CLINICAL MICROBIOLOGY CASCADE REPORTING

1. CASCADE REPORTING
Dr.P.B.PRAVEENKUMAR
FIRST YEAR POST GRADUATE
DEPARTMENT OF MICROBIOLOGY
THANJAVUR MEDICAL COLLEGE

2. SYNOPSIS
• Antimicrobial suppression
• Types of antimicrobial suppression
• Overview of CLSI 2022 and CLSI 2023
• CLSI and EUCAST difference
• Types of Breakpoints
• Comments in clinical microbiology reporting
• Two stage reporting model
• WHONET – Our college reporting/antibiogram
software

3. ANTIMICROBIAL SUPPRESSION
• Withholding (Not releasing) the
antimicrobial susceptibility test (AST)
results of certain antimicrobial agents
from the final patient report.
(NOT IN ROUTINE ANTIBIOGRAM)
• Purpose: To encourage appropriate use
of antimicrobial agents.
• Antimicrobial suppression will be done
by THREE METHODS.

4. THREE METHODS OF
ANTIMICROBIAL SUPPRESSION
• Selective reporting
• Cascade reporting
• Testing limitation

5. SELECTIVE REPORTING
Reporting results for specific antimicrobial
agents while suppressing others based on some
criteria
• Organism identification
• Mechanism of resistance
• Body site
• Clinical setting
• Patient demographics
• Aberrant results
• Unavailability of clinical breakpoints

6. ORGANISM IDENTIFICATION
CLINICALLY INEFFECTIVE CLINICALLY NOT REPORTED
Drugs may display susceptible
results in in vitro but clinically
ineffective.
Example:
1st or 2nd generation
cephalosporins and
aminoglycosides for salmonella
infections
Drugs which are effective
against organism but no break
points available. So not
reported.
Example:
Cefepime, Piperacillin
tazobactam, meropenem,
imipenem, ertapenem effective
against salmonella, but not
reported since no breakpoints
given by CLSI

7. MECHANISM OF RESISTANCE
• No need to modify the AST reports even if
any organism is found to be ESBL / AmpC
producing.
• If ICR (Inducible clindamycin resistance) is
found by AST report it as resistance regardless
of their zone size or MIC.

8. BODY SITE
No..ssssss in AST report
Respiratory specimen – Daptomycin
CSF – 1st,2nd generation cephalosporins,
erta/doro/imipenem, clindamycin, tetracycline,
macrolides, quinolones, aminoglycosies
Urine specimen – Chloramphenicol, macrolides,
clindamycin
Non urine specimens – Ciprofloxacin,
levofloxacin, nitrofurantoin, norfloxacin, nalidixic
acid

9. CLINICAL SETTING
• IV drugs – OPD setting C/S report
• Impaired RFT patients – Aminoglycosides,
colistin, vancomycin

10. PATIENT DEMOGRAPHICS
• Suppress antibiotics with known adverse
effect.
Example:
Ciprofloxacin, chloramphenicol & tetracycline
supressed from pediatric case reports

11. ABERRANT RESULTS
• First line drugs are susceptible, second line
drugs are resistant.
So, here suppress the second line drug status.
Example:
Ceftriaxone – S
Meropenem - R

12. UNAVAILABILITY OF
BREAKPOINT
• Don’t report that particular drug if breakpoint
is not available.
EVEN DON’T ADMIT IT IN
ANTIBIOGRAM POLICY

13. CASCADE REPORTING
• Reporting of AST results involves reporting
of broader spectrum/costlier/second line
drugs only when narrow
spectrum/cheaper/first line drugs are found
to be not susceptible
• Another set of drugs – Restricted/extensive
spectrum/high costly

14. THINGS TO BE REMEMBER
WHILE CASCADE REPORTING
• Pharmacy availability of drug
• Local antimicrobial resistance
• Clinical consensus and patient status
• Following standard guidelines like CLSI or
EUCAST
• Cascade reporting not cascade testing
• Inclusion into antibiogram (Except BP not
available)

