Approach

Depending on the species of Bartonella and clinical manifestation, the treatment approach for bartonellosis may vary. The course of the disease may also vary, from spontaneous resolution in some cases to fatal infections in other cases. There are only limited data available from prospective randomised trials to guide treatment. Bartonella infections with a high risk of complications or mortality (e.g., Oroya fever, infectious endocarditis, bacillary angiomatosis) should be treated with empiric antibiotic therapy.[54] There is insufficient evidence to recommend one regimen over another, and treatment is generally based on microbiology susceptibility data and physician experience/opinion.

Endocarditis (Bartonella henselae or Bartonella quintana)

Untreated cases of Bartonella endocarditis can lead to cardiac complications including valvular damage, abscesses, and heart failure.

When Bartonella is confirmed as the pathogen for endocarditis, the patient is preferably treated with gentamicin (14 days) in combination with doxycycline (6 weeks).[10][55]​​​​ If there is a concern for kidney injury, rifampicin plus doxycycline should be used (6 weeks).[56][57]​​​ When B henselae or B quintana is suspected as a cause of endocarditis and confirmatory tests are pending, ceftriaxone is given as an additional coverage for other bacteria.[10][55]​​​​Other Bartonella species (including B bacilliformis) can cause endocarditis, but this is very rare; seek advice from an infectious disease specialist if the patient has confirmed endocarditis due to an unusual Bartonella species.[10]​​[17][47]​​​​

It is important to note that ceftriaxone does not provide antimicrobial coverage for Bartonella species and should be discontinued once the diagnosis is confirmed.

There was previously some concern about using doxycycline in younger children due to the possible risk of teeth staining.[58][59]​ However, although older tetracyclines were associated with staining of permanent teeth in young children, no evidence suggests that doxycycline causes any such tooth staining. Therefore, the American Academy of Pediatrics (AAP) recommend that doxycycline may be used in children aged <8 years for short durations (i.e., ≤21 days).[57] If an effective alternative exists, this is preferred for longer treatment courses.

Due to the lack of effective alternative antibiotics for Bartonella endocarditis and serious nature of the infection, doxycycline use is warranted in children of all ages despite the longer treatment course (>21 days). Consultation with a paediatric infectious disease specialist is recommended.[57] In the UK, doxycycline is not recommended for children aged <12 years, except in severe infections when there are no alternative options.

The treatment of Bartonella endocarditis should be individualised in immunocompromised patients, as a prolonged course of therapy may be necessary. The recommended treatment for confirmed Bartonella endocarditis in adults with HIV is intravenous doxycycline plus intravenous or oral rifampicin for 6 weeks, followed by intravenous or oral doxycycline monotherapy for ≥3 months. Doxycycline plus gentamicin, both administered intravenously, for 14 days followed by intravenous or oral doxycycline monotherapy for ≥3 months is an alternative option, but is less preferred because of the potential for nephrotoxicity with gentamicin.[56] Children with HIV infection should be managed under specialist guidance. 

If the patient has extensive valve damage and leakage leading to congestive heart failure or embolic lesions, they may require valve replacement. All patients should be followed clinically and monitored closely for any complications, such as embolic events and congestive heart failure. A follow-up echocardiogram may be helpful in visualising resolution of valvular vegetations, where applicable.

Supportive care for Bartonella endocarditis is the same as for other types of endocarditis: careful attention to fluid and electrolytes balance, ECG monitoring, and management for heart failure.

Cat-scratch disease (Bartonella henselae): no endocarditis, hepatic involvement or bacillary angiomatosis

Immunocompetent patients tend to present with a mild to moderate infection that is self-limiting in its course and does not require antibiotics.[10][45] Symptoms generally subside within several weeks.

