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Disseminated Infection with Mycobacterium gordonae: Report of a Case and Critical Review of the Literature Miriam Weinberger, Stacey L. Berg, Irwin M. Feuerstein, Philip A. Pizzo, and Frank G. Witebsky
From the Pediatric Branch, National Cancer Institute, and the Microbiology Service, Clinical Pathology Department, and the Department of Radiology, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland; and the Department of Radiology, Georgetown University, Washington, D.C.
Mycobacterium gordonae (formerly Mycobacterium aquae)
is frequently isolated in diagnostic laboratories but is almost always considered nonpathogenic [1-4]. It is widely distributed in the environment [5] and, as a result of its presence in water sources, has often been involved in nosocomial pseudoinfections and pseudoepidemics [6-1 1]. Our recent experience with a case in which M. gordonae was associated with a true disseminated infection prompted us to review the literature regarding this organism. Methods
Case Report
In the evaluation of the case to be described, two bone marrow specimens were each cultured on three Middlebrook 7H 11 plates (Remel Laboratories, Lanexa, KA); in addition, the first specimen was cultured in a BACTEC 13A bottle (Becton-Dickinson Diagnostic Instrument Systems, Sparks, MD). Blood was cultured in a BACTEC 13A bottle only. Specimens obtained at lung biopsy were ground and then cultured on a Middlebrook 7H 11 slant (Remel) and in a BACTEC 12B bottle (Becton-Dickinson) without PANTA (polymyxin B, amphotericin B, nalidixic acid, trimethoprim,
Received 26 August 1991; revised 14 January 1992. Reprints or correspondence: Dr. Frank G. Witebsky, Microbiology Service, National Institutes of Health, Building 10, Room 2C385, Bethesda, Maryland 20892. Clinical Infectious Diseases 1992;14:1229-39 © 1992 by The University of Chicago. All rights reserved. 1058-4838/92/1406-0008$02.00
and azlocillin). Each of the other specimens was cultured on a Middlebrook 7H 11 slant and in a BACTEC 12B bottle with PANTA; the exception was the CSF specimen, for which no PANTA was added. Urine and gastric aspirate were digested and decontaminated with NaOH and N-acetylcysteine and then concentrated before culture, while CSF was concentrated but not digested and decontaminated. Direct acid-fast smears were prepared with the first bone marrow specimen, the samples obtained at lung biopsy, the gastric aspirate, and one of the urine specimens. Except for the urease test, biochemical tests were performed according to standard methods [12]; the urease test was done with Bacto-Urea R broth (Difco Laboratories, Detroit) by a micromethod developed in our laboratory. A probe for M. gordonae (Gen-Probe, San Diego) was used according to the manufacturer's directions for the identification of the organism from solid medium. Susceptibility testing was performed in our laboratory by the proportion method [12] with use of commercially prepared susceptibility testing plates (DiMed, Roseville, MN). The organism was sent to three reference laboratories for identification and susceptibility testing: Mayo Medical Laboratories, Rochester, MN; the National Jewish Center for Immunology and Respiratory Medicine, Denver; and the Veterans Administration Reference Laboratory for Tuberculosis and Other Mycobacterial Diseases, West Haven, CT. Literature Review
The MEDLINE and BIOSIS data bases were searched in all languages; the key words used were M. gordonae and M.
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Mycobacterium gordonae is only rarely a cause of infection despite its ubiquity in the environment. We describe an 11-year-old girl with disseminated infection due to M. gordonae whose course was complicated by renal failure requiring hemodialysis but who recovered after 15 months of chemotherapy. In a literature search we identified 23 additional cases of infection attributed to M. gordonae, with involvement of the lungs (eight), soft tissue (seven), the peritoneal cavity (three), the cornea (one), and with disseminated disease (five patients, including ours). Two patients were infected with human immunodeficiency virus. We assessed the patterns of infection characteristic of each site and the antibiotic sensitivities of the isolates. Adequate documentation of M. gordonae infection (e.g., amount of growth per culture, detection of specific biochemical characteristics, and confirmation of the organism's identity by a reference center) was lacking in many reports. M. gordonae should not automatically be dismissed as a contaminant when isolated from clinical material. Additional studies are required to establish the extent of this organism's pathogenic role.
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aquae. We included in the final analysis only those case re-
ports that provided information about the patient's history, the source of the M. gordonae isolate, the treatment, and the outcome. Results Case Report
well as wedge-shaped densities at the periphery of the middle right and left lungs. Abdominal sonography showed increased attenuation of the hepatic parenchyma, slightly increased parenchymal echogenicity of the left kidney, and an enlarged spleen (>20 cm) without focal abnormalities. The results of a bone scan were normal. A bone marrow biopsy showed multiple noncaseating granulomas, but no organisms were seen on special staining. The patient underwent an open lung biopsy on day 13 of hospitalization. At the time of surgery, multiple round granular lesions were found to be scattered through both lung fields, and a larger nodule was seen in the superior segment of the right lower lobe. Biopsies were performed on the larger nodule and on three other nodules from the right lower lobe. Histologic studies of all specimens revealed multiple necrotizing granulomas and numerous acid-fast bacilli. Microbiological results. Acid-fast staining of smears of the two lung biopsy specimens sent for microbiological studies revealed rare to few acid-fast bacilli. Acid-fast staining of slides prepared directly from the gastric aspirate, the bone marrow specimen, and one of the urine specimens gave negative results. Bone marrow, gastric aspirate, and lung biopsy specimens (obtained on 5 May, 10 May, and 17 May, respectively) developed a scant to light growth of organisms on solid medium (-10-50 colonies per piece of solid medium); the organism also grew from each specimen cultured in liquid medium. A culture of sputum that had been obtained from the patient at her local hospital yielded a Mycobacterium species; this organism was sent to the microbiology laboratory at the National Institutes of Health for identification. The blood culture, the CSF culture, and three urine cultures yielded no mycobacteria. Smooth, yellow-orange colonies appeared on solid medium after 14-18 days of incubation at 36°C in 8% CO 2 . The colonies were scotochromogenic, and the organism was acid fast upon both auramine-rhodamine and Kinyoun staining. The following biochemical tests were positive: Tween 80 hydrolysis at 5 days, catalase at 68°C, and urease. The semiquantitative test for catalase revealed a value of >45 mm. The following tests were considered negative: arylsulfatase at 3 and 14 days, niacin accumulation, nitrate reduction, iron uptake, and growth on MacConkey agar and on 5% NaCl. A complete biochemical workup was done on the isolates from the bone marrow, from the gastric aspirate, and from one of the two lung biopsy specimens; the results were identical for each isolate. The colonial morphology of the isolate from the second lung biopsy specimen and of the isolate obtained from the patient's sputum at her local hospital was identical to that of the other isolates. The Gen-Probe probe for M. gordonae was applied to each of the three isolates that had been subjected to biochemical workup and to the isolate from the local hospital; the probe gave positive results for all four isolates (27.2%-36.9% hybridization).
