469
Disseminated Nocardia brasiliensis Infection with Septic Arthritis Brian S. Koll, Arthur E. Brown, Timothy E. Kiehn, and Donald Armstrong
From the Infectious Disease Service. Department of Medicine. and the Department ofPediatrics. Memorial Sloan-Kettering Cancer Center. New York; and Cornell University Medical College. New York. New York
An unusual case of disseminated Nocardia brasiliensis infection is presented. The patient, who had been receiving chronic dexamethasone therapy for 4 years, had pneumonia and septic arthritis ofthe left knee due to N. brasiliensis. To our knowledge, this is the first report from the United States of a synovial joint infection with this organism. Disseminated disease due to N. brasiliensis is infrequently reported; it is most often seen in the immunocompromised patient and is often unresponsive to therapy.
Case Report A 36-year-old man with a history of a right cerebellar and brain-stem astrocytoma (Grade III) who had received chronic dexamethasone therapy for 4 years was admitted to the hospital with a cough productive of brown sputum. He also noted a 3-week history ofleft-sided pleuritic chest pain, edema of his lower extremities, malaise, dyspnea on exertion, and fever. Two and one-half months previously, he had developed septic arthritis of the right knee due to Staphylococcus aureus. He was treated with intravenous oxacillin (2 g every 4 hours) for 6 weeks, followed by a 4-week course of oral dicloxacillin (500 mg every 6 hours). The patient had last received chemotherapy with carboplatin and carmustine for his tumor 8 months before this admission. He continued to receive dexa-
Received 14 January 1992; revised 2 April 1992. Presented in part at the 7th International Symposiumon Infections in the Immunocompromised Host. 21-24 June 1992. Boulder. Colorado. Reprints or correspondence: Dr. Arthur E. Brown. Infectious Disease Service. Memorial Sloan-Kettering Cancer Center. Box 272. 1275 York Avenue. New York. New York 10021. Clinical Infectious Diseases 1992;15:469-72 © 1992 by The University of Chicago. All rights reserved. 1058-4838/92/1503-0010$02.00
methasone for headaches presumed to be secondary to progression of his disease. While receiving dexamethasone, he also received aerosol pentamidine as prophylaxis for Pneumocystis carinii pneumonia. He was a former house painter and a lifelong resident of New York and had never traveled outside the United States. He pursued gardening as a hobby. The patient appeared acutely ill; his temperature was 39.0°C, blood pressure, 110/70 mm Hg: pulse, lOO/min; and respirations, 20/min. Abnormal physical findings included oral thrush, bilateral rhonchi, diminished breath sounds at the left base, and dullness to percussion over the left lower lung field. He had 2+ pitting edema of his lower extremities and nontender, non erythematous ballottable effusions of both knees and his left elbow. His joints had full range of motion. His neurological examination was notable for evidence of right cerebellar dysfunction. His skin was without nodules or ulcerations. Evidence of onychomycosis was observed. Laboratory findings included the following: hemoglobin level, 11.2 g/dl.; hematocrit. 35%; leukocyte count, 3,800/ mm ', with 86% granulocytes, 10% lymphocytes, and 4% monocytes: platelet count, 120,000/mm 3 ; and normal levels of serum electrolytes. An arterial blood gas analysis performed when the patient was breathing room air showed a pH of7.56; Pao2, 129 mm Hg; reo, 31 mm Hg; and serum bicarbonate level, 27 mEq/L. A chest radiograph showed a left loculated pleural effusion, which did not layer, with underlying atelectasis. Expectorated sputum, bronchoalveolar lavage fluid and washings, and joint fluid from the left knee and left elbow were sent to the microbiology laboratory. The joint aspirates were yellow and cloudy in appearance. Gram stains of the respiratory samples and left knee aspirate showed many polymorphonuclear cells and gram-positive, beaded, branching, filamentous bacilli that were acid-fast when stained with the modified Kinyoun stain. A gram stain of the elbow fluid showed many polymorphonuclear cells and gram-positive cocci in clusters. N. brasiliensis and the Mycobacterium avium complex were recovered from the pulmonary samples. N. brasiliensis was recovered from the knee fluid, and S. aureus was recovered from the elbow fluid. Cultures of blood,
Downloaded from http://cid.oxfordjournals.org/ at Cambridge University on August 31, 2015
One genus of the actinomycetes, Nocardia, is estimated to cause 500-1,000 infections per year in the United States alone [I]. Nocardia asteroides. Nocardia brasiliensis. and Nocardia caviae are the primary human pathogens of the genus. Systemic disease is usually caused by N. asteroides and occurs most often in the immunocompromised host with T lymphocyte and macrophage defects. N. brasiliensis is most commonly associated with skin and soft-tissue infections, but it can, like N. asteroides, cause pleuropulmonary. neurological, and disseminated disease. We report a case of disseminated N. brasiliensis infection that occurred in an immunocompromised host and involved the synovium of the left knee joint and the lungs. Review of the English-language literature produced no other case report from the United States ofdisseminated N. brasiliensis infection with septic arthritis.
