Pulmonary infection with Mycobacterium avium-intracellulare: diagnosis, clinical patterns, treatment.

Most physicians fail to recognize Mycobacterium avium-intracellulare (MAI) as a major pathogen for pulmonary disease among patients admitted to hospitals throughout the United States. In a review of all records of positive MAI cultures during the 10 years beginning July 1, 1979, at The Mount Sinai Hospital, New York City, we have identified 244 patients who had pulmonary disease primarily or secondarily complicated by MAI. We also identified another 243 patients as false positive for MAI infection. We classed as false positives patients who had no subsequent positive culture and whose clinical picture was and remained incompatible with MAI infection. We identified four distinct clinical patterns in the 244 patients with true positive MAI infections: (a) pulmonary nodules ("tuberculomas") indistinguishable from pulmonary neoplasms (78 patients); (b) chronic bronchitis or bronchiectasis with sputum repeatedly positive for MAI or granulomas on biopsy (58 patients, virtually all older white women); (c) cavitary lung disease and scattered pulmonary nodules mimicking M. tuberculosis infection (12 patients); (d) diffuse pulmonary infiltrations in immunocompromised hosts, primarily patients with AIDS (96 patients). The diagnosis should be established either by surgical resection and culture of resected nodules, or by three repeated positive acid-fast bacillus cultures of sputum or fluid and tissue obtained by bronchoscopy, or by biopsy of other tissue which shows granulomas and one or more positive MAI cultures. Surgical resection is the best treatment for "solitary" MAI nodules. Multiple antituberculous drug therapy is indicated for patients with chronic infection that impairs function or causes hemoptysis. The presence of MAI in the sputum or lung aspirates of patients with AIDS usually heralds the presence of a preterminal disseminated infection.

Mycobacterium avium and Mycobacterium intracellulare infections in patients with and without AIDS.

A genetic probe (Gen-Probe) was used to evaluate potential epidemiologic and susceptibility differences of Mycobacterium avium complex (MAC) strains isolated from 154 patients with and without the acquired immunodeficiency syndrome (AIDS). Genetic analysis revealed that 98% of the 45 patients with AIDS harbored only M. avium regardless of the anatomic or geographic source of the isolate; in contrast, approximately 40% of MAC isolates recovered from 109 patients without AIDS were M. intracellulare. Most M. intracellulare of respiratory origin recovered from patients without AIDS were involved in infectious processes. When 95 MAC isolates (M. avium, n = 53; M. intracellulare, n = 42) were evaluated for in vitro susceptibility to primary or secondary antimycobacterial drugs, significant differences were noted. M. intracellulare was more susceptible to streptomycin, rifampin, and ethambutol than M. avium; the converse was true for ethionamide. The results of this study suggest potentially important differences in disease spectrum and in vitro susceptibility profile for M. avium and M. intracellulare.

Mycobacteria and cryptococci cultured from the buffy coat of AIDS patients prior to symptomatology: a rationale for early therapy.

Culture of the buffy coat layer of the peripheral blood of 14 AIDS patients demonstrated sustained mycobacteremia or fungemia: 11 with Mycobacterium avium-intracellulare, 2 with Cryptococcus neoformans, and one with Mycobacterium tuberculosis. The early detection of these agents prior to the onset of overt symptomatology of disseminated infection due to these microorganisms allowed speculations on an early phase bacteremia and the proposal of prompt inception of antimicrobial therapy while the microbial burden is still manageable. The method also obviates the need for more invasive techniques.

The clinicopathological spectrum of non-tuberculous mycobacterial osteoarticular infections.

We studied the clinicopathological features of eight patients in whom a non-tuberculous mycobacterium was unexpectedly isolated from osteoarticular material obtained at operation. Three distinct types of infection with non-tuberculous mycobacteria were found: tenosynovitis, synovitis, and osteomyelitis. Tissue specimens from these sites showed a spectrum of pathological findings, including (1) virtually no inflammation, (2) mild to severe non-specific chronic inflammation, (3) granulomas without necrosis, and (4) caseating epithelioid granulomas that were indistinguishable from those of tuberculosis. In six patients the infection responded well to adequate surgical excision alone. In the remaining two the infection responded to surgical intervention and antituberculous therapy.