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Clinical presentation. An 11-year-old girl was well until October 1988, when she presented to her local hospital in Las Vegas with gross hematuria and a right renal mass. She underwent right radical nephrectomy. The histologic diagnosis was malignancy compatible with papillary renal clear-cell carcinoma with osseous metaplasia. Microscopic examination of the lymph nodes resected from the renal hilum and periaortic area revealed metastatic infiltration. No further therapy was administered. In April 1989 the patient was seen again at her local hospital with a 4-week history of fever to 40°C, fatigue, dry cough, nausea, vomiting, and weight loss (3 kg). New pulmonary lesions were found by computed tomography of the chest, and the patient was referred to the National Cancer Institute for further evaluation. At admission on 4 May 1989, the patient was noted to be a well-developed girl who appeared ill and had a temperature of 40°C. The findings on physical examination were unremarkable. The patient had an indwelling single-lumen Hickman-Broviac catheter that had been inserted at the time of her nephrectomy in October 1988. Examination of the exit site revealed no signs of infection. Laboratory studies yielded the following values: hemoglobin, 71 g/L (7.1 g/dL); white blood cell count 2.1 X 10 9/L (68% neutrophils, 7% band forms, 4% mononuclear cells, and 21% lymphocytes); platelet count, 154 X 10 9/L; blood urea nitrogen (BUN), 5.4 mmol/L (15 mg/dL); serum creatinine, 114.9 Amol/L (1.3 mg/dL); bilirubin, 6.8 Armol/L (0.4 mg/dL); alkaline phosphatase, 600 U/L (normal, 3 months. In four cases the duration of therapy ranged from 9 to 22 months (median, 15 months); in a single instance (case 11) treatment was given intermittently for 8 years. None of these cases was cured; in four the findings on chest roentgenogram improved and the disease stabilized, while in the fifth the disease progressed despite therapy during 8 years of follow-up. In three of these cases, sputum cultures first were positive and then became negative within 5-12 months of the initiation of therapy; in a fourth all cultures of sputum samples obtained during treatment were negative. Sputum conversion to negative was noted in the case of an additional patient (case 8), who received only 2 weeks of antimycobacterial chemotherapy; this patient subsequently stopped taking his medications, and his sputum specimens again became positive. Three of the eight patients with pulmonary infection died. One patient (case 7), who had several sputum specimens positive for M. gordonae, died 10 weeks after diagnosis; autopsy revealed findings suggestive of mycobacterial disease, but samples of lung tissue for mycobacterial cultures apparently were not obtained. A second patient (case 12) died shortly after the open lung biopsy that revealed a process compatible with mycobacterial infection; culture of tissue obtained during this procedure yielded M. gordonae. The death of a third patient (case 8) was presumably caused by concurrent small-cell lung carcinoma. Patients with soft-tissue infection involving the extremities, who ranged in age from 30 to 70 years (median, 40 years), were predominantly women (five of seven cases). In six cases the infection involved an upper extremity (the hand in four instances and the elbow in two). Both the sole of the foot and the wrist were involved in one case; at the latter site the infection was thought to have been caused by autoinoculation. Except in this last case, no systemic symptoms were reported. The presenting symptoms were a function of the site of involvement: patients with infection of the hand pre-
sented with one or two subcutaneous nodules, and those with elbow involvement presented with swelling. Chronic draining ulcers developed in two cases, one of olecranon bursitis after a surgical procedure (case 16) and one of penetrating trauma to the sole of the foot (case 18). In one instance (case 20), the presentation also included impaired voluntary flexion of the fingers secondary to rupture of the tendon of the flexor digitorum longus muscle. Altogether, three patients (cases 17-19) had a history of penetrating trauma, and one (case 20) had underlying immunosuppression. Treatment consisted of surgery in two cases, antimycobacterial chemotherapy in two, and both surgery and chemotherapy in three; one of the last group of patients (case 17) underwent biopsy only and received only 2 weeks of chemotherapy. Five infections were cured: one with surgery alone, two with chemotherapy alone, and two with both chemotherapy and surgery. One patient (case 20) with bilateral transplanted kidneys and chronic rejection died shortly after diagnosis as a result of her underlying renal disease. Peritonitis was described in three patients whose ages ranged from 28 to 39 years (median, 36 years). In one case the infection involved the liver. Fever, weight loss, and hepatomegaly were noted at presentation in all three cases. One patient was undergoing chronic ambulatory peritoneal dialysis, which may have provided the portal of entry for M. gordonae. Two patients recovered after receiving combination antimycobacterial chemotherapy for at least 6-9 months. One patient with HIV infection (case 23) died, presumably of a brain lesion; no autopsy was done. A single patient with chronic keratitis, who probably came into contact with M. gordonae while cutting weeds, has been described. His infection had a chronic progressive course for 3 years and was definitively treated with penetrating keratoplasty. The in vitro sensitivities of the M. gordonae isolates to various antimycobacterial drugs were reported in 19 cases
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Lamellar corneal biopsy: few inflammatory cells
Radiodiagnostic studies
Weinberger et al.
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Table 3. Antibiotic sensitivity patterns in 19 isolates of M. gordonae. Result for isolate from indicated case no. 1
2
4
5
8
9
10
11
12
13
15
16
17
18
Isoniazid Ethambutol Rifampin Streptomycin Kanamycin Amikacin PAS Ethionamide Ansamycin Cycloserine Capreomycin Clofazimine Ciprofloxacin TMP-SMZ
R E SS E R E S S S — — S — R
E S E E S — R R
R ER S R S S ES S RS S S S R S S -
R R S
R R S
R R R R R -
R S R S
S
— —
R R S S RS — — — — S — — R — — — — S -
—
—
S —S S S — S R — — R R — — — R R — —
R S S R
S S
R S R S S — R S — S
S S
6
—
-
—
-
— — — —
S S
—
_ -
—
R S S —
— R
—
R — —
19
21
22
R R ES S S S S — — E — S — —
24 —
S S S S S — —
—
—
—
—
—
—
—
—
—
—
—
—
-
S
NOTE. Abbreviations: PAS = p-aminosalicylic acid; TMP-SMZ = trimethoprim-sulfamethoxazole; R = resistant, S = sensitive, and E = equivocal (the organism was sensitive according to one reference center but resistant according to another, or the organism was sensitive when tested at a higher drug concentration but resistant at a lower drug concentration). A minus sign indicates that testing was not done.
(table 3). It is not surprising that the methods of sensitivity testing differed among the various centers, as there is no standardized procedure for such testing of this organism. M. gordonae was generally resistant to isoniazid (76%) and to paminosalicylic acid (64%). Seventy-two percent of isolates were sensitive to ethambutol, 61% to rifampin, 88% to cycloserine, 71% to kanamycin, and 54% to streptomycin. All of three isolates tested were found to be sensitive to amikacin. One isolate each was tested against ciprofloxacin, trimethoprim-sulfamethoxazole, and ansamycin; all were sensitive. Equivocal results were obtained with some antimycobacterial agents tested against some isolates. Systemic antimycobacterial chemotherapy was initiated in a total of 20 cases. Ethambutol was included in 18 (90%) of the drug regimens, rifampin in 17 (85%), and isoniazid in 14 (70%). Aminoglycosides were used only infrequently: streptomycin in four cases, amikacin (systemic) in two, and kanamycin in one. Although 13 patients (54%) received a regimen that included three or more drugs, a number of the organisms isolated from these patients were resistant in vitro to one drug (three isolates), two drugs (three isolates), or even four drugs (one isolate, case 11) in the combination. Biochemical characteristics were reported for the M. gordonae isolates from 11 patients (46%; cases 3, 5, 6, 8-10, 12, 13, 18, 21, and 22). All 11 isolates gave a positive result for Tween 80 hydrolysis, all of six for catalase (with testing assumed to have been done at 68°C because it was not specified as semiquantitative), both of two for semiquantitative catalase, three (43%) of seven for urease, and one (33%) of three for arylsulfatase. None of the isolates reduced nitrate (10 tested) or produced niacin (five tested). The results of
the biochemical tests appeared typical for M. gordonae [12], except for a somewhat high frequency of urease positivity. Discussion M. gordonae is ubiquitous in the environment and is commonly isolated from soil and water sources, including house dust and tap water [5]. In addition, the occurrence of M. gordonae in the hospital environment, especially in water sources, has been documented repeatedly [6-10, 41]. In some studies the organism was traced to a water source after an increased rate of isolation from clinical material prompted an epidemiological investigation [6, 7, 9, 10]. A cluster of isolates of M. gordonae from bronchoscopy specimens was traced to a contaminated dye solution that was added to the topical anesthetic used before the procedure [8]. Likewise, a commercial antimicrobial powder (PANTA) widely used in the BACTEC procedure for the decontamination of specimens from nonsterile sites upon their submission for mycobacterial culture was found to be contaminated by M. gordonae [11]. These reports all testify to the fact that M. gordonae is widespread in the environment and can easily be introduced into clinical specimens during collection or processing. Such contamination has taken place as the consequence of either incidental colonization of the oropharynx [6, 8, 9] or direct inoculation of the specimen [7, 10, 11]. The relative rarity of reported cases of disease attributed to M. gordonae despite widespread exposure of humans to the organism is indicative of the relatively low pathogenicity of this species. Because M. gordonae is ubiquitous, is relatively nonpathogenic, and is notorious for contaminating clinical
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Drug
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Disseminated Infection with M. gordonae
(42%), and only about 10 isolates (42%) had their identity as M. gordonae confirmed by a reference laboratory.
