12. CHANDLER EW, HICKLIN MD, BLACKMON JA: Demonstration of the agent of Legionnaires' disease in tissue. N Engi J Med 297: 1218, 1977 13. Follow-up on respiratory disease Pennsylvania. Morb Mortal Wkly Rep 26: 93, 1977 14. FRASER DW, WACHSMUTH K, Bo..
C, et al: Antibiotic treatment of guineapigs infected with agent of Legionnaires' disease. Lancet 1: 175, 1978 15. Isolates of organisms resembling Legionnaires' disease bacterium from environmental sources - Bloomington, Indiana. Morb Mortal Wkly Rep
27: 283, 1978 16. Isolation of organisms resembling Legionnaires' disease bacterium Tennessee. Ibid, p 368 17. Isolation of organisms resembling Legionnaires' disease bacterium Georgia. Morb Mortal Wkly Rep 27: 415, 1978
Legionnaires' disease in a renal transplant recipient HILDA J. CANOS, MD; ALLAN R. RONALD, MD, FRC p[c], FACP; JOHN R. JEFFERY, MD, FRCP[C]
The Legionnaires' disease bacillus, Legionella pneumophila,1 is now recognized as an important cause of pneumonia, particularly in persons with compromised immune defences. Recent reports of its occurrence in renal transplant recipients should lead to an increasing awareness of this potentially fatal disease and result in its immediate treatment once it is suspected. We report the first documented case of Legionnaires' disease in a renal transplant recipient in Canada. Case report A 30-year-old man with chronic renal failure secondary to glomerulonephritis received a cadaveric renal allograft Oct. 19, 1977. Immunosuppressive therapy with azathioprine, cyclophosphamide (infused intermittently) and prednisone was given. The immediate post-transplant period was complicated by acute tubular necrosis and allograft rejection requiring hemodialysis. Methylprednisolone infusions and high doses of prednisone given orally resulted in improved renal function. The patient was discharged from hospital a month after the operation: the serum creatinine concentration From the department of medicine, Health Sciences Centre and the University of Manitoba, Winnipeg Reprint requests to: Dr. Hilda J. Canos, Section of nephrology, Health Sciences Centre, 700 William Ave., Winnipeg, Maa. R3E 0Z3
was 300 .mo1/1 (3.4 mg/dl), and he was taking prednisone (70 mg/d) and azathioprine (100 mg/d). Four days after the patient's discharge congestive heart failure developed. A chest roentgenogram showed mild pulmonary edema and a circular zone of increased density in the lower lobe of the right lung (Fig. 1). Worsening dyspnea and a cough producing white foamy sputum necessitated his readmission to hospital 4 days later. The patient reported no fever, chest pain, headache, myalgia, arthralgia or gastrointestinal symptoms. He was alert and moderately dyspneic. The blood pressure was
140/70 mm Hg, pulse rate 1 20/mm, respiratory rate 24/mm and temperature 38.5 0C. Inspiratory and expiratory rhonchi in the middle and lower lobes of the right lung and dullness in the lower aspect of that lung as well as a third heart sound were heard. The kidney allograft was enlarged and very firm. The hemoglobin concentration was 5.0 g/dl, the leukocyte count 10.3 x 10./l (with 89% neutrophils, 6% band forms, 3% lympho.. cytes and 2% monocytes) and the platelet count 330 x 10./l. The blood urea nitrogen concentration was 54.6 mmol/l (153 mg/dl) and the serum creatinine concentration
44 '44 '4-'
44" 44444', -
':444, -
FIG 1-Circular infiltrate in lower lobe of right lung 4 days before ad mission.
'4
FIG 2 Extensive consolidation of lower lobe of right lung at time of admission.
