Treatment experience of multidrug-resistant tuberculosis in Florida, 1994-1997.

OBJECTIVE: To study the clinical characteristics and results of patients with diagnoses of multidrug-resistant tuberculosis (MDR-TB) in the state of Florida. METHODS: Retrospective chart review of all patients (n = 81) with diagnoses of MDR-TB in Florida between January 1, 1994, and July 31, 1997. RESULTS: The average number of resistant drugs was 4.8 (range, 2 to 11). Of 81 patients, 46 patients (57%) completed adequate therapy, 26 patients (32%) died, and 9 patients (11%) never completed a satisfactory course of treatment. Patients who received at least part of their therapy at A. G. Holley State Hospital, a specialized tuberculosis (TB) treatment center, had significantly higher treatment completion rates (79%) than those treated as outpatients alone (48% treatment completion rate, p < 0.001), even after the exclusion of patients who were acutely ill and died within 2 months of diagnosis. CONCLUSION: In Florida, a specialized TB care program for MDR-TB, including at least partial inpatient therapy, yielded higher treatment completion rates compared to outpatient treatment alone.

Use of rifabutin with protease inhibitors for human immunodeficiency virus-infected patients with tuberculosis.

Drug interactions between rifamycins and highly active antiretroviral therapy (HAART) have raised concerns in the treatment of human immunodeficiency virus (HIV)-infected patients with tuberculosis. We conducted a study of this interaction by measuring serum drug levels of all HIV-infected patients with tuberculosis who were admitted to A. G. Holley State Tuberculosis Hospital (Florida) from October 1997 through December 1998, who were concomitantly treated with rifabutin and HAART. All 25 patients studied became culture-negative within 2 months of initiation of therapy for tuberculosis and remained negative for a median of 13 months follow-up after completion of therapy. HIV viral loads (mean+/-SEM) decreased significantly from 4.95+/-0.21 log10 copies/mL before initiation of HAART to 2.77+/-0.07 log10 copies/mL before discharge (P<.001); 20 of 25 patients achieved viral loads of <500copies/mL. In summary, the concomitant use of rifabutin and HAART can lead to successful treatment of HIV-infected patients with tuberculosis without increased side effects.

Mesothelial cells in tuberculous pleural effusions of HIV-infected patients.

The scarcity of mesothelial cells is a well-known characteristic of tuberculous pleural effusions. We report three HIV-infected patients with tuberculous pleural effusions, in which mesothelial cells were found in significant numbers in the pleural fluid. Clinicians should be aware that the altered immune responses that occur in HIV-infected patients may affect the cytologic profile of tuberculous pleural effusions, and they should be cautious not to exclude this diagnosis based solely on the presence of mesothelial cells in the fluid.

Paradoxical worsening of tuberculosis following antiretroviral therapy in patients with AIDS.

Transient worsening of tuberculous symptomatology and lesions following antituberculous therapy (paradoxical response) has previously been described as a rare occurrence. To determine the incidence of paradoxical responses in patients with AIDS and TB who are treated with antituberculous therapy and subsequently with combination antiretroviral therapy (ARV), we conducted a prospective study of 33 HIV-seropositive TB patients treated with anti-TB therapy and antiretroviral therapy (Group 1) compared with 55 HIV-seronegative TB patients treated with anti-TB therapy (Group 2) and 28 HIV-seropositive TB patients treated with anti-TB therapy but not on antiretrovirals (historical control; Group 3). In Group 1 patients, paradoxical responses were temporally more related to the initiation of ARV than to the initiation of anti-TB therapy (mean +/- SD: 15 +/- 11 d versus 109 +/- 72 d [p < 0.001]) and occurred much more frequently (12 of 33; 36%) compared with Group 2 (1 of 55; 2%) (p < 0.001) or with Group 3 (2 of 28; 7%) (p = 0.013). The majority of patients who experienced paradoxical responses and received tuberculin purified protein derivative (PPD) in Group 1 had their tuberculin skin tests convert from negative to strongly positive after ARV. These observations suggest that a paradoxical response associated with enhanced tuberculin skin reactivity may occur after the initiation of ARV in HIV-infected TB patients. Furthermore, the skin test conversion after the initiation of ARV may have important public health implications.