The ability to obtain multiple positive specimens is determined by the site of infection. For example, in the reviewed cases of soft-tissue infection of an extremity or keratitis, the infection was confined to a small area that was completely resected when the initial diagnostic specimen was obtained. However, multiple positive specimens were obtained in the majority of the other cases, including all five cases of disseminated disease, six of eight cases of pulmonary disease, and one of three cases of peritoneal disease. Similarly, acid-fast organisms were observed in smears or histologic specimens in the majority of cases, including all five cases of disseminated disease, six of eight cases of pulmonary disease, six of seven cases of soft-tissue infection, two of three cases of peritonitis, and the one case of keratitis. In addition, granulomas and/or giant cells were observed in 12 cases (table 2). Of note, the culture of the corneal biopsy specimen from the patient with keratitis (case 24) reportedly yielded only one colony of M. gordonae, although acid-fast organisms were also found in histologic studies. Thus it is possible that M. gordonae was only a contaminant in this case, while the true pathogen was not isolated. The response to treatment and the elimination of the organism were also related to the site of infection. Pulmonary disease was not cured but rather ran a chronic course. However, the organism was eliminated from the sputum of four of the five patients with pulmonary disease who survived for >6 months. Soft-tissue infections were frequently cured, but elimination of the organism from clinical specimens was more difficult to demonstrate since the site of infection was sometimes completely resected during the initial diagnostic procedure or during treatment. The discrepancy between the elimination of M. gordonae from the sputum of some patients with pulmonary infection and the chronic course of their disease raises the question of colonization, with another etiology of the underlying pulmonary process [44]. Unfortunately, lung tissue (studies of which revealed granuloma formation) was obtained from only two patients (cases 7 and 12); M. gordonae was isolated from only one of these two lung specimens. In the other six cases, histologic documentation of invasive disease was not reported. The experience culled from the 24 reported cases provides an opportunity to assess some of the features of M. gordonae infection. Generally, patients with the same site of involvement had similar patterns of infection. Patients with pulmonary infections were older, were most often male, and had underlying pulmonary abnormalities. Their sputum became negative for M. gordonae during treatment, but their pulmonary disease manifested a chronic course. Patients with soft-tissue infection were younger, and most were female. These patients seldom had systemic symptoms
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specimens, any disease attributed to this organism must be carefully documented. Furthermore, chronic colonization by M. gordonae has been suggested [4, 34] and should be ruled out before the organism is assigned an etiologic role in a given disease process. The following criteria may be helpful in establishing the diagnosis of a true infection caused by M. gordonae: multiple isolations of the organism from the same body site or from different body sites; the detection of the organism in smears or in histologic sections; the growth of the organism from culture of a single specimen on several different media; the presence of multiple colonies on each culture medium; the presence of a clinical illness and/or a histopathological process consistent with a mycobacterial etiology; the response of the clinical illness and/or the histopathological process to appropriate antimycobacterial therapy; and the elimination of the organism from clinical specimens as the clinical condition improves. Some of these criteria are similar to those suggested by other researchers [17-19, 42, 43]. In light of the variability of the clinical conditions that are potentially attributable to M. gordonae, these criteria should not be applied rigidly but rather should serve as guidelines. In addition, since M. gordonae is a rare cause of disease, it is important that reports of infections attributed to this organism document how it was identified by stating the results of the specific biochemical tests used, preferably with confirmation by a reference laboratory. In the case we describe herein, disseminated infection with M. gordonae was well documented. The organism was both isolated from and observed in several specimens from multiple sources, and it was grown on various media. The results of histologic studies were compatible with mycobacterial disease, and the infection responded to antimycobacterial therapy. The biochemical characteristics of the patient's isolate were typical for M. gordonae except for urease positivity, and the identity of the organism was confirmed by three reference laboratories. M. gordonae was isolated from a bone marrow specimen to which PANTA was not added. It was also isolated in solid medium (without added PANTA) from every specimen positive in liquid medium (with added PANTA). At the time that the specimens from our patient were being cultured, the rate of isolation of M. gordonae did not increase in our laboratory. These facts eliminate the PANTA solution as the source of the organism. In recent years an increasing number of infections with M. gordonae have been reported, but many of them have been poorly documented [34-40]. Of the 24 cases described in tables 1 and 2, many did not fulfill all the criteria suggested above. The approximate amount of mycobacterial growth was noted in only eight cases (33%), and more than one positive culture was reported in only 13 cases (54%). Results of some biochemical tests were presented for only 10 isolates
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pecially in pulmonary infections. More detailed reporting may help to establish the relation between the isolation of M. gordonae from a clinical specimen and an infectious process in a given patient and to determine the true incidence of infection with this organism. References
1. Runyon EH. Anonymous mycobacteria in pulmonary disease. Med Clin North Am 1959;43:273-90. 2. Woods GL, Washington JA II. Mycobacteria other than Mycobacterium tuberculosis: review of microbiologic and clinical aspects. Rev Infect Dis 1987;9:275-94. 3. Berlin OGW. Mycobacteria. In: Baron EJ, Finegold SM, eds. Bailey and Scott's diagnostic microbiology. 8th ed. St. Louis: CV Mosby, 1990;597-640. 4. Wolinsky E. Nontuberculous mycobacteria and associated diseases. In: Kubica GP, Wayne LG, eds. The mycobacteria. A sourcebook. Part B. New York: Marcel Dekker, 1984; l 141-207. 5. Tsukamura M. The "non-pathogenic" species of mycobacteria: their distribution and ecology in non-living reservoirs. In: Kubica GP, Wayne LG, eds. The mycobacteria. A sourcebook. Part B. New York: Marcel Dekker, 1984;1339-59. 6. Gangadharam PRJ, Lockhart JA, Awe RJ, Jenkins DE. Mycobacterial contamination through tap water [letter]. Am Rev Respir Dis 1976;113:894. 7. Dizon D, Mihailescu C, Bae HC. Simple procedure for detection of Mycobacterium gordonae in water causing false-positive acid-fast smears. J Clin Microbiol 1976;3:21 I. 8. Steere AC, Corrales J, von Graevenitz A. A cluster of Mycobacterium gordonae isolates from bronchoscopy specimens. Am Rev Respir Dis 1979;120:214-6. 9. Panwalker AP, Fuhse E. Nosocomial Mycobacterium gordonae pseudoinfection from contaminated ice machines. Infect Control 1986;7:67-70. 10. Stine TM, Harris AA, Levin S, Rivera N, Kaplan RL. A pseudoepidemic due to atypical mycobacteria in a hospital water supply. JAMA 1987;258:809- l 1. 1 1. Tokars J1, McNeil MM, Tablan OC, et al. Mycobacterium gordonae pseudoinfection associated with a contaminated antimicrobial solution. J Clin Microbiol 1990;28:2765-9. 12. Kent PT, Kubica GP. Public health mycobacteriology. A guide for the level III laboratory. Atlanta: Centers for Disease Control, 1985:71120. 13. Gonzales EP, Crosby RMN, Walker SH. Mycobacterium aquae infection in a hydrocephalic child (Mycobacterium aquae meningitis). Pediatrics 1971;48:974-7. 14. Lohr DC, Goeken JA, Doty DB, Donta ST. Mycobacterium gordonae infection of a prosthetic aortic valve. JAMA 1978;239:1528-30. 15. Chan J, McKitrick JC, Klein RS. Mycobacterium gordonae in the acquired immunodeficiency syndrome [letter]. Ann Intern Med 1984;101:400. 16. Turner DM, Ramsey PG, Ojemann GA, Ralph DD. Disseminated Mycobacterium gordonae infection associated with glomerulonephritis. West J Med 1985;142:391-3. 17. Kumar UN, Varkey B. Pulmonary infection caused by Mycobacterium gordonae. Br J Dis Chest 1980;74:189-92. 18. Craig CP, Kreitzer SM. Non-tuberculous mycobacterial infections: human infections due to Mycobacterium gordonae. Infectious Disease Reviews 1980;6:79-88. 19. Clague H, Hopkins CA, Roberts C, Jenkins PA. Pulmonary infection with Mycobacterium gordonae in the presence of bronchial carcinoma. Tubercle 1985;66:61-3.
