Sensi-Disc™ Antimicrobial Susceptibility
 BBL
Test™Discs
English:
Français :
pages
pages
1–4
4–7
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Italiano:
Seiten
pagine
7–9
9 – 11
Español:
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páginas
páginas
11 – 13
13 – 16
8840621
2011/07
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INTENDED USE – These discs are used for semi-quantitative in vitro susceptibility testing by the agar disc diffusion test procedure of common, rapidly growing and certain fastidious bacterial pathogens. These include the Enterobacteriaceae, Staphylococcus spp., Pseudomonas
spp., Acinetobacter spp., Enterococcus spp., Vibrio cholerae and, by modified procedures, Haemophilus influenzae, Neisseria gonorrhoeae,
Streptococcus pneumoniae and other streptococci. NOTE: Special procedures are required for testing pneumococci, enterococci and methicillin/oxacillin-resistant staphylococci, for performing β-lactamase tests and for screening and confirmatory tests for ESBLs; see the “RESULTS”
section.
For zone diameter interpretive criteria adopted in France, refer to the instructions in the French language section of this insert.
SUMMARY AND EXPLANATION – Agar diffusion methods employing dried filter paper discs impregnated with specific concentrations of antimicrobial agents were developed in the 1940s. In order to eliminate or minimize variability in this testing, Bauer et al. developed a standardized procedure in which Mueller Hinton Agar was selected as the test medium.1,2
Various regulatory agencies and standards-writing organizations subsequently published standardized reference procedures based on the
Bauer-Kirby method. Among the earliest and most widely accepted of these standardized procedures were those published by the U.S. Food
and Drug Administration (FDA)3 and the World Health Organization (WHO).4,5 The procedure was adopted as a consensus standard by the
Clinical and Laboratory Standards Institute (CLSI, formerly NCCLS) and is periodically updated.6,7 The latest CLSI documents should be consulted for current recommendations.
PRINCIPLES OF THE PROCEDURE – Discs containing a wide variety of antimicrobial agents are applied to the surface of Mueller Hinton Agar
plates (or Haemophilus Test Medium Agar for H. influenzae, GC II Agar with IsoVitaleX™ Enrichment for N. gonorrhoeae or Mueller Hinton
Agar with 5% Sheep Blood for S. pneumoniae, β-hemolytic and viridans group streptococci) that have been inoculated with pure cultures of
clinical isolates. Following incubation, the plates are examined and the zones of inhibition surrounding the discs are measured and compared
with established zone size ranges for individual antimicrobial agents in order to determine the agent(s) most suitable for use in antimicrobial
therapy.
REAGENTS – Sensi-Disc™ brand discs are 6-mm discs prepared by impregnating high quality absorbent paper with accurately determined
amounts of antibiotic or other chemotherapeutic agents. Discs are clearly marked on both sides with letters and numbers designating the
agent and the drug content. (See chart giving concentrations of reactive ingredients.) The drug content of discs is assayed by the methods
established by the FDA or by methods similar or comparable to those published in the United States Federal Register.
Sensi-Disc agents are furnished in cartridges containing 50 discs each. The last disc in each cartridge is marked “X” and contains the drug as
coded. Cartridges are for use in BBL™ Sensi-Disc™ Dispensers; these include a Single Disc Dispenser, an 8-Place Dispenser for 100 mm-style
Petri dishes, 6- and 8-Place Self-Tamping Dispensers for 100 mm-style dishes and a Self-Tamping 12-Place Dispenser for 150 mm-style plates.
Warnings and Precautions: For in vitro Diagnostic Use.
Follow directions for use; disc performance depends not only on disc potency, but on use of proper inoculum and control cultures, functional
pretested plates, proper storage temperature and other factors.
Observe aseptic techniques and established precautions against microbiological hazards throughout all procedures. Sterilize cultures, containers and other contaminated materials after use.
Storage Instructions:
1. On receipt, store discs at -20 – +8°C. If the laboratory refrigerator is frequently opened and closed, and a suitable temperature is not maintained, place there a supply sufficient only for use within a week. Some discs (e.g., β-lactams) should preferably be kept frozen at -20°C.
2. Allow containers to come to room temperature before opening. Return unused discs to the refrigerator when application of discs has
been completed. Once opened, discs should be placed in a tightly sealed, desiccated container for storage.
3. Use the oldest discs first.
4. Discard expired discs. Also, cartridges from which discs have been frequently removed during a week and discs left out overnight in the
laboratory should be discarded, or else the discs should be tested for acceptable performance prior to continued use.
5. If the discs form incorrect zones with the recommended control organisms, the entire procedure should be checked; faulty zone size may
be due to the disc, the inoculation, the preparation or depth (about 4 mm) of medium, or other factors.
The expiration date applies only to discs in intact containers, stored as directed.
SPECIMENS – Specimens should not ordinarily be employed in this test. See Directions, which include preparation of inoculum. If possible,
cultures should be derived from specimens obtained from patients prior to the initiation of antimicrobial therapy.
PROCEDURE
Material Provided: Sensi-Disc™ susceptibility test discs as labeled.
Materials Required But Not Provided: Ancillary culture media, reagents, quality control organisms and laboratory equipment required to
perform disc diffusion susceptibility testing by the standardized procedure. Prepare a 0.5 McFarland turbidity standard by adding 0.5 mL of
0.048 M BaCl2 [1.175% (wt/vol) BaCl2•2H2O] to 99.5 mL of 0.18 M [0.36N] H2SO4 [1% (vol/vol)]. Verify by using a spectrophotometer with a
1-cm light path and matched cuvette; absorbance at 625 nm should be 0.08 – 0.13.
Directions, Including User Controls:6
1. Preparation of inoculum with test and control cultures.
a. Perform a Gram stain. Use only pure cultures.
b. Select three to five similar colonies and transfer with inoculation needle or loop into 4 – 5 mL of a suitable broth such as Trypticase™ Soy
Broth (or Mueller Hinton Broth for fastidious organisms).
c. Incubate the broth cultures at 35°C for 2 – 6 h, if necessary, to develop a turbidity equivalent to the 0.5 McFarland turbidity standard
(approximately 1 to 2 x 108 CFU/mL). Alternatively, make a direct broth or saline suspension of colonies selected from an agar plate incubated overnight (a nonselective medium such as blood agar, or chocolate agar for H. influenzae and N. gonorrhoeae, should be used).
The direct colony suspension method is preferred for Staphylococcus spp., S. pneumoniae and other streptococci, Haemophilus spp. and
N. gonorrhoeae.6
d. Dilute, if required, to obtain turbidity equivalent to the 0.5 McFarland turbidity standard. For diluent, use sterile broth or saline.
Alternatively, standardize the inoculum photometrically; to facilitate inoculum adjustment of rapidly growing organisms, the Prompt™
Inoculation System (volumetric inoculum preparation device) may be used.8
Overnight broth cultures should not be used as inoculum.
2. Inoculation.
a. Within 15 min, dip a sterile cotton swab into the properly adjusted inoculum and rotate it firmly several times against the upper inside
wall of the tube to express excess fluid.
b. Streak the entire agar surface of a Mueller Hinton Agar (or other appropriate agar) plate three times, turning the plate 60° between
streakings to obtain even inoculation.
c. The lid may be left ajar for 3 – 5 min, but no more than 15 min, to allow for any surface moisture to be absorbed before applying the
drug-impregnated discs.
3. Select appropriate discs (such as recommended in reference 7, Tables 1A and 1B of M100 [M2]).
4. Apply the discs by means of a BBL™ dispenser, using aseptic precautions. Deposit discs so that the centers are at least 24 mm apart. It is
preferable to deposit penicillin and cephalosporin discs so that they are no less than 10 mm from the edge of the Petri dish, and their centers are at least 30 mm apart. Avoid placing such discs adjacent to one another. With H. influenzae, N. gonorrhoeae and S. pneumoniae, use
no more than nine discs per 150 mm plate or four discs per 100 mm plate. If discs have been placed on the agar with other than the SelfTamping Dispensers, press them down with a sterile needle or forceps to make contact with the surface.
5. Within 15 min, place the plates agar side up in a 35 ± 2°C incubator (for Staphylococcus spp., testing at temperatures above 35°C may not
detect methicillin-resistant staphylococci (MRS); for N. gonorrhoeae, incubate at 36 ± 1°C [do not exceed 37°C]). Haemophilus spp., N. gonorrhoeae, S. pneumoniae and other streptococci should be incubated in an atmosphere enriched with 5% CO2.
6. Examine the plates after 16 – 18 h of incubation (20 – 24 h for N. gonorrhoeae, S. pneumoniae and other streptococci). A full 24 h of incubation is recommended for Staphylococcus spp. to detect methicillin/nafcillin/oxacillin/vancomycin-resistant staphylococci and Enterococcus
spp. for vancomycin resistance. The diameters of the zones of complete inhibition are measured, as determined by gross visual inspection.
Zones are measured to the nearest whole millimeter. For further details in measuring zones of inhibition, consult the reference.6 If only
isolated colonies grow, the inoculum is too light and the test should be repeated. Zones around discs containing different drugs are not
comparable for the purpose of comparing activity of drugs. See the Zone Diameter Interpretive Chart, which gives expected values from
testing common aerobes. Zone measurement may be simplified by using a BBL™ Sensi-Disc™ Zone Interpretation Set.
7. Control tests using prescribed cultures should be included each day susceptibility testing is performed or weekly if satisfactory performance can
be documented according to the CLSI standard.6 Typical zone sizes of E. coli ATCC™ 25922, S. aureus ATCC 25923, P. aeruginosa ATCC 27853,
H. influenzae ATCC 49247, H. influenzae ATCC 49766, N. gonorrhoeae ATCC 49226, S. pneumoniae ATCC 49619, E. coli ATCC 35218 (β-lactamaseproducing strain), E. faecalis ATCC 29212 (for quality control testing of gentamicin 120 µg and streptomycin 300 µg discs) and Klebsiella pneumoniae ATCC 700603 (for screening and confirmatory tests for ESBLs) are given in the chart (or footnotes) and indicate the correct performance of
the entire procedure. E. faecalis ATCC 29212 (or 33186) is also recommended for evaluating new lots of Mueller Hinton Agar for low thymine and
thymidine content (see footnote tt). H. influenzae ATCC 10211 is recommended as a useful additional quality control strain to verify the growth
promotion properties of Haemophilus Test Medium Agar.7
RESULTS 6,7 – NOTE: Recommended interpretive criteria are based on usual dosage regimens and routes of administration in the U.S.
Beginning in 2006, CLSI established zone diameter interpretive ranges for Neisseria meningitidis, Burkholderia cepacia and Stenotrophomonas
maltophilia. For these ranges, consult CLSI M100-S217 or the latest M100 supplement available. In addition, CLSI guideline M45 – Methods for
Antimicrobial Dilution and Disk Susceptibility Testing of Infrequently Isolated or Fastidious Bacteria – can be consulted to obtain information for testing a variety of organisms including Campylobacter, Corynebacterium spp., Bacillus spp., etc.9 For organisms not found in the accompanying table, or
the references mentioned, studies are not yet adequate to develop reproducible definitive standards for interpretation of results. If necessary, a dilution method usually will be the most appropriate testing method, which may require submitting the organism to a reference laboratory.
In some instances, CLSI has implemented new zone diameter ranges for interpretive or quality control criteria. When this has occurred, footnote
“aa” has been added indicating that the FDA-approved zone diameters provided differ from the current CLSI recommendations.
Compare recorded zone diameters with those in the chart; results with a specific organism may be reported as Resistant, Intermediate or Susceptible.
For some organism/antimicrobial agent combinations, the absence or rare occurrence of resistant strains precludes defining any results categories
other than “Susceptible.” For strains yielding results suggestive of a “nonsusceptible” category, organism identification and antimicrobial susceptibility test results should be confirmed. Subsequently, the isolates should be saved and submitted to a reference laboratory that will confirm results
using a CLSI reference dilution method.6
A rapid b-lactamase test (e.g., using Cefinase™ discs) may yield clinically relevant information earlier than results of a disc diffusion test with
Haemophilus spp., N. gonorrhoeae and Moraxella catarrhalis; it is the only reliable test for detecting b-lactamase-producing Enterococcus spp. A
positive b-lactamase test predicts resistance to penicillin, ampicillin and amoxicillin among Haemophilus spp., N. gonorrhoeae and M. catarrhalis and
resistance to penicillin, including amino-, carboxy- and ureido-penicillins among staphylococci and enterococci. A negative b-lactamase test does not
rule out resistance due to other mechanisms. Do not test members of the Enterobacteriaceae, Pseudomonas spp. and other aerobic gram-negative
bacilli because the results may not be predictive of susceptibility to the b-lactams most often used for therapy. Accurate detection of b-lactamase in
staphylococci may require induction of the enzyme and incubation of a nitrocefin-based test for up to 1 h. Induction can be easily accomplished by
testing the growth from the zone margin surrounding an oxacillin disc test. Care must be exercised to ensure accurate results, including testing of
known positive and negative control strains at the time clinical isolates are examined.6
Enterobacteriaceae: When fecal isolates of Salmonella and Shigella spp. are tested, only ampicillin, a quinolone and trimethoprim/sulfamethoxazole
should be reported routinely. In addition, chloramphenicol and a third generation cephalosporin should be tested and reported for extraintestinal
isolates of Salmonella spp. For Salmonella and Shigella spp., aminoglycosides and first and second generation cephalosporins and cephamycins may
appear active in vitro but are not effective clinically and should not be reported as susceptible.7
Enterobacter, Citrobacter, and Serratia may develop resistance during prolonged therapy with third generation cephalosporins. Therefore, isolates
that are initially susceptible may become resistant within 3 to 4 days after initiation of therapy. Testing of repeat isolates may be warranted.7
Extended-spectrum b-lactamases (ESBLs) are enzymes produced by gram-negative bacilli that arise by mutation in genes for common plasmid-mediated b-lactamases. Strains of Klebsiella spp. and E. coli that produce ESBLs may be clinically resistant to therapy with penicillins, cephalosporins, or
aztreonam, despite apparent in vitro susceptibility to some of these agents. Some of these strains will show zones of inhibition below the normal
susceptible population but above the standard breakpoints for certain extended-spectrum cephalosporins or aztreonam; such strains should be
screened for potential ESBL production by using the ESBL screening breakpoints before reporting results for penicillins, extended-spectrum cephalosporins or aztreonam. Other strains may test intermediate or resistant by standard breakpoints to one or more of these agents. In all strains with
ESBLs the zone diameters for one or more of the extended-spectrum cephalosporins or aztreonam should increase in the presence of clavulanic acid
as determined in phenotypic confirmatory testing. For all confirmed ESBL-producing strains, the test interpretation should be reported as resistant
for all penicillins, cephalosporins, and aztreonam. See footnote t for ESBL screening and confirmatory tests. The decision to perform ESBL screening
tests on all urine isolates should be made on an institutional basis, considering prevalence, therapy and infection control issues.7 To screen Proteus
mirabilis for ESBL production, see M100.7
Non-Enterobacteriaceae: Non-Enterobacteriaceae other than P. aeruginosa, Acinetobacter spp., B. cepacia and S. maltophilia should be tested by the
dilution method (see M710). For B. cepacia and S. maltophilia, consult CLSI M100-S21 for zone diameter interpretative standards and quality control.
P. aeruginosa may develop resistance during prolonged therapy with all antibiotics. Isolates that are initially susceptible may become resistant within
3 to 4 days after initiation of therapy and testing of repeat isolates may be warranted.7
The susceptibility of Pseudomonas aeruginosa isolated from patients with cystic fibrosis can be reliably determined by the disc method, but may
require extended incubation up to 24 h before reporting as susceptible.7
Staphylococcus spp.: Staphylococcus spp. may develop resistance during prolonged therapy with quinolones. Therefore, isolates that are initially
susceptible may become resistant within 3 to 4 days after initiation of therapy. Testing of repeat isolates may be warranted.7
Methods for the detection of methicillin-resistant staphylococci include the oxacillin disc test, the cefoxitin disc test and tests for mecA or the protein
encoded by mecA, the penicillin-binding protein 2a (PBP 2a, also called PBP 2′). In the past, the presence of resistance to other classes of agents was
an indication of methicillin (oxacillin) resistance. However, some methicillin-resistant S. aureus (MRSA), such as those found in community-associated
infections, are not multiply-resistant.6
MRSA and methicillin-resistant, coagulase-negative staphylococci should be reported as resistant (or not reported) to all other penicillins, carbapenems, cephems, and b-lactam/b-lactamase inhibitor combinations, regardless of in vitro test results with those agents. This is because most cases of
documented methicillin-resistant infections have responded poorly to b-lactam therapy, and convincing clinical data have yet to be presented that
document clinical efficacy for b-lactams versus MRS. For oxacillin-susceptible S. aureus and coagulase-negative staphylococci, results for parenteral
and oral cephems, b-lactam/b-lactamase inhibitor combinations, and carbapenems, if tested, should be reported according to the results generated
using routine interpretive criteria. For oxacillin-resistant S. aureus and coagulase-negative staphylococci (MRS), other b-lactam agents; i.e., penicillins,
b-lactam/b-lactamase inhibitor combinations, cephems, and carbapenems, may appear active in vitro, but are not effective clinically. Results for these
drugs should be reported as resistant or should not be reported. This is because most cases of documented MRS infections have responded poorly
to b-lactam therapy, or because convincing clinical data have yet to be presented that document clinical efficacy for those agents. Routine testing of
urine isolates of S. saprophyticus is not advised, because infections respond to concentrations achieved in urine of antimicrobial agents commonly
used to treat acute, uncomplicated urinary tract infections (e.g., nitrofurantoin, trimethoprim/sulfamethoxazole or a fluoroquinolone).6,7
To obtain information on predicting mecA-mediated resistance in Staphylococcus spp. using cefoxitin (30 µg), consult CLSI M100-S21.