470
Koll et al.
Microbiology Methods and Results Dry, cream-colored colonies of N. brasiliensis grew on blood agar plates that had been incubated for 3 days at 37.0°C in the bacteriology laboratory and on plates of brainheart infusion medium incubated at 30.0°C for 3 days in the mycology laboratory. The organism produced aerial hyphae; hydrolyzed casein, tyrosine, and urea; and did not hydrolyze xanthine. Antimicrobial susceptibility was determined by the standard disk diffusion method with use of the Prompt inoculation system (Baxter Healthcare, West Sacramento, CA) and 150-mm blood agar plates (BBL Microbiology Systems, Cockeysville, MD). Zones of inhibition for antimicrobial agents on blood agar plates after a 48-hour incubation were amikacin, >30 mm; ampicillin, 0 mm; cefamandole, 0 mm; cefazolin, 0 mm; cefoxitin, 0 mm; ceftriaxone, 20 mm; cefuroxime, 20 mm; chloramphenicol, 0 mm; erythromycin, > 30 mm; gentamicin > 30 mm; oxacillin, 0 mm; penicillin, 0 mm; piperacillin, 0 mm; tetracycline, > 30 mm; ticarcillin/ clavulanic acid, >30 mm; TMP-SMZ, >30 mm; and vancomycin, 0 mm.
Discussion N. brasiliensis. a gram-posurve, filamentous bacterium, was first isolated in 1909 from a mycetoma of the leg of a
Brazilian male. It was first isolated in North America from a Mexican laborer in southern California in 1921. The first case in a United States citizen was a cutaneous infection, which was reported in 1954 [2]. Since then, infection due to N. brasiliensis has been reported with increasing frequency in a variety of clinical situations in different geographic areas of the country; 63% of the cases reported have occurred in Texas, North Carolina, Georgia, Oklahoma, and Florida. The majority of cases occurred in various tropical and subtropical parts of the world [3]. N. brasiliensis has been responsible for a variety of clinical syndromes. Seventy-two percent of the cases have occurred in immunocompetent hosts [3]. These patients were usually male, with a mean age of40 years. They presented with cutaneous, subcutaneous, or lymphocutaneous infections that mimicked staphylococcal, streptococcal, or sporotrichotic infections [2,4-6]. Pulmonary disease is less frequently seen, and it usually occurs via extension of a primary cutaneous lesion through the chest wall [3]. While N. asteroides may colonize the respiratory tract, as observed in patients who never develop clinical disease or radiographic abnormalities [7, 8], we are not aware of any cases of respiratory colonization with N. brasiliensis. Immunocompromised individuals have accounted for as many as 28% of patients with N. brasiliensis infections; these patients are also more likely to have systemic disease. Sixtyone percent of cases were associated with pleuropulmonary involvement, while 75% were associated with disseminated or CNS involvement [3]. Reports of dissemination are infrequent. Our case is the 14th reported case of disseminated N. brasiliensis disease, and, to our knowledge, is the first reported case in the United States ofdisseminated N. brasiliensis infection involving a synovial joint. Table 1 contains selected clinical information on 14 cases (including ours) of disseminated infection. Factors associated with disseminated infection have included a history of trauma, immunosuppression related to neoplastic disease, corticosteroid therapy, infection with the human immunodeficiency virus, and diabetes mellitus [3-6, 9-11, 12a, 13]. Our patient was immunosuppressed secondary to having received therapy with corticosteroids, which predisposed him to disseminated N. brasiliensis infection. The administration of corticosteroids to laboratory animals has been shown to decrease their resistance to infection caused by a variety of strains of Nocardia by effecting T lymphocyte and macrophage functions, which facilitate the invasion of tissue by these organisms [4]. The initial site of infection is usually the skin, although primary pulmonary infections have been reported. Of the 14 cases of disseminated infection summarized in table I, two were believed to be due to dissemination from the lung [3, 10]. Osteomyelitis due to N. brasiliensis has been reported [3, 10]. Septic arthritis caused by this organism was described once before in a Mexican male with chronic renal insuffi-
Downloaded from http://cid.oxfordjournals.org/ at Cambridge University on August 31, 2015
urine, and skin scrapings of the patient's pretibial areas were negative. Plain films ofthe knees and left elbow did not show signs of osteomyelitis. Results of echocardiography were normal. The patient was initially treated with intravenous vancomycin (I g every 12 hours) for the infection due to S. aureus and ceftriaxone (2 g every 12 hours) for that due to N. brasiliensis. On the basis of initial antibiotic susceptibility test results, ceftriaxone was chosen, as the patient refused trirnethoprim-sulfamethoxazole (TMP-SMZ) because of his history of myelodysplastic syndrome, which had manifested as severe anemia when he received oral TMP-SMZ in the past. An aminoglycoside was also initially refused because of his deafness. Intravenous TMP-SMZ (3 mg/kg every 6 hours, based on the trimethoprim component) and amikacin (5 mg/ kg every 8 hours) were eventually added to the regimen after 4 days of treatment, when his clinical situation deteriorated. All follow-up cultures of synovial fluid and bronchoalveolar lavage fluid were negative. Eventually the patient required intubation and hemodynamic support. He died of respiratory failure after receiving a 20-day course of antibiotic therapy. Testing for antibodies to the human immunodeficiency virus (HIV) was refused by the patient before his death. Studies to determine his T lymphocyte count were not done, and consent for an autopsy was refused, as was postmortem HIV testing.
