Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

acute infection, nonpregnant, no severe immunodeficiency: at low risk of persistent focalized infection

1st line – consider oral antibiotic therapy

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ACUTE
|
acute infection, nonpregnant, no severe immunodeficiency: at low risk of persistent focalized infection
1st line – 

consider oral antibiotic therapy

Acute infection is typically mild and self-limited, and usually spontaneously resolves within 2 weeks.[5][38]

Treatment is not recommended for patients with acute infection without valvulopathy who are asymptomatic. However, if symptomatic, it should be treated with oral antibiotics, as these may shorten the duration of the disease and decrease hospitalization risk.[87]​ Treatment is most effective if given within the first three days of symptom onset.[33]​

The recommended first-line treatment is doxycycline.[26] If the patient cannot tolerate doxycycline, then other antibiotics may be used (e.g., moxifloxacin, clarithromycin, rifampin, or trimethoprim/sulfamethoxazole).[2][84]​

Systemic fluoroquinolone antibiotics such as moxifloxacin may cause serious, disabling, and potentially long-lasting or irreversible adverse events. This includes, but is not limited to: tendinopathy/tendon rupture; peripheral neuropathy; arthropathy/arthralgia; aortic aneurysm and dissection; heart valve regurgitation; dysglycemia; and central nervous system effects including seizures, depression, psychosis, and suicidal thoughts and behavior.[88]​ Prescribing restrictions apply to the use of fluoroquinolones, and these restrictions may vary between countries. In general, fluoroquinolones should be restricted for use in serious, life-threatening bacterial infections only. Some regulatory agencies may also recommend that they must only be used in situations where other antibiotics, that are commonly recommended for the infection, are inappropriate (e.g., resistance, contraindications, treatment failure, unavailability). Consult your local guidelines and drug formulary for more information on suitability, contraindications, and precautions.

Treatment course: 14 days.

Primary options

doxycycline: 100 mg orally twice daily

Secondary options

moxifloxacin: 400 mg orally once daily

OR

clarithromycin: 500 mg orally (immediate-release) twice daily

OR

rifampin: 300 mg orally twice daily

OR

sulfamethoxazole/trimethoprim: 160 mg orally twice daily

More

Plus – supportive care

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ACUTE
|
acute infection, nonpregnant, no severe immunodeficiency: at low risk of persistent focalized infection
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Patients with acute infection should be advised to rest in bed and drink plenty of fluids.

Antitussives can be used for cough.

Acetaminophen or nonsteroidal anti-inflammatory drugs (NSAIDs) are not recommended for fever and discomfort since they can worsen liver involvement and worsen infection, respectively.

acute infection, nonpregnant, no severe immunodeficiency: at high risk of persistent focalized infection

1st line – doxycycline plus hydroxychloroquine

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ACUTE
|
acute infection, nonpregnant, no severe immunodeficiency: at high risk of persistent focalized infection
|
with IgG aCL antibodies ≥75 GPLU
1st line – 

doxycycline plus hydroxychloroquine

Patients with acute infection and high levels of IgG anticardiolipin (aCL) antibodies (i.e., ≥75 GPLU [G antiphospholipid units]) are at risk of valvulopathy, vegetation (in acute endocarditis), and progression to chronic endocarditis and thrombosis.[55][57][71][77]

The immunomodulatory drug hydroxychloroquine can prevent the thrombogenic properties of antiphospholipid antibodies.[89][90][91][92] Hydroxychloroquine can also reduce the risk of developing persistently positive antiphospholipid antibodies and lupus anticoagulant.[93][94] Therefore, combination treatment with doxycycline plus hydroxychloroquine is recommended for patients with IgG aCL antibodies ≥75 GPLU.

High-risk populations should be screened for glucose-6-phosphate dehydrogenase deficiency before receiving hydroxychloroquine therapy.

Treatment course: patients should be given this combination therapy until IgG aCL levels are reduced to <75 GPLU.

