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Bartonella endocarditis
Journal of Cardiology Cases 13 (2016) 1–3
Contents lists available at ScienceDirect
Journal of Cardiology Cases journal homepage: www.elsevier.com/locate/jccase
Case Report
Bartonella endocarditis Roxana Ghashghaei (MD)*, Irene Thung (MD), Grace Y. Lin (MD, PhD), Rebecca E. Sell (MD) University of California San Diego Medical Center, San Diego, CA, USA
A R T I C L E I N F O
A B S T R A C T
Article history: Received 10 April 2015 Received in revised form 7 August 2015 Accepted 11 August 2015
Blood culture-negative endocarditis presents a clinical and diagnostic challenge. Here, we describe a patient with a delayed diagnosis of Bartonella henselae endocarditis. ß 2015 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.
Keywords: Culture negative endocarditis Bartonella endocarditis Aortic valve vegetation
Introduction This case illustrates an initial presentation of Bartonella endocarditis which was masked by an admission to the trauma service for a fall and alcohol withdrawal. He was subsequently found to have an aortic valve vegetation which was positive for Bartonella henselae on autopsy. This case highlights the diagnostic challenge as well as treatment regimens available for treating Bartonella endocarditis. Case report A 54-year-old African-American man with a history of alcohol abuse was admitted to the trauma service with delirium after a fall. His blood alcohol level was elevated and given his inebriated state, minimal history could be obtained. He required increasing doses of benzodiazepines and intubation for presumed delirium tremens and airway protection. Despite appropriate management of alcohol withdrawal, the patient was intermittently febrile and developed a mild leukocytosis. Physical examination on day 3 noted splinter hemorrhages on multiple fingers, a fading sub-conjunctival hemorrhage of the right lower eyelid, and a systolic ejection murmur best heard at the left upper sternal border. Diffuse cervical and inguinal lymphadenopathy was also noted on physical examination. Blood, sputum, and urine cultures were negative on multiple occasions. On hospital day 5, given increasing concern for
* Corresponding author at: 200 West Arbor Drive, San Diego, CA 92103, USA. Tel.: +1 949 331 6550; fax: +1 949 552 5572. E-mail address: [email protected] (R. Ghashghaei).
endocarditis, a transthoracic echocardiogram was obtained which revealed hypokinesis of the anterior wall (ejection fraction 42%) with vegetation seen attached to the aortic valve (Fig. 1). The left ventricular systolic dysfunction was thought to be secondary to alcoholic cardiomyopathy which typically manifests as left ventricular dilatation with systolic dysfunction. Blood cultures were held for greater than 10 days to evaluate for Haemophilus, Aggregatibacter (previously Actinobacillus), Cardiobacterium, Eikenella corroden, Kingella organisms and were ultimately negative. Throughout the hospitalization, the patient’s white blood cell count remained elevated between 12 000 and 16 500 white blood cells/mcL. Meanwhile, C-reactive protein was also abnormally elevated at 13 mg/dL and erythrocyte sedimentation rate was high at 54 mm/h. An infectious disease consultant felt that these findings were consistent with culture-negative endocarditis and recommended treatment with vancomycin and ceftriaxone which was initiated to cover organisms associated with community-acquired and culture-negative endocarditis. Vancomycin and ceftriaxone were started on hospital day 3 and continued throughout the hospitalization. Despite continued therapy, the patient’s delirium persisted and he was unable to be extubated. To decipher the etiology of his persistent encephalopathy in the setting of culture-negative endocarditis, further work-up with cultures and serologies was obtained. B. henselae IgG was positive with a titer of greater than 1:1024, while IgM was negative. On hospital day 34, the patient was started on intravenous doxycycline for presumed Bartonella endocarditis, and continued on vancomycin and ceftriaxone. A cardiothoracic surgeon evaluated the patient but declined to offer him surgery given his decompensated health status. A family discussion was held and the decision was made to transition the patient to comfort care. He died soon thereafter.
http://dx.doi.org/10.1016/j.jccase.2015.08.011 1878-5409/ß 2015 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.
R. Ghashghaei et al. / Journal of Cardiology Cases 13 (2016) 1–3
2
performed and found to be negative for Bartonella organisms (Fig. 3C). The formalin-fixed, paraffin-embedded tissue was subsequently analyzed via polymerase chain reaction (PCR), which demonstrated the presence of B. henselae DNA. Discussion
Fig. 1.
Vegetation seen on echocardiography. A transthoracic echocardiography revealed the vegetation (Veg; arrow) attached to the aortic valve. It also showed that there is evidence of aortic valve sclerosis. The left ventricle was noted to be mildly dilated and to have a mildly depressed systolic function (ejection fraction 42%).