CMA JOURNAL/JUNE 23, 1979/VOL 120 1537
was 415 .mol/l (4.7 mg/dl). Serum electrolyte concentrations and resuits of liver function studies were normal. Arterial tensions of oxygen and carbon dioxide were 70 and 25 mm Hg respectively with the patient breathing room air. A chest roentgenogram showed slight cardiomegaly and extensive consolidation of the lower lobe of the right lung with an air bronchogram; the left lung was clear (Fig. 2). The sputum was blood-streaked, and Gramstaining showed occasional pus cells and gram-positive bacilli, a few gram-negative bacilli and numerous gram-positive cocci. Vigorous pulmonary physiotherapy and parenteral therapy with penicillin (6 million U/d) were started. On the second hospital day the patient's respiratory distress increased. The sputum became slightly purulent, but no organisms could be cultured. Worsening azotemia and oliguria necessitated hemodialysis. Despite clinical evidence of allograft rejection, immunosuppressive therapy was reduced because of the presence of infection.2 On the fifth hospital day the patient's condition had not improved and no causative organism had been identified. A chest roentgenogram showed increasing consolidation. Cytomegalovirus and Pneumocystis carinji infections were considered very likely. Therapy with trimethoprim (60 mg)-sulfamethoxazole (400 mg) was started; it was given three times the first day, then twice a day thereafter. A renal biopsy confirmed rejection. On the sixth hospital day bronchoscopy and transbronchial biopsy were performed, but the results did not yield a diagnosis. Infection with Mycoplasma pneumoniae and L. pneumophila were considered. Treatment with erythromycin (500 mg orally four times a day) was started. Within 24 hours the patient became afebrile. The following day the dyspnea and cough had lessened slightly, but the chest roentgenogram was unchanged. An open lung biopsy on the eighth hospital day revealed fibrinous deposits on the pleura of the
lower lobe of the right lung. Examination of histologic specimens showed severe diffuse alveolar damage, acute intra-alveolar and interstitial inflammation with atypical type 2 pneumonocyte proliferation, and exudation with numerous foamy macrophages. No inclusion bodies, bacteria, fungi or P. carinji were identified. The following day culture of the lung tissue yielded a light growth of Proteus mirabilis and Kiebsiella pneumoniae. Treatment with trimethoprim-sulfamethoxazole was discontinued. For 48 hours after the lung biopsy the patient had intermittent rises in temperature to 38.40C; thereafter he was afebrile. Treatment with penicillin was continued for 14 days and that with erythromycin for 18 days. Low-dose immunosuppressive therapy was also continued. There was gradual improvement in the clinical signs and in renal function. A chest roentgenogram on the 10th hospital day showed some resolution of the consolidation in the superior segment of the lower lobe of the right lung. On the 21st hospital day the patient's temperature again spiked to 38 0C in association with leukocytosis and tachypnea, though he was still taking erythromycin. Blood, urine and sputum cultures were negative. Chest roentgenograms revealed no change in the consolidation but showed an extrapleural loculation of fluid suggestive of empyema. Therapy with cephalothin (2 g/d) was started, and 3 days later the patient became afebrile. After 4 days of therapy cephalothin was discontinued and cephalexin (2 g/d) substituted. The patient was discharged after 6 weeks in hospital. The serum creatinine concentration was 177 .mol/l (2.0 mg/dl) and a chest roentgenogram showed persistence of the consolidation and extrapleural fluid loculation. Because of the extrapleural fluid loculation therapy with cephalexin was continued for 34 days, until roentgenograms showed further improvement. Cultures for cytomegalovirus were negative. Viral and Mycoplasma
1538 CMA JOURNAL/JUNE 23, 1979/VOL. 120
