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Campylobacter jejuni Pericarditis in a Renal Transplant Recipient on Sirolimus Therapy
CASE
R EPORT
Campylobacter jejuni Pericarditis in a Renal Transplant Recipient on Sirolimus Therapy Isabel Fradejas, M.S.,1 Francisco Lopez-Medrano, M.D.,2 Esther González-Montes, M.D.,3 Angeles Orellana, M.D.,1 Fernando Chaves, M.D.,1 1 Servicio de Microbiología, 2Unidad de Enfermedades Infecciosas, 3Servicio de Nefrología, Hospital Universitario, Madrid, Spain
Introduction Campylobacter species are curved, motile, microaerophilic, nonspore-forming, Gram-negative rods. The genus Campylobacter includes 22 species, with Campylobacter jejuni, Campylobacter coli, and Campylobacter fetus being the most common species causing Corresponding author: Fernando Chaves, Servicio de Microbiología, Hospital Universitario 12 de Octubre, Avenida de Córdoba sn, Madrid 28041, Spain. Tel: (34) 917792404. E-mail: fernando.chaves@salud. madrid.org
human disease. A variety of animals are implicated as reservoirs for Campylobacter spp., and human infections usually follow ingestion of improperly handled or cooked food, primarily poultry products (1). In Europe, campylobacteriosis is the most prevalent zoonotic disease in humans, and its estimated incidence has remained constant over the past several years (2). Enteric and extraintestinal illnesses are associated with Campylobacter spp.; gastrointestinal disease is often related to C. jejuni and C. coli, whereas C. fetus causes extraintestinal infections, such as bacteremia and other intravascular infections.
Clinical Microbiology Newsletter 37:21,2015 | ©2015 Elsevier
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We describe a case of C. jejuni pericarditis in a renal transplant recipient with pericardial effusion, likely secondary to the immunosuppressive drug sirolimus. The final etiologic diagnosis required molecular amplification by universal 16S rRNA PCR on the pericardial fluid. The patient’s pericarditis infection resolved following pericardiocentesis and a course of broad-spectrum antibiotic therapy.
Case Report A 60-year-old male with end stage renal disease secondary to polycystic kidney disease underwent renal transplantation 9 years prior to this admission. His immunosuppressive therapy consisted of sirolimus (3 mg/day) and prednisone (5 mg/day). From the beginning of his post-transplantation period, the patient presented with chronic diarrhea, with approximately 4 to 6 bowel movements per day. He also had two episodes of urinary tract infection caused by Morganella morganii in the 3 months before his current admission. The patient presented to the emergency room with a 2-day history of fever, dry cough, and pleuritic chest pain. He also complained about a mild increase in bowel movements (approximately 8 per day) over the past week. The stool consistency was watery, and the stool contained no mucus or blood. The patient denied experiencing abdominal or joint pain, vomiting, or having symptoms of urinary tract infection. On physical examination, he had a pulse rate of 82 bpm, blood pressure of 81/66 mm Hg, and no fever, and appeared in good general condition. Chest and abdominal examinations were normal. Laboratory values were normal, except for a serum creatinine level of 52.3 mg/L, urea of 1,360 mg/L, lactate dehydrogenase (LDH) of 256 U/L, and C-reactive protein of 188.5 mg/L. The peripheral white blood cell (WBC) count was 8.4 X 106/L, with 89.5% neutrophils and 6.1% lymphocytes. Chest X ray revealed severe cardiomegaly with tracheal shifting. No infiltrations or costophrenic angle clamping was revealed. An echocardiogram showed pericardial effusion with hemodynamic compromise, and therefore, the patient was admitted to the intensive care cardiology unit. He underwent urgent pericardiocentesis, and a catheter was left in place for 3 days. Three hundred milliliters of hemopurulent pericardial fluid was collected for hematological, biochemical, microbiological, and pathological analyses. After the pericardiocentesis was performed, the patient developed a fever, prompting the collection of blood and urine specimens for culture. In addition, empiric antibiotic therapy with intravenous ceftriaxone was started (1 g/day). The WBC count on the pericardial fluid was 142,000 cells/μl, with 80% neutrophils and 20% lymphocytes. The red blood cell count was 1,970,565 cells/μl. The patient also had a glucose level of 5 mg/ dl, a protein level of 5.10 g/dl, and an LDH level of 5,114 U/L. A direct Gram-stained smear of the specimen showed inflammatory cells; no microorganisms were detected. Considering these results and suspecting that the patient had purulent pericarditis, his ceftriaxone therapy was discontinued and replaced with intravenous meropenem (1 g/day) for 3 weeks. He also received a single dose of 700 mg of daptomycin and 1 g of amikacin, both intravenously.