During autopsy, the kidney showed multiple infarcts with an associated thrombus (Fig. 2). Dissection of the heart revealed the vegetation attached to the aortic valve (Fig. 3A). Bartonella is not readily identified with a Gram stain; therefore, a Steiner stain was
Fig. 2.
Bartonella is a facultative intracellular Gram-negative aerobic rod that is an important cause of culture-negative endocarditis and the source of up to 3% of all cases of infective endocarditis. Three Bartonella species have been implicated: B. henselae, B. quintana, and B. elizabethan [1]. Diagnosis of Bartonella endocarditis is challenging due to its subacute clinical course and presence of nonspecific symptoms. Bartonella serology is often used for the diagnosis. An IgG antibody titer >1/800 has a positive predictive value of 95%. Bartonella serologies should therefore be checked in patients who present with culture-negative endocarditis and have characteristics that raise clinical suspicion for Bartonella infection including a history of lice or cat infestation, history of significant alcohol use, persistent lymphadenopathy on examination, abscess formation in the liver, or concomitant encephalopathy [2]. However, one of the pitfalls of serologic testing is its crossreaction with Coxiella burnettii [3]. Overall, PCR is the most specific diagnostic method and has 92% sensitivity for valvular biopsies. PCR can also distinguish among the various Bartonella species and detect Bartonella DNA despite the use of antibiotic therapy [4]. Treatment recommendations for Bartonella endocarditis are based on case series. The standard of care is 2 weeks of gentamicin plus 6 weeks of ceftriaxone with or without 6 weeks of doxycycline [5]. One study reviewing 101 patients with Bartonella endocarditis found that patients receiving an aminoglycoside were more likely to recover. Surgical valve repair is usually required for cure as
Embolization to the kidney. Gross examination (A) demonstrates a 1.0 cm 0.5 cm infarct (arrow). Microscopic examination (B) at 100 of magnification demonstrates a wedge-shaped infarct (*), at the edge of which is an arteriole. Higher magnification (200) of the infarcted area (C) reveals necrotic glomeruli and tubules. Magnification of the arteriole (200) at the edge of the infarct (D) demonstrates an organized and recanalized thrombus within the vessel lumen (arrow).
R. Ghashghaei et al. / Journal of Cardiology Cases 13 (2016) 1–3
Fig. 3.
3
Valve vegetation. Gross examination (A) demonstrates a vegetation (arrow) located on the aortic valve (*). (B) Low magnification (40) demonstrates that the vegetation (top left) is connected to the aortic valve (lower half). The inset shows that the vegetation is composed of predominantly fibrin and acute and chronic inflammatory cells. A Steiner stain (C) magnified at 100 is negative for organisms.
Bartonella endocarditis typically causes extensive valve damage [6]. Our patient’s initial presentation of Bartonella endocarditis was masked by an admission to the trauma service for a fall and alcohol withdrawal. Unfortunately, Bartonella was not considered as the causative agent until he failed to improve and the encephalopathy persisted. The diagnosis of Bartonella endocarditis was made via serology tests, but ultimately the patient died. Despite antibiotic therapy, the presence of Bartonella was confirmed by PCR on autopsy. This case illustrates the subtle presentation of Bartonella endocarditis, the importance of maintaining a low clinical suspicion for unusual organisms, and the utility of post-mortem PCR. Conflict of interest All authors have participated in this study and have reviewed and agreed with the content of the article. There are no conflicts of interest regarding this manuscript. None of the article contents is under consideration for publication in any other journal or has been published in any journal.
References [1] Edouard S, Nabet C, Lepidi H, Fournier PE, Raoult D. Bartonella, a common cause of endocarditis: a report on 106 cases and review. J Clin Microbiol 2015;53: 824–9. [2] Breitschwerdt EB, Sontakke S, Hopkins S. Neurological manifestations of Bartonellosis in immunocompetent patients: a composite of reports from 2005– 2012. J Neuroparasitol 2012;3:1–15. [3] La Scola B, Raoult D. Serological cross-reactions between Bartonella quintana, Bartonella henselae, and Coxiella burnetti. J Clin Microbiol 1996;34: 2270–4. [4] Breitkopf C, Hammel D, Scheld HH, Peters G, Becker K. Impact of a molecular approach to improve the microbiological diagnosis of infective heart valve endocarditis. Circulation 2005;111:1415–21. [5] Baddour LM, Wilson WR, Bayer AS, Fowler VG, Bolger AF, Levison ME, Ferrieri P, Gerber MA, Tani LY, Gewitz MH, Tong DC, Steckelberg JM, Baltimore RS, Shulman ST, Burns JC, et al. Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: endorsed by the Infectious Diseases Society of America. Circulation 2005;111:e394–434. [6] Raoult D, Fournier PE, Vandenesch F, Manardi JL, Eykyn SJ, Nash J, James E, Benoit-Lemercier C, Marrie TJ. Outcome and treatment of Bartonella endocarditis. Arch Intern Med 2003;163:226–30.