CID 1992; 15 (September)
Disseminated Nocardia brasiliensis Infections
CID 1992; 15 (September)
Table 1.
[Reference]
Summary of data from cases of disseminated Nocardia brasiliensis infection.
Age(y)/sex
Underlying condition (therapy)
[5]
42/M
Multiple myeloma (steroids)
[II]
65/M
391M
[10]
67/M
Diabetes mellitus
[10]
18/M
Unknown
[4]
40/M
[12] [12]
51/F 22/M
Hodgkin's disease (steroids) Not specified Not specified
[12]
57/M
Not specified
[3]
25/M
[3]
37/F
Chronic granulomatous disease Unknown
[6]
56/M
[12a]
41/M
[PRJ
36/M
TMP-SMZ
Chronic obstructive pulmonary disease (steroids) AIDS
Astrocytoma (steroids) =
Sites of infection Subcutaneous tissue, perinephric abscess Skin, soft tissue, urine
Outcome
Therapy Sulfonarnides, incision drainage
+
Sulfonarnides. tetracycline,
Died
Cured
hydroxystilbarnidine, incision
+ drainage
Subcutaneous tissue, CNS, lungs, spleen, psoas abscess Lung, pleura, skin Lung, liver, spleen, bone marrow, stool Lungs. skin
Sulfonarnides, penicillin, incision + drainage
Died
Sulfonarnides, penicillin
Died
Unknown
Died
Sulfonamides
Cured
Lung, skin, brain Lung. bone, thyroid Lung, pleura, meninges Lungs, skin, bone, CNS
TMP-SMZ TMP-SMZ TMP-SMZ
Died Lost to follow-up Died
TMP-SMZ, erythromycin. cycloserine
Cured
Lungs. skin, bone, eNS Skin, lungs
Sulfonarnides. cycloserine. incision + drainage TMP-SMZ
Died
Paraspinal abscess, urine. sputum Synovia, lungs
None initially, then sulfadiazine
Died
Ceftriaxone, TMP-SMZ. amikacin
Died
trimethoprim-sulfarnethoxazole: and PR
ciency who had received a renal allograft and chronic prednisone and azathioprine therapy. He had arthritis of his left knee and pneumonia. He was treated with TMP-SMZ for 5 months, and his infection resolved [14]. Response to therapy is unusual in disseminated N. brasiliensis infections. The mortality rate associated with disseminated infection is 67%; on the other hand, all patients who have had skin and soft-tissue infections recovered, as did five of six patients with pulmonary involvement alone [3]. The mortality rate among patients with nocardial infections who receive corticosteroids is higher than that among individuals who do not receive these agents, even in the presence of severe underlying disease [4]. Therapy with sulfonamides alone is not optimal for disseminated N. brasiliensis disease [3]. TMP-SMZ is believed to be
=
Died
present report.
a better agent as it is characterized by synergy in vitro, and better clinical outcomes have been reported for local disease, although data from comparative clinical trials are not available [12, IS]. Our patient did not respond to late treatment with TMP-SMZ, although cultures of his synovial and bronchoalveolar lavage fluids became sterile while he was receiving therapy. There were two cures and four deaths among patients treated with sulfonamides alone (table I). Other agents that have been used for treatment include amikacin, ampicillin, erythromycin, minocycline, cefuroxirne, cefotaxime, imipenern, amoxicillin/clavulanic acid, and ciprofloxacin [15-17]. It should be noted that N. brasiliensis has been shown to be resistant to many of the above agents and, like N. asteroides, does produce a ,B-lactamase, which is believed to be intrinsic to the organism [16, 18]. Susceptibil-
Downloaded from http://cid.oxfordjournals.org/ at Cambridge University on August 31, 2015
[9]
Systemic lupus erythematosus, diabetes mellitus (steroids) Unknown
NOTE.