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During his stay in the hospital, the patient had several medical complications. Briefly, after undergoing pericardiocentesis and despite the initiation of broad-spectrum antimicrobial therapy, he remained intermittently febrile. Following pericardiocentesis and deterioration of his renal function, he also developed left-side heart failure. Sirolimus was replaced by tacrolimus on day 5 of admission because of toxic levels and its likely being the cause of the pericardial effusion and chronic diarrhea. In the microbiology laboratory, the blood, pericardial, and urine specimens were processed by using standard procedures. In brief, blood specimens were inoculated into aerobic and anaerobic culture bottles and incubated at 37°C in the Bact/ALERT 3D automated blood culture system (bioMérieux, Durham, NC). The pericardial fluid was plated onto blood and MacConkey agars (incubated at 37°C in air), chocolate agar (incubated at 37°C in air supplemented with 5% CO2), and blood agar and Bacteroides Bile Esculin Agar plates (incubated anaerobically at 37°C). A thioglycolate broth incubated at 37°C was also inoculated. Both blood and pericardial fluid cultures were negative for bacterial growth after 5 and 7 days of incubation, respectively. The urine culture was also negative after overnight incubation. Despite these results, an infectious etiology appeared likely, considering the biochemical results of the pericardial fluid. Universal 16S rRNA PCR on the pericardial fluid was then performed. The amplified product was sequenced and compared to all bacterial sequences available from the GenBank database by using the BLAST program (http://blast. ncbi.nlm.nih.gov/Blast.cgi). The results showed 100% similarity to the sequence of C. jejuni. The patient was continued on meropenem therapy for 21 days. He remained afebrile, and his pericarditis resolved; however, his chronic diarrhea persisted in spite of the replacement of sirolimus with tacrolimus. Stool cultures were requested 8 days after admission, but no pathogenic microorganism was isolated, and a test for the detection of Clostridium difficile toxins was negative. The patient was discharged after 26 days of hospitalization but continues to be followed as an outpatient for evaluation of his chronic diarrhea.
Discussion Vascular and cardiac complications, specifically pericarditis, are rare manifestations of C. jejuni infection. There are four documented cases of pericarditis caused by C. jejuni in the literature: a patient with secondary infection of underlying pericardial effusion due to hypothyroidism (3), a young traveler with no relevant history (4), a 15-year-old patient with enterocolitis (5), and a patient with X-linked agammaglobulinemia (6). To our knowledge, this is the first case of C. jejuni-related pericarditis in a renal transplant recipient. C. jejuni-related myocarditis and myopericarditis are the most frequently reported cardiac complications documented in the medical literature (7). Two cases of septic aneurysm (abdominal aortic pseudoaneurysm and popliteal aneurysm) caused by the microorganism have also been described (8,9). An important point concerning C. jejuni infections, and especially documented pericarditis cases, is that the microorganism is not usually isolated from blood cultures. Even though C. jejuni is the most common species of Campylobacter causing disease in humans,
bacteremias are frequently caused by other species, such as C. fetus. There are two main reasons why Campylobacter, and especially C. jejuni, bacteremia may be underreported. The first is differential susceptibility to serum: C. jejuni is serum susceptible, whereas other species, such as C. fetus, are serum resistant (10). Second, the median time for growth in blood culture bottles is approximately 5 to 10 days for C. jejuni (11), and therefore, some authors recommend a 2-week incubation period for blood culture bottles or subculture of the contents of these bottles onto solid medium after the standard 5-day incubation period if Campylobacter infection is suspected (12). More information is needed to establish the optimal time of incubation to recover C. jejuni from blood culture bottles. In addition, C. jejuni grows best at 42°C, unlike other species of Campylobacter, and