Similarly, to obtain information on testing Staphylococcus spp. for inducible clindamycin resistance consult M100-S21.
Enterococcus spp.: Enterococci may be resistant to penicillin and ampicillin because of the production of low-affinity, penicillin-binding proteins
(PBPs), or the production of b-lactamase. The disc diffusion test can accurately detect isolates with altered PBPs, but it will not reliably detect b-lactamase producing strains. The latter strains are best detected by using a direct b-lactamase test;6 e.g., with Cefinase nitrocefin discs or chromogenic
cephalosporin discs.
For Enterococcus spp., cephalosporins, aminoglycosides (except for high level resistance screening), clindamycin and trimethoprim/sulfamethoxazole
may appear active in vitro but are not effective clinically and isolates should not be reported as susceptible.
Haemophilus spp.: Only results of testing with ampicillin, one of the third-generation cephalosporins, chloramphenicol and meropenem should be
reported routinely with cerebrospinal fluid isolates of H. influenzae.
Amoxicillin/clavulanic acid, azithromycin, clarithromycin, cefaclor, cefprozil, loracarbef, cefdinir, cefixime, cefpodoxime, cefuroxime axetil and telithromycin are oral agents that may be used as empiric therapy for respiratory tract infections due to Haemophilus spp. The results of susceptibility tests
with these antimicrobial agents are often not useful for management of individual patients. However, susceptibility testing of Haemophilus spp.
with these compounds may be appropriate for surveillance or epidemiologic studies.
Streptococcus spp. other than S. pneumoniae: Susceptibility testing of penicillins and other b-lactams approved by the U.S. Food and Drug
Administration for treatment of S. pyogenes or S. agalactiae is not necessary for clinical purposes and need not be done routinely, since as with vancomycin, resistant strains have not been recognized. Interpretive criteria are provided for pharmaceutical development, epidemiology or monitoring
for emerging resistance. Any strain found to be intermediate or resistant should be referred to a reference laboratory for confirmation.
To obtain information on testing β-hemolytic streptococci for inducible clindamycin resistance consult M100-S21.7
LIMITATIONS OF THE PROCEDURE
1. The test as herein described applies primarily to rapidly growing aerobic pathogens. For fastidious bacteria other than H. influenzae,
N. gonorrhoeae, S. pneumoniae and other streptococci, consult M100 (N. meningitidis) or M45.7,13 Otherwise, test by the dilution method.
Testing of anaerobes requires special procedures.11
2. The classifications of Resistant, Intermediate and Susceptible vary only by one millimeter, which is within normal laboratory error. Some
cultures may give a borderline zone that varies from day to day or from laboratory to laboratory; such cultures are relatively uncommon.
3. For detecting pneumococcal and enterococcal resistance, strictly adhere to CLSI recommended methods.6
4. Antimicrobial agents other than those listed in the Chart may be in current use. Susceptibility tests employing these agents should be interpreted
on the basis of presence or absence of a definite zone of inhibition and should be considered as only qualitative until such time as interpretive
zones have been established. All zone diameters should be recorded.
5. ESBL confirmatory testing is only valid when the four discs (cefotaxime, cefotaxime/clavulanic acid, ceftazidime, ceftazidime/clavulanic acid) are
used simultaneously. Individual usage of these discs is not recommended by CLSI.6,7
6. Accurate results are a function of the correct storage and maintenance of quality control organisms. This is especially true for E. coli ATCC 35218
and K. pneumoniae ATCC 700603, because spontaneous loss of the plasmid encoding the β-lactamase has been documented. Refer to CLSI standard M2 for recommendations on the correct storage and maintenance of quality control organisms.6
7. The ability to detect vancomycin-resistant Staphylococcus aureus (VRSA) with this product is unknown. Additional testing methods as recommended by the Centers for Disease Control and Prevention (CDC) should be used when performing susceptibility testing on S. aureus isolates,
particularly methicillin-resistant S. aureus (MRSA). These tests include nonautomated MIC methods (e.g., broth microdilution or agar dilution) and
a vancomycin agar screen test (Brain Heart Infusion Agar with 6 µg/mL of vancomycin). These methods require a full 24 h of incubation to detect
VRSA. For additional information, refer to the CDC web site.12
REFERENCES
1. Bauer, A.W., W.M.M. Kirby, J.C. Sherris, and M. Turck. 1966. Antibiotic susceptibility testing by a standardized single disk method. Am. J. Clin.
Pathol. 45:493-496.
2. Ryan, K.J., F.D. Schoenknecht, and W.M.M. Kirby. 1970. Disc sensitivity testing. Hospital Practice 5:91-100.
3. Federal Register. 1972. Rules and regulations. Antibiotic susceptibility discs. Fed. Regist. 37:20525-20529. Erratum, 38:2756, 1973.
4. Ericsson, H.M., and J.C. Sherris. 1971. Antibiotic sensitivity testing. Report of an international collaborative study. Acta Pathol. Microbiol. Scand. Sec.
B. Suppl. 217:1-90.
5. World Health Organization Expert Committee on Biological Standardization. 1977. Technical report series 610. W.H.O., Geneva.
6. Clinical and Laboratory Standards Institute. 2009. Approved standard M2-A10. Performance standards for antimicrobial disk susceptibility tests, 10th ed.
CLSI, Wayne, Pa.
7. Clinical and Laboratory Standards Institute. 2011. M100-S21 (M2). Disk Diffusion Supplemental Tables, CLSI, Wayne Pa.
8. Baker, C.N., C. Thornsberry, and R.W. Hawkinson. 1983. Inoculum standardization in antimicrobial susceptibility testing: evaluation of overnight
agar cultures and the rapid inoculum standardization system. J. Clin. Microbiol. 17:450-457.
9. Clinical and Laboratory Standards Institute. 2010. Approved guideline M45-A2. Methods for antimicrobial dilution and disk susceptibility testing of
infrequently isolated or fastidious bacteria. 2nd ed., CLSI, Wayne, Pa.
10. Clinical and Laboratory Standards Institute. 2009. Approved standard M7-A8. Methods for dilution antimicrobial susceptibility tests for bacteria that
grow aerobically, 8th ed. CLSI, Wayne, Pa.
11. Clinical and Laboratory Standards Institute. 2007. Approved standard M11-A7. Methods for antimicrobial susceptibility testing of anaerobic bacteria,
7th ed. CLSI, Wayne, Pa.
12. Centers for Disease Control and Prevention. www.cdc.gov/ncidod/dhqp/ar_visavrsa_labFAQ.html
13. Bushby, S.R.M. 1973. Trimethoprim-sulfamethoxazole: in vitro microbiological aspects, p. 10-30. In M. Finland and E.H. Kass (ed.), Trimethoprim-sulfamethoxazole: microbiological, pharmacological, and clinical considerations. University of Chicago Press, Chicago.
Zone Diameter Interpretive Chart †
Antimicrobial
Agent
Disc
Potency
Code
Zone Diameter
Control Zone
Interpretive Standards (mm)
Diameter Limits (mm)
E.
S.
P.
H.
H.
coli
aureus aeruginosa influenzae influenzae
ResisInter- SuscepATCC
ATCC
ATCC
ATCC
ATCC
tant mediate a tible b
49766 c
25922
25923
27853
49247 c
AMD-10 10 µg
Amdinocillin f
Enterobacteriaceae
≤15 —
≥16
23 – 29
—
—
Amikacin
AN-30 30 µg
Enterobacteriaceae, P. aeruginosa,
Acinetobacter and staphylococci
≤14
15 – 16
≥17
19 – 26
20 – 26
18 – 26
Ampicillin/
SAM-20
10/10 µg
19 – 24g,ii 29 – 37
—
Sulbactam g,h,i
Enterobacteriaceae, P. aeruginosa,
Acinetobacter q and staphylococci j
≤11
12 – 14ii ≥15ii
Haemophilus spp. c,k
≤19 —
≥20
N.
S.
gonorrhoeae pneumoniae
ATCC
ATCC
49226 d
49619 e
—
—
Carbenicillin
CB-100
100 µg
23 – 29
—
18 – 24
Enterobacteriaceae and Acinetobacter
≤19ii 20 – 22ii ≥23
P. aeruginosa
≤13
14 – 16
≥17
CEC-30 30 µg
23 – 27 27 – 31
—
Cefaclor h,i
Enterobacteriaceae u and staphylococci j
≤14
15 – 17
≥18
c,k
Haemophilus spp.
≤16
17 – 19
≥20
Cefamandole
MA-30 30 µg
Enterobacteriaceae and staphylococci j
≤14
15 – 17
≥18
26 – 32
26 – 34
—
14 –22c
30 – 36e
—
30 – 38c
—
—
25 – 31c
—
24 – 31c
— —
Streptococci (non-S. pneumoniae, β-hemolytic
≥24ii
only)aaa,ccc
CFM-5
5 µg
23 – 27
—
—
Cefixime h
Enterobacteriaceae v
≤15
16 –18
≥19
c
Haemophilus spp.
— —
≥21
25 – 33c
—
— —
N. gonorrhoeae d
≥31
37 – 45d
Cefmetazole
CMZ-30 30 µg
26 – 32 25 – 34
—
Enterobacteriaceae and staphylococci j
≤12
13 – 15
≥16
N. gonorrhoeae d
≤27
28 – 32w ≥33
31 – 36d
28 – 35e
Cefonicid
CID-30 30 µg
25 – 29 22 – 28
—
Enterobacteriaceae and staphylococci j
≤14
15 – 17
≥18
Haemoph
—
C
op
on
A
o
m
X
A
H m
N
V
C
o
n
n
OX
podo m
H
N
D
H
w
w
dm
A
C
C
dm
u n A d
C
bu
H
A
H m
N
n
A
— —
— —
o m
OX
A
H m
N
C
on
—
—
—
— —
—
—
—
—
O
— —
—
— —
m
— —
m
m
A
H m
N
V
u o m
m
XM
—
H
N
m
w
—
C ph o h n
—
Ch o
—
mph n o
H
m
m
C no
n
N
Cp o o
n
—
—
—
—
— —
—
w
A
H m
N
C
h om
H
n
m
n
m
Co
n
—
DO
m
A
m
m
Do
n
D
—
Do p n m
—
—
m
C nd m
—
—
—
—
—
— —
— —
— —
— —
—
A
no
N
n
NX
2
—
—
19 – 27
16 – 21
17 – 25
19 – 26
24 – 31e
28 – 34
—
MEM-10 10 µg
28 – 34 29 – 37ii 27 – 33
Meropenem h,i
Enterobacteriaceae, P. aeruginosa,
Acinetobacter and staphylococci j
≤13
14 – 15
≥16
Haemophilus spp. c
— —
≥20
MZ-75 75 µg
23 – 29
—
19 – 25
Mezlocillin ii
Moxalactam
MOX-30 30 µg
Enterobacteriaceae, P. aeruginosa,
Acinetobacter and staphylococci j
≤14
15 – 22
≥23
20 – 25e
19 – 25
25 – 30
—
28 – 35
18 – 24
17 – 25
20 – 28c
Nafcillin
NF-1 1 µg
Staphylococcus aureus j,nn
≤10
11 – 12
≥13
—
16 – 22
—
Nalidixic Acid
NA-30 30 µg
Enterobacteriaceae z
≤13
14 – 18
≥19
N-30 30 µg
Neomycin f
≤12
13 – 16
≥17
22 – 28
—
—
17 – 23
18 – 26
—
Netilmicin
NET-30 30 µg
Enterobacteriaceae, P. aeruginosa,
Acinetobacter and staphylococci
≤12
13 – 14
≥15
22 – 30
22 – 31
17 – 23
Nitrofurantoin
F/M-300
300 µg
Enterobacteriaceae, staphylococci and
enterococci
≤14
15 – 16
≥17
NOR-10
10 µg
Norfloxacin ii
ddd
Enterobacteriaceae
, P. aeruginosa,
20 – 25
18 – 22
—
28 – 35
17 – 28
22 – 29
—
22 – 31
—
≤12
13 – 16
≥17
≤17
18 – 21
≥ 22
≤14
15 – 16
≥17
—
Ofloxacin
OFX-5 5 µg
29 – 33 24 – 28 17 – 21
Enterobacteriaceaeddd, P. aeruginosa,
aa
Acinetobacter and staphylococci ≤12
13 – 15
≥16
— —
—
Haemophilus spp. c
≥16
31 – 40c
N. gonorrhoeae d
≤24
25 – 30wŽ≥31
43 – 51d
S. pneumoniae e and other streptococci
(non-S. pneumoniae, b-hemolytic only) e
≤ 12
13 – 15
≥16
Oxacillin
OX-1 1 µg
—
18 – 24
—
Staphylococcus aureus j,nn,oo
≤10
11 – 12
≥13
Staphylococci, coagulase-negative j,nn
≤17
—
≥18
S. pneumoniae (for
penicillin G susceptibility) e,h
— —
≥20
OA-2 2 µg
Oxolinic Acid f
≤10 —
≥11
20 – 24 10 – 13
—
P-10 10 U
—
26 – 37
—
Penicillin h
Staphylococcus spp. j,pp
≤28 —
≥29
Enterococcus spp. n,o
≤14 —
≥15
L. monocytogenes f
≤19
20 – 27
≥28
N. gonorrhoeae d,qq,ii
≤26
27 – 46 w ≥47
26 – 34d
Streptococci (non-S. pneumoniae, — —
≥24ii
b-hemolytic only) e,i,rr,aaa,ccc
Piperacillin
PIP-100
100 µg
Enterobacteriaceae and Acinetobacter
≤17
18 – 20
≥21
P. aeruginosa
≤17 —
≥18
Piperacillin/
TZP-110
100/10 µg
Tazobactam g
Enterobacteriaceae and Acinetobacter ii
≤17
18 – 20
≥21
Staphylococcus spp. j,ii and P. aeruginosa ii
≤17 —
≥18
aa,dd
PB-300
300 U
Polymyxin B
≤8
9 – 11
≥12
24 – 30g
—
300 µg
6
10 µg
≤11
7 – 9 hh
12 – 14
≥15
≤12
13 – 16
25 – 31e
16 – 21e
≤12 e,bbb
24 – 30e
25 – 33
24 – 30g 27 – 36 25 – 33ii
12 – 16
≥10
25 – 34e,ii
45 – 54d
Moxifloxacin
MXF-5
5 µg
28 – 35 28 – 35
—aa
Enterobacteriaceaef,ddd and Staphylococcus spp.aa ≤15
16 – 18
≥19
H. influenzaec and H. parainfluenzaec
— —
≥18
31 – 39c
—
S. pneumoniaee
≤14
15 – 17
≥18
—
—
—
—
19 – 24e,ii,cc
25 – 30 e
21 – 27 e
23 – 29d
—
12 – 20
14 – 22
—
15 – 23
24 – 34
—
≥17
Telavancin
TLV-30 30 µg
—
16 – 20
—
17 – 24
Staphylococcus aureus
—
—
(including methicillin-resistant isolates) f
≥15
Streptococcus pyogenes, Streptococcus agalactiae,
Streptococcus anginosus group (S. anginosus,
S. constellatus and S. intermedius)e,f
—
—
≥15
Enterococcus faecalis
—
—
(vancomycin-susceptible isolates only) f
≥15
Telithromycin
TEL-15
15 µg
—
24 – 30
—
S. aureus
—aa —aa
≥22
Haemophilus spp.c
≤11
12 – 14
≥15
17 – 23
—
S. pneumoniaee
≤15
16 – 18
≥19
27 – 33
Te-30
30 µg
18 – 25 24 – 30
—
Tetracycline ee
Enterobacteriaceaeaa, P. aeruginosa,
Acinetobacteraa, staphylococci,
enterococci yy and V. cholerae m
≤14
15 – 18
≥19
—
Haemophilus spp. c
≤25
26 – 28
≥29
14 – 22c
N. gonorrhoeae d,uu
≤30
31 – 37w ≥38
30 – 42d
S. pneumoniae and other streptococci e
≤18
19 – 22
≥23
27 – 31e
Ticarcillin/
TIM-85
75/10 µg
Clavulanic Acid g
Enterobacteriaceae and Acinetobacter
≤14
15 - 19
≥20
P. aeruginosa
≤14 —
≥15
j
Staphylococcus spp.
