Utility of rifampin blood levels in the treatment and follow-up of active pulmonary tuberculosis in patients who were slow to respond to routine directly observed therapy.

STUDY OBJECTIVE: The standard daily dose of rifampin in directly observed treatment of Mycobacterium tuberculosis (TB) is 600 mg, taken orally. The purpose of this study was to assess the efficacy of standard dose rifampin therapy in patients who were slow to respond to routine directly observed therapy (DOT). METHODS: Patients with non-drug-resistant pulmonary TB who were receiving 600 mg of oral rifampin by DOT were eligible for inclusion. Patients were deemed slow to respond if their sputum smears and cultures remained positive for M tuberculosis and if the patient's condition did not improve clinically or radiographically after 3 months of treatment. Serum rifampin levels were ascertained to determine the adequacy of the standard rifampin dosing. Patients with subtherapeutic blood levels had their rifampin dose increased to 900 mg, and rifampin levels were repeated. Rifampin dosage was increased again if blood levels were still subtherapeutic. No antitubercular medications were added to the treatment regimen. The total weekly dose of the other standard treatment drugs was not increased. RESULTS: Of 124 new patients with active pulmonary TB, 6 patients were identified as slow to respond to the standard antitubercular DOT. All six patients had subtherapeutic serum rifampin levels. All six patients responded clinically, radiographically, and mycobacteriologically after an increase in rifampin dosage to reach target drug blood level. CONCLUSIONS: Standard dosing with rifampin resulted in a poor clinical response and subtherapeutic serum levels in six patients. Increasing the dosage of rifampin improved the outcome without additional side effects. In TB patients who are slow to respond to standard treatment, an inadequate dose of rifampin should be suspected. Current antituberculer drug administration does not include adjusted dosage for rifampin.

Nontubercular mycobacterial pulmonary infection in immunocompetent men.

BACKGROUND: Nontubercular mycobacteria (NTM) are increasingly recognized to cause lung disease in immunocompetent patients. We studied the occurrence of pulmonary infection due to NTM in immunocompetent men. METHODS: We retrospectively analyzed all sputum mycobacterial cultures at our institution over a 5-year period. Charts were reviewed to identify patients who met the American Thoracic Society's criteria for mycobacterial pulmonary infection. RESULTS: From the 7,380 sputum mycobacterial cultures obtained, 46 male patients had NTM identified. Forty-two patients were immunocompetent. Five of these patients were found to have NTM--2 with Mycobacterium kansasii, 2 with Mycobacterium avium-intracellulare, and 1 with Mycobacterium gordonae. All 5 patients responded to antimycobacterial therapy. CONCLUSION: Twelve percent of our population of immunocompetent men from whom NTM were isolated from sputum were infected. This study should alert the clinician that NTM cause treatable pulmonary disease in immunocompetent men.

Peripartum cardiomyopathy: echocardiogram to predict prognosis.

Peripartum cardiomyopathy is an uncommon complication of human pregnancy that threatens both the mother and fetus with maternal congestive heart failure. Clinicians must be aware of this problem in order to provide prompt diagnosis and effective treatment that will insure a favorable return of normal left ventricular function.

Right atrial myxoma with extracardiac manifestations.

Right atrial myxoma is a rare intracardiac tumor that is often difficult to diagnose. Pulmonary embolism from tumor fragments originating from the tumor mass is a potentially fatal complication. Early diagnosis of cardiac myxoma is important since surgical treatment leads to resolution with low rates of recurrence and good long-term survival. The presence of a cardiac myxoma can be heralded by nonspecific constitutional symptoms as well as by disturbances in the clotting mechanism.

Demographic changes in tuberculosis: high risk groups.

We conducted a statistical analysis of all verifiable tuberculosis (TB) cases in Tennessee from 1990 through 1996 to determine the demographic changes in TB. We studied variables, including age, sex, race, site of the disease, and possible impact of known risk factors such as human immunodeficiency virus (HIV) infection, homelessness, foreign birth, and residency in extended care facility. The percentage increase in all such categories, except in the nursing home population, had a statistically significant increase. Unlike national epidemiologic findings, foreign-born TB comprised less than 1% of the total cases. Association of HIV as a co-infection increased from 16 (2.7%) in 1990 to 41 (8.1%) in 1996. These findings will have significant impact on TB control measures and the clinical practice of TB cases in Tennessee and other areas of the southeastern US.

