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Mycobacterium gordonae: An unusual peritoneal pathogen in a patient undergoing continuous ambulatory peritoneal dialysis
Mycobacteriumgordonae:An Unusual Peritoneal Pathogen in a Patient Undergoing Continuous Ambulatory Peritoneal Dialysis ROGER D. LONDON, M.D., BECA DAMSKER, M.D., ERIC P. NEIBART, M.D., BARBARA KNORR, M.D., EDWARDJ. BOTTONE, Ph.D. New York, New York
p
eritonitis is a major complication of continuous ambulatory peritoneal dialysis (CAPD). The vast majority (60 to 70 percent) of these infections are caused by gram-positive species, whereas gram-negative species account for approximately 20 percent; fungi and mycobacteria comprise 0 to 5 percent of reported infectious complications of CAPD [1]. In previous reports [2,3], the incidence of culturenegative peritonitis ranged from 8 percent to 27 percent. The etiology of culture-negative peritonitis is debatable and undoubtedly related to inadequate culture techniques for the recovery of an unsuspected microbial species. The current case stYesses the importance of pursuing the diagnosis of an unusual pathogen in culture-negative peritonitis highlighted by the absence of clinical improvement despite prolonged antimicrobial therapy. CASE REPORT A 36-year-old CAPD patient with a previous history of intravenous drug and ethanol abuse presented to The Mount Sinai Hospital with a 40-pound weight loss, two-month history of fever, anemia, hepatosplenomegaly, abnormal liver function test results, and a peritoneal fluid cell count of 190 cells/ml, with 60 polymorphonuclear leukocytes, 10 lymphocytes, 13 monocytes, and 13 eosinophils. Following admission, seven cultures of blood and eight of peritoneal fluid were found to be sterile. Bone marrow aspirate and biopsy showed diminished iron stores and decreased erythroid series. Granulomas were not seen and culture results of stains for fungi and acid-fast bacilli were negative. Liver biopsy revealed centrilobular fibrosis with sinusoidal dilatation and steatosis. Serologic studies were positive for autoantibodies (direct Coombs'), antinuclear antibodies, double-stranded DNA, hepatitis B surface antibody, and VDRL. Negative results were obtained for the microhemagglutination test for Treponema pallidum and for hepatitis B surface antigen and human immunodeficiency virus (enzyme-linked immunosorbent assay). Sonography and computerized tomography of the abdomen revealed only hepatosplenomegaly. Because the patient continued to have fever, abdominal pain, and an elevated peritoneal fluid cell count (742/ ml), the prospect of an unusual microorganism was From the Divisionof Nephrology,Departmentof Microbiology,and Division of Infectious Diseases,The Mount Sinai Hospitaland Mount Sinai Schoolof Medicine, NewYork, New York. Requestsfor reprints shouldbe addressed to Dr. RogerD. London,Box 1243, RenalDivision,Departmentof Medicine, The Mount Sinai MedicalCenter, One Gustave L. Levy Place, New York, NewYork 10029-6574. ManuscriptsubmittedApril 22, 1988, and accepted in revisedform August8, 1988.
entertained. Peritoneal fluid (100 ml) was filtered through a 0.45-/~ filter (Nalgene Co., Rochester, New York) and the filter was washed with 0.5 ml sterile saline. Gram-, Giemsa-, and Kinyoun-stained smears were prepared and cultures were inoculated. No microorganisms were observed on Gram- or Giemsastained smears, but slightly curved, beaded, acid-fast bacilli were observed in the Kinyoun-stained smears (Figure l). Under direct vision, the Tenckhoff catheter was removed and a peritoneal biopsy was performed, which subsequently yielded negative results for granuloma. After removal of the catheter, defervescence occurred, and the patient did well on hemodialysis and was discharged. Antimycobacterial therapy was not initiated because it was believed that catheter removal would be sufficient to eradicate his mycobacterial infection. One month later, attempted reinsertion of a Tenckhoff catheter was unsuccessful because of adhesions, and active mycobacterial infection was assessed clinically and microbiologically. Antimycobacterial therapy with isoniazid, rifampin, ethambutol, and post-dialysis amikacin was begun. After one month of therapy, the patient was readmitted with a small bowel obstruction and fever. His obstruction did not resolve with the insertion of a Cantor tube, and he underwent an exploratory laparotomy during which the adhesions were lysed and an ileocolic anastomosis was performed. The antimycobacterial regimen was continued, and the patient has done well clinically with weight gain and no signs of continued or recurrent infection. Amikacin was discontinued after two months when hearing loss occurred, and therapy with pyrazinamide was initiated. Six months later, he continues to gain weight and remains infection-free while receiving pyrazinamide, isoniazid, ethambutol, and rifampin.
