Criteria for Disk Susceptibility Tests and Quality Control Guidelines

Transcription

1 JOURNAL OF CLINICAL MICROBIOLOGY, Jn. 1988, p /88/ $02.00/0 Copyright C 1988, Americn Society for Microiology Vol. 26, No. 1 Criteri for Disk Susceptiility Tests nd Qulity Control Guidelines for the Cefoperzone-Sulctm Comintion ARTHUR L. BARRY,* RONALD N. JONES, AND THE COLLABORATIVE ANTIMICROBIAL SUSCEPTIBILITY TESTING GROUPt The Clinicl Microiology Institute, Tultin, Oregon Received 6 July 1987/Accepted 16 Septemer 1987 For in vitro susceptiility tests with cefoperzone nd sulctm ( I-lctmse inhiitor), 75/30-,ig disks my e used with the interpretive zone size rekpoints tht re currently used for 75-,ug cefoperzone disks. For dilution tests, 2:1 rtio of cefoperzone to sulctm is recommended. For qulity control purposes, MIC limits tht re used to monitor cefoperzone tests were lso pplied to tests with the comintion of drugs. For grm-negtive control strins, zone size limits were clculted to e 1 mm smller thn those used for cefoperzone disks. To monitor the sulctm portion of the comintion, Acinetocter clkoceticus susp. nitrtus ATCC ws selected; zones with 75/30-,ig disks were 26 to 32 mm in dimeter, nd roth microdilution MICs rnged from 1.0/0.5 to 8.0/4.0,ug/ml. With cefoperzone lone, MICs for Acinetocter clcoceticus susp. nitrtus were 16 to 64,ug/ml nd zones rnged from 14 to 18 mm in dimeter. For neroic dilution tests, only Bcteroides thetiotomicron ATCC is recommended for cefoperzonesulctm; MICs rnged from 8.0/4.0 to 32/16,ig/ml. Although cefoperzone is reltively stle to stphylococcl 1-lctmses nd to most chromosomlly medited P-lctmses from grm-negtive cilli, it cn e hydrolyzed y some plsmid-medited P-lctmses tht my e produced y memers of the fmily Enteroctericee (6, 9, 11). Cephlosporinses produced y most memers of the Bcteroides frgilis group will lso hydrolyze cefoperzone (1, 3, 4). The spectrum of useful nticteril ctivity of cefoperzone my e expnded when it is comined with,-lctmse inhiitor (6, 9, 11). Sulctm is penicillinic cid sulfone with limited nticteril ctivity ut with the ility to irreversily ind with mny,-lctmse enzymes (5). In the presence of sulctm, the nticteril ctivity of cefoperzone should e expnded to include most neroic cteri nd mny of the P-lctmse-producing enteric cilli tht re endemic in some institutions. Cefoperzone nd sulctm hve een comined for prenterl dministrtion, nd we hve een concerned with the question of how in vitro susceptiility tests should e performed with tht comintion. In previous report (8), we concluded tht for roth or gr dilution tests, 2 prts cefoperzone should e comined with 1 prt sulctm. In the present report, we confirm the utility of this 2:1 rtio nd lso define qulity control guidelines for roth microdilution susceptiility tests nd for neroic gr dilution tests. In ddition, studies were performed to define disk content, interpretive criteri, nd qulity control guidelines for the disk diffusion susceptiility tests. * Corresponding uthor. t In ddition to dt given y The Clinicl Microiology Institute, qulity control dt were contriuted y the following prticipnts: S. D. Allen, Indin University Medicl Center, Indinpolis, IN 46223; L. W. Ayers, The Ohio Stte University Medicl Center, Columus, OH 43210; P. C. Fuchs, St. Vincent Medicl Center, Portlnd, OR 97225; E. H. Gerlch, St. Frncis Medicl Center, Wichit, KA 67214; J. A. Wshington nd T. L. Gvn, The Clevelnd Clinic Foundtion, Clevelnd, OH 44106; L. B. Reller, University of Colordo Medicl Center, Denver, CO 80262; nd C. Thornserry, Centers for Disese Control, Atlnt, GA MATERIALS AND METHODS Antimicroil gents. Cefoperzone nd sulctm were provided y Pfizer, Inc. (New York, N.Y.). Disks were prepred y BBL Microiology Systems (Cockeysville, Md.). Bcteril isoltes. Bcteril isoltes were collected from vriety of medicl centers throughout the United Sttes. The isoltes were initilly selected to include pproximtely equl numers of cefoperzone-susceptile nd -resistnt strins within most species. Consequently, the chllenge set of isoltes does not represent the type of isoltes tht would e expected in norml prctice. Included in this evlution were 189 memers of the fmily Enteroctericee, 62 Pseudomons species, nd 21 Acinetocter clcoceticus isoltes. Additionl studies were performed with 87 neroic cteril isoltes, including 62 memers of the B. frgilis group nd 25 grm-positive neroic cteril isoltes. Antimicroil susceptiility tests. Broth microdilution susceptiility tests were performed ccording to the procedures outlined y the Ntionl Committee for Clinicl Lortory Stndrds (NCCLS [13]). Aneroes were lso tested y the NCCLS roth microdilution technique (14). For oth sets of microorgnisms, douling dilutions of cefoperzone rnged from 0.12 to 64,ug/ml nd four different sets of dilutions were prepred. To one set of douling dilutions, sulctm ws dded t finl concentrtion of 4.0,ug/ml. To the second set of dilutions, 8.0,ug of sulctm per ml ws dded. The third series contined cefoperzone comined with sulctm in 2:1 rtio (2 prts cefoperzone nd 1 prt sulctm). The fourth series of cefoperzone dilutions ws tested without dded sulctm. Finlly, douling dilutions of sulctm (0.5 to 64,ug/ml) were tested without dded cefoperzone. The disk diffusion test ws performed ccording to the method outlined y the NCCLS (12). Sulctm ws dded to 75-,ug cefoperzone disks to give finl disk content of 15 or 30 jxg. Qulity control guidelines. Three different collortive studies were performed to define qulity control prmeters for susceptiility tests. One study involved replicte disk diffusion tests performed in six seprte lortories y the

