Bactericidal action of pulsed exposure to rifampicin, ethambutol, isoniazid & pyrazinamide on Mycobacterium tuberculosis in vitro

The bactericidal action of pulsed exposure to rifampicin (R), ethambutol (Emb), isoniazid (I) and pyrazinamide (Z) togcthcr on alternate days (REmbIZ) and as REmb and IZ separately on alternate days (REmb/IZ) on M.tuberculosis H37Rv, two isolates of M.tuberculosis sensitive to these drugs, as well as four isolates resistant to one or more drugs, was studied using an in vitro method. The experimental duration was 6 days. REmbIZ and REmb/IZ appeared to have equally good bactericidal action on M.tuberculosis strains in the in vitro system. The results suggest that splitting REmbIZ into REmb and IZ on alternate days in short course chemotherapy regimens for tuberculosis may not affect the bactericidal action of the regimens

BCG: Do we have an alternative?

Vaccination is generally used as a form of immunoprophylaxis, so that administration of the vaccine even a long. time before exposure to the wild-type infectious organism should afford protection. Since effector T and B cells are short-lived, a prime requisite for a vaccine is to generate immunological memory.1 In the case organisms such as mycobacteria which are obligate intracellular pathogens and which elicit granulomatous tissue reactions, artificial immunisation with live bacteria is required to induce protection.2,3 The only existing vaccine against tuberculosis is the BCG (Bacille Calmette - Guerin), an attenuated strain of M.bovis and it is mandatory or officially recommended in 182 countries or territories. Under the Expanded Programme on Immuisation (EPT) started by the Government of India in 1978, BCG is recommended to be given to all infants 3-9 months after birth.

Non-tuberculous mycobacteria - an overview.

There have been sporadic reports of non-tuberculous mycobacteria (NTM) causing disease in the early part of this century. isolation of NTM from patients with pulmonary disease became more common after sputum culture for the diagnosis of pulmonary tuberculosis had become routine by the 1950s1. Since then important strides have been made in the taxonomy and identification of non-tuberculous mycobacteria, as well as clarifying their role as human pathogens and importance in human pulmonary disease. It is now well established that mycobacteria other than mammalian tubercle bacilli and M.leprae. are important human pathogens.2,3 Various names have been suggested for this group of organisms such as para-tubercle bacilli, pseudotubercle bacilli, unclassified mycobacteria, anonymous mycobacteria, atypical mycobacteria, opportunistic mycobacteria, tuberculoid mycobacteria and mycobacteria other than tubercle bacilli (MOTT). The name non - tuberculous mycobacteria (NTM), now used by the International Working Group on Mycobacterial Taxonomy (IWGMT) is gradually gaining acceptance among mycobacteriologists

In vitro activity of rifampicin, rifapentine and rifabutin against South Indian isolates of M. tuberculosis

M. tuberculosis isolates from 51 resistant and 52 susceptible to Rifampicin patients were concurrently tested for in vitro susceptibility to Rifampicin, Rifapentine and Rifabutin. All the 52 Rifampicin susceptible strains were susceptible to Rifapentine, the geometric mean MICs being 13.3 m g/ml for Rifampicin and 6.0 m g/ml for Rifapentine. However, the geometric mean MIC for Rifabautin was as low as 13 m g/ml. All 51 Rifampicin resistant strains were also resistant to Rifapentine, indicating a complete cross-resistance between the two compounds. However, 11 (22%) of the Rifampicin resistant strains were found to be susceptible to Rifabutin. The geometric mean; MICs of the 40 resistant strains were 22 m g/ml for Rifampicin and113 m g/ml for Rifabutin. Thus, even among Rifampicin resistant strains, Rifabutin showed a 1.97 fold higher activity; the difference in the means attained statistical significance

Protective response in guineapigs exposed to Mycobacterium avium intracellulare/ M. scrofulaceum, BCG & south Indian isolates of M. tuberculosis