471
472
Koll et al.
ity testing should always be performed. The disk diffusion method is reliable for assessing antibiotic sensitivities [12].
Conclusions N. brasiliensis is responsible for a variety of clinical syn-
References I. Beaman BL, Burnside J, Edwards B, Causey W. Nocardial infections in the United States, 1972-1974. J Infect Dis 1976;134:286-9. 2. Moore M, Lane C, Gaul L. Nocardiosis of the knee caused by Nocardia brasiliensis. Arch Dermatol 1954;70:302-10. 3. Smego RA, Gallis HA. The clinical spectrum of Nocardia brasiliensis infection in the United States. Rev Infect Dis 1984;6: 164-80. 4. Karassik S, Subramanyam L. Green R, Brook J. Disseminated Nocardia brasiliensis infection. Arch Dermatol 1976; 112:370-2. 5. Mahvi T. Disseminated nocardiosis caused by Nocardia brasiliensis. Arch Dermatol 1964;89:426-31. 6. Schreiner 0, De Castro P, Jorizzo J, Solomon AR, Holder WR. Disseminated Nocardia brasiliensis infection following cryptococcal disease. Arch Dermatol 1986; 122: I 186-90.
7. Frazier A, Rosenow E, Roberts G. Nocardiosis-a review of 25 cases occurring during 24 months. Mayo Clin Proc 1975;50:657-63. 8. Young L, Armstrong D. Blevins A. Lieberman P. Nocardia asteroides infection complicating neoplastic disease. Am J Med 1971;50:35667. 9. Berd D. Nocardia brasiliensis infection in the United States: a report of nine cases and a review of the literature. Am J Clin Pathol 1973;60:254-8. 10. Causey W, Sieger B. Systemic nocardiosis caused by Nocardia brasiliensis. Am Rev Respir Dis 1974;109:134-7. II. Diamond R, Bennett J. Disseminated Nocardia brasiliensis infection. Arch Intern Med 1973;131:735-6. 12. Wallace RJ, Septimus EJ, Williams TW, et al. Use of'trirnethoprirn-sulfamethoxazole for treatment of infections due to Nocardia. Rev Infect Dis 1982;4:315-25. 12a.Kim J. Minamoto GY, Grieco MH. Nocardial infection as a complication of AIDS: report of six cases and review. Rev Infect Dis 1991; 13:624-9. 13. Simpson G, Stinson EB, Egger MJ, Remmington JS. Nocardial infections in the immunocompromised host: a detailed study in a defined population. Rev Infect Dis 1981;3:492-507. 14. Cons F, Trevino A, Lavalle C. Septic arthritis due to Nocardia brasiliensis. J Rheumato1 1985; 12:1019-21. 15. Stamm A, McFall 0, Dismukes W. Failure of sulfonamides and trimethoprim in the treatment of nocardiosis. Arch Intern Med 1983; 143:383-5. 16. Wallace RJ, Nash DR. Johnson WK, Steele LC, Steingrube VA. (3-lactam resistance in Nocardia brasiliensis is mediated by (3-lactamase and reversed in the presence of c1avulanic acid. J Infect Dis 1987;156:959-66. 17. Telzak E, Hii J, Polsky B. Kiehn T. Armstrong D. Nocardia infection in the acquired immunodeficiency syndrome. Diagn Microbiol Infect Dis 1989;12:517-9. 18. Wallace RJ, Steele LC, Surnter G, Smith JM. Antimicrobial susceptibility patterns of Nocardia asteroides. Antimicrob Agents Chemother 1988;32: 1776-9.
Downloaded from http://cid.oxfordjournals.org/ at Cambridge University on August 31, 2015
dromes. In the immunocompromised patient with T lymphocyte and macrophage dysfunctions, the organism can cause disseminated disease that is often unresponsive to appropriate antibiotic therapy. In this paper we report a case of synovial as well as pulmonary infection, both of which are unusual manifestations of disseminated infection with N. brasiliensis, in a patient who was immunosuppressed as a result of receiving corticosteroid therapy. A high index of suspicion, precise diagnostic studies, and immediate administration of therapy may help to decrease the mortality associated with N. brasiliensis infections in the immunologically compromised host.
