Epidemiology and treatment of invasive Bartonella spp. infections in the United States.

OBJECTIVES: Bartonella spp., renowned for cat-scratch disease, has limited reports of dissemination. Tissue and blood cultures have limitations in detecting this fastidious pathogen. Molecular testing (polymerase chain reaction, PCR) and cell-free DNA have provided an avenue for diagnoses. This retrospective observational multicenter study describes the incidence of disseminated Bartonella spp. and treatment-related outcomes. METHODS: Inclusion criteria were diagnosis of bartonellosis via diagnosis code, serology testing of blood, polymerase chain reaction (PCR) of blood, 16/18S tests of blood or tissue, cultures of blood or tissue, or cell-free DNA of blood or tissue from January 1, 2014, through September 1, 2021. Exclusions were patients who did not receive treatment, insufficient data on treatment course, absence of dissemination, or retinitis as dissemination. RESULTS: Patients were primarily male (n = 25, 61.0%), white (n = 28, 68.3%), with mean age of 50 years (SD 14.4), and mean Charlson comorbidity index of 3.5 (SD 2.1). Diagnosis was primarily by serology (n = 34, 82.9%), with Bartonella henselae (n = 40, 97.6%) as the causative pathogen. Treatment was principally doxycycline with rifampin (n = 17, 41.5%). Treatment failure occurred in 16 (39.0%) patients, due to escalation of therapy during treatment (n = 5, 31.3%) or discontinuation of therapy due to an adverse event or tolerability (n = 5, 31.3%). CONCLUSIONS: In conclusion, this is the largest United States-based cohort of disseminated Bartonella spp. infections to date with a reported 39% treatment failure. This adds to literature supporting obtaining multiple diagnostic tests when Bartonella is suspected and describes treatment options.

Bartonella and Coxiella infections presenting as systemic vasculitis: case series and review of literature.

OBJECTIVES: Coxiella and Bartonella spp. display particular tropism for endothelial or endocardial tissues and an abnormal host response to infections with induced autoimmunity. We aimed, through a case series combined with a comprehensive literature review, to outline characteristics of Coxiella and Bartonella infections presenting as systemic vasculitis. METHODS: We retrospectively included cases of definite Coxiella and Bartonella infections presenting with vasculitis features and performed a comprehensive literature review. RESULTS: Six cases of Bartonella infections were added to 18 cases from literature review. Causative pathogens were mainly B. henselae. Bartonella infection mimicked ANCA-associated vasculitis in 83% with PR3-ANCA and presented as cryoglobulinaemic vasculitis in 8%. GN was present in 92%, and 88% had endocarditis. Complement fractions were low in 82% and rheumatoid factor positive in 85%. Kidney biopsies showed cell proliferation, mostly crescentic, with pauci-immune GN in 29%. Outcome was favourable, with the use of antibiotics alone in one-third. Five cases of Coxiella infections were added to 16 from literature review. Sixteen had small-vessel vasculitides, mainly cryoglobulinaemia vasculitis in 75%. One patient had polyarteritis nodosa-like vasculitis and four large-vessel vasculitis. Outcome was good except for one death. A highly sensitive next generation sequencing analysis on three Coxiella- and two Bartonella-related vasculitides biopsies did not find any bacterial DNA. CONCLUSION: Coxiella and Bartonella are both able to induce vasculitis but display distinct vasculitis features. Bartonella mimics PR3-ANCA-associated vasculitis in the setting of endocarditis, whereas Coxiella may induce vasculitis involving all vessel sizes.

Laboratory Diagnosis of 37 Cases of Bartonella Endocarditis Based on Enzyme Immunoassay and Real-Time PCR.

