Most often asked questions

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Most often asked questions

• Jenny Andrews

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Current Working Party members
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Aim of the Working Party

• Provide recommendations appropriate for
  susceptibility testing in the UK and Ireland
• Continually review the recommendations, taking
  into account the introduction of new antibiotics
  and emerging mechanisms of resistance
• Provide support for users of the BSAC method

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BSAC recommendations

• 1991- Guide to sensitivity testing (Questionnai
  re- 91 would consider using a standardized
  method)
• 1998-Summer BSAC Newsletter (Standardized Disc
  Testing Method)
• 1999- Amendments and additions
• 2001-July
• Supplement
• Version 2 (website)
• 2005- Version 4

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Scientists outside the UK asking for help
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Other requests for help

• Degree/projects- have given advice to 29
  individuals (USA Georgia Acidovora
  avenae found on water melons-advice given by
  Trevor Winstanley)
• Veterinary laboratories
  (Northern Ireland, Scotland, England, Turkey,
  Australia) Chris Teale represents this group
  on the working party
• Pharmaceutical industry

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Main topics to be discussed

• Organisms
• Method
• Control
• UTI
• Respiratory
• Staphylococci
• Enterobacteriaceae
• Enterococci
• N. gonorrhoeae

• Mechanisms of resistance
• Etest
• NEQAS
• Website

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Organisms
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Method

• Template (written and supported by Trevor
  Winstanley)
• Preparation of inoculum
• Direct sensitivity tests (blood cultures
  urines)
• Can Oxoid Iso-Sensitest agar be substituted by
  media from other manufacturers?
• Disc contents not used in the UK (SRGA data)

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Control strains

• Filling the gaps in the recommendations (BSAC
  rolling programme) devising intra-laboratory
  ranges until recommendations available
• Controls repeatedly outside the acceptable range
  rolling programme(meropenem ATCC 27853 P.
  aeruginosa- no change gentamicin NCTC 6571 S.
  aureus under review trimethoprim NCTC ATCC E.
  coli zone ranges increased 28-34mm to 30-37mm
  20-26mm to 25-31 mm respectively co-amoxiclav E.
  coli NCTC 11560 range reduced from 18-23 mm to
  12-18mm)
• Using the acceptable ranges laboratories detected
  that one commercial supply of ciprofloxacin discs
  were under-dosed
• Control ranges for N. gonorrhoeae ATCC 49226
• Providing controls to India, Egypt

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Organisms associated with uncomplicated UTIs in
women of child-bearing age
NB. Complicated UTIs and S. epidermidis and S.
aureus (usually associated with more serious
infections)- use systemic Zone diameter BPs

• E. coli
• P. mirabilis
• Enterococci
• S. saprophyticus
• Group B streptococci

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UTI

• Cotrimoxazole because of blood and skin
  disorders associated with this combination there
  are no BSAC recommendations
  CSM recommendations cotrimoxazole should only
  be used for UTIs when there is evidence of
  susceptibility and a good reason to prefer this
  combination to a single antibiotic.
• Trimethoprim John Washington enterococci should
  be regarded as resistant because they utilise
  exogenous folate in vivo which is absent from the
  medium used for testing, therefore isolates
  appear falsely susceptible in vitro to
  trimethoprim and co-trimoxazole
• An exhaustive search of the literature was unable
  to support the hypothesis of Washington
• Recommendations now available for trimethoprim

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UTI

• Gaps often antibiotics used systemically
  therefore use these recommendations
• Coliforms absent from the recommendations-where
  distribution is not good and there is overlap
  between the susceptible and resistant populations
  (e.g. cephalexin).
• ID to species level is essential for applying
  expert rules (for amoxicillin/ampicillin/co-amoxic
  lav, These interpretative standards apply only
  to E. coli and P. mirabilis and not species that
  have chromosomal penicillinases (Klebsiella spp.)
  or those that typically have inducible AmpC (e.g.
  Enterobacter spp., Citrobacter spp. And Serratia
  spp.)
• In the absence of a definitive ID, use the
  recommendations most appropriate for the
  presumptive ID, accepting that on some occasions
  the interpretation may be incorrect. A more
  cautious approach is to use the systemic
  recommendations.

