INTERPRETATIVE READING

Tan Thean Yen

To Interpret
interpret explain the meaning of (information, words, or actions)

To Interpret
analyse susceptibility results based: organism identification all antibiotic results (pattern) interpret susceptibility based on above

Courvalin P. Interpretive reading of in vitro antibiotic susceptibility tests (the antibiogramme). Clinical Microbiology and Infection. 1996;2:S26S34.

Why interpret?
To detect unusual results that need further testing or confirmation To report appropriate antibiotic results for the organism-infection combination To detect emerging resistance

Expert rule
Description of action to be taken, based on current evidence, in response to specific antimicrobial susceptibility test results

E X P E R T R U L E

If you obey all of the rules, you miss all of the fun. - Katharine Hepburn

Actions
Recommendations on reporting
E X P E R T R U L E

Inference of susceptibility Edit results from S to I or R, from I to R, but NEVER I or R to S

Suppression of results Addition of comments Advice on further tests Advice on referral of isolates
Brown, D. Concepts and needs for expert rules and intrepretive reading of the antibiogram. The EUCAST perspective

Requirements
Identification of the organism (fully)
E X P E R T R U L E

May need to test an extended range of appropriate antibiotics Access to a set of expert rules

Three areas to cover

1. Intrinsic resistance 2. antibiogram reading 3. Exceptional phenotypes

Part One

INTRINSIC RESISTANCE

I N T R I N S I C R E S I S T A N C E

resistance which is a characteristic of the species Susceptible results?

errors in identification or susceptibility testing drug should be used with caution

Chromosomal (born with it)

Examples
I N T R I N S I C R E S I S T A N C E

Organism Enterobacteriaceae Gram-positive organism Klebsiella species Proteus mirabilis Serratia marcescens

Antibiotic resistance Vancomycin Aztreonam Ampicillin Nitrofurantoin Polymyxins Polymyxins

I N T R I N S I C R E S I S T A N C E

Livermore DM, et al. Interpretative reading: recognizing the unusual and inferring resistance mechanisms from resistance phenotypes. J Antimicrob Chemother. 2001 Jul 1;48(suppl 1):87102

I N T R I N S I C R E S I S T A N C E

http://www.eucast.org/expert_rules/

Part Two

ANTIBIOGRAM READING

A N T I B I O G R A M R E A D I N G

Test susceptibility Infer resistance mechanism Interpret clinical susceptibility on the basis of the resistance mechanism

Canton, R. Expert Rules In Susceptibility Testing Rationale, Advantage And Disadvantages. ECCMID 31 March-3 April, 2012

Species identification

Antibiotic susceptibility

E X P E R T R U L E

REPORT

Species identification Antibiogram interpretation Antibiotic susceptibility

E X P E R T R U L E

deduce phenotype clinical relevance

additional tests deduce biochemical resistance 1. re-define susceptibility (categorical) 2. deduce susceptibility to non-tested antibiotics 3. clinical comments 4. clinical advice

REPORT

Simple..
A N T I B I O G R A M R E A D I N G

Staphylococcus aureus Result: Infer: Interpret:

resistant to cefoxitin resistance mediated by mecA resistant to all beta-lactams

More complicated..
A N T I B I O G R A M R E A D I N G

Enterobacteriaceae Result:
tobramycin non-susceptible amikacin & gentamicin susceptible

Infer: Interpret:

acquired AAC(6)-I enzyme report amikacin as Intermediate

Escherichia coli
A N T I B I O G R A M R E A D I N G

Antibiotic Ampicillin Amoxicillin-clavulanate Piperacillin-tazobactam Cephalothin Ceftriaxone Ceftazidime Cefepime Cefoxitin Ertapenem Gentamicin Amikacin Ciprofloxacin Trimethoprim-sulfamethoxazole

Category R S S R R S R S S S S S S

Infer: Extended spectrum beta-lactamase (CTX-M)

