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173 Cutaneous and Pulmonary Infections Caused by Mycobacterium vaccae Ray Hachem, Issam Raad, Kenneth V. I. Rolston, Estella Whimbey, Ruth Katz, Jeffrey Tarrand, and Herman Libshitz From the Section of Infectious Diseases. Department of Medical Specialties. the Division of Laboratory Medicine, the Department of Pathology. and the Department of Diagnostic Radiology, The University of Texas M. D. Anderson Cancer Center, Houston. Texas Mycobacterium vaccae is a rapidly growingmycobacterial speciesthat was previously not considered a human pathogen. We report four cases of M. vaccae infection that occurred in the southern United States; one patient had cutaneous disease,and three patients had cavitary lung disease.Two of the three patients with pulmonary disease had a history of exposure to cattle. The conditions of all patients improved with therapy: the cutaneous infection responded to therapy with minocycline and trimethoprim-sulfamethoxazole, and the pulmonary infections responded to therapy with ciprofloxacin. Clinicians have become increasingly aware that species of mycobacteria previously considered nonpathogenic can cause serious disease in immunocompromised patients. Infections caused by the rapidly growing mycobacteria are now more frequently recognized [1, 2] and appear to be endemic in the southern United States, from Georgia to Texas [1]. Mycobacterium vaccae, one of the rapidly growing mycobacteria previously considered nonpathogenic, has been associated with pulmonary infections and soft-tissue infections in four patients at The University of Texas M.D. Anderson Cancer Center (Houston) over the last 3 years. To our knowledge, this is the first report of M vaccae infection as a cause of invasive disease in humans. Case Reports Case 1. A 67-year-old man who was found to have chronic myelocytic leukemia in July 1992 developed fever and a 4 X 2-cm raised, tender, erythematous nodule on his left thigh during a period of chemotherapy-induced myelosuppression. An ultrasonogram of the thigh did not reveal any underlying abscess. Examination of fluid obtained by fine-needle aspiration revealed granulomatous inflammation (figure 1). Many colonies of M. vaccae were isolated from a culture of this aspirate; however, acid-fast stains were negative. A 4-week course of trimethoprim-sulfamethoxazole (TMP-SMZ) and minocycline resulted in a reduction in his temperature and significant regression of the skin lesion. However, the patient died I month later after he was readmitted to the hospital with chemotherapyinduced myelosuppression, fever, gastrointestinal hemorrhage, Received 7 September 1995; revised 1 February 1996. Reprints or correspondence: Dr. Issam Raad, Section ofInfectious Diseases47, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030. Clinical Infectious Diseases 1996;23:173-5 © 1996 by The University of Chicago. AlI rights reserved. 1058--4838/96/2301-0025$02.00 and right middle-lobe pneumonia of unknown etiology. Permission for autopsy was denied. Case 2. A 45-year-old man with multiple cavitary lung lesions of several months' duration and right lower-lobe pneumonia was referred to our center for further evaluation ofpossible lung cancer. The patient had a history of exposure to cattle 2 years earlier. On admission, he complained of a cough productive of frothy sputum that had been present for 3 weeks and right-sided pleuritic chest pain; physical examination revealed a pleural friction rub. A CT scan of the chest revealed a cavitary lesion in the right upper lobe and a right pleural effusion with air-fluid levels. Sputum cultures for bacteria. fungi, and viruses were negative. The patient was treated for 1 week with intravenous ciprofloxacin, and a partial clinical response was observed. One week later, he underwent bronchoscopy, right thoracotomy, anterior segmentectomy of the upper lobe, and mediastinal lymph node dissection. The histopathology was consistent with empyema and fibrosing pleuritis; there was no evidence of malignancy. Stains for acid-fast