How to prescribe antibiotics: maybe it`s not as simple as you think…

Microbiology Nuts & Bolts
Test Yourself Session 4
Begin here
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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.
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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
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Which of the following is the most
likely life-threatening infection that
should be considered?
Choose A, B, C or D for the answer you feel best
fits the question
A
B
C
D
Urinary tract infection
Meningitis
Encephalitis
Community acquired pneumonia
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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
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Dorothy
• Dorothy had various investigations performed
and was started on antibiotics
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Which of the following are the most
useful investigations for encephalitis?
Choose A, B, C or D for the answer you feel best
fits the question
A
B
C
D
FBC,
FBC,
FBC,
FBC,
U&Es, lumbar puncture, MRI scan
U&Es, blood cultures, CT scan
U&Es, lumbar puncture, CT scan
clotting, lumbar puncture
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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
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Which of the following antibiotics should
be started empirically?
Choose A, B, C or D for the answer you feel best
fits the question
A
B
C
D
Cefotaxime
Benzylpenicillin + Aciclovir
Cefotaxime, Amoxicillin + Aciclovir
Cefotaxime + Aciclovir
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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
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Dorothy
• She has a lumbar puncture performed and the
result come back as:
– Red blood cells = 62 x 109/L
– White blood cells = 57 x 109/L
• 90% Lymphocytes
• 10% Neutrophil polymorphs
– Protein 0.87 g/L
– Glucose 2.9 mmol/L
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Which of the following organisms is
most likely to cause this CSF result?
Choose A, B, C or D for the answer you feel best
fits the question
A
B
C
D
Mycobacterium tuberculosis
Herpes Simplex Virus
Listeria monocytogenes
Streptococcus pneumoniae
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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.
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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
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What is the correct treatment of HSV
encephalitis?
Choose A, B, C or D for the answer you feel best
fits the question
A
B
C
D
PO Aciclovir
IV Aciclovir
PO Valaciclovir
IV Valaciclovir
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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
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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
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What blood test should be
monitored for patients on Aciclovir?
Choose A, B, C or D for the answer you feel best
fits the question
A
B
C
D
Full Blood Count
Liver Function Tests
International Normalised Ratio
Urea & Electrolytes
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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
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After 14 days, when can the IV
Aciclovir be stopped?
Choose A, B, C or D for the answer you feel best
fits the question
A
B
C
D
When
When
When
When
the
the
the
the
symptoms have resolved
MRI scan is normal
CSF has no WBCs in it
CSF PCR is negative
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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
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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
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What % of patients have long-term
sequelae after HSV encephalitis?
Choose A, B, C or D for the answer you feel best
fits the question
A
B
C
D
80%
60%
40%
20%
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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
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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
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What is the treatment of HSV
meninigitis?
Choose A, B, C or D for the answer you feel best
fits the question
A
B
C
D
1 week of IV Aciclovir
2 weeks of IV Aciclovir
3 weeks of IV Aciclovir
Until the CSF PCR is negative
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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
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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
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Incorrect please try again
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