BASICS

  • Fastidious intracellular Gram-negative bacilli
    • At least 20 distinct species, 8 known to cause disease in humans
    • Bartonella henselae and B. quintana most common in North America
  • Infections manifest in 2 broad categories
    • Localized skin lesions and prominent regional lymphadenitis (cat scratch disease [CSD])
    • Bacteremia with localized vascular lesions in various organs and potential for persistent disseminated infection
  • System(s) Affected: Cardiovascular; Gastrointestinal; Hemic/Lymphatic/Immunologic; Musculoskeletal; Nervous; Pulmonary; Skin/exocrine
  • Synonym(s): Bartonellosis

Vector avoidance

  • CSD: Predominantly children
  • Others: Predominantly adults
  • Carri´on disease: 12.7/100 person-years in endemic areas
  • CSD: Estimated 9.3/100,000 in US (~25,000 cases annually)
  • Endocarditis: Estimated 3–4% of cases, up to 1/3 of “culture negative” cases
  • Others: Unknown
  • Seroprevalence studies of B. henselae suggests many childhood infections are asymptomatic.
  • Studies of B. quintana in homeless populations suggest seroprevalence of 10%.
  • Vector exposure with cutaneous inoculation
    • B. bacilliformis: Lutzomyia sandflies, limited to Andean South America
    • B. quintana: Human body louse, typically in alcoholic, homeless men
    • B. henselae: Domestic cat (especially scratch/bite from kitten)
    • Others: Unknown
  • Cell-mediated immune dysfunction (particularly in bacillary angiomatosis/bacillary peliosis)
    • HIV infection, especially with CD4+ lymphocyte count <100/mcL
    • Chronic steroid, immunosuppressant, or alcohol use
  • Erythrocyte and endothelial cell invasion
  • Stimulation of angiogenesis
  • B. bacilliformis: Carri´on disease
  • B. quintana: Trench fever, bacillary angiomatosis (subcutaneous and osseous lesions), bacillary peliosis, endocarditis
  • B. henselae: CSD, acute and persistent bacteremia, bacillary angiomatosis (hepatosplenic lesions), bacillary peliosis, endocarditis (preexisting valvular disease), neurologic manifestations
  • B. clarridgeiae, B. elizabethae, B. grahamii, B. vinsonii, B. washoensis: Case reports of CSD, bacteremia, endocarditis, myocarditis, others.
  • DIAGNOSIS
    • Diagnosis of typical CSD traditionally requires at least 3 of the following
      • Animal contact (usually cat) resulting in a scratch, abrasion, or ocular lesion
      • Positive serologic test
      • Characteristic lymph node pathology
      • No evidence of other cause
    • Diagnosis of other syndromes requires high clinical suspicion and identification of compatible syndrome; if test results are not helpful, response to appropriate antibiotics may be suggestive.
    • Carri´on disease (aka Bartonellosis; usually has 2 distinctive stages: An acute, life-threatening illness associated with high fever, hemolytic anemia, and a chronic, benign cutaneous eruption consisting of raised, reddish-purple nodules.
      • Oroya fever (acute bacteremia): In severe cases, abrupt onset 3 weeks after inoculation. Profound anemia, many complications, may be fatal.
      • Asymptomatic persistent bacteremia: <15% of untreated Oroya fever survivors
      • Verruga peruana: Crops of nodular angiomatous skin lesions months after Oroya fever; mucosal and internal lesions also; involute in months to years
    • Typical CSD (up to 90% of cases)
      • Days after inoculation 2–3-mm nontender papules develop at the trauma site; progress to reddened then crusted vesicles
      • Tender regional adenopathy 1–8 weeks postinoculation; fever, malaise, headache
      • Usually involves nodes of upper extremities, neck, head
      • Suppuration of nodes common, but only 10% require drainage
      • Resolution in 2–4 months for majority
    • Atypical CSD
      • Parinaud oculoglandular syndrome: Unilateral granulomatous conjunctivitis and preauricular lymphadenitis
      • Neuroretinitis: Abrupt, painless unilateral vision loss; macular star exudate, papilledema; self-limited, with return of visual acuity
      • Encephalopathy: Rapid progression from headache to lethargy, coma, and seizure; sequelae rare
      • Other manifestations self-limited, sequelae rare: Granulomatous hepatitis/splenitis, osteolysis, atypical pneumonitis, fever of unknown origin, mononucleosis-type syndrome, others
    • Bacteremia (short-term mortality uncommon)
      • B. quintana (urban trench fever, Wolhynia fever, shin-bone fever, quintan fever): Incubation days–weeks; sudden onset of fever, headache, leg pain; self-limited illness may be brief (4–5 days), prolonged (2–6 weeks), most commonly paroxysmal (3–5 episodes of 5 days’ duration). Insidious course in HIV.
      • B. henselae: If HIV-infected, insidious onset of fatigue, malaise, aches, weight loss, recurring fevers, headache; localizing findings uncommon. If HIV-uninfected, abrupt onset of fever (may persist or relapse), myalgias, arthralgias, headache; localizing findings unusual; may persist without symptoms.
    • Endocarditis: Fever, dyspnea, murmur, embolic phenomena; aortic valve involvement most common
    • Bacillary angiomatosis: Mostly immunocompromised hosts (e.g., HIV-infected); involves skin (crops of subcutaneous or dermal nodules and/or skin-colored to purple papules; may ulcerate with serous or bloody drainage and crusting), regional lymph nodes, internal organs
    • Bacillary peliosis: Involves liver and spleen in immunosuppressed persons; can involve lymph nodes; nonspecific clinical manifestations
    • Neurologic syndromes in HIV: Cognitive dysfunction, behavioral disturbances; may be mistaken for dementia, psychiatric disease
    • Skin testing reagents: Not recommended
    • Giemsa-stained blood smear may show B. bacilliformis adherent to erythrocytes
    • Non-bacilliformis species
      • Indirect fluorescent antibody and enzyme immunoassay tests are available
        • Interpretation complicated by variable correlation between titers and disease stage, lack of uniformity among serologic tests, and cross-reactivity among Bartonella species and other bacteria.

