Atypical mycobacteria in a tuberculosis hospital Godfrey L. Gale, mb,

ch b, frcs

Cultures from 80 out of 1667 patients (4.8%) admitted consecutively to a tuberculosis hospital grew atypical mycobacteria. With four strict criteria it was concluded that the mycobacteria isolated were the cause of the disease in 47 of these patients. The majority of these organisms were resistant to most, and in seven cases to all, of the antituberculous drugs. Ten

patients responded poorly to treatment

and 14 patients (30%) died, 8 of these from uncontrollable pulmonary infection with the atypical organisms. It is suggested that a recent, simplified classification of mycobacteria proposed by Runyon be adopted. Les cultures de 80 sur 1667 patients (4.8%) admis consecutivement a un hdpital pour tuberculeux ont mis en evidence des mycobacteries

atypiques. S'appuyant

criteres rigoureux,

les

sur quatre on a conclu que

mycobacteries isolees

etaient la de la maladie chez 47 de ces patients. La majorite de ces organismes etaient resistants a la plupart, et dans sept cas a tous, les medicaments antituberculeux. Dix patients ont mal cause

repondu (30%)

au

traitement et 14

patients

morts, 8 d'entre eux d'une infection pulmonaire incontrolable causee par des organismes atypiques. II est suggere qu'une classification recente et simplifiee des mycobacteries, sont

proposee par

Runyon,

soit

adoptee.

In the 41/i-year period Jan. 1, 1970 to June 30, 1974 there were 1667 admis¬ sions to the tuberculosis unit at the Toronto Hospital, Weston. Cultures from 80 of these patients (4.8%) grew

atypical mycobacteria. The object of this paper is to analyse this experience and also to draw atten¬ tion to Runyon's new classification of atypical mycobacteria, which may prove of value in the diagnosis and treatment of disease due to these or¬ ganisms. Criteria for a causal relationship The finding of atypical mycobacteria does not necessarily prove that these organisms are the causal agent of dis¬ ease present nor, in fact, does it prove that there is any disease present. Therefore, in my analysis I used the following four criteria of a causal rela¬ tionship between the mycobacteria Reprint requests to: Dr. G.L. Gale, Chief of medical staff, Toronto Hospital, Weston, ON M9N 3M6

(edin) recovered and the condition of the

drugs in this series, but the majority of the atypical mycobacteria isolated 1. There must be clinical evidence were resistant to most, and in seven of disease. cases to all, of the drugs available. The 2. There must be radiologic evidence commonest effective drugs were rifam¬ of disease in the lungs or urinary tract. pin, cycloserine and ethionamide. For 3. The atypical mycobacteria must two patients, both of whom died, re¬ be recovered repeatedly. sistance reports were not obtained. 4. Mycobacterium tuberculosis must In view of the serious problem of never be recovered. drug resistance, effective chemotherapy must be based on sensitivity studies, Patients and bacteriologic findings and in all instances multiple drug ther¬ In 67 patients the atypical mycobac¬ apy must be given. This should include, teria were cultured from the sputum, if possible, three of the four main drugs in 11 patients from urine, in 1 patient (streptomycin, isoniazid [INH], rifam¬ from a skin ulcer and in 1 patient from pin and ethambutol) or, if the organism cervical lymph nodes. Using the above is resistant to these drugs, at least three four criteria I concluded that in 47 of of the "second-line" drugs (capreomythe 80 patients the disease present had cin, kanamycin, pyrazinamide, ethiona¬ been caused by the mycobacteria mide, para-aminosalicylic acid and isolated. Of these 47 patients, whose cycloserine). Unless acute, spreading data form the basis of this study, 45 disease is present it is usually wise to had pulmonary disease, 1 had a skin await sensitivity reports before initiating ulcer and 1 had infection of cervical chemotherapy. Prior to the period under study two lymph nodes. For none of the 11 patients from patients underwent a successful lobecwhom atypical mycobacteria were cul¬ tomy in this hospital for residual cavitatured from the urine were the above tion; M. kansasii was the infecting or¬ criteria satisfied and they have there¬ ganism. There were no thoracic surgical fore not been included in this study. procedures performed in the present Three of them had proven renal tuber¬ series because either (a) the patient culosis; the other eight had no definite responded well to chemotherapy, the pyelographic changes and it was not sputum converting to negative, and sur¬ possible to culture the mycobacteria gical treatment was thought to be un¬ repeatedly. I have never, in fact, en¬ necessary; or (b) extensive bilateral countered disease other than in lungs, disease contraindicated surgery, parti*lymph nodes or skin in which I could cularly if resistant organisms precluded confidently affirm that atypical myco¬ adequate antibiotic coverage. Localized bacteria were the causal agents. progressive disease that fails to respond Of the 47 patients 35 were males to chemotherapy should, however, be and 12 females. Their ages ranged from considered for surgical treatment. 12 to 86 years and only nine were less than 50. This sex and age dis¬ Results In this series of patients, followed tribution is characteristic of infection with atypical mycobacteria, especially for at least 6 months, the results of treatment were disappointing. Success pulmonary disease. The species of atypical mycobacteria depended primarily on whether ade¬ cultured were as follows: M. kansasii, quate chemotherapy was available. Good results (sputum conversion, 15 patients; M. intracellulare, 13 pa¬ good radiologic clearing, no residual tients; group III unspecified, 12 pa¬ in 14 pa¬ tients; M. xenopei, 2 patients; and M. cavitation) were obtained 2 the whose cases tients, including fortuitum, M. thermoresistibile, M. are described below, 1 having cer¬ flavescens and M. marinum (formerly vical lymphadenitis and the other, skin called M. balnei), 1 patient each. In ulceration. Fair results (sputum conver¬ seven of these patients more than one either un¬ species of Mycobacterium was recov¬ sion but orchest radiograph residual changed showing cavitation) listed above but the ered, organisms were obtained in 9 patients and poor were believed to be the main infecting results (sputum still positive, chemo¬ agents. ineffective) in 10. Fourteen pa¬ therapy Treatment tients (30%) died (Table I). Eight had Fourteen different antituberculous pulmonary infection that had not been drugs have been used in Canada and controlled by chemotherapy. The con¬ 10 are in current use. There was no dition of the other six had shown some clear-cut pattern of resistance to these improvement with chemotherapy.

