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Transcript of Most often asked questions Jenny Andrews. Current Working Party members MedicalScientificIndustry...
Most often asked questionsMost often asked questions
Jenny Andrews
Current Working Party membersCurrent Working Party membersMedical 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 PartyAim 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 recommendationsBSAC 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
SupplementVersion 2 (website)
2005- Version 4
Scientists outside the UK Scientists outside the UK asking for helpasking 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 helpOther 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 discussedMain topics to be discussed
Organisms Method Control UTI Respiratory Staphylococci Enterobacteriaceae Enterococci N. gonorrhoeae
Mechanisms of resistance Etest NEQAS Website
OrganismsOrganismsOrder of priority Comment Order of
priorityComment
-haemolytic streptococci
Acinetobacter spp.
Under review
S. maltophilia Helicobacter spp.
Refer to Reference Group
Bacillus spp. Andrews & Wise JAC 2002;49;1040-1042
Listeria spp. SRGA recommendations
Campylobacter spp. B. cepacia For the future
P. multocida Fungi (India) Not the remit of this WP
Anaerobic organisms In progress M. tuberculosis Not the remit of this WP
Coryneforms In progress
MethodMethod
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 strainsControl 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 UTIsOrganisms associated with uncomplicated UTIsin women of child-bearing age
E. coliP. mirabilisEnterococciS. saprophyticusGroup B streptococci
NB. Complicated UTIs and S. epidermidis and S. aureus (usually associated with more serious infections)- use systemicZone diameter BPs
UTI 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
UTIUTI 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.’
RespiratoryRespiratory H. influenzae:H. influenzae: Interpretation of amoxicillin/co-amoxiclav and Interpretation of amoxicillin/co-amoxiclav and
cefuroximecefuroxime 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)
RespiratoryRespiratoryS.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
RespiratoryRespiratory 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 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.’
StaphylococciStaphylococci
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
StaphylococciStaphylococci
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
0
5
10
15
20
25
30
35N
um
ber
of
iso
late
s
6 8 10 12 14 16 18 20 22 24 26 28 30Zone diameter (mm)
MIC 0.5–4mg/L
MIC 8–64mg/L
Teicoplanin 30 ug disc with CNS - Cambridge
MIC 0.5 – 4 mg/L
MIC 8-64 mg/L
MIC and zone diameter BPs for ampicillin, MIC and zone diameter BPs for ampicillin, amoxicillin and co-amoxiclav for interpreting the amoxicillin and co-amoxiclav for interpreting the
susceptibility of Enterobacteriaceaesusceptibility 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 Enterobacteriaceae:Reporting LLR to fluoroquinolonesfluoroquinolones
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.
EnterococciEnterococci
Recommendations for tetracyclineDetection of glycopeptide
susceptibility – usually solved if plates incubated for 24 h to allow micro-colonies to be visualised
N. gonorrhoeaeN. 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 Detection of mechanisms of resistanceresistance
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 beta-lactamase mediated resistance. October 2004
Dissociated resistance
BSAC web site (www.bsac.org.uk) in the BSAC Standardized Disc Susceptibility Method section, Additional Methods
EtestEtest
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
NEQASNEQAS
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
WebsiteWebsite
Availability of latest versionAutomatic notification of changesWould it be possible to have a
Word file available to download
Final commentFinal 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)