2 14 BARRY ET AL. J. CLIN. MICROBIOL. s *1r u E - CI > s > _ s i i Og Disks _ il _ _5115,u Di _75/l5jjgDlsk Zone Dlmeter (mm) tion tests with three stndrd neroic control strins (14-16). The stndrd reference method (15) ws used y five different lortories, nd 100 MICs were generted for ech control strin. RESULTS ' Interpretive criteri for cefoperzone-sulctm disks were the sme s those for cefoperzone lone, since oth 2 types of disks contined 75,ug of cefoperzone. We evluted cefoperzone disks which contined 15 F.g of sulctm, s well s those with 30,ug of sulctm. Figure 1 presents the scttergrms tht compre MICs (2:1 rtios) to zone dimeters with 272 eroic or fculttively neroic grm-negtive cilli, nd the regression sttistics re listed in Tle 1. Currently recommended zone size interpretive criteri for tests with 75-,ug cefoperzone disks could e pplied to either one of the comintion disks (75/15- or 75/30-,ug disks). Although oth comintion disks performed stisfctorily, the 75/30-,ug disks were slightly etter ecuse lrger zones were otined with microorgnisms with MICs ner the rekpoints. A 1.8% mjor (flse-resistnt) error rte with 75/15-,ug disks ws completely eliminted when 75/30-,ug disks were used. Very mjor (flse-susceptile) errors were <1% with either disk. Minor errors (intermedite with one method nd susceptile or resistnt with the 311 other) occurred less frequently with 75/30-,ug disks. As previously reported with 75-,ug cefoperzone disks lone (10), minor interpretive error rtes exceeded 10%. The current study included disproportiontely lrge numer of strins for which cefoperzone MICs were elevted nd perzone-sul- FIG. 1. Scttergrms compring MICs of cefo ctm (2:1 rtios) to zone dimeters with 75/30-,ug ccefoperzone- minor discrepncy rtes were 18 to 22% (Tle 1). sulctm disks (top) nd zones with 75/15-,ug di5sks (ottom). The results of microdilution susceptiility tests with four Horizontl nd verticl lines represent interpretive reekpoints tht mjor groups of cteril pthogens re summrized in Tle re currently recommended for tests with cefoperzoine lone. 2. Seprte dilution tests with streptococci nd stphylococci reveled no significnt chnge in the ctivity of cefoperzone when sulctm ws dded (dt not shown). Pseudomons species nd the neroic grm-positive miprotocol tht ws outlined y Gvn et l. (7). 1Fhe cefoper- croorgnisms were lso unffected y the ddition of sulc- tm, ut there ws some strin-to-strin vrition, presum- zone-sulctm dt were compred to those eccumulted in 1981 (10) with 75->xg cefoperzone disks. Rejplicte roth ly due to the effect of sulctm on specific,-lctmses. microdilution susceptiility tests were lso performed c- On the other hnd, species tht commonly produce,bl. (2). In lctmses were profoundly influenced y dding the inhi- cording to the protocol outlined y Brry et ddition to the stndrd control strins, we evluted tests itor. For exmple, memers of the B. frgilis group were with A. clcoceticus susp. nitrtus ATCC This reltively resistnt to cefoperzone, ut 80% were suscepti- to the le to 16,ug of cefoperzone per ml when 8.0,ug of strin ws considered ecuse it is quite suscelptile sulctm component of the comintion nd reltively sulctm per ml ws dded. With these species, sulctm resistnt to the cefoperzone component. The ther control reduced most MICs of cefoperzone y four- to eightfold. strins were not influenced y the presence of suilctm nd Among the enteric cilli tht were included in this series, thus only monitored the cefoperzone in the disks or micro- nerly hlf of the cefoperzone-resistnt strins were condilution trys. The third study involved replic,te gr dilu- verted to the susceptile ctegory y ddition of sulctm TABLE 1. Regression sttistics compring zone dimeters (millimeters) to MICs (Iog2 + 9,ug/ml) for 272 cteril isoltes Antimicroil disk content Regression formul' Correltion % Agreement % Discrepncy coefficient Minor Mjor Very mjor Cefoperzone, 75,ug y = x Cefoperzone-sulctm 75/15,ug y = x /30,ug y = x Isoltes included memers of the fmily Enteroctericee (189), Pseudomons spp. (62), nd Acinetocter spp. (21). Cefoperzone disk tests compred with MICs of cefoperzone nd cefoperzone-sulctm disk tests compred with MICs of cefoperzone/sulctm (2:1 rtio). y = MIC; x = zone dimeter.

