Most often asked questions
Jenny Andrews
Current Working Party members
Medical
Scientific
Industry
Alasdair MacGowan
(President BSAC)
Bristol
Derek Brown
(Chairman)
Cambridge
Colin Booth
(Oxoid)
Gunnar Kahlmeter
(Chairman of EUCAST)
Sweden
Jenny Andrews
(Secretary)
SMDC Birmingham
Jon Hobson
(Mast)
Nizam Damani
Belfast
David Livermore
HPA, Colindale
Ian Morrissey
(GR Micro, London)
Nicholas Brown
Cambridge
Curtis Gemmell
Glasgow
Robin Howe
Cardiff
John Perry
Newcastle
Trevor Winstanley
Sheffield
Christopher Teale
VLA, Shrewsbury
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
BSAC recommendations

1991- Guide to sensitivity testing
(Questionnaire- 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
Scientists outside the UK
asking for help
Abu Dhabi
Kenya
Spain
Australia
Malawi
Sri Lanka
Bermuda
Malta
Switzerland
Brazil
New Zealand
Turkey
Germany
Nigeria
Uganda
India
Pakistan
USA
Jamaica
Portugal
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
Main topics to be discussed

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Organisms
Method
Control
UTI
Respiratory
Staphylococci
Enterobacteriaceae
Enterococci
N. gonorrhoeae


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Mechanisms of resistance
Etest
NEQAS
Website
Organisms
Order of priority
Comment
Order of
priority
Comment
-haemolytic
streptococci

Acinetobacter
spp.
Under review
S. maltophilia

Helicobacter
spp.
Refer to Reference
Group
Listeria spp.
SRGA
recommendations
Bacillus spp.
Andrews & Wise
JAC 2002;49;10401042
Campylobacter spp.

B. cepacia
For the future
P. multocida

Fungi (India)
Not the remit of
this WP
M. tuberculosis
Not the remit of
this WP
Anaerobic organisms In progress
Coryneforms
In progress
Method

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


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)
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
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
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
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-amoxiclav, `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.’
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 [coamoxiclav 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)
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 >128
mg/L; MIC BP 0.5 mg/L
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
T>MIC of 25% with 250 mg and 37% with 500
mg dosing, suggested conservative T>MIC for
cephalosporins in the community practice is 4050%; 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.’
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/cefoxitin to
detect resistance `Staphylococci exhibiting resistance to
meticillin/oxacillin/cefoxitin should be regarded as
resistant to other penicillins, cephalosporins, carbapenems
and combinations of -lactam and -lactamase inhibitors’
Applies to S. saprophyticus
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
Teicoplanin 30 ug disc with CNS - Cambridge
Number of isolates
35
MIC 0.5
– 4 mg/L
MIC
0.5–4mg/L
30
MIC 8-64
mg/L
MIC
8–64mg/L
25
20
15
10
5
0
6
8
10 12 14 16 18 20 22 24 26 28 30
Zone diameter (mm)
MIC and zone diameter BPs for ampicillin,
amoxicillin and co-amoxiclav for interpreting the
susceptibility of Enterobacteriaceae
Date
Recommendations
Before February 2003
Ampicillin & co-amoxiclav only ; MIC BPs - S 8
mg/L, R 16 mg/L; ZD S 18 mm. Laboratories
commenting that many systemic isolates had zones that
`straddled’ the ZD BP
After February 2003
Ampicillin, amoxicillin & co-amoxiclav; S 16 mg/L,
R 32 mg/L; ZD S 14mm.
Using the modified criteria some Enterobacteriaceae
with chromosomal AmpC enzyme producers were
misclassified as susceptible using this criteria
January 2005
Ampicillin, amoxicillin & co-amoxiclav ; MIC BPs - S
8 mg/L, I =16 mg/L, R 16 mg/L; ZD S 15, 12-14 mm
= I, R  11 mm.
Enterobacteriaceae:Reporting LLR to
fluoroquinolones
Site of infection/organism
Comment
Urines: should laboratories
test ciprofloxacin or
nalidixic acid
LLR to FQs (no zone to nalidixic acid 30
g disc) but S to ciprofloxacin. Using Nal
alone would mean that 25-40% of isolates
with LLR would be reported resistant to
ciprofloxacin. The organism is probably
susceptible because of the concentration of
drug at the site of infection.
Salmonella infections
For ciprofloxacin there is clinical evidence
to indicate a poor response in systemic
infections caused by Salmonella spp. With
reduced susceptibility to FQs (ciprofloxacin
MICs 0.125-1 mg/L). This reduced
susceptibility is most reliably detected with
nalidixic acid 30 g disc.
Enterococci
 Recommendations
for tetracycline
 Detection of glycopeptide
susceptibility – usually solved if plates
incubated for 24 h to allow microcolonies to be visualised
N. gonorrhoeae

2002 GRASP survey showed that resistance to
ciprofloxacin had risen to 9.8%, indicating that the target
of >95% 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
Detection of mechanisms of
resistance
ESBLs
BSAC web site (www.bsac.org.uk) method of detection
and link to HPA recommendations
FQR
Nalidixic acid to detect resistance in H. influenzae, M.
catarrhalis, N. gonorrhoeae, N. meningitidis- footnotes to
tables recommend 30 g nalidixic acid disc
-lactamase H. influenzae. M. catarrhalis, staphylococci, methods of
detection see BSAC web site (www.bsac.org.uk) David
Livermore’s Power Point presentation: Detection of betalactamase mediated resistance. October 2004
Dissociated BSAC web site (www.bsac.org.uk) in the BSAC
Standardized Disc Susceptibility Method section,
resistance
Additional Methods
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
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
Website
 Availability
of latest version
 Automatic notification of changes
 Would it be possible to have a
Word file available to download
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)