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

uncomplicated disease

1st line – dual antibiotic therapy

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ACUTE
|
uncomplicated disease
|
non-pregnant adults and children aged ≥8 years
1st line – 

dual antibiotic therapy

Brucellosis is considered uncomplicated if there are acute non-specific features in the absence of focal infection.

The World Health Organization recommends that adults and children aged ≥8 years should be treated with a tetracycline for 6 weeks (doxycycline is preferred due to its less frequent dose schedule and lower risk of adverse effects), plus either a parenteral aminoglycoside (streptomycin for 2-3 weeks or gentamicin for 7-10 days) or oral rifampicin for 6 weeks.[75] 

The US Centers for Disease Control and Prevention (CDC) recommend an oral regimen for uncomplicated disease (a tetracycline or trimethoprim/sulfamethoxazole plus rifampicin for a minimum of 6 weeks).[62]​​

Relapses are usually treated with the same regimen as initially used, as resistance to antimicrobials is rarely the cause.

Primary options

doxycycline: 100 mg orally twice daily

or

tetracycline: 500 mg orally four times daily

-- AND --

gentamicin: 5 mg/kg intramuscularly/intravenously once daily

or

streptomycin: 1 g intramuscularly once daily

Secondary options

doxycycline: 100 mg orally twice daily

or

tetracycline: 500 mg orally four times daily

-- AND --

rifampicin: 600-900 mg/day orally given in 1-2 divided doses

OR

trimethoprim/sulfamethoxazole: 160/800 mg orally twice daily

and

rifampicin: 600-900 mg/day orally given in 1-2 divided doses

1st line – dual antibiotic therapy or monotherapy

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ACUTE
|
uncomplicated disease
|
pregnant or breastfeeding adults
1st line – 

dual antibiotic therapy or monotherapy

Brucellosis is considered uncomplicated if there are acute non-specific features in the absence of focal infection.

Optimum treatment of pregnant and breastfeeding women is based on anecdotal reports.[58] A 6-week course of oral rifampicin is generally recommended.[41][42] Rifampicin plus trimethoprim/sulfamethoxazole for 4 weeks is an acceptable alternative.[58]

Trimethoprim/sulfamethoxazole is not recommended in the first trimester of pregnancy as it has been associated with an increased risk of congenital malformations. The recommended regimen should only be used if the benefits of treatment outweigh the risks.

A specialist should be consulted for guidance on antibiotic selection in these patients.

Primary options

rifampicin: 600-900 mg/day orally given in 1-2 divided doses

OR

rifampicin: 600-900 mg/day orally given in 1-2 divided doses

and

trimethoprim/sulfamethoxazole: 160/800 mg orally twice daily

More

1st line – dual antibiotic therapy

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ACUTE
|
uncomplicated disease
|
children aged <8 years
1st line – 

dual antibiotic therapy

Brucellosis is considered uncomplicated if there are acute non-specific features in the absence of focal infection.

Tetracyclines are generally contraindicated in children aged <8 years due to the risk of tooth discoloration and inhibition of bone growth. Therefore, tetracyclines can be replaced by trimethoprim/sulfamethoxazole in children aged <8 years. The World Health Organization (WHO) recommends trimethoprim/sulfamethoxazole for 6 weeks, plus either an aminoglycoside (streptomycin for 3 weeks or gentamicin for 7-10 days) or rifampicin for 6 weeks.[75]

The US Centers for Disease Control and Prevention (CDC) recommend an oral regimen for uncomplicated disease (trimethoprim/sulfamethoxazole plus rifampicin for 4-6 weeks).[62]​​

Primary options

trimethoprim/sulfamethoxazole: 8-10 mg/kg/day orally given in 2 divided doses

More

and

rifampicin: 15-20 mg/kg/day orally given in 1-2 divided doses, maximum 900 mg/day

