Download Answer to Antibiotic Questions

Antibiotic treatment of the critically ill
Case 1
Likely site of infection
The most likely source of infection here is his chest. He has general signs of infection (fever),
with specific chest signs (cough, hypoxia). The presence of x-ray changes confirm this as a
diagnosis of pneumonia. The presence of hypotension and renal dysfunction indicate this is
likely to be a severe infection
Likely Pathogen – there are a number of patient factors that must be taken into account to
predict the likely organism. This patient has a community acquired pneumonia, and he is
not immuno-compromised, therefore Streptococcus pneumonia (also called pneumococcus)
is the most common cause. This is a gram positive cocci.
Other common causes are haemophillus influenzae, mycoplasma pneumoniae, moraxella
catarrhalis or the influenza virus.
Legionella is a potential cause, but usually associated with foreign travel or local outbreaks.
Despite best efforts, in 30-50% of cases no organism is identified. In 20%, more than one
pathogen is isolated.
If this were hospital acquired, the above pathogens could still be responsible. However,
there is a more diverse group of potential bacteria including gram negative organisms (E.coli,
klebsiella) and anaerobic bacteria.
In the immuno-compromised, there is an even greater breadth of potential causes. Fungal
and viral infections, as well as unusual bacteria, are all possible. However, an
immunocompromised person can obviously still develop a pneumococcal pneumonia. HIV
infection should be considered in any patient with severe infection, and testing should
always be offered.
Special considerations
This patient has renal dysfunction. It is useful to know if this is acute or chronic – if it is an
acute problem then it could continue to deteriorate. Many antibiotics are renally excreted,
so their levels can build up and cause toxicity in the presence of renal failure. Some drugs,
most notably aminoglycosides such as gentamicin, are renally toxic so careful consideration
of risk-benefit ratios need to be undertaken before using this drug in patients with renal
dysfunction.
What questions should you ask him and his family
Does he have any allergies. If he says yes, you must explore the nature of this allergy and
decide if it is a true allergy or not. Penicillin is a common cause of anaphylaxis (which can be
fatal), however it is also an extremely useful antibiotic so it should not be discarded lightly.
What antibiotic should you give
All hospitals will have local guidelines which reflect local disease and resistance prevalences.
These will cover the most likely pathogens.
GG&C recommends calculating the CURB65 score for all patients to stratify their mortality
and help decide upon appropriate therapy. This score gives patients 1 point for each of the
following features, meaning the range of possible scores is from 0 – 5.
Confusion
Urea
Respiratory rate
Blood pressure
Age
New confusion (abbreviated mental score <8)
>7mmol/L
30 or over
Systolic <90mmHg or diastolic <60mmHg
65 or older
Presence of sepsis syndrome is also to be calculated. Sepsis is defined as presence of the
systemic inflammatory response syndrome (SIRS), identified by having 2 or more of the SIRS
features, plus documented or highly suspicious source of infection.
The SIRS criteria are as follows:
<360C or >380C
>20
<4 or >12
>90
Temperature
Respiratory rate
White cell count
Heart rate
Using these two pieces of information, the patients can be classified into three groups: nonsevere; moderate; severe.
Non-severe
= CURB65 score 0 or 1 and no sepsis syndrome (mortality <3%)
Antibiotics choices
EITHER
Amoxicillin 500mg oral 8 hourly
OR
Doxycycline oral 200mg loading dose, then 100mg daily
OR
Moderate
Clarithromycin oral 500mg 12 hourly
= CURB65 score 2 and no sepsis syndrome (mortality 9%)
Antibiotic choices
Amoxicillin 500mg oral 8 hourly
AND EITHER
OR
Severe
Doxycyline oral 200mg loading dose, then 100mg daily
Clarithromycin oral 500mg 12 hourly
=CURB65 score 3≤ or pneumonia with any CURB65 score and sepsis
syndrome (mortality 17-57%)
Antibiotic choices
Clarithromycin 500mg oral or IV 12 hourly
AND
Penicillin allergy:
EITHER
Amoxicillin 1g IV 8 hourly (if no previous on antibiotics)
OR
Co-amoxiclav 1.2g IV 8 hourly (if already had antibiotics)
Mild pneumonia - choose either doxycyclin or clarithromycin
Moderate pneumonia – clarithromycin on its own
Severe pneumonia – vancomycin plus either clarithromycin or
doxycycline
Case 2
Likely cause of her infection
This patient has a sudden onset of symptoms in a previously fit and healthy young woman.
