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Fulltext A partially randomised trial of pretomanid, moxifloxacin and pyrazinamide for pulmonary TB

Tweed CD, Wills GH, Crook AM, Amukoye E, Balanag V, Ban AYL, et al.

Int J Tuberc Lung Dis, 2021 Apr 01;25(4):305-314.
PMID: 33762075 DOI: 10.5588/ijtld.20.0513

BACKGROUND: Treatment for TB is lengthy and toxic, and new regimens are needed.METHODS: Participants with pulmonary drug-susceptible TB (DS-TB) were randomised to receive: 200 mg pretomanid (Pa, PMD) daily, 400 mg moxifloxacin (M) and 1500 mg pyrazinamide (Z) for 6 months (6Pa200MZ) or 4 months (4Pa200MZ); 100 mg pretomanid daily for 4 months in the same combination (4Pa100MZ); or standard DS-TB treatment for 6 months. The primary outcome was treatment failure or relapse at 12 months post-randomisation. The non-inferiority margin for between-group differences was 12.0%. Recruitment was paused following three deaths and not resumed.RESULTS: Respectively 4/47 (8.5%), 11/57 (19.3%), 14/52 (26.9%) and 1/53 (1.9%) DS-TB outcomes were unfavourable in patients on 6Pa200MZ, 4Pa200MZ, 4Pa100MZ and controls. There was a 6.6% (95% CI -2.2% to 15.4%) difference per protocol and 9.9% (95%CI -4.1% to 23.9%) modified intention-to-treat difference in unfavourable responses between the control and 6Pa200MZ arms. Grade 3+ adverse events affected 68/203 (33.5%) receiving experimental regimens, and 19/68 (27.9%) on control. Ten of 203 (4.9%) participants on experimental arms and 2/68 (2.9%) controls died.CONCLUSION: PaMZ regimens did not achieve non-inferiority in this under-powered trial. An ongoing evaluation of PMD remains a priority.

Matched MeSH terms: Pyrazinamide*
Fulltext Contralateral pleural effusion during chemotherapy for tuberculous pleural effusion

Puri MM, Arora VK

Med J Malaysia, 2000 Sep;55(3):382-4.
PMID: 11200723

A 25 year old woman developed a right pleural effusion 6 weeks after commencement of short course chemotherapy for left sided tuberculous pleural effusion. Since the patient improved following continuation of the same treatment, it is presumed to be a case of paradoxical response to anti-tuberculosis treatment.

Matched MeSH terms: Pyrazinamide/adverse effects; Pyrazinamide/therapeutic use
Lupus vulgaris in an immunocompromised patient

Jalalonmuhali M, Lee YY, Lee CK, Ismail R, Chandran PA

Int J Dermatol, 2014 Feb;53(2):234-7.
PMID: 22913324 DOI: 10.1111/j.1365-4632.2012.05463.x
Matched MeSH terms: Pyrazinamide/therapeutic use
An apparently healthy young man with a peculiar-looking chest radiograph

Khajotia R, Manthari K

Can Fam Physician, 2011 Mar;57(3):311-3.
PMID: 21402968
Matched MeSH terms: Pyrazinamide/therapeutic use
Management and treatment outcomes of MDR-TB: results from a setting with high rates of drug resistance

Ahmad N, Javaid A, Basit A, Afridi AK, Khan MA, Ahmad I, et al.

Int J Tuberc Lung Dis, 2015 Sep;19(9):1109-14, i-ii.
PMID: 26260834 DOI: 10.5588/ijtld.15.0167

Although Pakistan has a high burden of multidrug-resistant tuberculosis (MDR-TB), little is known about the management and treatment outcomes of MDR-TB patients in Pakistan.

Matched MeSH terms: Pyrazinamide/therapeutic use*
Mechanisms of antihyperuricemic effect of Phyllanthus niruri and its lignan constituents

Murugaiyah V, Chan KL

J Ethnopharmacol, 2009 Jul 15;124(2):233-9.
PMID: 19397979 DOI: 10.1016/j.jep.2009.04.026

