Endocarditis caused by Bartonella

INTRODUCTION — 

Bartonella was first described as a cause of endocarditis in two separate reports in 1993 [1,2] and has subsequently become appreciated as a significant cause of "culture-negative" endocarditis [3-11]. In the United States, Bartonella is one of the most common, if not the most common, cause of culture-negative endocarditis. Globally, Bartonella endocarditis has been identified in 40 countries [12].

At least eight Bartonella species have been reported to cause infective endocarditis in humans: B. quintana, B. henselae, B. elizabethae, B. vinsonii, B. koehlerae, B. clarridgeiae, B. washoensis, and B. alsatica [3,13-16]. However, more than 95 percent of the cases have involved either B. quintana or B. henselae.

This topic will review the epidemiology, clinical manifestations, diagnosis, and treatment of Bartonella endocarditis. Other Bartonella infections are discussed in separate topic reviews. (See "Microbiology, epidemiology, clinical manifestations, and diagnosis of cat scratch disease" and "Bartonella infections in people with HIV" and "Bartonella quintana infections: Clinical features, diagnosis, and treatment" and "South American bartonellosis: Oroya fever and verruga peruana".)

EPIDEMIOLOGY — 

The epidemiologic features of patients documented to have Bartonella endocarditis have varied considerably. Most reports have involved adults, although multiple cases have also been described in children [10,12,17]. Overall, approximately 70 percent of reported cases have involved men [11,12,18,19]. Case reports and case series have also described Bartonella endocarditis in persons with HIV [1,12,20], and there are rare reports of Bartonella endocarditis in persons who have undergone solid organ transplantation [21].

Certain risk factors appear to be associated with Bartonella endocarditis. These include:

●Demographic factors and exposures – Available data suggest that lack of housing, alcohol use disorder, and infestation with body lice are associated with B. quintana endocarditis, whereas contact with cats serves as the major risk factor for B. henselae endocarditis [3,4,19,20].

●Valvular heart disease – A significant proportion (approximately 40 to 60 percent) of persons with Bartonella endocarditis have prior cardiac valvular disease, particularly when B. henselae is the cause of the endocarditis [3,11,22]. As an example, in a large series, which included 22 patients with Bartonella endocarditis, approximately 55 percent had evidence of preexisting cardiac valvular disease [3].

●Congenital heart disease – Multiple cases of Bartonella endocarditis have been reported that involved children, adolescents, and adults with congenital heart disease [12,23-26]. The timely recognition and diagnosis of Bartonella endocarditis in persons with congenital heart disease are particularly important, since delayed diagnosis can have severe consequences, especially if repair of a valve or graft is required.

CLINICAL MANIFESTATIONS — 

Patients with Bartonella endocarditis have clinical manifestations similar to other patients with subacute bacterial endocarditis as described by the Duke criteria [27]. The epidemiologic features of patients with documented Bartonella endocarditis are described above. (See 'Epidemiology' above.)

Affected patients typically present with subacute, nonspecific symptoms that include fever, fatigue, weakness, and weight loss. In addition, most patients have evidence of a murmur on cardiac auscultation. Based on reports from several case series, embolic events appear to be common with Bartonella endocarditis, but the true incidence is difficult to determine due to limited data [3,11,12,18,20]. In some patients, one or more typical features of endocarditis, such as fever, elevated white blood cell count, and elevated erythrocyte sedimentation rate (ESR), may be absent [11].

Although most cases involve native valves, case reports of prosthetic valve endocarditis have also been described. In one series reporting 16 cases Bartonella endocarditis, 10 (63 percent) had a prosthetic valve [20]. Some reports have noted that patients with prosthetic valve Bartonella endocarditis may have an aggressive disease course characterized by valvular perforation or rapid progression of heart failure [23,28,29].