Mycobacterial meningitis. Retrospective analysis from 1970 to 1983.

The clinical presentation and course of tuberculous meningitis in 21 patients treated between 1970 and 1983 are analyzed. Tuberculous meningitis may present as acute, subacute, or chronic meningitis. Although characteristic cerebrospinal fluid findings of lymphocytic pleocytosis, low glucose level, and elevated protein level occur in the majority of cases, there are many atypical presentations. The protein level, glucose level, and white blood cell count may be normal, and there may be a predominance of polymorphonuclear cells rather than lymphocytes in the cerebrospinal fluid. Poor prognostic factors in this series were age greater than 65, underlying diseases, and stage 3 presentation. Incorrect or inadequate therapy had a disastrous outcome. Nontuberculous mycobacteria rarely are involved in central nervous system disease. Tuberculous meningitis must be considered in the differential diagnosis of any patient with fever and change in sensorium. A deteriorating mental status and falling cerebrospinal fluid glucose level in the presence of negative findings on bacterial culture and india ink preparation should lead to strong consideration for empiric initiation of anti-tuberculous therapy.

Nontuberculous mycobacteria in pleural fluid. Assessment of clinical significance.

We reviewed the case records of 22 patients from whose pleural fluid a nontuberculous Mycobacterium (NTM) was isolated. Three patients had pleural effusions definitely due to NTM infection, with evidence of NTM infection in other tissues; 16 had pleural effusions of known etiology unrelated to the isolated NTM and no other evidence of NTM infection; and three had pleural effusions of undetermined etiology and no other evidence of NTM infection. The case histories of the three patients with pleural effusions due to NTM are presented and the significance of the isolation of NTM from the remaining 19 patients is discussed. Criteria are proposed for evaluating the significance of NTM isolated from pleural fluid.

Mycobacterium avium-intracellulare-associated colitis in a patient with the acquired immunodeficiency syndrome.

A 40-year-old bisexual man with the acquired immunodeficiency syndrome developed abdominal pain and bloody diarrhea. At sigmoidoscopy, the mucosa of the rectum and sigmoid colon was edematous, erythematous, and friable, with multiple linear and oval erosions. Histologic examination of rectal biopsies demonstrated innumerable acid-fast bacilli free and within macrophages of the lamina propria. Mycobacterium avium-intracellulare was cultured from the rectal biopsy specimens. Pulmonary tissue and bone marrow cultures also demonstrated this organism. Therapy with several antimycobacterial agents resulted in improvement of symptoms. Among immunocompromised patients the spectrum of enteric pathogens causing colitis should be expanded to include Mycobacterium avium-intracellulare, a potentially treatable organism.

The spectrum of pathology of nontuberculous mycobacterial infections in open-lung biopsy specimens.

The diagnosis of pulmonary nontuberculous mycobacterial (NTM) infection may be difficult to establish unless open-lung biopsy is performed. Mycobacteria were present in resected lung tissues from forty patients at the Mount Sinai Hospital during the period 1969-1980. M. avium-intracellulare was cultured in 24 patients, M. tuberculosis in six, M. gordonae in three, and M. fortuitum in two. In five instances, mycobacteria were seen in smears of lung tissues but failed to grow in culture. Three distinct clinicopathologic groups of patients with NTM were recognized. (1) Eighteen patients had solitary pulmonary nodules resected with the clinical diagnosis of lung cancer. Histologically, they exhibited granulomas with varying degrees of necrosis. Mediastinal lymph nodes had no granulomas, except in one case. (2) Seven patients presented with roentgenologic evidence of bilateral, diffuse interstitial infiltration. M. avium-intracellulare or M. gordonae were isolated from lung tissue which histologically showed interstitial fibrosis and organizing pneumonia. In only one instance a few non-caseating epitheloid cell granulomas were found. Three of these patients had underlying malignancies treated with chemotherapy and one other had arthritis. The other three had no underlying diseases. (3) Three patients had multiple discrete infiltrates on chest roentgenograms. M. avium-intracellulare was isolated from their lung tissues. One of these patients exhibited necrotizing granulomatous vasculitis indistinguishable from Wegener's granulomatosis. It is apparent that classical "tuberculosis-like" granulomatous reaction is the most common histologic pattern but should not be expected in all patients with NTM infections.