antibiotic-containing selective media, such as Skirrow or Campy-BAP agar, are usually required for its isolation (1). Accordingly, our clinical specimens (blood and pericardial fluid) were not incubated under the best conditions of temperature and atmosphere to isolate C. jejuni, and a longer period of incubation could have made detection of the microorganism possible. With all cultures showing no bacterial growth, the unexpected detection of C. jejuni genetic material in the pericardial fluid demonstrates the value and utility of molecular testing to establish the laboratory diagnosis of an infectious disease, especially when caused by a bacterium that is difficult to culture. Moreover, long-term therapy with sirolimus, an inhibitor of response to interleukin 2, has also been associated with pericardial effusion and pericardial tamponade (13-15). In our case, sirolimus may have been the main cause of the pericardial effusion, while C. jejuni might have caused a secondary infection of the pericardial fluid, following bacteremia from a primary intestinal source. However, blood and stool cultures were negative using conventional methods. C. jejuni gastrointestinal infection might have occurred weeks before admission, and therefore, intestinal symptoms usually associated with the microorganism could have gone unnoticed because of the patient’s chronic diarrhea. In summary, even though C. jejuni is a rare cause of pericarditis, it should be considered, especially in patients with a history of recent diarrhea. In our case, the patient suffered from chronic diarrhea, which could have masked the symptoms of Campylobacter gastrointestinal infection. Furthermore, pericardial fluid was not processed properly because C. jejuni as a cause of the patient’s
pericarditis was not clinically suspected. This case also emphasizes the value of using molecular methods to detect microorganisms that are difficult to culture or those that might not be suspected as the cause of infection.
References 1. Fitzgerald, C. and I. Nachamkin. 2010. Campylobacter and Arcobacter, p. 885-899. In J. Versalovic et al. (ed.), Manual of clinical microbiology, 10th ed. ASM Press, Washington, DC. 2. Lahuerta, A. et al. 2011. Zoonoses in the European Union: origin, distribution and dynamics—the EFSA-ECDC summary report 2009. Euro Surveill. 16:19832. 3. Lieber, I.H., E.R. Rensimer, and C.D. Ericsson. 1981. Campylobacter pericarditis in hypothyroidism. Am. Heart J. 102:462-463. 4. Rahmna, M. 1979. Bacteraemia and pericarditis from Campylobacter infection. Br. J. Clin. Pract. 33:331. 5. Nowakowski, M.L.D., D. Listopadzki, and S.R. Freeman. 2004. Pericarditis associated with Campylobacter jejuni enterocolitis. Hosp. Physician 40:39-42. 6. Rafi, A. and J. Matz. 2002. An unusual case of Campylobacter jejuni pericarditis in a patient with X-linked agammaglobulinemia. Ann. Allergy Asthma Immunol. 89:362-367. 7. Alzand, B.S. et al. 2010. Campylobacter jejuni: enterocolitis and myopericarditis. Int. J. Cardiol. 144:e14-16. 8. Roan, J.N., W.C. Ko, and C.W. Luo. 2009. Abdominal septic aortic pseudoaneurysm caused by Campylobacter jejuni infection: report of a case. Surg. Today 39:137-140. 9. Hannu, T. et al. 2005. Three cases of cardiac complications associated with Campylobacter jejuni infection and review of the literature. Eur. J. Clin. Microbiol. Infect. Dis. 24:619-622. 10. Allos, B.M. and M.J. Blaser. 2009. Campylobacter jejuni and related species, p. 2793-2802. In G.L. Mandell, J.E. Bennett, and R. Dolin (ed), Mandell, Douglas, and Bennett’s principles and practice of infectious diseases, 7th ed. Elsevier Churchill-Livingstone, Philadelphia, PA. 11. Wang, W.L. and M.J. Blaser. 1986. Detection of pathogenic Campylobacter species in blood culture systems. J. Clin. Microbiol. 23:709-714. 12. Louwen, R. et al. 2012. Campylobacter bacteremia: a rare and underreported event? Eur. J. Microbiol. Immunol. 2:76-87. 13. Bertrand, D. et al. 2013. Sirolimus therapy may cause cardiac tamponade. Transpl. Int. 26:e4-7. 14. Steele, G.H. et al. 2008. Pericardial effusion coincident with sirolimus therapy: a review of Wyeth’s safety database. Transplantation 85:645-647. 15. Truong, U., A.J. Moon-Grady, and L. Butani. 2005. Cardiac tamponade in a pediatric renal transplant recipient on sirolimus therapy. Pediatr. Transplant 9:541-544.