patient:

612 CMA JOURNAL/APRIL 3, 1976/VOL. 114

The following two case reports illus¬ trate the effectiveness of chemotherapy in nonpulmonary disease due to atypic¬ al

mycobacteria.

Table I.Data of 14 patients who died from

mycobacteria

Patient no.

Age (yr)

Sex

pulmonary infection with atypical

Organism cultured

Cause of death

Resistance of organism to antituberculous drugs*

Case 1 In a 12-year-old girl enlarged lymph nodes developed on the right side of the neck in January 1970. A biopsy established

the diagnosis of granulomatous disease but there was no response to chemotherapy. Over the next 4 months two successive block dissections were performed; in each instance rapid recurrence of the disease followed. She was admitted to hospital in May 1970 with, again, a large and growing mass in the neck. The organism cultured was M. intracellulare, resistant to every antibiotic except streptomycin and etham¬ butol. These two drugs were given together with INH; resolution and eventual cure resulted. Case 2 In a 40-year-old housewife a 1.5 x 2.0-cm ulcer developed on the front of the left wrist and a small ulcer on the tip of the left index finger. M. marinum (for¬ merly called M. balnei) was cultured. The infection was probably contracted in the local swimming pool, where she swam regularly. The organism was sensitive only to rifampin and ethambutol and large doses of these drugs were given. The ulcer on the wrist was treated by skin grafting at the Toronto General Hospital by Dr. J. Turner, with an excellent result and sound healing.

