Heart & Lung xxx (2014) 1e3
Contents lists available at ScienceDirect
Heart & Lung journal homepage: www.heartandlung.org
Acute limb ischemia due to Candida lusitaniae aortic valve endocarditis Amish Patel, MD *, Walid Almuti, MBBS, Hari Polenakovik, MD ** Department of Internal Medicine, Wright State University Boonshoft School of Medicine, Dayton, OH, USA
a r t i c l e i n f o
a b s t r a c t
Article history: Received 14 March 2014 Received in revised form 22 March 2014 Accepted 24 March 2014 Available online xxx
We present a case of a 35-year-old male with history of intravenous heroin use, who presented with acute limb ischemia and was found to have Candida lusitaniae endocarditis. After an urgent intervention to salvage the right lower extremity, successful outcome of his infection was achieved by a combined surgical and antifungal treatment. Ó 2014 Elsevier Inc. All rights reserved.
Keywords: Candida lusitaniae Endocarditis Emboli Limb ischemia
Introduction Candida endocarditis is a relatively rare, but is one of the most serious manifestations of invasive candidiasis.1 Candida spp usually produces large vegetations on heart valves that have high propensity to embolize and are associated with high rates of morbidity and mortality.2 Treatment is difficult and invariably requires surgical resection of the affected valve followed by prolonged course of antifungal therapy.3 Herein, we present a case of Candida lusitaniae endocarditis manifesting as acute limb ischemia.
Case report A 35-year-old male presented with a 3-day history of progressive right leg weakness and numbness. On the day of admission his right leg and foot became cold, he lost sensation in his right leg and foot and was unable to move his foot at all. He admitted to using heroin intravenously 1 week prior to presentation. His temperature was 38.9 C, pulse 110 beats per minute but blood pressure was normal. Physical examination was notable for cold right leg and * Corresponding author. 128 East Apple Street, Weber CHE 2nd floor, Dayton, OH 45409, USA. Tel.: þ1 937 208 2873. ** Corresponding author. Fax: þ1 937 208 2621. E-mail addresses: [email protected] (A. Patel), haralampie1909@ gmail.com (H. Polenakovik). 0147-9563/$ e see front matter Ó 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.hrtlng.2014.03.010
absent pulses in the right leg. Initial laboratory work was notable for an elevated creatine phophokinase (1395 units/liter), aspartate transaminase (97 units/liter), alanine transaminase (79 units/liter) and alkaline phosphotase (143 units/liter), but was otherwise unremarkable. Ankle brachial Index was 0.47 in the right leg and 0.99 in the left leg. Angiogram of the aorta and legs revealed occlusion of the distal right common iliac artery and external iliac artery with distal embolus in the popliteal artery extending into the tibioperoneal trunk and anterior tibial arteries (Fig. 1). Urgent right femoral, right external iliac artery and right popliteal embolectomy with four compartment fasciotomies were performed. Histopathology of removed embolus revealed fibrin thrombus with inflammatory debris. Gram stain showed gram-negative bacilli but no organisms grew on specimen culture. Transesophageal echocardiogram revealed a large 2 2 cm density on the aortic valve consistent with vegetation (Fig. 2). Blood cultures grew Candida species. Empiric liposomal amphotericin B and 5-flucytosine were commenced. Patient underwent resection of native aortic valve and placement of 25 mm Edwards pericardial tissue heart valve. Histopathology of the resected valve (Gomori Methenamine stain) disclosed pseudohyphae indicative of Candida endocarditis. Blood isolate was later identified as C. lusitaniae, which was fully susceptible to all antifungals tested. The patient received 4 weeks of amphotericin B and flucytosine following first negative blood culture, followed by 8 weeks of fluconazole 400 mg daily. At 8 months follow up, he has had no recurrence of the infection or relapse.
2
A. Patel et al. / Heart & Lung xxx (2014) 1e3
Fig. 1. Three-dimensional reconstruction of computed tomography angiogram of the aorta and lower extremities. The coronal view shows occlusion of distal right common iliac and external iliac artery.
