Download NES Core Course on Antimicrobials

NES Core Course on Antimicrobials
Case study 1
Hospital Treatment of Community Acquired Pneumonia (CAP)
AM, a 66 year old male presents to hospital with fever (39.2 oC), pleuritic chest
pain and cough. On arrival he is tachypnoeic (RR 32/min) and hypotensive (BP
88/57 mmHg). His WCC is raised at 18x109/l, his CRP is 203mg/l and urea is
raised at 7.3mmol/l. Arterial blood gases show a type I respiratory failure picture
and he remains profoundly hypoxaemic despite maximal oxygen therapy. The
decision is made to admit AM to intensive care for ventilatory and cardiovascular
support. He is mechanically ventilated and commenced on inotropes to maintain
his blood pressure. A diagnosis of severe CAP is made.
PMH:
Hypertension
Current Medication:
Aspirin 75mg daily
Lisinopril 20mg twice daily
Simvastatin 20mg nocte
No known drug allergies (NKDA)
1. What is the definition of pneumonia?
In GP practice:
Symptoms of an acute lower respiratory tract infection, with new focal chest signs
on examination (e.g. crepitations) and at least one systemic feature (e.g. fever,
shivers, sweats and/or temp >380C and no other explanation for illness).
In hospital practice:
Symptoms and signs consistent with an acute lower respiratory tract infection
associated with new radiographic shadowing on chest x-ray for which there is no
other explanation (e.g. not pulmonary oedema or pulmonary embolism) (BTS
2004).
2. What are the possible pathogens?
The most common pathogens are Streptococcus pneumoniae and Haemophilus
influenzae. Other pathogens include Legionella spp., Mycoplasma pneumoniae,
Gram-negative enteric bacteria, Chlamydia spp. and Staphylococcus aureus.
3. How should severity be assessed?
Cap is a potentially serious condition with a mortality rate of approximately 20%
in the UK. Several tools have been developed to assess severity and ensure that
-1-
patients with severe pneumonia are managed promptly and effectively, e.g.
Pneumonia Severity Index (PSI) and CURB-65 (CRB-65 in community).
The CURB-65 tool is the most common tool used in the UK.
C= confusion – new (AMT ≤8) (AMT=Abbreviated Mental Test, scored out of 10)
U= urea > 7 mmol/L (omitted in community assessment)
R= respiratory rate ≥ 30 breaths per min
B= blood pressure; systolic < 90 and/or diastolic ≤60mmg Hg
65= Age ≥ 65 years

Patients who have a CRB-65/CURB-65 score of 0 are at low risk of death and
do not normally require hospitalisation for clinical reasons.
 Patients who have a CRB-65/CURB-65 score of 1 or 2 are at increased risk of
death and hospital referral and assessment should be considered, particularly
with a score of 2.
 Patients who have a CRB-65/CURB-65 score of 3 or more are at high risk of
death and require urgent hospital admission and possibly high
dependency/intensive care.
The Scottish National Audit Programme – Community Acquired Pneumonia
(SNAP-CAP) is a National programme which aims to improve outcomes for
patients with CAP.
SNAP-CAP uses a care bundle approach (c.f. Scottish Patient Safety
Programme) and quality improvement methodology.
Care bundle to be delivered within 4 hours of presentation at hospital
1. O2 saturations 94-98% (88-92% in patients at risk of hypercapnia).
2. Severity assessment using CURB-65 score) to decide whether admission is
required and direct antibiotic treatment.
3. Antibiotics given according to local policy and based on severity assessment –
mild cases given oral antibiotics and severe cases (CURB-65 3-5) given IV
antibiotics.
4. What score does AM have?
CURB-65 score = 4 (Urea>7, Resp. rate>30, Blood pressure low, Age>65 years)
5. What is appropriate therapy?
With CURB-65 score of 4, AM is at high risk of death. Urgent admission is
required and IV antibiotics should be administered as soon as possible.
