PubMed HealthSearch

Biomedical subjects

M D Iseman

Publications and source records attributed to M D Iseman.

At least 19 recordsLinked to original sources

A leap of faith. What can we do to curtail intrainstitutional transmission of tuberculosis?

Large-scale, epidemic transmission of tuberculosis to patients, nonprofessional staff, nurses, and physicians has been documented recently in hospitals, clinics, acquired immunodeficiency syndrome (AIDS) residencies, and correctional facilities. Prominent factors in these outbreaks have included human immunodeficiency virus (HIV) infection and AIDS, delayed diagnosis of tuberculosis, multidrug-resistant strains of tuberculosis that resulted in protracted shedding of mycobacteria, and ventilation patterns in buildings that resulted in the accumulation of infectious particles. Multiple deaths from tuberculosis have resulted. Various strategies, including vaccines, masks, augmented ventilation, air filters, and ultraviolet irradiation have been proposed to control this situation. Although no well-controlled studies exist to document the utility of any of these modalities, ultraviolet germicidal irradiation seems both the best theoretical model and the most practical tactic. Ultraviolet systems should be widely deployed throughout high-risk institutions.

Air Microbiology

The combined effect of rifampin and pyrazinamide within the human macrophage.

A recent study in the murine model suggested that a combination of rifampin and pyrazinamide used as preventive therapy might shorten the duration of treatment time. Clinical trials using this combination have been initiated, but significant results will not be available for many years. The ex vivo human macrophage model has been instructive in expanding our knowledge of the activity of chemotherapeutic agents against intracellular virulent tubercle bacilli. Prior studies have shown rifampin to have a bactericidal effect in this model while even at clinically unachievable levels, pyrazinamide had only a bacteriostatic impact. This study finds an enhanced bacteriostatic effect when low, nonbactericidal levels of rifampin are combined with clinically achievable levels of pyrazinamide but not with higher bactericidal levels of rifampin. Adding pyrazinamide 2 days after the introduction of rifampin clearly enhanced the combined killing effect. However, reversing the order and adding rifampin 2 days after the introduction of pyrazinamide produced a result weaker than introducing the agents simultaneously. Our findings do not support the use of these agents as a potentially effective preventive therapy combination, but they suggest that the timing of the administration of these chemotherapeutic agents could be an important factor in their effectiveness.

Colony Count, Microbial

Pectus excavatum and scoliosis. Thoracic anomalies associated with pulmonary disease caused by Mycobacterium avium complex.

We studied the frequency of pectus excavatum or otherwise abnormally narrowed anterior-posterior thoracic dimension and of thoracic scoliosis among consecutive series of 67 patients with pulmonary disease due to Mycobacterium avium complex and 55 patients with pulmonary Mycobacterium tuberculosis. Among those with M. avium, pectus excavatum and abnormal narrowing was present in 27% and scoliosis was seen in 52%; overall, 47 of the 67 (70%) had one or both of these anomalies. By comparison, of those with M. tuberculosis only 5% had pectus excavatum or abnormal narrowing, only 13% had scoliosis; and none had both. The prevalence of pectus excavatum and abnormal narrowing among female M. avium complex patients was significantly greater than among female tuberculosis patients (p = 0.05) or in the general population (p less than 0.001). Among male M. avium complex patients, pectus excavatum and abnormal narrowing was significantly more common than in the general population (p less than 0.001) but not significantly different than among male tuberculosis patients (p = 0.264). For all M. avium complex versus all M. tuberculosis patients the prevalence of pectus excavatum abnormal narrowing was significantly greater (p = 0.013). Scoliosis was significantly more common among all M. avium complex patients than among M. tuberculosis patients or the general population. We believe that these anomalies, which are associated with a variety of heritable connective disorders, are phenotypic markers of patients who are at increased risk for pulmonary disease due to environmental mycobacteria, such as M. avium complex.

Adult

Chronic tuberculous empyema with bronchopleural fistula resulting in treatment failure and progressive drug resistance.

We treated five patients with a past history of tuberculous pleural infection that led to chronic, quiescent, loculated empyema. Reactivation of TB was associated with formation of BPF and recovery of drug-susceptible Mycobacterium tuberculosis from sputum. All patients had recurrence of positive sputum cultures that yielded tubercle bacilli resistant to drugs they were receiving. The lungs demonstrated gross thickening with calcification of both visceral and parietal pleura. Two patients underwent retreatment chemotherapy followed by decortication-empyemectomy and lung resection surgery; both are now culture-negative for TB. One patient received retreatment chemotherapy but refused surgery; he remains clinically stable with negative sputum cultures. Two other patients' organisms became drug-resistant and they remain sputum-culture positive. We believe that thick, calcified pleural walls limit penetration of drugs into the infected empyema space, resulting in suboptimal drug concentrations and drug resistance. Intensified chemotherapy and surgical intervention should be considered in these cases.