Clinical Microbiology Newsletter 37:21,2015 | ©2015 Elsevier
175
R EPORT
Campylobacter jejuni Pericarditis in a Renal Transplant Recipient on Sirolimus Therapy Isabel Fradejas, M.S.,1 Francisco Lopez-Medrano, M.D.,2 Esther González-Montes, M.D.,3 Angeles Orellana, M.D.,1 Fernando Chaves, M.D.,1 1 Servicio de Microbiología, 2Unidad de Enfermedades Infecciosas, 3Servicio de Nefrología, Hospital Universitario, Madrid, Spain
Introduction Campylobacter species are curved, motile, microaerophilic, nonspore-forming, Gram-negative rods. The genus Campylobacter includes 22 species, with Campylobacter jejuni, Campylobacter coli, and Campylobacter fetus being the most common species causing Corresponding author: Fernando Chaves, Servicio de Microbiología, Hospital Universitario 12 de Octubre, Avenida de Córdoba sn, Madrid 28041, Spain. Tel: (34) 917792404. E-mail: fernando.chaves@salud. madrid.org
human disease. A variety of animals are implicated as reservoirs for Campylobacter spp., and human infections usually follow ingestion of improperly handled or cooked food, primarily poultry products (1). In Europe, campylobacteriosis is the most prevalent zoonotic disease in humans, and its estimated incidence has remained constant over the past several years (2). Enteric and extraintestinal illnesses are associated with Campylobacter spp.; gastrointestinal disease is often related to C. jejuni and C. coli, whereas C. fetus causes extraintestinal infections, such as bacteremia and other intravascular infections.
Clinical Microbiology Newsletter 37:21,2015 | ©2015 Elsevier
173
We describe a case of C. jejuni pericarditis in a renal transplant recipient with pericardial effusion, likely secondary to the immunosuppressive drug sirolimus. The final etiologic diagnosis required molecular amplification by universal 16S rRNA PCR on the pericardial fluid. The patient’s pericarditis infection resolved following pericardiocentesis and a course of broad-spectrum antibiotic therapy.
Case Report A 60-year-old male with end stage renal disease secondary to polycystic kidney disease underwent renal transplantation 9 years prior to this admission. His immunosuppressive therapy consisted of sirolimus (3 mg/day) and prednisone (5 mg/day). From the beginning of his post-transplantation period, the patient presented with chronic diarrhea, with approximately 4 to 6 bowel movements per day. He also had two episodes of urinary tract infection caused by Morganella morganii in the 3 months before his current admission. The patient presented to the emergency room with a 2-day history of fever, dry cough, and pleuritic chest pain. He also complained about a mild increase in bowel movements (approximately 8 per day) over the past week. The stool consistency was watery, and the stool contained no mucus or blood. The patient denied experiencing abdominal or joint pain, vomiting, or having symptoms of urinary tract infection. On physical examination, he had a pulse rate of 82 bpm, blood pressure of 81/66 mm Hg, and no fever, and appeared in good general condition. Chest and abdominal examinations were normal. Laboratory values were normal, except for a serum creatinine level of 52.3 mg/L, urea of 1,360 mg/L, lactate dehydrogenase (LDH) of 256 U/L, and C-reactive protein of 188.5 mg/L. The peripheral white blood cell (WBC) count was 8.4 X 106/L, with 89.5% neutrophils and 6.1% lymphocytes. Chest X ray revealed severe cardiomegaly with tracheal shifting. No infiltrations or costophrenic angle clamping was revealed. An echocardiogram showed pericardial effusion with hemodynamic compromise, and therefore, the patient was admitted to the intensive care cardiology unit. He underwent urgent pericardiocentesis, and a catheter was left in place for 3 days. Three hundred milliliters of hemopurulent pericardial fluid was collected for hematological, biochemical, microbiological, and pathological analyses. After the pericardiocentesis was performed, the patient developed a fever, prompting the collection of blood and urine specimens for culture. In addition, empiric antibiotic therapy with intravenous ceftriaxone was started (1 g/day). The WBC count on the pericardial fluid was 142,000 cells/μl, with 80% neutrophils and 20% lymphocytes. The red blood cell count was 1,970,565 cells/μl. The patient also had a glucose level of 5 mg/ dl, a protein level of 5.10 g/dl, and an LDH level of 5,114 U/L. A direct Gram-stained smear of the specimen showed inflammatory cells; no microorganisms were detected. Considering these results and suspecting that the patient had purulent pericarditis, his ceftriaxone therapy was discontinued and replaced with intravenous meropenem (1 g/day) for 3 weeks. He also received a single dose of 700 mg of daptomycin and 1 g of amikacin, both intravenously.