complement-fixation titres were insignificant. Dieterle silver-impregnation staining and direct fluorescent antibody staining of formalin-fixed lung tissue gave positive results for L. pneumophila. Immunofluorescent antibody titres of serum obtained monthly for 8 months before renal transplantation had been consistently 1:256, but 5 months after the patient's discharge the titre was 1:8192. At that time the patient was well and a chest roentgenogram showed complete clearing of the consolidation. Discussion Numerous sporadic cases of Legionnaires' disease have been reported since the isolation of the bacterium that caused an epidemic of febrile respiratory illness among persons who attended the American Legion convention in Philadelphia in July 1 976.. This bacterium is associated with high morbidity and mortality and caused 29 deaths in 182 cases in the Philadelphia outbreak.4 Epidemiologic data and the lobular distribution of the pneumonia in close association with the bronchioles suggest that the portal of entry is the respiratory tract.5'6 Legionnaires' disease affects mostly middle-aged or older individuals who have an underlying chronic illness.5'7 The mortality is high in those whose immune mechanisms are suppressed.8 The use of steroids as part of treatment has been associated with a mortality of 56%, compared with an overall mortality of 16% .. The bacterium is a pleomorphic, fastidious gram-negative bacillus that can be cultured from lung tissue and pleural fluid on Mueller-Hinton agar and can be demonstrated in a transtracheal aspirate by direct fluorescent antibody staining.3'4'7'9 It can be identified with the Dieterle silverimpregnation stain in formalin-fixed lung tissue; however, this stain is not specific.3 There is limited experience with the use of gram-staining.4'6 Some of the histologic features of the lung tissue are distinctive, such
as prominent cellular infiltration of the alveoli, extensive lysis of the alveolar inflammatory infiltrate, and interstitial edema with inflammatory cells and debris.6 A definitive diagnosis, however, depends on culture of the bacterium and its immunologic demonstration by direct fluorescent antibody staining.7 A retrospective diagnosis can be confirmed serologically by an increase of fourfold or greater in the indirect fluorescent antibody titre, which may remain elevated for several months or several years.8'10-'4 The onset of the disease can be insidious, but rapid clinical deterioration can follow if treatment is not given.' No single clinical manifestation or laboratory finding is diagnostic. The illness is characterized by fever and systemic and respiratory symptoms with or without pneumonia."13'1' Encephalopathy, azotemia and renal failure may occur.1' Transient abnormalities in liver function may be present."8 A chest roentgenogram is abnormal in 90% of cases, with unilateral or bilateral patchy infiltrates progressing to widespread consolidation."6 In vivo and in vitro evidence indicates that oral or parenteral administration of erythromycin is the most effective therapy for this disease."16 Defervescence has been reported to occur in less than 24 hours after therapy is started.8 Roentgenographic evidence of resolution of the pneumonia usually appears in 10 days but may lag behind clinical improvement by several days or several weeks.5 Our patient's disease had an atypical initial presentation. Systemic symptoms were absent prior to admission except for increasing dyspnea. Fever and cough were first noted 4 days after the pulmonary infiltrate was detected. Liver function was normal in our patient, in contrast to other cases.'0 The patient's initial clinical course was fulminant, but the fever resolved promptly with erythromycin therapy. The recurrence of fever and deterioration of renal function were likely due to allograft rejection, for they responded to high-dose steroid ther-
apy. Cephalosporin therapy was continued because K. pneumoniae was cultured from lung tissue and because there was roentgenographic evidence of empyema. Pneumonia in a person whose immune mechanisms are suppressed is a serious problem. In the presence of a fulminant clinical and roentgenographic picture it should always be treated aggressively. There are not many diagnostic clues in the clinical features of Legionnaires' disease, but pneumonia with minimal sputum production, especially with insignificant results from Gramstaining of the sputum, should make one suspect the disease. It is easier to make a presumptive diagnosis in an epidemic with a common source of exposure than in an isolated case. A significant amount of time is required to make a definitive serologic diagnosis, and histologic identification of the bacillus is not always easy or immediate. Since the disease has potentially grave consequences, especially among those whose immune mechanisms are suppressed, a high index of suspicion is necessary so that prompt treatment can be given. Pneumonia in renal transplant recipients