Antimicrobial Susceptibility Testing: Advanced Course

Cascade Reporting

Cascade Reporting I. Selecting Antimicrobial Agents for Testing and Reporting Selection of the most appropriate antimicrobials to test & report is a decision best made by each clinical laboratory in consultation with: Infectious disease practitioners Pharmacy Pharmacy & Therapeutics committee Infection Control committee Considerations of antimicrobials include: clinical efficacy prevalence of resistance (& minimizing the emergence of resistance) cost FDA clinical indications for use current consensus for first-choice and alternative drugs tests of selected agents may be useful for infection control purposes

Test/Report Groups. Group A are considered appropriate for inclusion in a routine, primary testing panel, as well as for routine reporting of results for the specific organism groups. 2. Group B includes antimicrobial agents that may warrant primary testing but they may be reported only selectively, such as when the organism is resistant to agents of the same antimicrobial class, as in Group A. Other indications for reporting the result might include a selected specimen source (eg, a third-generation cephalosporin for enteric bacilli from cerebrospinal fluid or trimethoprim-sulfamethoxazole for urinary tract isolates); a polymicrobial infection; infections involving multiple sites; cases of patient allergy, intolerance, or failure to respond to an agent in Group A; or for purposes of infection control.. Group C includes alternative or supplemental antimicrobial agents that may require testing in those institutions that harbor endemic or epidemic strains resistant to several of the primary drugs (especially in the same class, eg, -lactams); for treatment of patients allergic to primary drugs; for treatment of unusual organisms (eg, chloramphenicol for extraintestinal isolates of Salmonella spp.); or for reporting to infection control as an epidemiological aid.. Group U ( urine ) includes antimicrobial agents (eg, nitrofurantoin and certain quinolones) that are used only or primarily for treating urinary tract infections. These agents should not be routinely reported against pathogens recovered from other sites of infection. Other agents with broader indications may be included in Group U for specific urinary pathogens (eg, P. aeruginosa and ofloxacin). 5. Group O ( other ) includes 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. 6. Group Inv. ( investigational ) includes antimicrobial agents that are investigational for the organism group and have not yet been approved by the FDA for use in the United States.

Cascade Reporting I. Selecting Antimicrobial Agents for Testing and Reporting Group A appropriate for inclusion in a routine, primary testing panel, appropriate for routine reporting of results for the specific organism groups

GROUP A PRIMARY TEST AND REPORT Cascade Reporting Table A. Enterobacteriaceae Pseudomonas aeruginosa Staphylococcus spp. Ampicillin d Ceftazidime Azithromycin b or clarithromycin b or erythromycin b Cefazolin e Gentamicin Tobramycin Gentamicin Tobramycin Piperacillin Clindamycin b *, Oxacillin i,k Cefoxitin i,k (surrogate test for oxacillin) Penicillin i Trimethoprimsulfamethoxazole Enterococcus spp. m Ampicillin n Penicillin o

GROUP A PRIMARY TEST AND REPORT Report routinely Cascade Reporting Table A. Enterobacteriaceae Pseudomonas aeruginosa Staphylococcus spp. Ampicillin d Ceftazidime Azithromycin b or clarithromycin b or erythromycin b Cefazolin e Gentamicin Tobramycin Gentamicin Tobramycin Piperacillin/ tazobactam Clindamycin b *, Oxacillin i,k Cefoxitin i,k (surrogate test for oxacillin) Penicillin i Trimethoprimsulfamethoxazole Enterococcus spp. m Ampicillin n Penicillin o

Cascade Reporting I. Selecting Antimicrobial Agents for Testing and Reporting 2. Group B includes antimicrobial agents that may warrant primary testing but they may be reported only selectively, such as when the organism is resistant to agents of the same antimicrobial class in Group A. Other indications for reporting: selected specimen source (urine), failure to respond to an agent in Group A, or for purposes of infection control