The protective immunity resulting from exposure to nontuberculous mycobacteria (NTM), BCG and virulent mycobacteria in different sequences was studied in the guineapig model employing strains prevalent in the south Indian BCG trial area and time kinetics to observe the immuno-modulation. The findings suggest that during the early course of challenge infection in guineapigs there was no interference with the immunity due to BCG, by prior exposure to NTM. In the animals sensitised with M. avium intracellulare before immunisation, the challenge infection was localised and confined to the site of inoculation, and only a few organisms reached the spleen.. However, at the later stages of the infection, as seen by the spleen viable counts at 12 wk, it appeared that the barrier at the localised site of infection may not be intact in the animals with prior exposure to NTM, and a few organisms disseminate to the spleen

In vitro activity of ofloxacin and ciprofloxacin against South Indian isolates of M. tuberculosis

Mycobacterium tuberculosis isolates from 104 south Indian patients, including 52 sensitive to Streptomycin (S), Isoniazid, (H) and Rifampicin (R), and 52 resistant to SHR/HR were tested for their in vitro susceptibility to Ciprofloxacin and Ofloxacin on Lowenstein-Jensen medium. The geometric mean for minimal inhibitory concentration (MIC) of Ciprofloxacin was 2.00 mcg/ml for sensitive strains and 2.17 mcg/ml for resistant strains, the overall mean being 2.08 mcg/ml. Considering Ofloxacin, the MICs for the different categories of strains were again similar, there being no difference between sensitive and resistant strains, the geometric means being 2.00 and 2.05 mcg/ml, respectively

In vitro activity of capreomycin and ciprofloxacin against South Indian isolates of M. tuberculosis

Mycobacterium tuberculosis isolated from 107 South Indian patients, including 53 isolates sensitive to Streptomycin (S), Isoniazid (H) and Rifampicin (R) and 54 resistant to SHR/HR were tested for their in vitro susceptibility to Capreomycin and Ciprofloxacin. Of these, 3 (6%) SHR sensitive strains and 8 (15%) SHR/HR resistant strains were probably resistant to Capreomycin. However, the difference did not attain statistical significance. Considering Ciprofloxacin, the percentage distributions of the MIC with the different categories of strains were similar, there being no difference between sensitive and resistant strains, the geometric means being 3.7 and 3.8 mcg/ml, respectively

What is new in the diagnosis of tuberculosis? Part II: Techniques for drug susceptibility testing

Drug susceptibility testing can be performed based on mycobacterial cultivation on solid media, either egg or agar-based. In the direct test a set of drug-containing and drug-free media is inoculated directly with concentrated specimen. The advantage of the direct method over indirect method is that the results are available sooner (within 3 weeks on agar plates), and better represent the patient’s original bacterial populatio

What is new in the diagnosis of tuberculosis? Part I; Techniques for diagnosis of tuberculosis

Despite the discovery of the tubercle bacillus more than a hundred years ago, and all the advances in our knowledge of the disease made since then, tuberculosis still remains one of the major health problems facing mankind, particularly in developing countries. Presently, about one third of the world�s population is infected with Mycobacterium tuberculosis. It is estimated that currently there are about 10 million new cases of tuberculosis every year with 3 million deaths occurring world-wide1. Currently, more people die of tuberculosis than from any other infectious disease. Death from tuberculosis comprises 25% of all avoidable deaths in developing countries. Nearly 95% of all tuberculosis cases and 98% of deaths due to tuberculosis are in developing countries and 75% of tuberculosis cases are in the economically productive age group . In India, out of a total population of over 1 billion, each year about 2 million develop active disease and up to half a million die . It implies that every minute, a death occurs due to tuberculosis in our country. It also imposes a cost on our economy in terms of current and future output losses because of premature deaths and ill health . To add to the existing burden, the situation is compounded by the large scale increase of new TB cases associated with increasing HIV infection

Effect of oral exposure of mycobacterium avium intracellulare on the protective imunity induced by BCG

The relative protective efficacy of oral administration of mycobacteria as compared to the conventional intradermal route of vaccination has been assessed in guinea pigs. Skin test reactivity to partially purified protein derivative and protective immunity to challenge with virulent Mycobacterium tuberculosis were used as parameters of protective immunity. Oral immunisation of guinea pigs either with BCG or with Mycobacterium avium intracellulare induces skin test reactivity and protective immunity comparable to that induced by intradermal route of vaccination. Oral exposure of Mycobacterium avium intracellulare prior to oral or intradermal dose of BCG did not interfere with the protective immunity induced by BCG in guinea pigs challenged with Mycobacterium tuberculosis H37Rv