ETHNOPHARMACOLOGICAL RELEVANCE: Phyllanthus niruri Linn. (Euphorbiaceae) is used as folk medicine in South America to treat excess uric acid. Our initial study showed that the methanol extract of Phyllanthus niruri and its lignans were able to reverse the plasma uric acid of hyperuricemic animals.
AIM OF THE STUDY: The study was undertaken to investigate the mechanisms of antihyperuricemic effect of Phyllanthus niruri and its lignan constituents.
MATERIAL AND METHODS: The mechanisms were investigated using xanthine oxidase assay and uricosuric studies in potassium oxonate- and uric acid-induced hyperuricemic rats.
RESULTS: Phyllanthus niruri methanol extract exhibited in vitro xanthine oxidase inhibition with an IC50 of 39.39 microg/mL and a moderate in vivo xanthine oxidase inhibitory activity. However, the lignans display poor xanthine oxidase inhibition in vitro and a relatively weak in vivo inhibitory activity at 10mg/kg. On the other hand, intraperitoneal treatment with Phyllanthus niruri methanol extract showed 1.69 folds increase in urinary uric acid excretion when compared to the hyperuricemic control animals. Likewise, the lignans, phyllanthin, hypophyllanthin and phyltetralin exhibited up to 2.51 and 11.0 folds higher in urinary uric acid excretion and clearance, respectively. The co-administration of pyrazinamide with phyllanthin exhibited a significant suppression of phyllanthin's uricosuric activity resembling that of pyrazinamide with benzbromarone.
CONCLUSIONS: The present study showed that the antihyperuricemic effect of Phyllanthus niruri methanol extract may be mainly due to its uricosuric action and partly through xanthine oxidase inhibition, whereas the antihyperuricemic effect of the lignans was attributed to their uricosuric action.

Matched MeSH terms: Pyrazinamide/pharmacology; Pyrazinamide/therapeutic use
Fulltext Applicability of the World Health Organization recommended new shorter regimen in a multidrug-resistant tuberculosis high burden country

Javaid A, Ahmad N, Khan AH, Shaheen Z

Eur Respir J, 2017 01;49(1).
PMID: 28049176 DOI: 10.1183/13993003.01967-2016
Matched MeSH terms: Pyrazinamide/administration & dosage
Fulltext A rare case of TB elbow synovitis in a patient with rheumatoid arthritis: a case report

Meryl Grace Lansing, Malehah Mohd Noh, Mohd Hakimi Nordin

Malaysian Journal of Medicine and Health Sciences, 2019;15(106):96-96.
MyJurnal

Introduction: Tuberculosis (TB) of the elbow joint is uncommon. Prompt diagnosis and treatment are important to prevent joint destruction and preserve function. We present a case of TB synovitis of the elbow joint in a patient with active rheumatoid arthritis (RA). Case description: A 56-year-old woman with a known seropositive RA on metho-trexate and Leflunomide was seen in the outpatient rheumatology clinic as part of her monthly follow-up. She com-plained of persistent bilateral elbow pain and swelling, despite optimisation of her disease-modifying antirheumatic drugs (DMARD) and steroid therapy. The suspicion for another diagnosis for her elbow symptoms stems from the persistent pain and swelling amidst increased titration of methotrexate and prednisolone dosages. Ultrasound scan of her elbows revealed bilateral complex olecranon bursitis with active synovitis. The left elbow aspiration yielded cloudy yellowish synovial fluid and the sample was sent for fluid culture, acid-fast bacilli (AFB) stain, and GeneXpert. No AFB was seen but the GeneXpert test confirmed the presence of Mycobacterium Tuberculosis. Thus, a diagnosis of TB synovitis of the left elbow was made, and she was promptly started on anti-tubercular therapy (ATT) consisting of Rifampicin, Isoniazid, Ethambutol and Pyrazinamide with the aim to complete 9 months of ATT. Conclusion: The diagnosis of tuberculous synovitis is challenging. In the absence of constitutional or respiratory symptoms, joint TB is usually low on the initial differential diagnosis in patients presenting with joint pain and swelling. The diagnosis is made even more difficult in patients with concomitant rheumatoid arthritis. This case demonstrates the importance of a high index of suspicion for TB, particularly when evaluating patients in high TB prevalence area with an underlying immunosuppressive state.

Matched MeSH terms: Pyrazinamide
Fulltext A double-edged sword: a case report on liver injury side-effect of anti-tuberculosis drug on liver tuberculosis patient

Azlina Ibrahim, Alvin Oliver Payus

Borneo Journal of Medical Sciences, 2020;14(1):49-53.
MyJurnal

Hepatic involvement in extra-pulmonary tuberculosis (TB) is rare, even in the endemic area. It has a high mortality rate as it can easily be misdiagnosed due to its rarity and non-specific presentations, and the treatment can be challenging for its hepatotoxic side-effect. A 55-year old man who was newly diagnosed with AIDS and pulmonary TB which complicated with anti-TB-induced transaminitis, presented with a few weeks history of fever and persistent diarrhoea. It was initially treated as microsporidia infection but the symptoms persisted despite given antiparasitic agent for more than a week. He was subjected to computed tomography (CT) scan of the abdomen and noted multiple hypoechoic lesion at multiple segments of the liver, which later confirmed to be liver TB by liver biopsy. As he could not tolerate Akurit-4 (Rifampicin 150 mg, Isoniazid 75 mg, Pyrazinamide 400 mg and Ethambutol 275 mg), the second-line treatment was given instead. He is currently well on regular clinic appointment. The objective of this case report is to share the rare occurrence of hepatic TB and the difficulty to treat it as the hepatotoxic effect of anti-TB medications complicate the liver damage due to the infection.

