APT Vignette Discussion Session and Master Cards Title: John Finch

1. APT VignetteDiscussion Session and Master CardsTitle: John Finch

2. Descriptive Information

3. Title: When antibiotics need to be given for months • Student Level: Final year (Academic Half Day): • Learning Objectives for this Vignette (focus): • The signs and symptoms of a chronic infection with important infection control implications. • The importance of radiological and microbiological diagnosis of infection. • The issues associated with the long-term prescription of anti-microbial drugs, drug resistance and toxicity. • The principles of managing a “sharps” injury. • The essential consideration of any other underlying disease.

4. Which of the 12 Outcomes this Vignette Can Cover (1) This Vignette is primarily designed to help the student achieve outcomes 1- 12. 1. Clinical Skills - Elicit key symptoms and signs of commonest sites of bacterial infection. - Recognise and interpret common symptoms and signs of inflammatory response. - Interpret symptoms and signs; distinguish between bacterial infection, viral infection and other causes of inflammatory response. - Make a diagnosis of severe pneumonia. - Formulate a management plan. - Record findings. 2. Practical Procedures - Measures of inflammatory response (pulse, temperature, respiratory rate). - Measures of severe pneumonia (blood pressure, respiratory rate, pulse, oximetry). - Relevant near patient testing techniques. - Technique for obtaining microbiology samples from commonest sites of bacterial infection. - Correct methods for storage and transport of microbiology specimens. - Blood culture. Core Resources

5. Which of the 12 outcomes this Vignette can Cover (2) 3. Patient Investigation - General principles of patient investigation. - Appropriate choice and use informed by local protocols. - Laboratory based investigations. - Radiology. 4. Patient Management - Management strategies for common clinical syndromes, including alternatives to antibiotics. - Deciding on duration of treatment, measures of response to treatment and of successful outcome. - Use and abuse of IV antibiotics. - Recognition of complications, persisting or recurrent symptoms and management plan for dealing with them. - Sepsis and its management. • Health Promotion and Disease Prevention - Principles of control of infection in the hospital and in the community. 6. Communication - Communication of therapeutic objectives, and management plan. - Accessing advice and sharing responsibility with infection control practitioners. Core Resources

6. Which of the 12 outcomes this Vignette can Cover (3) 7. Appropriate Information Handling Skills • Minimum dataset to be recorded in order to support a decision to prescribe antibiotics. • Local antibiotic policy. • Local guidelines. • National guidelines. • Keeping up to date with resistance. • Personal record keeping for professional development: building a portfolio of achievement of learning outcomes. 8. Understanding of Social, Basic and Clinical Sciences and Underlying Principles • Host defences, immunological and non-immunological. • Pathology of inflammation and sepsis. • Mechanisms and spread of antibiotic resistance. • Classes of antibiotics used and shared allergies. • Pharmacokinetics in relation to drug selection for common infections. • Infection control. • Epidemiology of resistance. • Appropriate Attitudes, Ethical Understanding and Legal Responsibilities • Principles of prudent antimicrobial prescribing. • Shared decision making. Core Resources

7. Which of the 12 outcomes the Vignette can Cover (4) 10. Appropriate Decision Making Skills, Clinical Reasoning and Judgement - Coping with uncertainty - What is an acceptable risk to withholding any antibiotics, when you are uncertain of your diagnosis? - What is an acceptable prevalence of resistance to first-line drugs in antibiotic policies? 11. Role of the Doctor within the Health Service - Role of other members of the multi-professional team in prudent antibiotic prescribing 12. Personal Development - Assessment of own competence as an antibiotic prescriber; evaluating own capabilities and personal effectiveness. Assessment of need for support in decision- making about antibiotics - Searching for appropriate learning resources for antibiotic prescribing and resistance - Recognising limits of current understanding and identifying areas that need to be refreshed or extended - Setting realistic but challenging learning goals as a basis for personal growth Core Resources

8. B. Case Details

9. History You are the Specialist Registrar in Medicine, and the consultant is away on “study leave”. It is now 11.30 a.m. and after giving a talk at the weekly “Grand Round” you now start the post-take ward round. The House Officer shows you the chest-x-ray of a patient who was admitted early last evening. The patient came to the United Kingdom several weeks ago, seeking asylum from an area of conflict and social disruption in a part of Central Africa. It is unclear how he travelled from his home, but his troubles started over 3 months ago when he lost his job as a nursing and mortuary assistant at the hospital of his home town. It appears that he has suffered considerable deprivation in the period since then, and he is reticent about his current circumstances. He said that he was staying with a group of fellow countrymen in the City. The House Officer tells you that the patient has been unwell for some time, and complains now of weight loss, night sweats and fever. He has a cough productive of thick yellow sputum.

