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Lung abscess due to corynebacterium equi. Report of the first case in a patient with acquired immune deficiency syndrome
Lung Abscess Due to Corynebacterium equi Report of the First Case in a Patient with Acquired Immune Deficiency Syndrome
JOHN H. SAMIES, M.D. BRUCE N. HATHAWAY, M.D. ROGER M. ECHOLS, M.D. JAMES M. VEAZEY, Jr., M.D. VERNON A. PILON, M.D. Albany, New York
A lung abscess and persistent bacteremia due to Corynebacterium equi are described in a bisexual man with the acquired immune deficiency syndrome (AIDS). Eleven of the 12 previously reported cases have occurred in immunocompromised humans. The occurrence of this infection in a patient with AIDS has not been previously
described, Development of resistance to beta-lactam antibiotics was noted following initial therapy. Because this organism resembles nonpathogenic organisms, it may easily be overlooked despite its ability to cause serious infection and persist even with aggressive antimicrobial and surgical therapy. Although the pathogenicity of Corynebacterium equi in domestic animals is well established, it is a rare pathogen in humans, having been described in only 12 patients in the literature. All but one of the previously reported human cases have been in immunocompromised patients. This is the first report of a patient with the acquired immune deficiency syndrome (AIDS) who had a lung abscess and persistent bacteremia due to C. equi. The microbiologic and clinical characteristics of this case illustrate the potential human pathogenicity of this organism.
CASE REPORT
From the Division of Infectious Diseases, Department of Medicine, and the Department of Pathology, Albany Medical College of Union University, Albany, New York. Requests for reprints should be addressed to Dr. Roger M. Echols, Division of Infectious Diseases, Albany Medical College, MS-103, Albany, New York 12208. Manuscript accepted December 12, 1984.
A 36-year-old bisexual former alcohol and intravenous drug abuser was seen in the Albany Medical Center Hospital emergency room on December 23, 1983 for persistent productive cough, fever of three weeks' duration, and recent onset of hemoptysis. He had been taking oral penicillin intermittently for 10 days with slight improvement in symptoms. His vital signs were temperature 102.4°F orally, blood pressure 114/70 mm Hg, and respirations 18 per minute. Oral candidiasis and shotty adenopathy of cervical, epitrochlear, axillary, inguinal, and femoral chains were present. Lungs were clear to auscultation and mild clubbing was present. The spleen tip was palpable and the liver span was 15 cm. Laboratory data included a white blood cell count of 3,700/mm 3, with 63 percent neutrophils, 20 percent band forms, 6 percent lymphocytes, 6 percent mononuclear ceils, 3 percent eosinophils, and 1 percent atypical lymphocytes. Hemoglobin level was 10.8 mg/dl and hematocrit was 32.6 volumes percent. Lactic dehydrogenase level was 304 IU/liter (normal 90 to 225) and serum glutamic oxaloacetic transaminase level was 70 IU/liter (normal less than 45). Results of chest radiography were normal. The aerobic bottle of one of two sets of blood culture specimens showed growth of gram-positive rods subsequently identified as C. equi by the New York State Health Department Laboratories. Sputum Gram stain showed white blood cells and a few gram-positive rods.