GROUP B PRIMARY TEST REPORT SELECTIVELY Table A. Cascade Reporting Enterobacteriaceae Amikacin Amikacin Ceftaroline h *Daptomycin j *Daptomycin j Aztreonam Linezolid Linezolid Amoxicillin-clavulanate Ampicillin-sulbactam Piperacillin-tazobactam Ticarcillin-clavulanate Cefuroxime Cefepime Pseudomonas aeruginosa Staphylococcus spp. Doxycycline Minocycline b Tetracycline a Enterococcus spp. m Vancomycin Cefepime Cefotetan Cefoxitin Cefotaxime d,e or ceftriaxone d,e Ciprofloxacin d Levofloxacin d Doripenem Ertapenem Imipenem Meropenem Piperacillin Trimethoprim-sulfamethoxazole d Ciprofloxacin Levofloxacin Doripenem Imipenem Meropenem Piperacillin-tazobactam Ticarcillin *, Vancomycin Rifampin g

GROUP B PRIMARY TEST REPORT SELECTIVELY Table A. Cascade Reporting Report routinely Test routinely *Cascade reported Enterobacteriaceae Amikacin* Amikacin* Ceftaroline h *Daptomycin j * *Daptomycin j * Aztreonam Linezolid* Linezolid* Amoxicillin-clavulanate* Ampicillin-sulbactam Piperacillin-tazobactam Ticarcillin-clavulanate Cefuroxime Cefepime Pseudomonas aeruginosa Staphylococcus spp. Doxycycline* Minocycline b Tetracycline a Enterococcus spp. m Vancomycin Cefepime* Cefotetan Cefoxitin Cefotaxime d,e or ceftriaxone d,e * Ciprofloxacin d Levofloxacin d Doripenem Ertapenem* Imipenem Meropenem* Piperacillin Trimethoprim-sulfamethoxazole d Ciprofloxacin Levofloxacin Doripenem Imipenem Meropenem Piperacillin-tazobactam Ticarcillin *, Vancomycin Rifampin g *

Cascade Reporting I. Selecting Antimicrobial Agents for Testing and Reporting. Group C includes alternative or supplemental antimicrobial agents that may require testing in those institutions that harbor endemic or epidemic strains resistant to several of the primary drugs, for treatment of patients allergic to primary drugs, for treatment of unusual organisms, or for reporting to infection control as an epidemiological aid

GROUP C SUPPLEMENTAL REPORT SELECTIVELY Table A. Cascade Reporting Enterobacteriaceae Aztreonam Ceftazidime Pseudomonas aeruginosa Staphylococcus spp. Chloramphenicol b Enterococcus spp. m Gentamicin (high-level resistance screen only) Ceftaroline Ciprofloxacin or levofloxacin or ofloxacin Moxifloxacin Streptomycin (high-level resistance screen only) Chloramphenicol b,d Gentamicin l Tetracycline a

GROUP C SUPPLEMENTAL REPORT SELECTIVELY Table A. Cascade Reporting Report routinely Test routinely Selectively reported Enterobacteriaceae Aztreonam Ceftazidime* Pseudomonas aeruginosa Staphylococcus spp. Chloramphenicol b Enterococcus spp. m Gentamicin (high-level resistance screen only) Ceftaroline Ciprofloxacin or levofloxacin or ofloxacin Moxifloxacin Streptomycin (high-level resistance screen only) Chloramphenicol b,d Gentamicin l Tetracycline a *

Clindamycin Erythromycin Oxacillin Vancomycin Chloramphenicol Cefazolin Penicillin Ceftriaxone Moxifloxacin Tetracycline Ampicillin Linezolid SXT Levofloxacin Gent Synergy Cascade Reporting: GPC Non-urine/Non-CSF Staphylococcus species (V2) R 2, 5 Streptococcus pneumoniae: non-sterile sites (V2) 9 Streptococcus pneumoniae: sterile sites (V2) 9 Viridans Streptococcus (KB & E-test or Microscan) MIC Enterococcus spp (V2) 6 -strep (GAS, GBS, GCS, GGS) spp: sterile sites (KB) (2) S.agalactiae: from OB screens (KB) 0 MIC 8 7 R Routinely reported. Always report as resistant. If SDD, I or R, report antimicrobials touching arrowhead