Discussion Fungal endocarditis is a rare entity accounting for only 2e4% of all cases of endocarditis.4 Candida species account for the most cases of fungal endocarditis.5 The mortality rate from fungal endocarditis has been shown to be as high as 72%.2 The most common anatomic site of univalvular fungal vegetations in patients with fungal endocarditis was found to be the aortic valve,2 as was the case with our patient. Complications from fungal endocarditis can be a wide range, the most common being embolization, neurological deficits and heart failure. Severe embolic complications as the first and only symptom are not uncommonly reported.6 In an analysis of 270 cases of fungal endocarditis over 30 years, embolization of major arterial vessels that resulted in focal ischemia occurred in 45% of the reported patients, and of those 42% had embolization in the major limb vessel of the femoral artery division.2 The acute limb ischemia experienced by our patient was managed according to the ACCF/AHA task force recommendations7 and resulted in preserved limb viability.
Fig. 2. Trans-esophageal echocardiogram of the aortic valve vegetations. White arrow indicates largest fungal vegetation identified in this case.
Intravenous drug use is reported to be a risk factor for invasive Candida infections including endocarditis.2,8,9 This has been theorized to be related to contamination of brown heroin with lemon juice, which is used to increase its solubility.10 Candida albicans is the most common etiology of fungal endocarditis, followed by non-albicans Candida spp, Aspergillus species and Histoplasma capsulatum.2 C. lusitaniae was first described as an opportunities infection in 1979.11 A recent review of thirty cases revealed that this Candida species typically affects immunocompromised patients and accounts for less than 5% of all invasive Candida infections.12 In vitro Amphotericin B resistance is much more common in C. lusitaniae compared to other Candida spp. However, several investigators reported poor correlation between in vitro susceptibilities to Amphotericin B and clinical outcome.12 Treatment guidelines for native valve Candida endocarditis strongly recommend surgical treatment within 1 week combined with antifungal treatment consisting of liposomal amphotericin B or caspofungin for 6e8 weeks with or without additional flucytosine, followed by fluconazole.3 Basis for these recommendations was from previous analyses that reported a significantly higher survival in patients treated with combined treatment with surgery and antifungal agents compared to antifungals alone.2 To the best of our knowledge, there are only three reported cases of C. lusitaniae endocarditis, of which only one was native valve endicarditits.13e15 Both prosthetic valve endocarditis cases had lethal outcome, where as the native valve endocarditis patient did well following valve replacement surgery and lifelong antifungal suppressive therapy.13e15 Conclusion Fungal endocarditis is very rare entity and is associated with a high morbidity and mortality rates. Candida spp usually produces large vegetations on heart valves that have high propensity to embolize. When intravenous drug user presents with embolization to large blood vessel Candida endocarditis should be suspected. Prompt diagnosis and aggressive surgical and medical treatment may produce favorable outcome. We believe that this is the second documented case of C. lusitaniae native valve endocarditis in the medical literature. References 1. Pappas PG, Kauffman CA, Andes D, et al, Infectious Diseases Society of America. Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis. 2009 Mar 1;48(5): 503e535. 2. Ellis ME, Al-Abdely H, Sandridge A, Greer W, Ventura W. Fungal endocarditis: evidence in the world literature, 1965e1995. Clin Infect Dis. 2001 Jan;32(1): 50e62. 3. Tacke D, Koehler P, Cornely OA. Fungal endocarditis. Curr Opin Infect Dis. 2013;26(6):501e507. 4. Gould FK, Denning DW, Elliott TS, et al. Guidelines for the diagnosis and antibiotic treatment of endocarditis in adults: a report of the Working Party of the British Society for Antimicrobial Chemotherapy. J Antimicrob Chemother. 2012;67:269e289. 5. Benjamin Jr DK, Miro JM, Hoen B, et al, The ICE-MD Study Group. Candida endocarditis: contemporary cases from the International Collaboration of Infectious Endocarditis Merged Database. Scand J Infect Dis. 2004;36:453e455. 6. Ribeiro S, Gaspar A, Assunção A, et al. Fungal endocarditis with central and peripheral embolization: case report. Rev Port Cardiol. 2012;31:449e453. 7. Anderson JL, Halperin JL, Albert NM, et al. Management of patients with peripheral artery disease (compilation of 2005 and 2011 ACCF/AHA guideline recommendations): a report of the American College of Cardiology Foundation/ American Heart Association Task Force on Practice Guidelines. Circulation. 2013 Apr 2;127(13):1425e1443. 8. Sousa C, Botelho C, Rodrigues D, Azeredo J, Oliveira R. Infective endocarditis in intravenous drug abusers: an update. Eur J Clin Microbiol Infect Dis. 2012 Nov;31(11):2905e2910. 9. Lefort A, Chartier L, Sendid B, et al. Diagnosis, management and outcome of Candida endocarditis. Clin Microbiol Infect. 2012;18:E99eE109.