April 1986
The American Journal of Medicine
Volume 80
685
CORYNEBACTERIUMEQUI LUNG ABSCESS--SAMIES ET AL
TABLE I
Antimicrobial Minimal Inhibitory Concentrations ( # g / m l )
Penicillin G Methicillin Ampicillin Cephalothin Gentamicin Kanamycin Erythromycin Chloramphenicol Clindamycin Tetracycline Vancomycin Rifampin
1/3/84
4•23•84
0.12 0.25 0.12 1.0 1.0 16 <0.25 4.0 4.0 8 <0.25 0.19
1.0 16 2.0 8 1.0 32 <0.25 8 4.0 4 0.5 0.19
6/15/84
4.0 16 8 64 1.0 16 <0.25 8 4.0 8 0.5 0.19
The patient continued to take oral penicillin as an outpatient and improved, with decreased cough and reso!ut!on of his fever. Upon discontinuation of penicillin, fever, rigors, pleuritic chest pain, and productive cough with occasional hemoptysis developed. Repeated chest radiography revealed a thin-walled cystic lesion in the left upper lobe that in retrospect had been present on the earlier study. Examination upon hospital admission on January 3, 1984 revealed thrush, diffuse adenopathy, rhonchi in the left upper lung field, and hepatosplenomegaly. Laboratory data showed an erythrocyte sedimentation rate of 113 mm per hour and a white blood cell count of 3,800/mm S with 89 percent neutrophils, 1 percent band forms, 4 percent lymphocytes, and 6 percent mononuclear cells. Lactic dehydrogenase level was 353 IU/liter. Total serum protein value was 8.6 mg/dl with an albumin level of 3.5 mg/dl. The patient demonstrated anergy to purified protein derivative, Candida, and mumps skin tests. T cell studies revealed an absolute T cell count of 1,064/mm 3 with 21 percent T4 and 41 percent T8 cells (T4/T8 ratio = 0.5). Two of three blood cultures showed growth of C. equi. Biopsy material from fiberoptic bronchoscopy revealed a leukocytoclastic inflammatory
Figure 1. Chest x-ray showing a large lung abscess caused by Corynebacterium equL
686
April 1986
The American Journal of Medicine
Volume 80
exudate and evidence of mild interstitial fibrosis. Results of ZiehI-Neelsen, Giemsa, and periodic acid-Schiff stains were negative as were results of cultures for aerobes, anaerobes, and acid-fast bacilli. Cryptococcus neoformans was cultured from the bronchial washings. C. neoformans grew subsequently in cerebrospinal fluid. Cerebrospinal fluid glucose level was 45 mg/dl and protein level was 60 mg/dl. The lymphocyte count in the cerebrospinal fluid was 1/mm 3. Results of serum and spinal fluid crtyptococcal antigen tests were positive. Serum cryptococcal antibody was not detected. Amphotericin B, 0.5 mg/kg per day intravenously, and 5-flucytosine, 37.5 mg/kg orally every six hours, were initiated on January 9. A third blood culture specimen from January 7 grew C. equi, and vancomycin treatment at 750 mg intravenously every 12 hours was begun on January 11. The sensitivity data from this and subsequent isolates are reported in Table I. Additionally, the patient had a positive VDRL test result at a dilution of 1:128 and he also began to receive penicillin G at 2 million units intravenously every four hours. Despite clinical .improvement, chest radiography continued to show an enlarging abscess in the left upper lobe. Ten repeated blood cultures showed no growth from January 10 to February 13. On January 21, penicillin therapy was discontinued because of a rash. Subsequent serum bactericidal titers against the C. equi were 1:32 peak and 1:16 trough. On February 13, vancomycin, amphotericin B, and 5-flucytosine were discontinued. The patient left the hospital against medical advice on February 14. On February 28, the patient was rehospitalized in a nearby hospital for fever and hemoptysis. Sputum culture specimens and multiple blood culture samples grew Corynebacterium species. The patient was treated with penicillin; however, the rash recurred and administration of clindamycin was begun at 600 mg intravenously every six hours. He required multiple blood transfusions for continuing hemoptysis, and on April 13 was transferred to Albany Medical Center Hospital. Blood and sputum cultures showed growth of C. equi, and chest radiography revealed a large (15 cm) left upper lobe abscess (Figure 1). Treatment with vancomycin at 750 mg intravenously every 12 hours was resumed, but the patient remained febrile with persistently positive results of sputum cultures for C. equi. Repeated lumbar puncture showed a glucose value of 58 mg/dl, protein value of 40 mg/dl, and a lympocyte count of 2/mm 3. On April 25, rifampin was added at 600 mg orally twice a day. The patient's fever resolved promptly with this regimen. The patient continued to have marked hemoptysis, and left pneumonectomy was performed on April 27. The resected lung revealed a thick-walled abscess and marked pleural thickening and pleural adhesions. The wall of the abscess was firm and tan in appearance with focal hemorrhage and central necrosis (Figure 2). Microscopically, this was characterized by central purulent necrosis surrounded by marked proliferation of periodic acid-Schiff-positive macrophages mixed with small numbers of lymphocytes and plasma cells. Small intracytoplasmic vacuoles within the macrophages contained pleomorphic coccobacillary gram-positive organisms (Figure 3). These were weakly acid-fast on modified acid-fast staining with Fite's stain. Four subaortic and peribronchial nodes also showed ab-
