Antibiotic Refresher talk

1. Antibiotic Refresher talk Sandra Martin Antibiotic Pharmacist Calderdale and Huddersfield NHS Trust

2. Antibiotic Pharmacist • DOH funding £12million over 3 years specifically for pharmacists to work with microbiologists and other healthcare professionals • 3 days/week (Monday-Wednesday) • Trustwide/liaise with PCT pharmacists • CRH ext 5623

3. Presentation • Bacteria - background • Routes of infection • Common diseases/bacteria • Antibiotics - background • Resistance to antibiotics • Common antibiotics used within the Trust • Prudent prescribing

4. Gram staining • Stain with crystal violet then iodine • Cell wall differences • Gram +ve cannot be decolourised • Some gram -ve have capsules for protection

5. Classification of bacteria • Three main groups • Gram positive - aerobes/anaerobes • Gram negative - aerobes/anaerobes • Acid-fast bacilli • Spirochetes • Chlamydiae/Rickettsiae/mycoplasmas not classed as bacteria

6. Growth-C,N,water Gas,temperature and pH requirements can vary Temperature-37C optimum pH 7.2-7.6 best Atmosphere CO2 required by all Oxygen Obligate aerobes eg Pseud.aeruginosa Obligate anaerobes C.tetani Facultatative anaerobes eg E.coli Bacteria physiology

7. Basic information • Reproduce by binary fission • Single bacteria can produce 280,000 billion bacteria in 24 hours • Human cell manages 1 division in 24 hours • Human body has 10 quadrillion cells but contains 100 quadrillion bacteria! • 100,000 bacteria per cm2 skin alone!

8. Endogenous eg own flora Exogenous Direct contact eg N.gonorrhoea Ingestion eg V.cholera Inoculation eg rabies Inhalation of airborne droplets or secretions which contaminate eg measles or tuberculosis Transmission of bacteria

9. Skin • Impervious to microorganisms • Few nutrients, pH • Commensal organisms eg Staph.aureus • Trauma eg cuts • Weak spots eg eyes, mouth,ears

10. Respiratory Tract • Enclosed air contains 1000 microorgs/m3 • Inhale 10,000 microorgs/24 hours • Mucociliary blanket at back of throat and nasal passages • particles trapped in hairs taken to back of throat and swallowed • aveoli - lining of macrophages

11. Intestinal tract • Must contend with food/drink • Commensal flora • Bacteria must survive pH of stomach and duodenum • Need to attach to/penetrate gut wall in competition to gut flora

12. Urinogenital system • Urine sterile/continually flushed • male urethra 20cm - bacteria must be introduced to bladder • female urethra 5cm - microorgs. Can traverse • Infection of bladder to kidney • Vagina - pH 5 (lactic acid)

13. Conjunctiva • Secretions from lacrimal/other glands • Mechanical cleansing (blinking) • Damage to conjunctiva/reduced secretions leads to infections eg contact lens wearers

14. Macrophages from bone marrow migrate to body tissues phagocytosis and kill bacteria synthesis of complement components and cytokines Polymorphs or neutrophils from bone marrow found mainly in circulation phagocytosis and intracellular killing Phagocytes: macrophages and neutrophils

15. Chemotaxis attachment engulfment (phagocytosis) intracellular killing Complement system cascade of proteins Antigens- bind specific antibodies secreted by lymphocytes Phagocytosis and intracellular killing

16. Bacteria overcome host defences • Overcome portals of entry • Modulation of immune response • Avoid phagocytosis • Survive after phagocytosis • Kill phagocytes

17. Common diseases and bacteria- see handout “Bacterial pathogens –aide memoire”

18. Definition of an Antibiotic • …substance produced by micro-organisms that selectively destroy or inhibit other microrganisms. • Bactericidal- kill bacteria • Bacteriostatic - suppress growth/reproduction of bacteria

19. Antibiotics have high profile in NHS • House of Lords Select committee on Science and Technology • “The Path of least resistance”, SMAC 1998 • “Resistance to antibiotics and other antimicrobial agents”, HSC 1999 • “Optimising the Clinical use of antibiotics”, CPSG 2001 • “Getting ahead of the curve”, DOH 2002 • “Winning ways - working together to reduce healthcare associated infection in England”, DOH 2003

20. Successes of antibiotics • Enabled huge advances in medicine • For two generation have altered our expectations of life and death • 1930’s 100-120/100,000 deaths from sepsis after childbirth - now nearly zero • Enabled organ transplantation (immunosuppressants)

21. Problems with antibiotics • Use selects for resistant bacteria • Resistant bacteria accumulate and spread • Resistance increases clinical complications, hospital stay and death • Development of new antibiotics is expensive (£300million) and slow • Modern medicine is threatened with increasing resistance and fewer new antibiotics