CID 1992; 15 (September)
Disseminated Nocardia brasiliensis Infection with Septic Arthritis Brian S. Koll, Arthur E. Brown, Timothy E. Kiehn, and Donald Armstrong
From the Infectious Disease Service. Department of Medicine. and the Department ofPediatrics. Memorial Sloan-Kettering Cancer Center. New York; and Cornell University Medical College. New York. New York
An unusual case of disseminated Nocardia brasiliensis infection is presented. The patient, who had been receiving chronic dexamethasone therapy for 4 years, had pneumonia and septic arthritis ofthe left knee due to N. brasiliensis. To our knowledge, this is the first report from the United States of a synovial joint infection with this organism. Disseminated disease due to N. brasiliensis is infrequently reported; it is most often seen in the immunocompromised patient and is often unresponsive to therapy.
Case Report A 36-year-old man with a history of a right cerebellar and brain-stem astrocytoma (Grade III) who had received chronic dexamethasone therapy for 4 years was admitted to the hospital with a cough productive of brown sputum. He also noted a 3-week history ofleft-sided pleuritic chest pain, edema of his lower extremities, malaise, dyspnea on exertion, and fever. Two and one-half months previously, he had developed septic arthritis of the right knee due to Staphylococcus aureus. He was treated with intravenous oxacillin (2 g every 4 hours) for 6 weeks, followed by a 4-week course of oral dicloxacillin (500 mg every 6 hours). The patient had last received chemotherapy with carboplatin and carmustine for his tumor 8 months before this admission. He continued to receive dexa-
Received 14 January 1992; revised 2 April 1992. Presented in part at the 7th International Symposiumon Infections in the Immunocompromised Host. 21-24 June 1992. Boulder. Colorado. Reprints or correspondence: Dr. Arthur E. Brown. Infectious Disease Service. Memorial Sloan-Kettering Cancer Center. Box 272. 1275 York Avenue. New York. New York 10021. Clinical Infectious Diseases 1992;15:469-72 © 1992 by The University of Chicago. All rights reserved. 1058-4838/92/1503-0010$02.00
methasone for headaches presumed to be secondary to progression of his disease. While receiving dexamethasone, he also received aerosol pentamidine as prophylaxis for Pneumocystis carinii pneumonia. He was a former house painter and a lifelong resident of New York and had never traveled outside the United States. He pursued gardening as a hobby. The patient appeared acutely ill; his temperature was 39.0°C, blood pressure, 110/70 mm Hg: pulse, lOO/min; and respirations, 20/min. Abnormal physical findings included oral thrush, bilateral rhonchi, diminished breath sounds at the left base, and dullness to percussion over the left lower lung field. He had 2+ pitting edema of his lower extremities and nontender, non erythematous ballottable effusions of both knees and his left elbow. His joints had full range of motion. His neurological examination was notable for evidence of right cerebellar dysfunction. His skin was without nodules or ulcerations. Evidence of onychomycosis was observed. Laboratory findings included the following: hemoglobin level, 11.2 g/dl.; hematocrit. 35%; leukocyte count, 3,800/ mm ', with 86% granulocytes, 10% lymphocytes, and 4% monocytes: platelet count, 120,000/mm 3 ; and normal levels of serum electrolytes. An arterial blood gas analysis performed when the patient was breathing room air showed a pH of7.56; Pao2, 129 mm Hg; reo, 31 mm Hg; and serum bicarbonate level, 27 mEq/L. A chest radiograph showed a left loculated pleural effusion, which did not layer, with underlying atelectasis. Expectorated sputum, bronchoalveolar lavage fluid and washings, and joint fluid from the left knee and left elbow were sent to the microbiology laboratory. The joint aspirates were yellow and cloudy in appearance. Gram stains of the respiratory samples and left knee aspirate showed many polymorphonuclear cells and gram-positive, beaded, branching, filamentous bacilli that were acid-fast when stained with the modified Kinyoun stain. A gram stain of the elbow fluid showed many polymorphonuclear cells and gram-positive cocci in clusters. N. brasiliensis and the Mycobacterium avium complex were recovered from the pulmonary samples. N. brasiliensis was recovered from the knee fluid, and S. aureus was recovered from the elbow fluid. Cultures of blood,
Downloaded from http://cid.oxfordjournals.org/ at Cambridge University on August 31, 2015
One genus of the actinomycetes, Nocardia, is estimated to cause 500-1,000 infections per year in the United States alone [I]. Nocardia asteroides. Nocardia brasiliensis. and Nocardia caviae are the primary human pathogens of the genus. Systemic disease is usually caused by N. asteroides and occurs most often in the immunocompromised host with T lymphocyte and macrophage defects. N. brasiliensis is most commonly associated with skin and soft-tissue infections, but it can, like N. asteroides, cause pleuropulmonary. neurological, and disseminated disease. We report a case of disseminated N. brasiliensis infection that occurred in an immunocompromised host and involved the synovium of the left knee joint and the lungs. Review of the English-language literature produced no other case report from the United States ofdisseminated N. brasiliensis infection with septic arthritis.