CORYNEBACTERIUMEQUI LUNG ABSCESS--SAMIESET AL
organism are well established. Several aspects of the biochemical composition of the cell wall, which contains mycolic acids conferring weak acid-fastness and a few biochemical reactions, suggest that it is more closely related to the Mycobacteriaeceae than to the Corynebacteriaceae [4]. For this report, we have retained the designation C. equi. C. equi is a well-known pathogen in veterinary medicine, causing suppurating pulmonary lesions in horses and occasionally causing suppurative visceral abscesses in horses and other animals including cattle (pyometra) and swine (cervical adenitis) [5]. As noted by Carpenter and Blom [6], the clinical presentation and course of C. equi infections in humans are quite similar to the presentation and course of mycobacterial diseases in immunocompromised patients. There are 12 reports in the literature with patients ranging in age from nine months to 64 years [6-13]. All but one of these cases occurred in patients with severe defects in cell-mediated immunity,
Figure 2. Resected lung abscess opened to show hemorrhagic necrotic center (C) and thick abscess wall ( W). scess formation with proliferation of macrophages containing intravacuolar intracytoplasmic gram-positive organisms. Budding yeast consistent with Cryptococcus was seen in one lymph node. The patient had resolution of his cough and hemoptysis following the pneumonectomy. Vancomycin and rifampin were discontinued on May 2 and the patient began to receive erythromycin 500 mg orally four times a day. Because of evidence of Cryptococcus in a mediastinal lymph node obtained at surgery, administration of ketoconazole 200 mg orally twice a day was also begun. Repeated lumbar puncture on May 4 showed a glucose value of 42 mg/dl, protein value of 62 mg/dl, and no cells. Results of a cerebrospinal fluid cryptococcal antigen test were negative. The patient was discharged on May 13 with erythromycin and ketoconazole as medications. In June, the patient was admitted to a hospital in northern Florida because of productive cough and hemoptysis. He again had bacteremia with C. equi, and at this time required placement of a left-sided chest tube for an empyema from which C. equi was cultured. As of the data of this report (August 28, 1984), the patient remains hospitalized with a chest tube required for pleural drainage and is currently being treated with oral erythromycin. COMMENTS
C. equi was first isolated by Magnusson [1] in 1923 from suppurating pulmonary lesions in foals. Subsequently, the organism has been found to have a natural reservoir in soil and is thought to be acquired via the respiratory route [2]. C. equi has been the subject of uncertain taxonomy with most recent attempts at classification resulting in its placement in the genus Rhodococcus [3]. Although the taxonomy is unsettled, guidelines for identification of the
Figure 3. Photomicrograph of abscess waft showing numerous granular macrophages. Some macrophages contain intracytop/asmic vacuoles (arrows) (hematoxylin and eosin stain; original magnification X 500, enlarged by 5 percent). Insef shows intracytoplasmic pleomorphic grampositive coccobacillary organisms (Brown and Hopps tissue Gram stain; original magnification X 800, enlarged by 5 percent).
April 1986
The American Journal of Medicine
Volume 88
687
CORYNEBACTERIUM EQUI LUNG ABSCESS--SAMIES ET AL
including seven with hematologic malignancy, four renal transplant recipients, and one patient receiving immunosuppressive therapy for plasma cell hepatitis. Eleven of the 12 patients presented with pneumonia, with upper lobe involvement in five patients and cavitary disease in seven patients. Four patients had empyemas from which the organism was isolated. Three patients died of progressive infection and nine patients were cured. Antibiotics were administered to all patients. Cure required prolonged antibiotic therapy and usually required Iobectomy or other drainage procedure. Coryneform organisms are commonly isolated from skin, the pharynx, the urethra, and the vagina of normal hosts. Because C. equi can be confused with coryneform organisms of little clinical significance, it may be overlooked despite its ability to cause fatal disease