15. CLSI 2022 versus CLSI 2023

16. GROUP A vs TIER 1
GROUPA TIER 1
Includes antimicrobial
agents considered
appropriate for inclusion in
a routine, primary testing
panel, as well as for
routine reporting of
results for the specific
organism group
Antimicrobial agents that
are appropriate for routine,
primary testing and
reporting

17. GROUP B vs TIER 2
GROUP B TIER 2
Antimicrobial agents that may warrant
primary testing, but they may be reported
only selectively, such as when
Organism is resistant to all the drugs in
group A
Selected specimen source (eg, a third-
generation cephalosporin for
Enterobacterales from CSF &
trimethoprim-sulfamethoxazole for
urinary tract isolates)
A polymicrobial infection
Infections involving multiple sites
Cases of patient allergy, intolerance, or
failure to respond to an antimicrobial
agent in group A
For infection prevention.
Antimicrobial agents
that are appropriate
for routine, primary
testing but may be
reported following
cascade reporting rules
established at each
institution

18. GROUP C vs TIER 3
GROUP C TIER 3
Alternative antimicrobial agents
that may necessitate testing in
those institutions that harbor
endemic or epidemic strains
resistant to several of the
primary drugs / for treatment of
unusual organisms / for
reporting to infection
prevention as an
epidemiological aid
Antimicrobial agents that are
appropriate for routine,
primary testing in institutions
that serve patients at high risk
for MDROs but should only
be reported following cascade
reporting rules established at
each institution

19. TIER 4
TIER 4
Antimicrobial agents that may warrant testing and reporting
by clinician request if antimicrobial agents in other tiers are not
optimal because of various factors

20. GROUP U vs URINE ONLY
GROUP U URINE ONLY (U)
Antimicrobial agents that are
used only / primarily for
testing UTIs
EXCEPTION:
Cefazolin surrogate marker for
oral cephalosporins placed in
both group A and U
Antimicrobial agents
designated by a “(U)” in tables
should be reported only on
organisms isolated from the
urinary tract

21. GROUP O vs OTHERS
GROUP O OTHERS
Antimicrobial agents that have
a clinical indication for the
organism group but are
generally not candidates for
routine testing and reporting
in the United States.
Antimicrobial agents with
established clinical breakpoints
designated that are generally
not candidates for testing and
reporting in the United States.

22. GROUP Inv VS Inv
GROUP Inv Inv
Antimicrobial agents that are
investigational for the organism
group and have not yet been
approved by the FDA for use
in the United states.
Antimicrobial agents that are
investigational for the organism
group have not yet been
approved by the FDA for use
in the United States.

23. CLSI guidelines for USA....then what
about India???
• Every laboratory should prepare their own
antimicrobial list in context with current CLSI
and in consensus with clinical team
• Should done this atleast yearly once.
• All group / tier drugs should be tested in day
1 itself
CASCADE REPORTING NOT CASCADE
TESTING

24. BREAK POINTS
TYPES:
Clinical breakpoint
ECV / ECOFF break point
PK-PD (Non species related) break point
Site specific break point

25. TYPES OF BREAK POINTS
Parameters Clinical BP ECOFF/ECV
BP
PK-PD BP
MIC
distribution
data
Yes Yes No
PK-PD data Yes No Yes
Clinical
outcome
data
Yes No No

26. CLINICAL BREAKPOINT
DEFINITION:
• Defined as the MIC or zone diameter value used to categorize
an organism into one of the interpretive categories (S or R or
I).
RECOGNISED COMMITTEES PROVIDING CLINICAL
BREAK POINTS:
• CLSI (1st preference)
• EUCAST (If 1st preference for particular BP is not available)
• FDA (If 1st and 2nd preference BP not available)
• Article based break points (If previous above references BP
not available)

27. RANDOM SWITCH BETWEEN CLSI AND
EUCAST GUIDELINES IN LABORATORY WILL
MAKE AST DATA INCOMPARABLE

28. CLSI INTERPRETATIONS
1) S – Susceptible
• MIC value or zone size satisfied
• When the drug given at standard dosage
• High likelihood of therapeutic success