Discussion Hansen in 1873

the first to M. Koch discovered M. tubercu¬ *PAS para-aminosalicylic acid. INH isoniazid. losis hominis in 1882. M. avium was identified in 1890 and M. bovis in Table II.Classification of mycobacteria, Public Health Laboratory, Toronto 1898. Soon other strains of mycobac¬ Classical M. tuberculosis BCG M. bovis teria were recognized and, by 1920, 40 mycobacteria M. bovis M. avian different species had been documented. Potential clinical significance In 1925, to clarify the situation, tuber¬ Atypical mycobacteria, culosis was defined as a "disease Runyon's Never or rarely significant Always or sometimes significant caused by the tubercle bacillus", and group M. kansasii (high catalase variety) I M. kansasii (low catalase variety) the other mycobacteria were termed M. marinum M. (formerly balnei) either "anonymous", because no def¬ inite names had been given to them, M. scrofulaceum M. gordonae (formerly M. aquae) M. szulgai or "atypical" though this term is clearly a misnomer because every one M. intracellulare M. terrae is, of course, typical of its own strain. M. gastri (formerly Battey bacillus) Little further research was done for M. triviale M. xenopei M. nonchromogenicum 3 decades. The sanatoria were crowded with patients suffering and dying from IV M. fortuitum M. smegmatis tuberculosis. Many were no doubt in¬ M. fortuitum (peregrinum) M. phlei fected with atypical strains, but no one M. chelonei (borstelense) M. vaccae M. diernhoferi had time to worry about matters that M.flavescens were apparently of interest only to re¬ M. rhodochrous search workers in laboratories. Species incertae sedis* Then in the 1950s, when the incid¬ M. africanum ence of tuberculosis began to decrease M. simiae and chemotherapy had become avail¬ able, workers became interested once again in the atypical strains. In 1956 Konno2 showed that only M. tubercu¬ losis hominis, among all the mycobac¬ teria, produced niacin in culture; so, *Species of uncertain clinical significance; these have not been isolated in Canada but appear to be pathogenic for the first time, a highly specific test in tropical countries.

identify leprae.1

a

was

mycobacterium

=

=

CMA JOURNAL/APRIL 3, 1976/VOL. 114 613

was available for this organism. In 1959 Runyon' published his well known classification of the mycobacteria, dividing them into four groups according to cultural characteristics. The current classification of mycobacteria in use at the Public Health Laboratory in Toronto is shown in Table II. The annual report of this laboratory for the year 1972-73 lists 1616 atypical strains identified out of approximately 60 000 specimens submitted for culture because of suspected tuberculosis. In 13 instances more than one strain was cultured from a specimen. Strains that did not conform biochemically to a specific species were simply reported according to Runyon's grouping. A number of publications on the atypical mycobacteria have appeared in Canada. One of the earliest was by Hiltz and Kloss4 in 1968, reporting 46 cases from the Nova Scotia Sanatorium. In 1969 Jeanes, Davies and McKinnon' reported the results of skin testing 24 763 secondary school students and several thousand volunteers across Canada with tuberculin and, simultaneously, Gause, Battey or avian antigens. The frequency of positive reactions to the atypical strains was several times the frequency of positive reactions to tuberculin and this sensitivity was surprisingly uniform across Canada. This was confirmed by Grzybowski, Brown and Stothard in a study conducted in British Columbia.6 In another study conducted in British Columbia Robinson and colleagues7 documented 29 cases of infection with atypical mycobacteria, 18 of pulmonary disease and 11 of cervical adenitis; 6 of the patients with pulmonary disease died. KIotz8 reported 12 cases of atypical mycobacteria in the urine but did not consider the organisms to be pathogenic in the urinary tract. Kahana, Richardson and Cole9 reported six cases illustrating the problems in diagnosis and treatment. Recently much intensive work has been done to determine the nature of mycobacterial species. Stanford and Grange10 examined over 1000 strains in immunodiffusion analyses, allotting the majority to 20 named species. The source of infection with atypical mycobacteria is still unknown, though soil, dust and drinking water have been suspected. It may be that most of these organisms are, in fact, "opportunistic" and will only multiply in tissues already "devitalized". We are always concerned, however, when M. kansasii or M. intracellulare is isolated, for these organisms sometimes appear to possess invasive powers in healthy tissues. Clinical experience has shown, on the other hand, that the infection is not usually contagious, indicating that there must

be some breakdown of host resistance before an infection is acquired. A simplified classification Runyon" appears to have clarified once again the complex and confusing subject of the identification of mycobacteria. He has abandoned his classification by groups and now recognizes only 10 kinds of mycobacterial diseases caused by the following 10 species or species complexes: M. leprae, M. ulcerans, M. tuberculosis complex, M. kansasii, M. marinum, M. simiae, M. szulgai, M. avium-scrofulaceum complex, M. xenopei and M. fortuitum complex. He urges that only the correct species name be used, that subspecies within a species complex no longer need to be clearly defined, that all nonpathogens be placed in a single category, and that many biochemical tests for species identification be discontinued because they have no clinical value. It is suggested that a classification such as Runyon now proposes be considered, so that the difficult and costly process of identification of mycobacterial species may be simplified.

