C'difficile infection, ESBL producing Enterobacteriacae and methicillin resistant S'aureus

1
C.difficile infection, ESBL producing
Enterobacteriacae and methicillin resistant
S.aureus

• Alasdair MacGowan,
• Professor of Clinical Microbiology and
  Antimicrobial Therapeutics,
• University of Bristol,
• Consultant Medical Microbiologist,
• North Bristol NHS Trust.

2
Structure

• 3 sections on C.difficile, ESBLs and MRSA
• Each section-
• MCQs
• 10 minutes from Alasdair MacGowan
• 5 minutes QA

3
Clostridium difficile Test Yourself!

• Clostridium difficile associated diarrorhea is-
• Diagnosed by culture of the organism T/F
• Only occurs in hospitalised patients T/F
• A mandatory infection control target for NHS
  Trusts T/F
• More trouble than its worth T/F

4
Risk Factors for C.difficile diarrhoea are-

• Too many pies T/F
• Increasing age T/F
• Long hospital stay T/F
• d) Being admitted to NBT T/F

5
Antibiotics and C.difficile Diarrhoea

• Co-amoxiclav is the treatment of
  choice T/F
• b) Vancomycin is commonly used as therapy T/F
• Cephalosporins and fluouroquinolones have a high
• risk of C.difficile infection T/F
• d) Is just an excuse for pharmacists to question
  my prescribing T/F

6
Clostridium difficile

• C.difficile is the major cause of antibiotic
  associated diarrhoea and colitis
• Mainly affects elderly treated with broad
  spectrum antibiotics
• C.difficile forms spore (like other clostridia)
  which are found in liquid faeces
• Spore able to survive in the environment and
  result in faecal oral spread
• Diagnosis by detection of C.difficile toxins
  (AB) in liquid stool

7
Epidemiology

• Increasing incidence in gt65 years from about
  15,000 cases in England in 2000, to 40,000 in
  2006 (voluntary reporting)
• Mandatory reporting shows an increase from approx
  45,000 cases in 2004, to 55-60,000 cases in 2006
  and a decline to 50,000 cases in 2007
• Majority of cases of C.difficile associated
  diarrhoea (CDAD) hospital acquired some occur
  in community

8
Local and National Incidence of C.difficile
mandatory reporting ?65 years
9
Risk Factors for C.difficile infection

• Increasing age (excluding infants)
• Severity of underlying diseases
• Non-surgical GI procedures
• Presence of a nasogastric tube
• Anti-ulcer medications (Proton Pump Inhibitors)
• ICU stay
• Duration of hospital stay
• Antibiotic exposure

10
Antibiotics and C.difficile

• 2nd/3rd generation cephalosporins
• (IV cefuroxime, ceftriaxone, cefotaxime)
• Clindamycin
• Co-amoxiclav/other aminopenicillins
• Fluouroquinolones
• Plus-
• Duration of therapy
• Poly pharmacy
• Antibiotic proplylaxis for gt24h

11
Pooled odds ratios for risk of C difficile with
selected antibiotics
Bignardi et al, 1998
12
Antibiotics restrictions applied to revised
guidelines.
OK to use flucloxacillinerythromycinco-trimoxaz
olevancomycin1st generation -cephalosporinspeni
cillintetracyclinesgentamicin
Restrict or remove cefuroximeceftriaxoneceftazi
dimeco-amoxiclavciprofloxacinlevofloxacinmoxif
loxacin
13
Impact of cephalosporin, fluoroquinolone,
co-amoxiclavrestricted policy
14
NBT C.difficile 2007-8 vs interventions
15
Management and Treatment of CDAD

• Supportive care (hydration, nutrition)
• Avoid antiperistaltic agents
• Stop (any unnecesary) antibiotics
• Assess severity
• Mild lt3 stools per day types 5-7
• Bristol Stool Chart (soft blobs, fluffy
  pieces, mushy stools, liquid, no solid pieces)
• Moderate 3-5 stools per day
• Severe peripheral WBC gt15x10a/L, falling eGFR,
  temp gt38.5oC, number of stools less reliable
• Mild to Moderate Oral metromidazole 400-500 mg
  TDS for 10-14d

16
Recurrent C.difficile associated diarrhoea

• 10-40 patients have recurrence
• Risk factors-
• Continued use of non-C.difficile antibiotics
  after a diagnosis of CDAD
• Use of Antacids
• Older age
• Long hospital stay

