JOURNAL OF CLINICAL MICROBIOLOGY, May 1992, p. 1317-1319
Vol. 30, No. 5
0095-1137/92/051317-03$02.00/0 Copyright © 1992, American Society for Microbiology
MIC and Disk Diffusion Quality Control Guidelines for Neisseria gonorrhoeae Susceptibility Tests of Cefdinir, Cefetamet, CI-960, Fleroxacin, Lomefloxacin, and Temafloxacin M. E. ERWIN,' R. N. JONES,l 2,3* F. P. KOONTZ,2 E. H. GERLACH,4 P. R. MURRAY,s AND J. A. WASHINGTON6 1 Anti-Infectives Research Center, Clinical Microbiology Laboratories,2 and Special Microbiology,3 University of Iowa College of Medicine, Iowa City, Iowa 52242; St. Francis Regional Medical Center, Wichita, Kansas 672144;Washington University School of Medicine, St. Louis, Missouri 631105; and The Cleveland Clinic Foundation, Cleveland, Ohio 441956 Received 12 September 1991/Accepted 27 January 1992
Cefdinir (FK482), cefetamet (Ro 15-8074), CI-960, fleroxacin, lomefloxacin, and temafloxacin have potent activities against Neisseria gonorrhoeae. They were tested in a multilaboratory study to establish quality control guidelines. Quality control ranges for N. gonorrhoeae ATCC 49226 were determined by using multiple GC agar lots, three disk lots, and a number of test replicates consistent with the M23-T guidelines of the National Committee for Clinical Laboratory Standards. The MIC ranges included 2 to 4 log2 dilution steps. The recommended inhibition zone diameter ranges were generally 7 to 8 mm and included .91.3% of all recorded study results.
With the increasing prevalence of antimicrobial agentresistant strains of Neisseria gonorrhoeae (4), different strategies for epidemiologic control must be investigated. Also, more drugs have been introduced as options for the successful treatment of these difficult-to-treat strains, thus requiring standardized testing methods. The National Committee for Clinical Laboratory Standards (NCCLS) Gonococcus Working Group and subsequent independent investigators have identified numerous additional compounds that should be added to those that have already been approved for testing against N. gonorrhoeae. Those drugs listed in the NCCLS method tables are ceftriaxone, penicillin, spectinomycin, cefotaxime, cefoxitin, ceftazidime, tetracycline, cefuroxime, cefixime, cefotetan, ofloxacin, enoxacin, and temafloxacin (11, 12, 15-17). This report summarizes the results submitted to the NCCLS from multilaboratory studies to establish MIC and disk quality control (QC) guidelines for cefdinir (FK482), cefetamet (Ro 15-8074), CI-960, fleroxacin, lomefloxacin, and temafloxacin by using the N. gonorrhoeae ATCC 49226 QC strain (11). QC parameters for another related compound, ciprofloxacin, have also been reported (5). Each drug described in this report has demonstrated potent in vitro activity against gonococci (1, 3, 6-8, 10). The following reagent powders were obtained from the indicated sources: cefdinir and CI-960, Warner-Lambert/ Parke-Davis (Ann Arbor, Mich.); cefetamet and fleroxacin, Hoffmann-La Roche Inc. (Nutley, N.J.); lomefloxacin, G. D. Searle and Company (Skokie, Ill.); and temafloxcin, Abbott Laboratories (North Chicago, Ill.). Susceptibility disks were manufactured by Becton Dickinson Microbiology Systems (Cockeysville, Md.) or Difco Laboratories (Detroit, Mich.). Three disk lots for each drug were used, with no more than two lots coming from one company. Seven lots of GC agar from three different manufacturers were also used,
*
Corresponding author.
