Antibiotic therapy Vaccines for healthcare worker

1. Antibiotic therapyVaccines for healthcare worker

2. Key points • Introduction • Choice of the proper antibiotic • Antimicrobial combinations • Choice of the route and efficacy assessment

3. Sir A. Fleming: discoverer of Penicillin Noble prize 1945

4. Antibiotics • PCNs • Cephalosporins • Carbapenem • Monobactams • Glycopeptide • Aminoglycoside • Fluroquinolone

5. PCN • PCN G • PCN V • Amoxicillin • Cloxacillin • Oxacillin • Ampicillin • Piperacillin • Methicillin

6. Choice of the proper agent • Identification of the organism • Antimicrobial susceptibility • The narrowest effective spectrum • Host factors (Allergy, Age, renal and liver, site of infection, pregnancy, metabolic abnormalities)

7. Identification of the organism • Gram stain (CSF, Pleural, synovial, peritoneal, urine, sputum) • ELISA / latex agglutination • PCR • CULTURE (best if before Abx) • Bacteriologic statistics (the application of knowledge of the organisms most likely to cause infection in a given clinical sitting)

8. Antimicrobial susceptibility • Disk diffusion method • Epsilometer (E-test) • Minimum inhibitory conc. (MIC) • Minimum bactercidal conc. (MBC) • Specialized testing for: fastidious organisms (obligate anaerobes), Haemophilus spp, pneumococci, MRSA • Resistance mechanism of the bacteria: • eg: Staph. aureus, E. coli, Enterbacter …..

9. Pharmacodynamic profile • Area under the curve / time curve to MIC (AUC / MIC) • Maximal serum conc. / MIC (C max / MIC) • Time during dosing interval that plasma conc. exceed the MIC (t / MIC)

10. Conc. & Time dependent dosing • Conc. dependent (FQ, Ag)  increase in conc leads to a more rapid rate of bacterial death (i.e. large dose at long intervals) • Time dependent (-lactams, vancomycin) reduction in bacterial density is proportional to the time that the conc. exceeds MIC (i.e. sufficient dose at appropriate intervals to keep conc. above MIC)

11. Organism A Concentration Time Organism B Organism C A : resistant; B : moderately susceptible; C very susceptible

12. Resistance selection days Antibiotic X Antibiotic X

13. Published data • Manuals • eg:Sanford’s • Medical letter on drugs and therapeutics • (nb: use this information within its context)

14. Host factors • Previous history of adverse reactions • Neutrophil function  neutropenic are treated aggressively • CLL, Multiple Myeloma, asplenia  treated empirically

15. Age • Renal function (impaired physiologic function) • Absorption • Tetracyclines • INH hepatotoxicity • Nephrotoxicity • Ag and cochlear toxicity

16. Genetic / metabolic • Hemolysis in G6PD deficiency • DM : sulfa drugs can potentiate the sulfonylurea hypoglycemic agents • - Dextrose load • - Poor IM absorption (use IV route)

17. Pregnancy • Safe : PCN, cephalosporin, erythromycin • Dangerous: tetracyclines (hepatic toxicity, dental discoloration) • ? metronidazole • FQ  Contrindicated • ?? rifampin, Ag, azithromyccin, clindamycin, imipenem,vancomycin, TMP • Abx dose needs to be increased?

18. Renal and liver fx • Vancomycin & Aminoglycosides

19. Site of infection • Optimal therapy requires concentrations > MIC at the site of infection • Meningitis • Endocarditis • Osteomylitis • Chronic prostatitis • Intraocular infections • Abscesses • Foreign body • UTI

20. Immune system • Abx can cause immune suppression esp. in the immunosuppressed patients • Suppress monocyte transformation, phagocytosis, chemotaxis, antibody production

21. Combinations • Some physicians use combinations for the sense of security  deleterious effects • Indications: 1) prevention of emergence of resistant bacteria : TB, staph endocarditis • 2) polymicrobial infections : abd. sepsis • 3) initial therapy: eg: Ag + piperacillin • 4)Synergism:…