Bartonella spp., mostly Bartonella quintana and B. henselae, are a common cause of culture-negative endocarditis. Serology using immunofluorescence assay (IFA) and PCR performed on cardiac tissues are the mainstays of diagnosis. We developed an enzyme immunoassay (EIA) and a novel multiplex real-time PCR assay, utilizing Bartonella genus-specific, B. henselae-specific, and B. quintana-specific SimpleProbe probes, for diagnosis of Bartonella endocarditis. We aimed to evaluate the performance of these assays. Thirty-seven patients with definite endocarditis, 18 with B. henselae, 18 with B. quintana, and 1 with B. koehlerae, were studied. Diagnosis was confirmed by conventional PCR and DNA sequencing of surgical cardiac specimens. Similar to the case with IFA, anti-Bartonella IgG titers of ≥1:800 were found in 94% of patients by EIA; cross-reactivity between B. henselae and B. quintana precluded species-specific serodiagnosis, and frequent (41%) but low-titer cross-reactivity between Coxiella burnetii antibodies and B. henselae antigen was found in patients with Q fever endocarditis. Low-titer (1:100) cross-reactivity was uncommonly found also in patients with brucellosis and culture-positive endocarditis, particularly Enterococcus faecalis endocarditis. Real-time PCR performed on explanted heart valves/vegetations was in complete agreement with results of sequence-based diagnosis with characteristic melting curves. The genus-specific probe identified five additional endocarditis-associated Bartonella spp. at the genus level. In conclusion, EIA coupled with a novel real-time PCR assay can play an important role in Bartonella endocarditis diagnosis and expand the diagnostic arsenal at the disposal of the clinical microbiologist. Since serology remains a major diagnostic tool, recognizing its pitfalls is essential to avoid incorrect diagnosis.

Atypical bartonellosis in children: What do we know?

AIM: To characterise Bartonella infections in a paediatric population requiring hospital admission and review its treatment. METHODS: Longitudinal observational retrospective data analysis of children and adolescents admitted with Bartonella infection at a paediatric tertiary hospital from 2010 to 2019. RESULTS: We identified 16 cases of bartonellosis, with a mean age of 8.0 ± 4.5 years old, no sex predominance and 14 had contact with cats. Most of the cases occurred in fall and winter. Clinical presentations included osteomyelitis/arthritis (n = 9), hepatosplenic disease (n = 2), lymphadenitis (n = 2), neuroretinitis (n = 2) and encephalitis (n = 1). Clinical diagnosis was confirmed by serology (n = 16) and Bartonella DNA detection in patient's lymph nodes/hepatic lesion (n = 3). Therapeutic approach varied according to the clinical presentation: azithromycin in lymphadenitis, rifampicin plus ciprofloxacin in hepatosplenic disease, rifampicin and doxycycline in neuroretinitis, ceftriaxone in encephalitis and azithromycin, cotrimoxazole or rifampicin plus azithromycin, cefuroxime, ciprofloxacin or doxycycline in osteomyelitis/arthritis. Immunodeficiency was excluded in seven patients. Seven patients' cats were screened by veterinarians and treated when infected (n = 5). CONCLUSIONS: In these clinical presentations, where other infections may be involved, a high index of suspicion is necessary, with emphasis on the epidemiological context. The association of systemic forms with immunodeficiency did not occur in our study. The lack of recommendations for treatment of atypical infection makes the approach of these cases a challenge. Randomised control studies are essential to define the best approach in each case.

Validation of Bartonella henselae Western Immunoblotting for Serodiagnosis of Bartonelloses in Dogs.

