Tentative interpretive criteria for disk diffusion susceptibility testing of sparfloxacin.

Susceptibility to sparfloxacin was tested simultaneously by the agar dilution and disk diffusion methods. For tests with 5-micrograms sparfloxacin disks, we propose that the breakpoints for the susceptibility and resistance categories should be > or = 19 and < or = 15 mm, respectively. Most minor discrepancies involved tests with pseudomonads.     

Tentative disk diffusion susceptibility interpretive criteria for pefloxacin.

Standardized broth microdilution and disk diffusion susceptibility tests for pefloxacin were performed on 585 clinical isolates. The 5-micrograms pefloxacin disk is recommended, and the following breakpoints are proposed: susceptible, greater than or equal to 19 mm (MIC, less than or equal to 2.0 micrograms/ml); resistant, less than or equal to 15 mm (MIC, greater than 4.0 micrograms/ml); and intermediate, 16 to 18 mm.     

Ceftizoxime interpretive criteria for in vitro susceptibility tests with Neisseria gonorrhoeae.

Ceftizoxime was tested in triplicate against 100 clinical strains of Neisseria gonorrhoeae in accordance with National Committee for Clinical Laboratory Standards guidelines to establish susceptibility testing interpretive criteria. The MICs for 50 and 90% of the strains tested were 0.008 and 0.03 microgram/ml, respectively. These results confirm those of other studies reporting ceftizoxime's excellent activity against gonococci. Because no resistant strains were identified, a breakpoint MIC of < or = 0.5 microgram/ml was selected, with a correlate zone diameter of > or = 32 mm. Ceftizoxime appears to represent an alternative to other beta-lactamase-stable beta-lactams for cost-effective therapy of uncomplicated gonorrhea.     

Preliminary interpretive susceptibility testing criteria for FK-037 with 30-microgram disks.

FK-037, a new parenteral cephalosporin, was tested against 483 organisms from clinical infections to establish preliminary susceptibility testing criteria with 30-micrograms disks. The proposed breakpoint zone diameters were > or = 17 mm (MIC correlate, < or = 8 micrograms/ml) for the susceptible category and < or = 13 mm (MIC correlate, > or = 32 micrograms/ml) for the resistant category. These interpretive guidelines produced no very major (false-susceptible) errors, 2.9% major (false-resistant) errors, and 6.2% minor errors for a total absolute agreement between methods of 90.9%.     

Proposed quality control and interpretive criteria for disk diffusion susceptibility testing with enoxacin.

The standardized disk diffusion test, in which a 10-micrograms enoxacin disk is used, was performed and microbroth dilution MICs were determined to establish individual test control values with Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus ATCC 25923, and S. aureus ATCC 29213. In addition, regression analysis correlating inhibitory zone diameter with MICs for approximately 400 gram-negative clinical isolates was performed. Based on linear regression and error rate-bounded analyses, criteria for the category calls of isolates are proposed.     

Tentative interpretive standards for agar disk diffusion antimicrobial susceptibility testing of cefoperazone.

Cefoperazone is a new cephalosporin with a very wide spectrum of activity, including activity against Pseudomonas aeruginosa. It has less activity on enterococci and Acinetobacter. Of the 459 selected bacterial strains tested in this study, only 1.5% (7 strains and 6 genera) had minimum inhibitory concentrations of greater than or equal to 128 micrograms/ml. For a minimum inhibitory concentration breakpoint of less than or equal to 32 micrograms/ml (susceptible), we recommend that the disk diffusion test be done with a 75-micrograms disk and breakpoints of greater than or equal to 18 mm for susceptible, 15 to 17 mm for intermediate, and less than or equal to 14 mm for resistant. Diffusion tests using these criteria yielded only 1.1% very major or major errors.     

Tentative disk diffusion susceptibility interpretive criteria for BMY-28142, a new cephalosporin.

A total of 750 bacterial isolates, including 37 different species, were tested for susceptibility to BMY-28142 by standardized broth microdilution and disk diffusion tests. The zone diameter interpretive criteria tentatively suggested for the 30-micrograms BMY-28142 disk are as follows: susceptible = greater than or equal to 18 mm (MIC less than or equal to 8.0 micrograms/ml), resistant = less than or equal to 14 mm (MIC greater than or equal to 32 micrograms/ml), and indeterminate = 15 to 17 mm.     

Proposed interpretive criteria and quality control parameters for testing in vitro susceptibility of Neisseria gonorrhoeae to ciprofloxacin.