bacilli were positive. Two weeks later, M. vaccae was isolated from an intraoperative culture of the right upper-lobe cavitary lesion. The organism was susceptible to isoniazid, rifampin, aminoglycosides, and ciprofloxacin, but it was resistant to streptomycin and ethambutol. Drug susceptibility testing was performed by the Texas Department of Health (Austin, TX) with use of the agar disk elution method reported by Stone et al. [3]. The patient was discharged and instructed to take oral ciprofloxacin, but he did not return for follow-up. Case 3. A 57-year-old man with poorly differentiated nonsmall-cell carcinoma of the lung presented with a dry cough and shortness of breath of 1 month's duration. The patient reported a 3-year history of exposure to cattle. A chest radiograph revealed a cavitary left upper-lung lesion and bilateral pneumonia. The patient received a IO-day course of erythromycin that did not result in improvement in his condition and then was given ticarcillin/clavulanic acid and gentamicin, with a good response. The only mycobacterial culture of sputum yielded many colonies of M. vaccae; however, a smear for 174 Hachem et al. em 1996;23 (July) isolate was susceptible to ciprofloxacin, doxycycline, and aminoglycosides but resistant to TMP-SMZ and erythromycin. The patient remained asymptomatic, and his chest radiograph showed marked improvement in his condition after 6 months of therapy with doxycycline and ciprofloxacin. Discussion Figure 1. Acid-fast bacilli stain of fluid obtained by fine-needle aspiration of a subcutaneous thigh lesion in a patient with Mycobacterium vaccae infection; focal granuloma formation is evidenced by a tight group of epithelioid histiocytes. acid-fast bacilli was negative. The isolate was susceptible to aminoglycosides, doxycycline, cefoxitin, TMP-SMZ, erythromycin, imipenem/cilastatin, and ciprofloxacin. The patient was treated for 7 more days with intravenous TMP-SMZ and ciprofloxacin and was then discharged in stable condition. One month later, he died of complications related to his underlying lung cancer. Permission for autopsy was not granted. Case 4. A 60-year-old man with squamous cell carcinoma of the nasopharynx was treated with chemotherapy and highdose radiotherapy to the supraclavicular nodes and upper larynx. A routine chest radiograph revealed a cavitary lesion in the right upper lobe. The patient had no history of exposure to tuberculosis and denied having cough, hemoptysis, night sweats, fever, chills, or shortness of breath. Two months later, the chest radiograph revealed progression of the right upper-lobe lesion and a new irregular patchy infiltrate in the left upper lobe. Skin testing with PPD (5 TU) yielded a 9-mm induration. The patient underwent bronchoscopy, and examination of bronchial biopsy specimens revealed multinucleated giant cells, consistent with mycobacterial disease. However, stains of the bronchial lavage fluid and bronchial tissue were negative for acid-fast bacilli. Empirical therapy with rifampin, ethambutol, and clarithromycin was started. One of the three mycobacterial sputum cultures subsequently yielded many colonies of M. vaccae. Smears of the sputum were negative for acid-fast bacilli. The M. vaccae, a rapidly growing nontuberculous mycobacterium, was first isolated, described, and named in 1963 by Bonicke and Juhasz [4]. Sixty-three strains of M. vaccae have been isolated from the environment in which cattle live, including the soil and water, as well as from bovine lactic ducts, skin nodules, and milk products. Because of the strong association of this mycobacterial species with cattle, it was named vaccae, the Latin word for cow. It is of interest that two of the three patients with pulmonary M. vaccae infection had long histories of exposure to cattle while living on farms. The M. vaccae isolates were identified in our laboratory as follows. All four strains were probe negative for Mycobacterium tuberculosis, Mycobacterium avium, Mycobacterium kansasii, and Mycobacterium gordonae. All strains grew on Lowenstein-Jensen medium