Antimicrobial susceptibility testing challenges

Linda JoyceSt Vincent’s Hospital Melbourne

Bacteria/antimicrobials without breakpoints (B.A.W.B.S.)

• Enterobacteriacae• Pseudomonas aeruginosa, Acinetobacter spp, Burkholderia

cepacia, Stenotrophomonas maltophilia, Other Non-Enterobacteriacae

• Staphylococcus spp• Enterococcus spp• Haemophilus influenzae and parainfluenzae• Neisseria gonorrhoeae• Streptococcus pneumoniae• Streptococcus spp beta haemolytic group, viridans group• Neisseria meningitidis• Anaerobes

• Abiotrophia /Granulicatella spp• Aeromonas/Plesiomonas spp• Bacillus spp (not B.anthracis)• Campylobacter jejuni/coli• Corynebacterium spp• Erysipelothrix rhusiopathiae• HACEK group • Helicobacter pylori• Lactobacillus spp• Leuconostoc spp• Listeria monocytogenes• Moraxella catarrhalis• Pasteurella spp• Pediococcus spp• Vibrio spp including Vibrio cholera• Potential agents of bioterrorism

includes Arcanobacterium, Brevibacterium, Cellulomonas,Dermacter,Leifsonia,Microbacterium,Oerksovia,Rothia and Turicella

B.anthracis, Y.pestis, B.mallei, B.pseudomallei, F.tularensis and Brucella spp

Aggregatibacter, Actinobacillus, Cardiobacterium, Eikenella, Kingella spp

Challenges in developing breakpoints for uncommon organisms

• Relatively few strains available• Resistant strains may be rare• No clinical trials• Most clinical data from case reports• Laboratory data from centres doing surveys and

studies• CLSI M45-A2 guidelines for breakpoints cannot be

as stringent as standards for common species

Unusual urine isolates

• Actinobaculum schaalii (4)• Actinomyces neuii (3)• Actinomyces turiscensis (1)• Aerococcus urinae (5)• Aerococcus sanguiicola (8)• Other Aerococcus spp (5)• Arthrobacter spp (1)

Option 1- don’t test just add a comment

• “Aerococcus urinae is usually susceptible to a wide range of antibiotics including beta lactams”

• “Actinobaculum schaalii is usually susceptible to beta lactam antibiotics but resistant to trimethoprim and ciprofloxacin”

• “Actinomyces turicensis is usually sensitive to penicillin. Augmentin is the drug of choice”.

Option 2 Provide an MIC

• If necessary, a dilution method is usually the most appropriate testing method

• Physicians should be informed of the limitations of the results and advised to interpret with caution

Examples of Bacteria/antibiotics without breakpoints

• Moraxella nonliquefaciens• Streptococcus pneumoniae/ Ciprofloxacin• Propionibacterium spp/ Vancomycin Rifampicin• Enterobacteriacae/ Colistin• Enterobacteriacae (not E.coli) /Fosfomycin• Burkholderia cepacia/ Piperacillin Tazobactam,

Tigecycline, Moxifloxacin• Capnocytophaga spp• Aerobic Actinomycetes including Nocardia, Gordonia,

Tsukamurella and Rhodococcus• Salmonella spp/ Azithromycin

Reporting

• 1. Discuss with clinicianPK/PD breakpointsEUCAST website MIC distributionsPublished case studies

• 2. Report the MIC only

SUMMARY

If there are no breakpoints , review the literature for clinical reports of MIC and treatment. • Either report with comment only

OR• If the isolate is clinically significant and MIC specifically

requested for the management of the patient, use broth micro dilution method or E tests, following documented methods and QC

• Report MIC only • Always discuss with clinician or add a qualifying

comment

Questions

PK/PD (Non-species related) breakpointsEUCAST Clinical Breakpoint Table v. 4.0, valid from 2014-01-01

These breakpoints should not be used when there are species specific breakpoints, such as values or "-" in the tables.

Penicillins MIC breakpoint (mg/L)

PK/PD (Non-species related) breakpoints are based on the following dosages (See section 8 in Rationale Documents)

S ≤ R >

Benzylpenicillin 0.25 2 The non-species related S/I and I/R breakpoints are based on 600 mg x 4 (2.4 g/day) and 2.4 g x 6 (14.4 g/day) doses respectively.

Ampicillin 2 8 The non-species related breakpoints are based on doses of at least 0.5 g x 3-4 (1.5-2 g/day).

Ampicillin-sulbactam 2 8

Amoxicillin 2 8 The non-species related breakpoints are based on doses of at least 0.5 g x 3-4 (1.5-2 g/day).

Amoxicillin-clavulanate 2 8

Piperacillin 4 16 Breakpoints apply to piperacillin-tazobactam dosage of 4 g x 3.

Piperacillin-tazobactam 4 16 Breakpoints apply to piperacillin-tazobactam dosage of 4 g x 3.

Ticarcillin 8 16

Ticarcillin-clavulanate 8 16