≤22 —
≥23
A
V
m
—
19 – 26
Levofloxacin
LVX–5 5 µg
29 – 37 25 – 30 19 – 26
Enterobacteriaceaeddd, P. aeruginosa,
Acinetobacter, staphylococci aa and enterococci
≤13
14 – 16
≥17
— —
Haemophilus spp. c ≥17
32 – 40c
—
S. pneumoniae and other streptococci ≤13
14 – 16
≥17
(non-S. pneumoniae, b-hemolytic only) e
Ticarcillin
TIC-75
75 µg
Enterobacteriaceae and Acinetobacter
≤14
15 – 19
≥20
P. aeruginosa
≤14 —
≥15
25 – 30e
26 – 32
—
20 – 28
Enterobacteriaceae, P. aeruginosa,
Acinetobacter and staphylococci j
≤13
14 – 15
≥16
Haemophilus spp. c
— —
≥16
21 – 29c
—
250 µg
Enterobacteriaceae, P. aeruginosa,
Acinetobacter, staphylococci and V. cholerae m
— —
— —
Gentamicin
Testing enterococci
GM-120
120 µg
6
7 – 9 hhŽ≥10
for high level resistance n,o,gg
Enterobacteriaceae,
GM-10 10 µg
P. aeruginosa, Acinetobacter and staphylococci
≤12
13 – 14
≥15
h,i
IPM-10 10 µg
Imipenem
Streptomycin
Testing enterococci
S-300
for high level resistance n,o,gg
Enterobacteriaceae
S-10
G-.25
Sulfisoxazole tt
—
—
28 – 35
≥16
Spectinomycin
SPT-100
100 µg
—
—
—
N. gonorrhoeae d
≤14
15 – 17w ≥18
— —
— —
13 – 15
Rifampin
RA-5 5 µg
8 – 10 26 – 34
—
Staphylococcus spp. and Enterococcus spp. yy
≤16
17 – 19
≥20
c
—
Haemophilus spp. ≤16
17 – 19
≥20
22 – 30c
S. pneumoniae e
≤16
17 – 18Ž≥19
Sparfloxacin
SPX–5 5 µg
30 – 38 27 – 33 21 – 29 ii
Staphylococcus spp. ≤15
16 – 18
≥19
S. pneumoniae e
≤15ii 16 – 18 ii ≥19
—
—
≤12
—
Quinupristin/Dalfopristin SYN-15 4.5/10.5 µg
—
21 – 28ii
Staphylococcus spp., ≤15
16 – 18
≥19
Enterococcus faecium and
S. pyogenese only
A
m
C
m
C
m
p o
C
N
C
A
N
o
X
— —
m
m
o
m
u n A d
C
—
m
C
C
C
— —
— —
E. coli and E. faecalis only
Gatifloxacin
GAT-5
5 µg
30 – 37 27 – 33 20 – 28mm
Enterobacteriaceaeddd and Staphylococcus spp.aa ≤14
15 – 17
≥18
P. aeruginosa, Acinetobacter spp. and enterococciz
≤14ii 15 – 17ii ≥18ii
—
H. influenzaec and H. parainfluenzaec
— —
≥18
33 – 41c
N. gonorrhoeaed
≤33
34 – 37
≥38
45 – 56d
S. pneumoniae and other streptococci ≤17ii 18 – 20ii ≥21ii
e
(non-S. pneumoniae, b-hemolytic only)
Gemifloxacin
GEM-5
5 µg
29 – 36 27 – 33ii19 – 25mm,ii
Enterobacteriaceaell,ddd
≤15
16 – 19
≥20
c
c
H. influenzae and H. parainfluenzae
— —
≥18
30 – 37
—
S. pneumoniaee
≤19
20 – 22
≥23
Acinetobacter, staphylococci and enterococci
NB-30 30 µg
Novobiocin f
(Mueller Hinton agar with sheep blood
for veterinary use)
FEP-30 30 µg
31 –37ii 23 – 29 24 – 30
Cefepime h,i
Enterobacteriaceae, P. aeruginosa,
Acinetobacter and staphylococci j
≤14
15 – 17
≥18
— —
—
Haemophilus spp. c
≥26
25 –31c
— —
N. gonorrhoeae d
≥31
37 – 46d,ii
Viridans Streptococci (non-S. pneumoniae) e,ccc
≤ 21ii 22 – 23ii ≥24ii
C
Erythromycin
E-15 15 µg
—
22 – 30
—
Staphylococcus spp. r and enterococci r,yy
≤13
14 – 22ii ≥23ii
S. pneumoniae and other streptococci e,r,s
≤15
16 – 20
≥21
FOS-200
200 µg
22 – 30ii 25 – 33
—
Fosfomycin z
Enterobacteriaceae and Acinetobacter
≤17
18 – 20
≥21
P. aeruginosa
≤15 —
≥16
MI-30 30 µg
Minocycline ee
aa
Enterobacteriaceae , P. aeruginosa,
Acinetobacteraa, staphylococci and enterococci yy ≤14
15 – 18
≥19
—
Cefazolin
CZ-30 30 µg
21 – 27ii 29 – 35
—
Enterobacteriaceae u and staphylococci j
≤14
15 – 17
≥18
CDR-5 5 µg
24 – 28 25 – 32
—
Cefdinir h
Enterobacteriaceaekk and methicillin-susceptible staphylococci j
≤16
17 – 19
≥20
Haemophilus spp. c
— —
≥20
Ertapenemh,i
ETP-10
10 µg
29 – 36 24 – 31 13 – 21
Enterobacteriaceae and Staphylococcus spp.j
≤15
16 – 18
≥19
Haemophilus spp.c
— —
≥19
20 – 28
27 – 33
Lomefloxacin
LOM-10 10 µg
27 – 33 23 – 29 22 – 28
Enterobacteriaceaeddd, P. aeruginosa,
Acinetobacter and staphylococci
≤18
19 – 21
≥22
— —
Haemophilus spp. c
≥22
33 – 41c
—
N. gonorrhoeae d
≤26
27 – 37
≥38
LOR-30 30 µg
23 – 29 23 – 31
—
Loracarbef h,i
Enterobacteriaceae u,kk and staphylococci j
≤14
15 – 17
≥18
Haemophilus spp. c,k
≤15
16 – 18
≥19
—
26 – 32c
24 – 30
Aztreonam
ATM-30 30 µg
28 – 36
—
23 – 29
Enterobacteriaceae, t P. aeruginosa & Acinetobacter ≤15
16 – 21
≥22
— —
Haemophilus spp. c
≥26
B-10 10 U
Bacitracin f
≤8
9 – 12
≥13
—
12 – 22
—
N.
S.
gonorrhoeae pneumoniae
ATCC
ATCC
49226 d
49619 e
—
Linezolid
LZD-30
30 µg
—
— —
Staphylococcus spp.
≥21
Enterococcus spp. ≤20
21 – 22
≥23
—
S. pneumoniae and other streptococci e
—
≥21
Azithromycin
AZM-15 15 µg
—
21 – 26
—
Staphylococcus spp. r
≤13
14 – 17
≥18
—
Haemophilus spp. c
— —
≥12
13 – 21c
S. pneumoniae and other streptococci e,r,s
≤13
14 – 17
≥18
19 – 25e
Azlocillin
AZ-75 75 µg
P. aeruginosa
≤17 —
≥18
Code
Disc
Potency
Kanamycin
K-30 30 µg
Enterobacteriaceae and staphylococci ≤13
14 – 17
≥18
—
≥24ii
— —
Antimicrobial
Agent
Zone Diameter
Control Zone
Interpretive Standards (mm)
Diameter Limits (mm)
E.
S.
P.
H.
H.
coli
aureus aeruginosa influenzae influenzae
ResisInter- SuscepATCC
ATCC
ATCC
ATCC
ATCC
tant mediate a tible b
25922
25923
27853
49247 c
49766 c
25 – 32ii
Amoxicillin/
20/10 µg
18 – 24g,ii 28 – 36
—
Clavulanic Acid g,h,i AmC-30
Enterobacteriaceae
≤13
14 – 17
≥18
j
Staphylococcus spp. ≤19 —
≥20
Haemophilus spp. c,k
≤19 —
≥20
15 –23c
AM-10 10 µg
16 – 22 27 – 35
—
Ampicillin h,l
Enterobacteriaceaeii and V. cholerae m ≤13
14 – 16
≥17
Staphylococci j,ii
≤28 —
≥29
Enterococcus spp. n,o,ii
≤16 —
≥17
Listeria monocytogenes f
≤19 —
≥20
Haemophilus spp. c,k,p
≤18
19 – 21
≥22
13 – 21c
Streptococci (non-S. pneumoniae, b-hemolytic
only) e,i,aaa,ccc
Zone Diameter Interpretive Chart †
24 – 30
—
24 –30g,ii 29 – 37
21 – 27ii
20 – 28
23 – 31jj
—
30 – 40zz
Tigecycline
TGC-15
15 µg
20 – 27 20 – 25 9 – 13mm
Enterobacteriaceaef,ss
≤14
15 - 18
≥19
f
—
—
S. aureus (including MRSA) ≥19
E. faecalis (vancomycin-susceptible isolates only)f
—
—
≥19
Streptococcus spp. (other than S. pneumoniae)e,f —
—
≥19
Tobramycin
NN-10
10 µg
Enterobacteriaceae, P. aeruginosa,
Acinetobacter and staphylococci
≤12
13 – 14
≥15
18 – 26
19 – 29
19 – 25
Trimethoprim
TMP-5 5 µg
Enterobacteriaceae and staphylococci
≤10
11 – 15
≥16
21 – 28
19 – 26
—
 BBL Sensi-Disc Antimicrobial Susceptibility Test Discs
(D sques Sens -D sc BBL pour ant b ogramme)
23 – 29cc
Trimethoprim/
SXT 1.25 µg
23 – 29ii 24 – 32
—
Sulfamethoxazole tt23.75 µg
Enterobacteriaceae, P. aeruginosa,
m
Acinetobacter, staphylococci and V. cholerae
≤10
11 – 15
≥16
—
Haemophilus spp. c
≤10
11 – 15
≥16
24 – 32c
S. pneumoniae e
≤15
16 – 18
≥19
20 – 28e
Vancomycin
Va-3 0
30 µg
—
17 – 21
—
— —
Staphylococcus spp. vv,ii
≥15
Enterococcus spp. n,o,ww
≤14
15 – 16
≥17
S. pneumoniae xx and other streptococci e
— —
≥17
20 – 27 e
an a
APPLICATION – Ces disques sont utilisés pour une évaluation semi-quantitative in vitro de la sensibilité aux antibiotiques des agents pathogènes
bactériens courants à croissance rapide ainsi que de certaines espèces exigeantes, par un antibiogramme par diffusion sur disque en gélose.
Les microorganismes concernés incluent : les Enterobacteriaceae, les genres Staphylococcus, Pseudomonas, Acinetobacter, Enterococcus, Vibrio
cholerae et, avec des procédures modifiées, Haemophilus influenzae, Neisseria gonorrhoeae, Streptococcus pneumoniae et d’autres streptocoques.
REMARQUE : Des procédures particulières sont nécessaires pour tester les pneumocoques, les entérocoques et les staphylocoques résistants à
la méticilline/oxacilline et pour réaliser des tests des bβ-lactamases et des tests de dépistage et de confirmation pour les ESBL ; voir la section
« Résultats ».
Pour la France: Les résultats seront interprétés en fonction du dernier communiqué du Comité de l’antibiogramme de la Société Française de
Microbiologie. Un guide d’interprétation conforme au communiqué du Comité de l’antibiogramme de la Société Française de Microbiologie pourra
être fourni sur simple demande à la société Becton Dickinson France S.A.S., Tel: 04 76 68 36 36.
† Adapted in part from CLSI Document M100-S21 (M2): Disk Diffusion Supplemental Tables, Performance Standards for Antimicrobial Susceptibility
Testing, with permission. The complete standard may be obtained from the Clinical and Laboratory Standards Institute, 940 West Valley Road, Suite
1400, Wayne, PA 19087-1898 USA. Values not in M100-S21 are explained in other footnotes. For appropriate MIC correlates, refer to M100-S21.6,7,9
aThe “Intermediate” category includes isolates with antimicrobial agent MICs that approach usually attainable blood and tissue levels and for which
response rates may be lower than for susceptible isolates. The “Intermediate” category implies clinical applicability in body sites where the drugs are
physiologically concentrated (e.g., quinolones and β-lactams in urine), or when a higher than normal dosage of a drug can be used (e.g., β-lactams).
The “Intermediate” category also includes “buffer zone” which should prevent small uncontrolled technical factors from causing major discrepancies in
interpretation, especially for drugs with narrow pharmacotoxicity margins.
bPolicies regarding generation of cumulative antibiograms should be developed in concert with the infectious disease service, infection control personnel, and the pharmacy and therapeutics committee. Under most circumstances, the percentage of susceptible and intermediate results should not be
combined into the same statistics.
cThese zone diameter standards and quality control limits apply only to tests with Haemophilus spp. using Haemophilus Test Medium (HTM) incubated in
5% CO2 (16♣-18 h). H. influenzae ATCC 10211 is recommended as a useful additional quality control strain to verify the growth promotion properties of
3
HTM. The zone margin should be considered as the area showing no obvious growth visible with the unaided eye. Faint growth of tiny colonies that
may appear to fade from the more obvious zone should be ignored in the measurement. When testing Haemophilus with amoxicillin/clavulanic acid
on HTM, include E. coli ATCC 35218 as the control strain. The acceptable limits for E. coli ATCC 35218 are 17-22 mm for amoxicillin/clavulanic acid when
incubated in ambient air.
dThese zone diameter standards and quality control limits are applicable only to tests performed using GC agar base and 1% defined growth supplement (e.g., BBL™ GC II Agar with IsoVitaleX™ Enrichment) incubated in 5% CO2 (20 – 24 h).
eThese zone diameter standards and quality control limits are applicable only to tests performed using Mueller Hinton agar supplemented with 5%
defibrinated sheep blood incubated in 5% CO2 (20 – 24 h). Interpretive standards apply to S. pneumoniae and other streptococci as indicated.
Results may be inaccurate if specified criteria are applied to organisms other than those listed. Interpretive criteria for streptococci other than S. pneumoniae are proposed based on population distributions of various species, pharmacokinetics of the antimicrobial agents, previously published literature
and the clinical experience of certain members of the CLSI subcommittee. Systematically collected clinical data were not available for review with
many of the compounds in the group.7 Despite the lack of reliable disc diffusion interpretive criteria for S. pneumoniae with certain β-lactams, S.
pneumoniae ATCC 49619 is the strain designated for quality control of all disc diffusion tests with all Streptococcus spp.
f FDA-approved zone size recommendations from drug manufacturers not included in CLSI M100-S21 (M2-A10).7
gAnother E. coli (ATCC 35218) has been designated for quality control of discs containing combinations of β-lactams and β-lactamase inhibitors. This
strain produces a β-lactamase which should be inactivated by the inhibitor. When used in conjunction with ATCC 25922, both components of the
combination discs can be monitored. Control limits with this strain for amoxicillin/clavulanic acid are 17-22 mm, for ampicillin is 6 mm (i.e., no zone),
for ampicillin/sulbactam are 13-19 mm, for piperacillin are 12-18 mm, for piperacillin/tazobactam are 24-30 mm, for ticarcillin is 6 mm (i.e., no zone)
and for ticarcillin/clavulanic acid are 21-25 mm. The E. coli ATCC 35218 control strain contains a plasmid-encoded β-lactamase (non-ESBL); therefore, the
organism is resistant to many penicillinase-labile drugs, but susceptible to β-lactam/ β-lactamase inhibitor combinations. The plasmid must be present in
the control strain for the quality control test to be valid; however, the plasmid may be lost during storage at refrigerator or freezer temperatures. See
“Limitations of the Procedure” and M2 for additional details.
hIsolates of pneumococci with oxacillin zone sizes of ≥ 20 mm are susceptible (MIC ≤ 0.06 µg/mL) to penicillin and can be considered susceptible
to ampicillin, amoxicillin, amoxicillin/clavulanic acid, ampicillin/sulbactam, cefaclor, cefdinir, cefepime, cefetamet, cefixime, cefotaxime, cefprozil,
ceftibuten, ceftriaxone, cefuroxime, cefpodoxime, ceftizoxime, ertapenem, imipenem, loracarbef, and meropenem for approved indications,
and these agents need not be tested. Penicillin and cefotaxime or ceftriaxone or meropenem MICs should be determined for those isolates with
oxacillin zone sizes ≤ 19 mm because zones of ≤ 19 mm occur with penicillin-resistant, intermediate, or certain susceptible strains. Isolates should
not be reported as penicillin resistant or intermediate based solely on an oxacillin zone ≤ 19 mm. Amoxicillin, ampicillin, cefepime, cefotaxime,
ceftriaxone, cefuroxime, ertapenem, imipenem, and meropenem may be used to treat pneumococcal infections; however, reliable disc diffusion
susceptibility tests with these agents do not yet exist. Their in vitro activity is best determined using an MIC method. Penicillin and cefotaxime or
ceftriaxone or meropenem should be tested by a reliable MIC method (such as that described in CLSI document M79) and reported routinely with
CSF isolates of S. pneumoniae. Such isolates should also be tested against vancomycin using the MIC or disc method. With isolates from other
sites, the oxacillin disc screening test may be used. If the oxacillin zone size is ≤ 19 mm, penicillin and cefotaxime or ceftriaxone MICs should be
determined. To determine susceptibility of streptococci other than S. pneumoniae to cefdinir, use the 10-unit penicillin disc; isolates with penicillin zone sizes ≥ 2
Ž 8 mm are susceptible to penicillin and can be considered susceptible to cefdinir.
iA streptococcal isolate that is susceptible to penicillin can be considered susceptible to ampicillin, amoxicillin, amoxicillin/clavulanic acid, ampicillin/sulbactam, cefaclor, cefazolin, cefdinir, cefepime, cefprozil, cefotaxime, ceftibuten (group A streptococci only), ceftriaxone, cefuroxime, cefpodoxime,
ceftizoxime, cephalothin, cephapirin, cephradine, imipenem, loracarbef, and meropenem for approved indications, and need not be tested against
those agents. Viridans streptococci isolated from blood and normally sterile body sites (e.g., cerebrospinal fluid, blood, bone, etc.), should be tested for
penicillin or ampicillin susceptibility using an MIC method.
jPenicillin-susceptible staphylococci are also susceptible to other penicillins, β-lactam/β-lactamase inhibitor combinations, cephems, and carbapenems
approved for use by the FDA for staphylococcal infections. Penicillin-resistant, oxacillin-susceptible strains are resistant to penicillinase-labile penicillins
but susceptible to other penicillinase-stable penicillins, β-lactam/β-lactamase inhibitor combinations, relevant cephems, and carbapenems. Oxacillin-resistant staphylococci are resistant to all currently available β-lactam antibiotics. Thus, susceptibility or resistance to a wide array of β-lactam antibiotics may
be deduced from testing only penicillin and oxacillin. Routine testing of other penicillins, β-lactam/β-lactamase inhibitor combinations, cephems, and
carbapenems is not advised.7 For oxacillin-resistant staphylococci, report as resistant or do not report.