17
Management of Recurrence

• First recurrence, treat as for first episode
• 3rd episode, treat with vancomycin 125 mg QDS po
• Alternatives (no evidence)
• Biotherapy
• Vancomycin 500 mg (no evidence)/10d QDS plus
  S.bouldardii 1g OD 28d
• Faecal transplant
• Pulsed Therapy
• Vancomycin 125 mg QDS 10ds, stop 14d, rifaximin
  400mg BD 14d
• Combination therapy
• Vancomycin 125 mg ODS plus rifampicin 600mg OD
  7-14 days
• Immunotherapy
• IV IG (400mg/kg single dose)

18
Clostridium difficile Test Yourself!

• Clostridium difficile associated diarrorhea is-
• Diagnosed by culture of the organism T / F
• Only occurs in hospitalised patients T / F
• A mandatory infection control target for NHS
  Trusts T / F
• More trouble than its worth T / F

19
Risk Factors for C.difficile diarrhoea are-

• Too many pies T / F
• Increasing age T / F
• Long hospital stay T / F
• d) Being admitted to NBT T / F

20
Antibiotics and C.difficile Diarrhoea

• Co-amoxiclav is the treatment of choice T / F
  
• b) Vancomycin is commonly used as therapy T / F
• Cephalosporins and fluouroquinolones have a high
• risk of C.difficile infection T / F
• d) Is just an excuse for pharmacists to question
  my prescribing T / F

21
ESBLs
22
Test yourself on ESBLs

• ESBL is short for-
• a) extremely short B.lactams T/F
• b) excessively small B.laces T/F
• c) extended spectrum B.lactamases T/F
• d) extremely susceptible B.lactamases T/F

23
ESBL enzymes are found in-

• E.coli T/F
• Klebsiella T/F
• Enterobacter T/F
• The imagination of microbiologists T/F

24
ESBL producing bacteria-

• Were discovered by Dr E.S.B. Levi T/F
• Commonly cause UTI in association
• with urinary catheters T/F
• Are commoner in patients who have
• received antibiotics T/F
• Are often multi-resistant to non-B.lactam
• antibiotics T/F

25
ESBL producing bacteria are best managed by-

• An intravenous cephalosporin T/F
• Passing the problem onto your partner/trainee/prac
  tice nurse T/F
• Ciprofloxicin if susceptible T/F
• The best oral therapy is not
• established T/F

26
What are ESBLs?

• Part of the Beta lactamase family of enzymes
  i.e. enzymatically digest B.lactams
  penicillins, cephalosporins etc.
• Many B.lactams commonest are TEM 1/2 which
  digest amoxicillin found in E.coli, H.influenzae
• some very rare.
• Usually found on plasmids (extra chromosomal DNA)
  easily pass between related bacteria, i.e.
  E.coli, Klebsiella etc.
• Plasmids normally encode for other unrelated
  resistancies,
• i.e. trimethoprim, fluoroquinolone, gentamicin.

27
Extended spectrum cephalosporins(cefotaxime,
ceftriaxone iv cefexime, cefpodoxime po)
28
Where do ESBLs come from?

• 1963 Ampicillin introduced
• 1965 TEM B.lactamases in E.coli
• 1974 TEM B.lactamases in H.influenzae
• 2000 TEM in 40-60 E.coli, 5-20 H.influenzae
• 2004 ESBL described in Germany evolve from
• a) mutation of TEM and other B.lactamases
• b) CTX-M gene sequence similar to naturally
  occurring sequences in Kluyvera sp

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(No Transcript)
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CTX-M producers E.coli, Klebsiella spp,
Enterobacter spp

• First described in UK, in Leeds, in 2000
• Commonest ESBL in UK
• Several major clones in hospital community
• Usually urinary isolates
• ESBLs produce resistance to penicillins,
• cephalosporins (without inhibitors), and
  associated with resistance to trimethoprim,
  fluoroquinolones, gentamicin

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UK Epidemiology Blood Stream Isolates
NB bias towards resistance at Southmead BSI
15-20 ESBL Hospital MSU 7-14 ESBL
Community MSU 4-6 ESBL
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Risk Factors for ESBL producer infection

• Prior to antibiotic use in last 90 days
  (especially cephalosporins, trimetroprim,
  fluouroquinolones, aminoglycosides)
• Previous hospitalisation in 90 days
• Age gt 60 years
• Co-morbidities especially diabetes mellitus
• ICU stay
• Vast majority of isolates urinary often in
  CSU no requirement
• for therapy