29. CLSI INTERPRETATIONS (cont.)
2) I – INTERMEDIATE
• Between S and R break point
Indicates:
Uncertain therapeutic effect
May give effect in increased dosage
May be active at sites where physiologically
concentrated (Urine) So no need to increase
dosage
Represents a buffer zone (Between S and R)

30. CLSI INTERPRETATIONS (cont.)
3) INTERMEDIATE WITH CARET SYMBOL
• New interpretative category created for this given
point below.......
• May be active at sites where physiologically
concentrated (Urine) So no need to increase
dosage
EXAMPLES:
For enterobacterales & pseudomonas – Beta
lactams & aminoglycosides
For Enterococcus - Quinolones

31. CLSI INTERPRETATIONS (cont.)
4) SDD (SUSCEPTIBLE DOSE DEPENDENT)
Almost same definition as INTERMEDIATE
EXAMPLES:
Cefepime, piperacillin, piperacillin tazobactam
for enterobacterales
Ceftaroline for Staphylococcus aureus
Daptomycin for Enterococcus faecium

32. CLSI INTERPRETATIONS (cont.)
5) R - Resistant
• MIC value or zone size satisfied
• When the drug given at standard dosage
• No likelihood of therapeutic success

33. CLSI INTERPRETATIONS (cont.)
6) NS – Non susceptible
• Only S break points, No R break points
• Indicates further evaluation, so repeat the test
• Indicates doubtful clinical efficacy
EXAMPLES:
Streptococcus pyogenes – Ampi, pen G, Xone,
taxim, vanco, Linezolid
S.pneumoniae & viridans – Vanco and LZ
Staph - Daptomycin

34. CLSI INTERPRETATIONS (cont.)
7) NOT SUSCEPTIBLE
• Includes I and R category as whole
• Entirely different from Non susceptible

35. EUCAST INTERPRETATIONS
• S – Susceptible, Standard dosing regimen
• I – Susceptible, increased exposure (SIE)
• R – Resistant
• No S – S break point is not available
• Area of technical uncertainty (ATU) –
Technical error, mismatch between disk
diffusion & MIC, better not report it as ATU
(JUST LEAVE IT AS BLANK)

36. ECV/ECOFF BREAK POINT
• Based on MIC distribution of large number of
isolates
Based on this:
Wild type (WT) isolates – No phenotypic
detection of resistance
Non wild type (NWT) isolates – Phenotypic
detection of resistance is there
NOT APPROVED BY CLSI OR EUCAST TO
APPLY THIS BP CLINICALLY

37. DETERMINATION OF ECV/ECOFF
BREAK POINT
1) Visual estimation (Eye ball method)
2) Statistical methods
• Normalised resistance interpretation method
(Kronwall)
• Iterative statistical method (ECOFFinder/
Turnidge method)
• 95% rule (Pfaller method)
• Multimode analysis (Meletiadis method)
• Cluster analysis (Canton method)

38. EXAMPLE FOR ECV/ECOFF BP
• Till 2020, there is no clinical BP for colistin in
enterobacterales, so we followed ECV BP
only....
• After 2020, colistin BP included in CLSI.
ECV – Term used by CLSI
ECOFF – Term used by EUCAST

39. PK PD BREAK POINT
• Used only when species specific clinical BP or
ECV/ECOFF BP not available
• Used when tested all agents with clinical BPs and
reported as R.
INTERPRETATION:
If MIC value more than PK PD BP – DON’T USE
If MIC value less than PK PD BP – USE IT

40. SITE SPECIFIC BREAKPOINTS
• For some organism-agent combinations different
breakpoints available for different sites.
EXAMPLES:
 For CSF
 For urine and non-urine
 For respiratory and non respiratory
SAMPLE/SITE WISE BREAK POINT MAY
GET EXTENDED IN FUTURE....AS OF
NOW VERY FEW SITE SPECIFIC DRUGS
IN CLSI....LITTLE MORE IN EUCAST