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or underlying diseases and responded favorably to treatment (surgery and/or chemotherapy). About half of this group had a history of penetrating trauma. Disseminated infection with M. gordonae developed in four patients with no underlying immunologic deficiency and in one patient with AIDS. All four immunocompetent patients had a foreign body in place; in three instances (cases 1, 2, and 4), this device was considered to be the portal of entry and the source for continuous shedding of M. gordonae. In our patient (case 5), an indwelling Hickman-Broviac catheter, which had been in place for 6 months, could have served as the portal of entry. However, the blood drawn through the line yielded no mycobacteria, and the exit site appeared normal on examination. It is possible that M. gordonae was introduced in this case during abdominal surgery 6 months before presentation. Removal of the foreign body appeared necessary for a successful outcome in the three cases (cases 1, 2, and 4). The foreign body remained in place in our case and apparently did not interfere with clinical or microbiological cure. The group of patients with peritonitis was small and heterogeneous. One of the three patients was undergoing chronic ambulatory peritoneal dialysis, which may have provided the portal of entry for M. gordonae [31]. The single case of keratitis had a chronic course and responded to surgical therapy. Overall, the outcome of infection with M. gordonae was related to the site of involvement and to the underlying disease. Patients with pulmonary infections had the poorest outcome. Three of these eight patients died, and two of these deaths (cases 7 and 12) may have been attributable to M. gordonae infection. No cures were reported in this group. Patients infected at other sites had a better outcome, with only three deaths, all due to underlying disease. Two patients (cases 3 and 23; 8%) had HIV infection. The small number of cases and the lack of complete clinical information make it impossible to determine whether infection with M. gordonae had any effect on the course and prognosis of HIV disease. Several authors have recently reported the isolation of M. gordonae from patients with AIDS or AIDSrelated complex [37, 45-47]. Although the clinical and microbiological data are incomplete, these reports suggest the possibility of an increasing role for M. gordonae as an opportunistic pathogen in AIDS. In summary, M. gordonae, despite its ubiquity in the environment, is only rarely a cause of infection. However, as is evident from our case report and review of the literature, M. gordonae can cause disease of widely varying severity and should not be dismissed automatically as a contaminant when isolated from clinical material. The clinical presentation, course, and outcome of infection with M. gordonae are a function of the site of involvement. Data substantiating the identification of M. gordonae or documenting the infection are frequently lacking. Histologic documentation may help to distinguish between colonization and invasive disease, es-
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35. Merchant R, Irani A, Shah UC, Daftary D, Sharma J, Joshi L. Disseminated non-tuberculous mycobacteriosis due to atypical type II-Mycobacteria gordonoe [sic]. Indian J Pediatr 1984;51:295-7. 36. Barnett SM. CT findings in tuberculous mediastinitis. J Comput Assist Tomogr 1986;10:165-6. 37. Bourgoignie JJ. Renal complications of human immunodeficiency virus type I. Kidney Int 1990;37:1571-84. 38. Sutker WL, Lankford LL, Tompsett R. Granulomatous synovitis: the role of atypical mycobacteria. Rev Infect Dis 1979;1:729-35. 39. Gribetz AR, Damsker B, Bottone EJ, Kirschner PA, Teirstein AS. Solitary pulmonary nodules due to nontuberculous mycobacterial infection. Am J Med 1981;70:39-43. 40. Marchevsky A, Damsker B, Gribetz A, Tepper S, Geller SA. The spectrum of pathology of nontuberculous mycobacterial infections in open-lung biopsy specimens. Am J Clin Pathol 1982;78:695-700. 41. Pelletier PA, du Moulin GC, Stottmeier KD. Prevalence of mycobacteria in a renal dialysis water system [abstract no L-12]. In: Abstracts of the annual meeting of the American Society for Microbiology. Washington, DC: American Society for Microbiology, 1988;413. 42. Jenkins DE. Recent clinical studies in the United States on atypical acid-fast bacilli. Bull Int Union Tuberc 1959;29:295-307. 43. Yamamoto M, Ogura Y, Sudo K, Hibino S. Diagnostic criteria for disease caused by atypical mycobacteria. Am Rev Respir Dis 1967;96:773-8. 44. Ahn CH, McLarty JW, Ahn SS, Ahn SI, Hurst GA. Diagnostic criteria for pulmonary disease caused by Mycobacterium kansasii and Mycobacterium intracellulare. Am Rev Respir Dis 1982;125:388-91. 45. Horsburgh CR Jr, Selik RM. The epidemiology of disseminated nontuberculous mycobacterial infection in the acquired immunodeficiency syndrome (AIDS). Am Rev Respir Dis 1989;139:4-7. 46. Ardito F, Damiano F, Venturi G, Archibusacci C, Nacci A. L'emocoltura nelle infezioni dell'immunodepresso. L'Igiene Moderna 1990;93:91-102. 47. Barber TW, Farber HW. Invasive Mycobacterium gordonae in patients seropositive for human immunodeficiency virus [abstract no 2126]. In: Final program and abstracts of the Sixth International Conference on AIDS. Marlow Heights, Maryland: Center for International Research, U.S. Bureau of the Census, 1990:385.
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20. Douglas JG, Calder MA, Choo-Kang YFJ, Leitch AG. Mycobacterium gordonae: a new pathogen? Thorax 1986;41:152-3. 21. Guarderas J, Alvarez S, Berk SL. Progressive pulmonary disease caused by Mycobacterium gordonae. South Med J 1986;79:505-7. 22. Aguado JM, GOmez-Garces JL, Manrique A, Soriano F. Pulmonary infection by Mycobacterium gordonae in an immunocompromised patient. Diagn Microbiol Infect Dis 1987;7:261-3. 23. de Gracia J, Vidal R, Martin N, Bravo C, Gonzalez T, Riba A. Pulmonary disease caused by Mycobacterium gordonae. Tubercle 1989;70:135-7. 24. Berman LB. Infection of synovial tissue by Mycobacterium gordonae [letter]. Can Med Assoc J 1983;129:1078 9. 25. Lorber B, Suh B. Bursitis caused by Mycobacterium gordonae: is surgery necessary? Am Rev Respir Dis 1983;128:565-6. 26. Shelley WB, Folkens AT. Mycobacterium gordonae infection of the hand. Arch Dermatol 1984;120:1064-5. 27. McIntyre P, Blacklock Z, McCormack JG. Cutaneous infection with Mycobacterium gordonae. J Infect 1987;14:71-8. 28. Gengoux P, Portaels F, Lachapelle JM, Minnikin DE, Tennstedt D, Tamigneau P. Skin granulomas due to Mycobacterium gordonae. Int J Dermatol 1987;26:181-4. 29. Nakagawa S. The flexor digitorum profundus tendon rupture caused by Mycobacterium gordonae tenosynovitis in a renal transplant recipient. Rin Sei Ge 1990;25:665-8. 30. Kurnik PB, Padmanabh U, Bonatsos C, Cynamon MH. Mycobacterium gordonae as a human hepato-peritoneal pathogen, with a review of the literature. Am J Med Sci 1983;285:45-8. 31. London RD, Damsker B, Neibart EP, Knorr B, Bottone EJ. Mycobacterium gordonae: an unusual peritoneal pathogen in a patient undergoing continuous ambulatory peritoneal dialysis. Am J Med 1988; 85:703-4. 32. Carcaba V, Carton JA, Fernandez LeOn A, de Diego I. Peritonitis por Mycobacterium gordonae en un paciente infectado por el virus de la immunodeficiencia humana. Med Clin (Bart) 1989;93:598. 33. Moore MB, Newton C, Kaufman HE. Chronic keratitis caused by Mycobacterium gordonae. Am J Ophthalmol 1986;102:516-21. 34. Kubala E. Some aspects of diseases caused by atypical mycobacteria. Scandinavian Journal of Respiratory Diseases [Supplement] 1972;80:11-6.