A. Patel et al. / Heart & Lung xxx (2014) 1e3 10. Bisbe J, Miro JM, Latorre X, et al. Disseminated candidiasis in addicts who use brown heroin: report of 83 cases and review. Clin Infect Dis. 1992;15: 910e923. 11. Holzschu DL, Presley HL, Miranda M, Phaff HJ. Identification of Candida lusitaniae as an opportunistic yeast in humans. J Clin Microbiol. 1979 Aug;10(2): 202e205. 12. Hawkins JL, Baddour LM. Candida lusitaniae infections in the era of fluconazole availability. Clin Infect Dis. 2003 Jan 15;36(2):e14ee18.
3
13. Wendt B, Haglund L, Razavi A, Rath R. Candida lusitaniae: an uncommon cause of prosthetic valve endocarditis. Clin Infect Dis. 1998 Mar;26(3):769e770. 14. Michel RG, Kinasewitz GT, Drevets DA, Levin JH, Warden DW. Prosthetic valve endocarditis caused by Candida lusitaniae, an uncommon pathogen: a case report. J Med Case Rep. 2009 May 14;3:7611. 15. Hariya A, Naruse Y, Kobayashi T, et al. Fungal endocarditis found at onset of lower limb acute aortic occlusion; report of a case. Kyobu Geka. 2005 Aug;58(9):831e834.
Contents lists available at ScienceDirect
Heart & Lung journal homepage: www.heartandlung.org
Acute limb ischemia due to Candida lusitaniae aortic valve endocarditis Amish Patel, MD *, Walid Almuti, MBBS, Hari Polenakovik, MD ** Department of Internal Medicine, Wright State University Boonshoft School of Medicine, Dayton, OH, USA
a r t i c l e i n f o
a b s t r a c t
Article history: Received 14 March 2014 Received in revised form 22 March 2014 Accepted 24 March 2014 Available online xxx
We present a case of a 35-year-old male with history of intravenous heroin use, who presented with acute limb ischemia and was found to have Candida lusitaniae endocarditis. After an urgent intervention to salvage the right lower extremity, successful outcome of his infection was achieved by a combined surgical and antifungal treatment. Ó 2014 Elsevier Inc. All rights reserved.
Keywords: Candida lusitaniae Endocarditis Emboli Limb ischemia
Introduction Candida endocarditis is a relatively rare, but is one of the most serious manifestations of invasive candidiasis.1 Candida spp usually produces large vegetations on heart valves that have high propensity to embolize and are associated with high rates of morbidity and mortality.2 Treatment is difficult and invariably requires surgical resection of the affected valve followed by prolonged course of antifungal therapy.3 Herein, we present a case of Candida lusitaniae endocarditis manifesting as acute limb ischemia.