174
Clinical Microbiology Newsletter 37:21,2015 | ©2015 Elsevier
During his stay in the hospital, the patient had several medical complications. Briefly, after undergoing pericardiocentesis and despite the initiation of broad-spectrum antimicrobial therapy, he remained intermittently febrile. Following pericardiocentesis and deterioration of his renal function, he also developed left-side heart failure. Sirolimus was replaced by tacrolimus on day 5 of admission because of toxic levels and its likely being the cause of the pericardial effusion and chronic diarrhea. In the microbiology laboratory, the blood, pericardial, and urine specimens were processed by using standard procedures. In brief, blood specimens were inoculated into aerobic and anaerobic culture bottles and incubated at 37°C in the Bact/ALERT 3D automated blood culture system (bioMérieux, Durham, NC). The pericardial fluid was plated onto blood and MacConkey agars (incubated at 37°C in air), chocolate agar (incubated at 37°C in air supplemented with 5% CO2), and blood agar and Bacteroides Bile Esculin Agar plates (incubated anaerobically at 37°C). A thioglycolate broth incubated at 37°C was also inoculated. Both blood and pericardial fluid cultures were negative for bacterial growth after 5 and 7 days of incubation, respectively. The urine culture was also negative after overnight incubation. Despite these results, an infectious etiology appeared likely, considering the biochemical results of the pericardial fluid. Universal 16S rRNA PCR on the pericardial fluid was then performed. The amplified product was sequenced and compared to all bacterial sequences available from the GenBank database by using the BLAST program (http://blast. ncbi.nlm.nih.gov/Blast.cgi). The results showed 100% similarity to the sequence of C. jejuni. The patient was continued on meropenem therapy for 21 days. He remained afebrile, and his pericarditis resolved; however, his chronic diarrhea persisted in spite of the replacement of sirolimus with tacrolimus. Stool cultures were requested 8 days after admission, but no pathogenic microorganism was isolated, and a test for the detection of Clostridium difficile toxins was negative. The patient was discharged after 26 days of hospitalization but continues to be followed as an outpatient for evaluation of his chronic diarrhea.
Discussion Vascular and cardiac complications, specifically pericarditis, are rare manifestations of C. jejuni infection. There are four documented cases of pericarditis caused by C. jejuni in the literature: a patient with secondary infection of underlying pericardial effusion due to hypothyroidism (3), a young traveler with no relevant history (4), a 15-year-old patient with enterocolitis (5), and a patient with X-linked agammaglobulinemia (6). To our knowledge, this is the first case of C. jejuni-related pericarditis in a renal transplant recipient. C. jejuni-related myocarditis and myopericarditis are the most frequently reported cardiac complications documented in the medical literature (7). Two cases of septic aneurysm (abdominal aortic pseudoaneurysm and popliteal aneurysm) caused by the microorganism have also been described (8,9). An important point concerning C. jejuni infections, and especially documented pericarditis cases, is that the microorganism is not usually isolated from blood cultures. Even though C. jejuni is the most common species of Campylobacter causing disease in humans,
bacteremias are frequently caused by other species, such as C. fetus. There are two main reasons why Campylobacter, and especially C. jejuni, bacteremia may be underreported. The first is differential susceptibility to serum: C. jejuni is serum susceptible, whereas other species, such as C. fetus, are serum resistant (10). Second, the median time for growth in blood culture bottles is approximately 5 to 10 days for C. jejuni (11), and therefore, some authors recommend a 2-week incubation period for blood culture bottles or subculture of the contents of these bottles onto solid medium after the standard 5-day incubation period if Campylobacter infection is suspected (12). More information is needed to establish the optimal time of incubation to recover C. jejuni from blood culture bottles. In addition, C. jejuni grows best at 42°C, unlike other species of Campylobacter, and antibiotic-containing selective media, such as Skirrow