3 VOL. 26, 1988 CRITERIA FOR DISK TESTS WITH CEFOPERAZONE-SULBACTAM 15 TABLE 2. Effects of sulctm on the in vitro ctivity of cefoperzone ginst selected eroic grm-negtive cilli nd rndomly smpled neroic microorgnisms Isoltes tested (n) nd ntimicroil gents (concn) Cumultive % inhiited t CPER concn (L>g/ml) of: s8.o Enteroctericee (189)C CPER S (4.0,ug/ml) S (8.0,ug/ml) S, 2:1 rtio Pseudomons species (62)d CPER S (4.0 1tg/ml) S (8.0,ug/ml) S, 2:1 rtio B. frgilis (62)e CPER S (4.0,ug/ml) S (8.0 p.g/ml) S, 2:1 rtio Grm-positive neroes (25Y CPER S (4.0 F±g/mI) S (8.0,ug/ml) S, 2:1 rtio Memers of the fmily Enteroctericee nd Pseudomons spp. were selected to include disproportiontely lrge numer of cefoperzoneresistnt strins; this is hot representtive of the type of strins tht would e expected in norml prctice. CPER, Cefoperzone; S, sulctm. C Includes isoltes of C. freundii (19), C. diversus (6), E. coli (16), Enterocter erogenes (26), Enterocter gglomerns (1), Enterocter cloce (37), Klesiell pneumonie (11), K. oxytoc (4), Proteus vulgris (3), Proteus mirilis (1), Morgnell morgnii (3), Providenci rettgeri (4), Providenci sturtii (16), Slmonell enteritidis (5), nd Serrti mrcescens (37). d Includes isoltes of P. eruginos (40), P. mltophili (8), P. fluorescens (5), P. cepci (3), P. putid (3), nd P. cidovorns (3). e Includes isoltes of B. frgilis (39), B. vulgtus (6), B. distsonis (6), B. thetiotomicron (5), B. ovtus (5), nd B. uniforms (1). f Includes isoltes of Clostridium perfrigens (5), Clostridium sporogenes (2), Clostridium ifermentns (2), Clostridium clostridjiforme (1), Clostridium rmosum (1), Eucterium lentum (3), Peptostreptococcus neroius (6), nd Peptococcus scchrolyticus (5). (51% were susceptile to 16,ug of cefoperzone per ml nd 72% were susceptile to 16/8.0,ug of cefoperzone-sulctm per ml). Of 10 cefoperzone-resistnt Escherichi coli strins, 9 were converted to the susceptile ctegory. Only 12 of 35 resistnt Enterocter species were converted, nd 9 of 18 cefoperzone-resistnt Citrocterfreundii were susceptile to the comintion. Four of seven cefoperzoneresistnt Klesiell spp. were susceptile to thé comintion, nd il 12 resistnt Serrti mrcescens isoltes were resistnt to the comintion (MIC, >16/8.0,ug/ml). Among cefoperzone-resistnt enteric cilli, MICs of cefoperzone were decresed 0 to 32-fold (verge 4.8-fold) when sulctm ws dded in 2:1 rtio of cefoperzone to sulctm. At concentrtions ner the rekpoints seprting susceptile nd resistnt ctegories, tests with fixed 2:1 rtio of drugs nd those with fixed concentrtions of 4.0 or 8.0,ug of sulctm per ml were not mrkedly different. For resons outlined elsewhere (8), we recommend use of 2:1 rtio for roth or gr dilution susceptiility tests. At lower concentrtions of cefoperzone, the fixed rtio is no more ctive thn cefoperzone lone ecuse sufficient concentrtions of sulctm re not present. The results of tests with A. clcoceticus isoltes re summrized in Tle 3. All 21 isoltes were susceptile to sulctm lone (MIC, 1.0 to 4.0,ug/ml) ut were reltively resistnt to cefoperzone lone (MIC, -16,ug/ml). When comined with 4.0 or 8.0,ug of sulctm per ml, ll 21 isoltes ppered to e inhiited y so.12,ug of cefoperzone per ml, ut inhiition ws solely due to the sulctm component of the comintion. When the two drugs were tested in 2:1 rtio of cefoperzone to sulctm, the comintion ws only slightly more ctive thn with the sulctm lone. Disk diffusion susceptiility tests were lso performed with the 21 A. clcoceticus isoltes. The verge zone dimeter round 75-p.g cefoperzone disks ws 16.2 mm, nd 15-pug sulctm disks