Aged

Surgical intervention in the treatment of pulmonary disease caused by drug-resistant Mycobacterium tuberculosis.

Of 99 patients with pulmonary disease caused by multiple-drug-resistant strains of Mycobacterium tuberculosis admitted to the National Jewish Center for Immunology and Respiratory Medicine from 1983 to 1988, 29 were selected for resection to supplement chemotherapy. All patients had organisms with high levels of resistance to all of the first line medications, including rifampin and isoniazid. Although the patients were treated preoperatively with multidrug regimens in an effort to reduce the mycobacterial burden, 20 of 29 were still sputum-culture-positive at the time of surgery. The bulk of the disease was manifest in one lung, but lesser amounts of contralateral disease were demonstrated in 27 of 29. Pneumonectomy was done in 15 patients; lobectomy or lobectomy plus was done in 14. Although physiologic studies before surgery indicated significant respiratory impairment in many of the patients, there were no operative deaths. There were two unrelated deaths in this series. Of the 27 survivors, 25 have remained sputum-culture-negative for a mean duration of 36 months. Compared with historical controls, resectional surgery appears to offer benefit to selected patients with pulmonary disease caused by M. tuberculosis with extensive levels of drug resistance.

Adult

The effects of exposure time, drug concentration, and temperature on the activity of ethambutol versus Mycobacterium tuberculosis.

In a series of dynamic in vitro studies designed to assess the activity of ethambutol (EMB) against Mycobacterium tuberculosis, we made the following observations. Ethambutol showed bactericidal action with 10 micrograms/ml concentration when in constant contact with M. tuberculosis. At a lower concentration, bactericidal action was evident up to 6 days; after that time, this effect was lost owing to the development of drug-resistant mutants. The bactericidal action of ethambutol in this model was similar to that of rifampin and isoniazid. Pulsed exposure for 96 h caused a four-log reduction in cfu counts, but the growth resumed rapidly. The bactericidal action of ethambutol was maximal at 37 degrees C and less at low temperatures. Ethambutol showed little activity against cultures growing at 8 degrees C continuously that were incubated for only 1 h at 37 degrees C. Against cultures growing at 8 degrees C that were brought to 37 degrees C for 6 h, its action was similar to that of rifampin. Ethambutol combined with other drugs showed bactericidal action, although the activity was less than that of the combination isoniazid-streptomycin.

Ethambutol

Community-based short-course treatment of pulmonary tuberculosis in a developing nation. Initial report of an eight-month, largely intermittent regimen in a population with a high prevalence of drug resistance.

A community-based tuberculosis case-finding and short-course chemotherapy program was conducted in a suburb of Manila and featured 1 month of daily isoniazid (INH), rifampin (RIF), ethambutol (EMB), and pyrazinamide (PZA) followed by 7 months of twice-weekly, high dose, directly observed INH + EMB + PZA. Church-affiliated lay workers obtained 1,990 sputum specimens from subjects who complained of chronic cough or wasting symptoms; 207 of the specimens were positive on Ziehl-Neelsen smears. On culture, 176 yielded a significant growth of M. tuberculosis. Of these 176 patients, 144 were selected to enter the study; 10 were lost because of withdrawal or death and four (2.7%) because of drug toxicity. This left 130 patients who were followed long-term. Remarkably, 80% (104) were initially shedding drug-resistant organisms; 26% (34) were resistant to one drug, 30% (40) were resistant to two drugs, and 24% (30) were resistant to three or more drugs. Responses to therapy corresponded closely to the extent of drug resistance: 80% (48 of 60) of patients with drug-susceptible or single resistance had a favorable outcome; 43% (28 of 65) were resistant to two or three drugs, and 0% (0 of 5) of those were resistant to four or more drugs. Notable findings of this study were the success of a community-based program in conducting prolonged, directly observed treatment, the unexpectedly high prevalence of multiple-drug-resistant organisms in this population, and the inadequacy of INH + PZA + EMB during the continuation phase of therapy in this setting.

Antitubercular Agents