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Infectious Diseases in Clinical Practice:
doi: 10.1097/IPC.0b013e31803097eb
Case Reports

Disseminated Mycobacterium szulgai Infection: Case Report and Review of Literature

Manalac, Tyrone Christopher MD; Bonilla, Hector MD

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Summa Health System, Akron City Hospital, Akron OH.

Address correspondence and reprint requests to Tyrone Christopher A. Manalac, MD, 55 Arch St, Suite 1B, Akron OH, 44304. E-mail: tyrone_MD@yahoo.com.

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Abstract

Mycobacterium szulgai is a nontuberculous mycobacteria that is an emerging pathogen particularly in immunocompromised patients. It is rarely associated with human disease and is an ubiquitous environmental mycobacterium that has the potential to cause localized and disseminated disease in both immunocompromised and healthy individuals. Although pulmonary disease is the most frequent clinical manifestation of infection, involvement of other organs such as joint, bone, skin, soft tissue, and cornea have been described. We report a 65-year-old malnourished man with non-Hodgkin lymphoma and chronic lymphocytic leukemia on chemotherapy, who developed disseminated M. szulgai infection. Mycobacterium szulgai was isolated from multiple joints. The patient was successfully treated with antibiotic therapy in combination with surgical incision and drainage of the affected joints. The patient later died of causes unrelated to his infection.

Since the 1980s, with the growing number of immunocompromised individuals, the nontuberculous mycobacteria (NTM) have been a significant contributor of morbidity and mortality. Mycobacterium avium-intracellulare complex, Mycobacterium gordonae, Mycobacterium fortuitum, and Mycobacterium kansasii are the most common of these pathogens. Mycobacterium szulgai is an NTM rarely associated with human disease. According to the Centers for Disease Control and Prevention (CDC), M. szulgai is accountable for less than 1% of the NTM human infection. Lung infection is the most common clinical presentation, often mimicking pulmonary tuberculosis, but other organs and tissues may also be involved. Patients who are immunosuppressed (with cancer, chemotherapy, HIV, or malnutrition) seem more prone to have localized or disseminated disease. We report a case of disseminated M. szulgai infection in an immunocompromised host, with review of the medical literature.

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CASE REPORT

A 65-year-old white man was admitted to the hospital on December 12, 2004 with a 2-week history of edema, erythema, pain, and local increase in temperature over the left arm, elbows, knees, and right foot. In addition, he reported fever, chills, shortness of breath, and a productive cough.

The patient had a history of chronic lymphocytic leukemia and low-grade non-Hodgkin lymphoma diagnosed in 1992 and treated with chemotherapy. The last course of chemotherapy, a month before this admission, consisted of cyclophosphamide and prednisone. He also had a history of severe mitral regurgitation, asthma, chronic obstructive pulmonary disease, and herpes zoster. In addition, he was recently diagnosed with disseminated histoplasmosis and cryptococcosis for which he was treated with itraconazole. The patient lived in a mobile home with his spouse, with no pets, no sick contacts, and no travel history. He smoked between 1 and 3 packs per day and denied alcohol use or recreational drugs.

His physical examination showed a chronically ill and malnourished man, with a temperature of 101.8°F, blood pressure of 114/49 mm Hg, heart rate of 92 beats per minute, respiratory rate of 18 breaths per minute, and a body mass index of 16.7. He had clinical signs of active arthritis, involving the elbows, knees, and the right foot. Other significant findings included bilateral rhonchi and hepatosplenomegaly.

Initial laboratory examination showed the following: white blood cell count (WBC), 7600 cells/cm3; neutrophils, 20%; bands, 20%; lymphocytes, 55%; platelets, 85,000 cells/cm3; hemoglobin, 9.9 g/dL; hematocrit, 30.5%; serum urea nitrogen, 19 mg/dL; creatinine, 0.5 mg/dL; albumin, 1.4 g/dL; total protein, 3.3 g/dL; alkaline phosphatase, 224 U/L; cholesterol, 78 mg/dL; and erythrocyte sedimentation rate, 58 mm/h. Chest radiograph and computed tomographic scan showed cardiomegaly, bilateral pleural effusions, and consolidation over the left side.

Arthrocentesis was performed on the right knee, yielding thick yellowish fluid. The Gram stain showed unstained cells (empty cells), and the acid-fast stain showed an acid-fast organism (Figs. 1, 2). Cultures for bacteria, fungi, and mycobacteria were ordered. The patient also underwent incision and drainage of the other affected joints, yielding similar purulent material. Analysis of this articular fluid revealed WBC of 17,710 cells/cm3, red blood cell of 5500 cells/cm3, macrophage of 7%, polymorphonuclear neutrophil of 83%, lymphocytes of 10%, and no crystals. Thoracentesis was also performed, and 550 mL of amber-colored pleural fluid was evacuated. The analysis of this fluid showed WBC of 53,000 cells/cm3, neutrophils of 3%, macrophages of 44%, protein of 1.2 g/dL, and lactate dehydrogenase of 63 IU/L. Pleural fluid cultures were negative for bacteria, fungus, or mycobacteria. With the suspicion of nocardiosis and possible mycobacterium infection, the patient empirically was started on ertapenem and trimethoprim-sulfamethoxazole. The patient had lysis of the fever and also improvement of clinical signs of the septic arthritis.