1 thank Miss M. Howes, Public Health Laboratory, Toronto, for the information about the atypical mycobacteria identified in her laboratory, and Dr. N.C. Delarue

for much helpful advice in the preparation of this material. References 1. Principles of Internal Medicine, HARRISON TR (ed), New York, Blakiston, 1950, p 901 2. KoNNo K: New chemical method to differentiate human-type tubercle bacilli from other mycobacteria. Science 124: 985, 1956 3. RUNYON EH: Anonymous mycobacteria in pulmonary disease. Med Clin North Am 43: 273, 1959 4. HILTZ JE, Kioss GA: Mycobacteriosis due to other than M. tuberculosis. Can Med Assoc J 99: 943, 1968 5. JEANES CWL, DAVIES JW, McKINNoN NE: Sensitivity to "atypical" acid-fast mycobacteria in Canada. Can Med Assoc J 100: 888, 1969 6. GRZYBOWSKI 5, BROWN MT, STOTHARD L: Infections with atypical mycobacteria in British Columbia. Ibid, p 896 7. ROBINSON BL, GRZYBOWSKI 5, BOWMER EJ, et al: Atypical mycobacterial disease in British Columbia, 1960-1967. Can Med Assoc J 101: 17, 1969 8. KLOTZ PG: Atypical acid-fast bacteria in urine. Can Med Assoc J 103: 283, 1970 9. KAHANA LM, RICHARDSON H, COLE FM: Clinical aspects of atypical mycobacterial infection. Can Med Assoc J 112: 321, 1975 10. STANFORD JL, GRANGE JM: The meaning and structure of species as applied to mycobacteria. Tubercle 55: 143, 1974 II. RUNYON EH: Ten mycobacterial pathogens. Ibid, p 235

Addendum Since this article was written, the study has been extended to Dec. 31, 1975. In this 6-year period atypical mycobacteria have been recovered from 112 out of 2161 patients admitted consecutively, of whom 62 were suffering from disease caused by the mycobacteria isolated. Sixteen of these 62 patients died and a further 14 responded poorly to chemotherapy.

Evaluation of stroke disability J. JIMENEz,* MD, FRCP[C]; E. KELTZ,t BA, OTR; M.C. STEIN4 BA, DSPA; M.M.E. WHITE,§ PTR

The disabilities resulting from a stroke are not well understood from the epidemiologic or functional point of view. The stroke may impair mental status, perception, sensation, communication and motor ability; the total resulting disability is related to the extent of impairment in each of these areas. A complete evaluation in all these areas has to be done to determine the degree of disability before any rehabilitation program is planned. A comprehensive approach to evaluating stroke disability is presented that includes correlating the degree of impairment in each of the *Professor, department of rehabilitation medicine, University of Toronto; physiatrist-in-chief, department of rehabilitation medicine, Mount Sinai and Baycrest hospitals, Toronto tSupervisor of occupational therapy, .supervisor of speech pathology, §supervisor of physiotherapy, department of rehabilitation medicine, Baycrest Hospital Reprint requests to: Dr. J. Jimenez, Department of rehabilitation medicine, Mount Sinai Hospital, 600 University Ave., Toronto, ON M5G 1X5

614 CMA JOURNAL/APRIL 3, 1976/VOL. 114

above-mentioned areas with the overall functional ability of the patient. D'un point de vue epidemiologique ou fonctionnel, l'invalidite cons6cutive a un accident vasculaire cerebral est mal per9ue. Un accident vasculaire cerebral peut affecter l'etat mental, Ia perception, les sensations, Ia communication et Ia capacite motrice; l'invalidite qui en resulte est proportionnelle a l'etendue de l'atteinte de chacun de ces facteurs. Une evaluation complete de tous les facteurs doit .tre entreprise afin d'6valuer le degre d'invalidite du patient avant de mettre au point un programme de rehabilitation. On presente un moyen d'aborder dans son ensemble l'evaluation de l'invalidite resultant d'un accident vasculaire c6rebral, moyen qui inclue Ia corr6lation du degre d'atteinte de chacun des facteurs enumeres precedemment avec Ia capacite fonctionnelle totale du patient.

Atypical mycobacteria in a tuberculosis hospital.

Cultures from 80 out of 1667 patients (4.8%) admitted consecutively to a tuberculosis hospital grew atypical mycobacteria. With four strict criteria i...
648KB Sizes 0 Downloads 0 Views