Bartonella spp. are etiological agents of life-threatening zoonotic diseases in dogs worldwide. Due to the poor sensitivity of immunofluorescent-antibody assays (IFAs), a reliable serodiagnostic test for canine bartonelloses is of clinical importance. The utility of Western blotting (WB) for the serodiagnosis of canine bartonelloses has not been critically investigated. The objective of this study was to characterize WB immunodominant proteins that could be used to confirm a serodiagnosis of bartonelloses. Using agar-grown Bartonella henselae San Antonio type 2 (SA2) whole-cell proteins, sera derived from four dog groups were tested by WB to assess immunodominant protein recognition patterns: group I consisted of 92 serum samples (10 preexposure and 82 postexposure serum samples) from 10 adult beagles experimentally inoculated with Bartonella spp., group II consisted of 36 serum samples from Bartonella PCR-positive naturally infected dogs, group III consisted of 26 serum samples from Bartonella PCR-negative and IFA-negative dogs, and group IV consisted of serum samples from 8 Brucella canis IFA-positive and 10 Rickettsia rickettsii IFA-positive dogs. Following experimental inoculation, 9 (90%) group I dogs were variably seroreactive to one or more of six specific immunodominant proteins (13, 17, 29, 50, 56, and 150 kDa). There was a strong but variable recognition of these proteins among 81% of group II dogs. In contrast, 24/26 group III dogs were not reactive to any immunodominant protein. In this study, the sensitivity and diagnostic accuracy of B. henselae SA2 WB were higher than those of B. henselae SA2 IFA testing. Some B. henselae SA2 immunodominant proteins were recognized by dogs experimentally and naturally infected with Bartonella spp. other than B. henselae Additional research is necessary to more fully define the utility of WB for the serodiagnosis of canine bartonelloses.

Prosthetic Valve Endocarditis with Bartonella washoensis in a Human European Patient and Its Detection in Red Squirrels (Sciurus vulgaris).

Members of the genus Bartonella are fastidious Gram-negative facultative intracellular bacteria that are typically transmitted by arthropod vectors. Several Bartonella spp. have been found to cause culture-negative endocarditis in humans. Here, we report the case of a 75-year-old German woman with prosthetic valve endocarditis due to Bartonella washoensis The infecting agent was characterized by sequencing of six housekeeping genes (16S rRNA, ftsZ, gltA, groEL, ribC, and rpoB), applying a multilocus sequence typing (MLST) approach. The 5,097 bp of the concatenated housekeeping gene sequence from the patient were 99.0% identical to a sequence from a B. washoensis strain isolated from a red squirrel (Sciurus vulgarisorientis) from China. A total of 39% (24/62) of red squirrel (S. vulgaris) samples from the Netherlands were positive for the B. washoensisgltA gene variant detected in the patient. This suggests that the red squirrel is the reservoir host for human infection in Europe.

First isolation and genotyping of Bartonella henselae from a cat living with a patient with cat scratch disease in Southeast Europe.

BACKGROUND: The bacterial genus Bartonella is distributed worldwide and poses a public health risk. Cat-scratch disease caused by B. henselae in Croatia was first described in 1957. It is present throughout the country: a survey of serum samples from 268 Croatian patients with lymphadenopathy showed that 37.7% had IgG antibodies. Despite this prevalence, we are unaware of reports of Bartonella culturing from infected humans or cats in Croatia or elsewhere in southeast Europe. CASE PRESENTATION: Here we describe the diagnosis of a 12-year-old child with lymphadenopathy in Croatia with cat-scratch disease based on antibody detection and clinical signs, and the subsequent culturing and genotyping of B.henselae from the cat's blood. The B. henselae isolate was grown on different blood agar plates and its identity was confirmed based on polymerase chain reaction (PCR) amplification of 16S ribosomal deoxyribonucleic acid (16S rDNA) and sequencing. Multi-locus sequence typing (MLST) identified the strain genotype as sequence type 5, commonly found zoonotic B. henselae strain in cats. The child recovered after azithromycin therapy, and B. henselae in the cat was eliminated within three months after doxycycline treatment. CONCLUSIONS: This is, to our knowledge, the first report of B. henselae culturing and MLST-based genotyping from cat's blood in southeast Europe. Our ability to detect B. henselae in blood through culturing but not PCR suggests that the prevalence of infected cats with low bacteremia is very high, suggesting the need to develop faster, more sensitive detection assays.