Immunocompromised patients with any severity of infection, or immunocompetent patients with large lymph nodes, should be treated with azithromycin for 5 days.[10][45][60] Alternatively, a combination of doxycycline and rifampicin can be used for 7 to 10 days. In patients with HIV, doxycycline or erythromycin monotherapy has been recommended as preferred therapy for treatment of cat-scratch disease.[56] Prolonged treatment (at least 3 months) is recommended for patients with HIV.[56]

Although tooth discoloration is a general concern in children aged <8 years (<12 years in the UK), the AAP recommends that doxycycline can be used irrespective of age for short durations (≤21 days).[57]

Several antibiotics, for example, clarithromycin, trimethoprim/sulfamethoxazole and ciprofloxacin, have been used for the treatment of cat-scratch disease with variable efficacy. However, evidence for their use in clinical practice is inconsistent and hence they should not be used in treatment. Rifampicin alone has been used for hepatosplenic bartonellosis.[61]

Patients with fever should receive appropriate antipyretics.

Needle aspiration is indicated for suppurative lymph nodes. Multiple aspirations may be necessary.

Patients with painful lymphadenopathy may require analgesics.

Trench fever or quintana fever (Bartonella quintana): no endocarditis or bacillary angiomatosis

B quintana infection generally causes a trench fever at the acute stage. It may resolve spontaneously, but it can progress to chronic bacteraemia and endocarditis in untreated cases. Patients in the acute and chronic stages should be treated with a combination of doxycycline and gentamicin. Adult patients are treated with oral doxycycline for 28 days and intravenous gentamicin for 14 days.[10][62][63]​​ Erythromycin and gentamicin can be used in adults who have a contraindication to doxycycline. Doxycycline is not recommended in children aged <8 years for longer than 21 days, as tooth discoloration is a concern.[57] In the UK, doxycycline is not recommended for children aged <12 years. Instead, gentamicin and erythromycin can be used as an alternative in this group of children. There are only anecdotal data to support doxycycline alone. 

Trench fever is transmitted by the human body louse (Pediculus humanus humanus), and humans are the only known reservoir. Body louse infestation (pediculosis) can usually be managed with improvements to personal hygiene, including changing into clean clothes at least once a week, and washing and machine drying clothing, bedding, and towels with hot water (at least 54°C [130°F]).[64]​ However, treatment with insecticides and/or a pediculicide may be advisable in the case of associated Bartonella infection to prevent reinfection or further transmission. Insecticides such as DDT, malathion, or permethrin may be used to treat clothing and bedding. Recommended pediculicides are the same as for head lice.[64] See Pediculosis capitis (Management approach). 

Bacillary angiomatosis (Bartonella henselae or Bartonella quintana)

This is a vascular proliferative disease caused by B henselae and B quintana in immunocompromised patients, especially those with HIV infection.[4][5] Bacillary angiomatosis occurs in late-stage HIV infection when CD4 counts are less than 50 cells/microlitre.[56] Appropriate therapy is important to prevent infection from spreading, with possibly fatal results.

The antibiotics of choice for the treatment of bacillary angiomatosis are erythromycin or doxycycline for 3 months or longer.[56] Doxycycline is not recommended in children aged <8 years for longer than 21 days, as tooth discoloration is a concern.[57]​ In the UK, doxycycline is not recommended for children aged <12 years.

Although there are insufficient published data to support its use, azithromycin for 3 months has also been used successfully.[65] Given its good coverage for both B quintana and B henselae, azithromycin may be used as an alternative to erythromycin or doxycycline.[56][57]​ Clarithromycin may also be considered as an alternative, but there is limited evidence to support its use.[56]

Body louse infestation (pediculosis) can usually be managed with improvements to personal hygiene, including changing into clean clothes at least once a week, and washing and machine drying clothing, bedding, and towels with hot water (at least 54°C [130°F]).[64]​ However, treatment with insecticides and/or a pediculicide may be advisable in the case of associated Bartonella infection to prevent reinfection or further transmission. Insecticides such as DDT, malathion, or permethrin may be used to treat clothing and bedding. Recommended pediculicides are the same as for head lice.[64] See Pediculosis capitis (Management approach). 