is often treated with a combination of antibiotics designed to cover a wide variety of pathogens, particularly opportunistic ones. The recognition of the Legionnaires' disease bacillus as a cause of pneumonia in this group of patients should make erythromycin one of the preferred antibiotics to be used before the causative organism is identified. Investigation should be pursued until the diagnosis is established. We thank the staff of the Center for Disease Control, Atlanta, Georgia, and Dr. G.R. Hogg, of the department of pathology, Health Sciences Centre, Winnipeg, for their assistance in making the diagnosis. This study was supported by a grant from the Manitoba Medical Services Foundation. References 1. BRENNER DJ, STEIGERWALT AG, Mc-
DADE JE: Classification of the Legionnaires' disease bacterium: Legionella pneumophila, genus novum, spe-
cies nova, of the family Legionellaceae, familia nova. Ann intern Med 90: 656, 1979 2. Biuoos WA, MERRILL JP, O'BRIEN TF, et al: Severe pneumonia in renal transplant patients. Ann Intern Med 75: 887, 1971 3. CHANDLER FW, HICKLIN MON JA: Demonstration of Legionnaires' disease Engi J Med 297: 1218,
MD, BLACKof the agent in tissue. N 1977
4. MCDADE JE, SHEPARD CC, FRASER DW, et al: Legionnaires' disease. Isolation of a bacterium and demonstration of its role in other respiratory disease. Ibid, p 1197 5. FRASER DW, TSAI TR, ORENSTEIN W,
et al: Legionnaires' disease. Description of an epidemic of pneumonia. Ibid, p 1189 6. WINN WC, GLAVIN FL, PERL DP, et al: Pathology of legionnaires' disease - 14 fatal cases from 1977 outbreak in Vermont. Arch Pathol Lab Med 102: 344, 1978 7. Center for Disease Control: Legionnaires' disease: diagnosis and management. Ann Intern Med 88: 363, 1978 8. KIRBY BD, SNYDER KM, MEYER RD, et al: Legionnaires' disease: clinical features of 24 cases. Ann intern Med 89: 297, 1978 9. LATTIMER GL, MCCRONE C, GALGON J: Diagnosis of Legionnaires' disease from transtracheal aspirate by direct fluorescent-antibody staining and isolation of the bacterium. N Engi J Med 299: 1172, 1978 10. BocK BV, KIRBY B, EDELSTEIN PH, et al: Legionnaires' disease in renaltransplant recipients. Lancet 1: 410, 1978 11. TERRANOvA W, COHEN ML, FRASER DW: 1974 outbreak of Legionnalres disease diagnosed in 1977. Lancet 2: 122, 1978 12. Institutional out-break of pneumonia.
Morb Mortal Wkly Rep 14: 265, 1965 13. Epidemic of obscure illness - Pontiac, Michigan. Morb Mortal Wkly Rep 17: 315, 1968 14. MACRAE AD, LEWIS MJ: Legionnaires' disease in Nottingham. Lancet 2: 1225, 1977 15. FRIEDMAN HM: Legionnaires' disease in non-Legionnaires. A report of five cases. Ann intern Med 88: 294, 1978 16. FRASER DW, WACHSMUTH K, Bo.P C, et al: Antibiotic treatment of guineapigs infected with agent of Legionnaires' disease. Lancet 1: 175, 1978
CMA JOURNAL/JUNE 23, 1979/VOL. 120 1539
C, et al: Antibiotic treatment of guineapigs infected with agent of Legionnaires' disease. Lancet 1: 175, 1978 15. Isolates of organisms resembling Legionnaires' disease bacterium from environmental sources - Bloomington, Indiana. Morb Mortal Wkly Rep
27: 283, 1978 16. Isolation of organisms resembling Legionnaires' disease bacterium Tennessee. Ibid, p 368 17. Isolation of organisms resembling Legionnaires' disease bacterium Georgia. Morb Mortal Wkly Rep 27: 415, 1978
Legionnaires' disease in a renal transplant recipient HILDA J. CANOS, MD; ALLAN R. RONALD, MD, FRC p[c], FACP; JOHN R. JEFFERY, MD, FRCP[C]
The Legionnaires' disease bacillus, Legionella pneumophila,1 is now recognized as an important cause of pneumonia, particularly in persons with compromised immune defences. Recent reports of its occurrence in renal transplant recipients should lead to an increasing awareness of this potentially fatal disease and result in its immediate treatment once it is suspected. We report the first documented case of Legionnaires' disease in a renal transplant recipient in Canada. Case report A 30-year-old man with chronic renal failure secondary to glomerulonephritis received a cadaveric renal allograft Oct. 19, 1977. Immunosuppressive therapy with azathioprine, cyclophosphamide (infused intermittently) and prednisone was given. The immediate post-transplant period was complicated by acute tubular necrosis and allograft rejection requiring hemodialysis. Methylprednisolone infusions and high doses of prednisone given orally resulted in improved renal function. The patient was discharged from hospital a month after the operation: the serum creatinine concentration From the department of medicine, Health Sciences Centre and the University of Manitoba, Winnipeg Reprint requests to: Dr. Hilda J. Canos, Section of nephrology, Health Sciences Centre, 700 William Ave., Winnipeg, Maa. R3E 0Z3