Case report A 35-year-old male presented with a 3-day history of progressive right leg weakness and numbness. On the day of admission his right leg and foot became cold, he lost sensation in his right leg and foot and was unable to move his foot at all. He admitted to using heroin intravenously 1 week prior to presentation. His temperature was 38.9 C, pulse 110 beats per minute but blood pressure was normal. Physical examination was notable for cold right leg and * Corresponding author. 128 East Apple Street, Weber CHE 2nd floor, Dayton, OH 45409, USA. Tel.: þ1 937 208 2873. ** Corresponding author. Fax: þ1 937 208 2621. E-mail addresses: [email protected] (A. Patel), haralampie1909@ gmail.com (H. Polenakovik). 0147-9563/$ e see front matter Ó 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.hrtlng.2014.03.010
absent pulses in the right leg. Initial laboratory work was notable for an elevated creatine phophokinase (1395 units/liter), aspartate transaminase (97 units/liter), alanine transaminase (79 units/liter) and alkaline phosphotase (143 units/liter), but was otherwise unremarkable. Ankle brachial Index was 0.47 in the right leg and 0.99 in the left leg. Angiogram of the aorta and legs revealed occlusion of the distal right common iliac artery and external iliac artery with distal embolus in the popliteal artery extending into the tibioperoneal trunk and anterior tibial arteries (Fig. 1). Urgent right femoral, right external iliac artery and right popliteal embolectomy with four compartment fasciotomies were performed. Histopathology of removed embolus revealed fibrin thrombus with inflammatory debris. Gram stain showed gram-negative bacilli but no organisms grew on specimen culture. Transesophageal echocardiogram revealed a large 2 2 cm density on the aortic valve consistent with vegetation (Fig. 2). Blood cultures grew Candida species. Empiric liposomal amphotericin B and 5-flucytosine were commenced. Patient underwent resection of native aortic valve and placement of 25 mm Edwards pericardial tissue heart valve. Histopathology of the resected valve (Gomori Methenamine stain) disclosed pseudohyphae indicative of Candida endocarditis. Blood isolate was later identified as C. lusitaniae, which was fully susceptible to all antifungals tested. The patient received 4 weeks of amphotericin B and flucytosine following first negative blood culture, followed by 8 weeks of fluconazole 400 mg daily. At 8 months follow up, he has had no recurrence of the infection or relapse.
2
A. Patel et al. / Heart & Lung xxx (2014) 1e3
Fig. 1. Three-dimensional reconstruction of computed tomography angiogram of the aorta and lower extremities. The coronal view shows occlusion of distal right common iliac and external iliac artery.
Discussion Fungal endocarditis is a rare entity accounting for only 2e4% of all cases of endocarditis.4 Candida species account for the most cases of fungal endocarditis.5 The mortality rate from fungal endocarditis has been shown to be as high as 72%.2 The most common anatomic site of univalvular fungal vegetations in patients with fungal endocarditis was found to be the aortic valve,2 as was the case with our patient. Complications from fungal endocarditis can be a wide range, the most common being embolization, neurological deficits and heart failure. Severe embolic complications as the first and only symptom are not uncommonly reported.6 In an analysis of 270 cases of fungal endocarditis over 30 years, embolization of major arterial vessels that resulted in focal ischemia occurred in 45% of the reported patients, and of those 42% had embolization in the major limb vessel of the femoral artery division.2 The acute limb ischemia experienced by our patient was managed according to the ACCF/AHA task force recommendations7 and resulted in preserved limb viability.
Fig. 2. Trans-esophageal echocardiogram of the aortic valve vegetations. White arrow indicates largest fungal vegetation identified in this case.
