Current treatment approach for human brucellosis

1. Uncomplicated disease in adults and children aged 8 years or older

2. Focal or complicated brucellosis

3. Children

• Age 8 years or older: doxycycline-based combination therapy may be used, usually with rifampicin or an initial aminoglycoside.
• Under age 8 years: avoid doxycycline in standard practice. Use trimethoprim-sulfamethoxazole (TMP-SMX) plus rifampicin for at least 6 weeks, with an aminoglycoside added initially for severe or focal infection.
• WHO states that the best regimen for young children is not fully established; TMP-SMX with rifampicin or an aminoglycoside is an accepted approach. WHO recommendations

4. Pregnancy

• Rifampicin, alone or combined with TMP-SMX, selected according to gestational age and clinical severity.
• TMP-SMX requires careful timing and folate considerations, and is generally avoided close to delivery because of neonatal bilirubin-related risk.

5. Important species-specific exception: Brucella abortus RB51

Key practice points

• Confirm diagnosis with culture, serology, or molecular testing where possible, and alert the laboratory when Brucella is suspected because of laboratory-acquired infection risk.
• Obtain focused assessment for spondylitis, sacroiliitis, epididymo-orchitis, endocarditis, and CNS involvement before labeling illness “uncomplicated.”
• Check interactions before prescribing rifampicin, including reduced effectiveness of many drugs such as hormonal contraceptives, anticoagulants, antiretrovirals, and some immunosuppressants.
• Monitor aminoglycoside renal toxicity and hearing/vestibular symptoms.
• Clinical recovery may take weeks to months. Recurrent fever after treatment needs evaluation for relapse, missed focal infection, nonadherence, or reinfection.
• Public-health notification requirements vary by country. In the US, brucellosis is nationally notifiable. CDC overview

Rifampicin: adverse effects, monitoring, and management

Expected and harmless

• Orange-red discoloration of urine, sweat, saliva, sputum, and tears. This is harmless, but may permanently stain soft contact lenses.
• Mild gastrointestinal upset: nausea, abdominal discomfort, reduced appetite.
• Mild headache, fatigue, or itch without rash can occur.

Important adverse effects

Monitoring plan

Before starting rifampicin

1. Medication and supplement review
   • Rifampicin is a strong enzyme inducer and can markedly lower concentrations of many medicines.
   • High-priority interactions include:
     • Hormonal contraception: pills, patches, rings, implants, and some oral progestins may be unreliable. Use a non-hormonal method or a regimen chosen by a clinician.
     • Warfarin: INR can fall substantially, requiring closer INR checks and dose adjustment.
     • HIV antiretrovirals: several regimens are contraindicated or need specialist substitution.
     • Immunosuppressants such as tacrolimus, cyclosporine, and sirolimus.
     • Some antifungals, antiseizure medicines, corticosteroids, direct oral anticoagulants, diabetes drugs, and opioid substitution therapy.
     • St John's wort can compound enzyme induction.
2. Baseline tests
   • ALT/AST, bilirubin, alkaline phosphatase.
   • CBC with platelet count.
   • Serum creatinine, with urinalysis if renal disease is suspected.
   • Pregnancy status and contraception plan where applicable.
3. Risk review
   • Existing liver disease, hepatitis B/C, regular alcohol intake, pregnancy/postpartum status, older age, malnutrition, HIV, and concurrent hepatotoxic medicines increase concern for liver injury.

During treatment

• Clinical review at least monthly, sooner during the first weeks or if high risk.
• Ask specifically about anorexia, nausea, vomiting, abdominal pain, jaundice, rash, fever, bruising/bleeding, urine output, and adherence.
• Repeat liver tests if symptoms occur, baseline tests are abnormal, liver-risk factors exist, or other hepatotoxic drugs are used. For brucellosis, this is especially relevant if rifampicin is combined with doxycycline and treatment is prolonged.
• Repeat CBC/platelets and creatinine if fever, rash, bleeding/bruising, anemia symptoms, or renal symptoms occur.
• If on warfarin, monitor INR very closely, especially when starting, stopping, or interrupting rifampicin.
• Check therapeutic drug monitoring or clinical effectiveness of narrow-therapeutic-index medicines, such as tacrolimus, when relevant.

When should rifampicin be stopped for possible hepatotoxicity?

• ALT/AST is at least 3 times the upper limit of normal with hepatitis symptoms, or
• ALT/AST is at least 5 times the upper limit of normal without symptoms, or
• bilirubin rises, jaundice develops, or there is impaired clotting/synthetic liver function.

Rechallenge

• Do not restart rifampicin yourself after a serious reaction.
• Avoid rechallenge after likely rifampicin-induced thrombocytopenia, hemolysis, nephritis, anaphylaxis, DRESS, SJS/TEN, or significant liver injury unless an infectious-disease or drug-allergy specialist makes a carefully monitored plan.
• After mild liver-enzyme elevation, clinicians usually exclude alternative causes, wait for recovery, then decide whether to reintroduce drugs sequentially or use an alternative regimen.