1. The Role of the Microbiology Laboratory in AMS programs
Maria Virginia Villegas, MD, MSc, FIDSA
Scientific Director Bacterial Resistance and Hospital Epidemiology Research Area
International Center for Medical Research and Training, Cali, Colombia CIDEIM

2. Antimicrobial Stewardship Core Team
Dellit TH, et al. Clin Infect Dis 2007; 44:

3. Aims of the talk
To discuss the important role of the microlab in an Antimicrobial Stewardship program
Antibiogram interpretation with footnotes to help the physicians make the right antibiotic choice
2. Elaborate the epidemiologic report that will be used to create the antibiotic guidelines( ex : using WHONET ).

4. LABORATORY REPORT S.aureus
Rifampin S
Ampicillin R
Vancomycin S
Oxacillin S
TMP-SMX S
Cefazoline R
Gentamicin S
Levofloxacin S

5. SUPPRESSION RULE OF ANTIBIOTICS
1. If S. aureus is susceptible to Oxacillin
Do not report Vancomycin or Quinolones.
PS: Oxacillin is reported with a footnote that specifically says that any Beta-lactam can be given
2. If the S. aureus isolate is MRSA
Report Vancomycin and other therapeutic options such as Linezolid, Daptomycin, Ceftaroline, Clindamycin and TMP-SMX.

6. For MRSA Report Vancomycin with the MIC and a footnote :
If the MIC is ≥ 2 µgms /ml DO NOT give Vancomycin because of the high risk for therapeutic failure ( > 50 % ) in severe infections/bacteremia.
If the MIC is ≥ 1 µgms /ml, it can be used with a loading dose of mg/kg, then 15 mg /kg every 12 hours AND re-evaluate the therapeutic response after 48 hours.
Interconsultation with infectious disease to define the use of Linezolid, Daptomycin, Ceftaroline , according to the site of infection and clinical conditions ( pneumonia vs bacteremia vs soft tissue infections ).

7. EXAMPLE OF MRSA MIC DISTRIBUTION FOR VANCOMYCIN

8. Influence of Vancomycin MIC on Outcome in S.aureus Infection
100
Failure
Success 90 80 70 60
Percent 50 40 30
A study by Moise-Broder in 2004 demonstrates the relationship between minimum inhibitory concentration (MIC) and treatment success
Increases in MIC from 0.5 to 1 to 2 were significantly associated with increasing treatment failure
Moise-Broder et al. Clin Infect Dis. 2004;38: 20 10
0.5 1 2
MIC
Moise-Broder et al. Clin Infect Dis. 2004;38:

9. LABORATORY REPORT P.aeruginosa
Amikacin S
Gentamicin R
Ceftazidime S
Cefepime S
Imipenem R
Ciprofloxacin S
Meropenem R
Pip/tazobactam S
Footnote : This P. aeruginosa has both OprD-mediated resistance mechanism and efflux pump activation. Other anti-pseudomonal agents can be used.

10. SUPPRESSION RULE OF ANTIBIOTICS
For P. aeruginosa:
●Report ALL the antibiotics with antipseudomonal activity with their respective MIC.
●Do not report other quinolones when there is resistance to Ciprofloxacin (cross resistance).
●Do not report ANY antibiotic without
antipseudomonal activity i.e.:
Ceftriaxone, Cefotaxime, TMP-SMX, Amp/sulbactam, Ertapenem etc.

11. LABORATORY REPORT E.coli
Amikacin S
Ampicillin R
Cefazolin R
Ceftazidime S
Cefepime S
Ceftriaxone S
Ciprofloxacin R
Meropenem S
Levofloxacin S
Pip/tazobactam S

12. SUPPRESSION RULE OF ANTIBIOTICS
Quinolones report for Gram (-) bacteria including P.aeruginosa :
▪ If ciprofloxacin is resistant, suppress other quinolones or put a footnote explaining that there is cross resistance.
▪ Ciprofloxacin is the most active quinolone against Gram(-) bacteria
▪ In contrast Moxifloxacin and Levofloxacin are more active against Gram(+) bacteria

13. LABORATORY REPORT E.cloacae
Amikacin S
Pip/tazobactam R
Cefazoline R
Ceftazidime R
Cefepime S
Ceftriaxone R
Cefoxitin R
Levofloxacin S

14. SUPPRESSION RULE OF ANTIBIOTICS
For AmpC GROUP : Footnote :
The use of third generation cephalosporin's is associated with high risk of clinical failure during treatment (especially in bacteremia and severe infections) Avoid their use as well as Beta-lactamase inhibitors.
The antibiotics of choice are : carbapenems (especially Ertapenem ), tigecycline ( only in mild infections, to de-escalate, or in allergies to B-lactams ), ciprofloxacin ( for UTI, skin infections ) and cefepime ( if there is also risk of Pseudomona ).

