Importance of plasma protein binding of antituberculosis drugs on the response to shortcourse chemotherapy

Recently, there has been an increasing concern over the consequences of altered plasma protein binding of drugs in disease states, malnutrition and concomittant drug use on the therapeutic efficacy and toxicity of many antituberculous drugs. The increasing awareness of the problems associated with altered plasma protein binding necessitates studying the plasma protein binding profile of drugs used in short- course therapy for tuberculosis since such a study has not been done regardless of the fact that malnutrition and multiple drug use is often unavoidable and where drug resistance and hepatotoxicity has been a major issue. A total of 5 clinically healthy volunteers and 18 smear-positive tuberculosis patients, who were undertaking a short-course chemotherapy at the Union Tuberculosis Institute, were recruited and the plasma protein level and their binding property to rifampicin, isonazid and pyrazinamide at steary-state were studied. The findings showed that although the total plasma protein level was not significantly reduced, there is decrease in the mean albumin level in relation to the globulin level in tuberculous patients. The protein binding profile showed rifampicin to be highly bound (74-87 per cent) and pyrazinamide to be moderately bound (22-40 per cent ) to plasma proteins but no significant binding was seen with isoniazid (0.7-2.4 per cent ). All 3 drugs achieved adequate serum concentration well above the MIC throughout the study accompanied by rapid clinical improment and sputum conversion to negativity in 88.9 per cent of patients within one month of treatment. No sign of hepatic toxicity was seen in the study. Two patients (11.1 per cent ) had relapse after completion of therapy. The study highlights the importance of plasma protein binding of drugs and its influence on the metabolism and interaction between drugs used concomitantly in short-course chemotherapy. The study also showed that addition of pyrazinamide in short-course chemotherapy is very effective and well tolerated but increase in dosage of pyrazinamide during the twice-weekly phase may be necessary to prevent relapse.

The relationship between congo red binding capacity and the virulence of Shigella strains

Study of pathogenic mechanisms of bacteria has been facilitated by the discovery of easily identifiable markers that are used to differentiate between virulent and avirulent organisms of a given bacterial species. One of these markers is a congo red binding phenotype. In this study, 55 isolates of shigellae were tested for their congo red binding capacity and the results were compared with those of HEp-2 tissue culture assay. Shigella isolates (85.45 percent) which invade into HEp-2 cells can also absorb congo red dye from the agar medium as well as from the solution. Non-invasive or avirulent Shigella (14.55 percent) cannot bind congo red resulting in white colonies formation. The present study shows that congo red binding capacity of virulent Shigella indicating that this assay can be used as a quick marker and inexpensive alternative to other invasive assays to determine the virulence of these bacteria.

Severe hypersensitivity reaction to streptomycin and para-aminosalicylic acid (case report)

A case of hypersensitivity reaction to Streptomycin and P A S was described. The late occurance of hypersensitivity reaction and the unusal features were discussed. The importance of recognizing the allergic reaction and the patience and careful supervision required in desensitisation were emphersized.