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Clinical Aspects of Antimicrobial Therapy

Clinical Aspects of Antimicrobial Therapy. CONTENTS OF LECTURE. Empiric Antibiotic Guidelines Antibiotic Policy, Audit, Surveillance Summary of commonly used antibiotics For this session a copy of the Empiric Antibiotics guidelines for SJH should be used by each student for clinical scenarios.

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Clinical Aspects of Antimicrobial Therapy

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  1. Clinical Aspects of Antimicrobial Therapy

  2. CONTENTS OF LECTURE • Empiric Antibiotic Guidelines • Antibiotic Policy, Audit, Surveillance • Summary of commonly used antibiotics • For this session a copy of the Empiric Antibiotics guidelines for SJH should be used by each student for clinical scenarios

  3. ANTIBIOTICS May be: • Bacteriostatic – inhibits growth of Bacteria, so acts by preventing bacteria from multiplying and then hosts defences deal with the small number of bacteria left • Bactericidial – kills Bacteria, so eliminates bacteria

  4. Available www.ndsc.ie

  5. Recommended Infrastructure Surveillance of Antimicrobial Resistance National Reference Laboratories Monitoring Supply and Use of Antimicrobials Development of Guidance for Appropriate Use of Antibiotics Education in relation to appropriate use of Antibiotics Development of Principles in relation to Infection Control Future Research in the Area On www.ndsc.ie SARI REPORT APRIL 2001 RECOMMENDED STRATEGIES

  6. St.James`s Hospital Empiric Antibiotic Guidelines-June 2005

  7. St.James`s Hospital Empiric Antibiotic Guidelines-June 2005 • These guidelines are developed on a yearly basis by the Antimicrobial Sub-Committee of the Pharmacy and Therapeutics Committee. Printed in the Prescriber`s guide, distributed throughout the hospital ( all doctors, pharmacists, wards etc) and available on the St.James`s intranet

  8. Objectives- to understand : • Principles of Antibiotic Guidelines • Therapeutic Drug Monitoring( Glycopeptides, Aminoglycosides) • Guidelines for Empiric Treatment of common infections • Principles of Surgical Prophylaxis • Empiric guidelines for Surgical Prophylaxis • Guidelines for the prevention of Endocarditis

  9. Principles of Antibiotic Guidelines • Guide to the empiric use of antibiotics. • Empiric treatment is the choice of antibiotic prior to sensitivity results being available • Avoid unnecessary use .If clinically feasible await results of microscopy/culture/susceptibility data for directed therapy

  10. Principles of Antibiotic Guidelines • Specimens for microbiology should be taken prior to commencement of empiric treatemnt. In an emergency , at a minimum a set of blood cultures should be taken e.g meningitis. • Ensure any history of allergy is documented on the cover of notes and drug kardex prior to commencing antibiotics • Prescribing Practice -Document reason for starting agent or any change

  11. Principles of Antibiotic Guidelines • Empiric antibiotics should be reviewed once Gram satin/ mcroscopy/culture/sensitivity or PCR available.Empiric therapy should be changed to directed therapy as soon as possible. Directed therapy should be the narrowest spectrum antibiotic to adequately cover the pathogens

  12. Principles of Antibiotic Guidelines • Pharmacokinetics and Pharmacodynamics issues may necessitate dose adjustments( e.g renal impairment etc). Doses of antibiotics should take into account creatinine clearance and review regularly. Consider co prescribed interacting drugs • Refer to BNF, hospital pharmacist, Microbiologist or Infectious disease physician if advice about dose is required

  13. Pharmacokinetics Mathematical study of the rate process involved in absorption, distribution, metabolism and excretion Pharmacodynamics Time course of drug effects and other interactions between antimicrobials and the bacterium(MIC, Post Antibiotic Effect and interactions between the immune system and the agent) Definitions

  14. Principles of Antibiotic Guidelines • All antibiotic prescriptions should be reviewed after 48 hours • Consider i/v to oral switch • In general avoid topical antibiotic use. When topical antibiotics are used do not use antibiotic used systemically • Consultations from Clinical Microbiology ext.2039 or Infectious Diseases Bleep 192 or ext. 2507/2402 are encouraged