15. LABORATORY REPORT Klebsiella pneumoniae
Amikacin S
Ampicillin R
Cefazolin R
Ceftazidime S/R
Cefepime S/R
Ceftriaxone R/R
Ertapenem S
Meropenem S
Levofloxacin S
Pip/tazobactam S/R

16. ESBL confirmatory test
C--NH
H2N S N
Caz O
CH3 N o C
CH3
COOH
CEFTAZIDIME
Caz + Clav
Ctx + Clav
ESBL
Ctx

17. SUPPRESSION RULE OF ANTIBIOTICS
For ESBLS Footnote :
This bacteria produces an Extended Spectrum Cephalosporin ( ESBL ) . The use of any cephalosporin and Aztreonam is associated with a high risk of clinical failure during treatment. Avoid their use, as well as Pip/taz and Cefepime
In the report: Ceftriaxone, Cefotaxime, Ceftazidime and Aztreonam SHOULD BE Resistant. Don’t report ( block it ) Pip/tazo and Cefepime.
3. Confirmatory test for ESBLS should always be included ( even for strains in the susceptible range).

18. Cefepime monotherapy for cefepime-susceptible ESBL-producing infections : MIC is important!!!
Mortality rates in 3 patient subgroups who received cefepime (n = 33)
stratified by MIC of cefepime
Lee, N. Y. et al Clin Infect. Dis. 6(4):

19. Low MIC <=2
AAC 2013

20. JAC 2012

21. Aims of the talk
To discuss the important role of the microlab in an Antimicrobial Stewardship program
Antibiogram interpretation with footnotes to help the physicians make the right antibiotic choice
2. Use of WHONET to elaborate the epidemiologic
report that will be used to create the antibiotic
guidelines.

22. Local Epidemiology ICU

23. Trends of Resistant Microorganisms
Third-generation cephalosporin-resistant Enterobacteriaceae
Meropenem-resistant
Pseudomonas aeruginosa
Trimesters in

24. Microbiological profile of the first five microorganisms by the most frequent sample types in General wards January-December 2014
Once you have the source of infection and the predominant micro-organisms, you can create specific Antibiotic Guidelines; in this case for : UTI, Skin and Soft Tissue Infections and UTI associated to Foley catheter.

25. Antibiotic Resistance Analysis in Gram-Negative Bacteria
Antibiotic resistance percentages for the most frequently isolated Gram-negative bacteria from ICUs, January-December 2012

26. MIC Analysis for Choosing the Antipseudomonal Antibiotic with the SMALLER Non-Susceptible Bacterial Population
Piperacillin/Tazobactam
Cefepime
Imipenem
Meropenem
MIC (µg/mL) %

27. Example to decide if adding or Not an Aminoglycoside to the Beta-Lactam therapy for P.aeruginosa
AMK (MIC)
MEM (MIC)
“According to the susceptibility tests performed, 69% of P. aeruginosa (n = 29) are susceptible to both amikacin and meropenem. Combination therapy with meropenem and amikacin would increase chance of appropriate therapy in 10.3%.”

28. Antibiotic Resistance Analysis in Gram-Positive Bacteria
Antibiotic resistance percentages for the most frequently isolated Gram-positive bacteria from ICUs, January-December 2012

29. Trends of Resistant Microorganisms Methicillin-Resistant S. aureus

30. Summary An AMS program should start in the microbiology laboratory.
The information generated through the microbiology lab is key for :
Helping the MD select the appropriate antibiotic, which will reduce therapeutic failures and the use of broad-spectrum antibiotics
Generating epidemiological data which will help the ID committee create and implement the Antibiotic Guidelines.

31. Thank you!