Microbiology
Mycobacterium gordonae was recovered from the sediment of five peritoneal dialysis specimens and one ascitic fluid specimen submitted for mycobacterial analysis. Yellow-pigmented colonies grew after three to seven weeks of incubation on Lowenstein-Jensen, 7 H l l , and modified Dubos Liquid medium (Gibco Laboratories, Madison, Wisconsin). The scotochromogenic isolate was identified as M. gordonae mainly on the basis of negative niacin and urease production, nitrate reduction, and 5 percent sodium chloride tolerance, and positive catalase and Tween 80 hydrolysis (five days). Confirmation as M. gordonae was achieved by Dr. G. P. Kubica of the Centers for Disease Control. The isolate tested courtesy of Dr. Rita Brenden by a disk diffusion method in 7H10 agar plates was found
November 1988 The American Journal of Medicine Volume 85
703
M. GORDONAEIN A CAPD PATIENT / LONDON ET AL
- )
. ", .ii. '
• )
.: -'::-~ i
~;_~ :~.~,,
' ,'i
i¢'5
Figure 1. Kinyoun-stained smear of concentrated peritoneal dialysis fluid showing slightly curved, beaded, acid-fast bacillus subsequently identified as M. gordonae (original magnification X 1,000, reduced by . 3 5 percent).
to be susceptible to ethambutol, rifampin, ethionamide, and kanamycin, moderately resistant to paraminosalicylic acid, and resistant to isoniazid.
COMMENTS Mycobacteria have rarely caused peritonitis in patients undergoing CAPD [1]. M. tuberculosis infections of peritoneal fluid have generally been considered to represent reactivation of a latent peritoneal focus. Nontubereulous mycobacterial infections in patients undergoing dialysis are rare, and a recent outbreak attributed to an M. chelonei-like organism was traced to a contaminated water source in an automated hemodialysis machine [4]. M. gordonae is a nontuberculous scotochromogenic species that is found in water, soil, and raw milk [5]. In normal hosts, M. gordonae may be encountered as a colonizer of the human body in the absence of clinical disease [5,6]. Instances of M. gordonae infection have been reported in the setting of immunosuppression, in patients with the acquired immunbdeficiency syndrome [7], and in those with Hodgkin's disease [8]. Other infections include pulmonary [9-11], olecranon bursitis [11], synovial [12,13], and peritonitis in an alcoholic patient [14]. Finally, analogous to our patient with a prosthetic device in place, meningitis in a hydrocephalic child with a ventriculoperitoneal shunt [15], and endocarditis of a prosthetic aortic valve [16], have been reported. The occurrence of M. gordoaae in our patient who was undergoing C A P D strengthens the association of nontuberculous mycobacterial infections with prosthetic devices. In our patient, there was no evidence of systemic or disseminated disease; rather, infection was confined to the peritoneum, raising the question of direct inoculation of contaminated water through the
704
November 1988
The American Journal of Medicine
peritoneal catheter. Additionally, since our patient was an intravenous drug abuser, the possibility does exist that M. gordonae could have been introduced intravenously or intraperitoneally through contaminated water or instruments. In this regard, peritoneal infection with M. gordonae differs from that caused by M. tuberculosis in which reactivation of previous disease seems to underscore pathogenesis. The current report is illustrative of several key points. In the setting of C A P D , the etiology of peritonitis must be aggressively sought in the febrile patient whose routine cultures do not reveal a c o m m o n pathogen. Concentration of peritoneal dialysis fluid as described herein may prove successful in visualizing the etiologic agent on direct-stained preparations and in the initiation of the appropriate cultural techniques. Through these endeavors, in the current case, M. gordonae was observed on several smears and repeatedly isolated, reaffirming its etiologic role [17]. Repeated isolation of a microbial species not frequently encountered as an etiologic agent of disease must be evaluated and considered significant. Treatment should be started promptly.
