The SLOMYCO Sensititre(®) panel method could provide a potential alternative to the reference agar dilution method, when DST in M. marinum is required, except for doxycycline.
Isoniazid, rifampicin, pyrazinamide, and ethambutol are commonly used for the treatment of tuberculosis. Drug exposure is occasionally associated with liver and/or skin injury. The aim of this study was to determine whether drug-specific T-cells are detectable in patients with adverse reactions and if so characterize the nature of the T-cell response. Peripheral blood mononuclear cells (PBMC) from 6 patients with anti-tuberculosis drug-related adverse reactions (4 liver, 2 skin) were used to detect drug-responsive T-lymphocytes. Positive lymphocyte transformation test and/or ELIspot results were observed with all 6 patients. Over 3400 T-cell clones were generated from isoniazid, rifampicin, pyrazinamide, or ethambutol-treated PBMC. CD4+ clones from all 3 patients were activated to proliferate and secrete cytotoxic mediators (granzyme B, perforin, FasL) and effector (IFN-γ, Il-13) and regulatory (Il-10) cytokines with isoniazid, but not rifampicin, pyrazinamide, or ethambutol. Il-17 was not detected, while only 1 clone secreted Il-22. Isoniazid-responsive clones were not activated with other anti-tuberculosis drugs or isonicotinic acid albumin adducts. Activation of the clones with isoniazid was MHC class II-restricted and dependent on antigen-presenting cells. Most clones were activated rapidly even in the presence of the enzyme inhibitor 1-aminobenzotriazole. However, a time-dependent pathway of activation involving auto-oxidation of isoniazid was also observed. The discovery of isoniazid-specific CD4+ T-cell clones in patients with liver and skin injury suggests that the adaptive immune system is involved in the pathogenesis of both forms of iatrogenic disease.
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In a referred, consecutive sample of 173 patients identified as treatment failures on DOT-SCC, 160 (92.5%) had culture-positive TB. Of those 160, 150 (93.8%) had active, pulmonary multidrug-resistant TB (MDR-TB, resistance to at least isoniazid [INH] and rifampicin [RIF]). Sixty of the 150 (40.0%) had isolates resistant to at least INH, RIF, ethambutol (EMB) and pyrazinamide (PZA), the initial first-line empiric treatment regimen used locally. Forty-four (29.3%) had isolates resistant to at least INH, RIF, EMB, PZA and streptomycin (SM), the first retreatment regimen. This series of patients had isolates resistant to a mean of 4.5 of the ten drugs tested. The local profile of multidrug resistance is very different from that obtained from national data from Peru.
To examine the incidence of major ADRs and risk factors associated with first-line anti-tuberculosis medications.
Mycobacterium marinum is an atypical mycobacterium usually found in non-chlorinated water. It rarely disseminates, except in the setting of a severely immunosuppressed patient, and usually follows a sporotrichotic type of distribution. We report the case of a 45-year-old man who had ankylosing spondylitis and was receiving infliximab and isoniazid for latent tuberculosis. The patient presented with a 5-month history of painful erythematous and suppurative nodules and abscesses on the right upper extremity. M. marinum was not isolated in cultures and histologic findings together with clinical examination provided evidence of sporotrichoid-like fish tank granuloma. The patient was treated with rifampin (rifampicin) and ethambutol for 8 months and responded satisfactorily while continuing to receive infliximab. In accordance with data in the published literature, isoniazid proved ineffective in preventing M. marinum infection in this patient. While mycobacterial complications of tumor necrosis factor-alpha (TNFalpha) inhibitor therapy are well established, our case appears to be the first reported instance of M. marinum infection in a patient taking infliximab. As anti-TNFalpha agents become increasingly used for a variety of conditions, awareness of the potential infectious complications associated with use of these agents will be vital for clinicians.
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Myrin®-P Forte is a fixed-dose combination (FDC) tablet containing rifampicin (RMP, 150 mg), isoniazid (INH, 75 mg), ethambutol (EMB) hydrochloride (275 mg) and pyrazinamide (PZA, 400 mg) developed for the treatment of tuberculosis (TB).