470
Koll et al.
Microbiology Methods and Results Dry, cream-colored colonies of N. brasiliensis grew on blood agar plates that had been incubated for 3 days at 37.0°C in the bacteriology laboratory and on plates of brainheart infusion medium incubated at 30.0°C for 3 days in the mycology laboratory. The organism produced aerial hyphae; hydrolyzed casein, tyrosine, and urea; and did not hydrolyze xanthine. Antimicrobial susceptibility was determined by the standard disk diffusion method with use of the Prompt inoculation system (Baxter Healthcare, West Sacramento, CA) and 150-mm blood agar plates (BBL Microbiology Systems, Cockeysville, MD). Zones of inhibition for antimicrobial agents on blood agar plates after a 48-hour incubation were amikacin, >30 mm; ampicillin, 0 mm; cefamandole, 0 mm; cefazolin, 0 mm; cefoxitin, 0 mm; ceftriaxone, 20 mm; cefuroxime, 20 mm; chloramphenicol, 0 mm; erythromycin, > 30 mm; gentamicin > 30 mm; oxacillin, 0 mm; penicillin, 0 mm; piperacillin, 0 mm; tetracycline, > 30 mm; ticarcillin/ clavulanic acid, >30 mm; TMP-SMZ, >30 mm; and vancomycin, 0 mm.
Discussion N. brasiliensis. a gram-posurve, filamentous bacterium, was first isolated in 1909 from a mycetoma of the leg of a
Brazilian male. It was first isolated in North America from a Mexican laborer in southern California in 1921. The first case in a United States citizen was a cutaneous infection, which was reported in 1954 [2]. Since then, infection due to N. brasiliensis has been reported with increasing frequency in a variety of clinical situations in different geographic areas of the country; 63% of the cases reported have occurred in Texas, North Carolina, Georgia, Oklahoma, and Florida. The majority of cases occurred in various tropical and subtropical parts of the world [3]. N. brasiliensis has been responsible for a variety of clinical syndromes. Seventy-two percent of the cases have occurred in immunocompetent hosts [3]. These patients were usually male, with a mean age of40 years. They presented with cutaneous, subcutaneous, or lymphocutaneous infections that mimicked staphylococcal, streptococcal, or sporotrichotic infections [2,4-6]. Pulmonary disease is less frequently seen, and it usually occurs via extension of a primary cutaneous lesion through the chest wall [3]. While N. asteroides may colonize the respiratory tract, as observed in patients who never develop clinical disease or radiographic abnormalities [7, 8], we are not aware of any cases of respiratory colonization with N. brasiliensis. Immunocompromised individuals have accounted for as many as 28% of patients with N. brasiliensis infections; these patients are also more likely to have systemic disease. Sixtyone percent of cases were associated with pleuropulmonary involvement, while 75% were associated with disseminated or CNS involvement [3]. Reports of dissemination are infrequent. Our case is the 14th reported case of disseminated N. brasiliensis disease, and, to our knowledge, is the first reported case in the United States ofdisseminated N. brasiliensis infection involving a synovial joint. Table 1 contains selected clinical information on 14 cases (including ours) of disseminated infection. Factors associated with disseminated infection have included a history of trauma, immunosuppression related to neoplastic disease, corticosteroid therapy, infection with the human immunodeficiency virus, and diabetes mellitus [3-6, 9-11, 12a, 13]. Our patient was immunosuppressed secondary to having received therapy with corticosteroids, which predisposed him to disseminated N. brasiliensis infection. The administration of corticosteroids to laboratory animals has been shown to decrease their resistance to infection caused by a variety of strains of Nocardia by effecting T lymphocyte and macrophage functions, which facilitate the invasion of tissue by these organisms [4]. The initial site of infection is usually the skin, although primary pulmonary infections have been reported. Of the 14 cases of disseminated infection summarized in table I, two were believed to be due to dissemination from the lung [3, 10]. Osteomyelitis due to N. brasiliensis has been reported [3, 10]. Septic arthritis caused by this organism was described once before in a Mexican male with chronic renal insuffi-
Downloaded from http://cid.oxfordjournals.org/ at Cambridge University on August 31, 2015