10. Clinical Signs • On examination: • Examination reveals an unwell and wasted young man, who is sweating profusely. His respiratory rate is 25/minute and his temperature is 39.50C. Patchy areas of bronchial and broncho-vesicular breathing can be heard over the mid-zone of the right lung field.

11. Investigations You note that the House Officer (HO) has the CXR ready, and that a number of tests for microbiology, biochemistry and haematology investigation are recorded in the patient’s notes. The HO’s diagnosis is also recorded here as “CAP” Sputum for MC&S √ Blood culture √ FBC ESR and CRP Start oral amoxicillin and erythromycin √

12. C. Question Categories

13. Consider a Working Diagnosis This case highlights important issues relating to a patient presenting with an infectious disease likely to be acquired from abroad 1.1 You review the CXR (The question button will access this). Describe the features that are seen here. 1.2 What is the working diagnoses here? 1.3 You note that the HO has only requested “MC&S” examination of the sputum specimens. What other test would you ensure that the laboratory does? 1.4 Later that day the SpR in Medical Microbiology ‘phones with the microscopy result that confirms your reasonable suspicions. What does this result show? (The question button will access this). 1.5 The likely diagnosis here has immediate infection control implications, which you as the SpR actioned at the outset! What are these? 1.6 The HO has diagnosed community acquired pneumonia. Are the antibiotics he prescribed correct for that diagnosis?

14. This case highlights important aspects in the diagnosis and management of tuberculosis (TB). Patient Management (1) 2.1 What are the important features of mycobacteria? 2.2 What sites in the body can TB be found? 2.3 What drug regime would you use to treat TB? 2.4 What are the side effects of these drugs? 2.5 Is there any underlying condition that you would consider here?

15. After the post-take ward round the phlebotomist takes blood from the patient for the requested laboratory tests. During this procedure, she sustains a “sharps” injury to a finger with the needle used for venepuncture on this patient. Patient Management (2) 3.1 What blood-borne viruses (BBV) would you consider in such a situation? 3.2 What are the approximate transmission rates for the viruses under consideration in these circumstances? 3.3 How can individuals who sustain a “sharps” injury be protected against infection by these viruses? 3.4 What actions must be taken after any “sharps” injury?

16. After one week, the patient shows no sign of improvement. He still has fever, night sweats and a productive cough. The blood culture taken on admission was reported as “No growth”, and the interim result of the first sputum processed states: “No growth. Profuse Acid-Fast bacilli seen; TB culture in progress”. Patient Management (3) Elaborate three possible reasons for the unresolved symptoms Reason 1 Reason 2 Reason 3 One of your reasons has the answer! What would you do now?

17. D. Best Practice Statements

18. Best Practice Statement (1) Tuberculosis • In any individual presenting with a chronic cough, and who has the symptoms and signs of a chest infection, always consider pulmonary tuberculosis. • If there is any doubt concerning an infectious disease, particularly if there are infection control implications, the relevant specialists must be contacted for immediate advice • If a CXR is requested, always ensure that it is reviewed as soon as possible. A CXR may prompt the diagnosis of tuberculosis being considered, and the need for appropriate Infection Control and Medical Microbiology intervention. The sooner TB is diagnosed, and “open” pulmonary TB in particular, the sooner treatment can start and any potential transmission to others can be stopped. For any patient with fever and weight loss always consider TB: active untreated TB always kills!

19. Best Practice Statement (2) Tuberculosis • Tuberculosis can be a complicated disease to treat, as taking three or more drugs for at least 6 months is difficult for some patients to comply with. Compliance not only ensures cure, but reduces the chance of drug-resistant organisms being selected. (With a “fully sensitive” isolate, patients are usually considered non-infectious after two weeks of correct treatment). • Compliance relies on good follow-up in the community, with liaison between the Public Health TB nurses, CCDCs and Chest Physicians being essential. Children should be referred to a Paediatrician with expertise in the management of TB in this age group. • Although fairly uncommon, the drugs used to treat TB can have serious side effects, and these should always be remembered.