Ciprofloxacin was subjected to a multilaboratory study designed to determine its in vitro susceptibility criteria for Neisseria gonorrhoeae and its quality control parameters for both agar dilution and disk diffusion susceptibility testing for this species. All clinical isolates were susceptible, i.e., MICs were less than or equal to 0.06 microgram/ml and zones of inhibition were greater than or equal to 36 mm. A resistant category could not be defined, but in vitro-selected mutants gave zones of less than or equal to 35 mm, and MICs for these strains were greater than or equal to 0.12 microgram/ml. For quality control of ciprofloxacin agar dilution tests on supplemented GC agar, MICs for Staphylococcus aureus ATCC 29213 ranged from 0.12 to 0.5 microgram/ml. For quality control of 5-micrograms ciprofloxacin disk tests, N. gonorrhoeae ATCC 49226 and S. aureus ATCC 25923 produced acceptable zone diameter ranges of 48 to 58 mm and 22 to 26 mm, respectively.     

Quality control parameters and interpretive criteria for in vitro susceptibility tests with the macrolide azithromycin

Quality control parameters for broth microdilution and disk diffusion susceptibility tests were defined and the interpretive criteria for disk diffusion tests reviewed. For interpretation of tests with 15 µg azithromycin disks, the following criteria are recommended: 19 mm for the susceptible category (MIC2.0 µg/ml) and 15 mm for the resistant category (MIC8.0 µg/ml). Using these criteria, there was 97 % overall agreement between broth dilution and disk diffusion tests;Haemophilus influenzae isolates were susceptible to azithromycin by both methods. The quality control strainStaphylococcus aureus ATCC 25923 gave zones of 21 to 26 mm in diameter in a six-laboratory collaborative study. In azithromycin broth microdilution tests the following MIC control limits are recommended:Escherichia coli ATCC 25922, 2.0–8.0 µg/ml;Staphylococcus aureus ATCC 29213, 0.25–1.0 µg/ml; andEnterococcus faecalis ATCC 29212, 1.0–4.0 µg/ml.Collaborating investigators contributing data to the quality control studies include P. C. Fuchs, St. Vincent Hospital and Medical Center, Portland, Oregon; S. D. Allen, Indiana University Medical Center, Indianapolis, Indiana; E. H. Gerlach, St. Francis Regional Medical Center, Wichita, Kansas; J. A. Washington, The Cleveland Clinic Foundation, Cleveland, Ohio; L. B. Reller, University of Colorado Medical Center, Denver, Colorado, USA.     

Proposed interpretive criteria and quality control parameters for ofloxacin susceptibility testing of Neisseria gonorrhoeae.

A multilaboratory study designed to determine the in vitro susceptibility criteria and quality control parameters for ofloxacin against Neisseria gonorrhoeae was conducted according to the guidelines of the National Committee for Clinical Laboratory Standards. Proposed susceptibility breakpoints are MICs of less than or equal to 0.25 microgram/ml for the agar dilution test and greater than or equal to 31 mm for the disk diffusion test. A category for resistance could not be defined. Proposed acceptable quality control MICs for N. gonorrhoeae ATCC 49226 and Staphylococcus aureus ATCC 29213 range from 0.004 to 0.03 microgram/ml and 0.25 to 1.0 microgram/ml, respectively. With 5-micrograms ofloxacin disks, acceptable inhibitory zone diameters for S. aureus ATCC 25923 and the N. gonorrhoeae control strains range from 22 to 27 mm and 43 to 51 mm, respectively.     

In vitro activity of Ro 19-5247 (T-2525) and interpretive criteria for disk diffusion susceptibility testing.

The activity of Ro 19-5247 (the active metabolite of the oral cephalosporin Ro 19-5248 [T-2588]) was compared with that of five orally active agents against a total of 331 bacterial strains. Ro 19-5247 was more active in vitro than amoxicillin, amoxicillin-clavulanate, cefaclor, cefuroxime, and cephalexin against members of the family Enterobacteriaceae. Amoxicillin-clavulanate and amoxicillin overall were more active than the other four agents against staphylococci. Ro 19-5247, amoxicillin-clavulanate, amoxicillin, and cefuroxime were equally active against nonenterococcal streptococci and more active than cefaclor and cephalexin. All six agents showed little or no activity against nonfermentative gram-negative bacteria. Against Streptococcus (Enterococcus) faecalis, only amoxicillin and amoxicillin-clavulanate were active. The interpretive criteria for in vitro susceptibility testing with 10- and 30-micrograms Ro 19-5247 disks were established by regression analysis to correlate the inhibitory zone sizes and MICs for the bacterial isolates. The suggested tentative zone size breakpoints for the 10-micrograms disk are as follows: susceptible, greater than or equal to 22 mm (MIC, less than or equal to 2 micrograms/ml); moderately susceptible, 20 to 21 mm (MIC, 4 micrograms/ml); and resistant, less than or equal to 19 mm (MIC, greater than or equal to 8 micrograms/ml).     