Contents lists available at ScienceDirect
Journal of Cardiology Cases journal homepage: www.elsevier.com/locate/jccase
Case Report
Bartonella endocarditis Roxana Ghashghaei (MD)*, Irene Thung (MD), Grace Y. Lin (MD, PhD), Rebecca E. Sell (MD) University of California San Diego Medical Center, San Diego, CA, USA
A R T I C L E I N F O
A B S T R A C T
Article history: Received 10 April 2015 Received in revised form 7 August 2015 Accepted 11 August 2015
Blood culture-negative endocarditis presents a clinical and diagnostic challenge. Here, we describe a patient with a delayed diagnosis of Bartonella henselae endocarditis.
Keywords: Culture negative endocarditis Bartonella endocarditis Aortic valve vegetation
Introduction This case illustrates an initial presentation of Bartonella endocarditis which was masked by an admission to the trauma service for a fall and alcohol withdrawal. He was subsequently found to have an aortic valve vegetation which was positive for Bartonella henselae on autopsy. This case highlights the diagnostic challenge as well as treatment regimens available for treating Bartonella endocarditis. Case report A 54-year-old African-American man with a history of alcohol abuse was admitted to the trauma service with delirium after a fall. His blood alcohol level was elevated and given his inebriated state, minimal history could be obtained. He required increasing doses of benzodiazepines and intubation for presumed delirium tremens and airway protection. Despite appropriate management of alcohol withdrawal, the patient was intermittently febrile and developed a mild leukocytosis. Physical examination on day 3 noted splinter hemorrhages on multiple fingers, a fading sub-conjunctival hemorrhage of the right lower eyelid, and a systolic ejection murmur best heard at the left upper sternal border. Diffuse cervical and inguinal lymphadenopathy was also noted on physical examination. Blood, sputum, and urine cultures were negative on multiple occasions. On hospital day 5, given increasing concern for
* Corresponding author at: 200 West Arbor Drive, San Diego, CA 92103, USA. Tel.: +1 949 331 6550; fax: +1 949 552 5572. E-mail address: [email protected] (R. Ghashghaei).
endocarditis, a transthoracic echocardiogram was obtained which revealed hypokinesis of the anterior wall (ejection fraction 42%) with vegetation seen attached to the aortic valve (Fig. 1). The left ventricular systolic dysfunction was thought to be secondary to alcoholic cardiomyopathy which typically manifests as left ventricular dilatation with systolic dysfunction. Blood cultures were held for greater than 10 days to evaluate for Haemophilus, Aggregatibacter (previously Actinobacillus), Cardiobacterium, Eikenella corroden, Kingella organisms and were ultimately negative. Throughout the hospitalization, the patient’s white blood cell count remained elevated between 12 000 and 16 500 white blood cells/mcL. Meanwhile, C-reactive protein was also abnormally elevated at 13 mg/dL and erythrocyte sedimentation rate was high at 54 mm/h. An infectious disease consultant felt that these findings were consistent with culture-negative endocarditis and recommended treatment with vancomycin and ceftriaxone which was initiated to cover organisms associated with community-acquired and culture-negative endocarditis. Vancomycin and ceftriaxone were started on hospital day 3 and continued throughout the hospitalization. Despite continued therapy, the patient’s delirium persisted and he was unable to be extubated. To decipher the etiology of his persistent encephalopathy in the setting of culture-negative endocarditis, further work-up with cultures and serologies was obtained. B. henselae IgG was positive with a titer of greater than 1:1024, while IgM was negative. On hospital day 34, the patient was started on intravenous doxycycline for presumed Bartonella endocarditis, and continued on vancomycin and ceftriaxone. A cardiothoracic surgeon evaluated the patient but declined to offer him surgery given his decompensated health status. A family discussion was held and the decision was made to transition the patient to comfort care. He died soon thereafter.
http://dx.doi.org/10.1016/j.jccase.2015.08.011 1878-5409/ß 2015 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.
R. Ghashghaei et al. / Journal of Cardiology Cases 13 (2016) 1–3
2
performed and found to be negative for Bartonella organisms (Fig. 3C). The formalin-fixed, paraffin-embedded tissue was subsequently analyzed via polymerase chain reaction (PCR), which demonstrated the presence of B. henselae DNA. Discussion
Fig. 1.
Vegetation seen on echocardiography. A transthoracic echocardiography revealed the vegetation (Veg; arrow) attached to the aortic valve. It also showed that there is evidence of aortic valve sclerosis. The left ventricle was noted to be mildly dilated and to have a mildly depressed systolic function (ejection fraction 42%).
During autopsy, the kidney showed multiple infarcts with an associated thrombus (Fig. 2). Dissection of the heart revealed the vegetation attached to the aortic valve (Fig. 3A). Bartonella is not readily identified with a Gram stain; therefore, a Steiner stain was
Fig. 2.
