BackgroundShortening tuberculosis (TB) treatment duration is a research priority. This paper presents data from a prematurely terminated randomized clinical trial, of 4-month moxifloxacin or gatifloxacin regimens, in South India.MethodsNewly diagnosed, sputum-positive HIV-negative pulmonary TB patients were randomly allocated to receive gatifloxacin or moxifloxacin, along with isoniazid and rifampicin for 4 months with pyrazinamide for first 2 months (G or M) or isoniazid and rifampicin for 6 months with ethambutol and pyrazinamide for first 2 months (C). All regimens were administered thrice-weekly. Clinical and bacteriological assessments were done monthly during treatment and for 24 months post-treatment. The Data and Safety Monitoring Board recommended termination of the trial due to high TB recurrence rates in the G and M regimens.ResultsOf 416 patients in intent-to-treat analysis, 6 (5%) of 124, 2 (2%) of 110 and 2 (2%) of 137 patients with drug-susceptible TB in the G, M and C arms respectively had unfavorable response at the end of treatment; during the next 24 months, 17 (15%) of 115, 11 (11%) of 104 and 8 (6%) of 132 patients respectively, had TB recurrence. Of 38 drug-resistant patients 1 of 8 and 3 of 26 in the G and C arms respectively had unfavourable response at the end of treatment; and TB recurrence occurred in 2 of 7 and 2 of 23 patients, respectively. The differences in TB recurrence rates between the G and C arms was statistically significant (p = 0.02). Gastro-intestinal symptoms occurred in 23%, 22% and 9% of patients in the G, M and C arms respectively, but most reactions were mild and manageable with symptomatic measures; 1% required regimen modification.Conclusions4-month thrice-weekly regimens of gatifloxacin or moxifloxacin with isoniazid, rifampicin and pyrazinamide, were inferior to standard 6-month treatment, in patients with newly diagnosed sputum positive pulmonary TB.Trial RegistrationClinical Trials Registry of India CTRI/2012/10/003060

Summaryobjective To define the bacteriological and histological correlates of the three predominant clinical forms of cutaneous tuberculosis and to evaluate the efficacy of a 9-month daily regimen containing rifampicin and isoniazid.methods In the dermatological clinics of two major teaching hospitals in Chennai, 213 patients with suspected clinical manifestations of cutaneous tuberculosis underwent examination and a skin biopsy for bacteriological and histological tests. They were treated with a daily regimen of rifampicin and isoniazid for 9 months and follow-up for 3 years.results Bacteriological and/or histological confirmation of tuberculosis was obtained in 88% of the cases. Lupus vulgaris lesions were seen mainly in the extremities and verrucosa cutis occurred predominantly on the sole and foot, while the cervical and axillary regions were the commonest sites for scrofuloderma. Ninety-two per cent of the patients showed resolution of the lesions within the first 6 months of chemotherapy; 1% failed to respond to this regimen. There was no relapse in any of the cases during the follow-up period of 3 years.conclusions Clinical findings were adequate to identify major forms of cutaneous tuberculosis as evidenced by bacteriological and histopathological examination. A daily regimen of rifampicin and isoniazid for 9 months was effective in treating cutaneous tuberculosis.

The in vitro activity of fluoroquinolones, including lomefloxacin, ofloxacin, ciprofloxacin, sparfloxacin, moxifloxacin and gatifloxacin, was evaluated against 55 clinical isolates of Mycobacterium tuberculosis by absolute concentration method on Lowenstein-Jensen (L-J) and Middlebrook's 7H11 media. Both ofloxacin susceptible and ofloxacin resistant strains of M. tuberculosis isolates were tested. The in vitro activities of these fluoroquinolones on the M. tuberculosis isolates were in the order: lomefloxacin < ciprofloxacin < or = ofloxacin < sparfloxacin < moxifloxacin = gatifloxacin. Gatifloxacin and moxifloxacin showed low minimal inhibitory concentrations (MIC) for both ofloxacin resistant and ofloxacin susceptible strains even though some cross resistances were observed.

