What is the best drug for brucellosis? A guide to combination therapy

October 6, 2025 •

4 min read

With over 500,000 new cases reported globally each year, brucellosis is a widespread zoonotic infection that requires specific antibiotic combinations to prevent treatment failure and relapse. The question of what is the best drug for brucellosis is complex, as the optimal regimen depends on factors like severity, patient age, and potential drug side effects.

Quick Summary

Brucellosis treatment relies on combination antibiotic regimens to reduce relapse risk. Standard approaches include doxycycline with either streptomycin or rifampin, with adjustments for patient needs and complications.

Key Points

Combination Therapy is Essential: Single antibiotic therapy for brucellosis carries a high risk of relapse and is not recommended.
Doxycycline + Aminoglycoside is Most Effective: The regimen combining doxycycline with streptomycin or gentamicin has the lowest reported relapse rates for uncomplicated brucellosis.
Doxycycline + Rifampicin is a Convenient Alternative: The all-oral doxycycline and rifampicin regimen offers better convenience and compliance but has a higher relapse risk than the aminoglycoside combination.
Consider Alternatives for Special Populations: Tetracyclines are contraindicated in pregnant women and children under 8, necessitating alternative regimens such as rifampicin with cotrimoxazole.
Triple Therapy for Complicated Cases: For severe or focal disease, a three-drug regimen including an aminoglycoside is often necessary for a longer duration to maximize treatment success.
Consult a Specialist for Best Results: Due to the disease's complexity and the nuances of different regimens, seeking guidance from an infectious disease specialist is recommended for optimal treatment.

Brucellosis, also known as Malta fever, is a bacterial infection spread from animals to humans, often through consuming unpasteurized dairy products. The bacteria, primarily Brucella spp., can cause a range of non-specific, flu-like symptoms, making diagnosis challenging. Because the bacteria can live inside cells, effective treatment requires a long course of combination antibiotic therapy to prevent high rates of relapse. Monotherapy, or using a single antibiotic, is generally discouraged due to poor outcomes. Treatment success depends on selecting the right combination, ensuring adequate duration, and achieving high patient adherence.

The Standard Approach to Brucellosis Treatment

For adults with uncomplicated brucellosis, medical organizations like the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC) recommend specific combination therapies. The choice of regimen balances efficacy, administration route, and patient tolerability.

Doxycycline Plus an Aminoglycoside

This regimen is widely considered the most effective for uncomplicated brucellosis, largely due to lower relapse rates compared to all-oral regimens.

Doxycycline: Typically administered orally for a duration of several weeks.
Streptomycin: Often administered intramuscularly for a period of 2 to 3 weeks as the traditional aminoglycoside option.
Gentamicin: Can be used as an alternative to streptomycin, administered intravenously or intramuscularly for a shorter duration, and is often more widely available.

Doxycycline Plus Rifampicin (All-Oral Regimen)

This is a common alternative due to its convenience as a fully oral regimen, which can improve patient compliance.

Doxycycline: Typically administered orally twice daily for several weeks.
Rifampicin: Often administered orally once daily for several weeks.

Considerations for Standard Regimens

While the doxycycline-aminoglycoside combination boasts a lower relapse rate (as low as 4.6%), the inconvenience and pain of injections can be a drawback for some patients. The all-oral doxycycline-rifampicin regimen, despite being more convenient, is associated with a higher relapse risk. The choice between these two main approaches often depends on patient preference, resource availability, and specific disease factors.

Comparing the Main Treatment Regimens


Feature	Doxycycline + Streptomycin (or Gentamicin)	Doxycycline + Rifampicin
Effectiveness (Relapse Rate)	Lower relapse rate (as low as 4.6% with DS).	Higher relapse rate (up to 16%) compared to the aminoglycoside regimen.
Administration	Requires parenteral (intramuscular or intravenous) administration of streptomycin or gentamicin.	Fully oral regimen, increasing patient convenience and adherence.
Tolerability	Potential for ototoxicity or nephrotoxicity with aminoglycosides, especially in older patients.	Potential for gastrointestinal side effects and drug interactions with rifampicin.
Primary Indication	Preferred for severe or complicated cases, especially in younger adults.	Suitable for uncomplicated cases where injection-based therapy is not feasible or desirable.
Evidence Level	High (AI), considered the gold standard for efficacy.	High (AI), but with known trade-offs for convenience.