OR

trimethoprim/sulfamethoxazole: 8-10 mg/kg/day orally given in 2 divided doses

More

-- AND --

gentamicin: 5 mg/kg intramuscularly/intravenously once daily

or

streptomycin: 30 mg/kg intramuscularly once daily

complicated disease

1st line – triple antibiotic therapy including an aminoglycoside

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ACUTE
|
complicated disease
|
without neurological manifestations
1st line – 

triple antibiotic therapy including an aminoglycoside

A triple antibiotic regimen is generally recommended for complicated infection, and courses may need to be prolonged for longer periods of time according to clinical and radiological response.[138]

There is little evidence regarding optimum duration of treatment in cases of complicated or focal disease (orchitis, sacroiliitis, spondylitis, endocarditis), but most authors favour triple antibiotic therapy for adults or adolescents with doxycycline and rifampicin (for at least 3-6 months) and an aminoglycoside (for the first 2 weeks only).[41][42][75][126][127]

In the absence of evidence, similar considerations may apply for children and should be evaluated on an individual basis for pregnant or breastfeeding women. Consultation with an infectious-diseases specialist is, therefore, advised before commencing treatment in pregnant or breastfeeding women and in children.

Doxycycline is generally not recommended in pregnancy due to concerns about fetal skeletal development and bone growth. Aminoglycosides are also not recommended in pregnancy due to concerns about fetal ototoxicity and renal toxicity. The recommended regimen should only be used if the benefits of treatment outweigh the risks.

Relapses are usually treated with the same regimen as initially used, as resistance to antimicrobials is rarely the cause.

Primary options

doxycycline: adults: 100 mg orally twice daily

-- AND --

rifampicin: adults: 600-900 mg/day orally given in 1-2 divided doses

-- AND --

gentamicin: adults: 5 mg/kg intramuscularly/intravenously once daily

or

streptomycin: adults: 1 g intramuscularly once daily

Consider – valve replacement

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ACUTE
|
complicated disease
|
without neurological manifestations
Consider – 

valve replacement

Additional treatment recommended for SOME patients in selected patient group

Brucella endocarditis usually affects the aortic valve and is responsible for a large proportion of the 1% to 5% mortality rate of brucellosis.[86]

Most patients end up needing valve replacement despite 6 months or more of antibiotic treatment.[5][41][42] There is evidence that early surgery improves mortality.[134]

1st line – triple antibiotic therapy excluding an aminoglycoside

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ACUTE
|
complicated disease
|
with neurological manifestations
1st line – 

triple antibiotic therapy excluding an aminoglycoside

A triple antibiotic regimen is generally recommended for complicated infection, and courses may need to be prolonged for longer periods of time according to clinical and radiological response.[138]

In cases of neurological manifestations (meningoencephalitis, focal brain or cranial nerve lesions), streptomycin or gentamicin use is usually discouraged because of questionable ability of aminoglycosides to penetrate the cerebrospinal fluid and the potential for neurotoxicity, which may further complicate the clinical presentation.[135] Ceftriaxone or trimethoprim/sulfamethoxazole may be added as the third drug for better central nervous system penetration.[41][42][48][135][136][137] Treatment is required for at least 6 months. 

In the absence of evidence, similar considerations may apply for children and should be evaluated on an individual basis for pregnant or breastfeeding women. Consultation with an infectious-diseases specialist is, therefore, advised before commencing treatment in pregnant or breastfeeding women and in children.

Doxycycline is generally not recommended in pregnancy due to concerns about fetal skeletal development and bone growth. Trimethoprim/sulfamethoxazole is not recommended in the first trimester of pregnancy as it has been associated with an increased risk of congenital malformations. The recommended regimen should only be used if the benefits of treatment outweigh the risks.

Relapses are usually treated with the same regimen as initially used, as resistance to antimicrobials is rarely the cause.

Primary options

doxycycline: adults: 100 mg orally twice daily

-- AND --

rifampicin: adults: 600-900 mg/day orally given in 1-2 divided doses

-- AND --

ceftriaxone: adults: 1-2 g intravenously/intramuscularly once daily

or

trimethoprim/sulfamethoxazole: adults: 160/800 mg orally twice daily

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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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