(Last updated: May 7, 2013; last reviewed: March 13, 2017)
Bartonella species cause infections that include cat scratch disease, retinitis, trench fever, relapsing bacteremia, endocarditis, bacillary angiomatosis (BA), and bacillary peliosis hepatis.1 The latter two manifestations occur only in individuals who are immunocompromised. BA is caused by either Bartonella quintana or Bartonella henselae.1,2 Twenty-four species and three subspecies of Bartonella have been isolated and are officially recognized (http://www.bacterio.cict.fr/b/bartonella.html), and eight have been isolated from humans. However, only B. henselae and B. quintana infections have been identified in HIV-infected patients.2 BA most often occurs late in HIV infection, in patients with median CD4 T lymphocyte (CD4 cell) counts <50 cells/mm3.2 In HIV-infected patients, bartonellosis is often a chronic illness, lasting for months to years, with BA lesions and intermittent bacteremia.
Development of BA lesions caused by B. henselae is statistically linked to cat exposure in patients with HIV infection.2 In contrast, BA caused by B. quintana is associated with body louse infestation and homelessness.2 The body louse serves as the vector of B. quintana in humans. To avoid exposure to B. quintana, HIV-infected patients should avoid body lice and, if infected, treat the infestation. The cat flea is the vector of B. henselae in cats. Cats are the most common vector (via a scratch) responsible for transmitting B. henselae to humans, most likely when their claws become contaminated with feces from B. henselae-infected fleas. In some areas of the United States, the prevalence of B. henselae bacteremia in pet cats approaches 50%.3 Control of cat flea infestation and avoidance of cat scratches are therefore critical strategies for preventing B. henselae infections in patients who are HIV infected.
BA lesions have been associated with nearly every organ system, but cutaneous lesions are the most readily identified. These lesions can be clinically indistinguishable from Kaposi sarcoma, pyogenic granuloma, and other skin conditions. BA also can cause subcutaneous nodules. Osteomyelitis is usually caused by B. quintana, and only B. henselae can cause bacillary peliosis hepatis. Although isolated organs can appear to be the principal focus of disease, BA represents a hematogenously disseminated infection, and systemic symptoms of fever, night sweats, and weight loss often accompany BA. Bartonella infection is a major cause of unexplained fever in patients with late-stage AIDS and should be considered in the differential diagnosis of patients with fever and CD4 counts <100 cells/mm3.4 Bartonella is a relatively common cause of culture-negative endocarditis in immunocompetent and immunocompromised humans and is most commonly caused by B. quintana and, less frequently, B. henselae.5
Diagnosis can be confirmed by histopathologic examination of biopsied tissue.6 BA lesions are characterized by vascular proliferation, and a modified silver stain (such as Warthin-Starry stain) usually demonstrates numerous bacilli. Tissue Gram staining and acid-fast staining are negative.
A well-characterized serologic test was developed at Centers for Disease Control and Prevention7 and is also available at some state health labs. In addition, several private laboratories offer serological testing, but none of these private laboratory tests has been evaluated for sensitivity or specificity with sera from HIV-infected patients with culture-documented Bartonella infection. In immunocompetent patients, anti-Bartonella antibodies might not be detectable for 6 weeks after acute infection; in contrast, by the time Bartonella infection is suspected in patients with late-stage HIV infection, they usually have been infected for months or even >1 year. Note that as many as 25% of Bartonella culture-positive patients never develop antibodies in the setting of advanced HIV infection.4 In those patients who do develop anti-Bartonella antibodies, monitoring of antibody levels can correlate with resolution and recrudescence of Bartonella infection.
Bartonella species can be isolated (with difficulty) from blood, using ethylenediaminetetraacetic acid (EDTA) tubes. The organisms have been isolated from tissue in only a few laboratories because of the fastidious nature of Bartonella.2 Polymerase chain reaction methods have been developed for identification and speciation of Bartonella but are not widely available.
