بسم الله الرحمن الرحيم

1. بسم الله الرحمن الرحيم Treatment of Brucellosis Shahid Beheshti University of medical sciences April 2008 By: Hatami H. MD. MPH

2. Antimicrobial therapy: • Shortens the course of illness • Lessens morbidity • Reduce the incidence of complications

3. Antimicrobial therapy: • Antimicrobial treatment must always be prescribed • Prolonged treatment is more likely to achieve permanent cure

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

5. 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

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

7. Doxycycline Pediatric dose • 5 mg/kg/d PO for 3 wk

8. Doxycycline Pregnancy • D - Unsafe in pregnancy

9. 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

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

11. Rifampin Adult dose • 600-900 mg PO/IV qd

12. Rifampin Pediatric dose • 10-20 mg/kg PO/IV qd, not to exceed 600 mg

13. 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

14. Rifampin Pregnancy • Safety for use during pregnancy has not been established.

15. 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)

16. Co-trimoxazole • (Bactrim, Septrin) • 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.

17. 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 . . .

18. Co-trimoxazole Adult dose • 2 tabs PO bid (160/800)8-10 mg/kg IV divided q6, 8, or 12h

19. Co-trimoxazole Pediatric dose • 5 mL/10 kg PO bid; 5 mL: 40/200

20. 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

21. 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;

22. 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

23. Co-trimoxazole Pregnancy • C - Safety for use during pregnancy has not been established.

24. Co-trimoxazole Precautions • Avoid in sulfa-allergic patients or in concurrent use with rifampin

25. 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.

26. 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

27. Gentamicin Pediatric dose • 5 mg/kg IM for 5 d, in combination with either doxycycline or TMP-SMZ

28. 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

29. 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

30. Gentamicin Pregnancy • D - Unsafe in pregnancy

31. 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

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

33. Streptomycin Adult dose • 15 mg/kg, not to exceed 1 g/d IM qd for 3 wk

34. Streptomycin Pediatric dose • 20-40 mg/kg IM qd, not to exceed 1 g qd

35. Streptomycin Contraindications • Documented hypersensitivity; • If possible avoid in patients with preexisting renal disease or vestibular disease because of ototoxicity and nephrotoxicity

36. 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

37. Streptomycin Pregnancy • D - Unsafe in pregnancy

38. 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

39. 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

40. 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

41. Brucellosis Antibiotics not recommended • Most penicillins • Most cephalosporins • Chloramphenicol • Erythromycin • Kanamycin • Sulfonamides

42. 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

43. 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

44. Indications for Corticosteroides • Prevention of Herxheimerlike reactions • Sever toxemia • Thrombocytopenia and related bleeding • Severe debility

45. Surgical treatment • Osteomyelitis • Paravertebral abscess • Suppurative lesions • Brucella endocarditis • Aneurysmal aortitis

46. 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

47. 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

48. With Thanks