was 300 .mo1/1 (3.4 mg/dl), and he was taking prednisone (70 mg/d) and azathioprine (100 mg/d). Four days after the patient's discharge congestive heart failure developed. A chest roentgenogram showed mild pulmonary edema and a circular zone of increased density in the lower lobe of the right lung (Fig. 1). Worsening dyspnea and a cough producing white foamy sputum necessitated his readmission to hospital 4 days later. The patient reported no fever, chest pain, headache, myalgia, arthralgia or gastrointestinal symptoms. He was alert and moderately dyspneic. The blood pressure was
140/70 mm Hg, pulse rate 1 20/mm, respiratory rate 24/mm and temperature 38.5 0C. Inspiratory and expiratory rhonchi in the middle and lower lobes of the right lung and dullness in the lower aspect of that lung as well as a third heart sound were heard. The kidney allograft was enlarged and very firm. The hemoglobin concentration was 5.0 g/dl, the leukocyte count 10.3 x 10./l (with 89% neutrophils, 6% band forms, 3% lympho.. cytes and 2% monocytes) and the platelet count 330 x 10./l. The blood urea nitrogen concentration was 54.6 mmol/l (153 mg/dl) and the serum creatinine concentration
44 '44 '4-'
44" 44444', -
':444, -
FIG 1-Circular infiltrate in lower lobe of right lung 4 days before ad mission.
'4
FIG 2 Extensive consolidation of lower lobe of right lung at time of admission.
CMA JOURNAL/JUNE 23, 1979/VOL 120 1537
was 415 .mol/l (4.7 mg/dl). Serum electrolyte concentrations and resuits of liver function studies were normal. Arterial tensions of oxygen and carbon dioxide were 70 and 25 mm Hg respectively with the patient breathing room air. A chest roentgenogram showed slight cardiomegaly and extensive consolidation of the lower lobe of the right lung with an air bronchogram; the left lung was clear (Fig. 2). The sputum was blood-streaked, and Gramstaining showed occasional pus cells and gram-positive bacilli, a few gram-negative bacilli and numerous gram-positive cocci. Vigorous pulmonary physiotherapy and parenteral therapy with penicillin (6 million U/d) were started. On the second hospital day the patient's respiratory distress increased. The sputum became slightly purulent, but no organisms could be cultured. Worsening azotemia and oliguria necessitated hemodialysis. Despite clinical evidence of allograft rejection, immunosuppressive therapy was reduced because of the presence of infection.2 On the fifth hospital day the patient's condition had not improved and no causative organism had been identified. A chest roentgenogram showed increasing consolidation. Cytomegalovirus and Pneumocystis carinji infections were considered very likely. Therapy with trimethoprim (60 mg)-sulfamethoxazole (400 mg) was started; it was given three times the first day, then twice a day thereafter. A renal biopsy confirmed rejection. On the sixth hospital day bronchoscopy and transbronchial biopsy were performed, but the results did not yield a diagnosis. Infection with Mycoplasma pneumoniae and L. pneumophila were considered. Treatment with erythromycin (500 mg orally four times a day) was started. Within 24 hours the patient became afebrile. The following day the dyspnea and cough had lessened slightly, but the chest roentgenogram was unchanged. An open lung biopsy on the eighth hospital day revealed fibrinous deposits on the pleura of the
lower lobe of the right lung. Examination of histologic specimens showed severe diffuse alveolar damage, acute intra-alveolar and interstitial inflammation with atypical type 2 pneumonocyte proliferation, and exudation with numerous foamy macrophages. No inclusion bodies, bacteria, fungi or P. carinji were identified. The following day culture of the lung tissue yielded a light growth of Proteus mirabilis and Kiebsiella pneumoniae. Treatment with trimethoprim-sulfamethoxazole was discontinued. For 48 hours after the lung biopsy the patient had intermittent rises in temperature to 38.40C; thereafter he was afebrile. Treatment with penicillin was continued for 14 days and that with erythromycin for 18 days. Low-dose immunosuppressive therapy was also continued. There was gradual improvement in the clinical signs and in renal function. A chest roentgenogram