in appropriate hosts. Although blood cultures showed growth in several of the reported cases, as in our patient, in all instances the bacteriologic diagnosis of pneumonitis has required bronchoscopy, biopsy, or thoracentesis. C. equi has been identified by sputum culture in only three of the clinical cases including our patient. Pathologically, necrotizing pneumonia with abscess formation has been noted in those cases in which pathologic specimens were studied. Our patient's operative specimen is remarkable because of the size of the abscess, the microscopic findings of C. equi as the sole organism, and the lymphocytic and histiocytic nature of the exudate without the presence of significant numbers of polymorphonuclear leukocytes. Although this organism causes a severe pathologic condition, the mechanism by which the damage occurs is unknown. The organism is predominantly an intracellular pathogen. Mutimer and Woolcock [14] studied 105
strains of C. equi from various sources for production of extracellular enzymes. They found that only lipase and phospholipase were detected in all strains. They concluded that C. equi does not rely on extracellular products for induction of tissue destruction. No difference in the ability to produce extracellular products was noted between environmental isolates and isolates from infected animals. One hundred isolates of C. equi from environmental and veterinary sources were tested for sensitivity to 26 antimicrobial agents by Woolcock and Mutimer [15]. The most active agents in vitro were penicillin G, doxycycline, erythromycin, lincomycin, and the aminoglycosides. Vancomycin, believed by some to be the drug of choice in treatment of Corynebacterium sepsis in immunocomproraised patients, was not tested. Our isolate was vancomycin-sensitive. In addition, following antibiotic therapy, we noted a significant increase in minimal inhibitory concentrations of beta-lactam antibiotics for our patient's organism. Beta-lactamase production was not detected by nitrocefin disk in our laboratory. On the basis of literature review and our recent experience, we conclude that C. equi may cause serious human infection in compromised hosts such as patients with AIDS. Because C. equi resembles nonpathogenic organisms, it may easily be overlooked. Management may require surgical resection as well as prolonged antibiotic therapy. Despite temporary clinical improvement, our patient has had persistent infection caused by this organism. ACKNOWLEDGMENT
We wish to thank Ellen McCormick, M.T., and the Microbiology Laboratory of Albany Medical Center Hospital for their assistance.
REFERENCES 1.
2. 3. 4. 5.
6. 7.
688
Magnusson H: Spezifische infektiose Pneumonie beim Fohlen. Ein neuer Eitererreger beim Pferde. Archiv fur Wissenschaftliche und Praktische Tierheilkunde 1923; 50: 22-38. Smith JE: Corynebacterium species as animal pathogens. J Appl Bacteriol 1966; 29:119-130. Goodfellow M, Beckham AR, Barton MD: Numerical classification of Rhodococcus equi and related actinomycetes. J Appl Bacteriol 1982; 53: 199-207. Lipsky BA, Goldberger AC, Tompkins LS, Plorde JJ: Infections caused by nondiphtheria corynebacteria. Rev Infect Dis 1982; 4: 1220-1235. Locksley RM: The lowly diphtheroid: nondiphtheria corynebacterial infections in humans--Medical Staff Conference, University of California, San Francisco. West J Med 1982; 137: 45-52. Carpenter JL, Blom J: Corynebacterium equi pneumonia in a patient with Hodgkin's disease. Am Rev Respir Dis 1976; 114: 235-239. Williams GD, Flanigan WJ, Campbell GS: Surgical management of localized thoracic infections in immunocompromised patients. Ann Thorac Surg 1971; 12: 471-482.
April 1986
The American Journal of Medicine
Volume 80
8. 9. t0. 11. 12. 13. 14. 15.
Savdie E, Pigott P, Jennis F: Lung abscess due to Corynebacterium equi in a renal transplant recipient. Med J Aust 1977; 1: 817-819. Golub B, Falk G, Spink WW: Lung abscess due to Corynebacterium equi--report of first human infection. Ann Intern Med 1967; 66: 1174-1177. Berg R, Chmel H, Mayo J, Armstrong D: Corynebacterium equi infection complicating neoplastic disease. Am J Clin Pathol 1977; 68: 73-77. Marsh JC, von Graevenitz A: Recurrent Corynebacterium equi infection with lymphoma. Cancer 1973; 32: 147-149. Gardner SE, Pearson T, Hughes WT: Pneumonitis due to Corynebacterium equi. Chest 1976; 70: 92-94. Van Etta LL, Filice GA, Ferguson RM: Corynebacterium equi: a review of twelve cases of human infection. Rev Infect Dis 1983; 5: 1012-1018. Mutimer MD, Woolcock JB: A note on hydrolytic enzymes of Corynebacterium equi. J Appl Bacteriol 1983; 55: 367-369. Woolcock JB, Mutimer MD: Corynebacterium equi: in vitro susceptibility to twenty-six antimicrobial agents. Antimicrob Agents Chemother 1980; 18: 976-977.