kRare, β-lactamase-negative, ampicillin-resistant (BLNAR) strains of Haemophilus influenzae should be considered resistant to amoxicillin/clavulanic acid,
ampicillin/sulbactam, cefaclor, cefetamet, cefonicid, cefprozil, cefuroxime, and loracarbef despite apparent in vitro susceptibility of some BLNAR strains
to these agents.
l
Class representative for ampicillin and amoxicillin.
mFor V. cholerae, the results of disc diffusion tests for ampicillin, tetracycline, trimethoprim/sulfamethoxazole and sulfonamides (i.e., percentage of susceptible, intermediate, and resistant) correlate well with results determined by broth microdilution. Tetracycline results can be used to predict the likely
susceptibility of isolates to doxycycline; do not use disc test for doxycycline or erythromycin because there is poor correlation with MIC results.
nAmpicillin is the class representative for ampicillin and amoxicillin. Ampicillin results may be used to predict susceptibility to amoxicillin/clavulanic
acid, ampicillin/sulbactam, piperacillin and piperacillin/tazobactam among non-β-lactamase-producing enterococci. Enterococci susceptible to
penicillin are predictably susceptible to ampicillin, amoxicillin, ampicillin/sulbactam, amoxicillin/clavulanic acid, piperacillin, and piperacillin/
tazobactam for non-β-lactamase-producing enterococci. However, enterococci susceptible to ampicillin cannot be assumed to be susceptible to
penicillin. If penicillin results are needed, testing of penicillin is required. Because ampicillin or penicillin resistance among enterococci due to βlactamase production is not reliably detected using routine disc or dilution methods, a direct, nitrocefin-based β-lactamase test is recommended
for blood and cerebrospinal fluid isolates. A positive β-lactamase test predicts resistance to penicillin, as well as amino-, carboxy- and ureido-penicillins. Certain penicillin- or ampicillin-resistant enterococci may possess high-level resistance (i.e., penicillin MICs ≥ 128 µg/mL or ampicillin
MICs ≥ 64 µg/mL). The disc test will not differentiate those with normal resistance from this high-level resistance. For enterococci recovered from
blood and CSF, the laboratory should consider determining the actual MIC for penicillin or ampicillin since enterococcal strains with normal
lower level resistance (penicillin MICs ≤ 64 µg/mL and ampicillin MICs ≤ 32 µg/mL) should be considered potentially susceptible to synergy with
an aminoglycoside (in the absence of high-level aminoglycoside resistance) whereas strains with higher level resistance may be resistant to such
synergy.6
oSynergy between ampicillin, penicillin or vancomycin and an aminoglycoside can be predicted for enterococci by using a high-level aminoglycoside
(gentamicin and streptomycin) screening test. Other aminoglycosides need not be tested because their activities against enterococci are not superior to
gentamicin and streptomycin.
pThe results of ampicillin susceptibility tests should be used to predict the activity of amoxicillin. The majority of isolates of H. influenzae that are
resistant to ampicillin and amoxicillin produce a TEM-type-β-lactamase. In most cases, a direct β-lactamase test can provide a rapid means of detecting
ampicillin and amoxicillin resistance.
qMay be reported for Acinetobacter spp. resistant to other agents.
r Not routinely reported on isolates from the urinary tract.
sSusceptibility and resistance to azithromycin, clarithromycin and dirithromycin can be predicted by using erythromycin.
tSee discussion of ESBLs under “RESULTS.” For screening and confirmatory tests for ESBLs in Klebsiella pneumoniae, K. oxytoca and E. coli, see
"RESULTS" section and reference 7. Screening breakpoints (Mueller Hinton agar, standard disc diffusion procedure, 35 ± 2ºC, ambient air,
16 – 18 h) are: aztreonam (≤ 27 mm), ceftazidime (≤ 22 mm), cefotaxime (≤ 27 mm), cefpodoxime (≤ 17 mm) and ceftriaxone (≤ 25 mm). Quality control
recommendations are E. coli ATCC 25922 (as listed in the chart); K. pneumoniae ATCC 700603 (aztreonam 9 – 17 mm), ceftazidime (10 – 18 mm), cefotaxime (17 – 25 mm), cefpodoxime (9 – 16 mm) and ceftriaxone (16 – 24 mm).7 The use of more than one antimicrobial agent for screening improves
the sensitivity of detection. Phenotypic confirmatory testing requires the use of both cefotaxime and ceftazidime, alone and in combination with clavulanic acid. A ≥ 5 mm zone diameter for either antimicrobial agent tested in combination with clavulanic acid versus its zone when tested alone = ESBL.
Quality Control recommendations are: negative strain E. coli ATCC 25922 which produces a ≤ 2 mm increase in zone diameter for antimicrobial agent
tested alone versus its zone diameter when tested in combination with clavulanic acid; positive strain K. pneumoniae ATCC 700603 which produces a
≥ 3 mm increase in cefotaxime zone diameter and a ≥ 5 mm increase in ceftazidime zone diameter. See "Limitations of the Procedure." See reference 7
for details of the procedure.
uCephalothin can be used to predict activity of cephalothin, cephapirin, cephradine, cephalexin, cefaclor and cefadroxil. Cefazolin, cefuroxime, cefpodoxime, cefprozil, and loracarbef (urinary isolates only) may be tested individually because some isolates may be susceptible to these agents when
resistant to cephalothin.
vNot applicable for testing Morganella spp.
wFor N. gonorrhoeae, an intermediate result for an antimicrobial agent indicates either a technical problem that should be resolved by repeat testing or
a lack of clinical experience in treating organisms with these zones. The latter seems to be the case for cefmetazole, cefotetan, cefoxitin, and spectinomycin. Strains with intermediate zones with the other agents have a documented lower clinical cure rate (85 - 95%) compared to >95% for susceptible
strains.
xCefotaxime, ceftizoxime or ceftriaxone should be tested and reported on isolates from CSF in place of cephalothin and cefazolin.
yBecause certain strains of Providencia spp. have been reported to give false-susceptible results with cefprozil discs, strains of this genus should not be
tested and reported with this disc.
zIndicated for urine isolates only. In addition to testing urine isolates, nalidixic acid may be used to test for reduced fluoroquinolone susceptibility in
isolates from patients with extraintestinal Salmonella infections. See footnote ddd.
aa FDA-approved zone diameters for interpretive and/or quality control criteria that differ from CLSI recommendations.
bb For V. cholerae, use with caution as the disc diffusion test may misclassify many organisms (higher minor error rate).
cc
No criteria have been established to support testing of this drug with Streptococcus pneumoniae. The control range is listed for quality control purposes only.
dd Colistin and polymyxin B diffuse poorly in agar and the accuracy of the diffusion method is thus less than with other antibiotics. Resistance is always
significant, but when treatment of systemic infections due to susceptible strains is considered, it is wise to confirm the results of a diffusion test with a
dilution method.
ee Organisms that are susceptible to tetracycline are also considered susceptible to doxycycline and minocycline. However, some organisms that are intermediate or resistant to tetracycline may be susceptible to doxycycline or minocycline or both.
ff
FDA-approved for S. saprophyticus and S. epidermidis (not S. aureus).
gg For control limits of gentamicin 120 µg and streptomycin 300 µg discs, use E. faecalis ATCC 29212 (gentamicin: 16 - 23ii mm; streptomycin:
14 - 20ii mm).
hh If the zone is 7 - 9 mm, the test is inconclusive and an agar dilution or broth microdilution screen test should be performed to confirm resistance.
ii
CLSI-recommended zone sizes that differ from FDA-approved zone size recommendations.
jj
No criteria have been established to support testing of this drug with H. influenzae. The control range is listed for quality control purposes only.
kk Because certain strains of Citrobacter, Providencia, and Enterobacter spp. have been reported to give false susceptible results with cefdinir and loracarbef discs, strains of these genera should not be tested and reported with these discs.
ll
FDA-approved for K. pneumoniae.
mm No criteria have been established to support testing of this drug with Pseudomonas aeruginosa. The control range is listed for quality control purposes
only.
nn If a penicillinase-stable penicillin is tested, oxacillin is the preferred agent and results can be applied to the other penicillinase-stable penicillins, cloxacillin, dicloxacillin, flucloxacillin, methicillin and nafcillin. Oxacillin is preferred because it is more resistant to degradation in storage, and because it is
more likely to detect heteroresistant staphylococcal strains. Cloxacillin discs should not be used because they may not detect oxacillin-resistant S. aureus.
Cefoxitin may be tested instead of oxacillin (see M100-S21). After incubation for a full 24 h, examine for light growth within the zone of inhibition of
the oxacillin disc using transmitted light (plate held up to light). Any discernable growth within the zone of inhibition is indicative of oxacillin resistance.
oo If oxacillin intermediate results are obtained for S. aureus, perform testing for mecA or PBP 2a, the cefoxitin disc test, an oxacillin MIC test or the oxacillin-salt agar screening test. Report the result of the alternative test rather than the intermediate result.
pp Penicillin-resistant, oxacillin-susceptible strains of Staphylococcus aureus produce β-lactamase and the testing of the 10-unit penicillin disc instead of the
ampicillin disc is preferred. Penicillin should be used to test the susceptibility of all β-lactamase-labile penicillins, such as ampicillin, amoxicillin, azlocillin, carbenicillin, mezlocillin, piperacillin, and ticarcillin. Likewise, a positive β-lactamase test predicts resistance to these agents.6 For oxacillin-resistant
staphylococci, report as resistant or do not report.
qq A positive β-lactamase test predicts resistance to penicillin, ampicillin, and amoxacillin. A β-lactamase test will detect one form of penicillin resistance
in N. gonorrhoeae and also may be used to provide epidemiologic information. Strains with chromosomally-mediated resistance can be detected only
by additional susceptibility testing, such as the disc diffusion method or the agar dilution MIC method. Gonococci with 10-unit penicillin disc zone
diameters of ≤19 mm are likely to be β-lactamase-producing strains. However, the β-lactamase test remains preferable to other susceptibility methods
for rapid, accurate recognition of this plasmid-mediated penicillin resistance.
rr
Susceptibility tests on S. pyogenes to penicillin are seldom necessary since this microorganism has continued to be universally susceptible to penicillin.
However, some strains of S. agalactiae may give penicillin-intermediate results.7
ss
Tigecycline has decreased in vitro activity against Morganella spp., Proteus spp. and Providencia spp.
tt
The sulfisoxazole disc can be used to represent any of the currently available sulfonamides. Blood-containing media (except for lysed horse blood) are
generally not suitable for testing sulfonamides or trimethoprim. Mueller Hinton agar should be as thymidine-free as possible for sulfonamide and/or
trimethoprim testing. To determine whether the Mueller Hinton agar has sufficiently low levels of thymine and thymidine, Enterococcus faecalis ATCC
29212 or ATCC 33186 may be tested with the trimethoprim-sulfamethoxazole disc (see ref. 13). An inhibition zone of ≥ 20 mm that is essentially free of
fine colonies indicates a sufficiently low level of thymine and thymidine.6
uu Gonococci with 30-µg tetracycline disc zone diameters of ≤ 19 mm usually indicate a plasmid-mediated tetracycline-resistant N. gonorrhoeae (TRNG)
isolate. These strains should be confirmed by a dilution test (MIC ≥ 16 µg/mL) and/or referred to a public health laboratory for epidemiologic investigation.
vv All staphylococcal isolates with vancomycin zone diameters of 14 mm or less should be tested by a reference MIC method. The disc diffusion procedure
will not differentiate strains with reduced susceptibility to vancomycin (MICs 4 to 8 µg/mL) from susceptible strains (MICs 0.5 to 2 µg/mL) even when
incubated 24 h. Additionally, vancomycin-resistant S. aureus (VRSA) strains (MICs ≥ 16 µg/mL) may produce only subtle growth around a vancomycin
disc. The vancomycin agar screen test described for enterococci (Brain Heart Infusion Agar with 6 µg/mL Vancomycin) may be used to enhance the
sensitivity of detecting vancomycin-intermediate and vancomycin-resistant strains of S. aureus incubating the plates for a full 24 h at 35°C.6 Use of a susceptible quality control strain, such as E. faecalis ATCC 29212 is critical to ensure specificity. E. faecalis ATCC 51299 may be used as a positive (i.e., resistant) control. Until further data on the prevalence or clinical significance of these isolates is known, laboratories may choose to examine MRSA strains
more carefully for elevated MICs to vancomycin.6 Currently, there are insufficient data to recommend using this agar screen test for coagulase-negative
staphylococci. Send any staphylococci determined to have an elevated MIC to vancomycin (≥ 4 µg/mL) to a reference laboratory.
ww When testing vancomycin against enterococci, plates should be held a full 24 h and examined using transmitted light; the presence of a haze or any
growth within the zone of inhibition indicates resistance. Organisms with intermediate zones should be tested by an MIC method as described in CLSI
document M7. See also the vancomycin agar screen test described in the MIC Table 2D (M100-S21).9
xx No S. pneumoniae strain with a vancomycin zone diameter of inhibition <17 mm has been observed; submit such strains to a reference laboratory.7
yy Because of limited alternatives, chloramphenicol, erythromycin, tetracycline (or doxycyline or minocycline) and rifampin may be used for vancomycinresistant enterococci (VRE) and consultation with an infectious disease practitioner is recommended.7
zz No criteria have been established to support testing of this drug with N. gonorrhoeae. The control range is listed for quality control purposes only.
aaa Strains of β-hemolytic streptococci with ampicillin, cefepime, cefotaxime, ceftriaxone or penicillin zone diameters of less than 24 mm have not been
observed; submit such strains to a reference laboratory.
bbb Deterioration in oxacillin disc content is best assessed with S. aureus ATCC 25923, with an acceptable zone diameter of 18 - 24 mm.
ccc For ampicillin, cefepime, cefotaxime, ceftriaxone and penicillin, Streptococci, b
β -hemolytic only includes the large-colony-forming pyogenic strains of
streptococci with group A (S. pyogenes), C or G antigens and strains with group B (S. agalactiae) antigen. For cefepime, cefotaxime and ceftriaxone,
Viridans Streptococci includes small-colony-forming β-hemolytic strains with group A, C, F or G antigens (S. anginosus, previously termed S. milleri) as
well as S. mitis, S. oralis, S. sanguis, S. salivarius, S. intermedius, S. constellatus, S. mutans and S. bovis.
ddd Fluoroquinolone-susceptible strains of Salmonella that test resistant to nalidixic acid may be associated with clinical failure or delayed response in
fluoroquinolone-treated patients with extraintestinal salmonellosis. Extraintestinal isolates of Salmonella should also be tested for resistance to nalidixic
acid. For isolates that test susceptible to fluoroquinolones and resistant to nalidixic acid, the physician should be informed that the isolate may not be
eradicated by fluoroquinolone treatment. A consultation with an infectious disease practitioner is recommended.
eee No criteria have been established to support testing of this drug with S. aureus. The control range is listed for quality control purposes only.
RESUME ET EXPLICATION – Les méthodes de diffusion en gélose utilisant des disques en papier filtre séchés contenant des concentrations
déterminées en agents antimicrobiens ont été mises au point au cours des années 40. Afin d’éliminer ou de minimiser la variabilité inhérente à ce
type de test, Bauer et al. ont mis au point une procédure standardisée dans laquelle la gélose Mueller Hinton était le milieu choisi pour le test.1,2
Divers organismes de réglementation et de rédaction des normes ont ensuite publié des procédures standardisées de référence en se basant sur la
méthode Bauer-Kirby. Les normes de la Food and Drug Administration (FDA)3 américaine et de l’Organisation mondiale de la santé (OMS)4,5 figurent
parmi les procédures standardisées les plus anciennes et les plus suivies. La procédure a été adoptée comme norme consensuelle par le Clinical and
Laboratory Standards Institute (CLSI, anciennement NCCLS) et fait l’objet de mises à jour périodiques.6,7 Les documents du CLSI les plus récents
doivent être consultés pour prendre connaissance des recommandations actuelles.
PRINCIPES DE LA METHODE – Des disques contenant toute une gamme d’agents antimicrobiens sont déposés sur la surface de la gélose Mueller
Hinton (ou de la gélose du test d’identification d’Haemophilus pour H. influenzae, de la gélose GC II enrichie d’IsoVitaleX pour N. gonorrhoeae ou
de la gélose Mueller Hinton avec 5 % de sang de mouton pour S. pneumoniae, les streptocoques b hémolytiques et du groupe viridans) dans des
boî tes de Pétri ensemencées avec des cultures pures d’isolats cliniques. Après incubation, les boî tes de Pétri sont examinées et les zones d’inhibition
entourant les disques sont mesurées et comparées aux gammes de taille de zone établies pour les différents agents antimicrobiens afin de
déterminer l’agent ou les agents les plus adéquats pour le traitement antimicrobien.
REACTIFS – Les disques Sensi-Disc sont des disques de 6 mm fabriqués à partir de papier absorbant de haute qualité imprégné d’antibiotiques ou
d’autres agents chimiothérapeutiques en quantités déterminées de manière précise. Les disques sont clairement identifiés des deux côtés par des
lettres et des chiffres désignant l’agent et sa concentration. (Voir le tableau des concentrations des composants actifs.) La teneur en agent des
disques est mesurée par les méthodes définies par la FDA ou par des méthodes similaires ou comparables à celles publiées dans le Federal Register
américain.
4
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Sensi-Disc™ Antimicrobial Susceptibility
 BBL
Test™Discs
English:
Français :
pages
pages
1–4
4–7
Deutsch:
Italiano:
Seiten
pagine
7–9
9 – 11
Español:
Português
páginas
páginas
11 – 13
13 – 16
8840621
2011/07
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INTENDED USE – These discs are used for semi-quantitative in vitro susceptibility testing by the agar disc diffusion test procedure of common, rapidly growing and certain fastidious bacterial pathogens. These include the Enterobacteriaceae, Staphylococcus spp., Pseudomonas
spp., Acinetobacter spp., Enterococcus spp., Vibrio cholerae and, by modified procedures, Haemophilus influenzae, Neisseria gonorrhoeae,
Streptococcus pneumoniae and other streptococci. NOTE: Special procedures are required for testing pneumococci, enterococci and methicillin/oxacillin-resistant staphylococci, for performing β-lactamase tests and for screening and confirmatory tests for ESBLs; see the “RESULTS”
section.
