Table 2.

Case description of patients diagnosed with blood culture-negative endocarditis due to Bartonella species (N=16)

Patients	Age, Gender	Risk factors/Comorbidities	Time of Illness (weeks)	Clinical Presentation	Laboratory/Imaging	Immunology Testing/Renal Biopsy	Bartonella Serology/Coxiella burnetii Testing	Bartonella PCR Testing	Echocardiogram Findings/Pathology	Management	Outcome
Patient 1	57, male	Mitral and aortic prosthetic mechanical valves due to rheumatic heart disease, diabetes	8	Fever, malaise, dyspnea, purpuric rash in lower extremities, volume overload	Anemia, leukopenia, renal failure, hematuria, abnormal liver enzymes, splenomegaly	Low complement, positive RF, negative ANCA, anti-MPO, and anti-PR3 Unable to do a renal biopsy due to active anticoagulation	Bartonella henselae IgG 1:256, IgM <1:20 Bartonella quintana IgG 1:128, IgM <1:20 Coxiella burnetii PCR negative	Bartonella PCR negative in blood and valve	Vegetation on the atrial side of the mitral valve with mod-severe dysfunction Pathology: active endocarditis with bacilli in clusters (sample collected during readmission)	8 weeks of ceftriaxone and doxycycline, 2 weeks of rifampin	Initial improvement of symptoms, renal failure, and decline of Bartonella IgG titers; no evidence of vegetations in repeat echocardiogram Readmitted later due to valvular dysfunction and heart failure exacerbation, underwent mitral valve replacement with resolution of symptoms
Patient 2	85, male	CKD, recent use of PDN and AZA for 3 months due to presumed GPA, cat exposure	22	Fever, malaise, chills, dyspnea, purpuric rash in lower extremities	Anemia, acute on chronic renal failure, hematuria, abnormal liver enzymes	Low complement, positive ANCA, and anti-PR3, negative anti-MPO Renal biopsy: focal sclerosing pauci-immune GN (compatible with GPA)	B. henselae IgG 1:4096, IgM <1:20 B. quintana IgG 1:2048, IgM <1:20 C. burnetii was not tested	Bartonella PCR negative in blood	Vegetation in the right atrium attached to the tricuspid leaflet	6 weeks of doxycycline and rifampin Continued treatment for GPA with AZA	Resolution/improvement of symptoms, no evidence of vegetations in repeat echocardiogram
Patient 3	33, male	Prosthetic aortic valve and root replacement due to bicuspid aortic valve	6	Fever, malaise, night sweats, chills, fatigue, volume overload	Anemia	Complement and ANCA not tested	B. henselae IgG 1:128, IgM <1:20 B. quintana IgG 1:256, IgM <1:20 C. burnetii serology negative	Bartonella PCR negative in blood and valve	Vegetation in the aortic valve with moderate to severe dysfunction with paravalvular and root abscess Pathology: fibrinous tissue with active infection (negative Warthin-Starry)	6 weeks of rifampin and levofloxacin, 2 weeks of gentamicin; aortic valve and root replacement	Resolution/improvement of symptoms and Bartonella titers
Patient 4	59, male	Bicuspid aortic valve, cat exposure	8	Fever, malaise, weight loss, confusion, small purpuric lesions in the left hand	Anemia, thrombocytopenia, acute renal failure, hematuria, abnormal liver enzymes	Normal complement, positive ANCA, anti-PR3, and anti-MPO No renal biopsy as creatinine improved with antibiotics (considered possible localized-renal ANCA vasculitis)	B. henselae IgG 1:32768, IgM <1:20 B. quintana IgG 1:16384, IgM <1:20 C. burnetii IgG phase II 1:512	Bartonella PCR positive from valve, negative from blood	Vegetation in the aortic valve with new severe valvular insufficiency and root abscess Pathology: infective endocarditis (negative Warthin-Starry; sample collected during readmission)	6 weeks of doxycycline and rifampin	Initial improvement of symptoms and Bartonella IgG titers Considered not a surgical candidate, but readmitted later due to severe aortic insufficiency and heart failure, underwent aortic valve and root replacement with resolution of symptoms
Patient 5	80, female	Prosthetic aortic valve due to aortic stenosis, cat exposure	43	Fever, malaise, weakness, weight loss	Pancytopenia, splenomegaly	Positive RF and ANA; complement and ANCA not tested	B. henselae IgG 1:262,144, IgM 1:320 WB positive for B. henselae C. burnetii phase I IgG 1:1024, phase II IgG 1:512; Coxiella PCR negative	Bartonella PCR negative in blood	Thickening of mitral and aortic valve	6 weeks of doxycycline and gentamicin	Resolution/improvement of symptoms and pancytopenia