A 61-year-old woman received a cadaveric renal transplant in 1972 and was maintained on chronic immunosuppression. Nonspecific granulomatous synovitis of the left hand developed in 1982. After recurrence of synovitis in 1984, surgical exploration of the left hand demonstrated "rice bodies" in a region of chronic synovitis from which Mycobacterium kansasii was isolated. Despite therapy with isoniazid, rifampin, and ethambutol, to which the organism was susceptible in vitro, synovitis recurred. Recovery was completed after extensive synovectomies, decreased immunosuppression, and 24-months of therapy, with the drugs listed above; there was no evidence of mycobacterial infection at sites other than the left hand at any time. The occurrence of persistent Mycobacterium kansasii infection is distinctly unusual even in transplant recipients. In patients refractory to conventional antituberculous therapy, surgical management should be considered as an important therapeutic component.
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To assess the prevalence of primary drug resistance in Pakistan.
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Cohort of consecutive smear-positive patients identified by screening before departure, and followed up until cure or failure, for a maximum of two years.
Transmission of Mycobacterium bovis from cattle to humans has been reported and can cause tuberculosis (Tb) and a problem in certain risk populations. Therefore, knowledge of resistance of M. bovis towards antibiotics used for therapy of human Tb could help avoiding cure delay and treatment cost increase when dealing with drug resistant organisms. We therefore evaluated the susceptibility of M. bovis isolates towards streptomycin, isoniazide, rifampicin, ethambutol, and ethionamide, the first line antibiotics for human Tb. Therefore, 185 clinical samples from cattle with clinical signs of tuberculosis were processed and submitted to culturing and bacterial isolates to identification and drug susceptibility testing using the proportion method. Among 89 mycobacterial strains, 65 were identified as M. bovis and none were resistant to any of the antibiotics used. Confirmation of present results by future studies, enrolling a large number of isolates and designed to properly represent Brazilian regions, may favor the idea of using isoniazide preventive therapy as part of a Tb control strategy in special situations. Also, nucleic acids from bacterial isolates were submitted to rifoligotyping, a recently described reverse hybridization assay for detection of mutations causing resistance towards rifampicin. Concordance between the conventional and the molecular test was 100%, demonstrating the use of such methodology for rapid evaluation of drug susceptibility in M. bovis.
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This study included 42 Moroccan patients who developed hepatotoxicity after TB treatment and 163 Moroccan controls without TB. We genotyped four selected variants of the NAT2 gene (NAT2*5, NAT2*6, NAT2*7, and NAT2*14) by Sanger sequencing for patients and real-time polymerase chain reaction for controls.
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A national programme to treat chronic tuberculosis patients with a directly observed standardised 18-month daily regimen, consisting of kanamycin (3 months only), ciprofloxacin, ethionamide, pyrazinamide, and ethambutol, was established in Peru in 1997. Compliance and treatment outcomes were analysed for the cohort started on treatment between October, 1997, and March, 1999. Total and average costs were assessed. Cost-effectiveness was estimated as the cost per DALY gained.
Tuberculosis of the rectum is rarely reported, even from areas where tuberculosis, and gastrointestinal tuberculosis in particular, is prevalent. The authors report a case of long tubercular stricture of the rectum and distal part of the sigmoid colon in a 12-year-old girl. Because of nonspecific symptoms and noncharacteristic radiological and endoscopic features, the diagnosis of this rare entity rests mainly on histological evidence of the classical tubercle in a surgical biopsy specimen.
The best six sampling timepoints in children were identified as 0 (pre-dose) and 0.42, 1.76, 3.37, 10.31 and 24 h post-dose. Thirty-one children were recruited and blood was drawn at these timepoints. Rifampicin, ethambutol and pyrazinamide were best described using a one-compartment model, while isoniazid was best described with a two-compartment model. Only 2/31 (6%), 20/31 (65%), 17/31 (55%) and 2/13 (15%) of children attained the WHO 2 h target therapeutic concentrations of rifampicin, isoniazid, pyrazinamide and ethambutol, respectively. Moreover, only 24/31 (77%), 6/31 (19%) and 8/31 (26%) achieved the AUCs associated with an optimal clinical response to rifampicin, pyrazinamide and isoniazid, respectively. No single risk factor was significantly associated with below-normal drug levels.
