Jodor A. Lim MD. FPCP

Disclosure

Lecturer, Adboard, Travel Grant

Vizcarra Pharma, Biomedis, GSK, Pfizer, Novartis, Brahms Diagnostics, Eli Lilly, Cathay Drug

Objectives To discuss the clinical importance of the antibiogram

in guiding clinicians on empiric antibiotic use

To review the antimicrobial susceptibility test and the standards behind the test

To present clinical scenarios and present three antibiograms which can be used in the clinical setting

Case No. 1 A 40 year old non diabetic non hypertensive female

was admitted with a history of fever and chills of 3 days duration. There were no other symptoms except for dysuria and flank pains.

Vital signs BP 100/70 HR 98 RR 20 T 38.2 degrees C

Physical exam showed hypogastric tenderness

Urinalysis revealed pyuria

Assessment - Acute Pyelonephritis

As a first year medical resident, what would you do A. You remembered your microbiology teacher and did

the initial diagnostic work ups which included your urine CS

B. You went back to your notes on the guidelines on UTI presented a week ago by an ID physician

C. You wake up your senior and ask him to tell you what his favorite antibiotic is for UTI.

D. You opted to just start the antibiotics that the med rep detailed a few hours back

E. You decided to check your antibiogram

Antibiogram

• Tabulation of frequency of susceptibility to individual antimicrobials by pathogens

• Summary profile of susceptibility or resistance patterns of frequently tested pathogens to antimicrobials commonly in use

• Differs per hospital

• Tabulation of susceptibility to individual drugs by site of infection or ward

• Trends in susceptibility/resistance pattern of microorganisms

Antibiogram

• Hospital Wide

• All organisms

• Specific Units

• Intensive Care Units

• High Risk Nurseries

• Burn Units

• Specific specimen

• Blood

• Respiratory

• Urine

• Stool

Antibiogram

• Should include “key” sentinel

organisms for monitoring • MRSA

• Multiply Resistant Organism

• Pseudomonas aeruginosa

• Acinetobacter

• ESBL producing Enterobacteriaceae

• E. coli

• Klebsiella

Antibiogram - Utility

• Provides guidance to clinicians for empiric therapy of

infection before the causative agent has been identified.

• Direct therapy after an organism has been identified but before susceptibility tests have been completed

• Guides ICC/QA/Pharmacy on antibiotic utilization and effect of restrictions

Total Number of Samples Received to include Positive and Negative Rate, January to December 2011 ,UPHDMC

Total No of Specimen Received for Culture & Sensitivity

Total No of Specimen with Isolates

Total No of Specimen without Growth

2908 1488 (51.1%) 1420

Antimicrobial Susceptibility Test

• is the determination of an organisms pattern of susceptibility or resistance to a battery of antimicrobial agents.

• Objective:

• to predict the outcome with the antimicrobial agents tested and guide the clinician in the selection of the most appropriate agent for a particular clinical problem

• to direct therapy toward the most narrow spectrum, least expensive agent to which the pathogen should respond

Laboratory Standards Organization a regulatory body that provide guidelines and

recommendations on methodologies, techniques, breakpoints and interpretative criteria in AST.

AST Methods Disk Diffusion/ Kirby Bauer Technique

Agar Dilution

Broth Dilution

Antibiotic Gradient/ E-Test

Automated Instrument Method VITEK (Biomerieux)

Phoenix (BD)

Disk Diffusion Method (Kirby Bauer Technique)

A standard qualitative disk diffusion test in which a commercially prepared filter paper disk is used impregnated with specified amount of antimicrobial agent

Advantages:

simple and reproducible

inexpensive

results are easily understood by clinicians

flexible regarding the selection of

antimicrobial agents for testing

Steps on Antimicrobial Susceptibility Testing (Disk Diffusion Method)

Inoculum Preparation

Inoculum Standardization

Agar Plate Inoculation

Antimicrobial Disk Application

Plate Incubation

Measurement of Zone Inhibition

Media Preparation

Reporting and Interpretation of Results

• Zone size of inhibition is interpreted by CLSI • Every regulatory body (CLSI) provides breakpoint settings on

every organism to determine the categories of S,I,R.