Primary options

doxycycline: 100 mg orally twice daily

and

hydroxychloroquine sulfate: 200 mg orally three times daily

Plus – supportive care

Back
ACUTE
|
acute infection, nonpregnant, no severe immunodeficiency: at high risk of persistent focalized infection
|
with IgG aCL antibodies ≥75 GPLU
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Patients with acute infection should be advised to rest in bed and drink plenty of fluids.

Antitussives can be used for cough.

Acetaminophen or NSAIDs are not recommended for fever and discomfort since they can worsen liver involvement and worsen infection, respectively.

1st line – doxycycline plus hydroxychloroquine

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ACUTE
|
acute infection, nonpregnant, no severe immunodeficiency: at high risk of persistent focalized infection
|
with significant valvulopathy
1st line – 

doxycycline plus hydroxychloroquine

Patients with acute infection and significant valvulopathy (e.g., history of rheumatic fever, bicuspid aortic valve, congenital heart disease, prosthetic heart valves, valve regurgitation, stenosis grade ≥II, mitral valve prolapse) are at high risk of endocarditis, which can be fatal if left untreated.

In these patients, combination treatment with doxycycline plus hydroxychloroquine for 12 months is recommended. This combination treatment has been shown to be highly effective in preventing endocarditis in such at-risk patients.[45]

High-risk populations should be screened for glucose-6-phosphate dehydrogenase deficiency before receiving hydroxychloroquine therapy.

For all acute infections with valvulopathy, monthly serologic and drug monitoring is of critical importance, and is associated with therapeutic success.[101][102][103] Doxycycline levels should be maintained at 5-10 mg/L and hydroxychloroquine levels at 0.8 to 1.2 mg/L.[104] The main causes of treatment failure and relapse are lack of monthly drug monitoring, insufficient levels of drug in the plasma, and absence of surgery in patients with vascular infections.

Treatment course: 12 months.

Primary options

doxycycline: 100 mg orally twice daily

and

hydroxychloroquine sulfate: 200 mg orally three times daily

Plus – supportive care

Back
ACUTE
|
acute infection, nonpregnant, no severe immunodeficiency: at high risk of persistent focalized infection
|
with significant valvulopathy
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Patients with acute infection should be advised to rest in bed and drink plenty of fluids.

Antitussives can be used for cough.

Acetaminophen or NSAIDs are not recommended for fever and discomfort since they can worsen liver involvement and worsen infection, respectively.

1st line – doxycycline plus hydroxychloroquine

Back
ACUTE
|
acute infection, nonpregnant, no severe immunodeficiency: at high risk of persistent focalized infection
|
with history of vascular graft or aneurysm: negative PET/CT scan
1st line – 

doxycycline plus hydroxychloroquine

Patients with acute infection and a history of vascular graft or aneurysm plus a negative 18F-fluorodeoxyglucose (FDG) PET/CT are at risk of developing persistent focalized infections (e.g., endocarditis).

High-risk populations should be screened for glucose-6-phosphate dehydrogenase deficiency before receiving hydroxychloroquine therapy.

Treatment course: 12 months.

Primary options

doxycycline: 100 mg orally twice daily

and

hydroxychloroquine sulfate: 200 mg orally three times daily

Plus – supportive care

Back
ACUTE
|
acute infection, nonpregnant, no severe immunodeficiency: at high risk of persistent focalized infection
|
with history of vascular graft or aneurysm: negative PET/CT scan
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Patients with acute infection should be advised to rest in bed and drink plenty of fluids.

Antitussives can be used for cough.

Acetaminophen or NSAIDs are not recommended for fever and discomfort since they can worsen liver involvement and worsen infection, respectively.

acute infection, nonpregnant, with severe immunodeficiency

1st line – doxycycline

Back
ACUTE
|
acute infection, nonpregnant, with severe immunodeficiency
1st line – 

doxycycline

Patients with acute infection and severe immunodeficiency (e.g., transplant patients, patients undergoing chemotherapy or corticosteroid therapy, patients with HIV and <200 CD4+ T cells, and patients with hematologic malignancy) are at high risk of developing persistent focalized infections, such as endocarditis.[95] Their care should be undertaken in consultation with an infectious disease specialist.