REFERENCES 1. Peterson PK, Matzke M, Keane WF: Current concepts in the management of peritonitis in patients undergoing continuous ambulatory peritoneal dialysis. Rev infect Dis 1987; 9: 604-612. 2. Golper TA, Hartstein AI: Analysis of the causative pathogens in uncomplicated CAPD-associatedperitonitis: duration of therapy, relapses, and prognosis. Am J Kidney Dis 1986; 7: 141-]45. 3. Rubin J, Rogers WA, Taylor HM, et al: Peritonitis during continuous ambulatory peritoneal dialysis. Ann intern Med 1980; 92: 7-13. 4. Band JD, Ward JI, Fraser DW, etal: Peritonitis due to a Mycobacteriumcheloneilike organism associated with intermittent chronic peritoneal dialysis. J infect Dis 1982; 145: 9-17. 5. Chapman JS: The atypical mycobacteria and human mycobacteriosis, 1st ed. New York: Plenum Medical, 1977; 85-99. 6. Du Moulin GC, Stottmeier KD: Waterborne mycobacteria: an increasing threat to health. ASM News 1986; 52: 525-529. 7. Chan J, McKitrick JC, Klein RS: Mycobacteriumgordonaein the acquired immunodeficiency syndrome (letter). Ann Intern Med 1984; 101: 400. 8. Aguado JM, Gomez-GarcesJL, Manrique A, Soriano A: Pulmonary infection by MycobacteriumBordonaein an immunocompromised host. Diagn Microbiol Infect Dis 1987; 7: 261-262. 9. DouglasJG, Calder MA, Choo-KangYFJ, Leitch AG: Mycobacteriumgordonae:a new pathogen? Thorax 1986; 41: 152-153. 10. Kumar UN, Varkey B: Pulmonary infection caused by Mycobacterium gordonae. Br J Dis Chest 1980; 74: 189-192. 11. Craig CP, Kreitzer SM: Non-tuberculous mycobacterial infections: human infections due to Mycobacteriumgordonae. Infect Dis Rev 1980; 6:79-83. 12. Berman LB: Infection of synovial tissue by Mycobacteriumgordonae(letter). Can Med Assoc J 1983; 129: 1078-1079, 13. Stutker WL, Lankford LL Tompsett R: Granuiomatous synovitis: the role of atypical mycobacteria. Rev Infect Dis 1979; 1: 729-735. 3.4. Kurnik PB, Padmanabh U, Bonatsos C, Cynamon MH: Mycobacteriumgordonaeas a human hepato-peritoneal pathogen, with a review of the literature. Am J Med Sci 1983; 285: 45-48. 15. Gonzales EP, Crosby RMN, Walker SH: Mycobacteriumaquae infection in a hydroencephalic child (Mycobacterium aquae meningitis). Pediatrics 1971; 48: 974-977. 16. Lohr DC, GoekenJA, Doty DB, Donta ST: Mycobacteriumgordonaeinfectionof a prosthetic aortic valve. JAMA 1978; 239: 1528-1530. 17. Wolinsky E: Nontuberculous mycobacteria and associated diseases. Am Rev Respir Dis 179: 119: 107-159.
Volume 85
p
eritonitis is a major complication of continuous ambulatory peritoneal dialysis (CAPD). The vast majority (60 to 70 percent) of these infections are caused by gram-positive species, whereas gram-negative species account for approximately 20 percent; fungi and mycobacteria comprise 0 to 5 percent of reported infectious complications of CAPD [1]. In previous reports [2,3], the incidence of culturenegative peritonitis ranged from 8 percent to 27 percent. The etiology of culture-negative peritonitis is debatable and undoubtedly related to inadequate culture techniques for the recovery of an unsuspected microbial species. The current case stYesses the importance of pursuing the diagnosis of an unusual pathogen in culture-negative peritonitis highlighted by the absence of clinical improvement despite prolonged antimicrobial therapy. CASE REPORT A 36-year-old CAPD patient with a previous history of intravenous drug and ethanol abuse presented to The Mount Sinai Hospital with a 40-pound weight loss, two-month history of fever, anemia, hepatosplenomegaly, abnormal liver function test results, and a peritoneal fluid cell count of 190 cells/ml, with 60 polymorphonuclear leukocytes, 10 lymphocytes, 13 monocytes, and 13 eosinophils. Following admission, seven cultures of blood and eight of peritoneal fluid were found to be sterile. Bone marrow aspirate and biopsy showed diminished iron stores and decreased erythroid series. Granulomas were not seen and culture results of stains for fungi and acid-fast bacilli were negative. Liver biopsy revealed centrilobular fibrosis with sinusoidal dilatation and steatosis. Serologic studies were positive for autoantibodies (direct Coombs'), antinuclear antibodies, double-stranded DNA, hepatitis B surface antibody, and VDRL. Negative results were obtained for the microhemagglutination test for Treponema pallidum and for hepatitis B surface antigen and human immunodeficiency virus (enzyme-linked immunosorbent assay). Sonography and computerized tomography of the abdomen revealed only hepatosplenomegaly. Because the patient continued to have fever, abdominal pain, and an elevated peritoneal fluid cell count (742/ ml), the prospect of an unusual microorganism was From the Divisionof Nephrology,Departmentof Microbiology,and Division of Infectious Diseases,The Mount Sinai Hospitaland Mount Sinai Schoolof Medicine, NewYork, New York. Requestsfor reprints shouldbe addressed to Dr. RogerD. London,Box 1243, RenalDivision,Departmentof Medicine, The Mount Sinai MedicalCenter, One Gustave L. Levy Place, New York, NewYork 10029-6574. ManuscriptsubmittedApril 22, 1988, and accepted in revisedform August8, 1988.