• CLSI Interpretative Criteria • S – Susceptible

• Implies that the isolates are inhibited by antimicrobial agent when the recommended dosage is used

• Zone size of inhibition fall within the susceptible range

• I – Intermediate

• A buffer zone

• Implies that the isolate maybe inhibited but the response maybe lower than expected

• R – Resistant

• Zone size of inhibition falls within the resistant range

AST is reported using NON-PROPRIETARY NAMES (generic) for the following reasons:

To minimize confusion

To emphasize the relatedness of the currently available drugs

CLSI Recommendations:

• Group A • agents appropriate for routine primary testing panel as well as for routine reporting of results. • Group B • agents for primary testing especially in nosocomial infection and reported selectively • Group C • alternative or supplemental agents on endemic and

epidemic strains resistant to several of the primary drugs • Group U • agents used primarily for UTI • Group O •Other agents with clinical indication for the organism but not candidate for routine test and report • Group Inv • Investigational agents for the organism but not yet approved

by FDA

Fastidious organisms • Haemophilus spp

• Neisseria gonorrhea

• Streptococcus pneumoniae

• Streptococcus spp. B hemolytic group

• Streptococcus viridans group

Non Fastidious Organisms • Enterobacteriaceae (including E. coli, Salmonella)

• Pseudomonas aeruginosa

• Staphylococcus spp.

• Enterococcus spp

General Comments for Fastidious organisms

Susceptibility and resistance to azithromycin, clarithromycin & dirithromycin can be predicted by testing erythromycin

Organisms that are susceptible to tetracycline are also considered susceptible to doxycycline and minocycline

S. Pneumo isolates susceptible to levofloxacin are predictably susceptible to gemifloxacin & moxifloxacin, but not vice versa

E.coli 17%

Klebsiella 16%

CNS 13%

Ps. Auruginosa 10%

Enterobacter 10%

Staph aureus 9%

Stap epid 4%

Proteus spp 4%

Others 17%

Distribution of Pathogens ARSP 2010 (n=22,122)

Non Fastidious Organisms Enterobacteriaceae (including Salmonella, Shigella)

Pseudomonas aeruginosa

Staphylococcus spp.

Enterococcus spp.

Comments for Enterobacteriaceae Cephalothin can be used to represent cephapirin,

cephalexin, cefaclor, cefadroxyl

Cefazolin, cefpodoxime, cefrozil, cefuroxime & loracarbef can be tested individually; some isolates can be sensitive to these even if resistant to cephalothin

Organisms susceptible to tetracycline are considered susceptible to doxycycline & minocycline. Some isolates intermediate or resistant to tetra maybe susceptible to doxy or mino or both

Comments on Enterobacteriareae

• When fecal isolates of Salmonella & Shigella spp are tested, only ampicillin, a flouroquinolone and trimethoprim/sulfamethoxazole should be reported routinely

• Chloramphenicol and a third generation cephalosporin should be tested for extraintestinal isolates for Salmonella spp

• Cefotaxime & ceftriaxone should be tested and reported on isolates from CSF in place of cephalothin and cefazolin

Case No. 1 A 40 year old non diabetic non hypertensive female

was admitted with a history of fever and chills of 3 days duration. There were no other symptoms except for dysuria and flank pains.