Antituberculosis drug-induced hepatotoxicity. The role of hepatitis C virus and the human immunodeficiency virus.

Until recently it was thought that age greater than 35 yr was the main risk factor for the development of drug-induced hepatitis (DIH) in patients receiving antituberculosis therapy. We conducted a study to determine whether infection with either the hepatitis C virus or the human immunodeficiency virus (HIV) were significant risk factors for the development of DIH in patients receiving antituberculosis therapy. Our study consisted of two parts. In the first part, 134 consecutive patients admitted for the treatment of tuberculosis (TB) were followed for the development of DIH. All of these patients were also screened for the presence of hepatitis C and HIV. In the second part of the study, those patients who were hepatitis C positive and who developed DIH on repeated reintroduction of the anti-TB drugs were offered a liver biopsy. If active inflammation, which may be suggestive of hepatitis C infection, was present on the biopsy specimen, treatment with alpha-interferon was begun and the anti-TB drugs were subsequently reintroduced. During the 18 mo of the study, 22 patients developed DIH. The relative risk of developing DIH if the patient was hepatitis C or HIV positive was fivefold and fourfold, respectively (p < 0.05). If a patient was coinfected with both hepatitis C and HIV the relative risk of developing DIH was increased 14.4-fold (p < 0.002). In the treatment part, four patients were treated with alpha-interferon, and all were able to undergo the reintroduction of anti-TB therapy without reoccurrence of DIH. Infection with hepatitis C and HIV are independent and additive risk factors for the development of DIH during TB therapy. The treatment of hepatitis C with alpha-interferon may allow the reintroduction of anti-TB agents in those who previously developed DIH when exposed to these drugs.

Hospital outbreak of multidrug-resistant Mycobacterium tuberculosis infections. Factors in transmission to staff and HIV-infected patients.

OBJECTIVE: To describe transmission of multidrug-resistant (MDR) Mycobacterium tuberculosis infection among patients and health care workers (HCWs) in a ward and clinic for human immunodeficiency virus (HIV)-infected patients in a hospital, four studies were conducted. METHODS: Case patients and control patients were persons who had been treated in the HIV ward or clinic, whose clinical course was consistent with tuberculosis and who had at least one positive culture for M tuberculosis between January 1, 1988, and January 31, 1990, resistant to at least isoniazid and rifampin (case patients), or whose isolates were susceptible to all drugs tested (control patients). In the first study, case patients and control patients were compared to identify risk factors for MDR tuberculosis. In the second study, inpatient and outpatient days of MDR tuberculosis case patients were compared to determine whether acid-fast bacillus (AFB) smear-positivity or aerosolized pentamidine use was associated with higher numbers of subsequent MDR tuberculosis cases among exposed patients. In the third study, restriction fragment length polymorphism analysis was performed on available MDR and sensitive M tuberculosis isolates. In the fourth study, skin test conversion rates among HCWs in the HIV ward and clinic were compared with those of HCWs in another ward, and the strength of the associations between skin test conversions among HCWs on the HIV ward and the number of person-days that AFB smear-positive case patients and control patients were on this ward was estimated. RESULTS: Case patients were more likely than control patients to have been exposed on the HIV ward or clinic to an AFB smear-positive case patient (P less than .001). Inpatient and outpatient days of MDR tuberculosis case patients were associated with more subsequent cases of MDR tuberculosis if exposing case patients were smear-positive or if they received aerosolized pentamidine (P less than or equal to .01). Of 13 MDR isolates, all had one of two restriction fragment length polymorphism patterns; 10 sensitive isolates had restriction fragment length polymorphism patterns that were different from each other. The HCW skin test conversion rate was higher on the HIV ward and clinic than on the comparison ward (P less than .01). The risk of occupational acquisition of infection increased in direct proportion to the number of person-days that AFB smear-positive case patients were on the HIV ward (r = .75; P = .005), but did not increase in proportion to the number of person-days that AFB smear-positive control patients were there (r = -.36; P = NS). After isolation measures for AFB smear-positive tuberculosis patients were improved, MDR tuberculosis cases decreased to seven of 214 tuberculosis patients. CONCLUSIONS: Nosocomial transmission of MDR M tuberculosis infection to patients and HCWs occurred on the HIV ward and clinic. Infectiousness of MDR tuberculosis case patients was associated with AFB sputum-smear positivity. Case patients with MDR tuberculosis created a greater risk of skin test conversion for HCWs on the HIV ward than drug-susceptible control patients.