Matched MeSH terms: Pyrazinamide
Fulltext Treating More with Less: Effectiveness and Event Outcomes of Antituberculosis Fixed-dose Combination Drug versus Separate-drug Formulation (Ethambutol, Isoniazid, Rifampicin and Pyrazinamide) for Pulmonary Tuberculosis Patients in Real-world Clinical Practice

Lai JML, Yang SL, Avoi R

J Glob Infect Dis, 2019 3 1;11(1):2-6.
PMID: 30814828 DOI: 10.4103/jgid.jgid_50_18

Introduction: Conventionally, a combination of four separate drugs (ethambutol, isoniazid, rifampicin, and pyrazinamide [EHRZ]) is the first-line pharmacotherapy for pulmonary tuberculosis (TB). In recent years, fixed-dose combination (FDC) formulation, where a single tablet contains the active ingredients of four aforementioned drugs, is gaining popularity due to its ease of administration.
Objective: To compare the real-world effectiveness of EHRZ and FDC treatment groups on a cohort registry by investigating the sputum conversion rate and treatment outcomes of both groups.
Methods: A total of 11,489 patients' data were extracted from the Sabah TB registry between January 2012 and June 2016, including EHRZ (n = 4188) and FDC (n = 7301) patients. Then, 1:1 propensity score matching was adopted to reduce the baseline bias. Caliper matching was conducted with maximum tolerance score set at 0.001. Confounders included in the propensity score matching were gender, nationality, diabetes, HIV status, smoking status, and chest X-ray status. Successful matching provided 4188 matched pairs (n = 8376) for final analysis.
Results: In this matched cohort of 4188 pairs, the 2-month sputum conversion rate of FDC group was significantly higher than the EHRZ group (96.3% vs. 94.3%; P < 0.001) whereas 6-month sputum conversion of both groups showed no significant difference. Treatment outcomes such as noncompliance rate, failure rate, and success rate have no significant difference (P > 0.05) in both the treatment groups. There was an incidental finding of reduced death rate among FDC group compared to the EHRZ group (0.2% vs. 0.5%; P = 0.034).
Conclusion: The FDC formulation has better sputum conversion rate at 2 months compared to conventional EHRZ regime as separate-drug formulation. It was also observed that FDC has a slight protective effect against all-cause death among TB patients. This protective effect of FDC, however, still needs to be proven further.

Matched MeSH terms: Pyrazinamide
Fulltext Evaluation of Adverse Reactions Induced by Anti-Tuberculosis Drugs in Hospital Pulau Pinang

Fei CM, Zainal H, Ali IAH

Malays J Med Sci, 2018 Sep;25(5):103-114.
PMID: 30914867 MyJurnal DOI: 10.21315/mjms2018.25.5.10

Background: The use of multi-drug regimens in tuberculosis (TB) treatment has been associated with undesirable adverse drug reactions (ADRs). This study aims to assess the incidence and impact of ADRs on TB treatment in Hospital Pulau Pinang.
Methods: This cross-sectional study was conducted via retrospective review of outpatients' medical records. Details regarding ADRs were identified by a pharmacist and verified by a consultant respiratory physician.
Results: A total of 91 cases, out of 210 patients enrolled in this study, were detected with 75 patients (35.7%) experienced at least one ADR. The three most common ADRs detected were cutaneous adverse drug reactions (CADRs) (21.0%), drug-induced hepatitis (DIH) (7.1%) and gastrointestinal disturbance (4.8%). Pyrazinamide was the most common causative agent and 15.7% of all TB patients required treatment modification due to ADRs. Females were shown to have a higher tendency to develop ADRs than the males in this study (P = 0.009). The development of ADRs was shown not to affect the TB treatment outcomes (P = 0.955).
Conclusion: The incidence of ADRs in this study was high so it is important to identify the risk factors for ADRs and the individuals who have those risk factors when initiating anti-TB drugs. These individuals require special attention when anti-TB drugs are initiated.

Matched MeSH terms: Pyrazinamide