Patient 6	77, female	Prosthetic mitral valve due to ischemic mitral regurgitation, CKD, chronic low-dose steroid use for presumed PMR, steroid-induced DM, cat exposure	13	Fever, malaise, dyspnea, weakness, weight loss	Pancytopenia, acute renal failure requiring hemodialysis	Negative ANCA, low complements Renal biopsy: ATN and MPGN secondary to IE	B. henselae IgG 1:1024, IgM 1:40 B. quintana IgG 1:128, IgM 1:160 C. burnetii was not tested	Bartonella PCR positive in blood	Vegetation in the mitral valve with stenosis	4 weeks of doxycycline, rifampin, and ceftriaxone	Death due to multiorgan failure before valvular surgery
Patient 7	62, male	DM, CABG for CAD, recent diagnosis of AIDS	8	Fever, malaise, weight loss	Anemia, neutropenia, abnormal liver enzymes	Complement and ANCA not tested	B. henselae IgG 1:128, IgM <1:20 B. quintana IgG 1:128, IgM <1:20 C. burnetii serology negative	Bartonella PCR negative in blood	Vegetation in the aortic valve	6 weeks of doxycycline, gentamicin, ampicillin	Resolution/improvement of symptoms and neutropenia, no evidence of vegetation in repeat echocardiogram
Patient 8	47, male	HTN, OSA	13	Altered mental status	Left Thalamic emboli/stroke	Complement and ANCA not tested	B. henselae IgG 1:256, IgM <1:20 B. quintana IgG 1:128, IgM <1:20 C. burnetii serology negative	Bartonella PCR negative in valve	Calcified mass on the posterior leaflet of the mitral valve Pathology: thrombotic vegetation with focal inflammation	6 weeks of doxycycline and ceftriaxone, 2 weeks of gentamicin; mitral valve repair with annuloplasty	No more embolic episodes
Patient 9	57, male	Prosthetic aortic valve due to RHD, CKD with a recent diagnosis of renal vasculitis on steroids, cat exposure	30	Fever, malaise, fatigue, headaches	Anemia, thrombocytopenia, abnormal liver enzymes, acute renal failure	Low complement, positive ANCA and anti-PR3, negative anti-MPO Renal biopsy: complex-mediated GN with C3 deposits and focal crescents secondary to IE, no ANCA vasculitis	B. henselae IgG 1:1024, IgM <1:20 B. quintana IgG 1:512, IgM <1:20 C. burnetii phase II IgG 1:256	Bartonella PCR negative in blood	Vegetation on the left cusp of the aortic valve	6 weeks of doxycycline and ceftriaxone, 2 weeks of gentamicin	Resolution/improvement of symptoms, cytopenias, and renal dysfunction, without immunosuppressors
Patient 10	80, male	Prosthetic aortic valve due to aortic regurgitation, CKD, DM, renal ANCA vasculitis on RTX and PDN 2 years prior to admission	48	Fever, malaise, weakness, weight loss, altered mental status	Anemia, acute renal failure, acute right hemispheric embolic stroke, PET scan showing splenic FDG avidity concerning for embolic event in the spleen	Negative ANCA, normal complement Renal biopsy not performed	B. henselae IgG >1:1024, IgM <1:20 B. quintana IgG >1:1024, IgM <1:20 C. burnetii PCR negative	Bartonella PCR positive in blood	Vegetation in the aortic valve with paravalvular abscess	2 weeks of ceftriaxone, planned 6 weeks of rifampin and 6 months of doxycycline (no surgical candidate)	Improvement of symptoms and renal failure with antimicrobials, loss in follow-up
Patient 11	55, female	Prosthetic aortic and mitral valve due to RHD, pulmonary valve homograft, CKD due to ATN, possible APS on PDN and Plaquenil, cat exposure	52	Fever, fatigue, malaise, weight loss, volume overload	Anemia, thrombocytopenia, acute on chronic renal failure, abnormal liver enzymes, splenomegaly	Low complement, positive ANCA, positive anti-PR3, negative anti-MPO Renal biopsy not performed due to anticoagulation	B. henselae IgG: > 1:1024, IgM: >1:20 B. quintana IgG: 1:1024, IgM: <1:20 C. burnetii phase II IgG 1:128	Bartonella PCR positive in pulmonary valve tissue, negative in blood	Vegetation in the pulmonary artery and ventricular aspect of the pulmonary prosthesis with severe regurgitation Pathology: Nodular calcification with mild acute inflammation	9 weeks of doxycycline, 2 weeks of rifampin and ceftriaxone; tricuspid valve repair and pulmonary valve replacement	Death post-surgery due to multiorgan failure (fungemia due to Candida tropicalis, pneumonia)
Patient 12	44, male	Alcohol abuse, renal failure due to presumed renal vasculitis, receiving a short course of steroids without improvement, cat exposure	26	Fever, fatigue, night sweats, weight loss	Anemia, leukopenia, acute renal failure, hematuria, proteinuria, splenomegaly	Low complement, positive RF, ANCA, and anti-PR3, negative anti-MPO Renal biopsy: immune-complex focal proliferative GN, likely infection-related	B. henselae IgG >1:1024, IgM >1:20 B. quintana IgG >1:1024, IgM <1:20 C. burnetii phase II IgG 1:256	B. henselae PCR positive in explanted mitral valve, negative in blood	Vegetation on the atrial and ventricular aspect of the mitral valve with mild-moderate regurgitation	6 months of doxycycline, 2 weeks of gentamicin	Initial improvement of symptoms, but no improvement of cytopenias and renal failure Patient required readmission to another hospital months later for mitral valve replacement, presenting resolution of cytopenias and improvement of renal function