    Advise lab if Bartonella infection is suspected so that blood, tissue, and cerebrospinal fluid cultures are prepared with appropriate media under optimal conditions; prolonged incubation required.

    • Polymerase chain reaction (PCR) and immunohistochemical labeling primarily research tools, although PCR of valve tissue can aid diagnosis of endocarditis
    • Drugs that may alter lab results: Antibiotics (cultures falsely negative)

    Ultrasonography, CT, or ECG as indicated

    • Biopsies for histology/culture of nodules, lymph nodes, or internal organs
    • Lumbar puncture if CNS involvement
    • Verruga peruana: Neovascular proliferation; bacteria uncommonly are identified.
    • CSD: Granulomas, stellate necrosis, mixed inflammatory infiltrates; bacilli in tissue may be demonstrable by silver impregnation stains (e.g., Warthin-Starry).
    • Endocarditis: Warthin-Starry–stained bacilli may be seen in vegetations.
    • Bacillary angiomatosis
      • Lobular proliferations of small blood vessels are seen, containing cuboidal endothelial cells interspersed with inflammatory cells, mostly neutrophils.
      • Warthin-Starry stain or electron microscopy may show clusters of bacilli
    • Bacillary peliosis: Blood-filled cystic structures. Warthin-Starry stain may show surrounding clumps of bacilli.
    • Typical CSD: Sporotrichosis, histoplasmosis, plague, tularemia, brucellosis, mycobacteria, staphylococci, streptococci, other agents associated with injection drug use; lymphoma; metastatic malignancy
    • Atypical CSD: Other agents causing similar syndromes
    • Non-bacilliformis bacteremia syndromes
      • Immunocompromised: Cryptococcus neoformans, Histoplasma capsulatum, Coccidioides immitis, Mycobacterium avium-complex
      • Arthropod exposure: Rickettsial infections, tularemia, plague, babesiosis, borreliosis
      • Cat/dog scratch/bite: Pasteurella
      • Influenza, infectious mononucleosis, hepatitis
    • Endocarditis: Other slow-growing bacteria (Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, Kingella, Coxiella)
    • Bacillary angiomatosis/bacillary peliosis: Kaposi sarcoma; pyogenic granuloma, hemangioma
    • Neurologic syndrome in HIV: Tertiary syphilis, cryptococcal meningitis, toxoplasmosis, progressive multifocal leukoencephalopathy, alcohol or drug abuse

TREATMENT

  • Outpatient for uncomplicated infection
  • Initial hospitalization may be necessary for IV antibiotics or complications.
  • CSD: Supportive therapy (e.g., aspiration suppurative nodes)
  • Systemic syndromes (including CSD-associated neuroretinitis and encephalopathy): Antibiotics

Fully active if uncomplicated

  • Oroya fever: Chloramphenicol 500 mg (pediatric dose 50–75 mg/dg/d) PO/IV q.i.d. + β-lactam for 14 days (not available in US) (1 ) [B]; ciprofloxacin 500 mg (250 mg for children 7–12 years) PO b.i.d. for 10 days
  • Verruga peruana: Rifampin 10/mg/kg/d (not to exceed 600 mg/d in children) for 10 days (1 ) [B])
  • Typical CSD: No clear benefit, although oral azithromycin may speed resolution of extensive lymphadenopathy: Adults and children >45.5 kg: 500 mg on day 1; 250 mg daily on days 2–5; children ≤45.5 kg: 10 mg/kg on day 1; 5 mg/kg daily on days 2–5 (1 ) [A]
  • Retinitis: Doxycycline 100 mg PO b.i.d. + rifampin 300 mg PO b.i.d. for 4–6 weeks (1 ) [B]
  • Trench fever or chronic B. quintana bacteremia: Doxycycline 200 mg PO daily for 4 weeks + gentamicin 3 mg/kg IV daily for 2 weeks (1 ) [A]
  • Bacillary angiomatosis: Erythromycin 500 mg (pediatric dose 40 mg/kg/d to maximum daily dose of 2 g/d) PO q.i.d. or doxycycline 100 mg PO b.i.d. for 3 months; consider longer course if immunocompromised (1 ) [B]
  • Bacillary peliosis: Erythromycin 500 mg (pediatric dose 40 mg/kg/d to maximum daily dose of 2 g/d) PO q.i.d. or doxycycline 100 mg PO b.i.d. for 4 months; consider longer course if immunocompromised (1 ) [B]
  • Endocarditis (culture positive): Gentamicin 3 mg/kg IV daily for 2 weeks + doxycycline 100 mg PO b.i.d. for 6 weeks (1 ) [B]
  • Endocarditis (culture negative): Gentamicin 3 mg/kg IV daily for 2 weeks + ceftriaxone 2 g IV/IM daily for 6 weeks +/– doxycycline 100 mg PO/IV b.i.d. for 6 weeks (1 ) [B]

FOLLOWUP

  • CSD: Spontaneous resolution usually in 2–4 months without specific therapy
  • Other syndromes: With proper treatment, full resolution; if relapse, consider long-term suppressive antibiotics after retreatment

Relapse, especially in HIV infection