For zone diameter interpretive criteria adopted in France, refer to the instructions in the French language section of this insert.
SUMMARY AND EXPLANATION – Agar diffusion methods employing dried filter paper discs impregnated with specific concentrations of antimicrobial agents were developed in the 1940s. In order to eliminate or minimize variability in this testing, Bauer et al. developed a standardized procedure in which Mueller Hinton Agar was selected as the test medium.1,2
Various regulatory agencies and standards-writing organizations subsequently published standardized reference procedures based on the
Bauer-Kirby method. Among the earliest and most widely accepted of these standardized procedures were those published by the U.S. Food
and Drug Administration (FDA)3 and the World Health Organization (WHO).4,5 The procedure was adopted as a consensus standard by the
Clinical and Laboratory Standards Institute (CLSI, formerly NCCLS) and is periodically updated.6,7 The latest CLSI documents should be consulted for current recommendations.
PRINCIPLES OF THE PROCEDURE – Discs containing a wide variety of antimicrobial agents are applied to the surface of Mueller Hinton Agar
plates (or Haemophilus Test Medium Agar for H. influenzae, GC II Agar with IsoVitaleX™ Enrichment for N. gonorrhoeae or Mueller Hinton
Agar with 5% Sheep Blood for S. pneumoniae, β-hemolytic and viridans group streptococci) that have been inoculated with pure cultures of
clinical isolates. Following incubation, the plates are examined and the zones of inhibition surrounding the discs are measured and compared
with established zone size ranges for individual antimicrobial agents in order to determine the agent(s) most suitable for use in antimicrobial
therapy.
REAGENTS – Sensi-Disc™ brand discs are 6-mm discs prepared by impregnating high quality absorbent paper with accurately determined
amounts of antibiotic or other chemotherapeutic agents. Discs are clearly marked on both sides with letters and numbers designating the
agent and the drug content. (See chart giving concentrations of reactive ingredients.) The drug content of discs is assayed by the methods
established by the FDA or by methods similar or comparable to those published in the United States Federal Register.
Sensi-Disc agents are furnished in cartridges containing 50 discs each. The last disc in each cartridge is marked “X” and contains the drug as
coded. Cartridges are for use in BBL™ Sensi-Disc™ Dispensers; these include a Single Disc Dispenser, an 8-Place Dispenser for 100 mm-style
Petri dishes, 6- and 8-Place Self-Tamping Dispensers for 100 mm-style dishes and a Self-Tamping 12-Place Dispenser for 150 mm-style plates.
Warnings and Precautions: For in vitro Diagnostic Use.
Follow directions for use; disc performance depends not only on disc potency, but on use of proper inoculum and control cultures, functional
pretested plates, proper storage temperature and other factors.
Observe aseptic techniques and established precautions against microbiological hazards throughout all procedures. Sterilize cultures, containers and other contaminated materials after use.
Storage Instructions:
1. On receipt, store discs at -20 – +8°C. If the laboratory refrigerator is frequently opened and closed, and a suitable temperature is not maintained, place there a supply sufficient only for use within a week. Some discs (e.g., β-lactams) should preferably be kept frozen at -20°C.
2. Allow containers to come to room temperature before opening. Return unused discs to the refrigerator when application of discs has
been completed. Once opened, discs should be placed in a tightly sealed, desiccated container for storage.
3. Use the oldest discs first.
4. Discard expired discs. Also, cartridges from which discs have been frequently removed during a week and discs left out overnight in the
laboratory should be discarded, or else the discs should be tested for acceptable performance prior to continued use.
5. If the discs form incorrect zones with the recommended control organisms, the entire procedure should be checked; faulty zone size may
be due to the disc, the inoculation, the preparation or depth (about 4 mm) of medium, or other factors.
The expiration date applies only to discs in intact containers, stored as directed.
SPECIMENS – Specimens should not ordinarily be employed in this test. See Directions, which include preparation of inoculum. If possible,
cultures should be derived from specimens obtained from patients prior to the initiation of antimicrobial therapy.
PROCEDURE
Material Provided: Sensi-Disc™ susceptibility test discs as labeled.
Materials Required But Not Provided: Ancillary culture media, reagents, quality control organisms and laboratory equipment required to
perform disc diffusion susceptibility testing by the standardized procedure. Prepare a 0.5 McFarland turbidity standard by adding 0.5 mL of
0.048 M BaCl2 [1.175% (wt/vol) BaCl2•2H2O] to 99.5 mL of 0.18 M [0.36N] H2SO4 [1% (vol/vol)]. Verify by using a spectrophotometer with a
1-cm light path and matched cuvette; absorbance at 625 nm should be 0.08 – 0.13.
Directions, Including User Controls:6
1. Preparation of inoculum with test and control cultures.
a. Perform a Gram stain. Use only pure cultures.
b. Select three to five similar colonies and transfer with inoculation needle or loop into 4 – 5 mL of a suitable broth such as Trypticase™ Soy
Broth (or Mueller Hinton Broth for fastidious organisms).
c. Incubate the broth cultures at 35°C for 2 – 6 h, if necessary, to develop a turbidity equivalent to the 0.5 McFarland turbidity standard
(approximately 1 to 2 x 108 CFU/mL). Alternatively, make a direct broth or saline suspension of colonies selected from an agar plate incubated overnight (a nonselective medium such as blood agar, or chocolate agar for H. influenzae and N. gonorrhoeae, should be used).
The direct colony suspension method is preferred for Staphylococcus spp., S. pneumoniae and other streptococci, Haemophilus spp. and
N. gonorrhoeae.6
d. Dilute, if required, to obtain turbidity equivalent to the 0.5 McFarland turbidity standard. For diluent, use sterile broth or saline.
Alternatively, standardize the inoculum photometrically; to facilitate inoculum adjustment of rapidly growing organisms, the Prompt™
Inoculation System (volumetric inoculum preparation device) may be used.8
Overnight broth cultures should not be used as inoculum.
2. Inoculation.
a. Within 15 min, dip a sterile cotton swab into the properly adjusted inoculum and rotate it firmly several times against the upper inside
wall of the tube to express excess fluid.
b. Streak the entire agar surface of a Mueller Hinton Agar (or other appropriate agar) plate three times, turning the plate 60° between
streakings to obtain even inoculation.
c. The lid may be left ajar for 3 – 5 min, but no more than 15 min, to allow for any surface moisture to be absorbed before applying the
drug-impregnated discs.
3. Select appropriate discs (such as recommended in reference 7, Tables 1A and 1B of M100 [M2]).
4. Apply the discs by means of a BBL™ dispenser, using aseptic precautions. Deposit discs so that the centers are at least 24 mm apart. It is
preferable to deposit penicillin and cephalosporin discs so that they are no less than 10 mm from the edge of the Petri dish, and their centers are at least 30 mm apart. Avoid placing such discs adjacent to one another. With H. influenzae, N. gonorrhoeae and S. pneumoniae, use
no more than nine discs per 150 mm plate or four discs per 100 mm plate. If discs have been placed on the agar with other than the SelfTamping Dispensers, press them down with a sterile needle or forceps to make contact with the surface.
5. Within 15 min, place the plates agar side up in a 35 ± 2°C incubator (for Staphylococcus spp., testing at temperatures above 35°C may not
detect methicillin-resistant staphylococci (MRS); for N. gonorrhoeae, incubate at 36 ± 1°C [do not exceed 37°C]). Haemophilus spp., N. gonorrhoeae, S. pneumoniae and other streptococci should be incubated in an atmosphere enriched with 5% CO2.
6. Examine the plates after 16 – 18 h of incubation (20 – 24 h for N. gonorrhoeae, S. pneumoniae and other streptococci). A full 24 h of incubation is recommended for Staphylococcus spp. to detect methicillin/nafcillin/oxacillin/vancomycin-resistant staphylococci and Enterococcus
spp. for vancomycin resistance. The diameters of the zones of complete inhibition are measured, as determined by gross visual inspection.
Zones are measured to the nearest whole millimeter. For further details in measuring zones of inhibition, consult the reference.6 If only
isolated colonies grow, the inoculum is too light and the test should be repeated. Zones around discs containing different drugs are not
comparable for the purpose of comparing activity of drugs. See the Zone Diameter Interpretive Chart, which gives expected values from
testing common aerobes. Zone measurement may be simplified by using a BBL™ Sensi-Disc™ Zone Interpretation Set.
7. Control tests using prescribed cultures should be included each day susceptibility testing is performed or weekly if satisfactory performance can
be documented according to the CLSI standard.6 Typical zone sizes of E. coli ATCC™ 25922, S. aureus ATCC 25923, P. aeruginosa ATCC 27853,
H. influenzae ATCC 49247, H. influenzae ATCC 49766, N. gonorrhoeae ATCC 49226, S. pneumoniae ATCC 49619, E. coli ATCC 35218 (β-lactamaseproducing strain), E. faecalis ATCC 29212 (for quality control testing of gentamicin 120 µg and streptomycin 300 µg discs) and Klebsiella pneumoniae ATCC 700603 (for screening and confirmatory tests for ESBLs) are given in the chart (or footnotes) and indicate the correct performance of
the entire procedure. E. faecalis ATCC 29212 (or 33186) is also recommended for evaluating new lots of Mueller Hinton Agar for low thymine and
thymidine content (see footnote tt). H. influenzae ATCC 10211 is recommended as a useful additional quality control strain to verify the growth
promotion properties of Haemophilus Test Medium Agar.7
RESULTS 6,7 – NOTE: Recommended interpretive criteria are based on usual dosage regimens and routes of administration in the U.S.
Beginning in 2006, CLSI established zone diameter interpretive ranges for Neisseria meningitidis, Burkholderia cepacia and Stenotrophomonas
maltophilia. For these ranges, consult CLSI M100-S217 or the latest M100 supplement available. In addition, CLSI guideline M45 – Methods for
Antimicrobial Dilution and Disk Susceptibility Testing of Infrequently Isolated or Fastidious Bacteria – can be consulted to obtain information for testing a variety of organisms including Campylobacter, Corynebacterium spp., Bacillus spp., etc.9 For organisms not found in the accompanying table, or
the references mentioned, studies are not yet adequate to develop reproducible definitive standards for interpretation of results. If necessary, a dilution method usually will be the most appropriate testing method, which may require submitting the organism to a reference laboratory.
In some instances, CLSI has implemented new zone diameter ranges for interpretive or quality control criteria. When this has occurred, footnote
“aa” has been added indicating that the FDA-approved zone diameters provided differ from the current CLSI recommendations.
Compare recorded zone diameters with those in the chart; results with a specific organism may be reported as Resistant, Intermediate or Susceptible.
For some organism/antimicrobial agent combinations, the absence or rare occurrence of resistant strains precludes defining any results categories
other than “Susceptible.” For strains yielding results suggestive of a “nonsusceptible” category, organism identification and antimicrobial susceptibility test results should be confirmed. Subsequently, the isolates should be saved and submitted to a reference laboratory that will confirm results
using a CLSI reference dilution method.6
A rapid b-lactamase test (e.g., using Cefinase™ discs) may yield clinically relevant information earlier than results of a disc diffusion test with
Haemophilus spp., N. gonorrhoeae and Moraxella catarrhalis; it is the only reliable test for detecting b-lactamase-producing Enterococcus spp. A
positive b-lactamase test predicts resistance to penicillin, ampicillin and amoxicillin among Haemophilus spp., N. gonorrhoeae and M. catarrhalis and
resistance to penicillin, including amino-, carboxy- and ureido-penicillins among staphylococci and enterococci. A negative b-lactamase test does not
rule out resistance due to other mechanisms. Do not test members of the Enterobacteriaceae, Pseudomonas spp. and other aerobic gram-negative
bacilli because the results may not be predictive of susceptibility to the b-lactams most often used for therapy. Accurate detection of b-lactamase in
staphylococci may require induction of the enzyme and incubation of a nitrocefin-based test for up to 1 h. Induction can be easily accomplished by
testing the growth from the zone margin surrounding an oxacillin disc test. Care must be exercised to ensure accurate results, including testing of
known positive and negative control strains at the time clinical isolates are examined.6
Enterobacteriaceae: When fecal isolates of Salmonella and Shigella spp. are tested, only ampicillin, a quinolone and trimethoprim/sulfamethoxazole
should be reported routinely. In addition, chloramphenicol and a third generation cephalosporin should be tested and reported for extraintestinal
isolates of Salmonella spp. For Salmonella and Shigella spp., aminoglycosides and first and second generation cephalosporins and cephamycins may
appear active in vitro but are not effective clinically and should not be reported as susceptible.7
Enterobacter, Citrobacter, and Serratia may develop resistance during prolonged therapy with third generation cephalosporins. Therefore, isolates
that are initially susceptible may become resistant within 3 to 4 days after initiation of therapy. Testing of repeat isolates may be warranted.7
Extended-spectrum b-lactamases (ESBLs) are enzymes produced by gram-negative bacilli that arise by mutation in genes for common plasmid-mediated b-lactamases. Strains of Klebsiella spp. and E. coli that produce ESBLs may be clinically resistant to therapy with penicillins, cephalosporins, or
aztreonam, despite apparent in vitro susceptibility to some of these agents. Some of these strains will show zones of inhibition below the normal
susceptible population but above the standard breakpoints for certain extended-spectrum cephalosporins or aztreonam; such strains should be
screened for potential ESBL production by using the ESBL screening breakpoints before reporting results for penicillins, extended-spectrum cephalosporins or aztreonam. Other strains may test intermediate or resistant by standard breakpoints to one or more of these agents. In all strains with
ESBLs the zone diameters for one or more of the extended-spectrum cephalosporins or aztreonam should increase in the presence of clavulanic acid
as determined in phenotypic confirmatory testing. For all confirmed ESBL-producing strains, the test interpretation should be reported as resistant
for all penicillins, cephalosporins, and aztreonam. See footnote t for ESBL screening and confirmatory tests. The decision to perform ESBL screening
tests on all urine isolates should be made on an institutional basis, considering prevalence, therapy and infection control issues.7 To screen Proteus
mirabilis for ESBL production, see M100.7
Non-Enterobacteriaceae: Non-Enterobacteriaceae other than P. aeruginosa, Acinetobacter spp., B. cepacia and S. maltophilia should be tested by the
dilution method (see M710). For B. cepacia and S. maltophilia, consult CLSI M100-S21 for zone diameter interpretative standards and quality control.
P. aeruginosa may develop resistance during prolonged therapy with all antibiotics. Isolates that are initially susceptible may become resistant within
3 to 4 days after initiation of therapy and testing of repeat isolates may be warranted.7
The susceptibility of Pseudomonas aeruginosa isolated from patients with cystic fibrosis can be reliably determined by the disc method, but may
require extended incubation up to 24 h before reporting as susceptible.7
Staphylococcus spp.: Staphylococcus spp. may develop resistance during prolonged therapy with quinolones. Therefore, isolates that are initially
susceptible may become resistant within 3 to 4 days after initiation of therapy. Testing of repeat isolates may be warranted.7
Methods for the detection of methicillin-resistant staphylococci include the oxacillin disc test, the cefoxitin disc test and tests for mecA or the protein
encoded by mecA, the penicillin-binding protein 2a (PBP 2a, also called PBP 2′). In the past, the presence of resistance to other classes of agents was
an indication of methicillin (oxacillin) resistance. However, some methicillin-resistant S. aureus (MRSA), such as those found in community-associated
infections, are not multiply-resistant.6
MRSA and methicillin-resistant, coagulase-negative staphylococci should be reported as resistant (or not reported) to all other penicillins, carbapenems, cephems, and b-lactam/b-lactamase inhibitor combinations, regardless of in vitro test results with those agents. This is because most cases of
documented methicillin-resistant infections have responded poorly to b-lactam therapy, and convincing clinical data have yet to be presented that
document clinical efficacy for b-lactams versus MRS. For oxacillin-susceptible S. aureus and coagulase-negative staphylococci, results for parenteral
and oral cephems, b-lactam/b-lactamase inhibitor combinations, and carbapenems, if tested, should be reported according to the results generated
using routine interpretive criteria. For oxacillin-resistant S. aureus and coagulase-negative staphylococci (MRS), other b-lactam agents; i.e., penicillins,
b-lactam/b-lactamase inhibitor combinations, cephems, and carbapenems, may appear active in vitro, but are not effective clinically. Results for these
drugs should be reported as resistant or should not be reported. This is because most cases of documented MRS infections have responded poorly
to b-lactam therapy, or because convincing clinical data have yet to be presented that document clinical efficacy for those agents. Routine testing of
urine isolates of S. saprophyticus is not advised, because infections respond to concentrations achieved in urine of antimicrobial agents commonly
used to treat acute, uncomplicated urinary tract infections (e.g., nitrofurantoin, trimethoprim/sulfamethoxazole or a fluoroquinolone).6,7
To obtain information on predicting mecA-mediated resistance in Staphylococcus spp. using cefoxitin (30 µg), consult CLSI M100-S21.
Similarly, to obtain information on testing Staphylococcus spp. for inducible clindamycin resistance consult M100-S21.
Enterococcus spp.: Enterococci may be resistant to penicillin and ampicillin because of the production of low-affinity, penicillin-binding proteins
(PBPs), or the production of b-lactamase. The disc diffusion test can accurately detect isolates with altered PBPs, but it will not reliably detect b-lactamase producing strains. The latter strains are best detected by using a direct b-lactamase test;6 e.g., with Cefinase nitrocefin discs or chromogenic
cephalosporin discs.