as follows: Becton Dickinson Microbiology Systems lots A4DY10 (common), A3DWXC, and K2GWPM; Difco lots 774960, 783222, and 785427; and Oxoid USA, Inc. (Columbia, Md.) lot 292-41686. The study design conformed to the guidelines presented in the NCCLS M23-T document (14). Susceptibility tests were performed by the agar dilution and disk diffusion methods recommended by the NCCLS for testing N. gonorrhoeae (15, 16). Briefly, replicate tests of N. gonorrhoeae ATCC 49226 were performed such that 20 MICs and 60 inhibition zone diameters were generated for each drug with each laboratory's unique medixum lot, and an additional 5 MICs and 15 inhibition zone diameters were produced for each drug with the common lot of GC agar base. Thus, each participating site provided 25 MICs and 75 inhibition zone diameters for each antimicrobial agent examined. Table 1 presents the agar dilution MIC results from the six laboratories. The common-lot results revealed a technical variation by one participating laboratory only when cefdinir was tested. That laboratory's cefdinir results were therefore excluded from the unique-lot analysis. A distinct MIC mode was established for the QC strain when it was tested against cefdinir, lomefloxacin, and temafloxacin. The MICs of all of these drugs were within a proposed MIC mode + 1 log2 dilution step range (2). Cefetamet MICs had a bimodal distribution. The actual cefetamet MIC probably was between the observed modes of 0.03 and 0.06 ,ug/ml (50 occurrences each). Furthermore, equal distributions were found at 0.015 and 0.12 ,ug/ml, requiring a four-dilution range (2). All MIC results for CI-960 and fleroxacin, two fluoroquinolones, were at two adjacent log2 dilutions. By using the QC statistical method suggested by Barry et al. (2), the proposed range for fleroxacin would be 0.015 to 0.03 ,ug/mI. All CI-960 MIC results were between 0.001 and 0.002 ,g/ml. The MIC occurrences at 0.0005 ,ug/ml were essentially nil (as determined by R.N.J.), and clinical laboratories very rarely test antimicrobial agents below 0.001-,ug/ml concentrations. 1317
1318
J. CLIN. MICROBIOL.
NOTES
TABLE 1. GC agar dilution MICs from a six-laboratory study with N. gonorrhoeae ATCC 49226 Antibiotic
No. of MIC occurrences at MIC (pug/ml) of:
Medium lot
'0.001
0.008
0.015
0.03
0.06
[10 0
56 20
34]" 5
0 0
0 0
[20 5
42 8
38 12
Unique Common
0 0
[60 25
60]
0 0
Unique Common
[0 0
100 25
20] 5
0 0
Unique Common
[0 0
76 30
44] 0
0 0
Cefdinir
Uniquea Common
Cefetamet
Unique Common
CI-960
Lomefloxacin Temafloxacin
0.004
0 0
Unique Common
Fleroxacin
0.002
60] 10
[60 20
0.12
0.25
20]
0 0
5
0
0 5
a Unique lot results excluded from one participating laboratory because of significant variation from the MIC mode for all participating laboratories. "Brackets indicate the proposed QC MIC range, usually the modal MIC t 1 log2 dilution step.
Therefore, a practical QC range of 90% of disk test zones were within the calculated ranges (12) (cefetamet, this study).
Modification of the median range statistic (increase of inhibition zone from 1 to 3 mm) was necessary for cefdinir, CI-960, fleroxacin, lomefloxacin, and temafloxacin to ensure a proposed QC range with .90% reagent performance with the control strain. In contrast, if a more traditional 95 or 98% confidence limit were used, the QC inhibition zone diameter range would be so lenient as to produce meaningless QC limits. The inhibition zone diameter produced by the three disk lots for each antimicrobial agent did not differ significantly. Also, the common-lot median inhibition zone diameter did not vary by more than 1 mm from that observed for all unique lots (Table 2). The proposed QC data for the six antimicrobial agents presented here expand the number of compounds against which N. gonorrhoeae strains can be reliably tested. Of the drugs tested, temafloxacin QC guidelines have been accepted by the NCCLS (17). QC guidelines for the remaining compounds should be considered tentative until they are officially adopted or modified by national standardization groups. Among the drugs tested, cefetamet, fleroxacin, and temafloxacin have already been used as single-dose regimens to treat uncomplicated gonorrhea, with excellent clinical success reported (9, 13, 18).