Bartonella Species, an Emerging Cause of Blood-Culture-Negative Endocarditis.

Since the reclassification of the genus Bartonella in 1993, the number of species has grown from 1 to 45 currently designated members. Likewise, the association of different Bartonella species with human disease continues to grow, as does the range of clinical presentations associated with these bacteria. Among these, blood-culture-negative endocarditis stands out as a common, often undiagnosed, clinical presentation of infection with several different Bartonella species. The limitations of laboratory tests resulting in this underdiagnosis of Bartonella endocarditis are discussed. The varied clinical picture of Bartonella infection and a review of clinical aspects of endocarditis caused by Bartonella are presented. We also summarize the current knowledge of the molecular basis of Bartonella pathogenesis, focusing on surface adhesins in the two Bartonella species that most commonly cause endocarditis, B. henselae and B. quintana. We discuss evidence that surface adhesins are important factors for autoaggregation and biofilm formation by Bartonella species. Finally, we propose that biofilm formation is a critical step in the formation of vegetative masses during Bartonella-mediated endocarditis and represents a potential reservoir for persistence by these bacteria.

Diagnosis and treatment of Bartonella endocarditis.

The Bartonella genus comprises more than 20 species of Gram-negative rods which are difficult to culture. These are facultative intracellular bacteria. Humans are reservoir hosts for B. quintana and B. bacilliformis or accidental hosts for other species. Bartonella is a cause of zoonosis. Bartonella infection can be completely asymptomatic or can be linked to various conditions. Our experience with Bartonella endocarditis from 2012-2017 is presented. The most effective diagnostic method for Bartonella endocarditis is PCR detection of DNA of the pathogen from excised valve tissue. The European Society of Cardiology (ESC) in the guidelines from 2015 recommends the combination doxycycline gentamycin for the treatment of Bartonella endocarditis.

Development of a Specific and Sensitive Enzyme-Linked Immunosorbent Assay as an In Vitro Diagnostic Tool for Detection of Bartonella henselae Antibodies in Human Serum.

Bartonella henselae causes cat scratch disease and several other clinical entities. Infections with B. henselae are frequently occurring; however, the infection is only rarely diagnosed, mainly due to a lack of knowledge in the medical community. Microscopic immunofluorescence assays (IFA) are widely used for the serodiagnosis of B. henselae infections but are laborious and time-consuming, and interpretation is subjective. An easy and reliable method for the serological diagnosis of B. henselae infections is needed to overcome the shortcomings of the current IFA. Here, we report the development of an ELISA detecting human anti-B. henselae antibodies from serum samples. By separating the water-insoluble fraction of B. henselae Houston-1 via ion-exchange chromatography, 16 subfractions were generated and tested for immunoreactivity via line blotting. One particular fraction (fraction 24) was selected and spotted on ELISA plates using an industrial production platform. By use of well-characterized human sera from the strictly quality-controlled serum library of the German National Consiliary Laboratory for Bartonella infections, the sensitivity of this ELISA was 100% for PCR-proven infections and 76% for clinically suspected infections at a specificity of 93%. This ELISA is therefore a reliable high-throughput method allowing the serodiagnosis of B. henselae infections.

Improvement of Bartonella henselae DNA Detection in Cat Blood Samples by Combining Molecular and Culture Methods.

Bartonella spp. are bacteria of worldwide distribution that cause asymptomatic to fatal infections in animals and humans. The most common zoonotic species is Bartonella henselae, for which cats are the major natural reservoir host. To better understand Bartonella sp. diagnostic limitations, we determined the frequency of bloodstream infection in 112 cats by comparing and combining the results of multiple conventional and nested PCRs from blood and liquid culture samples. Using liquid culture conventional PCR, Bartonella sp. DNA was amplified from 27.7% of samples (31/112) compared to 90.2% of samples (101/112) by combining nested PCR from blood and liquid culture, indicating that PCR testing of more than one type of sample provides better sensitivity than a standalone PCR and that bloodstream infection is very frequent among cats in southeastern Brazil. This study reinforces the need for multistep testing for Bartonella sp. infection to prevent false-negative diagnostic results, even in reservoir hosts such as cats that typically maintain higher bacteremia levels.