Clindamycin Erythromycin Oxacillin Vancomycin Chloramphenicol Cefazolin Penicillin Ceftriaxone Moxifloxacin Tetracycline Ampicillin Linezolid SXT Levofloxacin Gent Synergy Cascade Reporting: GPC Non-urine/Non-CSF Staphylococcus species (V2) R 2, 5 Streptococcus pneumoniae: non-sterile sites (V2) 9 Streptococcus pneumoniae: sterile sites (V2) 9 Viridans Streptococcus (KB & E-test or Microscan) MIC Enterococcus spp (V2) 6 -strep (GAS, GBS, GCS, GGS) spp: sterile sites (KB) (2) S.agalactiae: from OB screens (KB) Perform D-test; Report Clinda-R if D-test positive. 2 If S. aureus and vanco MIC = 2, add comment code VANCO2 : Vancomycin MIC = 2 µg/ml. For isolates with a vancomycin minimum inhibitory concentration (MIC) of 2, the patient s clinical response should determine the continued use of vancomycin, independent of the MIC. 0 MIC 8 7

Clindamycin Erythromycin Oxacillin Vancomycin Chloramphenicol Cefazolin Penicillin Ceftriaxone Moxifloxacin Tetracycline Ampicillin Linezolid SXT Levofloxacin Gent Synergy Cascade Reporting: GPC Non-urine/Non-CSF Staphylococcus species (V2) R 2, 5 Streptococcus pneumoniae: non-sterile sites (V2) 9 Streptococcus pneumoniae: sterile sites (V2) 9 Viridans Streptococcus (KB & E-test or Microscan) MIC Enterococcus spp (V2) 6 -strep (GAS, GBS, GCS, GGS) spp: sterile sites (KB) (2) S.agalactiae: from OB screens (KB) 0 MIC 8 7 CF (Cystic Fibrosis) isolates only If MRSA, report chloramphenicol and linezolid. Report Cefazolin as resistant if Oxacillin is resistant. 5 If testing manually, use E-test (not KB).

Clindamycin Erythromycin Oxacillin Vancomycin Chloramphenicol Cefazolin Penicillin Ceftriaxone Moxifloxacin Tetracycline Ampicillin Linezolid SXT Levofloxacin Gent Synergy Cascade Reporting: GPC Non-urine/Non-CSF Staphylococcus species (V2) R 2, 5 Streptococcus pneumoniae: non-sterile sites (V2) 9 Streptococcus pneumoniae: sterile sites (V2) 9 Viridans Streptococcus (KB & E-test or Microscan) MIC Enterococcus spp (V2) 6 -strep (GAS, GBS, GCS, GGS) spp: sterile sites (KB) (2) S.agalactiae: from OB screens (KB) 6 If vancomycin-r E.casseliflavus or E.gallinarum, add comment NOTVRE to report. 7 Report Gentamicin synergy only for Blood isolates; Report as resistant when Ampicillin resistant & Vancomycin resistant regardless of test result. 8 Report only on VRE. 0 MIC 8 7

Clindamycin Erythromycin Oxacillin Vancomycin Chloramphenicol Cefazolin Penicillin Ceftriaxone Moxifloxacin Tetracycline Ampicillin Linezolid SXT Levofloxacin Gent Synergy Cascade Reporting: GPC Non-urine/Non-CSF Staphylococcus species (V2) R 2, 5 Streptococcus pneumoniae: non-sterile sites (V2) 9 Streptococcus pneumoniae: sterile sites (V2) 9 Viridans Streptococcus (KB & E-test or Microscan) MIC Enterococcus spp (V2) 6 -strep (GAS, GBS, GCS, GGS) spp: sterile sites (KB) (2) S.agalactiae: from OB screens (KB) 0 MIC 8 7 9 Transcribe the Penicillin MIC result into both the Pen IV and Pen oral MIC fields in the LIS. 0 Do not report but add comment BETAS to report ( Beta-hemolytic streptococci are routinely susceptible to penicillins and cephalosporins. ) Report CTX (meningitis) and CTX (non-meningitis) results.

