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Coventry and Warwickshire Pathology
Antibiotic Senior Academic Half Day
Matt Rogers & James Clayton
Consultant Microbiologists
February 2011
Coventry and Warwickshire Pathology
Objectives of the session• By the end of the session you will be able to:
• Describe the factors that need to considered when making the choice to prescribe an antibiotic
• Develop an understanding of key pathogens and their susceptibility to antibiotics. You will be able to relate this to the antibiotic policy within your Trust
• Define what is meant by the term Antibiotic stewardship• Be aware of key DOH guidelines (Clostridium difficile) that direct the
development of antibiotic policies• Name the antibiotics associated with Clostridium difficile• State the minimum requirements of how to prescribe an antibiotic• Name the key issues around route and duration of antibiotics and
how this affects patients
Coventry and Warwickshire Pathology
Antibiotic stewardship
• Ensures the optimisation of antibiotic use– Only use when necessary– Control who uses what– Control route and duration– Respond to changing
needs– Respond to changing
Evidence/Policies– Robust policing, review and
stop strategies– E prescribing
Coventry and Warwickshire Pathology
A bit of backgroundA potted history of Antibiotics
• The use of antimicrobials in the treatment of infection is one of the triumphs of modern medicine.
Coventry and Warwickshire Pathology
History of Antibiotics
• Before the discovery of the sulphur drugs in 1932, treatment of infectious disease was limited to mercury, arsenic, and quinine.
• Penicillin was discovered in 1929.
Alexander Fleming
Coventry and Warwickshire Pathology
History of Antibiotics
• Penicillin was not manufactured on a large scale for non-military use until 1949.
Coventry and Warwickshire Pathology
History of Antibiotics
Decade Antibiotics
1940s & 1950s
StreptomycinSynthetic penicillinsCephalosporinsChloramphenicolTetracyclines.
1960s Quinolones
2000s Oxazolidinone (Linezolid®)Glycylcycline (Tigecycline®)
2010s ?? Long acting glycopeptides – phase 3 trials
Coventry and Warwickshire Pathology
Resistance always developsExamples
Staphylococcus aureus
Penicillin resistance 1950/60sMRSA - Meticillin resistance since 1970sVRSA - Vancomycin resistance in 2001
Enterococci VRE: Vancomycin Resistant Enterococci
Coliforms Quinolone resistanceESBLs: Extended Spectrum Beta-lactamasesMetallo Beta-lactamases (NDM-1)
Coventry and Warwickshire Pathology
Antimicrobial resistance
• Multiple resistance genes • Plasmids• Spread
• Factors leading to resistance:– Inappropriate clinical use of ABx– Poor infection control– Excessive ABx use in non clinical settings:
• animal husbandry• shipping
Coventry and Warwickshire Pathology
Coventry and Warwickshire Pathology
Coventry and Warwickshire Pathology
Key antibiotic changes
– Stop use of cefuroxime throughout the Trust
– Use lower risk augmentin (but monitor C.difficile rates)
– Reduce use of ciprofloxacin (consider penicillin allergy)
– Antibiotic policy available under Clinical Guidelines on the intranet
– Antibiotic guideline credit cards distributed
Coventry and Warwickshire Pathology
Cefuroxime Spend by UHCW NHS Trust
£0
£500
£1,000
£1,500
£2,000
£2,500
£3,000Ap
r-07
May
-07
Jun-
07Ju
l-07
Aug-
07Se
p-07
Oct
-07
Nov
-07
Dec
-07
Jan-
08Fe
b-08
Mar
-08
Apr-
08M
ay-0
8Ju
n-08
Jul-0
8Au
g-08
Sep-
08O
ct-0
8N
ov-0
8D
ec-0
8Ja
n-09
Feb-
09M
ar-0
9Ap
r-09
May
-09
Jun-
09Ju
l-09
Aug-
09Se
p-09
Oct
-09
Nov
-09
Dec
-09
Jan-
10Fe
b-10
Mar
-10
Apr-
10M
ay-1
0Ju
n-10
Jul-1
0Au
g-10
Sep-
10O
ct-1
0N
ov-1
0D
ec-1
0Ja
n-11
Feb-
11M
ar-1
1
Expe
nditu
re
Diagnostics and Service Division
Medicine and Emergency Division