entertained. Peritoneal fluid (100 ml) was filtered through a 0.45-/~ filter (Nalgene Co., Rochester, New York) and the filter was washed with 0.5 ml sterile saline. Gram-, Giemsa-, and Kinyoun-stained smears were prepared and cultures were inoculated. No microorganisms were observed on Gram- or Giemsastained smears, but slightly curved, beaded, acid-fast bacilli were observed in the Kinyoun-stained smears (Figure l). Under direct vision, the Tenckhoff catheter was removed and a peritoneal biopsy was performed, which subsequently yielded negative results for granuloma. After removal of the catheter, defervescence occurred, and the patient did well on hemodialysis and was discharged. Antimycobacterial therapy was not initiated because it was believed that catheter removal would be sufficient to eradicate his mycobacterial infection. One month later, attempted reinsertion of a Tenckhoff catheter was unsuccessful because of adhesions, and active mycobacterial infection was assessed clinically and microbiologically. Antimycobacterial therapy with isoniazid, rifampin, ethambutol, and post-dialysis amikacin was begun. After one month of therapy, the patient was readmitted with a small bowel obstruction and fever. His obstruction did not resolve with the insertion of a Cantor tube, and he underwent an exploratory laparotomy during which the adhesions were lysed and an ileocolic anastomosis was performed. The antimycobacterial regimen was continued, and the patient has done well clinically with weight gain and no signs of continued or recurrent infection. Amikacin was discontinued after two months when hearing loss occurred, and therapy with pyrazinamide was initiated. Six months later, he continues to gain weight and remains infection-free while receiving pyrazinamide, isoniazid, ethambutol, and rifampin.
Microbiology
Mycobacterium gordonae was recovered from the sediment of five peritoneal dialysis specimens and one ascitic fluid specimen submitted for mycobacterial analysis. Yellow-pigmented colonies grew after three to seven weeks of incubation on Lowenstein-Jensen, 7 H l l , and modified Dubos Liquid medium (Gibco Laboratories, Madison, Wisconsin). The scotochromogenic isolate was identified as M. gordonae mainly on the basis of negative niacin and urease production, nitrate reduction, and 5 percent sodium chloride tolerance, and positive catalase and Tween 80 hydrolysis (five days). Confirmation as M. gordonae was achieved by Dr. G. P. Kubica of the Centers for Disease Control. The isolate tested courtesy of Dr. Rita Brenden by a disk diffusion method in 7H10 agar plates was found
November 1988 The American Journal of Medicine Volume 85
703
M. GORDONAEIN A CAPD PATIENT / LONDON ET AL
- )
. ", .ii. '
• )
.: -'::-~ i
~;_~ :~.~,,
' ,'i
i¢'5
Figure 1. Kinyoun-stained smear of concentrated peritoneal dialysis fluid showing slightly curved, beaded, acid-fast bacillus subsequently identified as M. gordonae (original magnification X 1,000, reduced by . 3 5 percent).
to be susceptible to ethambutol, rifampin, ethionamide, and kanamycin, moderately resistant to paraminosalicylic acid, and resistant to isoniazid.