Doxycycline alone is recommended for these patients. Hydroxychloroquine is not recommended in these patients.

Long-term doxycycline is recommended for patients with long-term immunodeficiency until the immunosuppression has resolved as reactivation can occur several months after primary infection in those who are immunocompromised.

In patients undergoing long-term doxycycline treatment (e.g., those who are immunocompromised), drug monitoring is of critical importance and is associated with therapeutic success.[101][102][103] Doxycycline should be maintained at 5-10 mg/L.[104] A lack of drug monitoring and/or insufficient levels of drug in the plasma may lead to treatment failure and relapse.

Treatment course: until immunosuppression has resolved.

Primary options

doxycycline: 100 mg orally twice daily

Plus – supportive care

Back
ACUTE
|
acute infection, nonpregnant, with severe immunodeficiency
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Patients with acute infection should be advised to rest in bed and drink plenty of fluids.

Antitussives can be used for cough.

Acetaminophen or NSAIDs are not recommended for fever and discomfort since they can worsen liver involvement and worsen infection, respectively.

acute infection, pregnant

1st line – trimethoprim/sulfamethoxazole

Back
ACUTE
|
acute infection, pregnant
1st line – 

trimethoprim/sulfamethoxazole

The care of pregnant women with acute infection should be undertaken in consultation with an infectious disease specialist and obstetric specialist. In pregnant women, long-term therapy with trimethoprim/sulfamethoxazole has been shown to protect against obstetric complications, including intrauterine death, spontaneous abortion, and premature delivery.[26][96]

Treatment with trimethoprim/sulfamethoxazole should not be given beyond 32 weeks gestation due to the risk of neonatal hemolysis.

After delivery, mothers with acute infection should be evaluated for risk of persistent focalized infection (e.g., endocarditis) and managed accordingly.

Primary options

sulfamethoxazole/trimethoprim: 160 mg orally twice daily

More

Plus – supportive care

Back
ACUTE
|
acute infection, pregnant
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Patients with acute infection should be advised to rest in bed and drink plenty of fluids.

Antitussives can be used for cough if not specifically contraindicated in pregnancy.

Acetaminophen or NSAIDs are not recommended for fever and discomfort since they can worsen liver involvement and worsen infection, respectively.

ONGOING

suspected or confirmed persistent focalized infection, with no severe immunodeficiency

1st line – doxycycline plus hydroxychloroquine

Back
ONGOING
|
suspected or confirmed persistent focalized infection, with no severe immunodeficiency
|
endocarditis
1st line – 

doxycycline plus hydroxychloroquine

Endocarditis is the most frequent persistent focalized infection (up to 70% of cases).[2]

The recommended treatment for C burnetii endocarditis is oral doxycycline plus hydroxychloroquine for 18 months in patients with native valve endocarditis, or for 24 months in those with prosthetic valve endocarditis or with foreign body-related C burnetii endocarditis (e.g., from a cardiovascular implantable electronic device/pacemaker).[2][5][98][26][86]

In patients with an implanted artificial pacemaker device, an 18F-FDG PET/CT scan is recommended.[22] If the scan shows high FDG uptake on the pacemaker device, the pacemaker pocket should be changed after 1 month of treatment has been completed. If PET/CT scan shows high FDG uptake on the intracavitary leads, there is no immediate need for removal, but a PET/CT scan should be performed again after 2 months of treatment. Expert opinion is required if high FDG uptake persists on the scan.

C burnetii endocarditis may be diagnosed in patients with severe heart valve disease (cardiac surgery unit) who have phase I IgG levels as low as 1:200.[105][106] In this specific context, treatment of endocarditis and vascular infection must be prescribed, even in the absence of infectious symptoms or absence of a positive PCR for C burnetii since mortality risk is high if left untreated.