Antibiotic choices:
Co-amoxiclav 1.2g three times daily IV PLUS clarithromycin 500mg twice daily IV
( bioavailability of clarithromycin ~ 60%)
Alternative options - levofloxacin IV +/- benzylpenicllin IV
Penicillin allergy – levofloxacin IV, ceftriaxone IV (if no history of anaphylaxis) or
vancomycin IV plus ciprofloxacin IV
-2-
6. If AM had recently had influenza, how might that alter therapy?
There is an increased incidence of Staphylococcal infection post influenza.
In view of the severity of CAP, Staph. aureus should be covered by adding
Flucloxacillin 1-2g qid IV.
7. What pharmaceutical care issues would you have for this patient?
1. Choice of antibiotic – discuss need for broad spectrum cover and risks/benefits
of using antibiotics associated with CDAD.
2. Route of administration - IV to oral switch policy (IVOST).
3. Course length - should be at least 10 days (14-21 days if staphylococci,
legionella or gram-negative enteric organism is suspected pathogen).
4. Review culture and sensitivity of samples and ensure empirical therapy
appropriate.
5. Monitor infection parameters closely – temperature, WCC, CRP, inotrope
requirements.
6. Monitor renal function – patients with sepsis often have deranged renal
function. If necessary adjust drug doses in line with recommendation in Renal
Drug Handbook. Remember to review doses as renal function improves.
7. Simvastatin / clarithromycin interaction – advise changing to pravastatin or
rosuvastatin for course of treatment or stopping the simvastatin. Check local
policy.
8. Ensure antihypertensive withheld until blood pressure returns to normal.
9. Ensure thromboprophylaxis given according to local policy.
10. Stress ulcer prophylaxis recommended in ventilated patients. Check local
policy for agents used.
-3-
Case study 2
Hospital Treatment of Hospital Acquired Pneumonia
DL, a 78 year old female nursing home resident was admitted to hospital with a
fractured neck of femur. She was taken to theatre where a dynamic hip screw
was inserted. During surgery, she became very hypotensive and tachycardic and
was taken to the high dependency unit post-operatively for monitoring. After 48
hours, she returned to the ward. On day 4, she became pyrexial (38.9 0C) and her
oxygen saturations fell to 91%. A full blood count showed an increased white cell
count (14.2 x 109/l) and her chest x-ray showed new infiltrates. A clinical
diagnosis of hospital acquired pneumonia (HAP) was made. Blood and sputum
samples were sent for culture and sensitivity testing.
PMH:
Ischaemic heart disease
Hypertension
Type 2 diabetes mellitus
Chronic renal failure
Recent stroke (discharged 6 weeks ago after 4 week admission)
Current Medication:
Aspirin 75mg daily
Atenolol 25mg daily
Gliclazide 160mg bd
Ramipril 5mg daily
Insulatard 12 IU nocte
Dipyridamole MR 200mg bd
Bendroflumethiazide 2.5mg daily
1. What is the definition of HAP?
HAP is usually defined as pneumonia developing ≥48 hours after admission to
hospital (i.e. the infection was not present or incubating at the time of admission).
HAP can be divided into early and late onset.
4-5 days of admission and tends to be
community-acquired pathogens. Late onset
admission and tend to be caused by hospital
different spectrum of antibiotic cover.
Early onset disease occurs within
caused by antibiotic-susceptible
infections develop >5 days after
acquired pathogens and require a
A related condition, healthcare-associated pneumonia (HCAP), has also been
described where pathogens are associated with recent hospitalisation and/or
antimicrobial therapy.
HCAP has been defined as pneumonia occurring in a patient who has:
 been admitted to hospital for 2 or more days within previous 90 days
-4-



been resident in a nursing home or long term care facility
attended a hospital within previous 30 days
received IV antibiotic therapy, chemotherapy or wound care within the
previous 30 days.