urine, and skin scrapings of the patient's pretibial areas were negative. Plain films ofthe knees and left elbow did not show signs of osteomyelitis. Results of echocardiography were normal. The patient was initially treated with intravenous vancomycin (I g every 12 hours) for the infection due to S. aureus and ceftriaxone (2 g every 12 hours) for that due to N. brasiliensis. On the basis of initial antibiotic susceptibility test results, ceftriaxone was chosen, as the patient refused trirnethoprim-sulfamethoxazole (TMP-SMZ) because of his history of myelodysplastic syndrome, which had manifested as severe anemia when he received oral TMP-SMZ in the past. An aminoglycoside was also initially refused because of his deafness. Intravenous TMP-SMZ (3 mg/kg every 6 hours, based on the trimethoprim component) and amikacin (5 mg/ kg every 8 hours) were eventually added to the regimen after 4 days of treatment, when his clinical situation deteriorated. All follow-up cultures of synovial fluid and bronchoalveolar lavage fluid were negative. Eventually the patient required intubation and hemodynamic support. He died of respiratory failure after receiving a 20-day course of antibiotic therapy. Testing for antibodies to the human immunodeficiency virus (HIV) was refused by the patient before his death. Studies to determine his T lymphocyte count were not done, and consent for an autopsy was refused, as was postmortem HIV testing.
CID 1992; 15 (September)
Disseminated Nocardia brasiliensis Infections
CID 1992; 15 (September)
Table 1.
[Reference]
Summary of data from cases of disseminated Nocardia brasiliensis infection.
Age(y)/sex
Underlying condition (therapy)
[5]
42/M
Multiple myeloma (steroids)
[II]
65/M
391M
[10]
67/M
Diabetes mellitus
[10]
18/M
Unknown
[4]
40/M
[12] [12]
51/F 22/M
Hodgkin's disease (steroids) Not specified Not specified
[12]
57/M
Not specified
[3]
25/M
[3]
37/F
Chronic granulomatous disease Unknown
[6]
56/M
[12a]
41/M
[PRJ
36/M
TMP-SMZ
Chronic obstructive pulmonary disease (steroids) AIDS
Astrocytoma (steroids) =
Sites of infection Subcutaneous tissue, perinephric abscess Skin, soft tissue, urine
Outcome
Therapy Sulfonarnides, incision drainage
+
Sulfonarnides. tetracycline,
Died
Cured
hydroxystilbarnidine, incision
+ drainage
Subcutaneous tissue, CNS, lungs, spleen, psoas abscess Lung, pleura, skin Lung, liver, spleen, bone marrow, stool Lungs. skin
Sulfonarnides, penicillin, incision + drainage
Died
Sulfonarnides, penicillin
Died
Unknown
Died
Sulfonamides
Cured
Lung, skin, brain Lung. bone, thyroid Lung, pleura, meninges Lungs, skin, bone, CNS
TMP-SMZ TMP-SMZ TMP-SMZ
Died Lost to follow-up Died
TMP-SMZ, erythromycin. cycloserine
Cured
Lungs. skin, bone, eNS Skin, lungs
Sulfonarnides. cycloserine. incision + drainage TMP-SMZ
Died
Paraspinal abscess, urine. sputum Synovia, lungs
None initially, then sulfadiazine
Died
Ceftriaxone, TMP-SMZ. amikacin
Died
trimethoprim-sulfarnethoxazole: and PR
ciency who had received a renal allograft and chronic prednisone and azathioprine therapy. He had arthritis of his left knee and pneumonia. He was treated with TMP-SMZ for 5 months, and his infection resolved [14]. Response to therapy is unusual in disseminated N. brasiliensis infections. The mortality rate associated with disseminated infection is 67%; on the other hand, all patients who have had skin and soft-tissue infections recovered, as did five of six patients with pulmonary involvement alone [3]. The mortality rate among patients with nocardial infections who receive corticosteroids is higher than that among individuals who do not receive these agents, even in the presence of severe underlying disease [4]. Therapy with sulfonamides alone is not optimal for disseminated N. brasiliensis disease [3]. TMP-SMZ is believed to be
=
Died
present report.
a better agent as it is characterized by synergy in vitro, and better clinical outcomes have been reported for local disease, although data from comparative clinical trials are not available [12, IS]. Our patient did not respond to late treatment with TMP-SMZ, although cultures of his synovial and bronchoalveolar lavage fluids became sterile while he was receiving therapy. There were two cures and four deaths among patients treated with sulfonamides alone (table I). Other agents that have been used for treatment include amikacin, ampicillin, erythromycin, minocycline, cefuroxirne, cefotaxime, imipenern, amoxicillin/clavulanic acid, and ciprofloxacin [15-17]. It should be noted that N. brasiliensis has been shown to be resistant to many of the above agents and, like N. asteroides, does produce a ,B-lactamase, which is believed to be intrinsic to the organism [16, 18]. Susceptibil-
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[9]
Systemic lupus erythematosus, diabetes mellitus (steroids) Unknown
NOTE.