Clindamycin Erythromycin Oxacillin Vancomycin Chloramphenicol Cefazolin Penicillin Ceftriaxone Moxifloxacin Tetracycline Ampicillin Linezolid SXT Levofloxacin Gent Synergy Cascade Reporting: GPC Non-urine/Non-CSF Staphylococcus species (V2) R 2, 5 Streptococcus pneumoniae: non-sterile sites (V2) 9 Streptococcus pneumoniae: sterile sites (V2) 9 Viridans Streptococcus (KB & E-test or Microscan) MIC Enterococcus spp (V2) 6 -strep (GAS, GBS, GCS, GGS) spp: sterile sites (KB) (2) S.agalactiae: from OB screens (KB) 0 MIC 8 7 2 For -hemolytic viridans strep (i.e., S.anginosis group) use the Viridans Streptococcus cascade. Report for S.aureus only. If Penicillin-S and Ceftriaxone-NS, restest and bring to rounds.

Oxacillin Vancomycin Cefazolin Penicillin Tetracycline Ampicillin Ciprofloxacin Nitrofurantoin Linezolid SXT Cascade Reporting: GPC Urine V2 Staphylococcus spp, 5 2 R 6 Enterococcus spp If S. aureus and vanco MIC = 2, add comment code VANCO2 : Vancomycin MIC = 2 µg/ml. For isolates with a vancomycin minimum inhibitory concentration (MIC) of 2, the patient s clinical response should determine the continued use of vancomycin, independent of the MIC. 2 Report Cefazolin as R if Oxacillin is R, and report Cefazolin as S if Oxacillin is S.

Oxacillin Vancomycin Cefazolin Penicillin Tetracycline Ampicillin Ciprofloxacin Nitrofurantoin Linezolid SXT Cascade Reporting: GPC Urine V2 Staphylococcus spp, 5 2 R 6 Enterococcus spp If vancomycin-resistant E.casseliflavus or E.gallinarum, add comment NOTVRE to report. Report only on VRE. 5. If testing manually, use E-test (not KB). 6. Report on S. aureus only.

Ampicillin Amox/Clav. Gentamicin Pip/Tazo Tobramycin Cefazolin Ceftriaxone Ertapenem 0 & Trimeth/Sulfa Ciprofloxacin Nalidixic Acid Cascade Reporting: Enterobacteriaceae non-csf V2 Amikacin Nitrofurantoin 2 Tetracycline 2 Ceftazidime 7 Cefepime 5 Meropenem 0 E. coli Pantoea spp. P. mirabilis Klebsiella spp Citrobacter koseri Citrobacter spp (except C. koseri) Enterobacter spp Hafnia alveii Serratia spp Morganella morganii Proteus vulgaris/penneri Providencia spp Salmonella spp Shigella spp n/a 9 R R R R R R R R R R 6 R R R R R R R 8 8 For Cipro susceptible Salmonella, test Nalidixic acid by KB. If Nalidixic Acid is S, report the Ciprofloxacin result. If Nalidixic Acid is I or R, report Ciprofloxacin and Nalidixic Acid and add the following comment to report: ( SALMFQ ) = Fluoroquinolone-susceptible strains of Salmonella that test non-susceptible to nalidixic acid may be associated with clinical failure or delayed response in fluoroquinolone-treated patients with extra intestinal salmonellosis. A consultation with an infectious disease practitioner is recommended.