at 37°C. The colonies were smooth, moist, and shiny; yellow-to-orange pigmentation was apparent in the light and in the dark. They were curved to rod-shaped, were nonmotile, and measured 1-2 J..lm X 0.5-0.8 us». Subcultures failed to yield growth at 52°C but did yield growth at 24°C. All strains were arylsulfatase negative and tellurite positive and grew in 5% NaCI; they demonstrated positive semiquantitative catalase and iron uptake and did not grow on MacConkey agar; and they produced smooth, moist, pigmented scotochromogenic colonies. Although some strains of Mycobacterium phlei are smooth, this species typically does not uptake iron. Although some strains of Mycobacterium thermoresistible may resemble M. vaccae biochemically, they normally grow at 52°C. Our identification scheme is based on the Centers for Disease Control and Prevention recommendations published by the Texas State Department of Health in 1991 [5]. M vaccae has not previously been reported to be pathogenic in humans. However, M. vaccae has been reported as a cause of clinical diseases, such as bovine nodular thelitis, in cows [6, 7]. The four patients with M. vaccae infection described in this report included one with cutaneous disease and three with pulmonary disease. The skin and the lungs are commonly involved in cases of infection due to rapidly growing mycobacteria [8]. In the case of the patient with the skin nodule, the diagnosis was confirmed by cytopathological examination, which revealed granulomatous inflammation (figure 1). The three pulmonary cases were characterized by pulmonary infiltrates and the isolation of M. vaccae from cultures of sputum or lung tissue in the absence of other identifiable causes of disease (e.g., fungal disease, malignancy, or tuberculosis). ern 1996;23 (July) Infection Due to Mycobacterium vaccae Susceptibility studies were done for the three patients with pulmonary disease [3]. Allthreepulmonary isolates weresusceptible to ciprofloxacin and aminoglycosides, and all three patients responded to treatment with ciprofloxacin. No susceptibility studies were done for the patient with cutaneous disease, and he responded to therapy withTMP-SMZ andminocycline (M vaccae may occasionally be susceptible to TMP-SMZ and tetracyclines). In conclusion, M vaccae may cause cutaneous or pulmonary infections in humans, and immunocompromised patients with cancer are especially vulnerable. A history of exposure to cattle shouldraise the clinical suspicion of infection with this pathogen in patients who have cutaneous or pulmonary disease. Further studies are required to delineate the epidemiology, clinical manifestations, and optimal therapy for M vaccae infection. References 1. Wallace RJ Jr, Swenson JM, Silcox VA, Good RC, Tschen JA, Stone MS. Spectrum of disease due to rapidly growing mycobacteria. Rev Infect Dis 1983; 5:657 - 79. 175 2. Rolston KV, Jones PG, Fainstein V, Bodey GP. Pulmonary disease caused by rapidly growing Mycobacteria in patients with cancer. Chest 1985; 87:503-6. 3. Stone MS, Wallace RJ Jr, Swenson JM, Thornsberry C, Christensen LA. Agar disk elution method for susceptibility testing of Mycobacterium marinum and Mycobacterium fortuitum complex to sulfonamides and antibiotics. Antimicrob Agents Chemother 1983;24: 486-93. 4. Bonicke R, Juhasz SE. Beschreibung der neuen Species Mycobacterium vaccae no. sp. Zentralbl Bakteriol [Orig A] 1962:133-5. 5. Laboratory procedures in mycobacteriology. Texas State Department of Health Workshop Publication. Austin, Texas: Texas State Department of Health, 1991. 6. Shimizu K, Hirose T, Sato M, Tsukamura M. Isolation of acid-fast organisms resembling Mycobacterium vaccae from a lesion of bovine nodular thelitis. Microbiol Immunol 1977; 21:469- 72. 7. Koehne G, Maddux R, Britt 1. Rapidly growing mycobacteria associated with bovine mastitis. Am J Vet Res 1981;42:1238-9. 8. Wallace RJ Jr. The clinical presentation, diagnosis, and therapy of cutaneous and pulmonary infections due to the rapidly growing mycobacteria, M. fortuitum and M. chelonae. Clin Chest Med 1989; 10:419-29.