There is a suggestion of very poor peripheral perfusion, since her peripheries are cold and
her blood pressure is unrecordable. These could be the result of any severe infection.
The low conscious level could potentially be secondary to low blood pressure. However, it is
more likely to reflect CNS infection, which is most likely to be acute bacterial meningitis.
There are a number of common organisms which cause this: Neisseria meningitides (which
is a gram negative coccus, also called meningococcus) and streptococcus pneumoniae (the
pneumococcus again) are the two most common, accounting for over 70% of cases outwith
the neonatal period.
The description of possible bruises is likely to be a petechial rash, caused by microhaemorrhages within the skin. This is the classic non-blanching rash, which is strongly
suggestive of meningococcal septicaemia.
Treatment:
This is an extremely serious condition with a high morbidity and mortality. This girl needs
urgent attention, which should follow an ABCDE approach.
A–
assess her airway.
If patent, move on.
If obstructed, open with a head-tilt, chin-lift or a jaw thrust.
Try simple adjuncts, eg. guedel.
Any concerns, speak to senior or ICU.
B–
assess respiratory rate, depth, pattern.
Examine - percuss and auscultate her chest.
Monitor oxygen saturations.
Investigations - ABG is very useful in any septic patient. It would be worth
requesting a chest x-ray, to exclude possible pneumonia (since there is little history
available from this patient.)
Intervention - Administer high flow oxygen, aim sats 94-98%
C–
assess heart rate, blood pressure, capillary refill time, peripheral warmth.
Examine – auscultate her heart.
Monitor – continuous ECG and blood pressure monitoring.
Investigations - Routine bloods including a lactate. Blood cultures.
Intervention – Insert large bore IV access and give a fluid challenge of 20ml/kg of
crystalloid solution.
D–
assess her Glasgow Coma Scale, pupil size and reactivity.
Investigatons - blood glucose (very important in anyone with a low conscious level).
E–
assess for any other signs to explain her obtunded state – eg. evidence of trauma,
obvious abscess. Check her temperature. Assess for neck stiffness.
Once this is completed, the patient should be stabilised and you will have gained some
useful information regarding her state. You can now think about the sepsis-6. These are 6
steps that should be taken in the first hour of recognition of sepsis. A good mnemonic for
remembering the details of this is BUFALO:
B – Blood Cultures
U – Measure urine output accurately. Catheterisation may be appropriate.
F – Fluid challenge. Typically 20ml/kg. If systolic <90 or lactate over 4, give 30ml/kg.
A – Antibiotics. Broad spectrum, tailored to likely diagnosis.
L – Lactate. Measure this.
O – Oyxgen. Titrate this to achieve oxygen saturations of 94-98%.
You should already have achieved some of these as part of your ABCDE assessment.
Antibiotic therapy
Again, there are local protocols advising which antibiotics should be given. These need to
cover the major pathogens and to access the CSF in adequate dose.
GGC guidelines recommend the following:
Age <50years and listeria not suspected:
Ceftriaxone 2g IV 12 hourly, plus Dexamethasone 10mg IV 6 hourly.
If patients have a true, life-threatening penicillin allergy then chloramphenicol can be used
in place of ceftriaxone – however, urgent discussion with microbiology/infectious diseases is
recommended.
For those aged 50 or older, or where listeria is suspected, the above regimen is given with
the addition of IV amoxicillin 2g every 4 hours.
Microbiological confirmation
Pathogen identification is very important, but this should not delay rapid administration of
antibiotics. Blood cultures can normally be taken quickly, before the antibiotics are given.
Throat swabs should be taken (neisseria meningitidis is often present as a throat commensal
– this can help identify resistance patterns). Clotted and EDTA blood samples (purple and
yellow top tubes) should be sent for bacterial PCR – this normally takes a few days to come
back.
CSF can be obtained by lumbar puncture, and this can have a gram stain and be cultured to
identify organisms. However, this may not be appropriate in this patients case. Her low
conscious level could be indicative of raised intracranial pressure. If a spinal needle is then
inserted into the spinal space and CSF is removed, there is a risk that the pressure gradient
generated will cause the brain to be pushed down towards the spinal cord, where it
becomes wedged in the foramen magnum. This causes ischaemia of essential parts of the
brain-stem and rapid death – a process known as coning. Therefore, this patient should be
treated with antibiotics and a lumbar puncture should be delayed until she has been
reviewed by a senior doctor – they will normally request an urgent CT to decide if a lumbar
puncture is safe or not.