Medical management of AIDS patients. Tuberculosis and nontuberculous mycobacterial disease.

AIDS has been responsible for a significant increase in mycobacterial disease, which in this setting is often extrapulmonary. In contrast to HIV-associated Mycobacterium avium complex disease, HIV-associated tuberculosis is normally transmissible between humans by the aerosol route, occurs earlier than most AIDS-related infections, and is readily treatable and preventable with conventional drugs.

Functional laryngeal obstruction relieved by panting.

A 49-year-old man presented with a two-day history of severe recurrent dyspnea and inspiratory stridor. A chest roentgenogram, computed tomographic scan of the neck, direct laryngoscopy, and bronchoscopy excluded organic upper airway obstruction. Laryngospasm occurred during the bronchoscopy. Although flow volume loops revealed severe upper airway obstruction (inspiratory and expiratory), airway resistance measured plethysmographically (during panting) was normal. Because of this observation, panting was recommended for relief of the patient's recurrent attacks of functional laryngeal obstruction. The panting maneuver immediately and completely relieved all 25 to 30 subsequent attacks. After the patient recovered clinically, a flow volume loop was repeated and was found to be normal. The marked discrepancy between severe flow limitation (as detected by flow volume loops) and normal airway resistance (measured plethysmographically) may be a diagnostic test for functional laryngeal obstruction, and panting may be an effective emergency measure for its relief. Relief by panting may also suggest the diagnosis. A second patient with an almost identical symptom complex is described, in whom the panting maneuver was also dramatically successful in promptly aborting recurrent severe attacks of airway obstruction and stridor.

Spontaneous lymphokine activated killer (LAK) activity in bronchoalveolar lavage cells from patients with bronchogenic carcinoma.

Bronchoalveolar lavage cells (BAC) are considered to be representative of cells that are in the interstitium and in patients with lung cancer, may represent, in part, cells that infiltrate cancerous tissue. We used bronchoalveolar lavage (BAL) specimens to test the hypothesis that cells within this region might be regulated locally by factors and show activities that are dependent on these growth and activation mediators. We showed previously that Natural Killer (NK) activity and IL2 titers were proportional. As compared to normal subjects, patients with all stages of bronchogenic carcinoma consistently had very high levels of IL2 in their bronchoalveolar lavage (BAL) fluid and this titer correlated with an increase in NK activity in the BAC both in absolute level and in relative level to the blood. Now, we report results that show that spontaneous lymphokine activated killer (LAK) activity also can be measured in most patients, but not all patients, that express IL2 titers. These findings support the hypotheses that different types of nonspecific cytotoxic cells are present and active in cancerous lung specimens secondary to the secretion of lymphokines from activated T lymphocytes in that region and that LAK activity is a physiological phenomenon that may be expressed in regional rather than systemic areas of the body.

Tuberculosis in acquired immune deficiency syndrome.