1239
Disseminated Infection with Mycobacterium gordonae: Report of a Case and Critical Review of the Literature Miriam Weinberger, Stacey L. Berg, Irwin M. Feuerstein, Philip A. Pizzo, and Frank G. Witebsky
From the Pediatric Branch, National Cancer Institute, and the Microbiology Service, Clinical Pathology Department, and the Department of Radiology, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland; and the Department of Radiology, Georgetown University, Washington, D.C.
Mycobacterium gordonae (formerly Mycobacterium aquae)
is frequently isolated in diagnostic laboratories but is almost always considered nonpathogenic [1-4]. It is widely distributed in the environment [5] and, as a result of its presence in water sources, has often been involved in nosocomial pseudoinfections and pseudoepidemics [6-1 1]. Our recent experience with a case in which M. gordonae was associated with a true disseminated infection prompted us to review the literature regarding this organism. Methods
Case Report
In the evaluation of the case to be described, two bone marrow specimens were each cultured on three Middlebrook 7H 11 plates (Remel Laboratories, Lanexa, KA); in addition, the first specimen was cultured in a BACTEC 13A bottle (Becton-Dickinson Diagnostic Instrument Systems, Sparks, MD). Blood was cultured in a BACTEC 13A bottle only. Specimens obtained at lung biopsy were ground and then cultured on a Middlebrook 7H 11 slant (Remel) and in a BACTEC 12B bottle (Becton-Dickinson) without PANTA (polymyxin B, amphotericin B, nalidixic acid, trimethoprim,
Received 26 August 1991; revised 14 January 1992. Reprints or correspondence: Dr. Frank G. Witebsky, Microbiology Service, National Institutes of Health, Building 10, Room 2C385, Bethesda, Maryland 20892. Clinical Infectious Diseases 1992;14:1229-39 © 1992 by The University of Chicago. All rights reserved. 1058-4838/92/1406-0008$02.00
and azlocillin). Each of the other specimens was cultured on a Middlebrook 7H 11 slant and in a BACTEC 12B bottle with PANTA; the exception was the CSF specimen, for which no PANTA was added. Urine and gastric aspirate were digested and decontaminated with NaOH and N-acetylcysteine and then concentrated before culture, while CSF was concentrated but not digested and decontaminated. Direct acid-fast smears were prepared with the first bone marrow specimen, the samples obtained at lung biopsy, the gastric aspirate, and one of the urine specimens. Except for the urease test, biochemical tests were performed according to standard methods [12]; the urease test was done with Bacto-Urea R broth (Difco Laboratories, Detroit) by a micromethod developed in our laboratory. A probe for M. gordonae (Gen-Probe, San Diego) was used according to the manufacturer's directions for the identification of the organism from solid medium. Susceptibility testing was performed in our laboratory by the proportion method [12] with use of commercially prepared susceptibility testing plates (DiMed, Roseville, MN). The organism was sent to three reference laboratories for identification and susceptibility testing: Mayo Medical Laboratories, Rochester, MN; the National Jewish Center for Immunology and Respiratory Medicine, Denver; and the Veterans Administration Reference Laboratory for Tuberculosis and Other Mycobacterial Diseases, West Haven, CT. Literature Review
The MEDLINE and BIOSIS data bases were searched in all languages; the key words used were M. gordonae and M.
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Mycobacterium gordonae is only rarely a cause of infection despite its ubiquity in the environment. We describe an 11-year-old girl with disseminated infection due to M. gordonae whose course was complicated by renal failure requiring hemodialysis but who recovered after 15 months of chemotherapy. In a literature search we identified 23 additional cases of infection attributed to M. gordonae, with involvement of the lungs (eight), soft tissue (seven), the peritoneal cavity (three), the cornea (one), and with disseminated disease (five patients, including ours). Two patients were infected with human immunodeficiency virus. We assessed the patterns of infection characteristic of each site and the antibiotic sensitivities of the isolates. Adequate documentation of M. gordonae infection (e.g., amount of growth per culture, detection of specific biochemical characteristics, and confirmation of the organism's identity by a reference center) was lacking in many reports. M. gordonae should not automatically be dismissed as a contaminant when isolated from clinical material. Additional studies are required to establish the extent of this organism's pathogenic role.
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aquae. We included in the final analysis only those case re-
ports that provided information about the patient's history, the source of the M. gordonae isolate, the treatment, and the outcome. Results Case Report
well as wedge-shaped densities at the periphery of the middle right and left lungs. Abdominal sonography showed increased attenuation of the hepatic parenchyma, slightly increased parenchymal echogenicity of the left kidney, and an enlarged spleen (>20 cm) without focal abnormalities. The results of a bone scan were normal. A bone marrow biopsy showed multiple noncaseating granulomas, but no organisms were seen on special staining. The patient underwent an open lung biopsy on day 13 of hospitalization. At the time of surgery, multiple round granular lesions were found to be scattered through both lung fields, and a larger nodule was seen in the superior segment of the right lower lobe. Biopsies were performed on the larger nodule and on three other nodules from the right lower lobe. Histologic studies of all specimens revealed multiple necrotizing granulomas and numerous acid-fast bacilli. Microbiological results. Acid-fast staining of smears of the two lung biopsy specimens sent for microbiological studies revealed rare to few acid-fast bacilli. Acid-fast staining of slides prepared directly from the gastric aspirate, the bone marrow specimen, and one of the urine specimens gave negative results. Bone marrow, gastric aspirate, and lung biopsy specimens (obtained on 5 May, 10 May, and 17 May, respectively) developed a scant to light growth of organisms on solid medium (-10-50 colonies per piece of solid medium); the organism also grew from each specimen cultured in liquid medium. A culture of sputum that had been obtained from the patient at her local hospital yielded a Mycobacterium species; this organism was sent to the microbiology laboratory at the National Institutes of Health for identification. The blood culture, the CSF culture, and three urine cultures yielded no mycobacteria. Smooth, yellow-orange colonies appeared on solid medium after 14-18 days of incubation at 36°C in 8% CO 2 . The colonies were scotochromogenic, and the organism was acid fast upon both auramine-rhodamine and Kinyoun staining. The following biochemical tests were positive: Tween 80 hydrolysis at 5 days, catalase at 68°C, and urease. The semiquantitative test for catalase revealed a value of >45 mm. The following tests were considered negative: arylsulfatase at 3 and 14 days, niacin accumulation, nitrate reduction, iron uptake, and growth on MacConkey agar and on 5% NaCl. A complete biochemical workup was done on the isolates from the bone marrow, from the gastric aspirate, and from one of the two lung biopsy specimens; the results were identical for each isolate. The colonial morphology of the isolate from the second lung biopsy specimen and of the isolate obtained from the patient's sputum at her local hospital was identical to that of the other isolates. The Gen-Probe probe for M. gordonae was applied to each of the three isolates that had been subjected to biochemical workup and to the isolate from the local hospital; the probe gave positive results for all four isolates (27.2%-36.9% hybridization).