TABLE 2. Comparison of median inhibition zone diameter results from five GC agar lots unique to each study site and the common lot processed by all study participantsa
Unique test lots
Common lot
QC range by statistical method
(disk content [,g])
Median zone diam (mm)
One-half of median range (mm)
median zone diam (mm)
Median (mm)
90% confidence limit (mm)
proposed
Cefdinir (5) Cefetamet (30) CI-960 (5) Fleroxacin (5) Lomefloxacin (10) Temafloxacin (5)
44 45 59 48 50 46
2 4 3 3 3 3
43 44 59 48 51 47
42-46 41-49 56-62 45-51 47-53 43-49
41-48 41-49 53-62 43-51
94.0 97.7 93.3 94.3 91.3 93.0
Antimicrobial agent
46-53 42-50
% Zones in
rangeb
a One laboratory with significant variation of the median inhibition zone diameter for all drugs compared with those obtained by all participating laboratories was excluded. A total of 300 tests were performed with unique test lots, and 75 tests were performed with common test lots. 6 Proposed QC ranges were derived from .90% confidence limit statistics.
VOL. 30, 1992
REFERENCES 1. Barrett, M. S., R. N. Jones, M. E. Erwin, D. M. Johnson, and B. M. Briggs. 1991. Antimicrobial activity evaluations of two new quinolones PD 127391 (CI-960, AM-1091) and PD131628. Diagn. Microbiol. Infect. Dis. 14:389-401. 2. Barry, A. L., P. C. Fuchs, R. N. Jones, and The Collaborative Antimicrobial Susceptibility Testing Group. 1989. Statistical criteria for selecting quality control limits for broth microdilution susceptibility tests with 39 different antimicrobial agents. Diagn. Microbiol. Infect. Dis. 12:13-42. 3. Briggs, B. M., R. N. Jones, M. E. Erwin, M. S. Barrett, and D. M. Johnson. 1991. In vitro activity evaluations of cefdinir (FK482, CI-983, PD 134393) a novel orally administered cephalosporin. Diagn. Microbiol. Infect. Dis. 14:425-434. 4. Centers for Disease Control. 1990. Plasmid-mediated antimicrobial resistances in Neisseria gonorrhoeae. United States, 1988 and 1989. Morbid. Mortal. Weekly Rep. 39:284-293. 5. Fuchs, P. C., A. L. Barry, C. Baker, P. R. Murray, and J. A. Washington. 1991. Proposed interpretive criteria and quality control parameters for testing in vitro susceptibility of Neisseria gonorrhoeae to ciprofloxacin. J. Clin. Microbiol. 29:2111-2114. 6. Hardy, D. J., R. N. Swanson, D. M. Hensey, N. R. Ramer, R. R. Bower, C. W. Hanson, D. T. W. Chu, and P. B. Fernandes. 1987. Comparative antibacterial activities of temafloxacin hydrochloride (A-62254) and two reference fluoroquinolones. Antimicrob. Agents Chemother. 31:1768-1774. 7. Hirai, K., H. Aoyama, M. Hosaka, Y. Oomori, Y. Niwata, S. Suzue, and T. Irikura. 1986. In vitro and in vivo antibacterial activity of AM-833, a new quinolone derivative. Antimicrob. Agents Chemother. 29:1059-1066. 8. Hirose, T., E. Okezaki, H. Kato, Y. Ito, M. Inoue, and S. Mitsuhashi. 1987. In vitro and in vivo activity of NY-198, a new difluorinated quinolone. Antimicrob. Agents Chemother. 31: 854-859. 9. Hook, E. W., M. Rodriguez, W. Mogabgag, and J. C. Craft. 1990. Program Abstr. 30th Intersci. Conf. Antimicrob. Agents Chemother., abstr. 101. 10. Jones, R. N., and A. L. Barry. 1987. Preliminary antimicrobial
NOTES
11.
12.
13. 14.
15.
16.
17.
18.
