Download Cutaneous and Pulmonary Infections Caused by Mycobacterium

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.