Bartonella vinsonii subsp. berkhoffii and B. henselae in dogs.

This study aimed to molecularly survey Bartonella in dogs from Chile. Quantitative real-time PCR (qPCR) for Bartonella spp. based on nuoG gene was performed in 139 blood samples taken from dogs belonging to rural localities of the Valdivia Province, Los Ríos region, southern Chile. nuoG qPCR-positive samples were submitted to conventional PCR assays for ftsZ, gltA, rpoB and nuoG genes and sequencing for speciation and phylogenetic analysis. Based upon qPCR results, Bartonella spp. occurrence in dogs was 4.3% (6/139). Out of six nuoG qPCR-positive samples, six, three, two and none showed positive results in cPCR assays based on gltA, ftsZ, rpoB and nuoG genes, respectively. Consistent sequencing results were obtained only for the ftsZ gene from sample #1532 (GeneBank accession number: MG252491), and gltA gene from samples #1535 (MG252490) and #1532 (148 bp fragment that was not deposited in GenBank). Phylogenetic analysis of ftsZ and gltA genes allowed speciation of two nuoG-positive samples, one as Bartonella vinsonii subsp. berkhoffii and the other as B. henselae. Bartonella vinsonii subsp. berkhoffii and B. henselae are detected for the first time in dogs from Chile, highlighting the importance of the canine population as a source of zoonotic agents and potential infection risk to humans.

Molecular detection and clinical characteristics of Bartonella bacilliformis, Leptospira spp., and Rickettsia spp. in the Southeastern Peruvian Amazon basin.

BACKGROUND: Acute febrile illness (AFI) represent a significant health challenge in the Peruvian Amazon basin population due to their diverse etiologies and the unavailability of specific on-site diagnostic methods, resulting in underreporting of cases. In Peru, one of the most endemic regions to dengue and leptospirosis is Madre de Dios, a region also endemic to emergent bacterial etiologic agents of AFI, such as bartonellosis and rickettsiosis, whose prevalence is usually underreported. We aimed to molecularly identify the presence of Leptospira spp., Bartonella bacilliformis, and Rickettsia spp. by Polymerase Chain Reaction in serum samples from patients with AFI from Puerto Maldonado-Madre de Dios in Peru. METHODS: Serum samples from patients with acute febrile illness were analyzed by real-time PCR for detecting the presence of Bartonella bacilliformis, Leptospira spp. and Rickettsia spp. RESULTS: Bartonella bacilliformis was the most prevalent bacteria identified in 21.6% (30/139) of the samples, followed by Leptospira spp. in 11.5% (16/139) and Rickettsia spp. in 6.5% (9/139) of the samples. No co-infections were observed between these bacteria. The most frequent symptoms associated with fever among all groups, were headaches, myalgias, and arthralgias. We found no statistically significant differences in the clinical presentation between patients infected with each bacterium. CONCLUSIONS: In a previous study, we shown the presence of dengue, chikungunya, Zika and oropouche virus. We were able to identify these pathogens in 29.5% of all the samples, with chikungunya and OROV as the most frequently found in 9.4 and 8.6% of all the samples, respectively. In this study we show that B. bacilliformis (21.6%), Leptospira spp. (11.5%) and Rickettsia spp. (6.5%) accounted for the main etiologies of AFI in samples from Puerto Maldonado-Madre de Dios, Perú. Our analysis of their clinical presentation, further shows the importance of implementing more sensitive and specific on-site diagnostic tools in the national surveillance programs.This study confirms that the un-specificity of signs and symptoms is not only associated with arboviral infections, but also with the clinical presentation of endemic bacterial infections.