1319
susceptibility interpretive criteria for cefetamet (Ro 15-8074) and cefteram (Ro 19-5247) disk tests. J. Clin. Microbiol. 25: 1796-1798. Jones, R. N., T. L. Gavan, C. Thornsberry, P. C. Fuchs, E. H. Gerlach, J. S. Knapp, P. Murray, and J. A. Washington II. 1989. Standardization of disk diffusion and agar dilution susceptibility tests for Neisseria gonorrhoeae: interpretive criteria and quality control guidelines for ceftriaxone, penicillin, spectinomycin, and tetracycline. J. Clin. Microbiol. 27:2758-2766. Jones, R. N., E. H. Gerlach, F. P. Koontz, P. R. Murray, M. A. Pfaller, J. A. Washington, M. E. Erwin, and C. C. Knapp. 1991. Development of Neissenia gonorrhoeae in vitro susceptibility test methods for cefixime including quality control guidelines. Diagn. Microbiol. Infect. Dis. 14:383-388. Lassus, A., 0. Renkonen, and J. ElImen. 1988. Fleroxacin versus standard therapy in gonococcal urethritis. J. Antimicrob. Chemother. 22:223-225. National Committee for Clinical Laboratory Standards. 1989. Tentative standard M23-T. Development of in vitro susceptibility testing criteria and quality control parameters. National Committee for Clinical Laboratory Standards, Villanova, Pa. National Committee for Clinical Laboratory Standards. 1990. Approved standard M2-A4. Performance standards for antimicrobic disk susceptibility tests. National Committee for Clinical Laboratory Standards, Villanova, Pa. National Committee for Clinical Laboratory Standards. 1990. Approved standard M7-A2. Standard methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. National Committee for Clinical Laboratory Standards, Villanova, Pa. National Committee for Clinical Laboratory Standards. 1991. Information supplement M100-S3, 3rd ed. National Committee for Clinical Laboratory Standards, Villanova, Pa. Tio, T. T., I. R. Sindhunata, H. H. T. Wagenvoort, M. F. Michel, and E. Stolz. 1990. Different doses of cefetamet pivoxil (Ro 15-8075) in the treatment of acute uncomplicated gonococcal urethritis in men. Antimicrob. Agents Chemother. 34:674-675.
Vol. 30, No. 5
0095-1137/92/051317-03$02.00/0 Copyright © 1992, American Society for Microbiology
MIC and Disk Diffusion Quality Control Guidelines for Neisseria gonorrhoeae Susceptibility Tests of Cefdinir, Cefetamet, CI-960, Fleroxacin, Lomefloxacin, and Temafloxacin M. E. ERWIN,' R. N. JONES,l 2,3* F. P. KOONTZ,2 E. H. GERLACH,4 P. R. MURRAY,s AND J. A. WASHINGTON6 1 Anti-Infectives Research Center, Clinical Microbiology Laboratories,2 and Special Microbiology,3 University of Iowa College of Medicine, Iowa City, Iowa 52242; St. Francis Regional Medical Center, Wichita, Kansas 672144;Washington University School of Medicine, St. Louis, Missouri 631105; and The Cleveland Clinic Foundation, Cleveland, Ohio 441956 Received 12 September 1991/Accepted 27 January 1992
Cefdinir (FK482), cefetamet (Ro 15-8074), CI-960, fleroxacin, lomefloxacin, and temafloxacin have potent activities against Neisseria gonorrhoeae. They were tested in a multilaboratory study to establish quality control guidelines. Quality control ranges for N. gonorrhoeae ATCC 49226 were determined by using multiple GC agar lots, three disk lots, and a number of test replicates consistent with the M23-T guidelines of the National Committee for Clinical Laboratory Standards. The MIC ranges included 2 to 4 log2 dilution steps. The recommended inhibition zone diameter ranges were generally 7 to 8 mm and included .91.3% of all recorded study results.