Patients with fever should receive appropriate antipyretics. Measures to improve immunity should be instituted in immunocompromised patients: for example, antiretroviral therapy for HIV/AIDS, or a decrease of immunosuppressive agents in transplant patients.

Peliosis hepatis or hepatosplenic micro-abscesses (Bartonella henselae)

Immunocompromised adults and children may present with peliosis hepatis characterised by dilated capillaries and blood-filled cavernous spaces in the liver. Patients manifest with fever, chills, gastrointestinal symptoms, and hepatosplenomegaly.

Peliosis hepatis should be treated with erythromycin or doxycycline for ≥3 months.[56] Doxycycline is not recommended in children aged <8 years for longer than 21 days, as tooth discoloration is a concern.[57]​ In the UK, doxycycline is not recommended for children aged <12 years.

Immunocompetent children may also present with hepatosplenic micro-abscesses secondary to B henselae infection. These respond well to a 2-week course of treatment with rifampicin alone or in combination with gentamicin or trimethoprim/sulfamethoxazole.[66]

Patients with fever should receive appropriate antipyretics. Measures to improve immunity should be instituted in immunocompromised patients: for example, antiretroviral therapy for HIV/AIDS, or a decrease of immunosuppressive agents in transplant patients.

Carrion's disease (Bartonella bacilliformis)

Oroya fever (acute phase Carrion's disease)

  • Treatment of Oroya fever should be initiated immediately upon diagnosis as mortality has been reported in 40% to 85% of untreated cases.[20]

  • The Peruvian government has released nationally standardised treatments for the acute phase that recommend ciprofloxacin as a first-line agent, owing to growing resistance to chloramphenicol.[67]​ Based on these guidelines, the following examples of treatment regimens have been recommended:[20]

    • In adults and adolescents (i.e., ≥14 years and ≥45 kg), uncomplicated cases are treated with oral ciprofloxacin for 14 days. Alternatives include amoxicillin/clavulanate, trimethoprim/sulfamethoxazole, or chloramphenicol. Severe cases are treated with ciprofloxacin plus ceftriaxone for 7-14 days. Alternative regimens for severe cases include ciprofloxacin plus either ceftazidime or amikacin.[20]

    • In pregnant or breastfeeding women, amoxicillin/clavulanate is recommended for uncomplicated cases, and ceftriaxone plus chloramphenicol for severe cases.[20]

    • In children aged <14 years, amoxicillin/clavulanate is recommended as the first-line treatment of uncomplicated cases, and ciprofloxacin plus ceftriaxone for severe cases.[20]

  • Patients with neurological manifestations should also receive dexamethasone. Other supportive measures include blood transfusion for severely anaemic patients and pericardiocentesis for patients who have pericarditis with effusion.[5][20]​​[48][68]

Verruga peruana (eruptive phase Carrion's disease)

  • Azithromycin is the recommended drug of choice for the treatment of verruga peruana in both adults and children. It is given orally for 7 days.[20]​ Azithromycin is also recommended for pregnant and breastfeeding women, but the dose and treatment course may differ.[20] Alternatives include rifampicin, ciprofloxacin, or erythromycin.[20][5][48][68]​ Ciprofloxacin is not recommended during pregnancy. Chloramphenicol and penicillins are not useful during this phase of infection.

  • Patients in the eruptive phase are usually less sick and do not need supportive care.

Bartonella vinsonii infection

There are case reports of the successful use of prolonged courses of doxycycline plus rifampicin with resolution of symptoms without relapse in patients infected with B vinsonii.[12] In one paediatric case, despite initial clinical improvement with azithromycin, the patient relapsed and was subsequently treated successfully with doxycycline. Consult a paediatric infectious disease expert for guidance on treatment of young children. Doxycycline is not recommended in children aged <8 years for longer than 21 days as tooth discoloration is a concern, but it may be used in severe infections when there are no effective alternatives.[57]​ In the UK, doxycycline is not recommended for children aged <12 years.

As demonstrated in the case reports, therapeutic progress can be monitored with follow-up serological testing.[12] 

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