or Campy-BAP agar, are usually required for its isolation (1). Accordingly, our clinical specimens (blood and pericardial fluid) were not incubated under the best conditions of temperature and atmosphere to isolate C. jejuni, and a longer period of incubation could have made detection of the microorganism possible. With all cultures showing no bacterial growth, the unexpected detection of C. jejuni genetic material in the pericardial fluid demonstrates the value and utility of molecular testing to establish the laboratory diagnosis of an infectious disease, especially when caused by a bacterium that is difficult to culture. Moreover, long-term therapy with sirolimus, an inhibitor of response to interleukin 2, has also been associated with pericardial effusion and pericardial tamponade (13-15). In our case, sirolimus may have been the main cause of the pericardial effusion, while C. jejuni might have caused a secondary infection of the pericardial fluid, following bacteremia from a primary intestinal source. However, blood and stool cultures were negative using conventional methods. C. jejuni gastrointestinal infection might have occurred weeks before admission, and therefore, intestinal symptoms usually associated with the microorganism could have gone unnoticed because of the patient’s chronic diarrhea. In summary, even though C. jejuni is a rare cause of pericarditis, it should be considered, especially in patients with a history of recent diarrhea. In our case, the patient suffered from chronic diarrhea, which could have masked the symptoms of Campylobacter gastrointestinal infection. Furthermore, pericardial fluid was not processed properly because C. jejuni as a cause of the patient’s
pericarditis was not clinically suspected. This case also emphasizes the value of using molecular methods to detect microorganisms that are difficult to culture or those that might not be suspected as the cause of infection.
References 1. Fitzgerald, C. and I. Nachamkin. 2010. Campylobacter and Arcobacter, p. 885-899. In J. Versalovic et al. (ed.), Manual of clinical microbiology, 10th ed. ASM Press, Washington, DC. 2. Lahuerta, A. et al. 2011. Zoonoses in the European Union: origin, distribution and dynamics—the EFSA-ECDC summary report 2009. Euro Surveill. 16:19832. 3. Lieber, I.H., E.R. Rensimer, and C.D. Ericsson. 1981. Campylobacter pericarditis in hypothyroidism. Am. Heart J. 102:462-463. 4. Rahmna, M. 1979. Bacteraemia and pericarditis from Campylobacter infection. Br. J. Clin. Pract. 33:331. 5. Nowakowski, M.L.D., D. Listopadzki, and S.R. Freeman. 2004. Pericarditis associated with Campylobacter jejuni enterocolitis. Hosp. Physician 40:39-42. 6. Rafi, A. and J. Matz. 2002. An unusual case of Campylobacter jejuni pericarditis in a patient with X-linked agammaglobulinemia. Ann. Allergy Asthma Immunol. 89:362-367. 7. Alzand, B.S. et al. 2010. Campylobacter jejuni: enterocolitis and myopericarditis. Int. J. Cardiol. 144:e14-16. 8. Roan, J.N., W.C. Ko, and C.W. Luo. 2009. Abdominal septic aortic pseudoaneurysm caused by Campylobacter jejuni infection: report of a case. Surg. Today 39:137-140. 9. Hannu, T. et al. 2005. Three cases of cardiac complications associated with Campylobacter jejuni infection and review of the literature. Eur. J. Clin. Microbiol. Infect. Dis. 24:619-622. 10. Allos, B.M. and M.J. Blaser. 2009. Campylobacter jejuni and related species, p. 2793-2802. In G.L. Mandell, J.E. Bennett, and R. Dolin (ed), Mandell, Douglas, and Bennett’s principles and practice of infectious diseases, 7th ed. Elsevier Churchill-Livingstone, Philadelphia, PA. 11. Wang, W.L. and M.J. Blaser. 1986. Detection of pathogenic Campylobacter species in blood culture systems. J. Clin. Microbiol. 23:709-714. 12. Louwen, R. et al. 2012. Campylobacter bacteremia: a rare and underreported event? Eur. J. Microbiol. Immunol. 2:76-87. 13. Bertrand, D. et al. 2013. Sirolimus therapy may cause cardiac tamponade. Transpl. Int. 26:e4-7. 14. Steele, G.H. et al. 2008. Pericardial effusion coincident with sirolimus therapy: a review of Wyeth’s safety database. Transplantation 85:645-647. 15. Truong, U., A.J. Moon-Grady, and L. Butani. 2005. Cardiac tamponade in a pediatric renal transplant recipient on sirolimus therapy. Pediatr. Transplant 9:541-544.
Clinical Microbiology Newsletter 37:21,2015 | ©2015 Elsevier
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