Laboratory Test Guide

Antibiograms and Antimicrobial Susceptibility Testing Information

Interpretive Guidelines

Definitions and Abbreviations

  • CLSI: Clinical Laboratory Standards Institute
  • EUCAST: European Committee on Antimicrobial Susceptibility Testing

Gram-Positive Bacteria

Enterococci – non-urine isolates

Gentamicin (500 mcg/mL)

  • A result of "Synergy likely" indicates that an isolate does not have high level resistance to gentamicin. This drug is therefore likely to be synergistic with a cell wall-active agent (e.g., ampicillin, penicillin, and vancomycin) provided the organism is susceptible to that agent.
  • A result of "Synergy unlikely" indicates high-level resistance to gentamicin, meaning it is not synergistic with cell wall-active agents.

Streptomycin (1000 mcg/mL)

  • A result of "Synergy likely" indicates that an isolate does not have high level resistance to streptomycin. This drug is therefore likely to be synergistic with a cell wall-active agent (e.g., ampicillin, penicillin, and vancomycin) provided the organism is susceptible to that agent.
  • A result of "Synergy unlikely" indicates high-level resistance to streptomycin, meaning it is not synergistic with cell wall-active agents.

Imipenem

EUCAST breakpoints; susceptible ≤4, resistant ≥16

Moxifloxacin

Currently there are no breakpoints for this antibiotic. However, moxifloxacin demonstrates in vitro activity against some Enterococcus species and a provisional breakpoint of susceptible ≤1 has been suggested (Andrews, et al. 1999). An infectious disease consult may be useful if you are considering using moxifloxacin for the treatment of Enterococcal infections.

Staphylococci

Clindamycin

A result of "R(comment)" or "Resistant (with comment)" indicates that an isolate has inducible clindamycin resistance. Clindamycin may still be used in combination regimes but should not be used alone to treat infections caused by bacteria with inducible resistance.

Viridans group Streptococci

Clindamycin

A result of "R(comment)" or "Resistant (with comment)" indicates that an isolate has inducible clindamycin resistance. Clindamycin may still be used in combination regimes but should not be used alone to treat infections caused by bacteria with inducible resistance.

Penicillin

In patients with streptococcal endocarditis, use American Heart Association (AHA) breakpoints for penicillin:

  • Susceptible ≤0.12µg/ml

  • Intermediate >0.12 to <0.5µg/ml

  • Resistant ≥0.5µg/ml

For further information, please see: Baddour, et al. 2015.

Imipenem

EUCAST breakpoint; susceptible ≤2, resistant ≥4

Moxifloxacin

Currently there are no existing breakpoints for this antibiotic. However, a provisional susceptible breakpoint of ≤1 has been suggested for S. pneumoniae and could be considered applicable to viridans group streptococci (Andrews, et al. 1999).

S. pneumoniae

Clindamycin

A result of "R(comment)" or "Resistant (with comment)" indicates that an isolate has inducible clindamycin resistance. Clindamycin may still be used in combination regimes but should not be used alone to treat infections caused by bacteria with inducible resistance.

Penicillin and Ceftriaxone

In the event that a patient is thought to have meningitis, but a CSF specimen has not been obtained, the “meningitis” interpretation should be used to guide therapeutic decisions.

Beta-hemolytic Streptococci

Clindamycin

A result of "R(comment)" or "Resistant (with comment)" indicates that an isolate has inducible clindamycin resistance. Clindamycin may still be used in combination regimes but should not be used alone to treat infections caused by bacteria with inducible resistance.

Imipenem

Per EUCAST: susceptibility can be inferred from the penicillin susceptibility result.

Moxifloxacin

EUCAST breakpoints; susceptible ≤0.5, resistant ≥2

Gram-Negative Bacteria

Enteric Gram Negative Rods (Enterobacteriacae)

Cefepime

Current CLSI interpretive breakpoints may not predict clinical efficacy. Only strains with MIC ≤1.0 may be regarded as fully susceptible. Strains with MICs 2.0-4.0 should be considered to have dose-dependent susceptibility. A cefepime MIC = 8 has been associated with clinical failure. (Bhat, et al. 2007; Crandon, et al. 2010; Lee, et al. 2007; Paterson, et al. 2001).

Piperacillin-Tazobactam

CLSI interpretive breakpoints may not predict clinical efficacy. PK/PD analyses support the EUCAST recommendation that only strains with piperacillin-tazobactam MICs ≤ 8 be considered susceptible (DeRyke, et al. 2007).

Fluoroquinolones – non-urine isolates

For serious infections, CLSI interpretive breakpoints may not predict clinical efficacy. PK/PD analyses suggest that ciprofloxacin and levofloxacin MICs should be ≤0.125-0.25 and ≤0.25-0.5, respectively, for isolates to be considered susceptible (DeRyke, et al. 2007; Frei, et al. 2008).