Patients with Bartonella endocarditis can also develop an immune-complex glomerulonephritis, which may manifest as unexplained hematuria or proteinuria on urinalysis [20,30-34]. Cases of anti-proteinase 3 (PR3)-positive glomerulonephritis in persons with Bartonella endocarditis have increasingly been reported in the past 10 years [20,31,32,35,36]. Many of the cases present as a necrotizing antineutrophil cytoplasmic antibody (ANCA)-positive glomerulonephritis, associated with antibodies against PR3 [20]. Some patients with PR3 antibodies and kidney insufficiency have been misdiagnosed with vasculitis prior to the diagnosis of Bartonella endocarditis [20]. In patients who initially present with glomerulonephritis and the cause is unknown, clinicians should consider evaluation for Bartonella endocarditis as a potential cause, especially if the patient has an epidemiologic risk for Bartonella, such as lack of housing, lice exposure, or contact with cats. (See "Clinical spectrum of antineutrophil cytoplasmic autoantibodies".)

FINDINGS ON ECHOCARDIOGRAPHY — 

Echocardiography shows valvular vegetations in approximately 90 percent of patients with Bartonella endocarditis [11]. These vegetations, however, do not appear to have unique or distinguishing features. (See "Role of echocardiography in infective endocarditis" and "Clinical manifestations and evaluation of adults with suspected left-sided native valve endocarditis", section on 'Cardiac imaging'.)

Approximately 60 percent of patients with Bartonella endocarditis have involved the aortic valve [11,12]. Several cases have involved multiple valves, usually the aortic and mitral or the aortic and tricuspid valves. The reason for the apparent predilection to infect the aortic valve is unknown. The predisposition for left-sided valve involvement may explain the high embolic complication rate with Bartonella endocarditis [20]. Isolated right-sided endocarditis appears to occur infrequently [11,37].

EVALUATION AND DIAGNOSIS — 

This section will review the approach to diagnosis, as well as the different diagnostic tests that are used.

Approach to diagnosis — Bartonella endocarditis should be suspected in patients with clinical and echocardiographic findings that suggest endocarditis if traditional blood cultures are negative after 72 to 96 hours of incubation and the patient has epidemiologic risk factors for Bartonella infection. (See 'Epidemiology' above.)

The evaluation of patients with possible Bartonella endocarditis should include:

●Obtaining at least two sets of blood cultures for Bartonella. It is important to communicate with the microbiology laboratory to ensure special methods are used to optimize yield for growth of Bartonella species. (See 'Culture' below.)

●Serologic testing for B. henselae and B. quintana; the test is highly predictive of endocarditis if there is a high titer for immunoglobulin G (IgG) antibodies to either of these species (eg, ≥1:1024 with the assay commonly used in the United States or ≥1:800 for the assay used in France) [18]. (See 'Serology' below.)

●Serum or plasma polymerase chain reaction (PCR) testing for Bartonella. (See 'Polymerase chain reaction' below.)

For patients who undergo surgical removal of a cardiac valve, Bartonella PCR should be performed on the tissue sample. In addition, a Warthin-Starry stain should be performed if feasible, although this test is labor intensive and not routinely performed as a tissue histologic stain. (See 'Polymerase chain reaction' below and 'Histopathology' below.)

A positive result for any of the three tests outlined above should be considered strong evidence for the diagnosis of Bartonella endocarditis [18,38]. In a retrospective study of 348 patients with suspected blood culture-negative endocarditis, Bartonella spp were identified as the etiologic agent in 99 patients (28 percent) when serologic tests and direct PCR from valve specimens (when available) were utilized along with culture [39]. In a subsequent prospective study involving 819 patients with culture-negative endocarditis [40], Bartonella species accounted for the diagnosis in 86 (18 percent) of the 476 patients who had a specific pathogen identified when serologic and PCR testing was included in the diagnostic evaluation.

Considerations for those with glomerulonephritis — Persons with Bartonella endocarditis who have evidence of glomerulonephritis should undergo evaluation for antineutrophil cytoplasmic antibody (ANCA) and proteinase 3 (PR3) antibodies. The diagnosis of immune-mediated glomerulonephritis is particularly important with Bartonella endocarditis, since use of an aminoglycoside as part of treatment of endocarditis would enhance the risk of nephrotoxicity in this setting.

Diagnostic tests — Serologic testing and PCR have supplanted cultures as the mainstay of diagnosis of Bartonella endocarditis. Nonetheless, we typically obtain all three types of tests on blood samples when the diagnosis is suspected; for tissue samples, we typically obtain PCR, culture, and histopathology.