  15. General Principles of Therapy • Avoid unnecessary use- e.g clinical well patient and CSU colonization, leg ulcers colonization, post-operative atelectasis • Choice of suitable drug • Toxicity e;g allergy, enhancement of toxicity, change of flora etc • Combined therapy • Prescribing Practice -Document reason for starting agent or any change

  16. General Principles of Therapy • Generic names to be used • Specify dose, number of doses or period of time , review at 48 hours with results of investigations and clinical status • If no improvement within 36-48 hours check • (1) Adequate dose and /or level of drug • (2) Host defences e.g drain abscess, removal of foreign material etc • (3) Is the drug active against fastidious or difficult organisms to isolate, consult with microbiologist

  17. General Principles of Therapy • Do regular antibiotic rounds/review use to avoid unnecessary prolonged courses • Oral if possible instead of I/V preparations • Criteria for I/V to Oral switch -Fever settled -wcc returning to normal -Patient clinically stable -No gastrointestinal upset

  18. General Principles of Therapy • Reserve Antibiotics • Use to be discussed with consultant or microbiologist • Reasons are to preserve usefulness by avoiding emergence of resistance • Where toxic effects do not justify use in trivial infections • Expense

  19. General Principles of Therapy • Antibiotic Tables ( see hospital policies) • for use empirically before results of Culture and Sensitivity available • Change when this information is available TO DIRECTED THERAPY • Specimens ( e.g for culture , PCR etc) should be taken before commencing therapy exception e.g meningitis) • In serious sepsis Parental route of Administration to be use

  20. General Principles of Therapy • Pharmacokinetics/ Pharmacodynamic may require dose/choice adjustment • Avoid use of topical antibiotics, use those not used systemically • Consultations Microbiologists or ID physicians • Treatment and Prophylaxis clearly defined

  21. CLASSIFICATION • Concentration dependent bactericidal activity -Aminoglycosides -Quinolones -Carbapenems • Time dependent bactericidal activity -B-lactams -Glycopeptides • Bacteriostatic Activity -Erythromycin -Tetracycline

  22. Therapeutic Drug Monitoring • TDM necessary to ensure therapeutic efficacy of a drug while ensuring toxic and sub therapeutic doses are avoided. • TDM is performed on drugs with narrow therapeutic indices such as glycopeptides ( e.g vancomycin) and aminoglycosides (e,g gentamicin) • These drugs may be associated with toxicity so levels should be regularly monitored

  23. ANTIBIOTIC ASSAYS • Assay when an antibiotic has a narrow therapeutic index e.g Aminoglysocides • Assay when normal route of excretion is impaired e.g. patient with renal impairment on vancomycin • Assay in patients receiving prolonged therapy for serious infection e.g. endocarditis • Assay in Neonates with serious infection • Assay if failure to respond to therapy • Assay to check compliance

  24. Concentration Dependent Killing Peak Example: Aminoglycosides Conc Therapeutic Range Trough1 Time

  25. Time Dependent Killing Example: Glycopeptides Conc MIC Time

  26. General advice on taking levels • It is important to ensure the levels are taken at the correct time. • Frequency: first level see tables, repeat levels twice weekly for those with stable renal function, more frequently if renal function rapidly changing • When: See tables. In general trough must be taken immediately before the next due dose.Peak one hour after administration of dose. • Levels done twice Saturday and once sunday

  27. General advice on taking levels • Label correctly: if intermittent irregular dosing label as trough • Random levels are not interpretable • Action to be taken on receipt of levels, • If level is within therapeutic range, continue current dosing • Putting an antibiotic on hold is not an appropriate intervention. Modify the dosing interval and / or dose. • Advice from clinical Microbiology(ext 2985) or ID Pharmacist

  28. In general interpretation of levels • If trough high, dosing interval needs to be prolonged where appropriate • If trough is low( subtherpeutic) dosing interval needs to be shortened and /or dose will need to be increased where appropriate • If peak high, dose needs to be reduced where appropriate • If peak low the dose may need to be increased where appropriate