20. Best Practice Statement (3) Tuberculosis TB is an excellent example of how good infection control practice can limit the Spread of an organism. • Always ensure that relevant information is communicated to other health care professionals regarding any risk to them; e.g. alert the laboratory staff by ensuring that the likelihood of TB is clearly indicated on the request form and other documents. Mortuary staff are another important group who may not usually be informed. • Always notify any diagnosis of TB to Public Health. This must be done where there is a radiological, histopathological, microscopy and/or culture diagnosis, PLUS where a patient has been started on empirical anti-TB therapy. • Always inform the Chest Physician of any new or relapsed case of TB. These clinicians are usually responsible for the long-term care of TB patients.

21. Best Practice Statement (4) Tuberculosis • TB treatment lasts at least 6 months, depending on the site of the body involved. Compliance, toxicity and drug resistance are important issues here. • Always consider any possible underlying disease process, based on occupational, social or travel history. This patient comes from a part of the world where there is a higher prevalence of HIV, and this should be considered. The patient must be carefully counseled by trained staff before an HIV test is done. • This process is clearly relevant for the correct management, by the appropriate physicians, of an HIV positive patient. • Risk assessment must be done as soon as possible when any person sustains a “sharps” injury. Where HIV transmission is a likelihood, this is a medical emergency, as anti-retroviral drugs needed to be started within one hour of the injury.

22. Summary of Management This patient presented with a history of travel, wasting, fever and a chronic cough. Pulmonary tuberculosis was considered promptly by the SpR when the CXR was reviewed with the clinical information. Important infection control, safety and Public Health issues were identified. The diagnosis was confirmed by positive microscopy using the Ziehl Neelsen stain. The patient was started on the usual first-line agents, but showed no improvement after 7 days. Drug compliance and/or drug resistance was considered (the latter confirmed by subsequent culture and susceptibility results), for which second line agents were needed. HIV co-infection was also considered; this had immediate implications when a “sharps” injury was sustained by the phlebotomist. MCQS

23. E. Correct/Appropriate AnswersF. Potential Responses and FeedbackG. References and Resources Master Cards:

24. 1.1 Describe the features here.

25. 1.1 Contd… Correct Response and Reason: The CXR Remember the process of reporting an X ray: • Check the patient details, and date (not shown here) • Check left/right/PA orientation of the X ray • Comment on the penetration • Comment on the bones • Comment on the soft tissues • Comment on the pathology “Fluffy infiltrate with patchy areas of consolidation involving the upper and lower parts of the right lower and right upper lobes respectively.” [Always ask for the lateral X ray as well]

26. 1.2 What is the working diagnosis? Correct Response and Reason: • Bacterial pneumonia • Pulmonary tuberculosis (In view of the history of travel, fungal infections such as Pneumocystis carinii and histoplasmosis may also be considered; the Medical Microbiologist should be consulted)

27. 1.3 You note that the HO has only requested “MC&S”examination of the sputum specimens. What other test would you ensure that the laboratory does? Correct Response and Reason: The Medical Microbiology laboratory should be contacted and asked to do a Ziehl Neelsen stain on the sputum specimens. Most laboratories will process specimens each weekday at least for the microscopy and culture of mycobacteria.

28. Later that day, the SpR in microbiology phones the HO reporting that the first sputum specimen collected last night contains numerous acid alcohol-fast bacilli (AAFB or AFB). 1.4 What does this result show?

29. 1.4 contd… Correct Response and Reason: The microscopy of mycobacteria Because they have a cell wall consisting largely of mycolic acids and glycolipids, mycobacteria do not stain with the gram stain. They are thus “gram-null”. Two staining methods are used: • Ziehl-Neelsen, whereby a dye such as the purple carbolfuchsin dye is forced into the cells on heating, acid-alcohol cannot remove the stain from mycobacteria, hence the term AAFB (acid-alcohol fast bacteria). Purple rods and clumps are seen against the background counter-stain of methylene blue. • Auramine is a fluorescent dye that binds to cell wall components of mycobacteria.

30. 1.5 The likely diagnosis here has immediate infection control Implications, which you as the SpR actioned at the outset! What are these? Correct Response and Reason: Infection control Mycobacterium tuberculosis is a significant infection control issue in hospitals and the community. “Smear-positive” patients with pulmonary TB are an important source of organisms that can infect others. The “at risk” exposure time is considered to be 6-8 hours or more, but this is probably less for immunocompromised individuals. When pulmonary TB is likely, or confirmed soon after admission by microscopy of sputum, the following should be done: • Nurse the patient in a side room, preferably one with negative pressure ventilation. (Never nurse immunocompromised patients in the same area!!) • Consult the Infection Control manual on the ward, and ascertain individual responsibilities (see the next two slides) • Communicate the information to nursing and ward staff • Inform the Infection Control team • Notify all suspected and confirmed TB cases to Public Health, including those patients started on empirical anti-TB treatment • Contact the Chest Physicians • Label Pathology specimens clearly. These disciplines are an example where safe practice should always take place (see last slide)