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Clinical presentation. An 11-year-old girl was well until October 1988, when she presented to her local hospital in Las Vegas with gross hematuria and a right renal mass. She underwent right radical nephrectomy. The histologic diagnosis was malignancy compatible with papillary renal clear-cell carcinoma with osseous metaplasia. Microscopic examination of the lymph nodes resected from the renal hilum and periaortic area revealed metastatic infiltration. No further therapy was administered. In April 1989 the patient was seen again at her local hospital with a 4-week history of fever to 40°C, fatigue, dry cough, nausea, vomiting, and weight loss (3 kg). New pulmonary lesions were found by computed tomography of the chest, and the patient was referred to the National Cancer Institute for further evaluation. At admission on 4 May 1989, the patient was noted to be a well-developed girl who appeared ill and had a temperature of 40°C. The findings on physical examination were unremarkable. The patient had an indwelling single-lumen Hickman-Broviac catheter that had been inserted at the time of her nephrectomy in October 1988. Examination of the exit site revealed no signs of infection. Laboratory studies yielded the following values: hemoglobin, 71 g/L (7.1 g/dL); white blood cell count 2.1 X 10 9/L (68% neutrophils, 7% band forms, 4% mononuclear cells, and 21% lymphocytes); platelet count, 154 X 10 9/L; blood urea nitrogen (BUN), 5.4 mmol/L (15 mg/dL); serum creatinine, 114.9 Amol/L (1.3 mg/dL); bilirubin, 6.8 Armol/L (0.4 mg/dL); alkaline phosphatase, 600 U/L (normal, 3 months. In four cases the duration of therapy ranged from 9 to 22 months (median, 15 months); in a single instance (case 11) treatment was given intermittently for 8 years. None of these cases was cured; in four the findings on chest roentgenogram improved and the disease stabilized, while in the fifth the disease progressed despite therapy during 8 years of follow-up. In three of these cases, sputum cultures first were positive and then became negative within 5-12 months of the initiation of therapy; in a fourth all cultures of sputum samples obtained during treatment were negative. Sputum conversion to negative was noted in the case of an additional patient (case 8), who received only 2 weeks of antimycobacterial chemotherapy; this patient subsequently stopped taking his medications, and his sputum specimens again became positive. Three of the eight patients with pulmonary infection died. One patient (case 7), who had several sputum specimens positive for M. gordonae, died 10 weeks after diagnosis; autopsy revealed findings suggestive of mycobacterial disease, but samples of lung tissue for mycobacterial cultures apparently were not obtained. A second patient (case 12) died shortly after the open lung biopsy that revealed a process compatible with mycobacterial infection; culture of tissue obtained during this procedure yielded M. gordonae. The death of a third patient (case 8) was presumably caused by concurrent small-cell lung carcinoma. Patients with soft-tissue infection involving the extremities, who ranged in age from 30 to 70 years (median, 40 years), were predominantly women (five of seven cases). In six cases the infection involved an upper extremity (the hand in four instances and the elbow in two). Both the sole of the foot and the wrist were involved in one case; at the latter site the infection was thought to have been caused by autoinoculation. Except in this last case, no systemic symptoms were reported. The presenting symptoms were a function of the site of involvement: patients with infection of the hand pre-
sented with one or two subcutaneous nodules, and those with elbow involvement presented with swelling. Chronic draining ulcers developed in two cases, one of olecranon bursitis after a surgical procedure (case 16) and one of penetrating trauma to the sole of the foot (case 18). In one instance (case 20), the presentation also included impaired voluntary flexion of the fingers secondary to rupture of the tendon of the flexor digitorum longus muscle. Altogether, three patients (cases 17-19) had a history of penetrating trauma, and one (case 20) had underlying immunosuppression. Treatment consisted of surgery in two cases, antimycobacterial chemotherapy in two, and both surgery and chemotherapy in three; one of the last group of patients (case 17) underwent biopsy only and received only 2 weeks of chemotherapy. Five infections were cured: one with surgery alone, two with chemotherapy alone, and two with both chemotherapy and surgery. One patient (case 20) with bilateral transplanted kidneys and chronic rejection died shortly after diagnosis as a result of her underlying renal disease. Peritonitis was described in three patients whose ages ranged from 28 to 39 years (median, 36 years). In one case the infection involved the liver. Fever, weight loss, and hepatomegaly were noted at presentation in all three cases. One patient was undergoing chronic ambulatory peritoneal dialysis, which may have provided the portal of entry for M. gordonae. Two patients recovered after receiving combination antimycobacterial chemotherapy for at least 6-9 months. One patient with HIV infection (case 23) died, presumably of a brain lesion; no autopsy was done. A single patient with chronic keratitis, who probably came into contact with M. gordonae while cutting weeds, has been described. His infection had a chronic progressive course for 3 years and was definitively treated with penetrating keratoplasty. The in vitro sensitivities of the M. gordonae isolates to various antimycobacterial drugs were reported in 19 cases
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Lamellar corneal biopsy: few inflammatory cells
Radiodiagnostic studies
Weinberger et al.
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Table 3. Antibiotic sensitivity patterns in 19 isolates of M. gordonae. Result for isolate from indicated case no. 1
2
4
5
8
9
10
11
12
13
15
16
17
18
Isoniazid Ethambutol Rifampin Streptomycin Kanamycin Amikacin PAS Ethionamide Ansamycin Cycloserine Capreomycin Clofazimine Ciprofloxacin TMP-SMZ
R E SS E R E S S S — — S — R
E S E E S — R R
R ER S R S S ES S RS S S S R S S -
R R S
R R S
R R R R R -
R S R S
S
— —
R R S S RS — — — — S — — R — — — — S -
—
—
S —S S S — S R — — R R — — — R R — —
R S S R
S S
R S R S S — R S — S
S S
6
—
-
—
-
— — — —
S S
—
_ -
—
R S S —
— R
—
R — —
19
21
22
R R ES S S S S — — E — S — —
24 —
S S S S S — —
—
—
—
—
—
—
—
—
—
—
—
—
-
S
NOTE. Abbreviations: PAS = p-aminosalicylic acid; TMP-SMZ = trimethoprim-sulfamethoxazole; R = resistant, S = sensitive, and E = equivocal (the organism was sensitive according to one reference center but resistant according to another, or the organism was sensitive when tested at a higher drug concentration but resistant at a lower drug concentration). A minus sign indicates that testing was not done.
(table 3). It is not surprising that the methods of sensitivity testing differed among the various centers, as there is no standardized procedure for such testing of this organism. M. gordonae was generally resistant to isoniazid (76%) and to paminosalicylic acid (64%). Seventy-two percent of isolates were sensitive to ethambutol, 61% to rifampin, 88% to cycloserine, 71% to kanamycin, and 54% to streptomycin. All of three isolates tested were found to be sensitive to amikacin. One isolate each was tested against ciprofloxacin, trimethoprim-sulfamethoxazole, and ansamycin; all were sensitive. Equivocal results were obtained with some antimycobacterial agents tested against some isolates. Systemic antimycobacterial chemotherapy was initiated in a total of 20 cases. Ethambutol was included in 18 (90%) of the drug regimens, rifampin in 17 (85%), and isoniazid in 14 (70%). Aminoglycosides were used only infrequently: streptomycin in four cases, amikacin (systemic) in two, and kanamycin in one. Although 13 patients (54%) received a regimen that included three or more drugs, a number of the organisms isolated from these patients were resistant in vitro to one drug (three isolates), two drugs (three isolates), or even four drugs (one isolate, case 11) in the combination. Biochemical characteristics were reported for the M. gordonae isolates from 11 patients (46%; cases 3, 5, 6, 8-10, 12, 13, 18, 21, and 22). All 11 isolates gave a positive result for Tween 80 hydrolysis, all of six for catalase (with testing assumed to have been done at 68°C because it was not specified as semiquantitative), both of two for semiquantitative catalase, three (43%) of seven for urease, and one (33%) of three for arylsulfatase. None of the isolates reduced nitrate (10 tested) or produced niacin (five tested). The results of
the biochemical tests appeared typical for M. gordonae [12], except for a somewhat high frequency of urease positivity. Discussion M. gordonae is ubiquitous in the environment and is commonly isolated from soil and water sources, including house dust and tap water [5]. In addition, the occurrence of M. gordonae in the hospital environment, especially in water sources, has been documented repeatedly [6-10, 41]. In some studies the organism was traced to a water source after an increased rate of isolation from clinical material prompted an epidemiological investigation [6, 7, 9, 10]. A cluster of isolates of M. gordonae from bronchoscopy specimens was traced to a contaminated dye solution that was added to the topical anesthetic used before the procedure [8]. Likewise, a commercial antimicrobial powder (PANTA) widely used in the BACTEC procedure for the decontamination of specimens from nonsterile sites upon their submission for mycobacterial culture was found to be contaminated by M. gordonae [11]. These reports all testify to the fact that M. gordonae is widespread in the environment and can easily be introduced into clinical specimens during collection or processing. Such contamination has taken place as the consequence of either incidental colonization of the oropharynx [6, 8, 9] or direct inoculation of the specimen [7, 10, 11]. The relative rarity of reported cases of disease attributed to M. gordonae despite widespread exposure of humans to the organism is indicative of the relatively low pathogenicity of this species. Because M. gordonae is ubiquitous, is relatively nonpathogenic, and is notorious for contaminating clinical
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Drug
CID 1992;14 (June)
Disseminated Infection with M. gordonae
(42%), and only about 10 isolates (42%) had their identity as M. gordonae confirmed by a reference laboratory.