Antibiotics should be prolonged in absence of good serologic outcome (i.e., two-fold decrease in dilution titer of phase I IgG, and absence of phase II IgM at 1 year).[86] In this case, monitoring should continue and drugs levels should be repeatedly measured to verify therapeutic drug levels. An expert opinion should be obtained if therapeutic drug levels are achieved without improvement in serologic outcomes.

For all persistent focalized infections, monthly serologic and drug monitoring is of critical importance, and is associated with therapeutic success.[101][102][103] Doxycycline should be maintained at 5-10 mg/L and hydroxychloroquine at 0.8 to 1.2 mg/L.[104] A lack of drug monitoring and/or insufficient levels of drug in the plasma may lead to treatment failure and relapse.

High-risk populations should be screened for glucose-6-phosphate dehydrogenase deficiency before receiving hydroxychloroquine therapy.

Treatment course: 18 (native valve endocarditis) or 24 months (prosthetic valve or foreign body-related endocarditis).

Primary options

doxycycline: 100 mg orally twice daily

and

hydroxychloroquine sulfate: 200 mg orally three times daily

Consider – valve replacement surgery

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ONGOING
|
suspected or confirmed persistent focalized infection, with no severe immunodeficiency
|
endocarditis
Consider – 

valve replacement surgery

Treatment recommended for SOME patients in selected patient group

Surgery should not be carried out routinely in patients with endocarditis.

Valve replacement surgery should only be considered for patients with infective endocarditis who have hemodynamic compromise.

If non-urgent surgery is required, this should be done following 3 weeks of antibiotic treatment.

1st line – doxycycline plus hydroxychloroquine

Back
ONGOING
|
suspected or confirmed persistent focalized infection, with no severe immunodeficiency
|
vascular infection, with or without vascular prosthetic material
1st line – 

doxycycline plus hydroxychloroquine

Vascular infections are a very important challenge in C burnetii infection treatment because antibiotics do not prevent vascular rupture.

The recommended treatment for C burnetii vascular infections is oral doxycycline plus hydroxychloroquine for 18 months in patients without vascular prosthetic material, or for 24 months in those with vascular prosthetic material, plus routine surgical resection of infected vascular tissue or infected vascular prosthetic material after 3 to 4 weeks of antibiotic treatment, unless surgery is urgently required.

For all persistent focalized infections, monthly serologic and drug monitoring is of critical importance, and is associated with therapeutic success.[101][102][103] Doxycycline should be maintained at 5-10 mg/L and hydroxychloroquine at 0.8 to 1.2 mg/L.[104] A lack of drug monitoring and/or insufficient levels of drug in the plasma may lead to treatment failure and relapse.

High-risk populations should be screened for glucose-6-phosphate dehydrogenase deficiency before receiving hydroxychloroquine therapy.

Treatment course: 18 (without vascular prosthetic material) or 24 months (with vascular prosthetic material).

Primary options

doxycycline: 100 mg orally twice daily

and

hydroxychloroquine sulfate: 200 mg orally three times daily

Plus – surgical resection

Back
ONGOING
|
suspected or confirmed persistent focalized infection, with no severe immunodeficiency
|
vascular infection, with or without vascular prosthetic material
Plus – 

surgical resection

Treatment recommended for ALL patients in selected patient group

Surgical resection of infected vascular tissue or prosthetic material should be carried out routinely in patients who have confirmed vascular infection as antibiotics alone do not prevent vascular rupture.[100]

Surgical resection is associated with an improved prognosis in vascular infection.[100] Absence of surgery may lead to treatment failure and relapse.

Timing for surgery is 3 to 4 weeks after initiation of antibiotic treatment, unless surgery is urgently required.

suspected or confirmed persistent focalized infection, with severe immunodeficiency

1st line – doxycycline

Back
ONGOING
|
suspected or confirmed persistent focalized infection, with severe immunodeficiency
|
endocarditis
1st line – 

doxycycline

Long-term doxycycline alone is recommended for patients with C burnetii endocarditis who have severe immunodeficiency (e.g., transplant patients, patients receiving chemotherapy or corticosteroid therapy, patients with HIV and <200 CD4+ T cells, or patients with hematologic malignancy).