Moxifloxacin – urine isolates only

No CLSI interpretive breakpoints are available. EUCAST interpretive breakpoints: susceptible ≤0.5, resistant ≥2

Pseudomonas aeruginosa

Cefepime

Current CLSI interpretive breakpoints may not predict clinical efficacy.Only strains with MIC ≤1.0 may be regarded as fully susceptible. Strains with MICs 2.0-4.0 should be considered to have dose-dependent susceptibility. A cefepime MIC = 8 has been associated with clinical failure. (Bhat, et al. 2007; Crandon, et al. 2010; Lee, et al. 2007; Paterson, et al. 2001).

Fluoroquinolones – non-urine isolates

For serious infections, CLSI interpretive breakpoints may not predict clinical efficacy. PK/PD analyses suggest that ciprofloxacin and levofloxacin MICs should be ≤0.125-0.25 and ≤0.25-0.5, respectively, for isolates to be considered susceptible (DeRyke, et al. 2007; Frei, et al. 2008). Many authorities recommend combination therapy for serious P. aeruginosa infections.

Acinetobacter

Tigecycline

No CLSI interpretive breakpoints are available. The FDA interpretive breakpoint for Enterobacteriacae (susceptible ≤2) is unlikely to predict clinical efficacy. Tigecycline only achieves steady-state serum concentrations of 0.4-0.6, and PK/PD analyses suggest that MICs should be ≤0.25 to be considered susceptible. Treatment failures have been reported with tigecycline monotherapy for serious Acinetobacter infections (Pankey, et al. 2005; Ambrose, et al. 2009; Anthony, et al. 2008).

Cefepime

Current CLSI interpretive breakpoints may not predict clinical efficacy.Only strains with MIC ≤1.0 may be regarded as fully susceptible. Strains with MICs 2.0-4.0 should be considered to have dose-dependent susceptibility. A cefepime MIC = 8 has been associated with clinical failure. (Bhat, et al. 2007; Crandon, et al. 2010; Lee, et al. 2007; Paterson, et al. 2001).

Fluoroquinolones – non-urine isolates

For serious infections, CLSI interpretive breakpoints may not predict clinical efficacy. PK/PD analyses suggest that ciprofloxacin and levofloxacin MICs should be ≤0.125-0.25 and ≤0.25-0.5, respectively, for isolates to be considered susceptible (DeRyke, et al. 2007; Frei, et al. 2008).

Piperacillin-Tazobactam

PK/PD analyses suggest that only strains with piperacillin-tazobactam MICs ≤8 should be considered susceptible (DeRyke, et al. 2007).

Stenotrophomonas maltophilia

Moxifloxacin

No CLSI or EUCAST breakpoints are available. However, EUCAST breakpoints for Enterobacteriacae may be tentatively used for guidance: susceptible ≤0.5, resistant ≥2

Yeast

Candida species

Susceptible Dose Dependent (SDD)

Susceptibility is dependent on achieving the maximal possible blood level. ID consult recommended.

Flucytosine

Flucytosine should be used in combination with another antifungal agent to prevent emergence of resistance (Drew, et al. 2013).

Candida glabrata

Voriconazole

Current data are insufficient to demonstrate a correlation between in vitro susceptibility testing and clinical outcome for Candida glabrata (CLSI 2012)

Candida parapsilosis

Micafungin

EUCAST interpretive criteria for C. parapsiolosis and micafungin: susceptible ≤2, resistant >2. C. parapsilosis harbors an alteration in the echinocandin target gene and the MIC's of the echinocandins are higher than for other Candida species (EUCAST 2013). Multiple studies have shown C. parapsilosis to be intrinsically less susceptible to micafungin and breakthrough cases of C. parapsilosis invasive infection have been reported (Pfeiffer, et al. 2010).

