Treatment of Brucellosis

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• Treatment of Brucellosis
• Shahid Beheshti University of medical sciences
• April 2008
• By Hatami H. MD. MPH

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Antimicrobial therapy

• Shortens the course of illness
• Lessens morbidity
• Reduce the incidence of complications

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Antimicrobial therapy

• Antimicrobial treatment must always be prescribed
• Prolonged treatment is more likely to achieve
  permanent cure

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Antimicrobial Regimens

• Doxycycline Rifampin
• Tetracycline Rifampin
• Tetracycline Streptomycin
• Co-trimoxazole Rifampin
• 3.G. Cephalosporines Ritampin
• Rifampin Doxycycline is the treatment of choice
  (WHO)

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Doxycycline

• Trials have established efficacy as treatment for
  brucellosis.
• Because of concerns regarding treatment failures,
  combination therapy with rifampin or an
  aminoglycoside now is recommended

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Doxycycline Adult dose

• 200 mg/d,
• usually divided into 100 mg PO bid
• may be administered IV if needed
• duration is 3-6 wk

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Doxycycline Pediatric dose

• 5 mg/kg/d PO for 3 wk

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Doxycycline Pregnancy

• D - Unsafe in pregnancy

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Doxycycline 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

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Rifampin

• Rifampin (Rifadin, Rimactane)
• Used in combination therapy with Doxycycline,
  TMP-SMZ, or Gentamicin for treatment of
  brucellosis.

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Rifampin Adult dose

• 600-900 mg PO/IV qd

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Rifampin Pediatric dose

• 10-20 mg/kg PO/IV qd, not to exceed 600 mg

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Rifampin / Interactions

• 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
• Decreases levels of methadone, precipitating
  withdrawal

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Rifampin Pregnancy

• Safety for use during pregnancy has not been
  established.

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Rifampin / Precautions

• Monitor liver enzymes before starting therapy and
  repeat if symptoms of potential hepatotoxicity
  develop
• Brownish discoloration of body fluids
• Stains contact lenses
• May cause drug-induced lupus
• Flu syndrome if taken irregularly or restarted
  after an interval of no medication, (fever,
  chills, myalgias, and dyspnea)

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Co-trimoxazole

• (Bactrim, Septrin)
• Used as adjunctive therapy with Gentamicin in
  treating infection in children lt8 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.

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Co-trimoxazole

• Results of Co-trimoxazole treatment in acute
  brucellosis have been very encouraging
• Disappearance of symptoms within 48 hours and
  normal temperatures within first week have been
  found
• Must be considered in treatment of
  neurobrucellosis, endocarditis, brucellosis in
  pregnancy and children . . .

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Co-trimoxazole Adult dose

• 2 tabs PO bid (160/800)8-10 mg/kg IV divided q6,
  8, or 12h

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Co-trimoxazole Pediatric dose

• 5 mL/10 kg PO bid 5 mL 40/200

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Co-trimoxazole Contraindications

• Documented hypersensitivity
• Relatively contraindicated in asthmatics, as
  sensitivity to the sulfa molecule may cause
  bronchospasm
• Relatively contraindicated in thrombocytopenic
  patients, as thrombocytopenia may worsen

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Co-trimoxazole Contraindications

• 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

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Co-trimoxazole Contraindications

• Increases levels of phenytoin, rifampin, and
  loperamide
• Increases activity of warfarin
• Enhances bone marrow suppression when
  administered with methotrexate
• Decreases effectiveness of oral contraceptives

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Co-trimoxazole Pregnancy

• C - Safety for use during pregnancy has not been
  established.

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Co-trimoxazole Precautions

• Avoid in sulfa-allergic patients or in concurrent
  use with rifampin

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Gentamicin

• Gentamicin (Garamycin, Gentacidin)
• 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.

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Gentamicin Adult dose

• Once daily dose 5.1 mg/kg IV/IM qd
• Multiple daily dose 2 mg/kg loading dose,
  followed by 1.7 mg/kg IV/IM q8h continue for 5 d

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Gentamicin Pediatric dose

• 5 mg/kg IM for 5 d, in combination with either
  doxycycline or TMP-SMZ

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Gentamicin Contraindications

• 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

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Gentamicin Interactions

• Increases nephrotoxicity of contrast agents,
  cyclosporin, cis-platinum, NSAIDs, amphotericin
  B, and vancomycin
• Increases ototoxicity of loop diuretics and
  noise potentiates neuromuscular blocking agents

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Gentamicin Pregnancy

• D - Unsafe in pregnancy

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Gentamicin 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

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Streptomycin

• Used in combination with doxycycline, especially
  for spondylitis or sacroiliitis
• Augments bacteriocidal action of other agents
  used to treat brucellosis.

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Streptomycin Adult dose

• 15 mg/kg, not to exceed 1 g/d IM qd for 3 wk

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Streptomycin Pediatric dose

• 20-40 mg/kg IM qd, not to exceed 1 g qd

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Streptomycin Contraindications

• Documented hypersensitivity
• If possible avoid in patients with preexisting
  renal disease or vestibular disease because of
  ototoxicity and nephrotoxicity

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Streptomycin Interactions

• Increases nephrotoxicity of contrast agents,
  cyclosporin, cis-platinum, NSAIDs, amphotericin
  B, and vancomycin
• Increases ototoxicity of loop diuretics and
  noise potentiates neuromuscular blocking agents

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Streptomycin Pregnancy

• D - Unsafe in pregnancy

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Streptomycin 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

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Brucellosis Exposure to Vaccines

• These are live vaccines, and B-19 is known to
  cause disease in humans.
• For the other vaccines the recommendations are
  the same
• A baseline blood sample should be collected for
  testing for antibodies

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Brucellosis Occupational exposure

• Antibiotics (doxycycline and rifampin for B-19
  and REV-1, or doxycycline alone for RB-51) for 3
  weeks
• At the end of that time you should be rechecked
  and a second blood sample should be collected.
• The same recommendations hold true for spraying
  vaccine in the eyes (6 weeks of treatment in this
  case) or spraying onto open wounds on the skin
• CDC, 2004

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Brucellosis Antibiotics not recommended

• Most penicillins
• Most cephalosporins
• Chloramphenicol
• Erythromycin
• Kanamycin
• Sulfonamides

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Chronic brucellosis

• The patient with chronic brucellosis presents a
  difficult therapeutic problem
• Long courses (2-6 months) of treatment may be
  required for patients with chronic brucellosis

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Pregnant women

• Toxicity of tetracycline is established
• Streptomycin is contra-indicated
• There is no evidence that Rifampin and
  Co-trimoxazole are harmful to developing human
  fetus

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Indications for Corticosteroides

• Prevention of Herxheimerlike reactions
• Sever toxemia
• Thrombocytopenia and related bleeding
• Severe debility

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Surgical treatment

• Osteomyelitis
• Paravertebral abscess
• Suppurative lesions
• Brucella endocarditis
• Aneurysmal aortitis

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Supportive treatment

• Rest in bed as long as they are febrile
• Glucose and electrolyte solutions in dehydrated
  patients
• Diet should be liberal in calories and
  carbohydrates
• Analgesics
• Laxatives

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Prognosis

• Brucellosis appropriately treated within the
  first month of symptom onset is curable
• Patients are frequently unable to work for up to
  2 month
• Immunity to reinfection follows initial brucella
  infection
• With early antimicrobial therapy cases of chronic
  brucellosis are rare

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• With Thanks