Symptomatic pulmonary hyalinizing granuloma.

An otherwise healthy 37-year-old man came to the emergency room with left-sided dull chest pain of 4 weeks' duration. Physical examination, laboratory studies, and electrocardiogram were all unremarkable. A chest x-ray film revealed calcified pulmonary nodules. Computed tomography of the chest confirmed bilateral parenchymal cavitary lesions. Via limited thoracotomy, a tan nodule measuring 2.5 to 3.0 cm in diameter was excised from the left upper lobe. Histopathologic examination revealed a well circumscribed lesion and extensive lamellar hyalinization. A few foci of finely granular calcification were present within the hyalinizing areas. After surgery and short-term use of nonnarcotic analgesics, the chest pain resolved. Although pulmonary hyalinizing granuloma (PHG) is known to produce cavitating lesions, calcification at multiple sites is also consistent with this diagnosis. Clinicians should remember to include PHG in the differential diagnosis of multiple pulmonary nodules.

Blastomycosis in northeast Tennessee.

STUDY OBJECTIVES: To study the epidemiologic and clinical features of blastomycosis in northeast Tennessee. DESIGN: Retrospective review of blastomycosis cases in the region from 1980 through 1995. SETTING: Hospitals located in the Tri-Cities region of northeast Tennessee. PATIENTS: Seventy-two patients with confirmed blastomycosis infection. INTERVENTIONS: None. RESULTS: During the 1980 to 1995 study period, we documented 72 cases of blastomycosis. The mean age was 52 years (range, 13 to 86 years), most were male (69.4%), and nine were immunocompromised. A possible environmental exposure was noted for 28 patients. Pulmonary involvement represented the most common site of infection (61 cases), but multiorgan involvement was common (17 cases). Most patients with pulmonary blastomycosis (66%) presented with a chronic illness, and radiologic findings usually revealed local consolidation or a mass-like lesion. Nine patients developed ARDS with an associated mortality rate of 89%, compared with a 10% mortality for non-ARDS pulmonary cases. Antifungal treatment regimens varied widely, with amphotericin B often used for sicker patients. An epidemiologic evaluation revealed that the mean yearly incidence rate for blastomycosis quadrupled between 1980 and 1987 (0.31 cases/ 100,000 population) and 1988 to 1995 (1.23 cases/100,000 population) (p=0.00001). Most new blastomycosis cases in the 1988 to 1995 period occurred in three counties in the region where significant new construction projects have been underway. CONCLUSION: Blastomycosis is endemic in northeast Tennessee and the number of cases is increasing, coinciding with major new construction in the region. Clinicians in the area must be alert to this condition.

Hypercalcemia and pulmonary tuberculosis in east Tennessee.

In a study of 83 patients with active pulmonary tuberculosis who were treated in East Tennessee, only three developed hypercalcemia. The incidence of hypercalcemia in East Tennessee is markedly lower than that quoted in earlier studies performed in the United States. The explanation for the infrequent occurrence of elevated serum calcium in our population is probably multifactorial, but does not appear to be related to the selection of antituberculous agents.

Pulmonary blastomycosis with acute respiratory failure as predominant clinical feature.

Two previously healthy young adults came to our community hospital with rapidly progressive respiratory failure. Investigation confirmed Blastomyces as the responsible etiologic agent. Despite adequate antifungal chemotherapy and intensive supportive care, both patients died, one within 24 hours and the other after 14 days. Overwhelming infection with Blastomyces dermatitidis can cause acute respiratory failure, possibly the adult respiratory distress syndrome, even in immunocompetent hosts.

Tuberculosis. Part I.