Mycobacterium xenopi: infection in an immunocompromised host.

Mycobacterium xenopi was isolated from bronchoscopic and resected lung specimens from a patient who had diabetes mellitus and chronic myelogenous leukemia. While in remission, the patient developed spreading pulmonary infiltrates and died. At postmortem examination, acid fast bacilli were found in enormous numbers in histologic preparations of pulmonary hilar and mesenteric lymph nodes. Concomitant pulmonary infection with Aspergillus, Pneumocystis carinii, and cytomegalovirus was also evident. The probable dissemination of M. xenopi to pulmonary hilar and mesenteric lymph nodes attests to its invasive potential in the immunocompromised host and reinforces its role as an agent of nontuberculous mycobacterial disease.

Solitary pulmonary nodules due to nontuberculous mycobacterial infection.

Resected solitary pulmonary nodules which histologically are granulomas and in which acid-fast bacilli are seen are usually assumed to be due to infection with Mycobacterium tuberculosis. We reviewed the culture results of all resected lung specimens submitted to the mycobacteriology laboratory from 1969 to 1979. Of the 20 specimens in which acid-fast bacilli were seen and which roentgenographically were solitary pulmonary nodules, 12 (60 percent) were due to infection with M. avium-intracellulare. In five granulomas, acid-fast bacilli were seen but failed to grow on culture. In one instance each, M. tuberculosis, M. fortuitum and M. gordonae grow on culture. Fiberoptic bronchoscopy was not diagnostic in 10 patients, although in one patient M. avium-intracellulare was cultured from the bronchial washings. Lymph nodes removed at mediastinoscopy from 12 patients did not contain granulomas. Since the physician was often unaware that cultures subsequently grew nontuberculous mycobacteria, most patients were treated with two drug regimens for presumed tuberculosis. Postoperative follow-up was available for 14 of the 20 patients, for a period ranging from four months to 10 years. There was no instance of dissemination of the infection to lung or pleura. We conclude that solitary pulmonary "tuberculomas" are often due to nontuberculous mycobacterial infection, particularly M. avium-intracellulare. When the lesion is due to nontuberculous mycobacteria and can be resected in its entirety, drug therapy is not indicated.

Nontuberculous mycobacteria as unsuspected agents of dermatological infections: diagnosis through microbiological parameters.

Nontuberculous mycobacteria were identified as the agents of dermatological lesions in seven patients seen at The Mount Sinai Hospital from 1969 to 1979. Three patients had water-associated cutaneous lesions, three had abscesses at the site of an injection, and one had an erosive nasal lesion. In each of these instances, the mycobacterial etiology was not suspected, and diagnosis was achieved only after careful microbiological studies. These experiences emphasize that a mycobacterial etiology should be sought in chronic cutaneous lesions occurring at traumatized sites.

Mycobacterium avium complex: significance of isolation from bone marrow culture.

Six patients with bone marrow cultures yielding Mycobacterium avium complex were encountered at the Mount Sinai Hospital between 1969 and 1976. One additional isolate of the same mycobacterial species was recovered from splenic cyst fluid of a seventh patient. Because none of the patients had illnesses apparently due to M. avium complex, the isolates were unexpected and unexplained. Six of the seven patients had other acute or chronic infectious processes, occurring alone or superimposed on a preexisting disease. These patients were therefore unusual, because nontuberculous mycobacteria have previously been obtained from bone marrow cultures exclusively in patients who had either disseminated or pleuropulmonary nontuberculous mycobacteriosis. The isolation of M. avium complex from the reticuloendothelial tissue of these seven patients may reflect an asymptomatic infection or alternatively may lack significance. Either premise can only be judged by continued careful evaluation of similar findings.

Recovery of Cryptococcus neoformans from modified Dubos liquid medium utilized for isolation of mycobacteria.

Cryptococcus neoformans was isolated from nine pathological specimens cultured for mycobacteria. Five of these were recovered only in liquid TBC medium in the absence of growth on conventional substrates.