The ability to obtain multiple positive specimens is determined by the site of infection. For example, in the reviewed cases of soft-tissue infection of an extremity or keratitis, the infection was confined to a small area that was completely resected when the initial diagnostic specimen was obtained. However, multiple positive specimens were obtained in the majority of the other cases, including all five cases of disseminated disease, six of eight cases of pulmonary disease, and one of three cases of peritoneal disease. Similarly, acid-fast organisms were observed in smears or histologic specimens in the majority of cases, including all five cases of disseminated disease, six of eight cases of pulmonary disease, six of seven cases of soft-tissue infection, two of three cases of peritonitis, and the one case of keratitis. In addition, granulomas and/or giant cells were observed in 12 cases (table 2). Of note, the culture of the corneal biopsy specimen from the patient with keratitis (case 24) reportedly yielded only one colony of M. gordonae, although acid-fast organisms were also found in histologic studies. Thus it is possible that M. gordonae was only a contaminant in this case, while the true pathogen was not isolated. The response to treatment and the elimination of the organism were also related to the site of infection. Pulmonary disease was not cured but rather ran a chronic course. However, the organism was eliminated from the sputum of four of the five patients with pulmonary disease who survived for >6 months. Soft-tissue infections were frequently cured, but elimination of the organism from clinical specimens was more difficult to demonstrate since the site of infection was sometimes completely resected during the initial diagnostic procedure or during treatment. The discrepancy between the elimination of M. gordonae from the sputum of some patients with pulmonary infection and the chronic course of their disease raises the question of colonization, with another etiology of the underlying pulmonary process [44]. Unfortunately, lung tissue (studies of which revealed granuloma formation) was obtained from only two patients (cases 7 and 12); M. gordonae was isolated from only one of these two lung specimens. In the other six cases, histologic documentation of invasive disease was not reported. The experience culled from the 24 reported cases provides an opportunity to assess some of the features of M. gordonae infection. Generally, patients with the same site of involvement had similar patterns of infection. Patients with pulmonary infections were older, were most often male, and had underlying pulmonary abnormalities. Their sputum became negative for M. gordonae during treatment, but their pulmonary disease manifested a chronic course. Patients with soft-tissue infection were younger, and most were female. These patients seldom had systemic symptoms
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specimens, any disease attributed to this organism must be carefully documented. Furthermore, chronic colonization by M. gordonae has been suggested [4, 34] and should be ruled out before the organism is assigned an etiologic role in a given disease process. The following criteria may be helpful in establishing the diagnosis of a true infection caused by M. gordonae: multiple isolations of the organism from the same body site or from different body sites; the detection of the organism in smears or in histologic sections; the growth of the organism from culture of a single specimen on several different media; the presence of multiple colonies on each culture medium; the presence of a clinical illness and/or a histopathological process consistent with a mycobacterial etiology; the response of the clinical illness and/or the histopathological process to appropriate antimycobacterial therapy; and the elimination of the organism from clinical specimens as the clinical condition improves. Some of these criteria are similar to those suggested by other researchers [17-19, 42, 43]. In light of the variability of the clinical conditions that are potentially attributable to M. gordonae, these criteria should not be applied rigidly but rather should serve as guidelines. In addition, since M. gordonae is a rare cause of disease, it is important that reports of infections attributed to this organism document how it was identified by stating the results of the specific biochemical tests used, preferably with confirmation by a reference laboratory. In the case we describe herein, disseminated infection with M. gordonae was well documented. The organism was both isolated from and observed in several specimens from multiple sources, and it was grown on various media. The results of histologic studies were compatible with mycobacterial disease, and the infection responded to antimycobacterial therapy. The biochemical characteristics of the patient's isolate were typical for M. gordonae except for urease positivity, and the identity of the organism was confirmed by three reference laboratories. M. gordonae was isolated from a bone marrow specimen to which PANTA was not added. It was also isolated in solid medium (without added PANTA) from every specimen positive in liquid medium (with added PANTA). At the time that the specimens from our patient were being cultured, the rate of isolation of M. gordonae did not increase in our laboratory. These facts eliminate the PANTA solution as the source of the organism. In recent years an increasing number of infections with M. gordonae have been reported, but many of them have been poorly documented [34-40]. Of the 24 cases described in tables 1 and 2, many did not fulfill all the criteria suggested above. The approximate amount of mycobacterial growth was noted in only eight cases (33%), and more than one positive culture was reported in only 13 cases (54%). Results of some biochemical tests were presented for only 10 isolates
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pecially in pulmonary infections. More detailed reporting may help to establish the relation between the isolation of M. gordonae from a clinical specimen and an infectious process in a given patient and to determine the true incidence of infection with this organism. References
1. Runyon EH. Anonymous mycobacteria in pulmonary disease. Med Clin North Am 1959;43:273-90. 2. Woods GL, Washington JA II. Mycobacteria other than Mycobacterium tuberculosis: review of microbiologic and clinical aspects. Rev Infect Dis 1987;9:275-94. 3. Berlin OGW. Mycobacteria. In: Baron EJ, Finegold SM, eds. Bailey and Scott's diagnostic microbiology. 8th ed. St. Louis: CV Mosby, 1990;597-640. 4. Wolinsky E. Nontuberculous mycobacteria and associated diseases. In: Kubica GP, Wayne LG, eds. The mycobacteria. A sourcebook. Part B. New York: Marcel Dekker, 1984; l 141-207. 5. Tsukamura M. The "non-pathogenic" species of mycobacteria: their distribution and ecology in non-living reservoirs. In: Kubica GP, Wayne LG, eds. The mycobacteria. A sourcebook. Part B. New York: Marcel Dekker, 1984;1339-59. 6. Gangadharam PRJ, Lockhart JA, Awe RJ, Jenkins DE. Mycobacterial contamination through tap water [letter]. Am Rev Respir Dis 1976;113:894. 7. Dizon D, Mihailescu C, Bae HC. Simple procedure for detection of Mycobacterium gordonae in water causing false-positive acid-fast smears. J Clin Microbiol 1976;3:21 I. 8. Steere AC, Corrales J, von Graevenitz A. A cluster of Mycobacterium gordonae isolates from bronchoscopy specimens. Am Rev Respir Dis 1979;120:214-6. 9. Panwalker AP, Fuhse E. Nosocomial Mycobacterium gordonae pseudoinfection from contaminated ice machines. Infect Control 1986;7:67-70. 10. Stine TM, Harris AA, Levin S, Rivera N, Kaplan RL. A pseudoepidemic due to atypical mycobacteria in a hospital water supply. JAMA 1987;258:809- l 1. 1 1. Tokars J1, McNeil MM, Tablan OC, et al. Mycobacterium gordonae pseudoinfection associated with a contaminated antimicrobial solution. J Clin Microbiol 1990;28:2765-9. 12. Kent PT, Kubica GP. Public health mycobacteriology. A guide for the level III laboratory. Atlanta: Centers for Disease Control, 1985:71120. 13. Gonzales EP, Crosby RMN, Walker SH. Mycobacterium aquae infection in a hydrocephalic child (Mycobacterium aquae meningitis). Pediatrics 1971;48:974-7. 14. Lohr DC, Goeken JA, Doty DB, Donta ST. Mycobacterium gordonae infection of a prosthetic aortic valve. JAMA 1978;239:1528-30. 15. Chan J, McKitrick JC, Klein RS. Mycobacterium gordonae in the acquired immunodeficiency syndrome [letter]. Ann Intern Med 1984;101:400. 16. Turner DM, Ramsey PG, Ojemann GA, Ralph DD. Disseminated Mycobacterium gordonae infection associated with glomerulonephritis. West J Med 1985;142:391-3. 17. Kumar UN, Varkey B. Pulmonary infection caused by Mycobacterium gordonae. Br J Dis Chest 1980;74:189-92. 18. Craig CP, Kreitzer SM. Non-tuberculous mycobacterial infections: human infections due to Mycobacterium gordonae. Infectious Disease Reviews 1980;6:79-88. 19. Clague H, Hopkins CA, Roberts C, Jenkins PA. Pulmonary infection with Mycobacterium gordonae in the presence of bronchial carcinoma. Tubercle 1985;66:61-3.