Minimum duration of antibiotic treatment is 18 months if native valve, and 24 months if foreign-body related endocarditis.

Doxycycline should be prolonged in absence of good serologic outcome (i.e., two-fold decrease in dilution titer of phase I IgG, and absence of phase II IgM at 1 year).[86] In this case, monitoring should continue and drug levels should be repeatedly measured to verify therapeutic drug levels. An expert opinion should be obtained if therapeutic drug levels are achieved without improvement in serologic outcomes. 

For all persistent focalized infections, monthly serologic and drug monitoring is of critical importance, and is associated with therapeutic success.[101][102][103] Doxycycline should be maintained at 5-10 mg/L.[104] A lack of drug monitoring and/or insufficient levels of drug in the plasma may lead to treatment failure and relapse.

Treatment course: 18 (native valve endocarditis) or 24 months (prosthetic valve- or foreign body-related endocarditis).

Primary options

doxycycline: 100 mg orally twice daily

Consider – valve replacement surgery

Back
ONGOING
|
suspected or confirmed persistent focalized infection, with severe immunodeficiency
|
endocarditis
Consider – 

valve replacement surgery

Treatment recommended for SOME patients in selected patient group

Surgery should not be carried out routinely in patients with endocarditis.

Valve replacement surgery should only be considered for patients with infective endocarditis who have hemodynamic compromise.

If non-urgent surgery is required, this should be done following 3 weeks of antibiotic treatment.

1st line – doxycycline

Back
ONGOING
|
suspected or confirmed persistent focalized infection, with severe immunodeficiency
|
vascular infection, with or without vascular prosthetic material
1st line – 

doxycycline

Vascular infections are a very important challenge in the treatment of C burnetii infection because antibiotics do not prevent vascular rupture.

Long-term doxycycline alone is recommended for patients with C burnetii vascular infection who have severe immunodeficiency (e.g., transplant patients, patients receiving chemotherapy or corticosteroid therapy, patients with HIV and <200 CD4+ T cells, or patients with hematologic malignancy), plus routine surgical resection of infected vascular tissue or infected vascular prosthetic material after 3 to 4 weeks of antibiotic treatment, unless surgery is urgently required.

Minimum duration of antibiotics treatment is 18 months in patients without vascular prosthetic material, or 24 months in those with vascular prosthetic material.

Doxycycline should be prolonged in absence of good serologic outcome (i.e., two-fold decrease in dilution titer of phase I IgG, and absence of phase II IgM at 1 year).[86] In this case, monitoring should continue and drug levels should be repeatedly measured to verify therapeutic drug levels. An expert opinion should be obtained if therapeutic drug levels are achieved without improvement in serologic outcomes. 

For all persistent focalized infections, monthly serologic and drug monitoring is of critical importance, and is associated with therapeutic success.[101][102][103] Doxycycline should be maintained at 5-10 mg/L.[104] A lack of drug monitoring and/or insufficient levels of drug in the plasma may lead to treatment failure and relapse.

Treatment course: 18 (without vascular prosthetic material) or 24 months (with vascular prosthetic material).

Primary options

doxycycline: 100 mg orally twice daily

Plus – surgical resection

Back
ONGOING
|
suspected or confirmed persistent focalized infection, with severe immunodeficiency
|
vascular infection, with or without vascular prosthetic material
Plus – 

surgical resection

Treatment recommended for ALL patients in selected patient group

Surgical resection of infected vascular tissue or prosthetic material should be carried out routinely in patients with confirmed vascular infection as antibiotics alone do not prevent vascular rupture.[100]

Surgical resection is associated with an improved prognosis in vascular infection.[100] Absence of surgery may lead to treatment failure and relapse.

Timing for surgery is 3 to 4 weeks after initiation of antibiotic treatment, unless surgery is urgently required.

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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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