Certificate in Pharmacy Practice Microbiology and Antibiotics

1. Certificate in Pharmacy PracticeMicrobiology and Antibiotics Written by: Alison G Eggleton (M Sc, M Ed, B Sc, M R Pharm S) Presented by: Nigel Gooding (Lead Pharmacist – Antibiotics) Updated December 2004

2. LSOP Course Objectives Microbiology • After completing this session, participants will be able to: • List the criteria for selecting antimicrobial agents and doses • List the tests for monitoring response to antimicrobial therapy • Select appropriate antimicrobial regimens for individual patients • Assess patients’ response to antimicrobial regimens

3. ObjectivesBy the end of this session students should be able to: • List 4 methods of microbial investigation and time taken to get results • Define 3 methods to establish the presence of an infection • Describe the factors affecting the choice of antibiotic (organism, drug and patient factors)

4. ObjectivesBy the end of this session students should be able to: • List 5 factors to monitor in patients on antibiotic therapy appropriate to the particular infection • State the most likely causative organisms in 4 common infections • State a suitable antibiotic regime for empirical therapy of infections • Demonstrate the practical application of theoretical knowledge of antibiotic therapy through case studies

5. Task 1 Write down three methods that can be used to classify bacteria Give an example of an organism for each method you have stated

6. Shape Cocci Rods Others such as spiral Staining properties Gram positive or negative Growth characteristics Presence or absence or oxygen in the growth medium Spore formation Flagellae Toxin production Classification of BacteriaBacteria can be classified according to:

7. Task 2: Microbiological Investigations Divide into four groups. Think about the following investigations: Naked eye Microscopy and staining Culture Sensitivity How can these tests be used in practice to establish presence of infection? How long will it take to get results back from these tests?

8. Naked Eye • Can establish presence of infection • Colour • purulent green sputum, cloudy CSF, cloudy urine • Smell • Strongly smelling urine • Finger prick tests, breath tests, dipstick tests • E.g. for Chlamydia, nitrite un urine (UTI), for H pylori • Results often immediate • Can be used to monitor clearing of infection

9. Microscopy and Staining • Check samples for presence of organisms • Shape and size of organism (e.g. rod, coccus) • Growth characteristics of organism (e.g diplococcus) • Additional growth characteristics (e.g. capsule formation, flagellae, spore formation) • Gram positive (blue/purple) or negative (red) • Results can be obtained the same day for most organisms

10. Culture • Significance of bacterial count used to confirm diagnosis • UTI = >105 organisms per ml • Organisms that only grow in certain growth media or under certain conditions • e.g. anaerobes • Presence of organism in a specific sample can diagnose the type of infection • CSF for meningitis • Blood for septicaemia, endocarditis • Difficult if infection is inaccessible • Bone

11. Culture - CSF • Purulent CSF – bacterial • Aseptic Meningitis – viral • WCC • Protein • Glucose • Gram stain

12. Culture • Results can take more than 24 hours • Delay in starting therapy can be dangerous for the patient in serious infection • May need to begin empirical antibiotic therapy

13. Sensitivity • Used to determine sensitivity to specific antibiotics • Reflects sensitivity to different antibiotics at usual therapeutic doses • Can be adapted to reflect local resistance patterns • Can be adapted to suit hospital formulary and/or antibiotic policy

14. Sensitivity • Samples must be taken before antibiotic therapy commences • Sensitivity results may not correlate with clinical results • Defective host defences • Impaired penetration of antibiotic • Mixed infection • Results take one day (if original culture used) or two days minimum (if pure culture grown)

15. Monitoring of Infections • Haematology • Body temperature • Biochemistry • Scanning techniques

16. Haematology • Increased white cell count can indicate infection • Cautions: • Less acute infection can have WCC in reference range • e.g. abscess, bacterial endocarditis • Concurrent drug therapy: • Steroids raise WCC when therapy is initiated or dose increased • Can mimic infection • Chemotherapeutic agents designed to stop cell growth are particularly effective in stopping WCC proliferation • Can disguise infection

17. Differential White Cell Count • ‘Shift to the left’ = Increase in polymorphonuclear leucocytes (leucocytosis) = bacterial infection • PMNs = neutrophils (particularly immature), basophils and eosinophils • Lymphocytosis = increase in lymphocytes = viral infection or whooping cough • Neutropenia = reduction in neutrophils (< 2500 per mm3) can indicate overwhelming infection • Eosinophilia = increase in eosinophils = parasitic or helminth infection

