Most often asked questions Jenny Andrews. Current Working Party members MedicalScientificIndustry Alasdair MacGowan (President BSAC) Bristol Derek Brown.

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)