JOHN H. SAMIES, M.D. BRUCE N. HATHAWAY, M.D. ROGER M. ECHOLS, M.D. JAMES M. VEAZEY, Jr., M.D. VERNON A. PILON, M.D. Albany, New York
A lung abscess and persistent bacteremia due to Corynebacterium equi are described in a bisexual man with the acquired immune deficiency syndrome (AIDS). Eleven of the 12 previously reported cases have occurred in immunocompromised humans. The occurrence of this infection in a patient with AIDS has not been previously
described, Development of resistance to beta-lactam antibiotics was noted following initial therapy. Because this organism resembles nonpathogenic organisms, it may easily be overlooked despite its ability to cause serious infection and persist even with aggressive antimicrobial and surgical therapy. Although the pathogenicity of Corynebacterium equi in domestic animals is well established, it is a rare pathogen in humans, having been described in only 12 patients in the literature. All but one of the previously reported human cases have been in immunocompromised patients. This is the first report of a patient with the acquired immune deficiency syndrome (AIDS) who had a lung abscess and persistent bacteremia due to C. equi. The microbiologic and clinical characteristics of this case illustrate the potential human pathogenicity of this organism.
CASE REPORT
From the Division of Infectious Diseases, Department of Medicine, and the Department of Pathology, Albany Medical College of Union University, Albany, New York. Requests for reprints should be addressed to Dr. Roger M. Echols, Division of Infectious Diseases, Albany Medical College, MS-103, Albany, New York 12208. Manuscript accepted December 12, 1984.
A 36-year-old bisexual former alcohol and intravenous drug abuser was seen in the Albany Medical Center Hospital emergency room on December 23, 1983 for persistent productive cough, fever of three weeks' duration, and recent onset of hemoptysis. He had been taking oral penicillin intermittently for 10 days with slight improvement in symptoms. His vital signs were temperature 102.4°F orally, blood pressure 114/70 mm Hg, and respirations 18 per minute. Oral candidiasis and shotty adenopathy of cervical, epitrochlear, axillary, inguinal, and femoral chains were present. Lungs were clear to auscultation and mild clubbing was present. The spleen tip was palpable and the liver span was 15 cm. Laboratory data included a white blood cell count of 3,700/mm 3, with 63 percent neutrophils, 20 percent band forms, 6 percent lymphocytes, 6 percent mononuclear ceils, 3 percent eosinophils, and 1 percent atypical lymphocytes. Hemoglobin level was 10.8 mg/dl and hematocrit was 32.6 volumes percent. Lactic dehydrogenase level was 304 IU/liter (normal 90 to 225) and serum glutamic oxaloacetic transaminase level was 70 IU/liter (normal less than 45). Results of chest radiography were normal. The aerobic bottle of one of two sets of blood culture specimens showed growth of gram-positive rods subsequently identified as C. equi by the New York State Health Department Laboratories. Sputum Gram stain showed white blood cells and a few gram-positive rods.