Interpret: Consider reporting ceftazidime as resistant OR Reporting presence of ESBL with comment

Klebsiella pneumoniae
A N T I B I O G R A M R E A D I N G

Antibiotic Ampicillin Amoxicillin-clavulanate Piperacillin-tazobactam Cephalothin Ceftriaxone Ceftazidime Cefepime Cefoxitin Ertapenem Gentamicin Amikacin Ciprofloxacin Trimethoprim-sulfamethoxazole

Category R R S R I R S R S S S S S

Infer: ampC enzyme (plasmid-acquired)

Interpret: Consider reporting ceftriaxone as resistant

Limitations
High complexity of resistance mechanisms Limited information about some mechanisms of resistance Multifactorial multiresistance Oversimplification of interpretative reading Mistakes when deducing mechanisms of resistance

Part Three

EXCEPTIONAL PHENOTYPE

E X C E P T I O N A L P H E N O T Y P E

Resistance in a species where resistance has not been seen or is rare

may change with time may also be regional or national differences

E X C E P T I O N A L P H E N O T Y P E

Resistance in a species where resistance has not been seen or is rare

errors in identification or susceptibility testing send the isolate to a reference laboratory for independent confirmation

Examples
E X C E P T I O N A L P H E N O T Y P E

Streptococcus pyogenes resistant to penicillin Staphylococcus aureus resistant to vancomycin Haemophilus inuenzae resistant to any thirdgeneration cephalosporin, carbapenems, and uoroquinolones

Examples
E X C E P T I O N A L P H E N O T Y P E

Anaerobes resistant to metronidazole Neisseria gonorrhoeae resistant to third-generation cephalosporin Enterobacteriaceae resistant to carbapenems

HOW TO BE AN EXPERT

ICU patient 28 days in hospital oxidase negative non-fermentative Gramnegative bacillus

Antibiotic Amoxicillin-clavulanate Piperacillin-tazobactam Ceftriaxone Ceftazidime Cefepime Imipenem Ertapenem Meropenem Amikacin Gentamicin Ciprofloxacin Trimethoprimsulfamethoxazole

Zone (mm) 6 6 6 26 18 6 6 6 6 6 30 35

Result R R R

ICU patient 28 days in hospital oxidase negative non-fermentative Gramnegative bacillus What is the likely organism?

R R R R R

How would you report susceptibility to: ceftazidime imipenem ciprofloxacin

Enterobacter cloacae
Antibiotic Amoxicillinclavulanate Cefoxitin Ceftriaxone Ceftazidime Cefepime Imipenem Ertapenem Meropenem Ciprofloxacin Trimethoprimsulfamethoxazole Zone (mm) 6 6 27 26 24 24 23 24 25 20 Result R R S S S S S S S S

Isolate from blood culture Patient with suspected ventilatorassociated pneumonia

Enterobacter cloacae
Antibiotic Amoxicillinclavulanate Cefoxitin Ceftriaxone Ceftazidime Cefepime Imipenem Ertapenem Meropenem Ciprofloxacin Trimethoprimsulfamethoxazole Zone (mm) 6 6 27 26 24 24 23 24 25 20 Result R R S S S S S S S S

Isolate from blood culture Patient with suspected ventilatorassociated pneumonia

How would you report susceptibility to: ceftriaxone cefepime imipenem

ARTIFICIAL INTELLIGENCE

Computerised expert modification

Disc susceptibility Adagio Biomic MIC equivalent Phoenix Vitek Microscan

Vitek AES

Changed cefepime to Resistant

Lab Information System Alerts

The Real Expert

Summary
Systems vary in accuracy design update frequency See Winstanley T, Courvalin P. Expert Systems in Clinical Microbiology. Clin Microbiol Rev. 2011; 24(3):51556.

Conclusions
Some resistant organisms may need supplemental methods to detect Susceptibility testing can be complicated Resistance mechanism or tested MIC? Not yet quite sure.