ANTIBIOTIC SUSCEPTIBILITY TESTING WHAT AFFECTS CHOICE OF ...

[Pages:12]ANTIMICROBIAL RESISTANCE

HOW CAN THE LAB HELP?

Dr. Susan Whittier Associate Director, Clinical Microbiology Service

5-6237 or whittie@

LEARNING OBJECTIVES

Describe difference between qualitative & quantitative antimicrobial susceptibility testing [AST] and the clinical value of each

Discuss resistance mechanisms utilized by gram negative bacteria

Recognize unusual/improbable AST result

ANTIBIOTIC SUSCEPTIBILITY TESTING

ROLE OF THE LAB

IMPLEMENT CURRENT CLSI (CLINICAL LAB STANDARDS INSTITUTE) GUIDELINES

TEST & REPORT DRUG SUSCEPTIBILITIES BASED ON PATHOGEN & SOURCE OF INFECTION

9 E.G. URINE, BLOODS 9 IN VIVO & IN VITRO CORRELATION 9 DRUG RESISTANCE MECHANISMS OF ACTION

ANNUAL ANTIBIOGRAMS

9 UNIT SPECIFIC, e.g. MICU, SICU, PICU 9 CHOOSE APPROPRIATE EMPIRIC THERAPY BASED ON

PREDICTABLE RESISTANCE PATTERNS

LAB REPORTING SYSTEMS

9 SIR vs. MIC

TESTING NEW ANTIMICROBIAL AGENTS

9 PROVIDE INTERPRETIVE CONSULTATION

WHAT AFFECTS CHOICE OF ANTIMICROBIAL AGENTS ?

ANTIMICROBIAL SUSCEPTIBILITY TEST RESULTS

PHARMACODYNAMICS 9 AUC:MIC90 RATIO 9 HALF LIFE OF DRUG 9 TIME ABOVE THE MIC 9 CONCENTRATION DEPENDENT KILLING Greater cidal activity with higher concen (e.g. aminoglycosides, B-lactams)

ANTIBIOGRAM

Antimicrobial susceptibility profile of pathogen

9 Guides empiric therapy based on intrinsic resistance patterns & predictable drug bug combinations

9 CAN YOU PROVIDE SOME EXAMPLES?

Fickle pathogens 9 S. maltophilia & Trimeth/sulfa 9 P. aeruginosa & cipro 9 K. pneumo & imipenem

Antibiogram NOW ON LINE!!

9 "Real-time" analysis 9 Make formulary decisions 9 Establish guidelines for antibiotic management

ANTIBIOTIC SUSCEPTIBILITY TESTS

MIC VALUE

9 LOWEST CONCENTRATION OF ANTIMICROBIAL WHICH WILL INHIBIT GROWTH

9 MICROSCAN or VITEK SEMIAUTOMATED 9 E-STRIPS (DISK GRADIENT) 9 TIME TO RESULTS: 18 - 24 HRS

SIR, NO MIC

9 QUALITATIVE INTERPRETATION 9 DISK DIFFUSION (KIRBY- BAUER) 9 TIME TO RESULTS: 18 - 24 HRS 9 NOT SUFFICIENT FOR STERILE FLUIDS

QUESTIONS TO ASK...... 9 S.aureus IS ERYTHRO RESISTANT

IS IT A PREDICTOR OF CLINDA RESISTANCE? 9 LAB REPORTS PENICILLIN RESISTANT GP A STREP

IS THIS BELIEVABLE? 9 LAB REPORTS YEAST FROM BLOOD CULTURE

WHAT EMPIRIC TREATMENT IS RECOMMENDED?

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SUSCEPTIBILITY TESTING Assumptions

BLOODSTREAM INFECTION

HOMOGENEOUS BACTERIAL POPULATION

SUCCESS = ERADICATION OF ORGANISM

Implications of Multi-Resistant Organisms

EPIDEMIOLOGY TREATMENT INFECTION

CONTROL TRANSPLANT

ELIGIBILITY

SUSCEPTIBILITY TESTING Reality

SITE OF INFECTION:

9 INFLAMED LUNG W/ PURULENT SECRETIONS 9 ABSCESS 9 CSF

HETEROGENEOUS BACTERIAL POPULATION

9 MULTIPLE SPECIES 9 MULTIPLE MORPHOTYPES

BIOFILM

ANTIMICROBIAL SUSCEPTIBILITY TESTING METHODOLOGIES

DISK DIFFUSION

Kirby-Bauer

BROTH DILUTION

Microbroth Microscan Vitek

E TEST

DISK DIFFUSION

PROS

9 EASY TO PERFORM 9 FLEXIBILITY 9 NO EQUIPMENT NEEDED

CONS

9 NON QUANTITATIVE 9 NON AUTOMATED 9 INACCURATE FOR POORLY DIFFUSING

DRUGS 9 DATA LACKING FOR SLOW GROWING

ORGANISMS

DISK DIFFUSION

2

BROTH DILUTION

PROS 9 QUANTITATIVE 9 WIDE RANGE OF ORGANISMS 9 COMMERICALLY PREPARED PANELS 9 AUTOMATION

CONS 9 PRE-DETERMINED FORMAT 9 LESS RELIABLE FOR CERTAIN ORGANISMS

E TEST

PROS

9 SIMPLE TO PERFORM 9 FLEXIBILITY

CONS

9 EXPENSIVE

E- STRIP MIC TEST

Gradient agar diffusion preformed antimicrobial gradient

Plastic coated strip MIC read at point of elliptical growth

inhibition Can use on fastidious organisms Confirmation of unusual resistance Expensive

E TEST

EXAMPLES OF FLAGGED RESULTS

E. coli : Imipenem Resistant S. pneumoniae: Vancomycin Resistant Kleb pneumo: Amikacin Resistant,

Gent/Tobra Susceptible S. aureus: Penicillin Susceptible E. cloacae: Ampicillin Susceptible A. baumanii: Aztreonam Susceptible

SUSCEPTIBILITY TESTING CURRENT CHALLENGES

Focus time, effort and finances on critical care patients

Does every patient isolate need an MIC?

How good are we at detecting resistance?

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WHEN IS MIC TESTING NECESSARY?

Life threatening infections

9 Endocarditis 9 Meningitis 9 Osteomyelitis

Immunocompromised patients Critically ill patients

HOW TO USE MIC DATA

For individual patient therapy

9 Selection of antibiotic 9 Dosage

Efficacy Efficiency Toxicity

9 Combination therapy

Investigation of unusual AST results Detection of specific resistance

mechanisms

USING MICs TO OPTIMIZE THERAPY

More institutions are utilizing MIC data to manage critical patients

Pharmacokinetics

Drug levels in blood, CSF, tissue, infection site vs the MIC

Pharmacodynamics

Drug properties that affect bacterial eradication rate vs the MIC

PHARMACOKINETICS

Antibiotic:

9 Route of administration 9 Dose 9 Metabolism 9 Elimination

Drug levels in blood and infected tissues

PK is what the body does to the drug

PHARMACODYNAMICS

Antibiotic penetration Receptor binding affinity Resistance mechanism Host immunity Virulence PD is what the drug does in the

body

PK/PD REQUIRE PRECISE MICs

Aminoglycosides

9 C max

Fluoroquinolones

9 AUC

Beta lactams

9 Time over the MIC

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NAME CALLING AST JARGON

MRSA - Methicillin-Resistant S.aureus 9 44% at CUMC

VISA- Vanco-intermediate S. aureus VRSA- Vanco-resistant S. aureus VRE- Vanco R E. faecium

9 81% in CUMC ESBLs in GNR

9 18% in CUMC

THE "USED TO BE" PREDICTABLE AST PATTERNS

ORGANISMS K. pneumo P. aeruginosa Salmonella S. aureus E. faecium Any organism

PREDICTABLE [Not so much...] Susceptible to Imipenem Susceptible to Cipro Susceptible to Cipro Susceptible to Vanco Susceptible to Linezolid Susceptible to at least one antibiotic

PREDICTABLE RESISTANCE

Salmonella, Shigella

9 Stool: Ampicillin, quinolone, T/S ONLY will be reported 9 Extraintestinal: above + chloramphenicol, 3rd gen

cephalosporin

Enterobacter, Serratia

9 Ampicillin & 1st & 2nd generation cephalosporins are NOT reported

9 Routine resistance

Stenotrophomonas

9 Inherent resistance to nearly all antimicrobics 9 ONLY T/S, Timentin & fluoroquinolone are reported Enterococcus 9 Cephalosporins, aminoglycosides, clinda, T/S will NOT be

reported

TOUGH BUGS ON THE BLOCK

MRSA & VRE 9 COST TO TREAT MRSA 3X MSSA

ESBLs Carbapenam- resistant GNR

9 Klebsiella pneumoniae 9 Acinetobacter baumannii 9 Pseudomonas aeruginosa 9 Stenotrophomonas maltophilia Metallo- ? ?Lactamases

AST NOT AS EASY AS IT SEEMS !