Proposed interpretive criteria and quality control parameters for testing susceptibility of Neisseria gonorrhoeae to beta-lactam-clavulanate combinations.

To support future clinical studies, in vitro susceptibility tests were examined to determine whether Neisseria gonorrhoeae could be tested reliably against two beta-lactam-clavulanate combinations. All isolates that were tested appeared to be susceptible to amoxicillin and ticarcillin in combination with clavulanic acid. In the absence of resistant isolates, only a breakpoint for a susceptible category could be defined for agar dilution tests with amoxicillin-clavulanic acid (MIC of less than or equal to 2.0/1.0 micrograms/ml is tentatively proposed). For disk diffusion tests, a corresponding breakpoint zone diameter of greater than or equal to 28 mm is suggested. The validity of the breakpoints for penicillinase-negative penicillin-resistant strains awaits clinical data. Proposed quality control limits for testing amoxicillin-clavulanic acid by agar dilution and disk diffusion methods are a MIC of 0.25/0.125 to 1.0/0.5 micrograms/ml and zones of 30 to 40 mm in diameter for N. gonorrhoeae ATCC 49226, a MIC of 0.125/0.06 to 0.5/0.25 micrograms/ml for Staphylococcus aureus ATCC 29213, and zones of 30 to 38 mm for S. aureus ATCC 25923. Ticarcillin-clavulanate is currently tested against other species by preparing doubling dilutions of ticarcillin with a constant 2 micrograms of clavulanate per ml. By that method, all gonococci were susceptible to low concentrations. However, the amount of clavulanic acid that is included (2 micrograms/ml) will, by itself, inhibit many strains of N. gonorrhoeae. Consequently, the role of ticarcillin in the combination cannot be determined, and such tests are not recommended.     

Temafloxacin disk potency and tentative interpretive criteria for susceptibility tests.

Temafloxacin disk susceptibility test criteria were evaluated by testing 697 bacterial isolates. Either 5- or 10-micrograms disks could be used satisfactorily. A 5-micrograms temafloxacin disk with zone size breakpoints of less than or equal to 12 mm for resistance (MIC, greater than 4.0 micrograms/ml) and greater than 16 mm for susceptibility (MIC, less than or equal to 2.0 micrograms/ml) is recommended.     

Levofloxacin disk potency and tentative interpretive criteria for susceptibility tests.

Levofloxacin disk susceptibility test criteria were evaluated by testing 350 bacterial isolates. Either 5- or 10-micrograms disks could be used satisfactorily. A 5-micrograms levofloxacin disk with zone size breakpoints of < or = 12 mm for resistance (MIC, > or = 8.0 micrograms/ml) and > or = 16 mm for susceptibility (MIC, < or = 2.0 micrograms/ml) is recommended.     

Ampicillin-sulbactam susceptibility testing criteria

In vitro studies in five different medical centers documented the susceptibility of 2,440 consecutive isolates of theEnterobacteriaceae against ampicillin-sulbactam disks of different potencies. For determination of MICs, both 2:1 or 1:1 ratios were used as long as the concentrations of sulbactam at the breakpoints remained the same, i.e. MIC 16/8.0 µg/ml or 8.0/8.0 µg/ml for the susceptible category. Disks containing 10 µg of ampicillin and 10 µg of sulbactam are still to be preferred with interpretive criteria of 15 mm for susceptible and 11 mm for resistant (MIC 64/32 µg/ml or 32/32 µg/ml). The reliability of the disk test actually diminished when the amount of sulbactam in the disk was increased.     

Development of interpretive criteria and quality control limits for macrolide and clindamycin susceptibility testing of Streptococcus pneumoniae.