For Enterococcus spp., cephalosporins, aminoglycosides (except for high level resistance screening), clindamycin and trimethoprim/sulfamethoxazole
may appear active in vitro but are not effective clinically and isolates should not be reported as susceptible.
Haemophilus spp.: Only results of testing with ampicillin, one of the third-generation cephalosporins, chloramphenicol and meropenem should be
reported routinely with cerebrospinal fluid isolates of H. influenzae.
Amoxicillin/clavulanic acid, azithromycin, clarithromycin, cefaclor, cefprozil, loracarbef, cefdinir, cefixime, cefpodoxime, cefuroxime axetil and telithromycin are oral agents that may be used as empiric therapy for respiratory tract infections due to Haemophilus spp. The results of susceptibility tests
with these antimicrobial agents are often not useful for management of individual patients. However, susceptibility testing of Haemophilus spp.
with these compounds may be appropriate for surveillance or epidemiologic studies.
Streptococcus spp. other than S. pneumoniae: Susceptibility testing of penicillins and other b-lactams approved by the U.S. Food and Drug
Administration for treatment of S. pyogenes or S. agalactiae is not necessary for clinical purposes and need not be done routinely, since as with vancomycin, resistant strains have not been recognized. Interpretive criteria are provided for pharmaceutical development, epidemiology or monitoring
for emerging resistance. Any strain found to be intermediate or resistant should be referred to a reference laboratory for confirmation.
To obtain information on testing β-hemolytic streptococci for inducible clindamycin resistance consult M100-S21.7
LIMITATIONS OF THE PROCEDURE
1. The test as herein described applies primarily to rapidly growing aerobic pathogens. For fastidious bacteria other than H. influenzae,
N. gonorrhoeae, S. pneumoniae and other streptococci, consult M100 (N. meningitidis) or M45.7,13 Otherwise, test by the dilution method.
Testing of anaerobes requires special procedures.11
2. The classifications of Resistant, Intermediate and Susceptible vary only by one millimeter, which is within normal laboratory error. Some
cultures may give a borderline zone that varies from day to day or from laboratory to laboratory; such cultures are relatively uncommon.
3. For detecting pneumococcal and enterococcal resistance, strictly adhere to CLSI recommended methods.6
4. Antimicrobial agents other than those listed in the Chart may be in current use. Susceptibility tests employing these agents should be interpreted
on the basis of presence or absence of a definite zone of inhibition and should be considered as only qualitative until such time as interpretive
zones have been established. All zone diameters should be recorded.
5. ESBL confirmatory testing is only valid when the four discs (cefotaxime, cefotaxime/clavulanic acid, ceftazidime, ceftazidime/clavulanic acid) are
used simultaneously. Individual usage of these discs is not recommended by CLSI.6,7
6. Accurate results are a function of the correct storage and maintenance of quality control organisms. This is especially true for E. coli ATCC 35218
and K. pneumoniae ATCC 700603, because spontaneous loss of the plasmid encoding the β-lactamase has been documented. Refer to CLSI standard M2 for recommendations on the correct storage and maintenance of quality control organisms.6
7. The ability to detect vancomycin-resistant Staphylococcus aureus (VRSA) with this product is unknown. Additional testing methods as recommended by the Centers for Disease Control and Prevention (CDC) should be used when performing susceptibility testing on S. aureus isolates,
particularly methicillin-resistant S. aureus (MRSA). These tests include nonautomated MIC methods (e.g., broth microdilution or agar dilution) and
a vancomycin agar screen test (Brain Heart Infusion Agar with 6 µg/mL of vancomycin). These methods require a full 24 h of incubation to detect
VRSA. For additional information, refer to the CDC web site.12
REFERENCES
1. Bauer, A.W., W.M.M. Kirby, J.C. Sherris, and M. Turck. 1966. Antibiotic susceptibility testing by a standardized single disk method. Am. J. Clin.
Pathol. 45:493-496.
2. Ryan, K.J., F.D. Schoenknecht, and W.M.M. Kirby. 1970. Disc sensitivity testing. Hospital Practice 5:91-100.
3. Federal Register. 1972. Rules and regulations. Antibiotic susceptibility discs. Fed. Regist. 37:20525-20529. Erratum, 38:2756, 1973.
4. Ericsson, H.M., and J.C. Sherris. 1971. Antibiotic sensitivity testing. Report of an international collaborative study. Acta Pathol. Microbiol. Scand. Sec.
B. Suppl. 217:1-90.
5. World Health Organization Expert Committee on Biological Standardization. 1977. Technical report series 610. W.H.O., Geneva.
6. Clinical and Laboratory Standards Institute. 2009. Approved standard M2-A10. Performance standards for antimicrobial disk susceptibility tests, 10th ed.
CLSI, Wayne, Pa.
7. Clinical and Laboratory Standards Institute. 2011. M100-S21 (M2). Disk Diffusion Supplemental Tables, CLSI, Wayne Pa.
8. Baker, C.N., C. Thornsberry, and R.W. Hawkinson. 1983. Inoculum standardization in antimicrobial susceptibility testing: evaluation of overnight
agar cultures and the rapid inoculum standardization system. J. Clin. Microbiol. 17:450-457.
9. Clinical and Laboratory Standards Institute. 2010. Approved guideline M45-A2. Methods for antimicrobial dilution and disk susceptibility testing of
infrequently isolated or fastidious bacteria. 2nd ed., CLSI, Wayne, Pa.
10. Clinical and Laboratory Standards Institute. 2009. Approved standard M7-A8. Methods for dilution antimicrobial susceptibility tests for bacteria that
grow aerobically, 8th ed. CLSI, Wayne, Pa.
11. Clinical and Laboratory Standards Institute. 2007. Approved standard M11-A7. Methods for antimicrobial susceptibility testing of anaerobic bacteria,
7th ed. CLSI, Wayne, Pa.
12. Centers for Disease Control and Prevention. www.cdc.gov/ncidod/dhqp/ar_visavrsa_labFAQ.html
13. Bushby, S.R.M. 1973. Trimethoprim-sulfamethoxazole: in vitro microbiological aspects, p. 10-30. In M. Finland and E.H. Kass (ed.), Trimethoprim-sulfamethoxazole: microbiological, pharmacological, and clinical considerations. University of Chicago Press, Chicago.
Zone Diameter Interpretive Chart †
Antimicrobial
Agent
Disc
Potency
Code
Zone Diameter
Control Zone
Interpretive Standards (mm)
Diameter Limits (mm)
E.
S.
P.
H.
H.
coli
aureus aeruginosa influenzae influenzae
ResisInter- SuscepATCC
ATCC
ATCC
ATCC
ATCC
tant mediate a tible b
49766 c
25922
25923
27853
49247 c
AMD-10 10 µg
Amdinocillin f
Enterobacteriaceae
≤15 —
≥16
23 – 29
—
—
Amikacin
AN-30 30 µg
Enterobacteriaceae, P. aeruginosa,
Acinetobacter and staphylococci
≤14
15 – 16
≥17
19 – 26
20 – 26
18 – 26
Ampicillin/
SAM-20
10/10 µg
19 – 24g,ii 29 – 37
—
Sulbactam g,h,i
Enterobacteriaceae, P. aeruginosa,
Acinetobacter q and staphylococci j
≤11
12 – 14ii ≥15ii
Haemophilus spp. c,k
≤19 —
≥20
N.
S.
gonorrhoeae pneumoniae
ATCC
ATCC
49226 d
49619 e
—
—
Carbenicillin
CB-100
100 µg
23 – 29
—
18 – 24
Enterobacteriaceae and Acinetobacter
≤19ii 20 – 22ii ≥23
P. aeruginosa
≤13
14 – 16
≥17
CEC-30 30 µg
23 – 27 27 – 31
—
Cefaclor h,i
Enterobacteriaceae u and staphylococci j
≤14
15 – 17
≥18
c,k
Haemophilus spp.
≤16
17 – 19
≥20
Cefamandole
MA-30 30 µg
Enterobacteriaceae and staphylococci j
≤14
15 – 17
≥18
26 – 32
26 – 34
—
14 –22c
30 – 36e
—
30 – 38c
—
—
25 – 31c
—
24 – 31c
— —
Streptococci (non-S. pneumoniae, β-hemolytic
≥24ii
only)aaa,ccc
CFM-5
5 µg
23 – 27
—
—
Cefixime h
Enterobacteriaceae v
≤15
16 –18
≥19
c
Haemophilus spp.
— —
≥21
25 – 33c
—
— —
N. gonorrhoeae d
≥31
37 – 45d
Cefmetazole
CMZ-30 30 µg
26 – 32 25 – 34
—
Enterobacteriaceae and staphylococci j
≤12
13 – 15
≥16
N. gonorrhoeae d
≤27
28 – 32w ≥33
31 – 36d
28 – 35e
Cefonicid
CID-30 30 µg
25 – 29 22 – 28
—
Enterobacteriaceae and staphylococci j
≤14
15 – 17
≥18
Haemoph
—
C
op
on
A
o
m
X
A
H m
N
V
C
o
n
n
OX
podo m
H
N
D
H
w
w
dm
A
C
C
dm
u n A d
C
bu
H
A
H m
N
n
A
— —
— —
o m
OX
A
H m
N
C
on
—
—
—
— —
—
—
—
—
O
— —
—
— —
m
— —
m
m
A
H m
N
V
u o m
m
XM
—
H
N
m
w
—
C ph o h n
—
Ch o
—
mph n o
H
m
m
C no
n
N
Cp o o
n
—
—
—
—
— —
—
w
A
H m
N
C
h om
H
n
m
n
m
Co
n
—
DO
m
A
m
m
Do
n
D
—
Do p n m
—
—
m
C nd m
—
—
—
—
—
— —
— —
— —
— —
—
A
no
N
n
NX
2
—
—
19 – 27
16 – 21
17 – 25
19 – 26
24 – 31e
28 – 34
—
MEM-10 10 µg
28 – 34 29 – 37ii 27 – 33
Meropenem h,i
Enterobacteriaceae, P. aeruginosa,
Acinetobacter and staphylococci j
≤13
14 – 15
≥16
Haemophilus spp. c
— —
≥20
MZ-75 75 µg
23 – 29
—
19 – 25
Mezlocillin ii
Moxalactam
MOX-30 30 µg
Enterobacteriaceae, P. aeruginosa,
Acinetobacter and staphylococci j
≤14
15 – 22
≥23
20 – 25e
19 – 25
25 – 30
—
28 – 35
18 – 24
17 – 25
20 – 28c
Nafcillin
NF-1 1 µg
Staphylococcus aureus j,nn
≤10
11 – 12
≥13
—
16 – 22
—
Nalidixic Acid
NA-30 30 µg
Enterobacteriaceae z
≤13
14 – 18
≥19
N-30 30 µg
Neomycin f
≤12
13 – 16
≥17
22 – 28
—
—
17 – 23
18 – 26
—
Netilmicin
NET-30 30 µg
Enterobacteriaceae, P. aeruginosa,
Acinetobacter and staphylococci
≤12
13 – 14
≥15
22 – 30
22 – 31
17 – 23
Nitrofurantoin
F/M-300
300 µg
Enterobacteriaceae, staphylococci and
enterococci
≤14
15 – 16
≥17
NOR-10
10 µg
Norfloxacin ii
ddd
Enterobacteriaceae
, P. aeruginosa,
20 – 25
18 – 22
—
28 – 35
17 – 28
22 – 29
—
22 – 31
—
≤12
13 – 16
≥17
≤17
18 – 21
≥ 22
≤14
15 – 16
≥17
—
Ofloxacin
OFX-5 5 µg
29 – 33 24 – 28 17 – 21
Enterobacteriaceaeddd, P. aeruginosa,
aa
Acinetobacter and staphylococci ≤12
13 – 15
≥16
— —
—
Haemophilus spp. c
≥16
31 – 40c
N. gonorrhoeae d
≤24
25 – 30wŽ≥31
43 – 51d
S. pneumoniae e and other streptococci
(non-S. pneumoniae, b-hemolytic only) e
≤ 12
13 – 15
≥16
Oxacillin
OX-1 1 µg
—
18 – 24
—
Staphylococcus aureus j,nn,oo
≤10
11 – 12
≥13
Staphylococci, coagulase-negative j,nn
≤17
—
≥18
S. pneumoniae (for
penicillin G susceptibility) e,h
— —
≥20
OA-2 2 µg
Oxolinic Acid f
≤10 —
≥11
20 – 24 10 – 13
—
P-10 10 U
—
26 – 37
—
Penicillin h
Staphylococcus spp. j,pp
≤28 —
≥29
Enterococcus spp. n,o
≤14 —
≥15
L. monocytogenes f
≤19
20 – 27
≥28
N. gonorrhoeae d,qq,ii
≤26
27 – 46 w ≥47
26 – 34d
Streptococci (non-S. pneumoniae, — —
≥24ii
b-hemolytic only) e,i,rr,aaa,ccc
Piperacillin
PIP-100
100 µg
Enterobacteriaceae and Acinetobacter
≤17
18 – 20
≥21
P. aeruginosa
≤17 —
≥18
Piperacillin/
TZP-110
100/10 µg
Tazobactam g
Enterobacteriaceae and Acinetobacter ii
≤17
18 – 20
≥21
Staphylococcus spp. j,ii and P. aeruginosa ii
≤17 —
≥18
aa,dd
PB-300
300 U
Polymyxin B
≤8
9 – 11
≥12
24 – 30g
—
300 µg
6
10 µg
≤11
7 – 9 hh
12 – 14
≥15
≤12
13 – 16
25 – 31e
16 – 21e
≤12 e,bbb
24 – 30e
25 – 33
24 – 30g 27 – 36 25 – 33ii
12 – 16
≥10
25 – 34e,ii
45 – 54d
Moxifloxacin
MXF-5
5 µg
28 – 35 28 – 35
—aa
Enterobacteriaceaef,ddd and Staphylococcus spp.aa ≤15
16 – 18
≥19
H. influenzaec and H. parainfluenzaec
— —
≥18
31 – 39c
—
S. pneumoniaee
≤14
15 – 17
≥18
—
—
—
—
19 – 24e,ii,cc
25 – 30 e
21 – 27 e
23 – 29d
—
12 – 20
14 – 22
—
15 – 23
24 – 34
—
≥17
Telavancin
TLV-30 30 µg
—
16 – 20
—
17 – 24
Staphylococcus aureus
—
—
(including methicillin-resistant isolates) f
≥15
Streptococcus pyogenes, Streptococcus agalactiae,
Streptococcus anginosus group (S. anginosus,
S. constellatus and S. intermedius)e,f
—
—
≥15
Enterococcus faecalis
—
—
(vancomycin-susceptible isolates only) f
≥15
Telithromycin
TEL-15
15 µg
—
24 – 30
—
S. aureus
—aa —aa
≥22
Haemophilus spp.c
≤11
12 – 14
≥15
17 – 23
—
S. pneumoniaee
≤15
16 – 18
≥19
27 – 33
Te-30
30 µg
18 – 25 24 – 30
—
Tetracycline ee
Enterobacteriaceaeaa, P. aeruginosa,
Acinetobacteraa, staphylococci,
enterococci yy and V. cholerae m
≤14
15 – 18
≥19
—
Haemophilus spp. c
≤25
26 – 28
≥29
14 – 22c
N. gonorrhoeae d,uu
≤30
31 – 37w ≥38
30 – 42d
S. pneumoniae and other streptococci e
≤18
19 – 22
≥23
27 – 31e
Ticarcillin/
TIM-85
75/10 µg
Clavulanic Acid g
Enterobacteriaceae and Acinetobacter
≤14
15 - 19
≥20
P. aeruginosa
≤14 —
≥15
j
Staphylococcus spp.