Molecular detection of Bartonella coopersplainsensis and B. henselae in rats from New Zealand.

AIM To identify Bartonella spp. in rats from New Zealand using molecular methods. METHODS DNA was extracted from the spleens of 143 black rats (Rattus rattus) captured in the Tongariro National Park, New Zealand. PCR was performed using Bartonella genus-specific primers amplifying segments of the 16S-23S rRNA internal transcribed spacer and citrate synthase (gltA) and beta subunit of the RNA polymerase (rpoB) genes. PCR products were sequenced and compared online with sequences stored in the database of the National Center for Biotechnology Information of the United States of America. RESULTS DNA sequences matching Bartonella coopersplainsensis and B. henselae were detected in samples from 22/143 (15.4%) and 3/143 (2.1%) rats, respectively. Co-occurrence of B. coopersplainsensis and B. henselae sequences was observed in the sample from one rat. CONCLUSIONS AND CLINICAL RELEVANCE Gram-negative fastidious bacteria belonging to the genus Bartonella are associated with a range of human diseases. Rodents play an important role as reservoirs of a broad range of Bartonella species. To our knowledge, this is the first report of a molecular detection of Bartonella spp. DNA in rodents from New Zealand, and the first identification of B. henselae DNA in rats, worldwide. Whereas the public health significance of B. coopersplainsensis remains undefined, B. henselae is the agent of cat scratch disease, and the presence of this bacterium in rats may have public health implications. Our results are preliminary and additional analyses of larger samples, preferably by bacterial culture, would provide more information on the prevalence and diversity of Bartonella spp., in particular B. henselae, in rats.

Molecular diagnosis of skin infections using paraffin-embedded tissue - review and interdisciplinary consensus.

Nucleic acid amplification techniques (NATs), such as PCR, are highly sensitive and specific methods that have become valuable supplements to culture and serology in the diagnosis of infectious disorders. However, especially when using formalin-fixed and paraffin-embedded tissue, these techniques are associated with both false-negative and false-positive results, a pitfall that is frequently misjudged. Representatives of the German Society of Hygiene and Microbiology (DGHM) and the German Society of Dermatology (DDG) therefore set out to develop a consensus - in the form of a review article - on the appropriate indications for NATs using paraffin-embedded tissue, its contraindications, and the key points to be considered in the pre- and post-analytical phase. Given that fresh, naive tissue is preferably to be used in the workup of a suspected infection, PCR analysis on paraffin sections represents an exception. The latter may be considered if an infection is suspected at a later point in time and fresh tissue has not been preserved or can no longer be obtained. Potential indications include confirmation of histologically suspected infections with Leishmania spp., Bartonella spp., Rickettsia spp., or in case of ecthyma contagiosum. Infections with, for example, mycobacteria or RNA viruses, on the other hand, are not considered useful indications for NATs using paraffin sections. In order to avoid misinterpretation of test results, it is essential that laboratory reports on NATs using paraffin-embedded tissue contain information on the indication/diagnostic circumstances, the required and chosen pre-analytical steps, the limitations of the method, and on diagnostic alternatives.

Management of Bartonella Prosthetic Valve Endocarditis without Cardiac Surgery.

Two cases of Bartonella prosthetic valve endocarditis were cured when treated for 2 weeks with gentamicin and 3 months with doxycycline. Clinical cure correlated with decreased Bartonella antibody titers. This report suggests a strategy to monitor, treat, and cure Bartonella prosthetic valve endocarditis.

Seroprevalence of Bartonella Species in Patients with Ocular Inflammation.