Serology — In patients with suspected Bartonella endocarditis, a strongly positive IgG serologic test is one of the Duke-ISCVID major criteria utilized to make the diagnosis (table 1) [41]. (See "Clinical manifestations and evaluation of adults with suspected left-sided native valve endocarditis", section on 'Establishing a diagnosis of IE'.)

Indirect immunofluorescence assay (IFA) is the preferred and most commonly used serologic method for diagnosing Bartonella infections. For persons with suspected Bartonella endocarditis, the IFA IgG titer is much more useful than IgM titers. Available data suggest that IgM antibody titers to Bartonella are often negative in persons with Bartonella endocarditis and therefore are not considered a reliable diagnostic test in this setting [38].

There are several limitations to serologic testing for diagnosis of Bartonella endocarditis. These include:

●Lack of uniform diagnostic criteria – Clearly defined, uniform cut-off titers for a positive Bartonella serology do not exist since there are subtle differences in the IFA assays used, and the predictive values of titers in relation to the different clinical manifestations and diseases caused by Bartonella infection can vary. As an example, although most laboratories in the United States consider an IgG titer of ≥1:64 or ≥1:128 to either B. henselae or B. quintana as a positive IgG test, persons with Bartonella endocarditis typically have a Bartonella IgG serologic titer of ≥1:1024. This titer of 1:1024 is roughly equivalent to an IgG titer of 1:800 for the assay used in French laboratories, where much of the endocarditis literature has been published [18,38].

The 2023 Duke-ISCVID criteria include an IFA IgG titer of ≥1:800 (using the French assay) for B. henselae or B. quintana as a major criterion (table 1) [41]. However, these suggested cut-off values should not be considered rigid required diagnostic criteria and a titer below 1:1024 (or below 1:800 with the French assay) should not be used to rule out Bartonella endocarditis, as several studies have shown some persons with Bartonella endocarditis will have IgG values below these cut-offs [18].

●Cross-reactivity – Significant cross-reactivity occurs at the species level between B. henselae and B. quintana as well as with some other Bartonella species [42].

Cross-reactions can also occur between Bartonella and Chlamydia spp. In one series, nine patients previously thought to have Chlamydia endocarditis were reclassified as Bartonella endocarditis based on cross-adsorption studies [3]. The process of cross-adsorption consists of incubating patient serum with the bacteria suspected of causing cross-reaction in the serologic test. The adsorption process removes antibodies to the bacterium that caused serologic cross-reaction, but the antibodies to the organism causing the disease remain.

Among patients with Bartonella endocarditis, there is frequent cross-reactivity with Coxiella antigens, which can produce a false-positive result for Coxiella (but it is usually Phase II antibodies and does not increase with time). Further information regarding Q fever can be found separately [43,44]. (See "Q fever: Epidemiology, microbiology, and diagnostic tests".)

In the United States, Bartonella serology testing is commercially available from several laboratories. Further details regarding serologic testing for Bartonella spp are found separately. (See "Microbiologic diagnosis of Bartonella infections", section on 'Serologic tests'.)

Polymerase chain reaction — Multiple commercial laboratories now offer PCR testing for Bartonella on blood or tissue samples. The 2023 Duke-ISCVID criteria include a positive PCR from blood for Bartonella spp as a major criterion; a positive PCR from valve tissue meets criteria for a definitive diagnosis of endocarditis (table 1) [41]. (See "Clinical manifestations and evaluation of adults with suspected left-sided native valve endocarditis", section on 'Establishing a diagnosis of IE'.)

●The use of PCR-based tests on cardiac valvular tissue has played an important role in the diagnosis of Bartonella endocarditis [22,45]. As an example, in one study, investigators reported positive PCR testing for Bartonella on cardiac valve tissue in greater than 95 percent of patients with Bartonella endocarditis [22]. The organism was detected even though more than 60 percent of these patients had their valves analyzed following the receipt of antibiotics. Although paraffin-embedded specimens can be used, the yield appears to be greater when using fresh valvular tissue.