41. ADDITIONAL TESTING METHODS
BY CLSI
• Supplemental test (Phenotypic detection of
resistance like CarbaNP, mCIM, eCIM, ICR)
• Screening test (Presumptive test & should be
cross checked using further tests as per CLSI;
Testing for one agent predicts susceptibility to
one or more agents in same class as per
EUCAST, Vancomycin screen agar, HLAR
test)
• Equivalent agent test (Testing of one agents
predicts testing of another agent; Ceftriaxone –
Cefotaxime, Erythro – Clarithro – Azithro)

42. EQUIVALENT TEST vs
SURROGATE MARKER TEST
CHARACTERRISTICS EQUIVALENT
TEST
SURROGATE
TEST
Prediction of S and
R results
Vice versa One directional
Testing agent
prediction
Can predict another
agent of same class
Can predict one or
more agents of the
same class
Used for Rx Both agents can
used
Surrogate agent
can’t used

43. TESTING LIMITATIONS
• Will happen in automated AST reports like
vitek
• This limitation is due to manufacturer not
obtained FDA approval for some drugs.

44. COMMENTS IN CLINICAL
MICROBIOLOGY REPORTING (CMR)
1) Comments for various report categories
Sterile or contaminated container
Uncertain pathogen

45. COMMENTS IN CLINICAL
MICROBIOLOGY REPORTING (CMR) (cont.)
2) COMMENTS FOR IN PROGRESS REPORTS

46. COMMENTS IN CLINICAL
MICROBIOLOGY REPORTING (CMR) (cont.)
3) Comments for patient related data missed in
the culture requisition form
4) Comments related to specimen collection
5) Comments as foot notes in AST report (I, I
with cadre, SDD)

47. COMMENTS IN CLINICAL
MICROBIOLOGY REPORTING (CMR) (cont.)
6) Comments specific to site specific culture
reporting
Time to positivity (TTP)
 Time taken for blood culture bottle to flag
positive
 Lesser the TTP more severe clinical outcome
 More the TTP less severity of clinical outcome
CRBSI (Central line blood specimen flagged 2
hours earlier than venipuncture specimen)

48. COMMENTS IN CLINICAL
MICROBIOLOGY REPORTING (CMR) (cont.)
7) Infection control advice
• Strict hand hygiene
• PPE kit
• Three feet distance between beds
• Single use dedicated equipment BP cuffs,
stethoscope, nebulizer

49. COMMENTS IN CLINICAL
MICROBIOLOGY REPORTING (CMR) (cont.)
8) Specific organism or drug related comments
9) Predicted susceptibility related comments
10) Intrinsic resistance comments
11) Comments related to Breakpoint to MIC
quotient and MIC guiding table

50. BREAKPOINT TO MIC QUOTIENT (BMQ)
• Defined as ratio of susceptible BP divided by
MIC of test isolate
• Otherwise called as MIC therapeutic index
• Higher BMQ, better therapeutic efficacy
EXAMPLE: (Escherichia coli isolate)
Amikacin with MIC 4 (Susceptible BP = 16) is
better than cefepime with MIC 1 (Susceptible BP
= 2)
BMQ of amikacin for this isolate is 16/4=4, BMQ
of cefepime for this isolate is 2/1=2

51. DO’S AND DONT’S IN BMQ
INTERPRETATION
• Only for MIC not for disk diffusion methods
• Don’t compare narrow spectrum with broad
spectrum
• Have a look on patient age, RFT, adverse
effect history
• BMQ will be calculated for drug with
susceptible break point (Exception is colistin
where there is no S break point as per CLSI, so
we can use Intermediate break point for BMQ)

52. TWO STAGE REPORTING (UK MODEL)
• First stage (Technical reporting)
One JR
One PG
One LT
• Second stage (Clinical reporting)
One microbiology Consultant
One JR
One SR
One PG
(For smaller hospitals only one team will do both
stages of reporting)

53. COMMON SOFTWARES IN INDIA
• WHONET (WHO)
• i-AMRSS (ICMR)
• CMR Software (JIPMER)

54. LET’S MAKE IT MICROBIOLOGY
DEPENDENCE SYNDROME (MDS)

55. THANK YOU!!!!