Multidrug resistance has become a problem in the management of tuberculosis, leading to an urgent need for research related to new regimens including the currently available drugs. The objectives of this study were: (i) to study the effect of the following second-choice three-drug combinations against multidrug-resistant (MDR) and drug-susceptible clinical isolates (levofloxacin, linezolid and ethambutol; levofloxacin, amikacin and ethambutol; and levofloxacin, linezolid and amikacin); and (ii) to compare the effect of these combinations with an isoniazid, rifampicin and ethambutol combination against drug-susceptible clinical isolates. A total of 9 MDR clinical and 12 drug-susceptible isolates (11 clinical isolates and the H37Rv reference strain) were studied using an adaptation of the chequerboard assay. The fractional inhibitory concentration index (FICI) was calculated as follows: FICI=FIC(A)+FIC(B)+FIC(C)=A/MIC(A)+B/MIC(B)+C/MIC(C), where A, B and C are the minimum inhibitory concentrations (MICs) of each antibiotic in combination and MIC(A), MIC(B) and MIC(C) are the individual MICs. The FICI was interpreted as synergism when the value was <0.75. The FICI of all the combinations ranged from 1.5 to 3, showing indifferent activity. No differences were found between MDR and drug-susceptible isolates, or between the second-choice combinations and the fourth combination against drug-susceptible isolates. In conclusion, the second-choice drugs are equally effective as the combination of isoniazid, rifampicin and ethambutol.
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Mycobacterium malmoense is an opportunistic pathogen with increasingly recognized clinical importance. It is mainly isolated in northern Europe and Great Britain, most often from patients with pulmonary infections. Conventional therapy of M. malmoense infections with antituberculosis drugs is often of limited value, and there is thus a need for improved drug regimens. The potential efficacies of new alternative drugs, such as quinolones, macrolides, amikacin, and rifabutin, are still unknown, and so is the pathogen's in vitro susceptibility to most of these drugs. In this study, we used the BACTEC system for determining the pattern of resistance of clinical M. malmoense isolates to a number of antibacterial drugs as well as their possible synergistic interactions when each of them was combined with ethambutol. The majority of the strains were resistant or moderately resistant to the drug when it was tested alone at selected concentrations. However, pronounced in vitro synergism was demonstrated for combinations of ethambutol with ciprofloxacin, amikacin, and rifampin, rendering most isolates susceptible to the combined drugs. Thus, for in vitro susceptibility testing of M. malmoense, examination of the possible synergistic effects of combined drugs also can be recommended.
The results suggest that decentralised care is a feasible option for anti-tuberculosis treatment and that guardians can supervise TB treatment just as well as health workers during the intensive phase of TB treatment.
A 22-year-old Asian male presented with fever, non-productive cough, right-sided pleuritic chest pain and was found to have a large right hydropneumothorax. A chest tube was placed. Pleural fluid analysis revealed a lymphocytic predominant exudate and he was subsequently started on four-drug daily anti-tuberculosis therapy (isoniazid, ethambutol, rifampin, pyrazinamide). Pleural biopsy revealed acid-fast bacilli. Given his persistent pleural effusion, he was given four doses of intrapleural tissue plasminogen activator (tPA) and dornase alpha (DNase) via his chest tube over a period of 6 days resulting in clinical and radiologic improvement. Pleural biopsy and pleural fluid culture specimens later revealed Mycobacterium tuberculosis. Intrapleural tPA-DNase therapy has demonstrated improved resolution of infections and shortened hospitalizations for parapneumonic infectious effusions. However, there is little literature on the use of intrapleural fibrinolytics specifically for pleural tuberculosis associated effusions. Furthermore, the American Thoracic Society does not comment on therapeutic thoracentesis or intrapleural fibrinolytic therapy in their recommendations for treatment of pleural tuberculosis. In our case of pleural TB-associated hydropneumothorax, the use of intrapleural tPA-DNase therapy facilitated pleural fluid drainage and resulted in near-complete resolution of the effusion.
