Multidrug Tuberculosis Therapy Research Articles

WQ-3810: A new fluoroquinolone with a high potential against fluoroquinolone-resistant Mycobacterium tuberculosis

Fluoroquinolone (FQ) resistance in Mycobacterium tuberculosis (Mtb), caused by amino acid substitutions in DNA gyrase, has been increasingly reported worldwide. WQ-3810 is a newly developed FQ that is highly active against FQ-resistant pathogens; however, its activity against Mtb has not been evaluated. Herein we examined the efficacy of WQ-3810 against Mtb through the use of recombinant Mtb DNA gyrases. In addition, in vitro antimycobacterial activity of WQ-3810 was evaluated against recombinant Mtb var. bovis Bacille Calmette–Guérin strains in which gyrase-coding genes were replaced with Mtb variants containing resistance-conferring mutations. WQ-3810 showed a higher inhibitory activity than levofloxacin against most recombinant DNA gyrases with FQ-resistance mutations. Furthermore, WQ-3810 showed inhibition even against a DNA gyrase variant harboring a G88C mutation which is thought to confer the highest resistance against FQs in clinical Mtb isolates. In contrast, the FQ susceptibility test showed that WQ-3810 had relatively weak mycobactericidal activity compared with moxifloxacin. However, the combination of WQ-3810 and ethambutol showed the greatest degree of synergistic activity against recombinant strains. Since FQs and ethambutol have been used in multi-drug therapy for tuberculosis, WQ-3810 might represent a new, potent anti-tuberculosis drug that can be effective even against FQ-resistant Mtb strains.

A Rare Manifestation of Tuberculosis in a Renal Transplant Patient: A Case Report

Cutaneous lesions in the presence of fever in patients undergoing immunosuppressive therapy are a diagnostic challenge and may represent manifestations of multiple diseases, such as fungal infections, nocardiosis, lymphoproliferative diseases, zoonosis, and tuberculosis. The authors report a case of a 66-year-old white man with chronic kidney disease since 2014 (chronic pyelonephritis) who had a renal transplant in the previous 6 months. Induction therapy was performed with thymoglobulin, and his current immunosuppression scheme included tacrolimus, mycophenolate mofetil, and prednisolone. The patient had no history of pulmonary tuberculosis. The patient presented with 2 cutaneous lesions, localized on the back and abdomen, that appeared to be firm, painful, subcutaneous, erythematous nodules with an approximately 5 cm diameter overlying an infected focus and purulent material inside. The patient also had a fever and fatigue. Blood analysis showed pancytopenia with an elevation of inflammatory markers and graft dysfunction. Tissue cultures and skin biopsy with histological analysis were performed. Histopathology of the lesion showed a nonspecific inflammatory infiltrate without granulomas, and acid-fast bacillus staining was negative. Nevertheless, serum QuantiFERON testing was positive. But polymerase chain reaction finally confirmed the presence of Mycobacterium tuberculosis, which confirmed the diagnosis of cutaneous tuberculosis. A chest computed tomography scan showed a lung pattern of miliary tuberculosis. The patient was treated with multidrug tuberculosis therapy, resulting in lesion clearance after 3 weeks. Tuberculosis is a serious infection, especially in high-risk patients, such as those in an immunocompromised state. The incidence of cutaneous tuberculosis is rare, but it should be considered in patients presenting with atypical skin lesions suggestive of an underlying infectious etiology.

Mycobacterium tuberculosis of the elbow joint

Mycobacterium tuberculosis(TB) affecting the elbow joint is rarely reported in the developed world. We present the case of an 85-year-old Caucasian female who complained of a chronically discharging and painful...

Phlyctenular Eye Disease: A Reappraisal

Purpose: Phlyctenular keratoconjunctivitis is a nonspecific allergic response in the cornea and/or conjunctiva to a variety of distinct conditions. Tuberculosis as an etiological association is being supplanted by staphylococcal infection and worm infestation in developed countries. Our aim was to determine the relative frequency of the various known etiological factors of phlyctenular keratoconjunctivitis, and the clinical profile of the disease as it exists today in India, a country where tuberculosis is still highly prevalent. Cases: This is a prospective study of 112 consecutive patients with phlyctenular eye disease seen over a 2-year period. Observations: In 86 patients (76.7%), phlyctenular eye disease was associated with tuberculosis. Worm infestation was found in 14 patients (12.4%), whereas 7 (6.2%) had staphylococcal blepharitis. Thirteen patients had evidence of multiple etiology, of which one causative factor was always tuberculosis. When tuberculosis was the only association, 37% patients had severe lesions, whereas only 11.5% patients without tuberculosis had such lesions. When tuberculosis along with another etiological factor was present, the incidence of severe lesions increased to 84.6%. Recurrence on follow-up was seen in three patients who were already on multidrug therapy for tuberculosis, and two who had tubercular allergy. Conclusions: Our study shows that tuberculosis is still a major cause of phlyctenular eye disease in India. Severe lesions are more common in patients with tuberculosis, especially when another etiological factor is associated. Recurrences are more common in patients with tuberculosis. Corneal lesions are less extensive than described in the literature and are no longer a significant cause of blindness.

Multidrug therapy for tuberculosis in children

Multidrug therapy for tuberculosis in children