COMMENTS Mycobacteria have rarely caused peritonitis in patients undergoing CAPD [1]. M. tuberculosis infections of peritoneal fluid have generally been considered to represent reactivation of a latent peritoneal focus. Nontubereulous mycobacterial infections in patients undergoing dialysis are rare, and a recent outbreak attributed to an M. chelonei-like organism was traced to a contaminated water source in an automated hemodialysis machine [4]. M. gordonae is a nontuberculous scotochromogenic species that is found in water, soil, and raw milk [5]. In normal hosts, M. gordonae may be encountered as a colonizer of the human body in the absence of clinical disease [5,6]. Instances of M. gordonae infection have been reported in the setting of immunosuppression, in patients with the acquired immunbdeficiency syndrome [7], and in those with Hodgkin's disease [8]. Other infections include pulmonary [9-11], olecranon bursitis [11], synovial [12,13], and peritonitis in an alcoholic patient [14]. Finally, analogous to our patient with a prosthetic device in place, meningitis in a hydrocephalic child with a ventriculoperitoneal shunt [15], and endocarditis of a prosthetic aortic valve [16], have been reported. The occurrence of M. gordoaae in our patient who was undergoing C A P D strengthens the association of nontuberculous mycobacterial infections with prosthetic devices. In our patient, there was no evidence of systemic or disseminated disease; rather, infection was confined to the peritoneum, raising the question of direct inoculation of contaminated water through the
704
November 1988
The American Journal of Medicine
peritoneal catheter. Additionally, since our patient was an intravenous drug abuser, the possibility does exist that M. gordonae could have been introduced intravenously or intraperitoneally through contaminated water or instruments. In this regard, peritoneal infection with M. gordonae differs from that caused by M. tuberculosis in which reactivation of previous disease seems to underscore pathogenesis. The current report is illustrative of several key points. In the setting of C A P D , the etiology of peritonitis must be aggressively sought in the febrile patient whose routine cultures do not reveal a c o m m o n pathogen. Concentration of peritoneal dialysis fluid as described herein may prove successful in visualizing the etiologic agent on direct-stained preparations and in the initiation of the appropriate cultural techniques. Through these endeavors, in the current case, M. gordonae was observed on several smears and repeatedly isolated, reaffirming its etiologic role [17]. Repeated isolation of a microbial species not frequently encountered as an etiologic agent of disease must be evaluated and considered significant. Treatment should be started promptly.
REFERENCES 1. Peterson PK, Matzke M, Keane WF: Current concepts in the management of peritonitis in patients undergoing continuous ambulatory peritoneal dialysis. Rev infect Dis 1987; 9: 604-612. 2. Golper TA, Hartstein AI: Analysis of the causative pathogens in uncomplicated CAPD-associatedperitonitis: duration of therapy, relapses, and prognosis. Am J Kidney Dis 1986; 7: 141-]45. 3. Rubin J, Rogers WA, Taylor HM, et al: Peritonitis during continuous ambulatory peritoneal dialysis. Ann intern Med 1980; 92: 7-13. 4. Band JD, Ward JI, Fraser DW, etal: Peritonitis due to a Mycobacteriumcheloneilike organism associated with intermittent chronic peritoneal dialysis. J infect Dis 1982; 145: 9-17. 5. Chapman JS: The atypical mycobacteria and human mycobacteriosis, 1st ed. New York: Plenum Medical, 1977; 85-99. 6. Du Moulin GC, Stottmeier KD: Waterborne mycobacteria: an increasing threat to health. ASM News 1986; 52: 525-529. 7. Chan J, McKitrick JC, Klein RS: Mycobacteriumgordonaein the acquired immunodeficiency syndrome (letter). Ann Intern Med 1984; 101: 400. 8. Aguado JM, Gomez-GarcesJL, Manrique A, Soriano A: Pulmonary infection by MycobacteriumBordonaein an immunocompromised host. Diagn Microbiol Infect Dis 1987; 7: 261-262. 9. DouglasJG, Calder MA, Choo-KangYFJ, Leitch AG: Mycobacteriumgordonae:a new pathogen? Thorax 1986; 41: 152-153. 10. Kumar UN, Varkey B: Pulmonary infection caused by Mycobacterium gordonae. Br J Dis Chest 1980; 74: 189-192. 11. Craig CP, Kreitzer SM: Non-tuberculous mycobacterial infections: human infections due to Mycobacteriumgordonae. Infect Dis Rev 1980; 6:79-83. 12. Berman LB: Infection of synovial tissue by Mycobacteriumgordonae(letter). Can Med Assoc J 1983; 129: 1078-1079, 13. Stutker WL, Lankford LL Tompsett R: Granuiomatous synovitis: the role of atypical mycobacteria. Rev Infect Dis 1979; 1: 729-735. 3.4. Kurnik PB, Padmanabh U, Bonatsos C, Cynamon MH: Mycobacteriumgordonaeas a human hepato-peritoneal pathogen, with a review of the literature. Am J Med Sci 1983; 285: 45-48. 15. Gonzales EP, Crosby RMN, Walker SH: Mycobacteriumaquae infection in a hydroencephalic child (Mycobacterium aquae meningitis). Pediatrics 1971; 48: 974-977. 16. Lohr DC, GoekenJA, Doty DB, Donta ST: Mycobacteriumgordonaeinfectionof a prosthetic aortic valve. JAMA 1978; 239: 1528-1530. 17. Wolinsky E: Nontuberculous mycobacteria and associated diseases. Am Rev Respir Dis 179: 119: 107-159.
Volume 85