≤22 —
≥23
A
V
m
—
19 – 26
Levofloxacin
LVX–5 5 µg
29 – 37 25 – 30 19 – 26
Enterobacteriaceaeddd, P. aeruginosa,
Acinetobacter, staphylococci aa and enterococci
≤13
14 – 16
≥17
— —
Haemophilus spp. c ≥17
32 – 40c
—
S. pneumoniae and other streptococci ≤13
14 – 16
≥17
(non-S. pneumoniae, b-hemolytic only) e
Ticarcillin
TIC-75
75 µg
Enterobacteriaceae and Acinetobacter
≤14
15 – 19
≥20
P. aeruginosa
≤14 —
≥15
25 – 30e
26 – 32
—
20 – 28
Enterobacteriaceae, P. aeruginosa,
Acinetobacter and staphylococci j
≤13
14 – 15
≥16
Haemophilus spp. c
— —
≥16
21 – 29c
—
250 µg
Enterobacteriaceae, P. aeruginosa,
Acinetobacter, staphylococci and V. cholerae m
— —
— —
Gentamicin
Testing enterococci
GM-120
120 µg
6
7 – 9 hhŽ≥10
for high level resistance n,o,gg
Enterobacteriaceae,
GM-10 10 µg
P. aeruginosa, Acinetobacter and staphylococci
≤12
13 – 14
≥15
h,i
IPM-10 10 µg
Imipenem
Streptomycin
Testing enterococci
S-300
for high level resistance n,o,gg
Enterobacteriaceae
S-10
G-.25
Sulfisoxazole tt
—
—
28 – 35
≥16
Spectinomycin
SPT-100
100 µg
—
—
—
N. gonorrhoeae d
≤14
15 – 17w ≥18
— —
— —
13 – 15
Rifampin
RA-5 5 µg
8 – 10 26 – 34
—
Staphylococcus spp. and Enterococcus spp. yy
≤16
17 – 19
≥20
c
—
Haemophilus spp. ≤16
17 – 19
≥20
22 – 30c
S. pneumoniae e
≤16
17 – 18Ž≥19
Sparfloxacin
SPX–5 5 µg
30 – 38 27 – 33 21 – 29 ii
Staphylococcus spp. ≤15
16 – 18
≥19
S. pneumoniae e
≤15ii 16 – 18 ii ≥19
—
—
≤12
—
Quinupristin/Dalfopristin SYN-15 4.5/10.5 µg
—
21 – 28ii
Staphylococcus spp., ≤15
16 – 18
≥19
Enterococcus faecium and
S. pyogenese only
A
m
C
m
C
m
p o
C
N
C
A
N
o
X
— —
m
m
o
m
u n A d
C
—
m
C
C
C
— —
— —
E. coli and E. faecalis only
Gatifloxacin
GAT-5
5 µg
30 – 37 27 – 33 20 – 28mm
Enterobacteriaceaeddd and Staphylococcus spp.aa ≤14
15 – 17
≥18
P. aeruginosa, Acinetobacter spp. and enterococciz
≤14ii 15 – 17ii ≥18ii
—
H. influenzaec and H. parainfluenzaec
— —
≥18
33 – 41c
N. gonorrhoeaed
≤33
34 – 37
≥38
45 – 56d
S. pneumoniae and other streptococci ≤17ii 18 – 20ii ≥21ii
e
(non-S. pneumoniae, b-hemolytic only)
Gemifloxacin
GEM-5
5 µg
29 – 36 27 – 33ii19 – 25mm,ii
Enterobacteriaceaell,ddd
≤15
16 – 19
≥20
c
c
H. influenzae and H. parainfluenzae
— —
≥18
30 – 37
—
S. pneumoniaee
≤19
20 – 22
≥23
Acinetobacter, staphylococci and enterococci
NB-30 30 µg
Novobiocin f
(Mueller Hinton agar with sheep blood
for veterinary use)
FEP-30 30 µg
31 –37ii 23 – 29 24 – 30
Cefepime h,i
Enterobacteriaceae, P. aeruginosa,
Acinetobacter and staphylococci j
≤14
15 – 17
≥18
— —
—
Haemophilus spp. c
≥26
25 –31c
— —
N. gonorrhoeae d
≥31
37 – 46d,ii
Viridans Streptococci (non-S. pneumoniae) e,ccc
≤ 21ii 22 – 23ii ≥24ii
C
Erythromycin
E-15 15 µg
—
22 – 30
—
Staphylococcus spp. r and enterococci r,yy
≤13
14 – 22ii ≥23ii
S. pneumoniae and other streptococci e,r,s
≤15
16 – 20
≥21
FOS-200
200 µg
22 – 30ii 25 – 33
—
Fosfomycin z
Enterobacteriaceae and Acinetobacter
≤17
18 – 20
≥21
P. aeruginosa
≤15 —
≥16
MI-30 30 µg
Minocycline ee
aa
Enterobacteriaceae , P. aeruginosa,
Acinetobacteraa, staphylococci and enterococci yy ≤14
15 – 18
≥19
—
Cefazolin
CZ-30 30 µg
21 – 27ii 29 – 35
—
Enterobacteriaceae u and staphylococci j
≤14
15 – 17
≥18
CDR-5 5 µg
24 – 28 25 – 32
—
Cefdinir h
Enterobacteriaceaekk and methicillin-susceptible staphylococci j
≤16
17 – 19
≥20
Haemophilus spp. c
— —
≥20
Ertapenemh,i
ETP-10
10 µg
29 – 36 24 – 31 13 – 21
Enterobacteriaceae and Staphylococcus spp.j
≤15
16 – 18
≥19
Haemophilus spp.c
— —
≥19
20 – 28
27 – 33
Lomefloxacin
LOM-10 10 µg
27 – 33 23 – 29 22 – 28
Enterobacteriaceaeddd, P. aeruginosa,
Acinetobacter and staphylococci
≤18
19 – 21
≥22
— —
Haemophilus spp. c
≥22
33 – 41c
—
N. gonorrhoeae d
≤26
27 – 37
≥38
LOR-30 30 µg
23 – 29 23 – 31
—
Loracarbef h,i
Enterobacteriaceae u,kk and staphylococci j
≤14
15 – 17
≥18
Haemophilus spp. c,k
≤15
16 – 18
≥19
—
26 – 32c
24 – 30
Aztreonam
ATM-30 30 µg
28 – 36
—
23 – 29
Enterobacteriaceae, t P. aeruginosa & Acinetobacter ≤15
16 – 21
≥22
— —
Haemophilus spp. c
≥26
B-10 10 U
Bacitracin f
≤8
9 – 12
≥13
—
12 – 22
—
N.
S.
gonorrhoeae pneumoniae
ATCC
ATCC
49226 d
49619 e
—
Linezolid
LZD-30
30 µg
—
— —
Staphylococcus spp.
≥21
Enterococcus spp. ≤20
21 – 22
≥23
—
S. pneumoniae and other streptococci e
—
≥21
Azithromycin
AZM-15 15 µg
—
21 – 26
—
Staphylococcus spp. r
≤13
14 – 17
≥18
—
Haemophilus spp. c
— —
≥12
13 – 21c
S. pneumoniae and other streptococci e,r,s
≤13
14 – 17
≥18
19 – 25e
Azlocillin
AZ-75 75 µg
P. aeruginosa
≤17 —
≥18
Code
Disc
Potency
Kanamycin
K-30 30 µg
Enterobacteriaceae and staphylococci ≤13
14 – 17
≥18
—
≥24ii
— —
Antimicrobial
Agent
Zone Diameter
Control Zone
Interpretive Standards (mm)
Diameter Limits (mm)
E.
S.
P.
H.
H.
coli
aureus aeruginosa influenzae influenzae
ResisInter- SuscepATCC
ATCC
ATCC
ATCC
ATCC
tant mediate a tible b
25922
25923
27853
49247 c
49766 c
25 – 32ii
Amoxicillin/
20/10 µg
18 – 24g,ii 28 – 36
—
Clavulanic Acid g,h,i AmC-30
Enterobacteriaceae
≤13
14 – 17
≥18
j
Staphylococcus spp. ≤19 —
≥20
Haemophilus spp. c,k
≤19 —
≥20
15 –23c
AM-10 10 µg
16 – 22 27 – 35
—
Ampicillin h,l
Enterobacteriaceaeii and V. cholerae m ≤13
14 – 16
≥17
Staphylococci j,ii
≤28 —
≥29
Enterococcus spp. n,o,ii
≤16 —
≥17
Listeria monocytogenes f
≤19 —
≥20
Haemophilus spp. c,k,p
≤18
19 – 21
≥22
13 – 21c
Streptococci (non-S. pneumoniae, b-hemolytic
only) e,i,aaa,ccc
Zone Diameter Interpretive Chart †
24 – 30
—
24 –30g,ii 29 – 37
21 – 27ii
20 – 28
23 – 31jj
—
30 – 40zz
Tigecycline
TGC-15
15 µg
20 – 27 20 – 25 9 – 13mm
Enterobacteriaceaef,ss
≤14
15 - 18
≥19
f
—
—
S. aureus (including MRSA) ≥19
E. faecalis (vancomycin-susceptible isolates only)f
—
—
≥19
Streptococcus spp. (other than S. pneumoniae)e,f —
—
≥19
Tobramycin
NN-10
10 µg
Enterobacteriaceae, P. aeruginosa,
Acinetobacter and staphylococci
≤12
13 – 14
≥15
18 – 26
19 – 29
19 – 25
Trimethoprim
TMP-5 5 µg
Enterobacteriaceae and staphylococci
≤10
11 – 15
≥16
21 – 28
19 – 26
—
 BBL Sensi-Disc Antimicrobial Susceptibility Test Discs
(D sques Sens -D sc BBL pour ant b ogramme)
23 – 29cc
Trimethoprim/
SXT 1.25 µg
23 – 29ii 24 – 32
—
Sulfamethoxazole tt23.75 µg
Enterobacteriaceae, P. aeruginosa,
m
Acinetobacter, staphylococci and V. cholerae
≤10
11 – 15
≥16
—
Haemophilus spp. c
≤10
11 – 15
≥16
24 – 32c
S. pneumoniae e
≤15
16 – 18
≥19
20 – 28e
Vancomycin
Va-3 0
30 µg
—
17 – 21
—
— —
Staphylococcus spp. vv,ii
≥15
Enterococcus spp. n,o,ww
≤14
15 – 16
≥17
S. pneumoniae xx and other streptococci e
— —
≥17
20 – 27 e
an a
APPLICATION – Ces disques sont utilisés pour une évaluation semi-quantitative in vitro de la sensibilité aux antibiotiques des agents pathogènes
bactériens courants à croissance rapide ainsi que de certaines espèces exigeantes, par un antibiogramme par diffusion sur disque en gélose.
Les microorganismes concernés incluent : les Enterobacteriaceae, les genres Staphylococcus, Pseudomonas, Acinetobacter, Enterococcus, Vibrio
cholerae et, avec des procédures modifiées, Haemophilus influenzae, Neisseria gonorrhoeae, Streptococcus pneumoniae et d’autres streptocoques.
REMARQUE : Des procédures particulières sont nécessaires pour tester les pneumocoques, les entérocoques et les staphylocoques résistants à
la méticilline/oxacilline et pour réaliser des tests des bβ-lactamases et des tests de dépistage et de confirmation pour les ESBL ; voir la section
« Résultats ».
Pour la France: Les résultats seront interprétés en fonction du dernier communiqué du Comité de l’antibiogramme de la Société Française de
Microbiologie. Un guide d’interprétation conforme au communiqué du Comité de l’antibiogramme de la Société Française de Microbiologie pourra
être fourni sur simple demande à la société Becton Dickinson France S.A.S., Tel: 04 76 68 36 36.
† Adapted in part from CLSI Document M100-S21 (M2): Disk Diffusion Supplemental Tables, Performance Standards for Antimicrobial Susceptibility
Testing, with permission. The complete standard may be obtained from the Clinical and Laboratory Standards Institute, 940 West Valley Road, Suite
1400, Wayne, PA 19087-1898 USA. Values not in M100-S21 are explained in other footnotes. For appropriate MIC correlates, refer to M100-S21.6,7,9
aThe “Intermediate” category includes isolates with antimicrobial agent MICs that approach usually attainable blood and tissue levels and for which
response rates may be lower than for susceptible isolates. The “Intermediate” category implies clinical applicability in body sites where the drugs are
physiologically concentrated (e.g., quinolones and β-lactams in urine), or when a higher than normal dosage of a drug can be used (e.g., β-lactams).
The “Intermediate” category also includes “buffer zone” which should prevent small uncontrolled technical factors from causing major discrepancies in
interpretation, especially for drugs with narrow pharmacotoxicity margins.
bPolicies regarding generation of cumulative antibiograms should be developed in concert with the infectious disease service, infection control personnel, and the pharmacy and therapeutics committee. Under most circumstances, the percentage of susceptible and intermediate results should not be
combined into the same statistics.
cThese zone diameter standards and quality control limits apply only to tests with Haemophilus spp. using Haemophilus Test Medium (HTM) incubated in
5% CO2 (16♣-18 h). H. influenzae ATCC 10211 is recommended as a useful additional quality control strain to verify the growth promotion properties of
3
HTM. The zone margin should be considered as the area showing no obvious growth visible with the unaided eye. Faint growth of tiny colonies that
may appear to fade from the more obvious zone should be ignored in the measurement. When testing Haemophilus with amoxicillin/clavulanic acid
on HTM, include E. coli ATCC 35218 as the control strain. The acceptable limits for E. coli ATCC 35218 are 17-22 mm for amoxicillin/clavulanic acid when
incubated in ambient air.
dThese zone diameter standards and quality control limits are applicable only to tests performed using GC agar base and 1% defined growth supplement (e.g., BBL™ GC II Agar with IsoVitaleX™ Enrichment) incubated in 5% CO2 (20 – 24 h).
eThese zone diameter standards and quality control limits are applicable only to tests performed using Mueller Hinton agar supplemented with 5%
defibrinated sheep blood incubated in 5% CO2 (20 – 24 h). Interpretive standards apply to S. pneumoniae and other streptococci as indicated.
Results may be inaccurate if specified criteria are applied to organisms other than those listed. Interpretive criteria for streptococci other than S. pneumoniae are proposed based on population distributions of various species, pharmacokinetics of the antimicrobial agents, previously published literature
and the clinical experience of certain members of the CLSI subcommittee. Systematically collected clinical data were not available for review with
many of the compounds in the group.7 Despite the lack of reliable disc diffusion interpretive criteria for S. pneumoniae with certain β-lactams, S.
pneumoniae ATCC 49619 is the strain designated for quality control of all disc diffusion tests with all Streptococcus spp.
f FDA-approved zone size recommendations from drug manufacturers not included in CLSI M100-S21 (M2-A10).7
gAnother E. coli (ATCC 35218) has been designated for quality control of discs containing combinations of β-lactams and β-lactamase inhibitors. This
strain produces a β-lactamase which should be inactivated by the inhibitor. When used in conjunction with ATCC 25922, both components of the
combination discs can be monitored. Control limits with this strain for amoxicillin/clavulanic acid are 17-22 mm, for ampicillin is 6 mm (i.e., no zone),
for ampicillin/sulbactam are 13-19 mm, for piperacillin are 12-18 mm, for piperacillin/tazobactam are 24-30 mm, for ticarcillin is 6 mm (i.e., no zone)
and for ticarcillin/clavulanic acid are 21-25 mm. The E. coli ATCC 35218 control strain contains a plasmid-encoded β-lactamase (non-ESBL); therefore, the
organism is resistant to many penicillinase-labile drugs, but susceptible to β-lactam/ β-lactamase inhibitor combinations. The plasmid must be present in
the control strain for the quality control test to be valid; however, the plasmid may be lost during storage at refrigerator or freezer temperatures. See
“Limitations of the Procedure” and M2 for additional details.
hIsolates of pneumococci with oxacillin zone sizes of ≥ 20 mm are susceptible (MIC ≤ 0.06 µg/mL) to penicillin and can be considered susceptible
to ampicillin, amoxicillin, amoxicillin/clavulanic acid, ampicillin/sulbactam, cefaclor, cefdinir, cefepime, cefetamet, cefixime, cefotaxime, cefprozil,
ceftibuten, ceftriaxone, cefuroxime, cefpodoxime, ceftizoxime, ertapenem, imipenem, loracarbef, and meropenem for approved indications,
and these agents need not be tested. Penicillin and cefotaxime or ceftriaxone or meropenem MICs should be determined for those isolates with
oxacillin zone sizes ≤ 19 mm because zones of ≤ 19 mm occur with penicillin-resistant, intermediate, or certain susceptible strains. Isolates should
not be reported as penicillin resistant or intermediate based solely on an oxacillin zone ≤ 19 mm. Amoxicillin, ampicillin, cefepime, cefotaxime,
ceftriaxone, cefuroxime, ertapenem, imipenem, and meropenem may be used to treat pneumococcal infections; however, reliable disc diffusion
susceptibility tests with these agents do not yet exist. Their in vitro activity is best determined using an MIC method. Penicillin and cefotaxime or
ceftriaxone or meropenem should be tested by a reliable MIC method (such as that described in CLSI document M79) and reported routinely with
CSF isolates of S. pneumoniae. Such isolates should also be tested against vancomycin using the MIC or disc method. With isolates from other
sites, the oxacillin disc screening test may be used. If the oxacillin zone size is ≤ 19 mm, penicillin and cefotaxime or ceftriaxone MICs should be
determined. To determine susceptibility of streptococci other than S. pneumoniae to cefdinir, use the 10-unit penicillin disc; isolates with penicillin zone sizes ≥ 2
Ž 8 mm are susceptible to penicillin and can be considered susceptible to cefdinir.
iA streptococcal isolate that is susceptible to penicillin can be considered susceptible to ampicillin, amoxicillin, amoxicillin/clavulanic acid, ampicillin/sulbactam, cefaclor, cefazolin, cefdinir, cefepime, cefprozil, cefotaxime, ceftibuten (group A streptococci only), ceftriaxone, cefuroxime, cefpodoxime,
ceftizoxime, cephalothin, cephapirin, cephradine, imipenem, loracarbef, and meropenem for approved indications, and need not be tested against
those agents. Viridans streptococci isolated from blood and normally sterile body sites (e.g., cerebrospinal fluid, blood, bone, etc.), should be tested for
penicillin or ampicillin susceptibility using an MIC method.
jPenicillin-susceptible staphylococci are also susceptible to other penicillins, β-lactam/β-lactamase inhibitor combinations, cephems, and carbapenems
approved for use by the FDA for staphylococcal infections. Penicillin-resistant, oxacillin-susceptible strains are resistant to penicillinase-labile penicillins
but susceptible to other penicillinase-stable penicillins, β-lactam/β-lactamase inhibitor combinations, relevant cephems, and carbapenems. Oxacillin-resistant staphylococci are resistant to all currently available β-lactam antibiotics. Thus, susceptibility or resistance to a wide array of β-lactam antibiotics may
be deduced from testing only penicillin and oxacillin. Routine testing of other penicillins, β-lactam/β-lactamase inhibitor combinations, cephems, and
carbapenems is not advised.7 For oxacillin-resistant staphylococci, report as resistant or do not report.
kRare, β-lactamase-negative, ampicillin-resistant (BLNAR) strains of Haemophilus influenzae should be considered resistant to amoxicillin/clavulanic acid,
ampicillin/sulbactam, cefaclor, cefetamet, cefonicid, cefprozil, cefuroxime, and loracarbef despite apparent in vitro susceptibility of some BLNAR strains
to these agents.
l
Class representative for ampicillin and amoxicillin.
mFor V. cholerae, the results of disc diffusion tests for ampicillin, tetracycline, trimethoprim/sulfamethoxazole and sulfonamides (i.e., percentage of susceptible, intermediate, and resistant) correlate well with results determined by broth microdilution. Tetracycline results can be used to predict the likely
susceptibility of isolates to doxycycline; do not use disc test for doxycycline or erythromycin because there is poor correlation with MIC results.