on the 10th hospital day showed some resolution of the consolidation in the superior segment of the lower lobe of the right lung. On the 21st hospital day the patient's temperature again spiked to 38 0C in association with leukocytosis and tachypnea, though he was still taking erythromycin. Blood, urine and sputum cultures were negative. Chest roentgenograms revealed no change in the consolidation but showed an extrapleural loculation of fluid suggestive of empyema. Therapy with cephalothin (2 g/d) was started, and 3 days later the patient became afebrile. After 4 days of therapy cephalothin was discontinued and cephalexin (2 g/d) substituted. The patient was discharged after 6 weeks in hospital. The serum creatinine concentration was 177 .mol/l (2.0 mg/dl) and a chest roentgenogram showed persistence of the consolidation and extrapleural fluid loculation. Because of the extrapleural fluid loculation therapy with cephalexin was continued for 34 days, until roentgenograms showed further improvement. Cultures for cytomegalovirus were negative. Viral and Mycoplasma
1538 CMA JOURNAL/JUNE 23, 1979/VOL. 120
complement-fixation titres were insignificant. Dieterle silver-impregnation staining and direct fluorescent antibody staining of formalin-fixed lung tissue gave positive results for L. pneumophila. Immunofluorescent antibody titres of serum obtained monthly for 8 months before renal transplantation had been consistently 1:256, but 5 months after the patient's discharge the titre was 1:8192. At that time the patient was well and a chest roentgenogram showed complete clearing of the consolidation. Discussion Numerous sporadic cases of Legionnaires' disease have been reported since the isolation of the bacterium that caused an epidemic of febrile respiratory illness among persons who attended the American Legion convention in Philadelphia in July 1 976.. This bacterium is associated with high morbidity and mortality and caused 29 deaths in 182 cases in the Philadelphia outbreak.4 Epidemiologic data and the lobular distribution of the pneumonia in close association with the bronchioles suggest that the portal of entry is the respiratory tract.5'6 Legionnaires' disease affects mostly middle-aged or older individuals who have an underlying chronic illness.5'7 The mortality is high in those whose immune mechanisms are suppressed.8 The use of steroids as part of treatment has been associated with a mortality of 56%, compared with an overall mortality of 16% .. The bacterium is a pleomorphic, fastidious gram-negative bacillus that can be cultured from lung tissue and pleural fluid on Mueller-Hinton agar and can be demonstrated in a transtracheal aspirate by direct fluorescent antibody staining.3'4'7'9 It can be identified with the Dieterle silverimpregnation stain in formalin-fixed lung tissue; however, this stain is not specific.3 There is limited experience with the use of gram-staining.4'6 Some of the histologic features of the lung tissue are distinctive, such
as prominent cellular infiltration of the alveoli, extensive lysis of the alveolar inflammatory infiltrate, and interstitial edema with inflammatory cells and debris.6 A definitive diagnosis, however, depends on culture of the bacterium and its immunologic demonstration by direct fluorescent antibody staining.7 A retrospective diagnosis can be confirmed serologically by an increase of fourfold or greater in the indirect fluorescent antibody titre, which may remain elevated for several months or several years.8'10-'4 The onset of the disease can be insidious, but rapid clinical deterioration can follow if treatment is not given.' No single clinical manifestation or laboratory finding is diagnostic. The illness is characterized by fever and systemic and respiratory symptoms with or without pneumonia."13'1' Encephalopathy, azotemia and renal failure may occur.1' Transient abnormalities in liver function may be present."8 A chest roentgenogram is abnormal in 90% of cases, with unilateral or bilateral patchy infiltrates progressing to widespread consolidation."6 In vivo and in vitro evidence indicates that oral or parenteral administration of erythromycin is the most effective therapy for this disease."16 Defervescence has been reported to occur in less than 24 hours after therapy is started.8 Roentgenographic evidence of resolution of the pneumonia usually appears in 10 days but may lag behind clinical improvement by several days or several weeks.5 Our patient's disease had an atypical initial presentation. Systemic symptoms were absent prior to admission except for increasing dyspnea. Fever and cough were first noted 4 days after the pulmonary infiltrate was detected. Liver function was normal in our patient, in contrast to other cases.'0 The patient's initial clinical course was fulminant, but the fever resolved promptly with erythromycin therapy. The recurrence of fever and deterioration of renal function were likely due to allograft rejection, for they responded to high-dose steroid ther-