471
472
Koll et al.
ity testing should always be performed. The disk diffusion method is reliable for assessing antibiotic sensitivities [12].
Conclusions N. brasiliensis is responsible for a variety of clinical syn-
References I. Beaman BL, Burnside J, Edwards B, Causey W. Nocardial infections in the United States, 1972-1974. J Infect Dis 1976;134:286-9. 2. Moore M, Lane C, Gaul L. Nocardiosis of the knee caused by Nocardia brasiliensis. Arch Dermatol 1954;70:302-10. 3. Smego RA, Gallis HA. The clinical spectrum of Nocardia brasiliensis infection in the United States. Rev Infect Dis 1984;6: 164-80. 4. Karassik S, Subramanyam L. Green R, Brook J. Disseminated Nocardia brasiliensis infection. Arch Dermatol 1976; 112:370-2. 5. Mahvi T. Disseminated nocardiosis caused by Nocardia brasiliensis. Arch Dermatol 1964;89:426-31. 6. Schreiner 0, De Castro P, Jorizzo J, Solomon AR, Holder WR. Disseminated Nocardia brasiliensis infection following cryptococcal disease. Arch Dermatol 1986; 122: I 186-90.
7. Frazier A, Rosenow E, Roberts G. Nocardiosis-a review of 25 cases occurring during 24 months. Mayo Clin Proc 1975;50:657-63. 8. Young L, Armstrong D. Blevins A. Lieberman P. Nocardia asteroides infection complicating neoplastic disease. Am J Med 1971;50:35667. 9. Berd D. Nocardia brasiliensis infection in the United States: a report of nine cases and a review of the literature. Am J Clin Pathol 1973;60:254-8. 10. Causey W, Sieger B. Systemic nocardiosis caused by Nocardia brasiliensis. Am Rev Respir Dis 1974;109:134-7. II. Diamond R, Bennett J. Disseminated Nocardia brasiliensis infection. Arch Intern Med 1973;131:735-6. 12. Wallace RJ, Septimus EJ, Williams TW, et al. Use of'trirnethoprirn-sulfamethoxazole for treatment of infections due to Nocardia. Rev Infect Dis 1982;4:315-25. 12a.Kim J. Minamoto GY, Grieco MH. Nocardial infection as a complication of AIDS: report of six cases and review. Rev Infect Dis 1991; 13:624-9. 13. Simpson G, Stinson EB, Egger MJ, Remmington JS. Nocardial infections in the immunocompromised host: a detailed study in a defined population. Rev Infect Dis 1981;3:492-507. 14. Cons F, Trevino A, Lavalle C. Septic arthritis due to Nocardia brasiliensis. J Rheumato1 1985; 12:1019-21. 15. Stamm A, McFall 0, Dismukes W. Failure of sulfonamides and trimethoprim in the treatment of nocardiosis. Arch Intern Med 1983; 143:383-5. 16. Wallace RJ, Nash DR. Johnson WK, Steele LC, Steingrube VA. (3-lactam resistance in Nocardia brasiliensis is mediated by (3-lactamase and reversed in the presence of c1avulanic acid. J Infect Dis 1987;156:959-66. 17. Telzak E, Hii J, Polsky B. Kiehn T. Armstrong D. Nocardia infection in the acquired immunodeficiency syndrome. Diagn Microbiol Infect Dis 1989;12:517-9. 18. Wallace RJ, Steele LC, Surnter G, Smith JM. Antimicrobial susceptibility patterns of Nocardia asteroides. Antimicrob Agents Chemother 1988;32: 1776-9.
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dromes. In the immunocompromised patient with T lymphocyte and macrophage dysfunctions, the organism can cause disseminated disease that is often unresponsive to appropriate antibiotic therapy. In this paper we report a case of synovial as well as pulmonary infection, both of which are unusual manifestations of disseminated infection with N. brasiliensis, in a patient who was immunosuppressed as a result of receiving corticosteroid therapy. A high index of suspicion, precise diagnostic studies, and immediate administration of therapy may help to decrease the mortality associated with N. brasiliensis infections in the immunologically compromised host.
CID 1992; 15 (September)