Vital signs BP 100/70 HR 98 RR 20 T 38.2 degrees C

Physical exam showed hypogastric tenderness

Urinalysis revealed pyuria

Assessment - Acute Pyelonephritis

Percent resistance of Escherichia coli from Urine Sample, Jan.-Dec., 2011

100

81.3

75.1

22.2

62.9

69.3

91.2

9

20.8

14.5

7.8

21.1

9.4

0 1.3

6

26.3 23.8

41.2

37.9 40.4 40.6

66.3

14.2

37.6

0

20

40

60

80

100

120

PEN

AM

P

PIP

AM

C

TCC

CEP

CZO CA

Z

CRO CTX FEP

CXA

ATM IP

M

MEM

AM

K

GEN

TOB

CIP

LVX

NO

R

OFX SXT

NIT

TCY

Escherichia coli N=313 ESBL (+) 34Antibiotic name Number %R %I %S

Ampicillin 293 80.2 5.5 14.3Piperacillin 288 74.3 8.3 17.4Amoxicillin/Clavulanic acid 293 21.8 47.4 30.7Ticarcillin/Clavulanic acid 145 64.1 20.7 15.2Piperacillin/Tazobactam 283 5.3 18 76.7Cephalothin 229 69.4 20.5 10Cefazolin 113 69.9 9.7 20.4Ceftazidime 292 19.2 4.1 76.7Ceftriaxone 271 19.2 10 70.8Cefotaxime 294 19.4 16.3 64.3Cefepime 290 19.3 0.3 80.3Cefuroxime axetil 291 24.4 66 9.6Aztreonam 294 20.1 10.9 69Doripenem 6 0 0 0Imipenem 294 0.3 0.3 99.3Meropenem 291 0.3 0 99.7Amikacin 291 5.5 16.8 77.7Gentamicin 287 27.2 4.2 68.6Tobramycin 290 24.1 9 66.9Ciprofloxacin 292 41.8 6.2 52.1Levofloxacin 260 39.2 2.7 58.1Norfloxacin 236 40.7 2.1 57.2Ofloxacin 234 40.6 2.1 57.3Trimethoprim/Sulfamethoxazole 262 65.3 2.7 32.1Nitrofurantoin 225 14.2 15.1 70.7Chloramphenicol 58 34.5 10.3 55.2Tetracycline 293 38.6 13 48.5

% Resistance of E coli (Urine) to Oral Abx,ARSP 2010

ARSP UPHDMC

Ampicillin 85.4 80.2

Cefuroxime – 59.8 (opd) 24.4

Ciprofloxacin – 57.4 41.8

Cotrimoxazole – 72.0 65.3

Coamoxyclav- 36.2 21.8

Nitrofurantoin 7.6 14.2

Case No 2. A 50 year old female, diabetic, non hypertensive was

admitted due to a progressing erythema over the R lower extremity. She presents with a history of fever and chills after the erythema was noted. She took some unrecalled antibiotics but noted no improvement. She was then brought to the emergency room and referred for admission

Vital Signs BP 140/90 HR 104 RR 24 T 39 degrees C

Physical Exam revealed erythema with warmth and tenderness over the R lower leg

Assessment – Cellulitis r/o Sepsis

Comments for Staphylococcus

Pen-susceptible staph are also susceptible to other penicillins, cephems,& carbapenems;

Pen-resistant , oxacillin-susceptible strains are resistant to penicillinase-labile penicillins but susceptible to other penicillinase-stable penicillins, BBLIC, relevant cephems & carbapenems

Oxacillin resistant staph are resistant to all currently available B lactam antibiotics.

Comments for Staphylococcus

Susceptibility or resistance to many B lactam antibiotics may be deduced from testing only pen and oxacilin or cefoxitin ( as a surrogate for oxacillin)

Routine testing of other penicillins, BBLIC, cephemsand carbapenems is not advised

Results of cefoxitin test can be used to predict mec A mediated oxacillin resistance in Staph aureus & S. lugdunensis.

For CNS, the cefoxitin disk is the preferred method

Percent Resistance of Staphylococcus aureus from all sources Jan.-Dec., 2011

92.8

68.5

72.2

66.7

7.7

4 6.1 5.3

20

5.6

13.5 12.1

18.2

12.1

0 0 0

3.5

8.2

0

10

20

30

40

50

60

70

80

90

100

PEN OXA AMC FOX GEN RIF CIP LVX NOR OFX SXT CLI AZM ERY NIT LNZ VAN CHL TCY

Staphylococcus aureus N=99MRSA(+) N=47 mecA(+) N=47 ICR(+) N=6

Antibiotic name %R %I %SPenicillin G 92.8 0 7.2Oxacillin 68.5 4.5 27Cefoxitin 66.7 0 33.3Gentamicin 7.7 6.6 85.7Rifampin 4 6.1 89.9Ciprofloxacin 6.1 31.6 62.2Levofloxacin 5.3 7 87.7Norfloxacin 20 10 70Ofloxacin 5.6 13.9 80.6Trimethoprim/Sulfamethoxazole 13.5 0 86.5Clindamycin 12.1 17.2 70.7Azithromycin 18.2 27.3 54.5Erythromycin 12.1 29.3 58.6Nitrofurantoin 0 0 100Linezolid 0 0 92.9Vancomycin 0 0 100Chloramphenicol 3.5 30.2 66.3Tetracycline 8.2 3.1 88.7

CIP SXT ERY OXA PEN VAN

6.3 5.8 8.7

54

95.2

0

%Resistance of Staph aureus ARSP 2010

%Resistance

0

10

20

30

40

50

60

70

80

90

100

Tetra=45 Oxa=56 Vanco=27 Erythro=56 Clinda=56 Chloram=50 SXT=59

Antibiotic = No. isolates tested

%

S

u

s

c

e

p

t

i

b

l

e

2009

2010

ARSP '09

2011

Antibiotic Susceptibility Pattern

All Wards / Exudates S. aureus (n=59)

0

10

20

30

40

50

60

70

2003 2004 2005 2007 2008 2009 2010 2011

PGH

ARSP

MRSA RATES

Case No 3 A 60 year old male was admitted to the ICU for ACS

r/o CHF 2o IHD. He has been intubated but has been stable for the past 4 days of stay. Urine output was accurately monitored while he was on a foley catheter. On the day of your duty, patient was noted to be febrile with tachypnea and tachycardia.