Patient 13	22, male	Prosthetic pulmonary valve due to tetralogy of Fallot complicated with pulmonary regurgitation, cat exposure	22	Fever, fatigue, malaise, night sweats, weight loss	Anemia, leukopenia, hepato-splenomegaly	Complement and ANCA not tested	B. henselae IgG >1:1024, IgM <1:20 B. quintana IgG >1:1024, IgM <1:20 C. burnetii phase II IgG 1:32	Bartonella sp PCR positive in explanted pulmonary valve, negative from blood	Thickening of the pulmonary prosthetic valve with moderate regurgitation Pathology: healing infective endocarditis with bacterial rods	4 months of doxycycline, 2 weeks of gentamicin	Initial improvement of symptoms and cytopenias Patient was re-admitted later due to septic emboli to the lung and possible paravalvular abscess requiring replacement of the pulmonary valve
Patient 14	56, male	Prosthetic aortic valve due to severe aortic regurgitation, dog and cat exposure	43	Right hemianopia, transient left-sided clumsiness	Anemia, brain emboli	Complement and ANCA not tested	B. henselae IgG 1:8192, IgM <1:20 B. quintana IgG 1:512, IgM <1:20 C. burnetii phase II IgG 1:64	Bartonella sp BRPCR from explanted valve (closely related with B. henselae), negative from blood	Vegetation on the aortic valve, with severe aortic regurgitation Pathology: active endocarditis with small bacterial rods consistent with Bartonella spp. (positive Warthin-Starry stain)	12 weeks of doxycycline, 2 weeks of rifampin; aortic valve replacement	Resolution/improvement of symptoms, slow improvement of Bartonella IgG titers
Patient 15	51, male	Prosthetic aortic valve due to bicuspid aortic valve, CKD, received PDN 20 mg daily for presumed renal vasculitis, cat exposure	26	Fatigue, malaise, dyspnea, extensive macular-purpuric rash in lower extremities	Anemia, acute on chronic renal failure requiring hemodialysis, hematuria, hepatosplenomegaly	Normal complement, positive ANCA and anti-PR3, negative anti-MPO, positive cryoglobulins III Renal biopsy: immune-complex focal proliferative GN likely infection-related	B. henselae IgG 1:32768, IgM <1:20, B. quintana IgG 1:128, IgM <1:20 C. burnetii negative serology	Bartonella sp BRPCR from explanted valve, negative from blood	New severe aortic regurgitation Pathology: healed infective endocarditis with chronic inflammation	12 weeks of doxycycline, 2 weeks of gentamicin Received plasmapheresis for management of cryoglobulinemia; aortic valve replacement	Resolution/improvement of symptoms (except for kidney failure), slow improvement of Bartonella IgG titers
Patient 16	57, female	No comorbidities	30	Fever, malaise, weight loss, volume overload	Anemia, splenomegaly, embolic phenomena to the spleen	Complement and ANCA not tested	B. henselae IgG 1:4096, IgM <1:20 B. quintana IgG 1:128, IgM <1:20 C. burnetii phase II IgG 1:32	B. quintana PCR from explanted aortic valve (PCR not performed in blood)	Vegetations in the aortic and mitral valves with root and perivalvular abscesses, severe aortic insufficiency Pathology: healing endocarditis with colonies of bacteria and focal valve destruction	52 weeks of doxycycline, 2 weeks of gentamicin; aortic and mitral valve replacement and aortic root debridement with pericardial patch reconstruction	Resolution/improvement of symptoms, slow improvement of Bartonella IgG titers

Abbreviations: AIDS, Acquired immunodeficiency syndrome; ANA, antinuclear antibody; ANCA, antineutrophil cytoplasmic antibodies; APS, antiphospholipid syndrome; ATN, acute tubular necrosis; AZA, Azathioprine; BRPCR, broad-range polymerase chain reaction; CABG, coronary artery bypass graft surgery; CAD, coronary artery disease; CKD, chronic kidney disease; DM, diabetes mellitus; FDG, fluorodeoxyglucose; GN, glomerulonephritis; GPA, Granulomatosis with polyangiitis; HTN, hypertension; IE, infective endocarditis; Ig, immunoglobulin; MPO, myeloperoxidase antibody; MPGN, Mesangial proliferative glomerulonephritis; OSA, obstructive sleep apnea; PCR, polymerase chain reaction; PDN, prednisone; PET, positron emission tomography; PR3, proteinase 3 antibody; RF, rheumatoid factor; RHD, rheumatic heart disease; RTX, rituximab; WB, western blot (test performed at Hôpitaux Universitaires de Marseille Timone, Marseille, France).