HIV-infected patients, specifically those who are severely immunocompromised (CD4 counts <100 cells/mm3), are at high risk of severe disease when infected by B. quintana and B. henselae. The major risk factors for acquisition of B. henselae are contact with cats infested with fleas and receiving cat scratches. Immunocompromised individuals should consider the potential risks of cat ownership (AIII). Patients who want cats should acquire animals that are older than age 1 year and in good health (BII). Cats should be acquired from a known environment, have a documented health history, and be free of fleas. Stray cats and cats with flea infestation should be avoided. Declawing is not advised, but HIV-infected individuals should avoid rough play with cats and situations in which scratches are likely (AII). Patients should avoid contact with flea feces (i.e., flea dirt), and any cat-associated wound should be washed promptly with soap and water (BIII). Care of cats should include a comprehensive, ongoing flea-control program under the supervision of a veterinarian (BIII). No evidence indicates any benefits to cats or their owners from routine culture or serologic testing of the pet for Bartonella infection or from antibiotic treatment of healthy, serologically positive cats (BII). The major risk factor for B. quintana infection is body lice infestation. Patients who are homeless or in marginal housing should be informed that body louse infestation can be associated with serious illness and provided with appropriate measures to eradicate body lice, if present (AII).
Primary chemoprophylaxis for Bartonella-associated disease is not recommended (BIII). However, note that in a retrospective case-control study, Mycobacterium avium complex prophylaxis using a macrolide or rifamycin was protective against developing Bartonella infection.2
Treating DiseaseAll HIV-infected patients with Bartonella infection should receive antibiotic treatment (AII). Guidelines for treatment of Bartonella infections have been published.8 No randomized, controlled clinical trials have evaluated antimicrobial treatment of bartonellosis in HIV-infected patients. Erythromycin and doxycycline have been used successfully to treat BA, peliosis hepatis, bacteremia, and osteomyelitis and are considered first-line treatment for bartonellosis on the basis of reported experience in case series (AII).1,2 Therapy should be administered for ≥3 months (AII). Doxycycline, with or without a rifamycin, is the treatment of choice for bartonellosis infection involving the central nervous system (CNS) (AIII). For severe Bartonella infections, combination therapy using erythromycin or doxycycline with a rifamycin is recommended (BIII); intravenous therapy may be needed initially (AIII). Treatment of confirmed Bartonella endocarditis should include doxycycline with the addition of gentamicin for 2 weeks (if tolerated); a rifamycin can be substituted for gentamicin in the setting of renal insufficiency (BII).8
Special Consideration with Regard to Starting ARTAntiretroviral-naive patients with Bartonella CNS or ophthalmic lesions should probably be treated with doxycycline and a rifamycin for 2 to 4 weeks before instituting antiretroviral therapy (CIII).
Monitoring of Response to Therapy and Adverse Effects (Including IRIS)Patients should have anti-Bartonella IgG antibody titers checked at the time of diagnosis and, if positive, should be followed with sequential titers every 6 to 8 weeks until a four-fold decrease is documented. This test is available at the Centers for Disease Control and Prevention and several large commercial labs. Patients treated with oral doxycycline should be cautioned about pill-associated ulcerative esophagitis that occurs most often when a dose is taken with only a small amount of liquid or at night just before retiring.10 Photosensitivity also can occur during doxycycline treatment. Adverse effects associated with macrolides include nausea, vomiting, abdominal pain, and elevations of liver transaminase levels. Serious side effects can occur during treatment with rifamycins, including hypersensitivity reactions (including thrombocytopenia, interstitial nephritis, and hemolytic anemia), and hepatitis. Administration of rifamycins strongly induces the cytochrome P450 enzyme system, which is an important consideration when other medications, including many ARV drugs, are taken simultaneously.
Managing Treatment FailureAmong patients who fail to respond to initial treatment, 1 or more of the second-line alternative regimens should be considered (AIII), again with treatment duration of ≥3 months. For patients with positive or increasing antibody titers, treatment should continue until a fourfold decrease is documented.
Preventing RecurrenceIf a relapse occurs after a minimum 3-month course of primary treatment, long-term suppression of infection with doxycycline or a macrolide is recommended, as long as the CD4 count remains <200 cells/mm3 (AIII).
Special Considerations During PregnancyInfection with Bartonella bacilliformis in immunocompetent patients during pregnancy has been associated with increased complications and risk of death.11 No data are available on the effect of B. henselae or B. quintana infections in pregnant women with concomitant HIV infection.
For Bacillary Angiomatosis, Peliosis Hepatis, Bacteremia, and Osteomyelitis:
If a relapse occurs after a ≥3 month course of primary treatment:
|Key to Abbreviations: ARV = antiretroviral; BID = twice daily; CD4 = CD4 T lymphocyte cell; CNS = central nervous system, IV = intravenously, PO = orally; q(n)h = every “n” hours|