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CBRNE - Brucellosis: Treatment & Medication
Updated: Apr 29, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Prehospital Care
Prehospital care for brucellosis is supportive.
- As the symptoms generally are vague and presentation rarely life threatening, emergency medical service (EMS) care should focus on stabilization, as needed, and transport.
- If a proximate bioterrorist attack is known or strongly suggested at the time of patient contact, appropriately decontaminate the patient. In the event of a covert undiscovered attack, patients may become symptomatic well after the time that decontamination is necessary.
- As in the care of any patient with a potentially transmissible disease, use appropriate precautions (eg, gloves, mask, gown).
- If the patient presents as part of a known, immediately proximate bioterrorism incident, EMS providers should notify the hospital to undertake appropriate decontamination and isolation measures.
Emergency Department Care
Given the nonspecific patient complaints, a diagnosis of brucellosis is unlikely in the ED. With an appropriate history, an astute clinician may suspect it.
- Respiratory isolation usually is not necessary, as long as close contact with the respiratory tract is not made. Wear masks for intubation, suctioning, or other maneuvers that may expose the caregiver to a large concentration of aerosolized particles.
- The appropriate antibiotic therapy for brucellosis is combination therapy with doxycycline and rifampin or streptomycin. If brucellosis is strongly suggested, consult a specialist to determine the proper antibiotic regimen. There is some evidence of growing resistance to rifampin in some areas, though ciprofloxacin and aminoglycosides maintain good coverage.
- Provide supportive care for any specific symptoms and obtain appropriate tests targeted to affected organ systems as determined by history and physical.
Consultations
- The primary specialist to consult is an infectious disease specialist. Determine proper serologic tests, cultures, further diagnostic evaluations, and the correct antibiotic therapy in conjunction with the infectious disease specialist.
- Depending on the degree of damage to individual organ systems, contact the appropriate specialist (eg, cardiology for endocarditis).
Medication
The appropriate antibiotic therapy for brucellosis has been studied to some degree. Doxycycline (100 mg PO bid for 6 wk) is the most appropriate monotherapy in simple infection; however, relapse rates approach 40% for monotherapy treatment. Rifampin (600-900 mg/d) usually is added to doxycycline for a full 6-week course. In patients with spondylitis or sacroiliitis, doxycycline plus streptomycin (1 g/d IM for 3 wk) was found to be more effective than the doxycycline/rifampin combination. Streptomycin currently is favored over rifampin for combination therapy of any significant infection. In pediatric patients older than 8 years, doxycycline (5 mg/kg/d for 3 wk) plus gentamicin (5 mg/kg/d IM for the first 5 d) was the recommended therapy. For children younger than 8 years, trimethoprim/sulfamethoxazole (TMP-SMZ) for 3 weeks and a 5-day course of gentamicin were most effective. TMP-SMZ also was effective in treating pregnant women, either as a single agent or in combination with rifampin or gentamicin.
Fluoroquinolones have a high relapse rate when used as monotherapy. Fluoroquinolones added to doxycycline have no advantage over the other regimens described, but may be preferred in an area where resistance to rifampin is high. No uniform recommendation exists for treatment of meningitis or endocarditis; however, TMP-SMZ plus rifampin remains the preferred combination. In endocarditis, early replacement of the infected valve is recommended, along with medical therapy. Corticosteroids are recommended in CNS infection, but data supporting their utility are lacking. Also prescribe symptomatic treatment for pain and fever.
A meta-analysis comparing rates of resistance among several potential biological weapons found that doxycycline was the most effective antibiotic, with lower rates of resistance than seen with fluoroquinolones. In brucellosis, doxycycline for 45 days with either streptomycin or gentamicin seems to be the best regimen based on recent data.
Antibiotics
Indicated to abolish infection. Therapy must cover all likely pathogens in the context of the clinical setting.
Doxycycline (Doryx, Vibramycin, Bio-Tab)
Several different controlled and retrospective trials have established efficacy as treatment for brucellosis. Because of concerns regarding treatment failures, combination therapy with rifampin or an aminoglycoside now is recommended, although it remains approved for use as monotherapy.
Adult
200 mg/d PO, usually divided into 100 mg PO bid; may be administered IV if needed; duration is 3-6 wk
Pediatric
5 mg/kg/d PO for 3 wk
None reported
Documented hypersensitivity
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
May cause photosensitivity; can cause nausea and erosive esophagitis, especially if taken hs; may deposit in teeth, although less than with tetracycline; safe to use in renal failure
Rifampin (Rifadin, Rimactane)
Used in combination therapy with doxycycline, TMP-SMZ, or gentamicin for treatment of brucellosis.