A CT scan should also be obtained prior to performing a lumbar puncture if age is >60; if the
patient has had seizures; if they are immunosuppressed or they have lateralising
neurological signs.
What would you tell her room mate
Meningitis is a notifiable disease, so public health must be informed of any cases.
Those who live with a patient with a proven episode of sepsis caused by neisseria
meningitidis have a 1 in 300 chance of developing disease in the following 30 days.
Antibiotic prophylaxis is recommended for those with close contact for 7 days prior to the
patient becoming unwell – this would include flat mates, partners, those sharing a common
eating area. GGC guidelines recommend a single dose of oral ciprofloxacin. Rifampicin is
also a possible option.
Prophylaxis should only be used after discussion with the local health protection unit. The
Brownlee infectious diseases unit in Gartnavel should be contacted for advice.
(Guidance
from
the
health
protection
http://www.hpa.org.uk/webc/hpawebfile/hpaweb_c/1194947389261)
Case 3
Sources: There is little information here, but there are a few likely sources.
agency.
Urinary Tract Infection (UTI) is a common type of hospital acquired infection. This patient is
likely to be catheterised, so this would increase the risk.
Hospital acquired pneumonia is also a common nosocomial infection. The shortness of
breath and low oxygen saturations may support this as a diagnosis – however, this can occur
due to sepsis of other origins, often as part of a multi-organ dysfunction.
Surgical site infection For any patient who has had recent surgery, a wound-site infection
or an infected collection has to be considered as a possible cause.
Investigations
The sepsis-6 should be performed for this patient, so that would include measuring Hb,
lactate and taking blood cultures. Some additional tests should be performed to help
quantify how unwell he is and to try to identify a source of infection:
Routine bloods: U&E, LFT
Arterial blood gas: quantify the level of hypoxia. Look for evidence of a metabolic acidosis
which may be present with sepsis.
Chest x-ray and urinalysis: screen for infection
Urine/sputum cultures:
Following examination and discussion with the surgical seniors, it is likely to be appropriate
to scan his abdomen and/or pelvis – this may be by ultrasound, but more likely to need a CT
to either confirm or refute a collection as the cause of this problem.
What antibiotics:
This will initially need to be broad-spectrum, reflecting the diagnostic uncertainty and the
fact that it is hospital acquired, which tends to increase the possible range of pathogens. As
previously, local guidelines should be followed, and microbiological help may be needed.
Any antibiotic regimen will need to consider the following issues:
Gram positive cover is important, as various streptocci can cause chest or urine infections.
Occasionally, staphylococci can be the problem.
Gram negative cover is also important – these are bacteria such as E.coli, klebsiella, proteus,
enterobacteriaceae and haemophillus. UTIs are often caused by gram negative bacteria,
however hospital acquired pneumonia can also be a gram negative. Intra-abdominal
infection is also commonly gram negative.
Abdominal infections (such as an infected collection) can often be caused by anaerobic
bacteria.
Co-amoxiclav (amoxicillin plus clavulonic acid) is a broad-spectrum, penicillin based drug. It
has reasonable activity against most of the above organisms and would be a reasonable first
choice.
Another possible choice would be the combination of amoxicillin, gentamicin and
metronidazole. Amoxicillin has a much narrower range than co-amoxiclav – it retains good
gram positive cover, but poorer gram negative and anaerobic. Gentamicin has excellent
gram negative cover and is present in high levels in the urine. Metronidazole has excellent
anaerobic cover.
Due to the uncertainty of the diagnosis, this is a more tricky case to treat and should
definitely be discussed with a senior clinician and possibly microbiology.
Case 4
This patient has clear evidence of a urinary tract infection, with probable pyelonephritis, as
suggested by the loin pain and the clear sepsis syndrome.
What organism
These are usually bowel pathogens. By far the most common cause is E. Coli, which is a
gram negative rod. Other relatively common pathogens include proteus and klebsiella, also
gram negative rods.
What antibiotic
This patient should be treated with intravenous antibiotics as she has clear evidence of
sepsis. GGC guidelines recommend IV amoxicillin 1g 8 hourly, plus two doses of IV
gentamicin.
Remember the possibility of pregnancy in a woman of this age – discuss this with a senior.
What if she is allergic to penicillin
Gentamicin monotherapy is advocated in penicillin allergy. It has excellent gram negative
cover and is present in the urine in high levels.