33
Antibiotic Therapy

• 3rd generation cephatosporins poor responses
  (i.e. IV ceftriaxone)
• Carbapenems best therapy, i.e. IV ertapenem 1g 24
  hrly IV
• Ciprofloxacin and aminoglycoside good outcome if
  susceptible
• (10-20)
• Oral therapies none proven
• Ciprofloxacin 500 mg BD (if sensitive)
• Nitrofurantoin 50 mg QDS (if sensitive and no
  tissue based infection)
• Co-amoxiclav 625 mg TDS po
• Co-amoxiclav plus cefixime 200 mg BD po
• Pivmecillinam 400 mg TDS po

34
Test yourself on ESBLs

• ESBL is short for-
• a) extremely short B.lactams T / F
• b) excessively small B.laces T / F
• c) extended spectrum B.lactamases T / F
• d) extremely susceptible B.lactamases T / F
  

35
ESBL enzymes are found in-

• E.coli T / F
• Klebsiella T / F
• Enterobacter T / F
• The imagination of microbiologists T / F

36
ESBL producing bacteria-

• Were discovered by Dr E.S.B. Levi T / F
• Commonly cause UTI in association
• with urinary catheters T / F
• Are commoner in patients who have
• received antibiotics T / F
• Are often multi-resistant to non-B.lactam
• antibiotics T / F

37
ESBL producing bacteria are best managed by-

• An intravenous cephalosporin T / F
• Passing the problem onto your partner/trainee/prac
  tice nurse T / F
• Ciprofloxicin if susceptible T / F
• The best oral therapy is not
• established T / F

38
MRSA (Methicillin Resistant Staphylococcus Aureus)

• Whats new-
• Mandatory elective admission screening for MRSA
• Decline in mandatory reporting of MRSA
  bacteraemias
• Update of antibiotic management guidelines

39
Pre-admission screening of elective admissions

• Announced in the Darzi Report 2007 (Our NHS, Our
  future, NHS next stage review)
• By April 2009 all elective admissions to be
  screened for MRSA
• excludes
• Ophthalmology day cases
• Dental day cases
• Endoscopy day cases
• Minor dermatology
• Children
• Maternity, except Caesarian Sections
• Mental Health
• Screen is a nose swab, wound swab if broken skin,
  CSU if urinary catheter
• MRSA positive patients require decontamination
• Mupyrocin nasal TDS 5d
• Octenisan body wash OD 5d - starting 2-3 days
  prior to admission

40
Pre-admission screening for MRSA

• Massive workload 20-25,000 patients/annum at
  NBT
• 1-5 are MRSA positive
• No convincing published evidence base
• To be extended to emergency admissions from 1st
  April 2011.

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MRSA Bacteraemia Rates Mandatory
Reporting 2001-2009 England
42
MRSA Bacteraemias Mandatory Reporting Local
Trusts
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Antibiotic Management Guidelines for MRSA
2008JAC (2009) 63, 849-61

• Skin and soft tissue infection
• Impetigo
• topical mupirocin or fusidic acid if susceptible
  (suggested)
• (retapamulin, non-inferior to fusidic acid)
• Abscess
• No antibiotics required after incision drainage
  small skin abscess (lt5 cm) without surrounding
  cellulitis
• Cellulitis/Surgical site
• doxycycline or clindamycin unless severe
  (strongly recommended) provided strain
  susceptible
• If clindamycin, tetracycline resistant, consider
  co-trimoxazole, linezolid
• Outpatient IV therapy, cost effective in
  moderate/severe infection, with glycopeptide
• or daptomycin (strongly recommended).

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Antibiotic management MRSA (continued)

• Simple UTI
• nitrofurantoin, trimethoprim,
• co-trimoxazole, tetracycline according to
  susceptibility (suggested)
• Conjunctivitis
• Topical gentamicin, fusidic acid or
  chloramphenicol if susceptible (strongly
  recommended)

45
Summary of UK MRSA susceptibility - 2007

• B.lactams 100 resistant
• Ciprofloxacin 89 resistant (91, NBT)
• Erythromycin 65 resistant (69, NBT)
• Fusidic acid 12 resistant (11, NBT)
• Gentamicin 5 resistant
• Minocycline 0 resistant (0, NBT)
• Mupirocin 3.6 resistant
• Rifampicin 1.2 resistant
• Tetracycline 1.2 resistant
• Trimethoprim 17 resistant
• Co-trimoxazole (4, NBT)