The acquired immune deficiency syndrome (AIDS) epidemic has resulted in a rising incidence of tuberculosis (TB) in the United States, especially in inner cities where AIDS is prevalent and among human immunodeficiency virus (HIV) infected subpopulations with a relatively high background prevalence of tuberculous infection (ie, intravenous drug abusers, Haitians, blacks). Because M tuberculosis is a relatively virulent organism among the AIDS related infections, TB occurs early (often as a sentinel disease) in the course of progressive HIV-induced immunosuppression. In this setting, TB commonly presents in a disseminated, extrapulmonary, or "unusual" form, and when pulmonary TB occurs, the chest radiographic picture is often atypical. Further, the tuberculin test is falsely negative in more than 50% of cases. A high index of suspicion and an aggressive diagnostic approach is required to avoid missing HIV-related tuberculous disease, which is communicable to the general population and is readily treatable with conventional anti-TB drugs. In order to control the rising incidence of AIDS-related TB, tuberculin skin testing must be performed early for all patients who are either HIV infected or are in high risk groups for HIV infection (while they can still react to tuberculin), and isoniazid prophylaxis carried out for those who are tuberculous infected.

Cresyl violet: a rapid, simple, easily interpretable stain for detecting Pneumocystis carinii in sputum.

Over a three-month period at the pathology laboratory of Jackson Memorial Hospital, 110 sputum samples from 62 hospitalized patients with suspected AIDS were examined for Pneumocystis carinii. Sputum specimens were either expectorated spontaneously (most patients) or expectorated after the inhalation of small amounts of nebulized normal saline. Each sputum sample was cytocentrifuged onto two slides. One slide was stained with Gomori methenamine-silver (GMS) and the other with cresyl violet (CV). Among the 62 study patients, 18 were proven to have no histologic evidence of P carinii pneumonia. Of the remaining 44 patients, P carinii organisms were found by GMS stain in 14 (32%) and by CV stain in 18 (41%). Among those with a positive CV stain, the diagnosis was made on the first sputum specimen in 14 patients and on the second specimen in the remaining four patients. CV stain is at least as sensitive as GMS in detecting P carinii cysts in the sputum of AIDS patients with P carinii pneumonia, and its diagnostic sensitivity may exceed 40% under field conditions. Further, CV stain is much simpler to prepare than GMS and much simpler to interpret than Giemsa. It could be easily adapted for general use to expedite the diagnosis and treatment of P carinii pneumonia.

Granulomatous vasculitides of the lung: a clinicopathologic approach to diagnosis and treatment.

The granulomatous vasculitides of the lung are uncommon. Overlap of their clinical and histopathologic features may create a confusing picture for the clinician and pathologist. This confusion is of concern because therapy differs depending on the exact diagnosis, with concomitant variations in associated drug toxicity. An integrated clinical and pathologic approach must be used to arrive at a prompt and accurate diagnosis. The true granulomatous vasculitides, a group that includes Wegener's granulomatosis, allergic granulomatosis and angiitis (Churg-Strauss syndrome), and necrotizing sarcoid granulomatosis, have various degrees of systemic involvement. Therapy is mainly immunosuppressive, and prognosis is generally good. The lymphoproliferative granulomatous vasculitides, which include benign lymphocytic angiitis and granulomatosis, lymphomatoid granulomatosis, and malignant lymphoma with angioinvasion, are progressively abnormal lymphoproliferative processes. Therapy may require combination chemotherapy, and prognosis is often poor.

Mycobacterial disease: epidemiology, diagnosis, treatment, and prevention.

TB is common in the setting of HIV-induced immunosuppression, especially among demographic groups with a high background prevalence of tuberculous infection. It is often the first (sentinel) infectious disease to appear, extrapulmonary and disseminated disease is common, the chest x-ray picture is frequently atypical, and the tuberculin skin test is often falsely negative. It therefore requires a high index of suspicion and an aggressive diagnostic approach to avoid missing HIV-related tuberculous disease, which is communicable from man to man by the aerosol route and which appears to be highly treatable with conventional anti-TB drugs. Identification and INH prophylaxis of tuberculous-infected, HIV-seropositive persons is likely to be very important in the prevention of tuberculous disease. MAI is also a very common pathogen that frequently produces extrapulmonary and disseminated disease among patients with AIDS. In contrast to TB, AIDS-related MAI disease occurs more uniformly among the AIDS risk groups, occurs late among the HIV-related infections, and is not effectively treated with current drug regimens.