Bartonella species, vector-borne etiologic agents of many systemic or self-limited infections, are responsible for a widening spectrum of diseases in humans, including inflammatory conditions of the eye. The aim of this study was to determine whether there is any relationship between uveitis and the evidence of Bartonella spp. infection in the serum, ocular fluid, and cataract mass in patients with intraocular inflammation. Polymerase chain reaction (PCR)-based tests and DNA sequencing were performed on surgery-extracted specimens of intraocular fluid and lens mass of 33 patients. Sera from 51 patients and 101 control subjects were tested for the presence of specific antibodies against Bartonella spp. Neither IgM-class antibodies against Bartonella spp. nor Bartonella spp. DNA were detected. A specific IgG-class antibody was found in 33.3% of the patients with uveitis. The rate of positive Bartonella serology was higher among the uveitis patients than that in control subjects. This high rate may in part result from unrecognized indirect mechanisms rather than the immediate presence and multiplication of Bartonella spp. in the eyeball. Nonetheless we believe that screening for Bartonella spp. should become part of the diagnostic workup in uveitis.

Bartonellosis, One Health and all creatures great and small.

BACKGROUND: Bartonellosis is a zoonotic infectious disease of worldwide distribution, caused by an expanding number of recently discovered Bartonella spp. OBJECTIVES: This review serves as an update on comparative medical aspects of this disease, including the epidemiology, pathogenesis, clinical diagnosis, treatment and challenges. RESULTS: Of comparative medical importance, Bartonella spp. are transmitted by several arthropod vectors, including fleas, keds, lice, sand flies, ticks and, potentially, mites and spiders. Prior to 1990, there was only one named Bartonella species (B. bacilliformis), whereas there are now over 36, of which 17 have been associated with an expanding spectrum of animal and human diseases. Recent advances in diagnostic techniques have facilitated documentation of chronic bloodstream and dermatological infections with Bartonella spp. in healthy and sick animals, in human blood donors, and in immunocompetent and immunocompromised human patients. The field of Bartonella research remains in its infancy and is rich in questions, for which patient relevant answers are badly needed. Directed Bartonella research could substantially reduce a spectrum of chronic and debilitating animal and human diseases, and thereby reduce suffering throughout the world. CONCLUSION: A One Health approach to this emerging infectious disease is clearly needed to define disease manifestations, to establish the comparative infectious disease pathogenesis of this stealth pathogen, to validate effective treatment regimens and to prevent zoonotic disease transmission.

[Presented with subarachnoid hemorrhage and then blood culture negative infective endocarditis: a case report and literature review].

The patient, a 43-year-old man, had paroxysmal headache three months ago, and he had complained the left occipital sharp pain, which could be alleviated by itself, with alalia and the right side of the upper limb numbness. Head computed tomography (CT) revealed a left temporal lobe intraparenchymal hemorrhage with the left side of the subarachnoid hemorrhage in small quantities. Digital subtraction angiography (DSA) revealed a suspicious aneurysm on the left internal carotid artery siphon. He had intermittent fever 1 month ago, with maximum body temperature 39 °C. He suffered headache again 20 days ago, with pain nature, duration and the way of easing up similar to the earlier onset. General examination demonstrated 2/6 grade blowing systolic murmurs at apex area. Neurological examination revealed that Babinski's sign was positive on the right side. Echocardiographic found an anterior mitral valve ve-getation on the 4th day in hospital. So his clinical diagnosis was infective endocarditis with cerebral embolism. He received vancomycin treatment immediately. His three blood cultures remained negative in hospital. His blood specimens were sent to Chinese Center for Disease Control and Prevention, indirect immunofluorescence method (IFA) IgG antibody detection revealed that the Bartonella henselae IgG antibody was positive. Therefore the clinical diagnosis was Bartonella endocarditis complicated with subarachnoid hemorrhage and cerebral embolism. Bartonella, an intracellular fastidious, gram-negative bacilli, was first documented as a cause of endocarditis in 1993 and since then has been increasingly recognized as an important etiology of infective culture-negative endocarditis. In cases of documented Bartonella endocarditis, the Infectious Diseases Society of America (IDSA) guidelines recommended 2 weeks of gentamicin plus 6 weeks of doxycycline treatment, to achieve a higher cure rate.