●PCR testing can also be performed on whole blood, plasma, or serum samples. In one study, investigators performed Bartonella PCR testing of serum samples taken from patients with a diagnosis of Bartonella endocarditis (based upon serologic, culture, and/or molecular detection in valvular tissue) [46]. In such patients, serum PCR testing demonstrated a sensitivity and specificity of 58 and 100 percent, respectively. In a French review of 106 cases of Bartonella endocarditis, PCR testing had a sensitivity of 92 percent for valvular biopsy specimens, 36 percent for serum samples, and 33 percent for blood samples [18].

Further details regarding PCR testing for Bartonella spp are found separately.

Culture — Using standard blood culture techniques and standard incubation periods, isolating Bartonella is extremely unlikely. Therefore, when obtaining samples to culture Bartonella, it is important to proactively communicate with microbiology laboratory personnel so they can optimize culture techniques and can extend the incubation period for a minimum of 28 days [3,39,40,47-50]. Details regarding culture techniques for Bartonella are found separately. (See "Microbiologic diagnosis of Bartonella infections", section on 'Culture'.)

●Blood cultures – Most patients with Bartonella endocarditis do not have positive blood cultures [12]. In a multicenter international study, only 5 of 22 patients (23 percent) diagnosed with Bartonella endocarditis had a positive blood culture at any time in their clinical course [3]. Blood culture techniques for Bartonella are discussed in detail separately. (See "Microbiologic diagnosis of Bartonella infections", section on 'Culture'.)

●Tissue culture of cardiac valves – Isolation of Bartonella from cardiac valvular tissue samples has a very low yield but should be attempted if valvular tissue is removed for culture-negative endocarditis. Tissue culture for Bartonella is further discussed separately. (See "Microbiologic diagnosis of Bartonella infections", section on 'Culture'.)

Histopathology — Cardiac valvular tissue stained with hematoxylin and eosin characteristically shows mildly inflamed connective tissue with focal granulation tissue reaction [4]. Warthin-Starry silver staining of these aggregates, if positive, reveals masses of small, dark-staining bacteria with a golden yellow background. When electron microscopy is performed, pleomorphic bacilli are seen predominantly located intracellularly [3]. Gram staining of cardiac valvular tissue is not useful for diagnosing Bartonella endocarditis. Although a positive Warthin-Starry stain on cardiac valve tissue meets Duke-ISCVID pathologic criteria for a definitive diagnosis of endocarditis, this test has largely been replaced by tissue PCR, primarily because the Bartonella tissue PCR test has higher sensitivity and is a much easier test to perform [41].

In one study of 15 patients with confirmed Bartonella endocarditis, the cardiac valve pathology showed more fibrotic and calcified changes, less vascularization, and less extensive vegetations; these features suggested chronic infection when compared with cases of infective endocarditis caused by other pathogens [51]. In addition, approximately 11 (85 percent) of 13 had a positive Warthin-Starry stain of the valve tissue and 10 (77 percent) of the 13 had a positive Bartonella immunohistologic test.

ANTIMICROBIAL THERAPY — 

The mainstay of treatment for Bartonella endocarditis is antimicrobial therapy. In some patients, surgical management may be required as well. The indications for surgery in patients with Bartonella endocarditis are the same as for other causes of infectious endocarditis. (See 'Surgery' below.)

There are insufficient data to guide definitive recommendations for treating Bartonella endocarditis since there are no randomized trials; the existing literature consists of case series and case reports [3,11,18]. In addition, most patients with Bartonella endocarditis have undergone cardiac valvular surgery with removal of the infected valve, making it difficult to assess the separate role of antibiotics.

Treatment guidelines for suspected and proven Bartonella endocarditis were put forth by an expert panel in 2004 [48] and were subsequently incorporated into the 2005 American Heart Association Infective Endocarditis guidelines [52]. The 2015 American Heart Association endocarditis guidelines did not provide specific treatment recommendations for Bartonella endocarditis, whereas the 2023 European Society of Cardiology proposed therapeutic regimens but acknowledged uncertainty regarding these recommendations [53,54].

The following recommendations differ from the 2004 and 2023 expert panel recommendations based on more recent data regarding kidney disease in persons with Bartonella endocarditis, particularly for persons with Bartonella-associated anti-proteinase 3 (PR3)-positive glomerulonephritis [31,32,35,36]. (See 'Clinical manifestations' above.)