  29. Example: Vancomycin Page 134 • Order bloods for renal function and calculate CrCl • Vancomycin is the first line glycopeptide in SJH • Normal dose normal renal function 1 g B.D • Recommended range -Trough- 5-12 mg/l Normally taken before 3rd dose Toxicity and Efficacy best determined by trough level

  30. Creatinine Clearance • CrCl= (x)(140-age)(IBW) Serum Creatinine X= 1.23 males, x= 1.04 for females Male IBW= 50 KG+ ( 2.3 kg) x (inches over 5 feet) Female IBW= 45.5KG + ( 2.3 kg) x (inches over 5 feet)

  31. Using Empiric Guidelines • Clinical symptoms/Signs • Table Format • Follow general principles covered early

  32. Example page 136 • 75 year gent with cough purulent sputum, pyrexia, confusion, RR 22/min BP 110/70mmHg,

  33. COMMUNITY ACQUIRED PNEUMONIA: WHAT’S CAUSING IT?

  34. Page 136 • Common pathogens? • Adult empiric therapy? • What tests to be sent • Then directed therapy

  35. Using empiric guidelines • Page 137 • 20 year presents with celluitis right arm • No history of therapy • Empiric therapy?

  36. Using Empiric guidelines page 138 • 60 year gent admitted with abdominal pain 12 hours duration , generalised guarding, boardlike rigidity • Air under diaphragm on CXR • Empiric therapy?

  37. Using guidelines page 141 • 20 year old presenting with severe headache, neck stiffness, non-blanching rash • Empiric treatment?

  38. Using Empiric Guidelines • Patient 48 age female presents with malaise, anorexia, fever for 3 weeks • New heart murmur heard

  39. Osler`s nodes Tender, s/c nodules Janeway lesions Nontender Erythematous, Haemorrhagic, Or pustular Lesions often On palms or soles

  40. Using Empiric guidelines page 145 • Common pathogens • Therapy? • Tests to be sent?

  41. Surgical Prophylaxis • Page 149 • For ERCP? • For femoral-popliteal bypass? • For Compound fracture?

  42. Guidelines for prevention of Endocarditis PAGE 151 • Patient with prosthetic valve undergoing dental extractions under general anaesthetic ( history of treatment of RTI 3 weeks earlier with co-amoxiclav)?

  43. Spectrum of Activity • Benzyl penicillin: mainly active against Gram Positive organisms e.g. Streptococci and Staphylococci • Ureidopenicillins: active against certain gram positive and gram negative organisms • Anti-pseudomonal Penicillins active against gram positive organisms(s) and gram negatives and pseudomonads • Cephalosporins: Broad spectrum of activity gram negative and positive organisms, different generations have different spectra of activity.

  44. Carbapenems • Imipenem, meropenem: have a very broad spectrum activity against gram-negative bacteria, anaerobes, streps • Now used to treat gram negative infections due to so called ESBL producing organisms eg, E coli, Klebsiella • Ertapenem is a new member of the group but its not active against Pseudomonas

  45. Cephalosporins: main uses • Cefuroxime: surgical prophylaxis • Cefotaxime/ceftriaxone: meningitis nosocomial infections excluding Pseudomonal, • Ceftazidime: nosocomial infections including Pseudomonal

  46. Other major antibiotic groups: aminoglycosides • Gentamicin, amikacin (tobramycin, streptomycin) • Mainly active against gram negative bacteria • Mainly used to treat nosocomial infections: pneumonia in ITU, septicaemia • Limiting factors are nephrotoxicity (and ototoxicity) and resistance • Also used in combination

  47. Current major antibiotic resistance problems: community infections • Respiratory tract: penicillin resistance in pneumococcus increasing • Gastrointestinal: quinolone resistance in Campylobacter • Sexually transmitted: penicillin, quinolone resistance in gonococcus • Urinary tract: beta lactam resistance in Esch coli • MRSA and MDRTB • Tropical: multidrug resistance in Salmonella typhi, Shigella spp, malaria

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