31. St Kilda NHS Trust Control of Infection Manual Guidelines for the Control of Tuberculosis This document was prepared for the Infection Control Committee by the Infection Control Team Review date: June 2007

32. Guidelines for the control of tuberculosis-contents Page List of contents 1 Introduction - What is Mycobacterium tuberculosis? 2 - Epidemiology and transmission 2 - The infection risk in the hospital setting 3 - The diagnosis of tuberculosis 3 - Multi-drug resistant TB (MDR TB) 3 Nursing staff-guidelines for the management of a suspected or confirmed case of pulmonary TB 4 Medical staff-guidelines for the management of a suspected or confirmed case of pulmonary TB 6 The use of negative pressure and other side-room facilities 8 Specimens collection, transport and the role of the Medical Microbiology laboratory 9 Treatment and referral of patients to the Chest Physician 11 Occupational Health-Tuberculosis and the Health Care Worker 13 Notification and Public Health issues in the hospital and community 14 Tuberculosis and the Hospital Mortuary 15 List and contact details of hospital and Public Health officers 16 References 17

33. In the Medical Microbiology laboratory, ALL sputum specimens, and any other specimens where TB investigations have been requested, are processed in a category 3 safety room. There is access only to designated staff, who must process specimens in a ventilated “safety hood”.

34. 1.6 The HO has diagnosed community acquired pneumonia. Are the antibiotics he prescribed correct for that diagnosis? Correct Response and Reason: Guidelines for the treatment of Community Acquired Pneumonia (CAP) This slide is a reminder of Medical Microbiology Vignette number 07. Please refer to this and the guidelines of the British Thoracic Society, and the Trust’s Antibiotic Guidelines which are available on the Intranet. (This is essential for your revision!)

35. 2.1 What are the important features of mycobacteria? Correct Response and Reason: The features of mycobacteria • Mycobacteria do not stain with the Gram stain. Their cell wall contains peptidoglycan, mycolic acids and glycolipids. Important pathogenic properties include cord factor (trehalose-6’6-dimycolate) and the “waxes D.” • Mycobacteria are slow growing and divide every 18 hours or so. Media for growth must contain albumin and glycerol. Liquid culture systems (similar to standard blood culture methods) have reduced times to positive culture to 1-2 weeks. • Antibodies are produced, but they have no role in the pathogenesis of disease. About 1/3 of the world’s population are infected with Mycobacterium tuberculosis, but clearly many less have active disease. Cell-mediated immunity is the defense system of the body here.

36. 2.2 At what sites in the body can TB be found? Correct Response and Reason: The sites of the body that can be involved in tuberculosis • Any organ system may be involved in a manifestation of the disease (because the organism usually disseminates widely in primary infection,) • About 80% of cases involve the lungs • Of the remaining 20% or so, the lymphatics, pleura, meninges and renal tract are not uncommon sites

37. 2.3 What drug regime would you use to treat TB? Correct Response and Reason: The treatment of tuberculosis • The first-line agents are rifampicin (RIF), isoniazid (INH), pyrazinamide (PZA), to which a fourth agent, ethambutol is often added. • As it is not active against dormant bacteria, PZA is usually stopped after 2 months. • The minimum period that the remaining agents are given is 6 months. • Second line agents, which are usually less effective, include ciprofloxacin, clarithromycin, cycloserine and amikacin.

38. 2.4 What are the side effects of these drugs? Correct Response and Reason: The side effects of anti-tuberculous agents • INH and RIF can cause hepatotoxity; PZA probably does not cause additional risk here. • Ethambutol can cause visual disturbances and optic neuritis. This side effect is more likely to occur in renal failure. Sedated patients, on the ICU for example, should probably be considered for an alternative 4th agent.

39. 2.5 Is there any underlying condition that you would consider here? Correct Response and Reason: • The patient comes from Sub-Saharan Africa, where TB is an important AIDS-defining illness. • The consideration of HIV is essential for the correct management of the patient. An important example is a female patient who is pregnant, where in addition to diagnosis and treatment for her, antiviral prophylaxis can significantly reduce transmission of the virus to the child. • Usually Gemto urinary medicine (GUM) staff are contacted to counsel a patient for an HIV test, as they have the training to conduct the process in a compassionate and confidential manner.