Preferred regimen — For nonpregnant adults with confirmed Bartonella endocarditis, we suggest combination therapy with the following regimen (algorithm 1):

●Doxycycline (100 mg orally or intravenous [IV] every 12 hours) for 12 weeks,

PLUS

●Rifampin (300 mg orally or IV every 12 hours) for the first six weeks of therapy.

Considerations for pregnant people and young children are discussed elsewhere. (See 'Considerations in pregnant persons and young children' below.)

If a patient with culture-negative endocarditis has suspected, but not proven, Bartonella infection, an additional agent, ideally ceftriaxone (2 g IV once daily for six weeks), should be added to cover other likely causes of culture-negative endocarditis. Although ceftriaxone probably has some activity against Bartonella [55], its role in this setting is primarily to treat common culture-negative endocarditis pathogens that are not effectively treated by doxycycline. (See "Antimicrobial therapy of left-sided native valve endocarditis", section on 'Culture-negative endocarditis'.)

Doxycycline is the key component of therapy for Bartonella endocarditis, based on available reports describing treatment of Bartonella endocarditis and other types of Bartonella infections [56-58]. However, since doxycycline is bacteriostatic, we suggest that it be used in combination with a second antimicrobial and administered for a prolonged duration. The use of a prolonged 12-week course of doxycycline for Bartonella endocarditis is also based on the lack of definitive data on treatment duration, the intracellular location of Bartonella, and the relatively low risk of developing serious adverse reactions with an extended course of oral doxycycline.

Rifampin should ideally be included as the second antimicrobial in combination with doxycycline. Although there are no studies that have examined use of rifampin in combination with a tetracycline for the treatment of Bartonella endocarditis, rifampin has excellent intracellular penetration, which is important when treating Bartonella infections, particularly Bartonella endocarditis. In addition, rifampin has been shown to be effective as a component of therapy with other serious Bartonella infections. Previously, gentamicin had been the preferred second agent, but we now prefer rifampin rather than gentamicin, given the significant risk of nephrotoxicity from gentamicin and increasing reports of PR3 antibodies and kidney insufficiency in patients with Bartonella endocarditis; gentamicin can be considered as an alternative for patients who cannot take rifampin (eg, due to drug interactions). (See 'Alternative regimens' below.)

Alternative regimens — The approach to choosing an alternative regimen for patients with confirmed Bartonella endocarditis depends on why the patient cannot take the preferred regimen (algorithm 1).

●If doxycycline cannot be used – For patients who are intolerant to doxycycline, azithromycin (500 mg IV/orally once daily) for 12 weeks is an alternative agent (algorithm 1). However, the efficacy of macrolides is likely lower compared with tetracyclines for the treatment of Bartonella endocarditis [48]. Considerations for regimen selection in pregnant patients and young children are discussed below. (See 'Considerations in pregnant persons and young children' below.)

Similar to doxycycline, azithromycin should be administered with a second agent (preferably rifampin). (See 'Preferred regimen' above.)

●If rifampin cannot be used – For patients who cannot use rifampin (eg, due to drug interactions), doxycycline plus gentamicin is a reasonable alternative in those with normal kidney function and no evidence of Bartonella-associated glomerulonephritis (algorithm 1). The preferred dose of gentamicin is 3 mg/kg/day given once daily for the initial 14 days of therapy; however, some experts dose gentamicin as 1 mg/kg IV every eight hours since this dosing regimen has been used in most of the Bartonella endocarditis case reports. The once-daily gentamicin dose should be adjusted, if needed, to ensure trough serum concentrations are <1 mcg/mL. If every-eight-hour dosing is used, doses should be adjusted to achieve peak serum concentrations of 3 to 4 mcg/mL and trough concentrations less than 1 mcg/ml; blood samples to evaluate the peak level should be obtained one hour after administration of the gentamicin and the trough level 24 hours after the first dose and then twice weekly thereafter. In addition, kidney function should be monitored closely.

The benefit of including aminoglycoside therapy was supported in a retrospective analysis of 101 patients with Bartonella endocarditis that found persons who received a regimen that included at least 14 days of an aminoglycoside had higher recovery and survival rates compared with those who were treated with a regimen without an aminoglycoside [11].

