Malnutrition and Pulmonary Tuberculosis

Sir—We read with interest the article by Oursler et al. [1] in which the authors concluded that comorbid illnesses and conditions, such as diabetes mellitus, renal failure, chronic obstructive pulmonary disease, and immunosuppression, are important predictors of mortality among patients with pulmonary tuberculosis (TB). These observations confirm the findings of earlier reports [2, 3] and provide additional evidence that pulmonary TB continues to a have a significant associated mortality rate, even in industrialized nations where advanced medical technology is available. The authors also found that the clustering of pulmonary TB infections, as determined by DNA fingerprinting, was not an independent factor associated with death. Although the investigators made an effort to obtain a history of weight loss, little attention was given to this factor as a possible predictor of mortality. In a study of hospitalized patients, malnutrition (defined as a body mass index of <90% of ideal body weight or considerable recent weight loss, as recorded by the evaluating clinician) was an important risk factor for a poor outcome [4]. It has also been observed that the mortality rate was 60% for patients with pulmonary TB who had respiratory failure necessitating mechanical ventilation, despite the administration of appropriate 4-drug anti-TB therapy. Nutritional status, as measured by serum albumin concentration and hemoglobin level, was an important predictor of survival [5]. Drug therapy and nutritional balance are 2 interrelated aspects of therapy for TB infection that are within the control of the physician. Other variables, such as the patient's demographic characteristics, the extent and duration of disease, the presence of comorbid illnesses, and drug susceptibility, are predetermined. Directly observed therapy was instituted as a means to enhance patient compliance with treatment regimens, to decrease the rates of treatment failure and relapse, and to prevent the emergence of acquired drug-resistant organisms. Standard-dose therapy works well for the majority of patients. However, therapeutic drug monitoring has been advocated for patients with end-stage liver or renal disease, for HIV-infected patients, and for patients who have slow response to standard anti-TB treatment [6]. In addition, recent reports have described patients without markers for adverse outcomes who nevertheless had poor responses to appropriate treatment [7–10]. The adverse outcomes were attributed to subtherapeutic levels of anti-TB drugs in each of the patients. Poor absorption of the anti-TB medications through the gastrointestinal tract was believed to be the pathophysiologic event that resulted in the observed subtherapuetic serum drug levels. Although several mechanisms have been proposed to explain the low serum levels of drugs observed in these patients, the nutritional status of the patient may be a contributing factor. Poor nutritional status results in a decrease in the plasma drug concentration time curve and an increased renal clearance of unbound drug. In effect, low serum levels of anti-TB drugs result in patients being administered fewer anti-TB medications or, in some cases, even monotherapy. The latter regimen could then lead to acquired drug resistance and may contribute to increased morbidity and mortality among patients with pulmonary TB. Therefore, nutritional status may be an important prognostic factor that has been largely overlooked by the medical community. Early and aggressive attention to improving patients' nutritional status may be an important intervention to ensure survival. Although the impact of improving the nutritional status of patients with pulmonary TB has yet to be determined, provision of adequate dietary intervention is an adjunctive therapeutic maneuver that should be undertaken. In addition, inadequate dosing of anti-TB drugs should also be considered a factor that contributes to the death of malnourished patients. For these patients, therapeutic drug monitoring on a case-by-case basis should be considered, which could allow for better control of each patient's anti-TB therapy. Recognition of the potential benefits of nutritional support and therapeutic drug monitoring offers others avenues that the clinician can modify, and it may reduce mortality associated with pulmonary TB.