Ampicillin Amox/Clav. Gentamicin Pip/Tazo Tobramycin Cefazolin Ceftriaxone Ertapenem 0 & Trimeth/Sulfa Ciprofloxacin Nalidixic Acid Cascade Reporting: Enterobacteriaceae non-csf V2 Amikacin Nitrofurantoin 2 Tetracycline 2 Ceftazidime 7 Cefepime 5 Meropenem 0 E. coli Pantoea spp. P. mirabilis Klebsiella spp Citrobacter koseri Citrobacter spp (except C. koseri) Enterobacter spp Hafnia alveii Serratia spp Morganella morganii Proteus vulgaris/penneri Providencia spp Salmonella spp Shigella spp n/a 9 R R R R R R R R R R 6 R R R R R R R 8 8 2 Report only for urinary isolates. If Vitek result is I or R, perform an alternate method of testing due to Vitek limitation. If Ceftriaxone is S, I or R and Ceftazidime and/or Cefipime is non-s (SDD, I or R), then report Ceftriaxone, Ceftazidime, and Cefepime.

Ampicillin Amox/Clav. Gentamicin Pip/Tazo Tobramycin Cefazolin Ceftriaxone Ertapenem 0 & Trimeth/Sulfa Ciprofloxacin Nalidixic Acid Cascade Reporting: Enterobacteriaceae non-csf V2 Amikacin Nitrofurantoin 2 Tetracycline 2 Ceftazidime 7 Cefepime 5 Meropenem 0 E. coli Pantoea spp. P. mirabilis Klebsiella spp Citrobacter koseri Citrobacter spp (except C. koseri) Enterobacter spp Hafnia alveii Serratia spp Morganella morganii Proteus vulgaris/penneri Providencia spp Salmonella spp Shigella spp n/a 9 R R R R R R R R R R 6 R R R R R R R 8 8 5 Only if Cefepime is non-s, continue cascade and report Ertapenem and Meropenem. 6 Perform an alternate method of testing for Pip/Tazo vs. Serratia marcescens due to a Vitek limitation. 7 If Ceftazidime is non-s or if Vitek flags the isolate as an ESBL, result the ESBL biochemical as Yes for E.coli, Klebsiella spp and P.mirabilis.

Ampicillin Amox/Clav. Gentamicin Pip/Tazo Tobramycin Cefazolin Ceftriaxone Ertapenem 0 & Trimeth/Sulfa Ciprofloxacin Nalidixic Acid Cascade Reporting: Enterobacteriaceae non-csf V2 Amikacin Nitrofurantoin 2 Tetracycline 2 Ceftazidime 7 Cefepime 5 Meropenem 0 E. coli Pantoea spp. P. mirabilis Klebsiella spp Citrobacter koseri Citrobacter spp (except C. koseri) Enterobacter spp Hafnia alveii Serratia spp Morganella morganii Proteus vulgaris/penneri Providencia spp Salmonella spp Shigella spp n/a 9 R R R R R R R R R R 6 R R R R R R R 8 8 8 If Ceftriaxone is non-susceptible, confirm results. Bring to rounds if non-susceptibility is confirmed. 9 Due to a Vitek limitation, Ampicillin is not routinely reported for Pantoea spp. If Ampicillin is requested, test by KB and cascade to Amox/Clav if Ampicillin is resistant.

Ampicillin Amox/Clav. Gentamicin Pip/Tazo Tobramycin Cefazolin Ceftriaxone Ertapenem 0 & Trimeth/Sulfa Ciprofloxacin Nalidixic Acid Cascade Reporting: Enterobacteriaceae non-csf V2 Amikacin Nitrofurantoin 2 Tetracycline 2 Ceftazidime 7 Cefepime 5 Meropenem 0 E. coli Pantoea spp. P. mirabilis Klebsiella spp Citrobacter koseri Citrobacter spp (except C. koseri) Enterobacter spp Hafnia alveii Serratia spp Morganella morganii Proteus vulgaris/penneri Providencia spp Salmonella spp Shigella spp n/a 9 R R R R R R R R R R 6 R R R R R R R 8 8 0. Even if not cascaded, if Ertapenem and/or Meropenem are non-susceptible, confirm by disk diffusion, including Imipenem. If non-susceptibility is confirmed, report Ertapenem, Meropenem and Imipenem and refer to Attachment 8 to see if the isolate meets the case definition for CRE.