April 1986
The American Journal of Medicine
Volume 80
685
CORYNEBACTERIUMEQUI LUNG ABSCESS--SAMIES ET AL
TABLE I
Antimicrobial Minimal Inhibitory Concentrations ( # g / m l )
Penicillin G Methicillin Ampicillin Cephalothin Gentamicin Kanamycin Erythromycin Chloramphenicol Clindamycin Tetracycline Vancomycin Rifampin
1/3/84
4•23•84
0.12 0.25 0.12 1.0 1.0 16 <0.25 4.0 4.0 8 <0.25 0.19
1.0 16 2.0 8 1.0 32 <0.25 8 4.0 4 0.5 0.19
6/15/84
4.0 16 8 64 1.0 16 <0.25 8 4.0 8 0.5 0.19
The patient continued to take oral penicillin as an outpatient and improved, with decreased cough and reso!ut!on of his fever. Upon discontinuation of penicillin, fever, rigors, pleuritic chest pain, and productive cough with occasional hemoptysis developed. Repeated chest radiography revealed a thin-walled cystic lesion in the left upper lobe that in retrospect had been present on the earlier study. Examination upon hospital admission on January 3, 1984 revealed thrush, diffuse adenopathy, rhonchi in the left upper lung field, and hepatosplenomegaly. Laboratory data showed an erythrocyte sedimentation rate of 113 mm per hour and a white blood cell count of 3,800/mm S with 89 percent neutrophils, 1 percent band forms, 4 percent lymphocytes, and 6 percent mononuclear cells. Lactic dehydrogenase level was 353 IU/liter. Total serum protein value was 8.6 mg/dl with an albumin level of 3.5 mg/dl. The patient demonstrated anergy to purified protein derivative, Candida, and mumps skin tests. T cell studies revealed an absolute T cell count of 1,064/mm 3 with 21 percent T4 and 41 percent T8 cells (T4/T8 ratio = 0.5). Two of three blood cultures showed growth of C. equi. Biopsy material from fiberoptic bronchoscopy revealed a leukocytoclastic inflammatory
Figure 1. Chest x-ray showing a large lung abscess caused by Corynebacterium equL
686
April 1986
The American Journal of Medicine
Volume 80
exudate and evidence of mild interstitial fibrosis. Results of ZiehI-Neelsen, Giemsa, and periodic acid-Schiff stains were negative as were results of cultures for aerobes, anaerobes, and acid-fast bacilli. Cryptococcus neoformans was cultured from the bronchial washings. C. neoformans grew subsequently in cerebrospinal fluid. Cerebrospinal fluid glucose level was 45 mg/dl and protein level was 60 mg/dl. The lymphocyte count in the cerebrospinal fluid was 1/mm 3. Results of serum and spinal fluid crtyptococcal antigen tests were positive. Serum cryptococcal antibody was not detected. Amphotericin B, 0.5 mg/kg per day intravenously, and 5-flucytosine, 37.5 mg/kg orally every six hours, were initiated on January 9. A third blood culture specimen from January 7 grew C. equi, and vancomycin treatment at 750 mg intravenously every 12 hours was begun on January 11. The sensitivity data from this and subsequent isolates are reported in Table I. Additionally, the patient had a positive VDRL test result at a dilution of 1:128 and he also began to receive penicillin G at 2 million units intravenously every four hours. Despite clinical .improvement, chest radiography continued to show an enlarging abscess in the left upper lobe. Ten repeated blood cultures showed no growth from January 10 to February 13. On January 21, penicillin therapy was discontinued because of a rash. Subsequent serum bactericidal titers against the C. equi were 1:32 peak and 1:16 trough. On February 13, vancomycin, amphotericin B, and 5-flucytosine were discontinued. The patient left the hospital against medical advice on February 14. On February 28, the patient was rehospitalized in a nearby hospital for fever and hemoptysis. Sputum culture specimens and multiple blood culture samples grew Corynebacterium species. The patient was treated with penicillin; however, the rash recurred and administration of clindamycin was begun at 600 mg intravenously every six hours. He required multiple blood transfusions for continuing hemoptysis, and on April 13 was transferred to Albany Medical Center Hospital. Blood and sputum cultures showed growth of C. equi, and chest radiography revealed a large (15 cm) left upper lobe abscess (Figure 1). Treatment with vancomycin at 750 mg intravenously every 12 hours was resumed, but the patient remained febrile with persistently positive results of sputum cultures for C. equi. Repeated lumbar puncture showed a glucose value of 58 mg/dl, protein value of 40 mg/dl, and a lympocyte count of 2/mm 3. On April 25, rifampin was added at 600 mg orally twice a day. The patient's fever resolved promptly with this regimen. The patient continued to have marked hemoptysis, and left pneumonectomy was performed on April 27. The resected lung revealed a thick-walled abscess and marked pleural thickening and pleural adhesions. The wall of the abscess was firm and tan in appearance with focal hemorrhage and central necrosis (Figure 2). Microscopically, this was characterized by central purulent necrosis surrounded by marked proliferation of periodic acid-Schiff-positive macrophages mixed with small numbers of lymphocytes and plasma cells. Small intracytoplasmic vacuoles within the macrophages contained pleomorphic coccobacillary gram-positive organisms (Figure 3). These were weakly acid-fast on modified acid-fast staining with Fite's stain. Four subaortic and peribronchial nodes also showed ab-