For those who cannot receive either gentamicin or rifampin as the second agent, a less preferable option is monotherapy with doxycycline alone. However, in this setting, we extend the duration of treatment for Bartonella endocarditis to 24 weeks (algorithm 1). If doxycycline cannot be used, then azithromycin should be given for 24 weeks.

Considerations in pregnant persons and young children — There are no data to guide treatment decisions in these patient groups. When choosing a treatment regimen for Bartonella endocarditis in pregnant persons and children <8 years of age, the benefit of using a regimen that contains doxycycline (the preferred regimen for treatment of Bartonella endocarditis) must be weighed against potential antimicrobial toxicity.

In pregnancy, the use of tetracyclines have generally been contraindicated because of the risk of hepatotoxicity in the patient [59] and adverse effects on fetal bone and teeth [60,61]. (See "Tetracyclines", section on 'Pregnant or breastfeeding women'.)

In children less than eight years of age, tetracycline has been associated with permanent tooth discoloration (yellow, gray, or brown discoloration), especially if used repeatedly or for prolonged courses. However, doxycycline binds less readily to calcium than other tetracyclines, and the risk of dental staining with doxycycline is minimal if a short course is administered [62-65]. The American Academy of Pediatrics permits use of doxycycline for ≤21 days in children of all ages [66], but there are limited safety data when doxycycline is used for >21 days in children less than eight years of age. (See "Tetracyclines", section on 'Young children'.)

Azithromycin, which is considered safe for use in pregnancy and in young children, is the best option as an alternative to doxycycline to treat Bartonella endocarditis. However, there is less experience with macrolides for treatment of endocarditis, and in general, they are felt to be less effective than doxycycline. (See 'Alternative regimens' above.)

If possible, pregnant individuals and children with Bartonella endocarditis should be managed in consultation with a maternal-fetal medicine or infectious diseases specialist, respectively.

SURGERY

Indications — The indications for surgery in patients with Bartonella endocarditis are the same as for other causes of infectious endocarditis, although persistent bacteremia is an unlikely indication in Bartonella endocarditis due to the prolonged time required for Bartonella growth in blood cultures [53]. Topic reviews that discuss the indications for surgery in patients with endocarditis are presented elsewhere. (See "Surgery for left-sided native valve infective endocarditis" and "Prosthetic valve endocarditis: Surgical management".)

In case reports of patients with Bartonella endocarditis, approximately 60 percent have undergone cardiac valvular surgery during initial hospitalization [3,4,22]. The reason for the high proportion of patients undergoing valvular surgery is not precisely known but is thought to result primarily from the higher incidence of preexisting valvular abnormalities, indolent course, and delayed diagnosis [11,18,48].

Implications for antimicrobial therapy — Some patients with Bartonella endocarditis undergo cardiac valvular surgery and the infected valve(s) is removed. This can impact the approach to antimicrobial therapy.

●If antimicrobial therapy was initiated prior to surgery – If antimicrobial therapy was started prior to surgery, the remaining course of doxycycline plus rifampin therapy should be completed postoperatively (ie, the patient should receive a total of 12 weeks of doxycycline and six weeks of rifampin) (table 2).

However, we modify this approach in a few situations (table 2):

•If there are more than six weeks of treatment remaining after surgery, we typically limit the postoperative regimen to a six-week course of doxycycline plus rifampin, assuming all infected valve tissue has been removed and the person is not immunocompromised. If the person is immunocompromised, we recommend completing the full total 12-week regimen of doxycycline.

•If the patient was receiving gentamicin and had not completed the two-week course of gentamicin prior to surgery, we do not continue gentamicin postoperatively. This is due to the enhanced risk of nephrotoxicity with an aminoglycoside during and following cardiac surgery and the likelihood that the burden of infection was reduced with the previous antibiotics and the removal of the valve.

•If there were <2 weeks of the treatment regimen remaining, or if the entire antimicrobial course had been completed prior to cardiac surgery, we give an additional two weeks of doxycycline postoperatively.

●If the diagnosis is made postoperatively – On occasion, a diagnosis of Bartonella endocarditis is made postoperatively and the patient has not received preoperative antimicrobial therapy. In this situation, a six-week course of doxycycline plus rifampin is probably sufficient, assuming all infected valve tissue has been removed and the person is not immunocompromised (table 2). If the person is immunocompromised, we recommend completing the full total 12-week regimen of doxycycline.

