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Treatment and Prevention of Brucellosis

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Robin Greaves

on 1 November 2012

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Transcript of Treatment and Prevention of Brucellosis

Treatment and Prevention of Brucellosis Goals of Therapy Dosing References Control the symptoms associated with Brucellosis
Prevent further complications
Chronic brucellosis
GI complications
Bone and joint complications (spondylitis)
Complications in pregnancy Preferred treatment:
Doxycycline 100 mg PO bid
Streptomycin 1 gram/day for 2-3 weeks or Gentamicin 5 mg/kg/day IV or IM for 7-10 days
Primary Alternative Treatment:
For adults and children older than 8 years
Doxycycline 100 mg PO twice daily
Rifampin 600-900 mg/day PO Katzung, B.G., Basic & Clinical Pharmacology, 11th Edition. McGraw Hill, NY.2009
Bennett, Luna. "Protein Synthesis Inhibitors". Class lecture. Chemical and Pharmacological Basis of Drug Action. Union University. September 2012
Philip, Ashok."Tetracyclines". Class lecture. Chemical and Pharmacological Basis of Drug Action. Union University. September 2012
Philip, Ashok."Fluoroquinolones". Class lecture. Chemical and Pharmacological Basis of Drug Action. Union University. September 2012
Corbel, MJ. Brucellosis in Humans and Animals. WHO 2006 http://www.who.int/csr/resources/publications/Brucellosis.pdf Doxycycline Mechanism of Action
Tetracycline antibiotic
Time dependent
Inhibits protein synthesis by reversibly binding the 30S subunit of bacterial ribosomes
Blocks the binding of the aminoacyl-tRNA of the mRNA ribosome
Prevents addition of amino acids on to the growing peptide chain Doxycycline Adverse Effects
Teeth discoloration in young children
Deposits in bone
Drug Interactions
Divalent cations-Fe2+, Ca2+, Mg2+, and Al3+
Rifampicin MAY increase plasma clearance of Doxycycline Treatment Preferred treatment:
Tetracycline + Aminoglycoside
Usually Doxycycline + Streptomycin or Gentamicin
Primary alternative treatment
Rifampin + Doxycycline
Secondary alternative treatment
Fluoroquinolone + Doxycycline or Rifampin
Sulfamethoxazole/Trimethoprim + Doxycycline or Rifampin or Streptomycin
In pregnancy:
Rifampin alone or in combination with TMP-SMX Dosing in Children Preferred treatment for children:
80/400 mg/kg/day PO BID for 6 weeks
+ streptomycin
30mg/kg/day IM QD for three weeks
or gentamicin
5 mg/kg/day IV or IM QD for 7-10 days
Alternatives include:
+ Rifampin
15 mg/kg/day PO each administered for 6 weeks
Rifampin plus an aminoglycoside Streptomycin and Gentamicin Mechanism of action
Aminoglycoside antibiotics
Concentration dependent
Initial binding to the cell walls of Gram negative bacteria and cause leakage of intracellular contents
Protein synthesis inhibitor
Post antibiotic effect
bacterial growth suppressed even after discontinuation of treatment Streptomycin and Gentamicin Adverse Effects
Nephrotoxicity (reversible)
Ototoxicity (irreversible)
Neuromuscular blockade
More associated with Myasthenia gravis
Drug Interactions
Penicillins-both are inactivated when mixed together or administered at the same site
Loop diuretics-potentiate ototoxicity Rifampin Mechanism of action
RNA synthesis inhibitor
binds the beta subunit of bacterial DNA-dependent RNA polymerase
Adverse effects
discoloration (orange appearance) of urine, sweat, tears, and contact lenses
cholestatic jaundice
flu-like symptoms Rifampin Contraindications
Drug interactions
strong inducer of most cytochrome P450 isoforms
decreases the effectiveness of oral contraceptives Fluoroquinolones Mechanism of action
DNA synthesis inhibitors
Inhibit DNA gyrase and topoisomerase II
Concentration dependent killing
Post antibiotic effect
Adverse effects
QT prolongation
arthropathy in children <18
Black Box Warning for increased risk of tendonitis and tendon rupture, especially in patients <60, taking corticosteroids, and patients with organ transplants. Fluoroquinolones Contraindications
Caution in patients with QT prolongation or uncorrected hypokalemia
Not recommended for those <18 years old
Drug interactions
CYP1A2 substrates
Warfarin (bleeding has been reported when taking with Cipro)
Class Ia and Class III antiarrhythmia drugs SMX/TMP Mechanism of action
Nucleic acid synthesis inhibitor
The synergism of both drugs inhibits the production of folic acid required to make purines and pyrimidines
Trimethoprim inhibits bacterial dihydrofolic acid reductase
Sulfamethoxazole inhibits dihydropteroate synthase
Time-dependent killing
Adverse effects
Bone marrow suppression
Hemolytic anemia (in pts with G6PD deficiency)
Kernicterus SMX/TMP Contraindications
Infants <2 mos old
Hepatic damage
Renal insuffiency
Drug interctions
Folic acid
increased bleeding risk
CYP2C8/9 subtrates
SMX/TMP is an inhibitor
ACEIs/ARBs/Potassium sparing diuretics
increased risk of hyperkalemia Patient Counseling FINISH ALL ANTIBIOTICS!!!
Avoid sun or use sunscreen
Can interfere with oral contraceptives
Can take with food to minimize GI upset
Report any severe GI side effects
Report any signs or symptoms of nephro/ototoxicity
Will cause discoloration of urine, sweat, saliva, feces, tears, and contact lenses.
Soft contact lenses can be permanently stained
Take 1 hr before or 2 hrs after a meal with a full glass of water
No alcohol
Take exactly as prescribed
Avoid sun or use sunscreen
Drink with plenty of water to prevent crystallization in the kidneys. Prevention of Brucellosis An animal vaccine is available, but there is currently no human vaccine.
In those who prepare animal vaccines or work closely with animals should:
exercise proper occupational and personal hygiene
see WHO guidelines for specific laboratory processes on preparing vaccines
be educated on the transmission and life cycle of Brucella
Infected animals should be eliminated to prevent the spread of infection.
Post exposure prophylaxis
Local wound care
Tetanus vaccine
6 week course of Doxycycline
The general public is most often exposed to Brucella through consumption of contaminated milk and dairy products.
Pastuerization effectively kills Brucella.
Raw milk or dairy products made from raw milk should be avoided.
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