CORYNEBACTERIUMEQUI LUNG ABSCESS--SAMIESET AL
organism are well established. Several aspects of the biochemical composition of the cell wall, which contains mycolic acids conferring weak acid-fastness and a few biochemical reactions, suggest that it is more closely related to the Mycobacteriaeceae than to the Corynebacteriaceae [4]. For this report, we have retained the designation C. equi. C. equi is a well-known pathogen in veterinary medicine, causing suppurating pulmonary lesions in horses and occasionally causing suppurative visceral abscesses in horses and other animals including cattle (pyometra) and swine (cervical adenitis) [5]. As noted by Carpenter and Blom [6], the clinical presentation and course of C. equi infections in humans are quite similar to the presentation and course of mycobacterial diseases in immunocompromised patients. There are 12 reports in the literature with patients ranging in age from nine months to 64 years [6-13]. All but one of these cases occurred in patients with severe defects in cell-mediated immunity,
Figure 2. Resected lung abscess opened to show hemorrhagic necrotic center (C) and thick abscess wall ( W). scess formation with proliferation of macrophages containing intravacuolar intracytoplasmic gram-positive organisms. Budding yeast consistent with Cryptococcus was seen in one lymph node. The patient had resolution of his cough and hemoptysis following the pneumonectomy. Vancomycin and rifampin were discontinued on May 2 and the patient began to receive erythromycin 500 mg orally four times a day. Because of evidence of Cryptococcus in a mediastinal lymph node obtained at surgery, administration of ketoconazole 200 mg orally twice a day was also begun. Repeated lumbar puncture on May 4 showed a glucose value of 42 mg/dl, protein value of 62 mg/dl, and no cells. Results of a cerebrospinal fluid cryptococcal antigen test were negative. The patient was discharged on May 13 with erythromycin and ketoconazole as medications. In June, the patient was admitted to a hospital in northern Florida because of productive cough and hemoptysis. He again had bacteremia with C. equi, and at this time required placement of a left-sided chest tube for an empyema from which C. equi was cultured. As of the data of this report (August 28, 1984), the patient remains hospitalized with a chest tube required for pleural drainage and is currently being treated with oral erythromycin. COMMENTS
C. equi was first isolated by Magnusson [1] in 1923 from suppurating pulmonary lesions in foals. Subsequently, the organism has been found to have a natural reservoir in soil and is thought to be acquired via the respiratory route [2]. C. equi has been the subject of uncertain taxonomy with most recent attempts at classification resulting in its placement in the genus Rhodococcus [3]. Although the taxonomy is unsettled, guidelines for identification of the
Figure 3. Photomicrograph of abscess waft showing numerous granular macrophages. Some macrophages contain intracytop/asmic vacuoles (arrows) (hematoxylin and eosin stain; original magnification X 500, enlarged by 5 percent). Insef shows intracytoplasmic pleomorphic grampositive coccobacillary organisms (Brown and Hopps tissue Gram stain; original magnification X 800, enlarged by 5 percent).
April 1986
The American Journal of Medicine
Volume 88
687
CORYNEBACTERIUM EQUI LUNG ABSCESS--SAMIES ET AL
including seven with hematologic malignancy, four renal transplant recipients, and one patient receiving immunosuppressive therapy for plasma cell hepatitis. Eleven of the 12 patients presented with pneumonia, with upper lobe involvement in five patients and cavitary disease in seven patients. Four patients had empyemas from which the organism was isolated. Three patients died of progressive infection and nine patients were cured. Antibiotics were administered to all patients. Cure required prolonged antibiotic therapy and usually required Iobectomy or other drainage procedure. Coryneform organisms are commonly isolated from skin, the pharynx, the urethra, and the vagina of normal hosts. Because C. equi can be confused with coryneform organisms of little clinical significance, it may be overlooked despite its ability to cause fatal disease