampicin-, isoniazid- and multidrug-resistant tuberculosis strain among the patients with recurrent tuberculosis. Xác định tỷ lệ các đột biến kháng rifampicin và isoniazid trong các chủng đề kháng phenotype 2. Determine proportion of the mutations concern to tuberculosis strains resistant to rifampicin và isoniazid. Methods: Doing susceptibility test by MODS assay for 50 tuberculosis strains isolated from patients with recurrent tuberculosis, realtime PCR was performed by using MTB Real-TM Resistance 4 kit to detect mutations in codon 531 of the rpoB gene related to rifampicine and mutations in codon 315 of the katG gene or in codon 209 of the inhA gene related to isoniazid. Results: Among tuberculosis strains isolated from patients with recurrent tuberculosis, there were 8% strains monoresistant to rifampicin and 60% multidrug-resistant strains. The Sacace MTB Real-TM resistance 4 kit detected 80% tuberculosis strains resistant to rifampicine with the mutation in rpoB gene codon 531 and 86,1% tuberculosis strains resistant to isoniazid with the mutation in katG gene codon 315 among the strains determined by MODS assay. Conclusion: The Sacace MTB Real-TM resistance 4 kit can’t detect rifampicine-/ isoniazid - resistant tuberculosis strains which have mutations in other codons of the above gene. Key words: M. tuberculosis, rifampicine-resistance, isoniazid-resistance, MODS, realtime PCR

A Rifapentine-Containing Inhaled Triple Antibiotic Formulation for Rapid Treatment of Tubercular Infection

The potential for rifapentine-containing oral therapeutic regimens to significantly shorten the current six-month anti-tubercular treatment regimen is confounded by high plasma protein binding of rifapentine. Inhaled aerosol delivery of rifapentine, a more potent anti-tubercular antibiotic drug, in combination with other first-line antibiotics may overcome this limitation to deliver a high drug dose at the pulmonary site of infection. A formulation consisting of rifapentine, moxifloxacin and pyrazinamide, with and without leucine, was prepared by spray-drying. This formulation was assessed for its physico-chemical properties, in vitro aerosol performance and antimicrobial activity. The antibiotic powders, with and without leucine, had similar median aerodynamic diameters of 2.58 ± 0.08μm and 2.51 ± 0.06μm, with a relatively high fine particle fraction of 55.5 ± 1.9% and 63.6 ± 2.0%, respectively. Although the powders were mostly amorphous, some crystalline peaks associated with the δ polymorph for the spray-dried crystalline pyrazinamide were identified. Stabilisation of the powder with 10% w/w leucine and protection from moisture ingress was found to be necessary to prevent overt crystallisation of pyrazinamide after long-term storage. In vitro biological assays indicated antimicrobial activity was retained after spray-drying. Murine pharmacokinetic studies are currently underway.

Intensified treatment with high dose Rifampicin and Levofloxacin compared to standard treatment for adult patients with Tuberculous Meningitis (TBM-IT): protocol for a randomized controlled trial