apy. Cephalosporin therapy was continued because K. pneumoniae was cultured from lung tissue and because there was roentgenographic evidence of empyema. Pneumonia in a person whose immune mechanisms are suppressed is a serious problem. In the presence of a fulminant clinical and roentgenographic picture it should always be treated aggressively. There are not many diagnostic clues in the clinical features of Legionnaires' disease, but pneumonia with minimal sputum production, especially with insignificant results from Gramstaining of the sputum, should make one suspect the disease. It is easier to make a presumptive diagnosis in an epidemic with a common source of exposure than in an isolated case. A significant amount of time is required to make a definitive serologic diagnosis, and histologic identification of the bacillus is not always easy or immediate. Since the disease has potentially grave consequences, especially among those whose immune mechanisms are suppressed, a high index of suspicion is necessary so that prompt treatment can be given. Pneumonia in renal transplant recipients is often treated with a combination of antibiotics designed to cover a wide variety of pathogens, particularly opportunistic ones. The recognition of the Legionnaires' disease bacillus as a cause of pneumonia in this group of patients should make erythromycin one of the preferred antibiotics to be used before the causative organism is identified. Investigation should be pursued until the diagnosis is established. We thank the staff of the Center for Disease Control, Atlanta, Georgia, and Dr. G.R. Hogg, of the department of pathology, Health Sciences Centre, Winnipeg, for their assistance in making the diagnosis. This study was supported by a grant from the Manitoba Medical Services Foundation. References 1. BRENNER DJ, STEIGERWALT AG, Mc-
DADE JE: Classification of the Legionnaires' disease bacterium: Legionella pneumophila, genus novum, spe-
cies nova, of the family Legionellaceae, familia nova. Ann intern Med 90: 656, 1979 2. Biuoos WA, MERRILL JP, O'BRIEN TF, et al: Severe pneumonia in renal transplant patients. Ann Intern Med 75: 887, 1971 3. CHANDLER FW, HICKLIN MON JA: Demonstration of Legionnaires' disease Engi J Med 297: 1218,
MD, BLACKof the agent in tissue. N 1977
4. MCDADE JE, SHEPARD CC, FRASER DW, et al: Legionnaires' disease. Isolation of a bacterium and demonstration of its role in other respiratory disease. Ibid, p 1197 5. FRASER DW, TSAI TR, ORENSTEIN W,
et al: Legionnaires' disease. Description of an epidemic of pneumonia. Ibid, p 1189 6. WINN WC, GLAVIN FL, PERL DP, et al: Pathology of legionnaires' disease - 14 fatal cases from 1977 outbreak in Vermont. Arch Pathol Lab Med 102: 344, 1978 7. Center for Disease Control: Legionnaires' disease: diagnosis and management. Ann Intern Med 88: 363, 1978 8. KIRBY BD, SNYDER KM, MEYER RD, et al: Legionnaires' disease: clinical features of 24 cases. Ann intern Med 89: 297, 1978 9. LATTIMER GL, MCCRONE C, GALGON J: Diagnosis of Legionnaires' disease from transtracheal aspirate by direct fluorescent-antibody staining and isolation of the bacterium. N Engi J Med 299: 1172, 1978 10. BocK BV, KIRBY B, EDELSTEIN PH, et al: Legionnaires' disease in renaltransplant recipients. Lancet 1: 410, 1978 11. TERRANOvA W, COHEN ML, FRASER DW: 1974 outbreak of Legionnalres disease diagnosed in 1977. Lancet 2: 122, 1978 12. Institutional out-break of pneumonia.
Morb Mortal Wkly Rep 14: 265, 1965 13. Epidemic of obscure illness - Pontiac, Michigan. Morb Mortal Wkly Rep 17: 315, 1968 14. MACRAE AD, LEWIS MJ: Legionnaires' disease in Nottingham. Lancet 2: 1225, 1977 15. FRIEDMAN HM: Legionnaires' disease in non-Legionnaires. A report of five cases. Ann intern Med 88: 294, 1978 16. FRASER DW, WACHSMUTH K, Bo.P C, et al: Antibiotic treatment of guineapigs infected with agent of Legionnaires' disease. Lancet 1: 175, 1978
CMA JOURNAL/JUNE 23, 1979/VOL. 120 1539