> 1 method sometimes needed 9 MRSA 9 VRE 9 ESBL

Review results for unusual antibiogram patterns

Update new interpretive guidelines Some microbes lack CLSI guidelines

ENDOCARDITIS CASE

61 yo male with persistent fevers Suspected subacute bacterial

endocarditis Two sets of blood cultures collected Positive the next day for coagulase

negative Staphylococcus AST panels are set up for isolates 1 & 2

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ENDOCARDITIS CASE

MIC VALUES

ISOLATE #1

ISOLATE #2

9 OXACILLIN 0.5

9 OXACILLIN 1.0

Resistant

Resistant

9 PENICILLIN 1.0

9 PENICILLIN 0.5

Resistant

Resistant

9 VANCO

1.0

Susceptible

9 VANCO

0.5

Susceptible

9 CLINDA

100,000 CFU/ml Staphylococcus aureus

OXACILLIN

4

RESISTANT

CHLORAMPHENICOL 4

SUSCEPTIBLE

LINEZOLID

2

SUSCEPTIBLE

RIFAMPIN

1

SUSCEPTIBLE

TRIMETH/SULFA

2/38 SUSCEPTIBLE

VANCOMYCIN

4

SUSCEPTIBLE

PUZZLE PIECES

Patient was started on vancomycin Urine cultures remained positive for S. aureus Further testing by lab

9 E test MIC = >256 RESISTANT!! Isolate was positive for

9 mecA OXACILLIN RESISTANCE 9 vanA VANCOMYCIN RESISTANCE

MECHANISM FROM VRE WHAT HAPPENED?????? Automated systems are unable to detect VRSA

CDC recommends utilization of vancomycin

screen agar plate

PUZZLE PIECES

Patient was started on vancomycin Urine cultures remained positive for

S. aureus

WHAT'S GOING ON?

E. faecalis VanA

S. aureus

VanA transfer

S. aureus

FATAL ATTRACTION Resident plasmid

VanA

E. faecalis

VanA S. aureus

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VISA

VISA? INTERMEDIATE TO VANCO

9 1ST ISOLATED IN 1996 IN JAPAN 9 8 PTS TO DATE IN USA 9 MECHANISM OF RESISTANCE: THICKENED CELL WALL

AND/OR AN EXTRACELLULAR MATRIX ?? 9 PATIENTS HAD PRIOR EXPOSURE TO LONG TERM

VANCOMYCIN THERAPY

2 VISA ISOLATES FOUND SUSCEPTIBLE TO OXACILLIN 9 ONE WAS MECA POS & ONE NEG

9 OXACILLIN RESISTANCE IS NOT NECESSARY FOR VISA PHENOTOYPE

NO CLONAL SPREAD OF SINGLE STRAIN

VRSA JUNE 2002

1st case in 40 yr old diabetic woman from Michigan

VRSA from dialysis cath tip

Recurrent foot ulcer infected with VRE & MRSA

MICHIGAN VRSA CASE

THE USA VRSA ISOLATE 9 MRSA ? METHICILLIN MIC >16 ug/mL 9 VANCOMYCIN MIC 1,024 ug/mL 9 SUSCEPTIBLE TO LINEZOLID, MINOCYCLINE, QUIN/DALFO, CHLORO and SXT

CONJUGATIVE TRANSFER 9 VRSA ISOLATE HAD vanA RESISTANCE GENE & mecA 9 vanA TRANSPOSON JUMPED FROM VRE CONJUGAL PLASMID TO A RESIDENT PLASMID IN MRSA STRAIN TO BECOME VRSA

CLSI Interpretive Criteria Vancomycin Staphylococcus spp.

VISA

VRSA

METHOD SUSCEPTIBLE INTERMEDIATE RESISTANT

MIC (?g/ml)

Disk (30 ?g) (mm)

55

4 15

8-16

32

-

-

VRSA (3 isolates encountered to date)

Isolate Vanco MIC1 (?g/ml)

1

1,024

2

32 2

3

64 2

1 Reference broth microdilution MIC

2 Missed or inconsistent results (some < 2 ?g/ml )

with automated methods

4/04 CDC RECOMMENDATION: ADD VANCOMYCIN AGAR SCREEN WITH AUTOMATED METHOD

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ICU SEPSIS

64 yo male patient, cardiac ICU post-CABG

Becomes febrile and hemodynamically unstable

Blood cultures x 2 are collected

Culture Results: 9 Klebsiella pneumoniae

Amikacin

8

S

Cefoxitin

4

S

?Based on AST, patient treated w/ ceftriaxone

?Remains febrile

Ceftazidime >32 R ?Blood cultures collected

Ceftriaxone 8

S ?Positive for K. pneumoniae

Imipenem

4

S ?What's going on?

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