With the increasing prevalence of antimicrobial agentresistant strains of Neisseria gonorrhoeae (4), different strategies for epidemiologic control must be investigated. Also, more drugs have been introduced as options for the successful treatment of these difficult-to-treat strains, thus requiring standardized testing methods. The National Committee for Clinical Laboratory Standards (NCCLS) Gonococcus Working Group and subsequent independent investigators have identified numerous additional compounds that should be added to those that have already been approved for testing against N. gonorrhoeae. Those drugs listed in the NCCLS method tables are ceftriaxone, penicillin, spectinomycin, cefotaxime, cefoxitin, ceftazidime, tetracycline, cefuroxime, cefixime, cefotetan, ofloxacin, enoxacin, and temafloxacin (11, 12, 15-17). This report summarizes the results submitted to the NCCLS from multilaboratory studies to establish MIC and disk quality control (QC) guidelines for cefdinir (FK482), cefetamet (Ro 15-8074), CI-960, fleroxacin, lomefloxacin, and temafloxacin by using the N. gonorrhoeae ATCC 49226 QC strain (11). QC parameters for another related compound, ciprofloxacin, have also been reported (5). Each drug described in this report has demonstrated potent in vitro activity against gonococci (1, 3, 6-8, 10). The following reagent powders were obtained from the indicated sources: cefdinir and CI-960, Warner-Lambert/ Parke-Davis (Ann Arbor, Mich.); cefetamet and fleroxacin, Hoffmann-La Roche Inc. (Nutley, N.J.); lomefloxacin, G. D. Searle and Company (Skokie, Ill.); and temafloxcin, Abbott Laboratories (North Chicago, Ill.). Susceptibility disks were manufactured by Becton Dickinson Microbiology Systems (Cockeysville, Md.) or Difco Laboratories (Detroit, Mich.). Three disk lots for each drug were used, with no more than two lots coming from one company. Seven lots of GC agar from three different manufacturers were also used,
*
Corresponding author.
as follows: Becton Dickinson Microbiology Systems lots A4DY10 (common), A3DWXC, and K2GWPM; Difco lots 774960, 783222, and 785427; and Oxoid USA, Inc. (Columbia, Md.) lot 292-41686. The study design conformed to the guidelines presented in the NCCLS M23-T document (14). Susceptibility tests were performed by the agar dilution and disk diffusion methods recommended by the NCCLS for testing N. gonorrhoeae (15, 16). Briefly, replicate tests of N. gonorrhoeae ATCC 49226 were performed such that 20 MICs and 60 inhibition zone diameters were generated for each drug with each laboratory's unique medixum lot, and an additional 5 MICs and 15 inhibition zone diameters were produced for each drug with the common lot of GC agar base. Thus, each participating site provided 25 MICs and 75 inhibition zone diameters for each antimicrobial agent examined. Table 1 presents the agar dilution MIC results from the six laboratories. The common-lot results revealed a technical variation by one participating laboratory only when cefdinir was tested. That laboratory's cefdinir results were therefore excluded from the unique-lot analysis. A distinct MIC mode was established for the QC strain when it was tested against cefdinir, lomefloxacin, and temafloxacin. The MICs of all of these drugs were within a proposed MIC mode + 1 log2 dilution step range (2). Cefetamet MICs had a bimodal distribution. The actual cefetamet MIC probably was between the observed modes of 0.03 and 0.06 ,ug/ml (50 occurrences each). Furthermore, equal distributions were found at 0.015 and 0.12 ,ug/ml, requiring a four-dilution range (2). All MIC results for CI-960 and fleroxacin, two fluoroquinolones, were at two adjacent log2 dilutions. By using the QC statistical method suggested by Barry et al. (2), the proposed range for fleroxacin would be 0.015 to 0.03 ,ug/mI. All CI-960 MIC results were between 0.001 and 0.002 ,g/ml. The MIC occurrences at 0.0005 ,ug/ml were essentially nil (as determined by R.N.J.), and clinical laboratories very rarely test antimicrobial agents below 0.001-,ug/ml concentrations. 1317