Figure 1
Figure 1
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Figure 2
Figure 2
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On the seventh day, the cultured synovial fluid showed a heavy growth of yellow smooth colonies on Lowenstein-Jensen slant. These colonies were acid-fast positive. The organism was later identified by the Ohio Department of Health as M. szulgai using high-performance liquid chromatography (HPLC). Susceptibility studies were done at the CDC, revealing the organism to be sensitive to isoniazid (5 μg/mL), rifampin, streptomycin (10 μg/mL), ethambutol, ethionamide, rifabutin, and ciprofloxacin; to have an intermediate resistance to isoniazid (0.2 μg/mL); and to be resistant to streptomycin (2 μg/mL).

Based on these susceptibility patterns, the patient's antibiotic regimen was changed to levofloxacin, clarithromycin, and rifampin. The patient showed further improvement and was transferred to the rehabilitation unit. He later died of respiratory failure.

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DISCUSSION

Mycobacteria are aerobic, nonspore-forming, bacillar organisms that contain mycolic acid and belong to the family Mycobacteriaceae.1 They do not stain with Gram stain and are resistant to decolorization by acid or alcohol and hence the term acid-fast bacilli.1 Almost a hundred species have been described, of which, approximately a third are associated with human disease.2,5,7,11 They have generally been divided into 2 groups-the "tuberculous mycobacteria" and the "NTM"-also known as "atypical mycobacteria" or "mycobacteria other than tubercle bacilli."7,11 Traditionally, NTM has been classified on the basis of colony morphology, growth rate, pigmentation, thermotolerance, and animal virulence.1,4,11,16 Biochemical tests and, more recently, rapid molecular systems (DNA-DNA hybridization, HPLC analysis of mycolic acids, and sequence and/or restriction analysis of the 16S ribosomal RNA, superoxide dismutase, and stress response genes) have aided in the identification of these organisms.1,7,8

Since the 1980s, there has been a rising incidence of NTM infections-directly attributable to immunosuppression from cancer chemotherapy or organ transplant, the acquired immune deficiency syndrome, and improved diagnostic methods.7,14,15 Several laboratory surveys in the United States reported the most common NTM pathogens in order of prevalence included: M. avium-intracellulare complex, M. gordonae, M. fortuitum, M. kansasii, Mycobacterium terrae, Mycobacterium chelonae, Mycobacterium xenopi, Mycobacterium flavescens, Mycobacterium simiae, and Mycobacterium marinum.5,7,14,15,32

Mycobacterium szulgai, named after Dr T. Szulga,6 was first described in 1972 and presently accounts for less than 1% of all NTM isolates by the CDC.6,32 It is classified under the Runyon group II organisms, exhibiting scotochromogenicity at 39°C and photochromogenicity at 25°C; colonies become visible after 7 days, developing pigment when cultured in the dark and during urease production.3,6,9,31 Arylsulfatase activity is also an important biochemical marker for the identification of M. szulgai.6,9 Other methods of identification for M. szulgai have been developed and include HPLC and gene amplification.3,23 When available, gene amplification and sequencing should be favored.12,25 Our isolate turned positive after 7 days of incubation in Lowenstein-Jensen slant. This early isolation can be explained by the heavy mycobacterium burden present in the patient's joints.

Mycobacterium szulgai has a worldwide distribution and is relatively uncommon in humans and nature; however, it is considered a true pathogen when isolated in humans.19-44 Mainly an environmental organism, it has been isolated from snails, tropical fishes, frogs, aquarium water, and hospital water supply systems.3,9,13,18,36,45 Human-to-human transmission has not been observed.10

Mycobacterium szulgai infection has been reported in all age groups, with predilection for the 21- to 40-year-old age group.17-44 Common symptoms include fever, weight loss, cough, and night sweats, and manifest rarely with joint pain and adenopathy.17-44 Pulmonary infection seems to be the most frequent clinical presentation, usually mimicking pulmonary tuberculosis.31-43 Other sites of infections include the soft tissues, bone, joints, cornea, and lymphatics. Infection has been reported more frequently in immunocompromised individuals and in patients with pulmonary tuberculosis, chronic obstructive pulmonary disease, HIV/acquired immune deficiency syndrome, alcohol/tobacco abuse, or malnutrition.17-44 Disseminated disease has also been well described in 2 cases.26,28 We present the third case reported with disseminated infection, which presented with constitutional symptoms (fever and chills) and multiple infected joints for which M. szulgai was isolated. This patient was a severely malnourished and immunocompromised host with leukemia, lymphoma, and a recent course of chemotherapy, which predisposed him to develop this infection.

Recently, the National Committee for Clinical Laboratory Standards published a document for standardization of susceptibility testing of all mycobacterial species, including the NTM; however, there have been no recommendations for M. szulgai.46 Studies, however, have shown that M. szulgai is generally susceptible in vitro to manystandard antimicrobial agents such as isoniazid, rifampin, ethambutol, ethionamide, streptomycin, cefoxitin, amikacin, and dapsone.6,7,17-44 No standard regimen for therapy exists, but most patients seem to respond to a combination of antituberculous antibiotics-isoniazid-rifampicin-ethambutol or rifampin-ethambutol-in conjunction with other antibiotic classes.19-44 Although the optimal duration of therapy is unknown, the length of therapy may range from 4 to 48 months.17-44 Resistance to cycloserine, p-aminosalicylate, pyrazinamide, kanamycin, isoniazid, and streptomycin has also been described.17-44

Our patient was initially treated medically with ertapenem and trimethoprim-sulfamethoxazole for the suspicion of nocardiosis and later with surgical drainage of the infected joints. With the identification of M. szulgai and the susceptibility profile reported by the CDC, the patient's treatment was changed to levofloxacin, clarithromycin, and rifampin. The patient had significant clinical improvement with therapy but later died of causes unrelated to the M. szulgai infection.

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