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Respiratory H. influenzae Interpretation of
amoxicillin/co-amoxiclav and cefuroxime

• Isolates with zone diameters 2-3 mm smaller than
  the zone diameter BP for co-amoxiclav reported S
  to amoxicillin cefuroxime (including NEQAS
  specimen 5853 co-amoxiclav MIC 0.5 mg/L MIC BP
  1 mg/L
• Zone diameter BPs reviewed and amended
• Currently there are occasional enquiries from
  laboratories regarding isolates with borderline
  susceptibility to the three agents (Becky Walker
  undertaking a higher degree to elucidate the
  mechanisms of resistance to the ?-lactam
  antibiotics)

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Respiratory

• S.pneumoniae Interpretation of resistance to
  penicillin - Organisms with a penicillin MIC ? 1
  mg/L are considered susceptible to ?-lactam
  antibiotics except in infections of the central
  nervous system.
• Recommendations for S. pneumoniae v trimethoprim-
  MIC 50 8 mg/L MIC90 gt128 mg/L MIC BP 0.5 mg/L
  

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Respiratory

• Interpretation of susceptibility of H. influenzae
  to cefaclor- Professor MacGowan The pK/pD data
  indicates cefaclor has borderline activity
  against H. influenzae, even for community use
  (free drug TgtMIC of 25 with 250 mg and 37 with
  500 mg dosing, suggested conservative TgtMIC for
  cephalosporins in the community practice is
  40-50 MIC50 2 mg/L, MIC90 8 mg/L, MIC BP 1
  mg/L). The outcome of infection will be difficult
  to predict and susceptibility testing is likely
  to have limited value.

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Staphylococci

• Recommendations using cefoxitin to detect
  resistance in S. aureus
• General problems with detection of methicillin
  resistance (possible penicillinase
  hyper-producing isolates PCR or latex for
  confirmation of resistance)
• Using ?-lactams other than meticillin/oxacillin/ce
  foxitin to detect resistance Staphylococci
  exhibiting resistance to meticillin/oxacillin/cefo
  xitin should be regarded as resistant to other
  penicillins, cephalosporins, carbapenems and
  combinations of ?-lactam and ?-lactamase
  inhibitors Applies to S. saprophyticus

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Staphylococci

• Mupirocin Harbath et al suggest that there is a
  need to detect LLR because there is an
  association with persistence of carriage.
• Risk factors for persistent carriage of
  methicillin-resistant Staphylococcus aureus.
  Harbath et al Clin Infect Dis. 2000 Dec
  31(6)1380-5
• Method developed by the BSAC using a 20 ?g
  mupirocin disc.
• Availability of discs

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Teicoplanin 30 ug disc with CNS - Cambridge
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MIC 0.5 4 mg/L
MIC 0.54mg/L
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MIC 8-64 mg/L
MIC 864mg/L
25
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Number of isolates
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10
5
0
6
8
10
12
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18
20
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28
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Zone diameter (mm)
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MIC and zone diameter BPs for ampicillin,
amoxicillin and co-amoxiclav for interpreting the
susceptibility of Enterobacteriaceae
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EnterobacteriaceaeReporting LLR to
fluoroquinolones
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Enterococci

• Recommendations for tetracycline
• Detection of glycopeptide susceptibility
  usually solved if plates incubated for 24 h to
  allow micro-colonies to be visualised

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N. gonorrhoeae

• 2002 GRASP survey showed that resistance to
  ciprofloxacin had risen to 9.8, indicating that
  the target of gt95 efficacy in first-line therapy
  was no longer achievable.
• Recommendations for cefixime(oral) ceftriaxone
  (intramuscular)
• Availability of ceftriaxone 5 ?g discs
• Which cephalosporin for gonorrhoea? Professor
  Catherine Ison et al on behalf of the North
  Thames Audit group.
• This report underscores the use of cefixime and
  ceftriaxone, but finds that cefuroxime is a poor
  alternative

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Detection of mechanisms of resistance
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Etest

• Availability of method for testing by the BSAC
  methodology (www.bsac.org.uk) in the BSAC
  Standardized Disc Susceptibility Method section,
  Additional Methods, The use of Etests with BSAC
  methodology
• Do we run a course for use of Etest

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NEQAS

• Derek Brown at Addenbrookes and the SMDC in
  Birmingham are the reference laboratories for MIC
  testing by BSAC methodology
• Questions arise when laboratories do not get the
  expected result (often occurs with organisms with
  borderline susceptibility)
• The Working Party tries to investigate the
  problems

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Website

• Availability of latest version
• Automatic notification of changes
• Would it be possible to have a Word file
  available to download

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Final comment

• 2002 University of Utah, USA
• I am very curious why your committee saw the
  need for a different disc susceptibility method.
  Do you find major inaccuracies in the NCCLS
  method? It would seem that even if your methods
  are equally accurate, it confuses the world
  community to have two different standards.
• (EUCAST Harmonization - Gunnar Kahlmeter)