Bartonella is a facultative intracellular Gram-negative aerobic rod that is an important cause of culture-negative endocarditis and the source of up to 3% of all cases of infective endocarditis. Three Bartonella species have been implicated: B. henselae, B. quintana, and B. elizabethan [1]. Diagnosis of Bartonella endocarditis is challenging due to its subacute clinical course and presence of nonspecific symptoms. Bartonella serology is often used for the diagnosis. An IgG antibody titer >1/800 has a positive predictive value of 95%. Bartonella serologies should therefore be checked in patients who present with culture-negative endocarditis and have characteristics that raise clinical suspicion for Bartonella infection including a history of lice or cat infestation, history of significant alcohol use, persistent lymphadenopathy on examination, abscess formation in the liver, or concomitant encephalopathy [2]. However, one of the pitfalls of serologic testing is its crossreaction with Coxiella burnettii [3]. Overall, PCR is the most specific diagnostic method and has 92% sensitivity for valvular biopsies. PCR can also distinguish among the various Bartonella species and detect Bartonella DNA despite the use of antibiotic therapy [4]. Treatment recommendations for Bartonella endocarditis are based on case series. The standard of care is 2 weeks of gentamicin plus 6 weeks of ceftriaxone with or without 6 weeks of doxycycline [5]. One study reviewing 101 patients with Bartonella endocarditis found that patients receiving an aminoglycoside were more likely to recover. Surgical valve repair is usually required for cure as
Embolization to the kidney. Gross examination (A) demonstrates a 1.0 cm 0.5 cm infarct (arrow). Microscopic examination (B) at 100 of magnification demonstrates a wedge-shaped infarct (*), at the edge of which is an arteriole. Higher magnification (200) of the infarcted area (C) reveals necrotic glomeruli and tubules. Magnification of the arteriole (200) at the edge of the infarct (D) demonstrates an organized and recanalized thrombus within the vessel lumen (arrow).
R. Ghashghaei et al. / Journal of Cardiology Cases 13 (2016) 1–3
Fig. 3.
3
Valve vegetation. Gross examination (A) demonstrates a vegetation (arrow) located on the aortic valve (*). (B) Low magnification (40) demonstrates that the vegetation (top left) is connected to the aortic valve (lower half). The inset shows that the vegetation is composed of predominantly fibrin and acute and chronic inflammatory cells. A Steiner stain (C) magnified at 100 is negative for organisms.
Bartonella endocarditis typically causes extensive valve damage [6]. Our patient’s initial presentation of Bartonella endocarditis was masked by an admission to the trauma service for a fall and alcohol withdrawal. Unfortunately, Bartonella was not considered as the causative agent until he failed to improve and the encephalopathy persisted. The diagnosis of Bartonella endocarditis was made via serology tests, but ultimately the patient died. Despite antibiotic therapy, the presence of Bartonella was confirmed by PCR on autopsy. This case illustrates the subtle presentation of Bartonella endocarditis, the importance of maintaining a low clinical suspicion for unusual organisms, and the utility of post-mortem PCR. Conflict of interest All authors have participated in this study and have reviewed and agreed with the content of the article. There are no conflicts of interest regarding this manuscript. None of the article contents is under consideration for publication in any other journal or has been published in any journal.
References [1] Edouard S, Nabet C, Lepidi H, Fournier PE, Raoult D. Bartonella, a common cause of endocarditis: a report on 106 cases and review. J Clin Microbiol 2015;53: 824–9. [2] Breitschwerdt EB, Sontakke S, Hopkins S. Neurological manifestations of Bartonellosis in immunocompetent patients: a composite of reports from 2005– 2012. J Neuroparasitol 2012;3:1–15. [3] La Scola B, Raoult D. Serological cross-reactions between Bartonella quintana, Bartonella henselae, and Coxiella burnetti. J Clin Microbiol 1996;34: 2270–4. [4] Breitkopf C, Hammel D, Scheld HH, Peters G, Becker K. Impact of a molecular approach to improve the microbiological diagnosis of infective heart valve endocarditis. Circulation 2005;111:1415–21. [5] Baddour LM, Wilson WR, Bayer AS, Fowler VG, Bolger AF, Levison ME, Ferrieri P, Gerber MA, Tani LY, Gewitz MH, Tong DC, Steckelberg JM, Baltimore RS, Shulman ST, Burns JC, et al. Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: endorsed by the Infectious Diseases Society of America. Circulation 2005;111:e394–434. [6] Raoult D, Fournier PE, Vandenesch F, Manardi JL, Eykyn SJ, Nash J, James E, Benoit-Lemercier C, Marrie TJ. Outcome and treatment of Bartonella endocarditis. Arch Intern Med 2003;163:226–30.