Physical exam revealed crackles on both mid to lung fields

CXR revealed congestion, but cannot r/o concomitant pneumonia

Urinalysis revealed pyuria

Assessment – VAP r/o UTI r/o Sepsis

Percent Resistance of Klebsiella pneumoniae from all sources, Jan-Dec 2011

94.8

56.8

38.9

54.1

19.4

64.3

84.8

30.8 32.3 31.2 31.2

37

30.8

0 1.7 2.2

10.3

20.2 21.6

28.2

20.9

29.2 31.9

41.5

50

21.2

29.3

0

10

20

30

40

50

60

70

80

90

100

AM

P

PIP

AM

C

TCC

TZP

CEP

CZO CA

Z

CRO CTX FEP

CXA

ATM DO

R

IPM

MEM

AM

K

GEN

TOB

CIP

LVX

NO

R

OFX SXT

NIT

CH

L

TCY

Klebsiella pneumoniae N=240 ESBL (+) N=30Antibiotic name Number %R %I %SAmpicillin 233 94.8 4.3 0.9Piperacillin 234 56.8 29.5 13.7Amoxicillin/Clavulanic acid 234 38.9 25.6 35.5Ticarcillin/Clavulanic acid 133 54.1 42.1 3.8Piperacillin/Tazobactam 217 19.4 35.9 44.7Cephalothin 70 64.3 10 25.7Cefazolin 46 84.8 6.5 8.7Ceftazidime 234 30.8 4.7 64.5Ceftriaxone 220 32.3 14.5 53.2Cefotaxime 234 31.2 24.4 44.4Cefepime 234 31.2 1.3 67.5Cefuroxime axetil 230 37 57.8 5.2Aztreonam 234 30.8 9.4 59.8Doripenem 5 0 0 0Imipenem 234 1.7 0.9 97.4Meropenem 229 2.2 0 97.8Amikacin 234 10.3 20.1 69.7Gentamicin 228 20.2 9.2 70.6Tobramycin 232 21.6 10.3 68.1Ciprofloxacin 234 28.2 19.7 52.1Levofloxacin 211 20.9 4.7 74.4Norfloxacin 72 29.2 11.1 59.7Ofloxacin 72 31.9 8.3 59.7Trimethoprim/Sulfamethoxazole 212 41.5 3.8 54.7Nitrofurantoin 70 50 27.1 22.9Chloramphenicol 160 21.2 6.9 71.9Tetracycline 232 29.3 11.2 59.5

Percent Resistance of Pseudomonas aeruginosa from all sources Jan.-Dec., 2011

ESBL (+) N=1Pseudomonas aeruginosa N=104 ampC (+) N=35

Antibiotic name Number %R %I %SPiperacillin 98 19.4 0 80.6Ticarcillin 84 56 0 44Piperacillin/Tazobactam 96 13.5 0 86.5Ceftazidime 102 30.4 4.9 64.7Cefepime 102 30.4 3.9 65.7Aztreonam 101 8.9 37.6 53.5Doripenem 16 0 0 0Imipenem 101 27.7 2 70.3Meropenem 101 29.7 2 68.3Amikacin 101 17.8 2 80.2Gentamicin 96 29.2 2.1 68.8Tobramycin 101 27.7 0 72.3Ciprofloxacin 101 29.7 5.9 64.4Levofloxacin 96 31.2 3.1 65.6Norfloxacin 20 35 0 65Ofloxacin 20 35 10 55Trimethoprim/Sulfamethoxazole 8 100 0 0Nitrofurantoin 15 100 0 0Tetracycline 10 80 10 10

19.4

56

13.5

30.4

80.6

30.4

8.9

0

27.7 29.7

17.8

29.2 27.7

29.7 31.2

35 35

100 100 100

80

0

20

40

60

80

100

120

PIP TIC TZP CAZ CTX FEP ATM DOR IPM MEM AMK GEN TOB CIP LVX NOR OFX SXT NIT CHL TCY

Philippine General Hospital The National University Hospital University of the Philippines Manila PHIC-Accredited Health Care Provider