22. Antibiotic use • 50 million prescriptions in England per year • 50% use in humans • 50% use in animals • 80% human use is in the Community • 50% Community use is for treatment of respiratory tract infections • 15% Community use is for UTI’s

23. Common antibiotics and their discovery

24. Selective activity of antibiotics against bacteria

25. Basis of resistance • Darwinian selection • Antibiotics kill sensitive organisms - resistant ones survive • Sensitive organisms become resistant by mutation • Some species are inherently resistant • Bacteria accumulate multiple resistance to unrelated antibiotics eg MRSA

26. Antibiotic use encourages resistance • Acquired resistance is absent from bacteria antedating the antibiotic era • Introduction of a new antibotic is repeatedly followed by resistance • Resistance develops in the normal bacteria flora of individuals receiving antibiotics • One dose of an antibiotic can change gut flora • Resistance is greatest in countries/units where use is greatest

27. Mechanisms of resistance • See “Mechanisms of resistance” handout

28. Common antibiotics used in the Trust • Classes of antibiotics • Where used • Separate handout for spectrum of activity for each antibiotic (“Common Antibiotics Vs bacterial pathogens”)

29. Benzylpenicillin (IV)- cellulitis Penicillin V (oral) Flucloxacillin - cellulitis Amoxicillin – chest infections,UTI’s Piperacillin/Tazobactam – neutropenic patients (Beta-lactamase inhibitor) Distributed widely – poor bone penetration 5% patients true allergy Beta-lactamase resistance Food can affect absorption Penicillins

30. 2nd generation cefalexin (oral), cefuroxime (IV) - septicaemia 3rd generation cefotaxime (IV) -septicaemia Ceftazidime – Pseudomonas infections Wide distribution 10% cross sensitivity with penicillin allergy Oral absorption can be poor Cephalosporins

31. Imipenem, meropenem (IV) – Reserved for severely ill patients Toxicity – fits at high dose Cross sensitivity to penicillin allergy Aztreonam (IV) Reserved for neutropenic patients and severely ill Used in combination with Vancomycin usually (Gram +ve cover) Carbapenems & Monopenems

32. Oxytetracycline, Tetracycline, Doxycycline – used 2nd line for chest infections, acne Avoid food/milk at same time (Poor absorption) Avoid in children/pregnant women (Tooth deposits) Tetracyclines

33. Gentamicin, amikacin (IV) Once daily gentamicin policy Neutropenic patients, urology Toxic to ears and kidneys (monitor levels) Post-antibiotic effect Aminoglycosides

34. Clarithromycin (IV), erythromycin (oral) Chest infections, cellulitis (Penicillin allergy) Stomach upset, rashes, rarely liver damage Clindamycin (IV/oral) – 2nd line cellulitis Good bone penetration Linked with Pseudomembranous colitis (C.difficile) Macrolides and Clindamycin

35. Vancomycin IV - MRSA infections Oral – C.diff infection Renal toxicity – monitor levels Slow administration – “red man syndrome” Teicoplanin – (IV) MRSA Loading doses Renal toxicity - Monitor renal function (?levels) Glycopeptides

36. Fusidate – (IV/oral) Skin/bone infections Resistance as monotherapy Liver toxicity Trimethoprim (oral/IV) – UTI’s Excreted via kidney Folate deficiency – avoid in pregnancy Fusidate and Trimethoprim

37. Ciprofloxacin – oral/IV 2nd line – Septicaemia, severly ill patients Reduce dose in renal impairment Levofloxacin – oral/IV 2nd line – chest infections Doesn’t interact with theophylline Quinolones

38. Metronidazole – oral/IV – anaerobes eg gynae infections Good absorption Nausea, metallic taste Rarely peripheral neuropathy Avoid with alcohol – disulfiram type reaction (sick!!) Imidazoles

39. Linezolid - oral (IV) MRSA £80/day Blood disorders – weekly FBC (Only licensed for 2 weeks) Weak MAO inhibitor Quinopristin & dalfopristin (IV) Gram positive Not used in our Trust – yet! £100/day! New antibiotics

40. Problem infections in hospitals • MRSA (Methicillin resistant Staphylcoccus aureus) • VRE (Vancomycin resistant enterococcus) • Clostridium difficile infections

41. Choosing the right drug • Route – IV or oral • Right dose – renal/hepatic/age/weight • Right duration • Narrow spectrum • Allergy status of patient • Culture/sensitivity • Prophylaxis Vs treatment

42. Ways to maximise antibiotic use • Antibiotic formularies – hospital and GP • Short course lengths – 5 days policy/IV to oral switch policy • Narrow Vs broad spectrum • Safety – TDM Vancomycin, gentamicin • Multidisciplinary approach • GP – Non Prescription pads • Public health campaigns eg “Don’t wear me out” & “Cherish your good flora!”

43. Getting ahead of the Curve • …until recently man kept ahead and new antimicrobials were developed faster than bacteria developed resistance…now microorganisms are “getting ahead”…