Intravenous drug use is reported to be a risk factor for invasive Candida infections including endocarditis.2,8,9 This has been theorized to be related to contamination of brown heroin with lemon juice, which is used to increase its solubility.10 Candida albicans is the most common etiology of fungal endocarditis, followed by non-albicans Candida spp, Aspergillus species and Histoplasma capsulatum.2 C. lusitaniae was first described as an opportunities infection in 1979.11 A recent review of thirty cases revealed that this Candida species typically affects immunocompromised patients and accounts for less than 5% of all invasive Candida infections.12 In vitro Amphotericin B resistance is much more common in C. lusitaniae compared to other Candida spp. However, several investigators reported poor correlation between in vitro susceptibilities to Amphotericin B and clinical outcome.12 Treatment guidelines for native valve Candida endocarditis strongly recommend surgical treatment within 1 week combined with antifungal treatment consisting of liposomal amphotericin B or caspofungin for 6e8 weeks with or without additional flucytosine, followed by fluconazole.3 Basis for these recommendations was from previous analyses that reported a significantly higher survival in patients treated with combined treatment with surgery and antifungal agents compared to antifungals alone.2 To the best of our knowledge, there are only three reported cases of C. lusitaniae endocarditis, of which only one was native valve endicarditits.13e15 Both prosthetic valve endocarditis cases had lethal outcome, where as the native valve endocarditis patient did well following valve replacement surgery and lifelong antifungal suppressive therapy.13e15 Conclusion Fungal endocarditis is very rare entity and is associated with a high morbidity and mortality rates. Candida spp usually produces large vegetations on heart valves that have high propensity to embolize. When intravenous drug user presents with embolization to large blood vessel Candida endocarditis should be suspected. Prompt diagnosis and aggressive surgical and medical treatment may produce favorable outcome. We believe that this is the second documented case of C. lusitaniae native valve endocarditis in the medical literature. References 1. Pappas PG, Kauffman CA, Andes D, et al, Infectious Diseases Society of America. Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis. 2009 Mar 1;48(5): 503e535. 2. Ellis ME, Al-Abdely H, Sandridge A, Greer W, Ventura W. Fungal endocarditis: evidence in the world literature, 1965e1995. Clin Infect Dis. 2001 Jan;32(1): 50e62. 3. Tacke D, Koehler P, Cornely OA. Fungal endocarditis. Curr Opin Infect Dis. 2013;26(6):501e507. 4. Gould FK, Denning DW, Elliott TS, et al. Guidelines for the diagnosis and antibiotic treatment of endocarditis in adults: a report of the Working Party of the British Society for Antimicrobial Chemotherapy. J Antimicrob Chemother. 2012;67:269e289. 5. Benjamin Jr DK, Miro JM, Hoen B, et al, The ICE-MD Study Group. Candida endocarditis: contemporary cases from the International Collaboration of Infectious Endocarditis Merged Database. Scand J Infect Dis. 2004;36:453e455. 6. Ribeiro S, Gaspar A, Assunção A, et al. Fungal endocarditis with central and peripheral embolization: case report. Rev Port Cardiol. 2012;31:449e453. 7. Anderson JL, Halperin JL, Albert NM, et al. Management of patients with peripheral artery disease (compilation of 2005 and 2011 ACCF/AHA guideline recommendations): a report of the American College of Cardiology Foundation/ American Heart Association Task Force on Practice Guidelines. Circulation. 2013 Apr 2;127(13):1425e1443. 8. Sousa C, Botelho C, Rodrigues D, Azeredo J, Oliveira R. Infective endocarditis in intravenous drug abusers: an update. Eur J Clin Microbiol Infect Dis. 2012 Nov;31(11):2905e2910. 9. Lefort A, Chartier L, Sendid B, et al. Diagnosis, management and outcome of Candida endocarditis. Clin Microbiol Infect. 2012;18:E99eE109.
A. Patel et al. / Heart & Lung xxx (2014) 1e3 10. Bisbe J, Miro JM, Latorre X, et al. Disseminated candidiasis in addicts who use brown heroin: report of 83 cases and review. Clin Infect Dis. 1992;15: 910e923. 11. Holzschu DL, Presley HL, Miranda M, Phaff HJ. Identification of Candida lusitaniae as an opportunistic yeast in humans. J Clin Microbiol. 1979 Aug;10(2): 202e205. 12. Hawkins JL, Baddour LM. Candida lusitaniae infections in the era of fluconazole availability. Clin Infect Dis. 2003 Jan 15;36(2):e14ee18.
3
13. Wendt B, Haglund L, Razavi A, Rath R. Candida lusitaniae: an uncommon cause of prosthetic valve endocarditis. Clin Infect Dis. 1998 Mar;26(3):769e770. 14. Michel RG, Kinasewitz GT, Drevets DA, Levin JH, Warden DW. Prosthetic valve endocarditis caused by Candida lusitaniae, an uncommon pathogen: a case report. J Med Case Rep. 2009 May 14;3:7611. 15. Hariya A, Naruse Y, Kobayashi T, et al. Fungal endocarditis found at onset of lower limb acute aortic occlusion; report of a case. Kyobu Geka. 2005 Aug;58(9):831e834.
