1. www.microbiologynutsandbolts.co.uk Microbiology Nuts & Bolts Test Yourself Session 2 Begin here

2. www.microbiologynutsandbolts.co.uk 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. www.microbiologynutsandbolts.co.uk Dorothy 81 years old nursing home resident Presents with  confusion and new incontinence On examination –Temperature 37.5 o C –Crackles throughout precordium –Cardiovascularly stable

4. www.microbiologynutsandbolts.co.uk How should Dorothy be managed? Admit to hospital with sepsis of unknown origin Dipstick a urine sample, treat for a presumed UTI Treat for community acquired pneumonia (CAP) Send an MSU and wait for result A B C D Choose A, B, C or D for the answer you feel best fits the question

5. www.microbiologynutsandbolts.co.uk Correct Answer: Dipstick a urine sample, treat for presumed UTI Urinary Tract Infection is the most likely cause of Dorothy’s confusion and incontinence and it is reasonable to treat her empirically A urine dipstick prior to this is prudent to help reassure that the diagnosis is likely to be correct There is no evidence presented here to suggest this patient is septic Crackles in the chest are usually due to heart failure, which in a older lady is more likely to be due to UTI than any other infection Delaying treatment whilst waiting for a laboratory result to come back is not necessary and may potentially lead to a more serious infection because antibiotics were not started soon enough

6. www.microbiologynutsandbolts.co.uk Dorothy After competing 3 days of antibiotics Dorothy is no better A repeat urine dipstick is done and then sent to the microbiology lab for microscopy, culture and sensitivity (MC&S) –Dipstick ++ leucs, ++ nitrite

7. www.microbiologynutsandbolts.co.uk What is the correct interpretation of the urine dipstick result? Definitely not UTI Definitely UTI UTI can probably be excluded UTI cannot be excluded A B C D Choose A, B, C or D for the answer you feel best fits the question

8. www.microbiologynutsandbolts.co.uk Correct Answer: UTI cannot be excluded The presence of leucocytes and bacterial nitrites in the urine sample means that a UTI can definitely not be excluded The negative predictive value of 97% in this situation of no leucocytes or nitrites would be able to exclude a UTI The positive predictive value of 60% in this situation does not prove a UTI but means it cannot be excluded

9. www.microbiologynutsandbolts.co.uk Dorothy Still no systemic signs of sepsis Check of recent bloods –eGFR >60ml/min Started on second line Nitrofurantoin 2 days later Much more confused, still incontinent Very distressed New onset vomiting and diarrhoea

10. www.microbiologynutsandbolts.co.uk What is likely to be the cause of Dorothy’s new symptoms? Clostridium difficile associated disease Encephalitis Antibiotic toxicity New infection e.g. Norovirus A B C D Choose A, B, C or D for the answer you feel best fits the question

11. www.microbiologynutsandbolts.co.uk Correct Answer: Antibiotic toxicity Nitrofurantoin toxicity presents with confusion, diarrhoea and vomiting and is usually due to prescribing Nitrofurantoin to someone in renal failure Nitrofurantoin is not active systemically and is only activated when excreted via the kidneys, in renal failure the prodrug builds up in the blood causing side effects It is much less likely that this lady has acquired a second infection

12. www.microbiologynutsandbolts.co.uk Dorothy Nitrofurantoin stopped Review of urine result from previously –Microscopy >100 x10 6 /L WBC, no epithelial cells –Culture E. coli –Resistant to Amoxicillin, Co-amoxiclav, Trimethoprim, Cephradine, Ciprofloxacin –Sensitive to Nitrofurantoin –Further results to follow

13. www.microbiologynutsandbolts.co.uk Why has the Nitrofurantoin not worked and Dorothy developed side effects despite an eGFR of >60ml/min? She was given too much Nitrofurantoin Her eGFR has changed eGFR is not accurate enough for dosing In her confusion she had too many tablets A B C D Choose A, B, C or D for the answer you feel best fits the question

14. www.microbiologynutsandbolts.co.uk Correct Answer: eGFR is not accurate enough for dosing Antibiotic dosing should be based upon the Cockcroft Gault equation which takes body mass in to account –Actual body weight or Ideal Body Weight (IBW) if weight > 20% above IBW –Also use IBW for patients with oedema & ascites

15. www.microbiologynutsandbolts.co.uk Dorothy Urine result –Microscopy >100 x10 6 /L WBC, no epithelial cells –Culture E. coli –Resistant to Amoxicillin, Co-amoxiclav, Trimethoprim, Cephradine, Ciprofloxacin –Sensitive to Nitrofurantoin –Further results to follow

16. www.microbiologynutsandbolts.co.uk What antibiotic should the patient be started on? IV Piptazobactam + Gentamicin PO Ciprofloxacin PO Co-amoxiclav IV Meropenem A B C D Choose A, B, C or D for the answer you feel best fits the question