Alternative and Special Considerations

Quinolone-Based Regimens: Combinations involving quinolones (e.g., ciprofloxacin, ofloxacin) with rifampicin are used, but clinical evidence suggests higher relapse rates compared to standard regimens. Quinolone monotherapy should be avoided due to very high relapse rates.
Triple Therapy: For severe or complicated cases, such as endocarditis or spinal brucellosis, a three-drug regimen (e.g., doxycycline, rifampicin, and an aminoglycoside) may be used for an extended duration. This can improve outcomes and reduce relapse rates in complex situations.
Rifampin and Cotrimoxazole: For pregnant women and children under 8 years, where tetracyclines are contraindicated, a combination of rifampicin and cotrimoxazole (trimethoprim-sulfamethoxazole) is the preferred treatment.

Factors Influencing Treatment Choice

Choosing the best regimen involves a careful evaluation of several factors:

Infection Severity and Type: Complicated cases involving the spine (spondylitis), heart (endocarditis), or central nervous system (neurobrucellosis) require longer, and potentially more aggressive, therapy, often involving three drugs.
Patient Age: Doxycycline is typically avoided in children under 8 due to the risk of dental staining. Age also affects the choice of aminoglycoside, as older patients face a higher risk of nephrotoxicity and ototoxicity.
Pregnancy: Tetracyclines and quinolones are contraindicated during pregnancy. Safer options like rifampicin plus cotrimoxazole are used, with cotrimoxazole avoided near term.
Patient Preference and Compliance: A patient's ability to complete a full course of treatment, including tolerating side effects and inconvenience, is critical for success. The convenience of an all-oral regimen must be weighed against its higher relapse risk.
Local Epidemiology: In regions where tuberculosis is prevalent, the long-term use of rifampicin for brucellosis can potentially contribute to drug resistance in tuberculosis. This may lead clinicians to favor alternative regimens like those containing aminoglycosides.

Conclusion: Choosing the Right Drug for Brucellosis

No single drug is the solution for brucellosis; rather, combination therapy for an extended period is essential to achieve cure and prevent relapse. The most effective option for uncomplicated adult cases is a combination of doxycycline and an aminoglycoside like streptomycin or gentamicin, but this involves injections. The all-oral regimen of doxycycline and rifampicin is a more convenient alternative but carries a higher risk of relapse. For special populations such as young children and pregnant women, specific, safer regimens are necessary. Ultimately, the selection of the best drug for brucellosis is a clinical decision that requires careful consideration of the infection type, the patient's individual circumstances, and local disease patterns. Consulting an infectious disease specialist is often recommended to determine the most appropriate course of action and ensure the best possible outcome.

For more information on brucellosis, including guidance on exposure, testing, and prevention, consult reliable sources like the CDC's official website.

Frequently Asked Questions

Brucellosis bacteria, Brucella spp., can reside inside host cells, making them difficult for a single antibiotic to eradicate completely. Monotherapy is associated with high relapse rates, which is why a combination of two or more antibiotics is the standard of care.

For uncomplicated brucellosis, treatment typically involves a 6-week course of antibiotics. For complicated or severe cases, such as those with focal infections, the duration of therapy is often extended to 8 weeks or more.

Doxycycline is generally contraindicated in children under 8 years of age due to the risk of dental discoloration. In these cases, alternative regimens, such as rifampicin combined with cotrimoxazole, are recommended.

While both are recommended regimens, the doxycycline and streptomycin combination is generally considered more effective, with a lower relapse rate. The doxycycline and rifampicin regimen is more convenient as it is all-oral, but it is associated with a higher risk of relapse.

Pregnant women cannot take tetracyclines (like doxycycline) or quinolones. The most commonly recommended regimen is a combination of rifampicin and cotrimoxazole, though cotrimoxazole may be avoided near term.

Gentamicin can be used as a substitute for streptomycin in combination therapy. It can be administered for a shorter period (e.g., 7–10 days) and may be more widely available in certain regions.

A brucellosis relapse is a recurrence of clinical symptoms and elevated Brucella antibody titers after initially responding to treatment. Relapses typically occur within 6 to 12 months after treatment ends. Risk factors include inadequate treatment duration, non-adherence, or certain focal infections.

Combination therapy is required because the Brucella bacteria are intracellular, meaning they hide and multiply inside the body's cells, making them harder to target. Combining drugs that act on the bacteria in different ways improves the chances of eradicating the infection completely and reduces the risk of relapse.