1318
J. CLIN. MICROBIOL.
NOTES
TABLE 1. GC agar dilution MICs from a six-laboratory study with N. gonorrhoeae ATCC 49226 Antibiotic
No. of MIC occurrences at MIC (pug/ml) of:
Medium lot
'0.001
0.008
0.015
0.03
0.06
[10 0
56 20
34]" 5
0 0
0 0
[20 5
42 8
38 12
Unique Common
0 0
[60 25
60]
0 0
Unique Common
[0 0
100 25
20] 5
0 0
Unique Common
[0 0
76 30
44] 0
0 0
Cefdinir
Uniquea Common
Cefetamet
Unique Common
CI-960
Lomefloxacin Temafloxacin
0.004
0 0
Unique Common
Fleroxacin
0.002
60] 10
[60 20
0.12
0.25
20]
0 0
5
0
0 5
a Unique lot results excluded from one participating laboratory because of significant variation from the MIC mode for all participating laboratories. "Brackets indicate the proposed QC MIC range, usually the modal MIC t 1 log2 dilution step.
Therefore, a practical QC range of 90% of disk test zones were within the calculated ranges (12) (cefetamet, this study).
Modification of the median range statistic (increase of inhibition zone from 1 to 3 mm) was necessary for cefdinir, CI-960, fleroxacin, lomefloxacin, and temafloxacin to ensure a proposed QC range with .90% reagent performance with the control strain. In contrast, if a more traditional 95 or 98% confidence limit were used, the QC inhibition zone diameter range would be so lenient as to produce meaningless QC limits. The inhibition zone diameter produced by the three disk lots for each antimicrobial agent did not differ significantly. Also, the common-lot median inhibition zone diameter did not vary by more than 1 mm from that observed for all unique lots (Table 2). The proposed QC data for the six antimicrobial agents presented here expand the number of compounds against which N. gonorrhoeae strains can be reliably tested. Of the drugs tested, temafloxacin QC guidelines have been accepted by the NCCLS (17). QC guidelines for the remaining compounds should be considered tentative until they are officially adopted or modified by national standardization groups. Among the drugs tested, cefetamet, fleroxacin, and temafloxacin have already been used as single-dose regimens to treat uncomplicated gonorrhea, with excellent clinical success reported (9, 13, 18).
TABLE 2. Comparison of median inhibition zone diameter results from five GC agar lots unique to each study site and the common lot processed by all study participantsa
Unique test lots
Common lot
QC range by statistical method
(disk content [,g])
Median zone diam (mm)
One-half of median range (mm)
median zone diam (mm)
Median (mm)
90% confidence limit (mm)
proposed
Cefdinir (5) Cefetamet (30) CI-960 (5) Fleroxacin (5) Lomefloxacin (10) Temafloxacin (5)
44 45 59 48 50 46
2 4 3 3 3 3
43 44 59 48 51 47
42-46 41-49 56-62 45-51 47-53 43-49
41-48 41-49 53-62 43-51
94.0 97.7 93.3 94.3 91.3 93.0
Antimicrobial agent
46-53 42-50
% Zones in
rangeb
a One laboratory with significant variation of the median inhibition zone diameter for all drugs compared with those obtained by all participating laboratories was excluded. A total of 300 tests were performed with unique test lots, and 75 tests were performed with common test lots. 6 Proposed QC ranges were derived from .90% confidence limit statistics.
