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1 Microbiology Nuts & Bolts Test Yourself Session 4 Begin here

2 The patient in this test yourself case is entirely fictitious, however it is based on many clinical scenarios the author has come in to contact with during his medical career. Any similarity to a real case is entirely coincidental.

3 Dorothy 83 year old lady, previously fit and well Past medical history of mild hypertension only Admitted as an emergency with acute confusion, aphasia and a fever followed by a seizure

4 Which of the following is the most likely life-threatening infection that should be considered? Urinary tract infection Meningitis Encephalitis Community acquired pneumonia A B C D Choose A, B, C or D for the answer you feel best fits the question

5 Correct Answer: Encephalitis Whilst UTIs and pneumonia are common causes of infection with subsequent confusion in the elderly, it is important to exclude the most serious infections first Meningitis and encephalitis are both serious infections, but the combination of fever, confusion and a focal neurological sign such as aphasia make encephalitis more probable A differential diagnosis is important and, in order not to miss the serious diseases, should initially take the form of: –Life-threatening –Common –Uncommon

6 Dorothy Dorothy had various investigations performed and was started on antibiotics

7 Which of the following are the most useful investigations for encephalitis? FBC, U&Es, lumbar puncture, MRI scan FBC, U&Es, blood cultures, CT scan FBC, U&Es, lumbar puncture, CT scan FBC, clotting, lumbar puncture A B C D Choose A, B, C or D for the answer you feel best fits the question

8 Correct Answer: FBC, U&Es, lumbar puncture, MRI scan Many hospitals would perform a CT scan before performing a lumbar puncture but in the context of encephalitis the CT is unlikely to show any abnormality. It is also unable to predict the likelihood of coning due to high intracranial pressure during a lumbar puncture FBC and U&Es are useful indicators of the type of response to infection the patient might have as well as ensuring the correct dose of antibiotics is used A lumbar puncture will allow cerebrospinal fluid (CSF) analysis and help to distinguish viral and bacterial infections MRI scans are abnormal in 90% of patients with encephalitis and are the most useful diagnostic test

9 Which of the following antibiotics should be started empirically? Cefotaxime Benzylpenicillin + Aciclovir Cefotaxime, Amoxicillin + Aciclovir Cefotaxime + Aciclovir A B C D Choose A, B, C or D for the answer you feel best fits the question

10 Correct Answer: Cefotaxime, Amoxicillin + Aciclovir At this stage the causative organism is not known and so the empirical treatment must cover all possible causes The most likely (and treatable) causes of encephalitis + / - meningitis are: –Streptococcus pneumoniae – covered by Cefotaxime (or Ceftriaxone) –Listeria monocytogenes – covered by Amoxicillin (or Ampicillin) –Herpes Simplex Virus – covered by Aciclovir When a definitive cause is found then treatment can be narrowed down but not until then. Antibiotic treatment should not be delayed in order to perform investigations, these are medical emergencies that need urgent treatment

11 Dorothy She has a lumbar puncture performed and the result come back as: –Red blood cells = 62 x 10 9 /L –White blood cells = 57 x 10 9 /L 90% Lymphocytes 10% Neutrophil polymorphs –Protein 0.87 g/L –Glucose 2.9 mmol/L

12 Which of the following organisms is most likely to cause this CSF result? Mycobacterium tuberculosis Herpes Simplex Virus Listeria monocytogenes Streptococcus pneumoniae A B C D Choose A, B, C or D for the answer you feel best fits the question

13 Correct Answer: Herpes Simplex Virus As Streptococcus pneumoniae is a bacteria it would cause a large rise in the neutrophil polymorphs and the protein and a drop in the glucose. Whilst the protein is slightly abnormal it is only slight, and the glucose is within the normal range without a peripheral glucose to compare to i.e. >2.2 mmol/L Mycobacterium tuberculosis and Listeria monocytogenes are usually intracellular bacteria and hence can cause a rise in lymphocytes in the CSF, but as they are both bacteria they would also be expected to cause the protein to rise very high and the glucose to drop. The picture of lymphocytes, normal or only slightly raised protein and normal glucose is consistent with a viral infection and Herpes Simplex Virus is the only virus in the list.