References

  1. 26373316Ambrose PG, et al. Application of patient population-derived pharmacokinetic-pharmacodynamic relationships to tigecycline breakpoint determination for staphylococci and streptococci. Diagn Microbiol Infect Dis 2009, 63:155-9. 19150707
  2. Andrews JM, Ashby JP, Jevons GM, and Wise R. Tentative minimum inhibitory concentration and zone diameter breakpoints for moxifloxacin using BSAC criteria. J Antimicrob Chemother 1999, 44:819-22. 10590284
  3. Anthony KB, et al. Clinical and microbiological outcomes of serious infections with multidrug-resistant gram-negative organisms treated with tigecycline. Clin Infect Dis 2008, 46:567-70. 18199038
  4. Baddour LM, et al. Infective Endocarditis in Adults: Diagnosis, Antimicrobial Therapy, and Management of Complications: A Scientific Statement for Healthcare Professionals from the American Heart Association Circulation 2015, Oct 13:132(15):1435-86. 26373316
  5. Bhat SV, et al. Failure of current cefepime breakpoints to predict clinical outcomes of bacteremia caused by gram-negative organisms. Antimicrob Agents Chemother 2007, 51:4390-5. 17938179
  6. Blondeau JM. A review of the comparative in-vitro activities of 12 antimicrobial agents, with a focus on five new respiratory quinolones'. J Antimicrob Chemother 1999, 43 Suppl B:1-11. 10382869
  7. CLSI M27-S4. Reference method for broth dilution antifungal susceptibility testing of yeasts; Third informational supplement. 2012.
  8. Crandon JL, Bulik CC, Kuti JL, and Nicolau DP. Clinical pharmacodynamics of cefepime in patients infected with Pseudomonas aeruginosa. Antimicrob Agents Chemother 2010, 54:1111-6. 20038614
  9. Crump JA, et al. Clinical response and outcome of infection with Salmonella enterica serotype Typhi with decreased susceptibility to fluoroquinolones: a United States foodnet multicenter retrospective cohort study. Antimicrob Agents Chemother 2008, 52:1278-84. 18212096
  10. DeRyke CA, Kuti JL, and Nicolau DP. Reevaluation of current susceptibility breakpoints for Gram-negative rods based on pharmacodynamic assessment. Diagn Microbiol Infect Dis 2007, 58:337-44. 17350206
  11. Drew RH, and Perfect JR. Pharmacology of flucytosine (5-FC). 2013, Accessed online 2013-12-7. UpToDate
  12. EUCAST. Micafungin and Candida spp.; rationale for the EUCAST clinical breakpoints, version 1.0. 2013. EUCAST
  13. Frei CR, Wiederhold NP, and Burgess DS. Antimicrobial breakpoints for gram-negative aerobic bacteria based on pharmacokinetic-pharmacodynamic models with Monte Carlo simulation. J Antimicrob Chemother 2008, 61:621-8. 18252694
  14. Lee SY, Kuti JL, and Nicolau DP. Cefepime pharmacodynamics in patients with extended spectrum beta-lactamase (ESBL) and non-ESBL infections. J Infect 2007, 54:463-8. 17067681
  15. Lodise TP Jr, Lomaestro B, and Drusano GL. Piperacillin-tazobactam for Pseudomonas aeruginosa infection: clinical implications of an extended-infusion dosing strategy. Clin Infect Dis 2007, 44:357-63. 17205441
  16. Pankey GA. Tigecycline. J Antimicrob Chemother 2005, 56:470-80. 16040625
  17. Paterson DL, et al. Outcome of cephalosporin treatment for serious infections due to apparently susceptible organisms producing extended-spectrum beta-lactamases: implications for the clinical microbiology laboratory. J Clin Microbiol 2001, 39:2206-12. 11376058
  18. Pfeiffer CD, et al. Breakthrough invasive candidiasis in patients on micafungin. J Clin Microbiol 2010, 48:2373-80. 20421445
  19. Roos JF, Bulitta J, Lipman J, and Kirkpatrick CM. Pharmacokinetic-pharmacodynamic rationale for cefepime dosing regimens in intensive care units. J Antimicrob Chemother 2006, 58:987-93. 16943209
  20. Tam VH, et al. Outcomes of bacteremia due to Pseudomonas aeruginosa with reduced susceptibility to piperacillin-tazobactam: implications on the appropriateness of the resistance breakpoint. Clin Infect Dis 2008, 46:862-7. 18279040
  21. Wisell KT, Kahlmeter G, and Giske CG. Trimethoprim and enterococci in urinary tract infections: new perspectives on an old issue. J Antimicrob Chemother 2008, 62:35-40. 18408238

    Associated Tests

    Code Name Specimen
    BLDC Blood Culture and Sensitivity Peripheral Blood
    BLDLC Blood Culture and Sensitivity (Line Draw) Blood from Line draw
    CSFANC CSF Bacterial Culture and Sensitivity (Special Anaerobic) with Gram Stain CSF, Cerebrospinal Fluid
    FLDANC Fluid Bacterial Culture and Sensitivity (Special Anaerobic) with Gram Stain Fluid from sterile site
    FLDC Fluid Bacterial Culture and Sensitivity with Gram Stain Fluid collected from Drains
    LRSC Lower Respiratory Bacterial Culture and Sensitivity with Gram Stain Sputum, Bronchial Wash, Tracheal...
    SKINC Skin Culture and Sensitivity with Gram Stain Skin (Superficial sites only)
    TISC Tissue Bacterial Culture and Sensitivity with Gram Biopsy, BX, Node, Tissue
    URNC Urine Culture and Sensitivity with Gram Midstream Urine, Catheterized Urine...
    URNXC Urine Culture and Sensitivity without Gram Midstream Urine, Catheterized Urine...
    WNDANC Wound Bacterial Culture and Sensitivity (Special Anaerobic) with Gram Stain Abscess, deep wound
    WNDC Wound Bacterial Culture and Sensitivity with Gram Stain Superficial wound, wound drainage