VOL. 30, 1992
REFERENCES 1. Barrett, M. S., R. N. Jones, M. E. Erwin, D. M. Johnson, and B. M. Briggs. 1991. Antimicrobial activity evaluations of two new quinolones PD 127391 (CI-960, AM-1091) and PD131628. Diagn. Microbiol. Infect. Dis. 14:389-401. 2. Barry, A. L., P. C. Fuchs, R. N. Jones, and The Collaborative Antimicrobial Susceptibility Testing Group. 1989. Statistical criteria for selecting quality control limits for broth microdilution susceptibility tests with 39 different antimicrobial agents. Diagn. Microbiol. Infect. Dis. 12:13-42. 3. Briggs, B. M., R. N. Jones, M. E. Erwin, M. S. Barrett, and D. M. Johnson. 1991. In vitro activity evaluations of cefdinir (FK482, CI-983, PD 134393) a novel orally administered cephalosporin. Diagn. Microbiol. Infect. Dis. 14:425-434. 4. Centers for Disease Control. 1990. Plasmid-mediated antimicrobial resistances in Neisseria gonorrhoeae. United States, 1988 and 1989. Morbid. Mortal. Weekly Rep. 39:284-293. 5. Fuchs, P. C., A. L. Barry, C. Baker, P. R. Murray, and J. A. Washington. 1991. Proposed interpretive criteria and quality control parameters for testing in vitro susceptibility of Neisseria gonorrhoeae to ciprofloxacin. J. Clin. Microbiol. 29:2111-2114. 6. Hardy, D. J., R. N. Swanson, D. M. Hensey, N. R. Ramer, R. R. Bower, C. W. Hanson, D. T. W. Chu, and P. B. Fernandes. 1987. Comparative antibacterial activities of temafloxacin hydrochloride (A-62254) and two reference fluoroquinolones. Antimicrob. Agents Chemother. 31:1768-1774. 7. Hirai, K., H. Aoyama, M. Hosaka, Y. Oomori, Y. Niwata, S. Suzue, and T. Irikura. 1986. In vitro and in vivo antibacterial activity of AM-833, a new quinolone derivative. Antimicrob. Agents Chemother. 29:1059-1066. 8. Hirose, T., E. Okezaki, H. Kato, Y. Ito, M. Inoue, and S. Mitsuhashi. 1987. In vitro and in vivo activity of NY-198, a new difluorinated quinolone. Antimicrob. Agents Chemother. 31: 854-859. 9. Hook, E. W., M. Rodriguez, W. Mogabgag, and J. C. Craft. 1990. Program Abstr. 30th Intersci. Conf. Antimicrob. Agents Chemother., abstr. 101. 10. Jones, R. N., and A. L. Barry. 1987. Preliminary antimicrobial
NOTES
11.
12.
13. 14.
15.
16.
17.
18.
1319
susceptibility interpretive criteria for cefetamet (Ro 15-8074) and cefteram (Ro 19-5247) disk tests. J. Clin. Microbiol. 25: 1796-1798. Jones, R. N., T. L. Gavan, C. Thornsberry, P. C. Fuchs, E. H. Gerlach, J. S. Knapp, P. Murray, and J. A. Washington II. 1989. Standardization of disk diffusion and agar dilution susceptibility tests for Neisseria gonorrhoeae: interpretive criteria and quality control guidelines for ceftriaxone, penicillin, spectinomycin, and tetracycline. J. Clin. Microbiol. 27:2758-2766. Jones, R. N., E. H. Gerlach, F. P. Koontz, P. R. Murray, M. A. Pfaller, J. A. Washington, M. E. Erwin, and C. C. Knapp. 1991. Development of Neissenia gonorrhoeae in vitro susceptibility test methods for cefixime including quality control guidelines. Diagn. Microbiol. Infect. Dis. 14:383-388. Lassus, A., 0. Renkonen, and J. ElImen. 1988. Fleroxacin versus standard therapy in gonococcal urethritis. J. Antimicrob. Chemother. 22:223-225. National Committee for Clinical Laboratory Standards. 1989. Tentative standard M23-T. Development of in vitro susceptibility testing criteria and quality control parameters. National Committee for Clinical Laboratory Standards, Villanova, Pa. National Committee for Clinical Laboratory Standards. 1990. Approved standard M2-A4. Performance standards for antimicrobic disk susceptibility tests. National Committee for Clinical Laboratory Standards, Villanova, Pa. National Committee for Clinical Laboratory Standards. 1990. Approved standard M7-A2. Standard methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. National Committee for Clinical Laboratory Standards, Villanova, Pa. National Committee for Clinical Laboratory Standards. 1991. Information supplement M100-S3, 3rd ed. National Committee for Clinical Laboratory Standards, Villanova, Pa. Tio, T. T., I. R. Sindhunata, H. H. T. Wagenvoort, M. F. Michel, and E. Stolz. 1990. Different doses of cefetamet pivoxil (Ro 15-8075) in the treatment of acute uncomplicated gonococcal urethritis in men. Antimicrob. Agents Chemother. 34:674-675.