in appropriate hosts. Although blood cultures showed growth in several of the reported cases, as in our patient, in all instances the bacteriologic diagnosis of pneumonitis has required bronchoscopy, biopsy, or thoracentesis. C. equi has been identified by sputum culture in only three of the clinical cases including our patient. Pathologically, necrotizing pneumonia with abscess formation has been noted in those cases in which pathologic specimens were studied. Our patient's operative specimen is remarkable because of the size of the abscess, the microscopic findings of C. equi as the sole organism, and the lymphocytic and histiocytic nature of the exudate without the presence of significant numbers of polymorphonuclear leukocytes. Although this organism causes a severe pathologic condition, the mechanism by which the damage occurs is unknown. The organism is predominantly an intracellular pathogen. Mutimer and Woolcock [14] studied 105
strains of C. equi from various sources for production of extracellular enzymes. They found that only lipase and phospholipase were detected in all strains. They concluded that C. equi does not rely on extracellular products for induction of tissue destruction. No difference in the ability to produce extracellular products was noted between environmental isolates and isolates from infected animals. One hundred isolates of C. equi from environmental and veterinary sources were tested for sensitivity to 26 antimicrobial agents by Woolcock and Mutimer [15]. The most active agents in vitro were penicillin G, doxycycline, erythromycin, lincomycin, and the aminoglycosides. Vancomycin, believed by some to be the drug of choice in treatment of Corynebacterium sepsis in immunocomproraised patients, was not tested. Our isolate was vancomycin-sensitive. In addition, following antibiotic therapy, we noted a significant increase in minimal inhibitory concentrations of beta-lactam antibiotics for our patient's organism. Beta-lactamase production was not detected by nitrocefin disk in our laboratory. On the basis of literature review and our recent experience, we conclude that C. equi may cause serious human infection in compromised hosts such as patients with AIDS. Because C. equi resembles nonpathogenic organisms, it may easily be overlooked. Management may require surgical resection as well as prolonged antibiotic therapy. Despite temporary clinical improvement, our patient has had persistent infection caused by this organism. ACKNOWLEDGMENT
We wish to thank Ellen McCormick, M.T., and the Microbiology Laboratory of Albany Medical Center Hospital for their assistance.
REFERENCES 1.
2. 3. 4. 5.
6. 7.
688
Magnusson H: Spezifische infektiose Pneumonie beim Fohlen. Ein neuer Eitererreger beim Pferde. Archiv fur Wissenschaftliche und Praktische Tierheilkunde 1923; 50: 22-38. Smith JE: Corynebacterium species as animal pathogens. J Appl Bacteriol 1966; 29:119-130. Goodfellow M, Beckham AR, Barton MD: Numerical classification of Rhodococcus equi and related actinomycetes. J Appl Bacteriol 1982; 53: 199-207. Lipsky BA, Goldberger AC, Tompkins LS, Plorde JJ: Infections caused by nondiphtheria corynebacteria. Rev Infect Dis 1982; 4: 1220-1235. Locksley RM: The lowly diphtheroid: nondiphtheria corynebacterial infections in humans--Medical Staff Conference, University of California, San Francisco. West J Med 1982; 137: 45-52. Carpenter JL, Blom J: Corynebacterium equi pneumonia in a patient with Hodgkin's disease. Am Rev Respir Dis 1976; 114: 235-239. Williams GD, Flanigan WJ, Campbell GS: Surgical management of localized thoracic infections in immunocompromised patients. Ann Thorac Surg 1971; 12: 471-482.
April 1986
The American Journal of Medicine
Volume 80
8. 9. t0. 11. 12. 13. 14. 15.
Savdie E, Pigott P, Jennis F: Lung abscess due to Corynebacterium equi in a renal transplant recipient. Med J Aust 1977; 1: 817-819. Golub B, Falk G, Spink WW: Lung abscess due to Corynebacterium equi--report of first human infection. Ann Intern Med 1967; 66: 1174-1177. Berg R, Chmel H, Mayo J, Armstrong D: Corynebacterium equi infection complicating neoplastic disease. Am J Clin Pathol 1977; 68: 73-77. Marsh JC, von Graevenitz A: Recurrent Corynebacterium equi infection with lymphoma. Cancer 1973; 32: 147-149. Gardner SE, Pearson T, Hughes WT: Pneumonitis due to Corynebacterium equi. Chest 1976; 70: 92-94. Van Etta LL, Filice GA, Ferguson RM: Corynebacterium equi: a review of twelve cases of human infection. Rev Infect Dis 1983; 5: 1012-1018. Mutimer MD, Woolcock JB: A note on hydrolytic enzymes of Corynebacterium equi. J Appl Bacteriol 1983; 55: 367-369. Woolcock JB, Mutimer MD: Corynebacterium equi: in vitro susceptibility to twenty-six antimicrobial agents. Antimicrob Agents Chemother 1980; 18: 976-977.