14 Dorothy An MRI scan is performed which shows changes indicative of HSV encephalitis The CSF sample is sent for PCR which confirms the presence of HSV, and confirms the diagnosis of HSV encephalitis

15 What is the correct treatment of HSV encephalitis? PO Aciclovir IV Aciclovir PO Valaciclovir IV Valaciclovir A B C D Choose A, B, C or D for the answer you feel best fits the question

16 Correct Answer: IV Aciclovir The treatment of HSV encephalitis is with intravenous aciclovir The oral absorption of aciclovir is only 15-20% and so it should never be used orally to treat serious infections There is no evidence to suggest that the oral pro-drug of aciclovir, Valaciclovir, is suitable for treating encephalitis and there is no IV formulation

17 Dorothy The patient was continued on IV Aciclovir and the other antibiotics were stopped She made little progress for the first few days, but from day 5 onwards she began to make rapid progress, her confusion and aphasia resolved By 14 days she had almost improved back to how she was before the infection and a discussion was had about how long to continue treatment

18 What blood test should be monitored for patients on Aciclovir? Full Blood Count Liver Function Tests International Normalised Ratio Urea & Electrolytes A B C D Choose A, B, C or D for the answer you feel best fits the question

19 Correct Answer: Urea & Electrolytes The main side effects of Aciclovir are nausea, rash, neurotoxicity and nephrotoxicity The only one of these that can be monitored for in blood is nephrotoxicity for which baseline and at least weekly U&Es should be taken

20 After 14 days, when can the IV Aciclovir be stopped? When the symptoms have resolved When the MRI scan is normal When the CSF has no WBCs in it When the CSF PCR is negative A B C D Choose A, B, C or D for the answer you feel best fits the question

21 Correct Answer: when the CSF PCR is negative The current recommendation from the British infection Association (BIA) is that the lumbar puncture should be repeated at 14 days and the Aciclovir stopped if the PCR is negative. If the PCR is positive then the Aciclovir should be continued and the PCR repeated every 7 days until it is negative This involves a repeat invasive procedure and a delay in waiting for the results and so is not often done, with a more pragmatic approach being to give 21 days if the repeat PCR is positive

22 Dorothy The patient made a good recovery and was discharged from hospital 4 weeks after admission having received 3 weeks of Aciclovir She was seen in the outpatient clinic 6 weeks later and complained that she was getting quite bad headaches

23 What % of patients have long-term sequelae after HSV encephalitis? 80% 60% 40% 20% A B C D Choose A, B, C or D for the answer you feel best fits the question

24 Correct Answer: 80% Up to 80% of patients have headaches or weakness after HSV encephalitis Long-term sequelae are more common in the elderly and in those in whom treatment with IV Aciclovir was delayed These long-term problems may slowly improve with time but the can also continue indefinitely; there is no specific treatment

25 Dorothy This patient had encephalitis, or infection and inflammation of the brain, however HSV can also cause meningitis without encephalitis Meningitis is inflammation of the membranes surrounding the brain which causes headache and photophobia Patients with meningitis do not normally have the focal neurological symptoms or seizures that are a feature of encephalitis

26 What is the treatment of HSV meninigitis? 1 week of IV Aciclovir 2 weeks of IV Aciclovir 3 weeks of IV Aciclovir Until the CSF PCR is negative A B C D Choose A, B, C or D for the answer you feel best fits the question

27 Trick Question! Answer: There is no specific treatment for HSV encephalitis, it is a self-limiting infection There is no evidence that antibiotics such as Aciclovir make any difference in HSV meningitis Patients should be advised about analgesia but otherwise the infection usually gets better without any treatment

28 Dorothy So Dorothy was investigated and treated correctly for her HSV encephalitis but despite this she had long-term complications However, without this good management the outcome would have been much worse The End

29 Incorrect please try again Return to previous slide

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