BackgroundTuberculous meningitis is the most severe form of tuberculosis. Mortality for untreated tuberculous meningitis is 100%. Despite the introduction of antibiotic treatment for tuberculosis the mortality rate for tuberculous meningitis remains high; approximately 25% for HIV-negative and 67% for HIV positive patients with most deaths occurring within one month of starting therapy. The high mortality rate in tuberculous meningitis reflects the severity of the condition but also the poor antibacterial activity of current treatment regimes and relatively poor penetration of these drugs into the central nervous system. Improving the antitubercular activity in the central nervous system of current therapy may help improve outcomes. Increasing the dose of rifampicin, a key drug with known poor cerebrospinal fluid penetration may lead to higher drug levels at the site of infection and may improve survival. Of the second generation fluoroquinolones, levofloxacin may have the optimal pharmacological features including cerebrospinal fluid penetration, with a ratio of Area Under the Curve (AUC) in cerebrospinal fluid to AUC in plasma of >75% and strong bactericidal activity against Mycobacterium tuberculosis. We propose a randomized controlled trial to assess the efficacy of an intensified anti-tubercular treatment regimen in tuberculous meningitis patients, comparing current standard tuberculous meningitis treatment regimens with standard treatment intensified with high-dose rifampicin and additional levofloxacin.Methods/DesignA randomized, double blind, placebo-controlled trial with two parallel arms, comparing standard Vietnamese national guideline treatment for tuberculous meningitis with standard treatment plus an increased dose of rifampicin (to 15 mg/kg/day total) and additional levofloxacin. The study will include 750 patients (375 per treatment group) including a minimum of 350 HIV-positive patients. The calculation assumes an overall mortality of 40% vs. 30% in the two arms, respectively (corresponding to a target hazard ratio of 0.7), a power of 80% and a two-sided significance level of 5%. Randomization ratio is 1:1. The primary endpoint is overall survival, i.e. time from randomization to death during a follow-up period of 9 months. Secondary endpoints are: neurological disability at 9 months, time to new neurological event or death, time to new or recurrent AIDS-defining illness or death (in HIV-positive patients only), severe adverse events, and rate of treatment interruption for adverse events.DiscussionCurrently very few options are available for the treatment of TBM and the mortality rate remains unacceptably high with severe disabilities seen in many of the survivors. This trial is based on the hypothesis that current anti-mycobacterial treatment schedules for TBM are not potent enough and that outcomes will be improved by increasing the CSF penetrating power of this regimen by optimising dosage and using additional drugs with better CSF penetration.Trial registrationInternational Standard Randomised Controlled Trial Number ISRCTN61649292

Appendicular tuberculosis: review of 155 published cases and a report of two cases.

This paper provides an overview of the literature on appendicular tuberculosis (ATB) between 1909 and 2010. We present two cases of primary ATB and a literature review of studies on ATB published in English and accessed via the Pubmed and Google Scholar databases. One hundred fifty-five published cases of ATB were reviewed, and two patients with primary ATB, treated and followed in our clinic, were reported. The age range of the patients (62 females, 60 males and 33 with unnoted gender) was between 2 and 60years, with a mean age of 27.1±10.6years. Of the patients who had applied to hospital, 59 had acute right lower quadrant pain, 46 had recurrent right lower quadrant pain, 19 had generalized pain, and 10 had chronic abdominal symptoms suggestive of subacute intestinal obstruction, while 47 patients were operated on with a diagnosis of acute appendicitis, 24 with recurrent appendicitis, 19 with TB peritonitis, 14 with mass in the right lower quadrant, 13 with subacute intestinal obstruction, and 7 with ATB. While appendectomy was not performed on 4 patients, one or more of the following procedures were done in the other 151 cases: appendectomy, hemicolectomy, ileocecal resection, or cecectomy. Different anti-tubercular treatment regimens with durations varying from 3weeks to 18months were applied to 60 patients. During the follow-up period of 3weeks to 15years, mortality occurred in 14 patients, sinus in five, and fistula in one patient. Secondary ATB was detected in 86 patients, primary ATB in 50, and no differential diagnosis could be made in 19 cases. Tuberculosis is a systemic disease with localized manifestations; therefore, anti-TB therapy must be initiated in any patient whose pathologic specimen reveals tuberculosis.

Rapidly enlarging mediastinal mass in a middle-aged patient with fever

A 47-year-old Indian female patient presented with lowgrade intermittent fever, anorexia and malaise of 4 months’ duration. She had a history of disseminated tuberculosis 2 years previously, for which she was successfully treated with first-line anti-tubercular drugs. On physical examination, she was found to have multiple matted cervical and axillary lymph nodes with mild splenomegaly. Laboratory results showed a raised erythrocyte sedimentation rate. Chest radiograph was normal (Figure 1). CT of the chest revealed multiple confluent rim-enhancing necrotic lymph nodes in the right axilla (Figure 2a). There was no mediastinal or hilar adenopathy and the lungs were clear (Figure 2b). Axillary lymph node biopsy was positive for acid fast bacilli. The patient was started on a modified antitubercular treatment regimen; however, her compliance for the chemotherapeutic drugs was poor and she continued to have constitutional symptoms. 5 months later, her condition worsened and she again presented to us with high-grade fever, anorexia, fatigability