17. www.microbiologynutsandbolts.co.uk Correct Answer: IV Meropenem Unfortunately there is no oral agent to treat Dorothy with so she will need intravenous antibiotics The sensitivity panel of this organism suggest the presence of a number of resistance mechanisms including a like Extended Spectrum Beta-Lactamase (ESBL) Enzyme excreted into periplasmic space which inactivates antimicrobials by cleaving the -lactam bond. Cause resistance to almost all -lactams including 3 rd -generation cephalosporins Associated with multiple antibiotic resistances Can be chromosome, plasmid or transposon encoded Can be constitutive or inducible The most consistently reliable antibiotic class to use empirically are the carbapenems such as Meropenem, Imipenem and Ertapenem

18. www.microbiologynutsandbolts.co.uk Dorothy Admitted to the local hospital and commenced on IV Meropenem Urine isolate confirmed as ESBL positive E. coli 24 hours into admission blood culture positive with Gram-negative bacillus which also identifies as E. coli

19. www.microbiologynutsandbolts.co.uk How long should Dorothy be treated for with IV Meropenem? 3 days Until afebrile then oral up to 7 days 7 days 14 days A B C D Choose A, B, C or D for the answer you feel best fits the question

20. www.microbiologynutsandbolts.co.uk Correct Answer: 7 days The blood culture being positive confirms a diagnosis of pyelonephritis and this requires 7 days of antibiotics There are no oral agents to treat this bacteria therefore she should be treated with IV antibiotics for the duration

21. www.microbiologynutsandbolts.co.uk ESBL Positive E. coli Most ESBL positive E. coli are still sensitive to the antibiotic Fosfomycin and so this can be used to treat simple UTIs in some patients

22. www.microbiologynutsandbolts.co.uk What is the correct dose of Fosfomycin for a simple UTI in a woman? 3g PO once 1g TDS IV 3g IV two doses 72 hours apart It should not be used in this situation A B C D Choose A, B, C or D for the answer you feel best fits the question

23. www.microbiologynutsandbolts.co.uk Correct Answer: 3g PO once Fosfomycin is an old fashion antibiotic which no longer has a license in the UK It is increasingly being used to treat resistant bacteria causing UTIs The dose for a simple UTI in a woman is one sachet of 3g once per oral For men the dose is an initial 3g sachet per oral followed by a second dose 72 hours later It is usually well tolerated with few side effects It can be difficult to get hold of in primary care so often there are arrangements with local hospitals to buy it in and arrange inter-pharmacy transfers for patients in the community

24. www.microbiologynutsandbolts.co.uk Dorothy Dorothy recovers from this episode of infection however 3 months later she has symptoms again suggestive of a UTI Her urine dipstick is positive

25. www.microbiologynutsandbolts.co.uk How should Dorothy be managed? Try Nitrofurantoin again Admit for IV Meropenem Trimethoprim Wait for culture result A B C D Choose A, B, C or D for the answer you feel best fits the question

26. www.microbiologynutsandbolts.co.uk Correct Answer: Admit for IV Meropenem It is very likely that this lady has another UTI UTIs are usually caused by the patients own bacteria getting in to the urine from the perineum The most common cause of UTI is E. coli In Dorothy’s case her own E. coli is resistant to most antibiotics and therefore her future UTIs are likely to be resistant An early admission may allow a shorter duration of treatment and prevent her getting in to the situation of having pyelonephritis as she did previously It may seem a bit like “using a hammer to crack a nut” but sometimes that is what you have to do

27. www.microbiologynutsandbolts.co.uk Dorothy After Dorothy was admitted this time her family asked if she could have any long-term antibiotics to prevent further episodes of infection

28. www.microbiologynutsandbolts.co.uk What would you recommend to the family about prophylactic antibiotics for Dorothy? No reason to give prophylaxis Regular oral Trimethoprim Weekly IM Meropenem No option for prophylaxis A B C D Choose A, B, C or D for the answer you feel best fits the question

29. www.microbiologynutsandbolts.co.uk Correct Answer: No option for prophylaxis Unfortunately due to the resistance of the E. coli causing these UTIs there is no suitable option for preventing these infections It is also debateable whether this is appropriate anyway although recurrent admission to hospital with potentially severe sepsis are a good reason for trying to prophylax if possible A better method for managing her is to try and use other methods for preventing the UTIs such as making sure Dorothy completely empties her bladder when she micturates Early treatment is the only real microbioogical option

30. www.microbiologynutsandbolts.co.uk Dorothy Dorothy was not started on antibiotic prophylaxis but was helped to try and prevent UTIs in other ways She had less frequent UTIs but did occasionally need to be admitted for short courses of IV antibiotics The End

31. www.microbiologynutsandbolts.co.uk Incorrect please try again Return to previous slide