22. Synergism • For resistant organisms • Limited data to support their benefit • e.g.: PCN + Ag  Enterococcal endocarditis • Oxacillin + Ag  Staph. endocarditis • Anti-pseudomonal - lactam + Ag  Pseudomonas bacteremia • Impaired host

23. Antagonism • Too many in vitro reports • Clinically was seen in : PCN + tetracyclines • 2 -lactams  induce  lactamases • More important in immunosuppressed pts

24. Adverse effects • 5% of pts will have a side effect • Combinations  more cost, more adverse effects

25. Anaphylaxis • Beta lactams are the most common ABx to cause anaphylaxis • PCN risk of anaphylaxis: 0.01% • Death occurs in 1 / 100,000 courses • 10 - 20% of pts who claim to have an allergy to PCN are truly allergic • 50% of pts with a positive skin test: reaction

26. Anaphylaxis • PCN cross reaction with Cephalosporins • Minimum cross reaction with carbapenem  1% • No cross reaction with Aztreonam (except ceftazidime)

27. Route • Oral  stable , mild infection (reliable pts) • IV  serious infections (sepsis) + DM

28. Monitoring the response • Clinically • Drug levels • Lab tests

29. Cost • If all other factors are equal, the least expensive drug should be chosen

30. Needle stick Risk of transmission - Hepatitis B virus 30% - Hepatitis C virus 3% - HIV 0.3%

31. HBV Vaccinerecommendations • HB vaccine offered for all HCW • Required in US (1991) • Human rights issues (what if they refused ??) • Check response after 1 month • Responders: ….. 10 IU/l • Non responders………. < 10 IU/l

32. HBV vaccine • Does not transmit the virus • 3 shots at 0, 1, 6 months • The series is administered once • A booster shot can be given in times of outbreak conditions • If you are exposed to HBV immediate vaccination is extremely helpful

33. HBV vaccine (cont) • You do not need to accept the vaccine • You can decline it and sign a declination form • If you are exposed to HBV or changed your mind, you can still receive it • Your employer might not offer you the vaccine if: • You are vaccinated • Have Antibodies • Contraindicated in your case

34. HBV (cont)

35. Response or no ??? • High risk practice • True non response vs. Waning Ab levels • One boost to differentiate • Non response: < 10 IU/l • Responders: > 10 IU/l NEJM Dec 2004

36. To boost or not to boost ?? • Currently, there is no proof that booster injections are indicated for the first two decades after successful immunization • After 3rd decade: ???? Studies are needed J clini Virology 2003

37. Influenza vaccine • Annually • In the fall season • even if late • 2 strains of A + 1 strain of B • No protection against other Flu like illnesses like • RSV • Para influenza • Adenovirus

38. Influenza vaccine • Weak or no association with Guillain Barre syndrome • 1 / million • Contraindication • Previous GB syndrome • ? Egg allergy • Allergic reaction to any component

39. Prevention - Rubella + Rubella IgG Immune _ Non-Immune MMR (avoid pregnancy x 2 m) 2 months _ _ Check titers Booster Inform patient + Immune

40. Rubella-risk • Risk of congenital infection • 1 + 2 month: 90% • 3rd month 50% • Termination of pregnancy is usually recommended in Western countries • > 16 weeks negligible • 12 – 16 weeks: deafness can occur

41. Congenital rubella syndrome: • growth retardation; malformations of the heart, eyes, or brain; deafness; and liver, spleen, and bone marrow problems.

43. Prevention - Varicella • Varicella • History of chicken pox: … immune • Positive titers ….. . .. . . immune • Absent titers: not immune • Give vaccine: 2 doses, 2 months apart • Postpone pregnancy 2 m after the second dose

44. Tetanus - Diphtheria vaccine • Once every ten years • Toxoid vaccine

45. Peneumococcal vaccine • Indicated for all immunocompromised adults • > 65 years • 1 or 2 doses

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