If rifampin cannot be used, then gentamicin should be used for the initial 14 days of therapy as an alternative but with very careful monitoring.

SOCIETY GUIDELINE LINKS — 

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Treatment and prevention of infective endocarditis".)

SUMMARY AND RECOMMENDATIONS

●Microbiology/epidemiology – At least eight species of Bartonella have been reported to cause infective endocarditis in humans, although the vast majority of cases have involved either B. quintana or B. henselae.

Homelessness, alcoholism, and infestation with body lice are associated with B. quintana endocarditis, whereas contact with cats and previous valvular disease are the major risk factors for B. henselae endocarditis. (See 'Epidemiology' above.)

●Clinical manifestations – Patients with Bartonella endocarditis present with fever, fatigue, weakness, and weight loss, similar to those with other forms of subacute bacterial endocarditis. Most also have evidence of a murmur on cardiac auscultation. Patients with Bartonella endocarditis can also develop an immune-complex glomerulonephritis. (See 'Clinical manifestations' above.)

●Evaluation and diagnosis – Bartonella endocarditis should be suspected in patients with clinical and echocardiographic findings that suggest endocarditis if traditional blood cultures are negative after 72 to 96 hours and the patient has epidemiologic risk factors for disease. The initial evaluation of patients with possible Bartonella endocarditis should include the following (see 'Evaluation and Diagnosis' above):

•Blood cultures using special methods to optimize growth. (See 'Culture' above.)

•Serologic testing using either an indirect immunofluorescence assay (IFA) or an enzyme-linked immunosorbent assay (ELISA). A titer for IgG antibodies of ≥1:800 (with the assay commonly used in France) to either B. henselae or B. quintana is a major criterion in the 2023 Duke-ISCVID criteria for endocarditis; this titer is equivalent to ≥1:1024 with the assay most commonly used in the United States (table 1). (See 'Serology' above.)

•Polymerase chain reaction (PCR)-based testing for Bartonella on serum or plasma. A positive result is a major criterion in the 2023 Duke-ISCVID criteria for endocarditis (table 1). (See 'Polymerase chain reaction' above.)

For patients with culture-negative endocarditis who undergo cardiac valve replacement, PCR-based testing and tissue culture for Bartonella should be performed on the cardiac valvular tissue. In addition, if possible, the tissue should be stained with Warthin-Starry silver staining, which may demonstrate masses of small, dark-staining bacteria. (See 'Polymerase chain reaction' above and 'Histopathology' above.)

●Antimicrobial therapy – The mainstay of treatment for Bartonella endocarditis is antimicrobial therapy (algorithm 1). In some patients, surgical management may be required as well. Treatment recommendations are based upon case series and case reports.

•For nonpregnant adults with proven Bartonella endocarditis, we suggest treatment with doxycycline (100 mg orally or intravenous [IV] every 12 hours for 12 weeks) plus rifampin (300 mg orally or IV every 12 hours for the first six weeks of therapy) (algorithm 1) (Grade 2C). (See 'Preferred regimen' above.)

•For those who cannot take rifampin, gentamicin (eg, 3 mg/kg IV every 24 hours for 14 days) is a reasonable alternative for those with normal kidney function (algorithm 1). A less preferred option is doxycycline alone for 24 weeks if the patient cannot take rifampin or gentamicin. (See 'Alternative regimens' above.)

For patients who are intolerant of doxycycline, azithromycin can be used (algorithm 1); however, macrolides should not be viewed as equivalent to tetracyclines for the treatment of Bartonella endocarditis. For pregnant patients and young children, the decision to use a prolonged course of doxycycline versus azithromycin must be determined on a case-by-case basis and ideally in conjunction with consultation with a maternal fetal-medicine specialist. (See 'Alternative regimens' above and 'Considerations in pregnant persons and young children' above.)

●Surgery – The indications for surgery in patients with Bartonella endocarditis are generally the same as for other causes of infectious endocarditis. However, the timing of surgery may impact the choice and duration of antimicrobial therapy. (See 'Surgery' above.)