(Guidelines for the management of HAP in the UK: Report of the Working Party
on HAP of the British Society for Antimicrobial Chemotherapy. Journal of
Antimicrobial Chemotherapy. 2008; 62: 5-34.)
2. What are the likely pathogens?
Early onset:
Often caused by community organisms such as Streptococcus pneumoniae or
Haemophilus influenzae.
Late onset: (or HCAP)
The longer the patient is in hospital, the wider the spectrum of likely pathogens
they have been exposed to and the more likely the organisms are to be resistant
used to treat early onset pneumonia.
Gram negative organisms such as Pseudomonas aeruginosa, Escherichia coli,
Klebsiella spp., Enterobacter spp. and Serratia spp. may be implicated as can
MRSA, MSSA, and anaerobes.
Empirical antibiotic therapy must take into account these factors.
3. What empirical therapy would you recommend for early onset HAP with no risk
factors?
Amoxicillin plus metronidazole or co-amoxiclav oral/IV depending on severity.
May add gentamicin if severe to give increased gram-negative cover.
Intravenous therapy is recommended where there are symptoms of infection
(sweats, chills, rigors etc.) PLUS 2 of the following:
Temp >38oC or < 36oC
HR > 90bpm
RR > 20/min
WCC < 4x 109/l or >12x 109/l.
Other options include oral ciprofloxacin, IV ceftriaxone, IV levofloxacin or oral
moxifloxacin. These agents may be more likely to be associated with CDAD and
therefore should be used with caution.
Moxifloxacin has also been associated with serious liver toxicity which may also
be a consideration.
4. In view of the clinical history, would you alter your choice?
There is a high risk that the infection has been caused by a pathogen more
associated with late-onset HAP and should be managed accordingly.
-5-
One possible empirical regime would be piperacillin/tazobactam 4.5g tds IV +/gentamicin (dose as per local policy).
Other options include ceftazadime plus ciprofloxacin, meropenem +/- gentamicin
(American Thoracic Society guidance).
5. Sputum culture grew MRSA. What antibiotic choices are there?
Vancomycin IV or linezolid IV/oral or teicoplanin IV. Consideration should also be
given to MRSA eradication - follow local policies (BSAC 2008).
6. Vancomycin has been selected. Suggest a suitable starting dose for this
patient (latest serum creatinine = 145 micromol/l, weight estimated at 56kg)
Creatinine Clearance = ~ 25ml/min
Hand out local algorithm to determine dose including loading dose instructions.
Loading is a fairly new concept – aim is to reach steady state quickly and
maintain adequate serum/tissue concentrations from onset of therapy.
Could also discuss vancomycin infusions – used in Intensive Care setting.
7. What pharmaceutical care issues require consideration in this patient?
Monitoring of vancomycin trough level – when should first level be taken, target
level, how often should levels be taken and how should regimen be altered if
levels out with target range?
Usually check trough level before 2nd or 3rd dose then every 48-72 hours. Check
more frequently if renal function unstable.
Target range is 10 – 15 mg/L (15 – 20mg/L for severe infections).
Usually adjust dosage interval if level is too high or low.
Monitor response to antibiotic treatment and advise on duration of therapy.
Review infection parameters daily. Consider IV to oral switch when clinically
improved. Course length should be minimum of 7 days.
Diabetic control may be problematic during period of infection and sliding scale
infusion of insulin may be required.
Assess patient’s ability to maintain oral fluid intake and medication.
-6-
Case study 3
Hospital Treatment of Infective Exacerbation of Chronic Obstructive
Airways Disease (COPD)
RB, a 64 year old gentleman with severe COPD has been feeling unwell for past
5 days. He complains of increased shortness of breath (SOB) and is coughing up
purulent sputum. His GP had given him a supply of amoxicillin and oral steroids
to keep at home following a similar previous episode and he has been taking
these for the past 4 days. Today, he called the GP with worsening symptoms.