Adult
600-900 mg PO/IV qd
Pediatric
10-20 mg/kg PO/IV qd; not to exceed 600 mg
Multiple drug-drug interactions; notably, decreases serum levels of most antiretrovirals; decreases effectiveness of beta-blockers; decreases effectiveness of oral contraceptives; decreases phenytoin levels; decreases effectiveness of anticoagulants and sulfonylureas; increases conversion of INH into its hepatotoxic metabolites; levels increase with concurrent use of antiretrovirals and TMP-SMZ; also decreases levels of methadone, precipitating withdrawal
Documented hypersensitivity; preexisting liver disease
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Monitor liver enzymes before starting therapy and repeat if symptoms of potential hepatotoxicity develop; causes brownish discoloration of body fluids; stains contact lenses; may cause drug-induced lupus; if taken irregularly or restarted after an interval of no medication, may cause "flu syndrome" with fever, chills, myalgias, and dyspnea
Sulfamethoxazole and trimethoprim (Bactrim, Septra)
Used as adjunctive therapy with gentamicin in treating infection in children <8 y; used as monotherapy or combined with rifampin or gentamicin to treat infection in pregnant females. Inhibits bacterial growth by inhibiting synthesis of dihydrofolic acid.
Adult
1 double strength tab PO bid (160/800)
8-10 mg/kg IV divided q6, 8, or 12h
Pediatric
5 mL/10 kg (40/200) PO bid
Competes with creatinine for tubular reabsorption and thus may increase serum creatinine; hyperkalemia observed in 20% of patients; may cause thrombocytopenia and aseptic meningitis; frequently causes GI disturbances; occasionally may cause severe reactions in form of Stevens-Johnson syndrome or TEN; increases levels of phenytoin, rifampin, and loperamide; increases activity of warfarin; enhances bone marrow suppression when administered with methotrexate; decreases effectiveness of oral contraceptives
Documented hypersensitivity; relatively contraindicated in asthmatics, as sensitivity to the sulfa molecule may cause bronchospasm; relatively contraindicated in thrombocytopenic patients, as thrombocytopenia may worsen
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Avoid in sulfa-allergic patients or in concurrent use with rifampin
Gentamicin (Garamycin, Gentacidin)
Aminoglycosides have been used for several years to treat brucellosis; studies to date have shown gentamicin to be the preferred aminoglycoside to treat infection as combined therapy with either TMP-SMZ or doxycycline in children. Adult dose is either once-daily dosing or a multiple-daily dose.
Adult
Once-daily dose: 5.1 mg/kg IV/IM qd
Multiple-daily dose: 2 mg/kg loading dose, IV followed by 1.7 mg/kg IV/IM q8h; continue for 5 d
Pediatric
5 mg/kg IM for 5 d, in combination with either doxycycline or TMP-SMZ
Increases nephrotoxicity of contrast agents, cyclosporin, cis -platinum, NSAIDs, amphotericin B, and vancomycin; increases ototoxicity of loop diuretics and noise; potentiates neuromuscular blocking agents
Documented hypersensitivity; avoid if possible in patients with impaired renal function or sensorineural deafness because of known nephrotoxicity and ototoxicity; once daily dosing is associated with decreased risk of nephrotoxicity
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution in patients with renal failure or if IV contrast is planned; check levels at minimum q3d and adjust dose based on level and calculated creatinine clearance
Streptomycin
Has been used for several years to treat brucellosis; used in combination with doxycycline, especially for spondylitis or sacroiliitis; augments bacteriocidal action of other agents used to treat brucellosis.
Adult
15 mg/kg IM; not to exceed 1 g/d IM qd for 3 wk
Pediatric
20-40 mg/kg IM qd; not to exceed 1 g qd
Increases nephrotoxicity of contrast agents, cyclosporin, cis -platinum, NSAIDs, amphotericin B, and vancomycin; increases ototoxicity of loop diuretics and noise; potentiates neuromuscular blocking agents
Documented hypersensitivity; if possible avoid in patients with preexisting renal disease or vestibular disease because of ototoxicity and nephrotoxicity
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution in renal failure and preexisting vestibulocochlear disease; adjust dose based on creatinine clearance ratio; determine BUN and creatinine prior to starting therapy; perform weekly audiograms for treatment duration
Corticosteroids
Indicated to reduce inflammation and improve neurologic outcome in patients with neurobrucellosis.
Dexamethasone (Decadron, AK-Dex)
Use of corticosteroids is reserved for symptomatic brucella meningitis. Although generally recommended, scientific evidence supporting their use is lacking. No consensus exists on optimal dosing, frequency, or duration of therapy.
Adult
0.15 mg/kg IV q8h
Pediatric
0.6 mg/kg/d IV divided into q6h doses for 2 d prior to starting antibiotics
Barbiturates, carbamazepine, phenytoin, rifampin, and isoniazid may reduce effectiveness; estrogens enhance effect
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Prolonged use may cause mood changes, seizures, hyperglycemia, GI bleeding, and HPA axis suppression; long-term use is rare
More on CBRNE - Brucellosis |
| Overview: CBRNE - Brucellosis |
| Differential Diagnoses & Workup: CBRNE - Brucellosis |
 Treatment & Medication: CBRNE - Brucellosis |
| Follow-up: CBRNE - Brucellosis |
| References |
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Further Reading
Keywords
Malta fever, Crimean fever, undulant fever, Brucella, zoonotic infection, brucellosis infection, brucellae, Brucella suis, Brucella melitensis, Brucella abortus, Brucella canis, Brucella species