18. Erythrocyte Sedimentation Rate • ESR • Non-specific indicator of infection • Increased in clinical conditions other than infection • e.g. Acute or chronic inflammation, infarction • Decreased by drug therapy other than successful antibiotic therapy • Steroids which suppress inflammation • Chemotherapy suppressing tumours

19. Temperature • Raised temperature can indicate infection • Cautions: • Temperature can be raised in other diseases • Cancers, acute MI, autoimmune disease such as SLE, temporal arteritis, PE, chronic liver disease

20. Temperature can be INCREASED by drug therapy • Drug fever due to hypersensitivity • Tissue injury (chemotherapy) • Increased metabolic rate (thyroxine) • Decreased ability to sweat (anti-cholinergics) • Idiosyncratic (neuroleptic malignant syndrome) • Drug fever with certain drugs e.g. penicillins, amphotericin, methyldopa, phenytoin etc) • Serum sickness due to vaccines and other drugs e.g. fluoxetine, ciprofloxacin, carbamazepine • Side effect of drug, especially foreign proteins e.g. immunoglobulins, interferons, vaccines, human albumin

21. Temperature can be DECREASED by drug therapy • Steroids reduce febrile response so patient may be afebrile even in severe infection

22. Biochemistry • C-reactive protein (CRP) • Increase in infection • Non-specific acute-phase protein • Caution: • Also altered in other conditions • e.g. acute or chronic inflammation, intra-abdominal leakage into gut, decreased protein intake, malnutrition

23. Radiography • Xray/ultrasound/CT scan/MRI scan used to establish presence and/or site of infection • chest x-ray, abdominal x-ray • White cell scan used to establish site of infection

24. Drug-Induced Infection • Reduction in immunoglobulins • Corticosteroids, immunosuppressants, anticonvulsives • Immunosuppressives & live vaccines • Reduction in gastric acidity • Pseudomembranous colitis • Candida infections

25. Task 3 : Monitoring of infections and antibiotic therapy Divide into four groups You have been given a list of signs and symptoms of four disease states: Cellulitis Urinary tract infection Lower respiratory tract infection Septicaemia Find the appropriate signs/symptoms from the list that are used to identify and can be used to monitor progress of therapy in these FOUR infections

26. Cellulitis • Tenderness • Pain • Swelling • Warmth • Erythema • Spreading infection

27. UTI • Urinary frequency • Dysuria • Haematuria • Smelly/discoloured urine • Proteinuria • Fever

28. Lower Respiratory Tract Infection • Cough • Green/yellow sputum • Fever • Chest pain • Tachypnoea

29. Septicaemia • Fever • Tachycardia • Tachypnoea • Rapid capillary refill • Coagulopathy

30. Task 4 - Factors affecting antibiotic choice • In your groups, think about the factors affecting choice of antibiotic • What are the TEN most important factors to consider? Remember to think about: • Organism factors • Drug factors • Patient factors • Be ready to present your ideas back to the whole group

31. Factors Affecting Antibiotic Choice Hazards of unnecessary prescribing: - • Resistance • Resistance in new organisms • Superinfection • Adverse effects

32. Factors Affecting Antibiotic Choice • Organism factors • ‘Best guess’ antibiotic therapy prior to results of MC&S • Cover for range of known likely causative organisms • Site of infection • Ensure antibiotic will penetrate to site • Effect of drug on the organism • Drug may kill the organism (bactericidal) • Drug may stop the organism growing (bacteriostatic) • Care with antibiotic choice • Some drugs only work on actively growing cells • Drugs which stop the organism growing (bacteriostatic) may render drugs which kill the organism (bactericidal) ineffective

33. Antibiotic resistance • Organisms resistant to certain antibiotics • MRSA, VRE, multiple drug resistance • Drug commonly inducing resistance • Sodium fusidate used alone in Staph.infection • Bacteria commonly demonstrating resistance • TB requires multiple drug therapy to affect different growth phases (dormant and active) • Local resistance patterns