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Isolation of mycobacteria in cystic fibrosis (CF) patients is increasingly being reported. Because of having long term antimicrobial treatment, CF patients are at risk of pulmonary infection with especially resistant nontuberculous mycobacteria (NTM) strains. The aim of the present study is to determine the prevalence of mycobacterium spp. and antimicrobial susceptibility in Turkish CF patients.
In this systematic review we present information relating to the effectiveness and safety of the following interventions: adding pyrazinamide in chemotherapy regimens lasting up to 6 months; adding rifampicin to isoniazid regimens; benefits of different regimens; chemotherapy for less than 6 months; daily chemotherapy; direct observation treatment; intermittent chemotherapy for 6 months or longer; isoniazid; low-level laser therapy for pulmonary tuberculosis; regimens containing quinolones; rifampicin plus isoniazid; substituting rifampicin with ethambutol in the continuous phase; and support mechanisms for directly observed treatment.
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To evaluate the clinical presentation, biochemical (ascites and serum) and laparoscopic findings, and to assess the efficacy of triple antituberculous therapy without rifampicin for 6 months in patients with tuberculous peritonitis.
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A total of 6743 pulmonary tuberculosis cases (4903 males, 1840 females) were included in this study. The treatment success rate (including cured and complete treatment) was 88% (95%CI 87%-89%). One hundred and eight-six (2.8%) patients died and 401 (5.9%) patients defaulted treatment. In multivariate analysis, treatment success was found to be associated with young age, lack of cavitation and compliance with treatment.
A cluster of three related cases of tuberculosis (TB) with primary multidrug resistance was investigated at the Centre Hospitalier Universitaire of Kigali (CHUK) in Rwanda. The patients were HIV-1/2 seronegative. Patients 1 and 2 were hospitalized in the same room of CHUK for one month. Patient 3 was a younger sibling of patient 2.
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The contention and treatment of Mycobacterium tuberculosis and other bacteria that cause infectious diseases require the use of new type of antibiotics. Pandinin 2 (Pin2) is a scorpion venom antimicrobial peptide highly hemolytic that has a central proline residue. This residue forms a structural "kink" linked to its pore-forming activity towards human erythrocytes. In this work, the residue Pro14 of Pin2 was both substituted and flanked using glycine residues (P14G and P14GPG) based on the low hemolytic activities of antimicrobial peptides with structural motifs Gly and GlyProGly such as magainin 2 and ponericin G1, respectively. The two Pin2 variants showed antimicrobial activity against E. coli, S. aureus, and M. tuberculosis. However, Pin2 [GPG] was less hemolytic (30%) than that of Pin2 [G] variant. In addition, based on the primary structure of Pin2 [G] and Pin2 [GPG], two short peptide variants were designed and chemically synthesized keeping attention to their physicochemical properties such as hydrophobicity and propensity to adopt alpha-helical conformations. The aim to design these two short antimicrobial peptides was to avoid the drawback cost associated to the synthesis of peptides with large sequences. The short Pin2 variants named Pin2  and Pin2  showed antibiotic activity against E. coli and M. tuberculosis. Besides, Pin2  presented only 25% of hemolysis toward human erythrocytes at concentrations as high as 100 µM, while the peptide Pin2  did not show any hemolytic effect at the same concentration. Furthermore, these short antimicrobial peptides had better activity at molar concentrations against multidrug resistance M. tuberculosis than that of the conventional antibiotics ethambutol, isoniazid and rifampicin. Therefore, Pin2  and Pin2  have the potential to be used as an alternative antibiotics and anti-tuberculosis agents with reduced hemolytic effects.
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Retrospective study of tuberculosis cases attended in a third- level hospital from 1993 to 1998.