Ceftriaxone ( rd gen) Gentamicin Tobramycin Amikacin Trimeth/Sulfa Ciprofloxacin Pip/Tazo Ceftazidime Cefepime Meropenem Levofloxacin Timentin Cascade Reporting: Non-Enterobacteriaceae non-csf V2 Pseudomonas aeruginosa 5 6 Pseudomonas spp () Other non-enteric bacilli () 5 Burkholderia cepacia Stenotrophomonas maltophilia Acinetobacter spp 2 2 Perform by manual MIC panel testing. 2 Amikacin must be tested by KB due to a Vitek-2 limitation; if you suspect the ID will be an Acinetobacter spp, set an AMK KB at the same time as you set up the AST panel. Also set PTZ KB as Vitek may not interpret results on Acinetobacter spp. other than A. baumannii. MIC testing only.

Ceftriaxone ( rd gen) Gentamicin Tobramycin Amikacin Trimeth/Sulfa Ciprofloxacin Pip/Tazo Ceftazidime Cefepime Meropenem Levofloxacin Timentin Cascade Reporting: Non-Enterobacteriaceae non-csf V2 Pseudomonas aeruginosa 5 6 Pseudomonas spp () Other non-enteric bacilli () 5 Burkholderia cepacia Stenotrophomonas maltophilia Acinetobacter spp 2 2 If Vitek result is resistant perform an alternate method of testing due to a Vitek limitation. 5 Report Amikacin if either Gentamicin or Tobramycin are non-s. 6 If Timentin is requested test by KB (not MIC panel).

Ampicillin Ceftriaxone Oxacillin Penicillin SXT Vancomycin Meropenem Cascade Reporting: GPC CSF Gram Positive Staphylococcus spp (V2) Streptococcus pneumoniae (V2) Viridans Streptococcus E-test E-test Enterococcus spp (V2), 2 Routinely reported. If Vancomycin MIC is > 2 for S. aureus, set up E-test for Vancomycin and bring to rounds if E-test MIC is > 2. If vanco MIC = 2, add comment code VANCO2 = Vancomycin MIC = 2 µg/ml. For isolates with a vancomycin minimum inhibitory concentration (MIC) of 2, the patient s clinical response should determine the continued use of vancomycin, independent of the MIC. 2 If testing manually, use E-test. Report CTX (meningitis) only and Penicillin (IV) only.

Amikacin Ampicillin Amox/Clav Ceftriaxone Ceftazidime Cefepime Gentamicin Pip/Tazo Meropenem Ertapenem SXT Tobramycin Cascade Reporting: GNR CSF Gram Negative E. coli (V2) P. Mirabilis Salmonella spp (V2) Shigella spp 2 All other enteric GNRs (V2) Non-enterics (V2) (non-fermenters) Routinely reported. If I or R, report antimicrobials touching arrowhead.. For E. coli, Klebsiella spp., and P. mirabilis: If Ceftazidime is non-s or if Vitek flags the isolate as ESBL, result ESBL biochem as Yes. 2. If Ceftriaxone is non-susceptible, confirm results. Bring to rounds if non-susceptibility is confirmed.. Even if not cascaded, if Ertapenem and/or Meropenem are confirmed as non-susceptible, report both.

Cascade Reporting SUMMARY: Use the CLSI M00 document as a guide. Decide with your ID, ID pharmacy, and IC clinicians what should be reported for your organism groups. What is routinely reported What is cascaded What is tested/reported only by special request Have clear guidance/training for your staff.

EXERCISE Develop a cascade reporting document (with footnotes!) for an inpatient population for the enterobacteriaceae using the CLSI M00-S2 along with the following directions from your Infectious Disease team: First line aminoglycoside is tobramycin Piperacillin/tazobactam reported out on all GNRs Cefepime should be reserved for resistant organisms Carbapenem of choice is imipenem, but should be reserved for resistant organisms Levofloxacin is used primarily, not ciprofloxacin Cefotaxime is the primary rd generation cephalosporin Include any special considerations for UTI organisms

DRUGS GN BUGs