34. Drug Factors • Known spectrum of activity • Route of administration/dose/frequency of administration • Pharmacokinetics • distribution to site of infection • penetration, water/lipid solubility, poor blood supply to affected area, blood brain barrier • effective drug concentration at site of infection • Post-antibiotic effect • Synergistic effect (may convert from bacteriostatic to bactericidal e.g. vancomycin + gentamicin for enterococci) • Drug interactions • Adverse effect profile • Cost • Formulary / EBM • Sodium content

35. Patient factors • Severity of infection • Immune status • (immunosuppressed, malnourished, old age) • Pharmacokinetic factors • (elderly and neo-nates, impaired renal or liver function) • Pharmacogenetic factors • G6PD deficiency, porphyria • Epidemiology • (recent travel, occupation, school-age) • PMH • Diabetes, heart valve replacement, trauma • Allergy status

36. MC&S Allergy status PMH Drug interactions WCC CRP +/- ESR Temperature Naked eye signs Clinical signs ADR’s Electrolyte contents Volume of dilutions Duration Dose/route Patient specific parameters Monitoring of Infections

37. Selection of Antibiotic Dose and Route • Selection of Antibiotics • The choice of antibiotic, the dose and the route of administration mainly depend on: • The type of infection • The most likely causative organism(s) • The severity of the infection • The likely spectrum of activity of the drug(s) given known resistance patterns

38. Task 5Divide into FOUR groups • Consider the details of seven patients with their drug charts • Identify and solve the pharmaceutical care issues surrounding antibiotic therapy • Be ready to report back to the group

39. ObjectivesBy the end of this session students should be able to: • List 4 methods of microbial investigation and time taken to get results • Define 3 methods to establish the presence of an infection • Describe the factors affecting the choice of antibiotic (organism, drug and patient factors)

40. ObjectivesBy the end of this session students should be able to: • List 5 factors to monitor in patients on antibiotic therapy appropriate to the particular infection • State the most likely causative organisms in 4 common infections • State a suitable antibiotic regime for empirical therapy of 4 infections • LRTI, UTI, Cellulitis, TB • Demonstrate the practical application of theoretical knowledge of antibiotic therapy through case studies

41. Thank you for all your hard work Please complete your evaluation

42. Tuberculosis

43. Tuberculosis • Causative organism • Mycobacterium tuberculosis • Slow growing • Acid fast • Aerobic bacillus

44. Tuberculosis - Pathology • Primary tuberculosis • Droplet infection + rapid multiplication in lungs • Dissemination via lymph nodes • Quickly asymptomatic • Cellular Immunity • Immune response after 2 - 8 weeks • Bacilli enter macrophages and form granulomatous lesions • Dormant but survive for many years • Activation • Host immune system depressed • Clinical Disease • Post primary tuberculosis • 10% risk of developing clinical disease after infection • Clinical Disease

45. Tuberculosis - diagnosis • CXR • shadowing, pleural effusion • Staining • positive for acid fast bacilli • Culture • sputum culture takes 4-8 weeks • sensitivity testing takes a further 3 weeks • Biopsy • Pleura, lymph nodes or lesions

46. Tuberculosis - Symptoms • Fever • Night sweats • Malaise • Dry cough +/- haemoptysis • Weight loss

47. Tuberculosis - Treatment • Initial phase • Reduce population of viable bacilli • Prevent emergence of drug resistant strains • Continuation phase • Eradicate slower growing dormant organisms • Longer treatment • Joint involvement • Resistant strains

48. Unsupervised 6-Month Drug Therapy • Initial phase • Three drugs (or four if risk of isoniazid resistance) for two months • Isoniazid • Rifampicin • Pyrazinamide • Add ethambutol if there is a risk of isoniazid resistance • Continuation phase • Two drugs for four months • Isoniazid • Rifampicin

49. Tuberculosis - Drugs • Isoniazid • Active against actively dividing bacilli in lung cavities • Adult dose: 300mg daily • Cautions • Hepatic impairment, renal impairment, alcoholism, slow acetylators • Side effects • N&V • Optic neuritis (give pyridoxine 10mg OD) • Peripheral neuropathy • Hepatotoxicity • Fever and rash • Haemolytic anaemia

50. Tuberculosis - Drugs • Isoniazid • Acetylator Status • Fast = higher dose required • Slow = risk of peripheral neuropathy • Drug Interactions • Enzyme inhibitor • Counselling • Take on empty stomach • Take as single dose • Watch for signs of liver dysfunction e.g N&V, jaundice, pale stools, dark urine, malaise