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or underlying diseases and responded favorably to treatment (surgery and/or chemotherapy). About half of this group had a history of penetrating trauma. Disseminated infection with M. gordonae developed in four patients with no underlying immunologic deficiency and in one patient with AIDS. All four immunocompetent patients had a foreign body in place; in three instances (cases 1, 2, and 4), this device was considered to be the portal of entry and the source for continuous shedding of M. gordonae. In our patient (case 5), an indwelling Hickman-Broviac catheter, which had been in place for 6 months, could have served as the portal of entry. However, the blood drawn through the line yielded no mycobacteria, and the exit site appeared normal on examination. It is possible that M. gordonae was introduced in this case during abdominal surgery 6 months before presentation. Removal of the foreign body appeared necessary for a successful outcome in the three cases (cases 1, 2, and 4). The foreign body remained in place in our case and apparently did not interfere with clinical or microbiological cure. The group of patients with peritonitis was small and heterogeneous. One of the three patients was undergoing chronic ambulatory peritoneal dialysis, which may have provided the portal of entry for M. gordonae [31]. The single case of keratitis had a chronic course and responded to surgical therapy. Overall, the outcome of infection with M. gordonae was related to the site of involvement and to the underlying disease. Patients with pulmonary infections had the poorest outcome. Three of these eight patients died, and two of these deaths (cases 7 and 12) may have been attributable to M. gordonae infection. No cures were reported in this group. Patients infected at other sites had a better outcome, with only three deaths, all due to underlying disease. Two patients (cases 3 and 23; 8%) had HIV infection. The small number of cases and the lack of complete clinical information make it impossible to determine whether infection with M. gordonae had any effect on the course and prognosis of HIV disease. Several authors have recently reported the isolation of M. gordonae from patients with AIDS or AIDSrelated complex [37, 45-47]. Although the clinical and microbiological data are incomplete, these reports suggest the possibility of an increasing role for M. gordonae as an opportunistic pathogen in AIDS. In summary, M. gordonae, despite its ubiquity in the environment, is only rarely a cause of infection. However, as is evident from our case report and review of the literature, M. gordonae can cause disease of widely varying severity and should not be dismissed automatically as a contaminant when isolated from clinical material. The clinical presentation, course, and outcome of infection with M. gordonae are a function of the site of involvement. Data substantiating the identification of M. gordonae or documenting the infection are frequently lacking. Histologic documentation may help to distinguish between colonization and invasive disease, es-
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35. Merchant R, Irani A, Shah UC, Daftary D, Sharma J, Joshi L. Disseminated non-tuberculous mycobacteriosis due to atypical type II-Mycobacteria gordonoe [sic]. Indian J Pediatr 1984;51:295-7. 36. Barnett SM. CT findings in tuberculous mediastinitis. J Comput Assist Tomogr 1986;10:165-6. 37. Bourgoignie JJ. Renal complications of human immunodeficiency virus type I. Kidney Int 1990;37:1571-84. 38. Sutker WL, Lankford LL, Tompsett R. Granulomatous synovitis: the role of atypical mycobacteria. Rev Infect Dis 1979;1:729-35. 39. Gribetz AR, Damsker B, Bottone EJ, Kirschner PA, Teirstein AS. Solitary pulmonary nodules due to nontuberculous mycobacterial infection. Am J Med 1981;70:39-43. 40. Marchevsky A, Damsker B, Gribetz A, Tepper S, Geller SA. The spectrum of pathology of nontuberculous mycobacterial infections in open-lung biopsy specimens. Am J Clin Pathol 1982;78:695-700. 41. Pelletier PA, du Moulin GC, Stottmeier KD. Prevalence of mycobacteria in a renal dialysis water system [abstract no L-12]. In: Abstracts of the annual meeting of the American Society for Microbiology. Washington, DC: American Society for Microbiology, 1988;413. 42. Jenkins DE. Recent clinical studies in the United States on atypical acid-fast bacilli. Bull Int Union Tuberc 1959;29:295-307. 43. Yamamoto M, Ogura Y, Sudo K, Hibino S. Diagnostic criteria for disease caused by atypical mycobacteria. Am Rev Respir Dis 1967;96:773-8. 44. Ahn CH, McLarty JW, Ahn SS, Ahn SI, Hurst GA. Diagnostic criteria for pulmonary disease caused by Mycobacterium kansasii and Mycobacterium intracellulare. Am Rev Respir Dis 1982;125:388-91. 45. Horsburgh CR Jr, Selik RM. The epidemiology of disseminated nontuberculous mycobacterial infection in the acquired immunodeficiency syndrome (AIDS). Am Rev Respir Dis 1989;139:4-7. 46. Ardito F, Damiano F, Venturi G, Archibusacci C, Nacci A. L'emocoltura nelle infezioni dell'immunodepresso. L'Igiene Moderna 1990;93:91-102. 47. Barber TW, Farber HW. Invasive Mycobacterium gordonae in patients seropositive for human immunodeficiency virus [abstract no 2126]. In: Final program and abstracts of the Sixth International Conference on AIDS. Marlow Heights, Maryland: Center for International Research, U.S. Bureau of the Census, 1990:385.
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20. Douglas JG, Calder MA, Choo-Kang YFJ, Leitch AG. Mycobacterium gordonae: a new pathogen? Thorax 1986;41:152-3. 21. Guarderas J, Alvarez S, Berk SL. Progressive pulmonary disease caused by Mycobacterium gordonae. South Med J 1986;79:505-7. 22. Aguado JM, GOmez-Garces JL, Manrique A, Soriano F. Pulmonary infection by Mycobacterium gordonae in an immunocompromised patient. Diagn Microbiol Infect Dis 1987;7:261-3. 23. de Gracia J, Vidal R, Martin N, Bravo C, Gonzalez T, Riba A. Pulmonary disease caused by Mycobacterium gordonae. Tubercle 1989;70:135-7. 24. Berman LB. Infection of synovial tissue by Mycobacterium gordonae [letter]. Can Med Assoc J 1983;129:1078 9. 25. Lorber B, Suh B. Bursitis caused by Mycobacterium gordonae: is surgery necessary? Am Rev Respir Dis 1983;128:565-6. 26. Shelley WB, Folkens AT. Mycobacterium gordonae infection of the hand. Arch Dermatol 1984;120:1064-5. 27. McIntyre P, Blacklock Z, McCormack JG. Cutaneous infection with Mycobacterium gordonae. J Infect 1987;14:71-8. 28. Gengoux P, Portaels F, Lachapelle JM, Minnikin DE, Tennstedt D, Tamigneau P. Skin granulomas due to Mycobacterium gordonae. Int J Dermatol 1987;26:181-4. 29. Nakagawa S. The flexor digitorum profundus tendon rupture caused by Mycobacterium gordonae tenosynovitis in a renal transplant recipient. Rin Sei Ge 1990;25:665-8. 30. Kurnik PB, Padmanabh U, Bonatsos C, Cynamon MH. Mycobacterium gordonae as a human hepato-peritoneal pathogen, with a review of the literature. Am J Med Sci 1983;285:45-8. 31. London RD, Damsker B, Neibart EP, Knorr B, Bottone EJ. Mycobacterium gordonae: an unusual peritoneal pathogen in a patient undergoing continuous ambulatory peritoneal dialysis. Am J Med 1988; 85:703-4. 32. Carcaba V, Carton JA, Fernandez LeOn A, de Diego I. Peritonitis por Mycobacterium gordonae en un paciente infectado por el virus de la immunodeficiencia humana. Med Clin (Bart) 1989;93:598. 33. Moore MB, Newton C, Kaufman HE. Chronic keratitis caused by Mycobacterium gordonae. Am J Ophthalmol 1986;102:516-21. 34. Kubala E. Some aspects of diseases caused by atypical mycobacteria. Scandinavian Journal of Respiratory Diseases [Supplement] 1972;80:11-6.
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