ISO 9001:2008 Certified

Hospital Infection Control Unit (HICU)

in cooperation with the

Bacteriology Section, Department of Central Laboratories

Distribution of Isolates (N=2,365)

18%

8%

24%

50

%

Exudates (Dec '11 - Feb '12)

Urine (Dec '11 - Feb '12)

Respiratory (Dec '11 - Feb '12)

Blood (Jan - Dec '11)

465 (19%)388 (16%)

350 (15%)

261 (11%)

210 (9%)195 (8%)

160 (7%)

146 (6%)

50 (2%)

122 (5%)

27 (1%)

S. epidermidis

P. aeruginosa

A. baumannii

E. coli

K. pneumo

S. aureus

K. ozaenae

E. cloacae

P. putida

P. agglomerans

Others

10 Most Common Organisms

ALL AREAS / ALL SPECIMENS (N=2,365) 2010 (4,340)

E. coli - 10% S. epidermidis - 13% P. aeruginosa - 12% K. pneumoniae - 8% S. aureus - 8% A. baumannii - 11% E. cloacae - 6% P. putida - 2% Enterococcus spp.-6% K. ozaenae -7% Others -19%

WARDS

E. coli

Enterococcus spp.

K. ozaenae

K. pneumoniae

P. aeruginosa

Others

5 Most Common Organisms

All Wards / Urine (n=173)

65 (38%)

22 (13%) 20

(12%)

12 (7%)

10 (6%)

44 (24%) 2010 (456)

E. coli -31% Enterococcus spp. -14% K. pneumoniae -10% K. ozaenae -9% E. cloacae -6% Others -30%

0

10

20

30

40

50

60

70

80

90

100

Am

pi=

61

Gen

ta=65

Am

ik=46

Cef

ta=61

Cef

tria

=63

Pip

tazo

=7

Imip

enem

=43

Mero

penem

=54

Azt

reo=

64

Cef

epim

e=35

Nitro

=57

SXT=63

%

S

u

s

c

e

p

t

i

b

l

e

2009

2010

ARSP '09

2011

Antibiotic Susceptibility Pattern

All Wards / Urine E. coli (n=175)

ICUs

A. baumannii

P. aeruginosa

E. cloacae

K. pneumoniae

K. ozaenae

Others

5 Most Common Organisms

All ICUs / Respiratory (n=190)

82 (43%)

29

(15%)

19 (10%)

18 (9%)

11 (6%)

31 (17%)

2010 (370)

A. baumannii -27% P. aeruginosa -22% K. pneumoniae -12% K. ozaenae -11% S. aureus -6% Others -22%

0

10

20

30

40

50

60

70

80

90

100

Am

ik=72

Am

pi-su

l=60

Cef

ta=79

Cef

tria

=77

Pip

tazo

Imip

enem

=60

Mero

penem

=69

SXT=78

Cef

epim

e=49

%

S

u

s

c

e

p

t

i

b

l

e

2009

2010

2011

Antibiotic Susceptibility Pattern

All ICUs / Respiratory A. baumannii (n=190)

0

10

20

30

40

50

60

70

80

90

100

Am

ik=28

Gen

ta=29

Cef

ta=28

Cip

ro=24

Pip

tazo

=5

Imip

enem

=24

Mero

penem

=29

Azt

reo=

29

Cef

epim

e=16

%

S

u

s

c

e

p

t

i

b

l

e

2009

2010

ARSP

2011

Antibiotic Susceptibility Pattern

All ICUs / Respiratory P. aeruginosa (n=29)

AMK CIP CAZ GEN NET TZP TOB IPM FEP

10.3

15.6

12.3

20.2 19.2

11.1

15.8

9.7

12.4

%Resistance of Pseudomonas aeruginosa ARSP 2010

%Resistance

% Resistance of Pseudomonas to Abx,ARSP 2010

ARSP UPHDMC

Amikacin 10.3 17.8

Ciprofloxacin 15.6 29.7

Ceftazidime 12.3 30.4

Gentamicin 20.2 29.2

Pip-tazo 11.1 13.5

Imipenem 9.7 27.7

Cefipime 12.4 30.4

Summary The antibiogram can assist a clinician in the choice of

empiric antibiotics

The individual antimicrobial susceptibility tests must follow standards in order to collate an accurate antimicrobial susceptibility report

The clinician must know how to use and interpret individual as well as collated antimicrobial susceptibility tests

Acknowledgement

Antimicrobial Resistance Surveillance Program, DOH

UP – PGH Hospital Infection Control Unit& IDS-MRL

University of Perpetual Help DALTA Medical Center