Tuberculosis has been a disease of human beings for thousands of years. In recent times it has waxed to become the feared White Plague of the eighteenth and nineteenth centuries and waned under the impact of effective chemotherapy until its elimination seemed possible by the early twenty-first century. The resurgence of tuberculosis in the past 10 to 15 years, caused by unanticipated events such as the appearance of the human immunodeficiency virus and deteriorating social conditions, also brought with it the problem of multiple drug resistance. Control measures such as tuberculin skin testing, perhaps somewhat forgotten when tuberculosis seemed to be a disease of the past, again became first-line defenses against spread of the disease. Environmental controls must be well understood and used effectively. Diagnosis of tuberculosis requires knowledge of the strengths and shortcomings of the various diagnostic methods and experience in their use. Practitioners are cautioned to remember that no diagnostic method, by itself, can be relied on to confirm or rule out tuberculosis. Well-tested diagnostic methods of chest radiograph, tuberculin skin testing, smear, and culture have been recently supplemented by rapid diagnostic tests based on amplification of bacterial RNA and DNA. More invasive diagnostic methods are sometimes required to diagnose extrapulmonary disease. Two-drug up to seven-drug therapy may be indicated for a case of tuberculosis, depending on evidence of the presence of multiple drug resistance. Duration of treatment can range from 6 to 12 months, also depending on identification of drug-sensitive or drug-resistant organisms. Failure of compliance can be a significant problem in patients who are homeless, or drug abusers, or who for various reasons cannot or will not complete a course of therapy. Directly observed therapy is strongly recommended for these patients, and for assistance in its administration the physician must cooperate with the local or state health department. The health department also must be notified whenever a case of tuberculosis is identified.

Nutritional status and mortality in respiratory failure caused by tuberculosis.

A retrospective analysis of the records of all patients admitted to the intensive care unit with respiratory failure and nonmiliary tuberculosis was conducted to determine variables that might be predictive of survival. Nutritional status, as reflected by the patient's serum albumin and hemoglobin, were the best predictors of survival and were more helpful than the widely accepted APACHE II scoring system. This observation suggests that early and aggressive attention to improving the patient's nutritional status may be as important as effective antitubercular therapy and mechanical ventilation in salvaging these individuals.

Plasmacytoma as a cause of obstructive sleep apnea.

Solitary extramedullary plasmacytomas are uncommon neoplasms. They occur most frequently in the upper aerodigestive tract and account for 4% of the nonepithelial tumors in this site. The evolution of a plasmacytoma is unsteady and symptoms at presentation have included dystonia, dysphagia, oral pain, cough, and dyspnea on exertion. Plasmacytoma of the upper aerodigestive tract has not been previously reported as a cause of obstructive sleep apnea.

Hemoptysis and hematemesis due to a broncholith: granulomatous mediastinitis.

A 40-year-old man had new onset of hemoptysis and hematemesis. Bronchoscopy revealed red, inflamed mucosa with apparent rich blood supply in the left primary bronchus. Computed tomography revealed calcified subcarinal lymph nodes with a small extension into the left primary bronchus. Shortly after admission, the patient had an episode of gastrointestinal bleeding. Esophagogastroduodenoscopy showed a lesion in the posterior wall of the esophagus, 12 cm from the upper incisors. During exploratory thoracotomy, a single piece of irregular-shaped tan tissue measuring 3.5 x 2.5 x 2.0 cm and engulfing the esophagus, carina, and left primary bronchus was dissected. A single stonelike mass, or broncholith, was found to involve both the trachea and the esophagus. Microscopic examination showed multiple caseating granulomas with surrounding lymphoid tissue and germinal centers. During 12 months of follow-up, the patient has remained asymptomatic. The chronic inflammation in this case suggested granulomatous mediastinitis, a rare disease whose mass-like effects may contribute to structural compression. The trachea and esophagus are rarely involved. Tuberculosis and histoplasmosis are thought to be the two most common causes of granulomatous mediastinitis. Chronic inflammation leading to calcification and broncholith may invade bronchial lumen or esophageal wall, causing life-threatening hemorrhage and necessitating prompt surgical intervention.

Extrapulmonary tuberculosis in Tennessee: lessons from the last decade.

In conclusion, extrapulmonary TB remains a significant fraction of the total TB cases in Tennessee. During the last few years, the percentage of extrapulmonary TB in Tennessee has been on the increase. Understanding these changes in the epidemiology of extrapulmonary TB will help the clinician in making a prompt diagnosis, leading to appropriate therapy. Understanding the changing trends at the national level may aid state health departments in reorganizing disease control programs, thus, facilitating the eradication of TB and other communicable diseases in Tennessee.