Rugby St Cross
Specialised Networks Division
Surgery Division
Women and Childrens
TRUST TOTAL
Coventry and Warwickshire Pathology
Total Oral Ciprofloxacin spend by UHCW NHS Trust(Includes inpatient, TTO & outpatient issues)
£0
£100
£200
£300
£400
£500
£600
£700Ap
r-07
May
-07
Jun-
07Ju
l-07
Aug-
07Se
p-07
Oct
-07
Nov
-07
Dec
-07
Jan-
08Fe
b-08
Mar
-08
Apr-
08M
ay-0
8Ju
n-08
Jul-0
8Au
g-08
Sep-
08O
ct-0
8N
ov-0
8D
ec-0
8Ja
n-09
Feb-
09M
ar-0
9Ap
r-09
May
-09
Jun-
09Ju
l-09
Aug-
09Se
p-09
Oct
-09
Nov
-09
Dec
-09
Jan-
10Fe
b-10
Mar
-10
Apr-
10M
ay-1
0Ju
n-10
Jul-1
0Au
g-10
Sep-
10O
ct-1
0N
ov-1
0D
ec-1
0Ja
n-11
Feb-
11M
ar-1
1
Expe
nditu
re
Diagnostics and Service Division
Medicine and Emergency Division
Rugby St Cross
Specialised Networks Division
Surgery Division
Women and Childrens
TRUST TOTAL
Coventry and Warwickshire Pathology
Antibiotic stewardship
• Ensures the optimisation of antibiotic use– Only use when necessary– Control who uses what– Control route and duration– Respond to changing
needs– Respond to changing
Evidence/Policies– Robust policing, review and
stop strategies– E prescribing
Coventry and Warwickshire Pathology
Antibiotic prescribingWhat’s important?
• When– Is there an infection?
• How– To diagnose. What specimens?
• Why– What is the indication/Likely pathogens?
• What– What antibiotic/route/duration
Coventry and Warwickshire Pathology
When?
• Diagnosing infection is a CLINICAL skill
• Basic signs and symptoms of infection
• Please remember apart from sterile sites (urine/csf/blood etc) most areas you culture WILL grow bacteria
Coventry and Warwickshire Pathology
When not to
• CSU-urine cloudy• ?Chest infection with
no evidence on CXR• Wound with serous
exudate• Sloughy Ulcers• Isolated spikes of
temp• To treat a high WCC
Coventry and Warwickshire Pathology
How?
• How to diagnose Infection???
• What specimens do you need to take?
• What investigations do you need to ask for?
Coventry and Warwickshire Pathology
Why?
• Why are we giving Antibiotics– Empirical/Prophylactic/Targeted
• Know your basic Microbiology
• The indication (UTI/LRTI etc)
• The setting (Pt+environment)– Hospital v Community (feasibility)
• The likely pathogens (CRRS)
Coventry and Warwickshire Pathology
Prophylaxis
• Therapy given to prevent an infection• Often given around surgery• Given to patients prone to particular
infections– Contacts of Neisseria meningitidis meningitis
• Given to patients who are specifically immunocompromised– Splenectomy– PCP prophylaxis in HIV
Coventry and Warwickshire Pathology
Surgical prophylaxis
• Used to be given for several days
• Evidence now suggests that peri-operative antibiotics adequate for most ‘clean’ operations
Coventry and Warwickshire Pathology
Principles of antibiotic prophylaxis
• The use of antibiotic prophylaxis involves a dilemma; it is highly effective in preventing infection, but can promote resistance.
• Limit to those individuals in whom the risk of infection is high.
Coventry and Warwickshire Pathology
Principles of antibiotic prophylaxis
• Which antibiotics?– should be targeted to the most likely pathogens.
• When?– administration as near the time of incision as possible.– Intravenous antibiotics should be given during the induction of
anaesthesia with repeat doses for longer procedures.
• Duration:– keep to a minimum (often even to a single-dose) to reduce the
chance of resistance developing. – The benefits of post-operative prophylaxis lasting more
than 12 h have not been proven.
Coventry and Warwickshire Pathology
Indications for antibiotic prophylaxis
• Contaminated or dirty operations – presence of bowel contents, pus, or infected foreign material
• Insertion of graft or prosthesis where development of infection would be serious.