nAmpicillin is the class representative for ampicillin and amoxicillin. Ampicillin results may be used to predict susceptibility to amoxicillin/clavulanic
acid, ampicillin/sulbactam, piperacillin and piperacillin/tazobactam among non-β-lactamase-producing enterococci. Enterococci susceptible to
penicillin are predictably susceptible to ampicillin, amoxicillin, ampicillin/sulbactam, amoxicillin/clavulanic acid, piperacillin, and piperacillin/
tazobactam for non-β-lactamase-producing enterococci. However, enterococci susceptible to ampicillin cannot be assumed to be susceptible to
penicillin. If penicillin results are needed, testing of penicillin is required. Because ampicillin or penicillin resistance among enterococci due to βlactamase production is not reliably detected using routine disc or dilution methods, a direct, nitrocefin-based β-lactamase test is recommended
for blood and cerebrospinal fluid isolates. A positive β-lactamase test predicts resistance to penicillin, as well as amino-, carboxy- and ureido-penicillins. Certain penicillin- or ampicillin-resistant enterococci may possess high-level resistance (i.e., penicillin MICs ≥ 128 µg/mL or ampicillin
MICs ≥ 64 µg/mL). The disc test will not differentiate those with normal resistance from this high-level resistance. For enterococci recovered from
blood and CSF, the laboratory should consider determining the actual MIC for penicillin or ampicillin since enterococcal strains with normal
lower level resistance (penicillin MICs ≤ 64 µg/mL and ampicillin MICs ≤ 32 µg/mL) should be considered potentially susceptible to synergy with
an aminoglycoside (in the absence of high-level aminoglycoside resistance) whereas strains with higher level resistance may be resistant to such
synergy.6
oSynergy between ampicillin, penicillin or vancomycin and an aminoglycoside can be predicted for enterococci by using a high-level aminoglycoside
(gentamicin and streptomycin) screening test. Other aminoglycosides need not be tested because their activities against enterococci are not superior to
gentamicin and streptomycin.
pThe results of ampicillin susceptibility tests should be used to predict the activity of amoxicillin. The majority of isolates of H. influenzae that are
resistant to ampicillin and amoxicillin produce a TEM-type-β-lactamase. In most cases, a direct β-lactamase test can provide a rapid means of detecting
ampicillin and amoxicillin resistance.
qMay be reported for Acinetobacter spp. resistant to other agents.
r Not routinely reported on isolates from the urinary tract.
sSusceptibility and resistance to azithromycin, clarithromycin and dirithromycin can be predicted by using erythromycin.
tSee discussion of ESBLs under “RESULTS.” For screening and confirmatory tests for ESBLs in Klebsiella pneumoniae, K. oxytoca and E. coli, see
"RESULTS" section and reference 7. Screening breakpoints (Mueller Hinton agar, standard disc diffusion procedure, 35 ± 2ºC, ambient air,
16 – 18 h) are: aztreonam (≤ 27 mm), ceftazidime (≤ 22 mm), cefotaxime (≤ 27 mm), cefpodoxime (≤ 17 mm) and ceftriaxone (≤ 25 mm). Quality control
recommendations are E. coli ATCC 25922 (as listed in the chart); K. pneumoniae ATCC 700603 (aztreonam 9 – 17 mm), ceftazidime (10 – 18 mm), cefotaxime (17 – 25 mm), cefpodoxime (9 – 16 mm) and ceftriaxone (16 – 24 mm).7 The use of more than one antimicrobial agent for screening improves
the sensitivity of detection. Phenotypic confirmatory testing requires the use of both cefotaxime and ceftazidime, alone and in combination with clavulanic acid. A ≥ 5 mm zone diameter for either antimicrobial agent tested in combination with clavulanic acid versus its zone when tested alone = ESBL.
Quality Control recommendations are: negative strain E. coli ATCC 25922 which produces a ≤ 2 mm increase in zone diameter for antimicrobial agent
tested alone versus its zone diameter when tested in combination with clavulanic acid; positive strain K. pneumoniae ATCC 700603 which produces a
≥ 3 mm increase in cefotaxime zone diameter and a ≥ 5 mm increase in ceftazidime zone diameter. See "Limitations of the Procedure." See reference 7
for details of the procedure.
uCephalothin can be used to predict activity of cephalothin, cephapirin, cephradine, cephalexin, cefaclor and cefadroxil. Cefazolin, cefuroxime, cefpodoxime, cefprozil, and loracarbef (urinary isolates only) may be tested individually because some isolates may be susceptible to these agents when
resistant to cephalothin.
vNot applicable for testing Morganella spp.
wFor N. gonorrhoeae, an intermediate result for an antimicrobial agent indicates either a technical problem that should be resolved by repeat testing or
a lack of clinical experience in treating organisms with these zones. The latter seems to be the case for cefmetazole, cefotetan, cefoxitin, and spectinomycin. Strains with intermediate zones with the other agents have a documented lower clinical cure rate (85 - 95%) compared to >95% for susceptible
strains.
xCefotaxime, ceftizoxime or ceftriaxone should be tested and reported on isolates from CSF in place of cephalothin and cefazolin.
yBecause certain strains of Providencia spp. have been reported to give false-susceptible results with cefprozil discs, strains of this genus should not be
tested and reported with this disc.
zIndicated for urine isolates only. In addition to testing urine isolates, nalidixic acid may be used to test for reduced fluoroquinolone susceptibility in
isolates from patients with extraintestinal Salmonella infections. See footnote ddd.
aa FDA-approved zone diameters for interpretive and/or quality control criteria that differ from CLSI recommendations.
bb For V. cholerae, use with caution as the disc diffusion test may misclassify many organisms (higher minor error rate).
cc
No criteria have been established to support testing of this drug with Streptococcus pneumoniae. The control range is listed for quality control purposes only.
dd Colistin and polymyxin B diffuse poorly in agar and the accuracy of the diffusion method is thus less than with other antibiotics. Resistance is always
significant, but when treatment of systemic infections due to susceptible strains is considered, it is wise to confirm the results of a diffusion test with a
dilution method.
ee Organisms that are susceptible to tetracycline are also considered susceptible to doxycycline and minocycline. However, some organisms that are intermediate or resistant to tetracycline may be susceptible to doxycycline or minocycline or both.
ff
FDA-approved for S. saprophyticus and S. epidermidis (not S. aureus).
gg For control limits of gentamicin 120 µg and streptomycin 300 µg discs, use E. faecalis ATCC 29212 (gentamicin: 16 - 23ii mm; streptomycin:
14 - 20ii mm).
hh If the zone is 7 - 9 mm, the test is inconclusive and an agar dilution or broth microdilution screen test should be performed to confirm resistance.
ii
CLSI-recommended zone sizes that differ from FDA-approved zone size recommendations.
jj
No criteria have been established to support testing of this drug with H. influenzae. The control range is listed for quality control purposes only.
kk Because certain strains of Citrobacter, Providencia, and Enterobacter spp. have been reported to give false susceptible results with cefdinir and loracarbef discs, strains of these genera should not be tested and reported with these discs.
ll
FDA-approved for K. pneumoniae.
mm No criteria have been established to support testing of this drug with Pseudomonas aeruginosa. The control range is listed for quality control purposes
only.
nn If a penicillinase-stable penicillin is tested, oxacillin is the preferred agent and results can be applied to the other penicillinase-stable penicillins, cloxacillin, dicloxacillin, flucloxacillin, methicillin and nafcillin. Oxacillin is preferred because it is more resistant to degradation in storage, and because it is
more likely to detect heteroresistant staphylococcal strains. Cloxacillin discs should not be used because they may not detect oxacillin-resistant S. aureus.
Cefoxitin may be tested instead of oxacillin (see M100-S21). After incubation for a full 24 h, examine for light growth within the zone of inhibition of
the oxacillin disc using transmitted light (plate held up to light). Any discernable growth within the zone of inhibition is indicative of oxacillin resistance.
oo If oxacillin intermediate results are obtained for S. aureus, perform testing for mecA or PBP 2a, the cefoxitin disc test, an oxacillin MIC test or the oxacillin-salt agar screening test. Report the result of the alternative test rather than the intermediate result.
pp Penicillin-resistant, oxacillin-susceptible strains of Staphylococcus aureus produce β-lactamase and the testing of the 10-unit penicillin disc instead of the
ampicillin disc is preferred. Penicillin should be used to test the susceptibility of all β-lactamase-labile penicillins, such as ampicillin, amoxicillin, azlocillin, carbenicillin, mezlocillin, piperacillin, and ticarcillin. Likewise, a positive β-lactamase test predicts resistance to these agents.6 For oxacillin-resistant
staphylococci, report as resistant or do not report.
qq A positive β-lactamase test predicts resistance to penicillin, ampicillin, and amoxacillin. A β-lactamase test will detect one form of penicillin resistance
in N. gonorrhoeae and also may be used to provide epidemiologic information. Strains with chromosomally-mediated resistance can be detected only
by additional susceptibility testing, such as the disc diffusion method or the agar dilution MIC method. Gonococci with 10-unit penicillin disc zone
diameters of ≤19 mm are likely to be β-lactamase-producing strains. However, the β-lactamase test remains preferable to other susceptibility methods
for rapid, accurate recognition of this plasmid-mediated penicillin resistance.
rr
Susceptibility tests on S. pyogenes to penicillin are seldom necessary since this microorganism has continued to be universally susceptible to penicillin.
However, some strains of S. agalactiae may give penicillin-intermediate results.7
ss
Tigecycline has decreased in vitro activity against Morganella spp., Proteus spp. and Providencia spp.
tt
The sulfisoxazole disc can be used to represent any of the currently available sulfonamides. Blood-containing media (except for lysed horse blood) are
generally not suitable for testing sulfonamides or trimethoprim. Mueller Hinton agar should be as thymidine-free as possible for sulfonamide and/or
trimethoprim testing. To determine whether the Mueller Hinton agar has sufficiently low levels of thymine and thymidine, Enterococcus faecalis ATCC
29212 or ATCC 33186 may be tested with the trimethoprim-sulfamethoxazole disc (see ref. 13). An inhibition zone of ≥ 20 mm that is essentially free of
fine colonies indicates a sufficiently low level of thymine and thymidine.6
uu Gonococci with 30-µg tetracycline disc zone diameters of ≤ 19 mm usually indicate a plasmid-mediated tetracycline-resistant N. gonorrhoeae (TRNG)
isolate. These strains should be confirmed by a dilution test (MIC ≥ 16 µg/mL) and/or referred to a public health laboratory for epidemiologic investigation.
vv All staphylococcal isolates with vancomycin zone diameters of 14 mm or less should be tested by a reference MIC method. The disc diffusion procedure
will not differentiate strains with reduced susceptibility to vancomycin (MICs 4 to 8 µg/mL) from susceptible strains (MICs 0.5 to 2 µg/mL) even when
incubated 24 h. Additionally, vancomycin-resistant S. aureus (VRSA) strains (MICs ≥ 16 µg/mL) may produce only subtle growth around a vancomycin
disc. The vancomycin agar screen test described for enterococci (Brain Heart Infusion Agar with 6 µg/mL Vancomycin) may be used to enhance the
sensitivity of detecting vancomycin-intermediate and vancomycin-resistant strains of S. aureus incubating the plates for a full 24 h at 35°C.6 Use of a susceptible quality control strain, such as E. faecalis ATCC 29212 is critical to ensure specificity. E. faecalis ATCC 51299 may be used as a positive (i.e., resistant) control. Until further data on the prevalence or clinical significance of these isolates is known, laboratories may choose to examine MRSA strains
more carefully for elevated MICs to vancomycin.6 Currently, there are insufficient data to recommend using this agar screen test for coagulase-negative
staphylococci. Send any staphylococci determined to have an elevated MIC to vancomycin (≥ 4 µg/mL) to a reference laboratory.
ww When testing vancomycin against enterococci, plates should be held a full 24 h and examined using transmitted light; the presence of a haze or any
growth within the zone of inhibition indicates resistance. Organisms with intermediate zones should be tested by an MIC method as described in CLSI
document M7. See also the vancomycin agar screen test described in the MIC Table 2D (M100-S21).9
xx No S. pneumoniae strain with a vancomycin zone diameter of inhibition <17 mm has been observed; submit such strains to a reference laboratory.7
yy Because of limited alternatives, chloramphenicol, erythromycin, tetracycline (or doxycyline or minocycline) and rifampin may be used for vancomycinresistant enterococci (VRE) and consultation with an infectious disease practitioner is recommended.7
zz No criteria have been established to support testing of this drug with N. gonorrhoeae. The control range is listed for quality control purposes only.
aaa Strains of β-hemolytic streptococci with ampicillin, cefepime, cefotaxime, ceftriaxone or penicillin zone diameters of less than 24 mm have not been
observed; submit such strains to a reference laboratory.
bbb Deterioration in oxacillin disc content is best assessed with S. aureus ATCC 25923, with an acceptable zone diameter of 18 - 24 mm.
ccc For ampicillin, cefepime, cefotaxime, ceftriaxone and penicillin, Streptococci, b
β -hemolytic only includes the large-colony-forming pyogenic strains of
streptococci with group A (S. pyogenes), C or G antigens and strains with group B (S. agalactiae) antigen. For cefepime, cefotaxime and ceftriaxone,
Viridans Streptococci includes small-colony-forming β-hemolytic strains with group A, C, F or G antigens (S. anginosus, previously termed S. milleri) as
well as S. mitis, S. oralis, S. sanguis, S. salivarius, S. intermedius, S. constellatus, S. mutans and S. bovis.
ddd Fluoroquinolone-susceptible strains of Salmonella that test resistant to nalidixic acid may be associated with clinical failure or delayed response in
fluoroquinolone-treated patients with extraintestinal salmonellosis. Extraintestinal isolates of Salmonella should also be tested for resistance to nalidixic
acid. For isolates that test susceptible to fluoroquinolones and resistant to nalidixic acid, the physician should be informed that the isolate may not be
eradicated by fluoroquinolone treatment. A consultation with an infectious disease practitioner is recommended.
eee No criteria have been established to support testing of this drug with S. aureus. The control range is listed for quality control purposes only.
RESUME ET EXPLICATION – Les méthodes de diffusion en gélose utilisant des disques en papier filtre séchés contenant des concentrations
déterminées en agents antimicrobiens ont été mises au point au cours des années 40. Afin d’éliminer ou de minimiser la variabilité inhérente à ce
type de test, Bauer et al. ont mis au point une procédure standardisée dans laquelle la gélose Mueller Hinton était le milieu choisi pour le test.1,2
Divers organismes de réglementation et de rédaction des normes ont ensuite publié des procédures standardisées de référence en se basant sur la
méthode Bauer-Kirby. Les normes de la Food and Drug Administration (FDA)3 américaine et de l’Organisation mondiale de la santé (OMS)4,5 figurent
parmi les procédures standardisées les plus anciennes et les plus suivies. La procédure a été adoptée comme norme consensuelle par le Clinical and
Laboratory Standards Institute (CLSI, anciennement NCCLS) et fait l’objet de mises à jour périodiques.6,7 Les documents du CLSI les plus récents
doivent être consultés pour prendre connaissance des recommandations actuelles.
PRINCIPES DE LA METHODE – Des disques contenant toute une gamme d’agents antimicrobiens sont déposés sur la surface de la gélose Mueller
Hinton (ou de la gélose du test d’identification d’Haemophilus pour H. influenzae, de la gélose GC II enrichie d’IsoVitaleX pour N. gonorrhoeae ou
de la gélose Mueller Hinton avec 5 % de sang de mouton pour S. pneumoniae, les streptocoques b hémolytiques et du groupe viridans) dans des
boî tes de Pétri ensemencées avec des cultures pures d’isolats cliniques. Après incubation, les boî tes de Pétri sont examinées et les zones d’inhibition
entourant les disques sont mesurées et comparées aux gammes de taille de zone établies pour les différents agents antimicrobiens afin de
déterminer l’agent ou les agents les plus adéquats pour le traitement antimicrobien.
REACTIFS – Les disques Sensi-Disc sont des disques de 6 mm fabriqués à partir de papier absorbant de haute qualité imprégné d’antibiotiques ou
d’autres agents chimiothérapeutiques en quantités déterminées de manière précise. Les disques sont clairement identifiés des deux côtés par des
lettres et des chiffres désignant l’agent et sa concentration. (Voir le tableau des concentrations des composants actifs.) La teneur en agent des
disques est mesurée par les méthodes définies par la FDA ou par des méthodes similaires ou comparables à celles publiées dans le Federal Register
américain.
4
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H n h h u h und B
gung
ü
B nK b
pn umon
K o o
und
o
h d n Ab hn
RG BN
ow
u ng b
n ng G n w
Mu
H n on Ag
nd d
B
h nd u on
h n
± C Umg bung u
h nd A
on m
mm C
dm
mm C o
m
mm
C podo m
mm und C
on
mm Qu
on o mp h ung n nd
o A CC
w nd
b
u g üh
K pn umon
A CC
A
on m
mm C
dm
mm C o
m
mm C podo m
mm und C
on
mm D V w ndung on m h
n m An b o um ü d
n ng
b
d N hw
mp nd h
h no p h
B
gung
o d n d Anw ndung on C o
m und C
d m u mm n
n und n Komb n on m C u n u
n
H mm on ndu hm
on
mm ü n n d
n m ob
nW
o
d n V b ndung m C u n u g
w d
g h n
m d H mm on w nn d
W
o
ng
w d = B Qu
on o mp h ung n nd n g
mm
o A CC
d
n V g öß ung d H mm on ndu hm
um
mm b
n m
n g p ü n n m ob
nW
o b w
g g nüb
n H mm on b
n
ü ung n Komb n on m C u n u po
mm K pn umon
A CC
d
n
8