40. 3.1 What blood-borne viruses (BBV) would you consider in such a situation? Correct Response and Reason: Blood-borne viruses: • Hepatitis B virus (HBV). • Hepatitis C virus (HCV). • Human immunodeficiency virus (HIV).

41. 3.2 What are the approximate transmission rates for the viruses under consideration in these circumstances? Correct Response and Reason: The approximate transmission rate of the three BBVs in a “sharps” injury is estimated to be: • HBV 30% (1 in 3 chance). • HCV 3% (1 in 30 chance). • HIV 0.3% (1 in 300 chance).

42. 3.3 How can individuals who sustain a “sharps” injury be protected against infection by these viruses? Correct Response and Reason: Protection against BBV transmission. The role of Occupational Health • HBV. All health care professionals should be vaccinated against the surface antigen of the virus, and they should know their immune status and last vaccination date. Non-responders to the vaccine, with no other underlying conditions to explain this, should be discouraged from working in units where there is direct working with the blood of patients, e.g. renal dialysis. If a “sharps” injury occurs, non-responders are given HBV immunoglobulin as soon as possible, and within 48 hours of the injury. • HCV. There is currently no vaccine or other recognized prophylaxis. • HIV. Antiviral combinations e.g. zidovudine, lamivudine and nelfinavir, given within an hour of the injury, and taken for 4 weeks, are recognized as being effective. Note that a “sharps” injury where untreated HIV is a consideration is a medical emergency.

43. 3.4 What actions must be taken after any “sharps” injury? Correct Response and Reason: How to manage a “sharps” injury-an incident where HIV is a known or possible risk is a medical emergency. • Immediately wash the wound thoroughly with fast-running water, and express any blood. • Contact the person in charge, and seek immediate advice from Occupational Health, GUM or Infection Control. • Ensure that a “risk assessment” is done as soon as possible. This includes ascertaining if the “donor” takes part in high-risk sexual practices, uses intravenous drugs, or is from a part of the world where there is a higher incidence of HIV.

44. Elaborate three possible reasons for the unresolved symptomsReason 1 The patient may not be compliant of the treatment. This would probably be uncommon in the hospital setting, but in the community Directly Observed Therapy (DOT) can be used to ensure compliance over the 6 months of therapy. The patient’s urine can be checked; if this is red-stained it means that Rifampicin, at least, is being taken. With doses over 150 mg, the hepatic excretory threshold of rifampicin is exceeded and renal excretion of this red-coloured drug then occurs.

45. Elaborate three possible reasons for the unresolved symptomsReason 2 With a history of recent travel from Central Africa, other agents should be considered. One example is malaria, which must be excluded by a competitent morphologist. (haematologist or biomedical scientist) Advice should be sought from the Medical Microbiologist or Infectious Diseases physician.

46. Elaborate three possible reasons for the unresolved symptomsReason 3 Drug resistant organisms are always an important consideration. Resistance to one agent such as isoniazid is not uncommon in certain communities. Multi-drug resistant Mycobacterium tuberculosis isolates (MDR-TB) are those resistant to two, (e.g. isoniazid and rifampicin), or more agents.

47. Department of Medical MicrobiologySt. Kilda’s NHS Trust

48. What to do now…. The final culture result confirms drug resistance to the 4 first-line agents. With the index of suspicion at one week, the following would be done: • Seek expert advice from the Chest Physicians, Medical Microbiologists, Infection Control and Infectious Diseases Physician. • The Medical Microbiologist will ensure that cultures sent to the Reference laboratory are “gene probed” for RIF resistance. • Consider starting at least 3 second-line agents.

49. Core Resources • JK Struthers and RP Westran (2003) Clinical Bacteriology. Manson Publishing (chapters 2, 4, 8, 14, 15). • Infection and Immunity module course book. • www.brit-horacic.org.uk/guide/guidelines.html • The British National Formulary (BNF.org) Chapter 5: Infections.

50. Multiple Choice Questions (1) Regarding rifampicin It inhibits bacterial protein synthesis. It induces P-450 cytochrome oxidase, which can alter the levels of Important drugs,including steroids such as the oral contraceptive. It is usually given intravenously. It also has activity against staphylococci and streptococci. It can colour the urine red. Regarding Mycobacterium tuberculosis Is the only species of mycobacteria that causes lung disease. Treatment with first-line agents against a fully sensitive organism is equally effective in both immunocompetent and immunocompromised individuals. It has a cell wall structure similar to gram-negative bacteria. Antibodies play no role in the disease process. It rarely disseminates from the lung. SUMMARY OF MANAGEMENT ANSWERS