A six-laboratory collaborative study was conducted to develop MIC and zone diameter quality control limits and interpretive criteria for antimicrobial susceptibility testing of Streptococcus pneumoniae with azithromycin, clarithromycin, dirithromycin, and clindamycin. The MICs of all of the agents plus erythromycin for 302 clinical isolates of pneumococci that had been selected with an emphasis on resistant strains were determined by use of the National Committee for Clinical Laboratory Standards (NCCLS)-recommended broth microdilution procedure. The zone diameters of the isolates were also determined for the same agents except erythromycin by the NCCLS disk diffusion test procedure. Repeated testing of S. pneumoniae ATCC 49619 with different sources and lots of media and disks allowed development of MIC and zone diameter quality control ranges for these agents. Interpretive criteria for the MIC of azithromycin were established and were as follows: susceptible, < or = 0.5 microgram/ml; intermediate, 1 microgram/ml; and resistant, > or = 2 micrograms/ml. The interpretive criteria advocated for the MICs of clarithromycin and clindamycin were as follows: susceptible, < or = 0.25 microgram/ml; intermediate, 0.5 microgram/ml; and resistant, > or = 1 microgram/ml. Comparison of MICs and disk diffusion zone diameters led to the development of interpretive criteria for the zone diameters for azithromycin, clarithromycin, and clindamycin that correlated well with these MIC breakpoints. Testing of this organism collection also led to the reestablishment of the erythromycin MIC breakpoints as being identical to those of clarithromycin, which resulted in equivalent cross-susceptibility and cross-resistance for the three macrolides that are currently marketed in the United States. Thus, the susceptibility of pneumococci to azithromycin and clarithromycin can be predicted accurately by testing only erythromycin in clinical laboratories. This recommendation, as well as the interpretive and quality control criteria that are described, have been accepted by NCCLS and are included in the latest NCCLS susceptibility testing guidelines.     

Disk diffusion susceptibility tests with norfloxacin: confirmation of proposed interpretive criteria

One hundred and eighty three clinical isolates of aerobic bacteria were tested against norfloxacin by both agar dilution (WHO-ICS) and disk diffusion test procedures (standardized FDA single disk test). Two experimental 10μg norfloxacin disks were studied. Results were analyzed in terms of recently recommended breakpoints for clinical susceptibility (MIC ? 16μg/ml, zone diameter ? 17 mm) and resistance (MIC ? 32μg/ml, zone diameter ? 12 mm). Excellent correlation was demonstrated by statistical analysis between paired MIC and zone size values (average value for each MIC; r=?0.9782). An MIC of 16μg/ml was found to correlate with a zone of 10.4 mm. Application of the recommended zone size breakpoints resulted in prediction of 177 isolates as being susceptible while six (3.3 %) were predicted to be either intermediate or resistant. The findings of this study validate the earlier recommendations stated above.     

Multicenter evaluation of the proposed quality control limits and interpretive zone standards for in vitro susceptibility testing with norfloxacin.

A seven-center collaborative study was carried out to evaluate the in vitro performance of the 10 micrograms norfloxacin disks on the basis of previously proposed interpretive susceptibility zone standards and quality control parameters. Of 7,858 clinical isolates tested, 93.2, 4.9, and 1.9% fell into the susceptible, moderately susceptible, and resistant groups, respectively. The quality control data based on a total of 1,368 zone diameter measurements compared quite favorably with the proposed performance limits as follows: Escherichia coli ATCC 25922, 28 to 35 mm versus 28 to 36 mm; Staphylococcus aureus ATCC 25923, 21 to 29 mm versus 17 to 29 mm; and Pseudomonas aeruginosa ATCC 27853, 23 to 27 mm versus 22 to 29 mm.     

Reassessment of susceptibility test interpretive criteria for ticarcillin and ticarcillin-clavulanic acid.

There are at least four different existing or proposed interpretive criteria for the disk diffusion susceptibility testing of ticarcillin and ticarcillin plus clavulanic acid (T/C). To assess these criteria, 570 gram-negative bacillary isolates were tested for susceptibility to ticarcillin and T/C by both disk diffusion and broth microdilution methods. These included 53 strains of the family Enterobacteriaceae selected for ticarcillin resistance and high-level beta-lactamase production. The broth microdilution test results were more influenced by increased beta-lactamase production than were disk diffusion results. In the absence of published data indicating which of the two standardized test methods better predicts clinical response, we conclude that until such data are available the more conservative National Committee for Clinical Laboratory Standards tentative criteria for tests with members of the Enterobacteriaceae are appropriate. Our data do not support the use of separate T/C interpretive criteria for Pseudomonas spp. and members of the Enterobacteriaceae. The appropriateness of different interpretive criteria needs further evaluation.     

Ramoplanin susceptibility testing criteria.

Ramoplanin and mupirocin are two antimicrobial agents that may be applied topically. They had similar potencies against susceptible gram-positive cocci, but they differed in their spectra of activity. In plastic microdilution trays, the in vitro activity of ramoplanin was slightly diminished but that activity was restored by the addition of bovine serum albumin (0.02%). Susceptible strains were defined as those for which MICs of ramoplanin were < or = 2.0 micrograms/ml (without bovine serum albumin) and which had > or = 11-mm zones around 60-micrograms ramoplanin disks. Criteria for a resistant category cannot be defined at this time.