On examination he was tachypnoeic, his sputum was still purulent and he was
struggling to cope. His oxygen saturations were 90% on room air therefore the
GP arranged admission to hospital for further investigation and treatment.
PMH:
Severe COPD – frequent admissions to hospitals with infective exacerbations.
Two courses of amoxicillin in past 6 weeks from GP.
Atrial fibrillation
Hypertension
Current Medication:
Combivent nebules – 1 nebule four times daily
Salbutamol 2.5mg nebules - when required for SOB
Prednisolone 40 mg once daily for past 4 days
Seretide 500 accuhaler – 1puff twice daily
Uniphyllin 300mg twice daily
Diltiazem SR (Tildiem) 90mg twice daily
Warfarin 3mg daily (INR 2.9 on admission)
Amoxicillin 500 mg three times daily for past 4 days
Home oxygen – 2l/min
Lansoprazole 30mg daily
1. What are the recommended criteria for prescribing antibiotics for infective
exacerbation of COPD?
The use of antibiotics in patients with an exacerbation remains contentious due
to conflicting results from trials. There are trials to support the use of antibiotics in
the following circumstances:
Purulent sputum PLUS either increased shortness of breath or increased sputum
volume (GOLD guidelines 2008 and NICE guidelines 2004).
2. What are the most common infective causes of an exacerbation?
The infectious agents in COPD exacerbations may be viral or bacterial.
The predominant bacteria recovered from the lower airways of patients with
COPD exacerbations are Haemophilus influenzae, Streptococcus pneumoniae,
and Moraxella catarrhalis. So-called atypical pathogens, such as Mycoplasma
-7-
pneumoniae and Chlamydia pneumoniae have been identified in patients with
COPD exacerbations, but because of diagnostic limitations their true prevalence
is not known – GOLD guidelines 2008. The causative organism of an
exacerbation may be unidentifiable in up to 30% of cases.
3. Which antibiotics are appropriate first line therapy?
Aminopenicillins (amoxicillin/ampicillin), macrolides or tetracyclines
4. Discuss appropriate antibiotic choices for this gentleman?
The potential bacteria that have not been covered by the amoxicillin are: Staph.
aureus, atypicals, P. aeruginosa and H. influenzae (penicillin resistant strain).
Ciprofloxacin - covers all of the above pathogens but not Strep. pneumoniae.
Co-amoxiclav - covers an atypical or pseudomonas infection. Note repeated
admissions to hospital - pseudomonas infection may have been acquired.
Clarithromycin - does not cover pseudomonas.
Tetracycline e.g. doxycycline - does not cover pseudomonas infection.
MRSA is also a potential infecting organism due to recent hospital admissions–
recommended treatment would be IV vancomycin or oral linezolid (local policy
may restrict use for this indication).
5. Medical staff decide to change his antibiotic treatment to ciprofloxacin.
Is this an appropriate choice?
Yes - ciprofloxacin would cover potential pathogens.
Suggested dosage is 500mg bd orally for 5 days.
Doxycycline would also be a suitable choice.
What pharmaceutical care issues are there for this patient with respect to his
antibiotic therapy?
1. Sputum sample should be obtained if possible and sent for microbiological
analysis – check culture and sensitivity results and review antibiotic therapy as
appropriate (N.B. only get positive culture results in small proportion of patients).
2. Theophylline and ciprofloxacin – drug interaction. Ciprofloxacin decreases the
elimination of theophylline by inhibition of cytochrome P450 (CYP1A2).
Adjust dose of Uniphyllin - some centres reduce dose by 50% in all patients,
others check level and adjust as necessary.
3. Warfarin and ciprofloxacin –ciprofloxacin may potentiate the effects of warfarin
(mechanism unclear). Monitor INR closely – note INR on admission was 2.9.
4. Risk of C. difficile due to age, frequent use of antibiotics and current broad
spectrum treatment – monitor for diarrhoeal symptoms.
-8-