• Immunocompromised patients
• Patients with cardiovascular abnormalities, may require specific antibiotic prophylaxis to reduce the risk of endocarditis – (NICE guidelines, BSAC guidelines)
Coventry and Warwickshire Pathology
Risk Factors for Surgical Site Infection
• Patient:– Extremes of age– Poor nutritional state– Obesity – Diabetes mellitus– Smoking– Co-existing infections at other
sites– Bacterial colonisation (e.g.
MRSA)– Immunosuppression– Prolonged postoperative stay
• Operation– Length of surgical scrub– Skin antisepsis– Preoperative shaving– Preoperative skin prep– Length of operation– Antimicrobial prophylaxis– Operating theatre ventilation– Inadequate instrument sterilisation– Foreign material in surgical site– Surgical drains– Surgical technique including
haemostasis, poor closure, tissue trauma
– Postoperative hypothermia
Coventry and Warwickshire Pathology
SIGN: Scottish Intercollegiate
Guidelines Networkwww.sign.ac.uk
www.sign.ac.uk/guidelines/fulltext/104/index.html
• SIGNqrg104.pdf
Coventry and Warwickshire Pathology
Empirical therapy
• Therapy given without knowing the causative organism
• Choice based on practical experience and evidence based medicine
• ‘Best guess therapy’, unlikely to cover all possibilities
Coventry and Warwickshire Pathology
Targeted therapy
• Therapy given when the infection and causative organism is known
• This is the best way of effective treatment
• We should know the actual sensitivity of the offending pathogen
Coventry and Warwickshire Pathology
What - Considerations in therapy
• Choice of agent includes:
• Recent DOH guidance (Clostridium difficile) – Has altered policies• Range of pathogens (Why?)• Infection site/drug penetration• Patient factors (allergy)
• The above should be covered by your antibiotic policy
• Combination therapy (synergy/antagonism)• Dose/Frequency• Route – IV/oral• IV/oral switch• Duration (5-7 days for most infection)
Coventry and Warwickshire Pathology
Patient factors
• Allergy• Other medications
(interactions)• Can they take PO• Tolerance• Compliance
Coventry and Warwickshire Pathology
Infection site
• Drug penetration e.g.• Antibiotics aren’t always
the answer– Infection prostheses -
SURGERY
• Bone/Soft tissue infections– Some drugs like the
aminoglycosides do not penetrate well
• Meningitis– Many drugs will not
penetrate CSF well
Coventry and Warwickshire Pathology
IV or oral
• What are the considerations
• Depends on site of infection
• Oral bioavailability of the antibiotic
• Clear aim/end point (treatment/suppression)
• Licencing
Coventry and Warwickshire Pathology
MAU AuditZoe Campbell F2 SHO
• Only those with Severe pneumonia according to CURB criteria should receive IV antibiotics
• 18 out of 25 patients received IV antibiotics
• 18 patients were classified mild/mod (? Oral antibiotics)
• 7 patients were classified severe (? IV antibiotics)
I.V.
Oral
Mild/Moderate
Severe
Coventry and Warwickshire Pathology
MAU Audit: IV/Oral Switch
• Only 2 out of 25 (8%) patients had an IV to oral switch or a review/stop date specified on initial clerking
No date specified
Date specified
Coventry and Warwickshire Pathology
Also How much?
• Unfortunate but Healthcare economics are always a consideration
• Particularly with some newer drugs– Antifungals– Antibacterials– Antivirals
Coventry and Warwickshire Pathology
‘No antibiotic’ option
• Our antibiotic options are running out.– Increasing resistance– Paucity of new drugs
• Avoid unnecessarily antibiotics – Often there to make us feel better rather than the
patient!– Unnecessary risk to patients
• Look for >1 marker of infection • Stop antibiotics as soon as possible
– Plan stop dates / review dates
Coventry and Warwickshire Pathology
Coventry and Warwickshire Pathology
What must an antibiotic prescription include?
• Must be documented with review dates in the patients notes
• Length of course or a Review date• (all i/v antibiotics must be reviewed at 48 hours and
changed to oral where clinically appropriate)
• Indication• All antibiotics must be reviewed daily
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