We compared the sensitivity and specificity of the phenol ammonium sulfate (PhAS) sediment smear microscopy method for detection of acid-fast bacilli with those of direct smear microscopy, using culture results for Mycobacterium tuberculosis as the "gold standard." The sensitivities of the PhAS and direct smear methods were 85% (465 of 547) and 83% (454 of 547), respectively, and the specificity of each method was 97%. The PhAS method was better accepted by the laboratory technicians and safer but necessitates an overnight sedimentation, which delays reporting of results until 1 day after sputum collection.Each year, there are an estimated 2 million tuberculosis deaths and 8 million new cases of tuberculosis worldwide (3, 13). In developing countries, diagnosis of pulmonary tuberculosis depends primarily on the identification of acid-fast bacilli (AFB) using Ziehl-Neelsen sputum smear microscopy, a technique more than 100 years old. The sensitivity of this method varies (7) and depends upon collection of sufficient sputum, proper preparation of smears, good staining technique, careful examination of smears, and availability of a good microscope. Several methods have been tried to improve smear microscopy for AFB (1, 4-6, 9, 11, 12), but these have limitations under field conditions. Developing new smear microscopy methods which would be feasible under field conditions remains a priority for improving the diagnosis of pulmonary tuberculosis. In developing countries, laboratory technicians sometimes tend to sidestep the sputum examination owing to apprehensions about the infectiousness of sputum samples and due to the cumbersome method of preparing direct smears from the mucus portion of the sample. We evaluated the sensitivity, specificity, and acceptability of a new smear microscopy method using phenol ammonium sulfate (PhAS) for sedimentation of sputum.The study was conducted at a large tertiary-care hospital in Chennai, Tamil Nadu, South India. Each patient attending the outpatient department of the hospital was screened for chest symptoms. One spot sputum specimen was collected in a McCartney bottle from each patient who reported having a cough for 3 weeks or longer. Patients who were on antituberculosis treatment at the time were excluded from the study. All samples were collected during the months of August and September 2001.Processing of sputum samples. Sputum specimens were transported and processed within 4 h of collection. Each sample was divided into two portions of 3 to 5 ml each by pouring the sample from one McCartney bottle to another, such that both portions were approximately equal in volume and appeared similar in quality. The two portions were randomly allocated; one to the modified Petroff method for culture of Mycobacterium tuberculosis (10) and the other to the PhAS sediment smear method. For the Petroff method, sputum was homogenized for 15 min in a shaker by using an equal volume of 4% sodium hydroxide. After centrifugation at 3,000 rpm for 15 min in a Megafuge 1.0 (Heraeus), the deposit ...

We compared the sensitivity and specificity of a modified Ziehl-Neelsen (modified-ZN) staining method for acid-fast bacilli (AFB) with that of the standard Ziehl-Neelsen (standard-ZN) staining method, using culture results with Mycobacterium tuberculosis as the "gold standard." The sensitivity (72%; 101 of 140) of the modified-ZN staining method, which uses 0.3% carbol fuchsin, was significantly lower than that of the standard-ZN staining method (84%; 117 of 140); the modified-ZN method missed 21% of cases detected by the standard-ZN method and 11% more of culture-positive samples than the standard-ZN method. The World Health Organization recommendation of 0.3% carbol fuchsin in the ZN method for staining AFB needs to be reconsidered.In developing countries, sputum acid-fast bacilli (AFB) smear microscopy is the primary tool for detecting pulmonary tuberculosis (5). The Ziehl-Neelsen (ZN) method is commonly used for staining sputum smears because of its simplicity and low cost. Revised National Tuberculosis Control Programme (RNTCP) guidelines recommend the use of 1% carbol fuchsin in the ZN method (2). However, recent World Health Organization (WHO) guidelines recommend using carbol fuchsin at a concentration of 0.3% (5). However, the reasons for reducing the concentration of carbol fuchsin from 1 to 0.3% are not documented. The efficacy of 0.3% carbol fuchsin over 1% carbol fuchsin in the ZN staining method has not been studied previously.A total of 586 sputum samples were collected from the same number of patients with symptoms of pulmonary tuberculosis attending two tuberculosis detection centers during the second and third quarters of 2001 in Chennai, India: the Tuberculosis Research Centre, Chetput, and the Government Hospital for Thoracic Medicine, Tambaram Sanatorium. Many of these patients were receiving rifampin-containing short-course regimens for pulmonary tuberculosis and were followed up in controlled clinical trials.Preparation of reagents. Carbol fuchsin (1%) was prepared from 10 g of basic fuchsin (Hi-Media) dissolved in 100 ml of methanol (Qualigens) and 50 ml of melted phenol (Qualigens) in a flask maintained at 60°C in a water bath. This solution was made up to 1,000 ml with distilled water. Carbol fuchsin (0.3%) was prepared from 33 ml of the above solution diluted to 100 ml with distilled water before use. Sulfuric acid (25%) was prepared from 250 ml of concentrated sulfuric acid (Qualigens) slowly added to 750 ml of distilled water. Methylene blue (0.1%) was prepared from 1 g of methylene blue (Qualigens) dissolved in 1,000 ml of distilled water.Two direct smears were prepared from each of the 586 sputum samples and coded. One set was stained by the standard-ZN method, in which 1% carbol fuchsin was used, and the other set was stained using the modified-ZN method, in which 0.3% carbol fuchsin was used for staining. The RNTCP guidelines were followed to stain the smears. The air-dried smear slides were fixed over a flame three to five times for 3 to 4 s. The slides were then placed on a sta...