produced zones verging 27.5 mm. When 15,ug of sulctm ws dded to 75-ktg cefoperzone disk, the verge zone dimeter ws 26.9 mm (essentilly the sme s with disks contining sulctm lone). When 30,ug of sulctm ws dded to 75-,ug cefoperzone disk, the men zone dimeter ws even lrger (29.8 mm). Qulity control prmeters of 75/30-,ug cefoperzone-sulctm disks re summrized in Tle 4. The control strins of E. coli, Stphylococcus ureus, nd Pseudomons eruginos were minimlly ffected y the presence of sulctm in the disks, i.e., zones round 75/30-,ug cefoperzonesulctm disks were generlly 1 mm smller thn those round 75-,ug cefoperzone disks. A single lot of 75-,ug cefoperzone disks ws included in the present study, nd the results were identicl to those otined in the originl 1981 study (10). The minor differences in zone size might only represent smll differences in the potency of the cefoperzone component of the disks, i.e., the sulctm component did not pper to influence the zone size very much, if t ll. A. clcoceticus susp. nitrtus ATCC ws susceptile to the sulctm in the comintion ut produced reltively smll (14 to 18 mm) zones with cefoperzone disks. Zone size limits of 26 to 32 mm should pply to tests with 75/30-,ug cefoperzone-sulctm disks. For monitoring the performnce of roth microdilution tests, five different control strins were evluted (Tle 5). A. clcoceticus susp. nitrtus ATCC ws gin found to e susceptile to the comintion ut ws resistnt to cefoperzone lone. For the other strins, control limits tht re eing used for cefoperzone cn e pplied to tests with the cefoperzone-sulctm comintion. For the ref- TABLE 3. In vitro susceptiility of 21 A. clcoceticus isoltes to sulctm nd cefoperzone Cefoperzone- Sulctm Cefoperzone sulctm lone lone (g/ml) No ( gml) No. (gml) No. 216/ > / / / / /0.25 <0.25 '4.0 Cefoperzone nd sulctm were comined in 2:1 rtio when tested, nd when comined with 4.0 or 8.0 p.g of sulctm per mi, il 21 isoltes ppered to e susceptile to so.12,ug of cefoperzone per ml ecuse of the sulctm portion of the comintion. No., Numer of times given MIC ws recorded.

4 16 BARRY ET AL. J. CLIN. MICROBIOL. TABLE 4. Zone size control limits for cefoperzone-sulctm nd cefoperzone with four control strins Inhiition zone (mm) for: Control strin Cefoperzone- Cefoperzone (75/30-l.g disks) (5k iky Medin Limits Medin Limits A. clcoceticus susp nitrtus ATCC P. eruginos ATCC E. coli ATCC S. ureus ATCC Zone size control limits were defined s the medin for l] lortories ± hlf the medin rnge of zone sizes recorded in two seprte collortive studies from multiple lortories. Dt for the Acinetocter sp. re those ccumulted during the current study using only one lot of disks. All other dt with cefoperzone re those ccumulted in 1981 from collortive study identicl to the current study design done y six lortories. Zone size limits for the P. eruginos nd E. coli strins re recommended y the NCCLS (16) for control of tests with 75-»tg cçfoperzone disks. For the S. ureus strin, control limits of 24 to 33 mm re recommended y the NCCLS (16). erence neroic gr dilution test, B. thetiotomicron ATCC ws the most useful control strin (Tle 6). Clostridium perfringens ATCC ws too susceptile nd too vrile in its susceptiility to cefoperzone-sulctm to e of much prcticl vlue for qulity control purposes (dt not shown). B. frgilis ATCC ws lso too vrile for monitoring tests with the comintion, ut it ws useful for monitoring cefoperzone lone. DISCUSSION Sulctm comines with some cliniclly relevnt IBlctmses in n irreversile mnner. If sufficient inhiitor is present t the site of infection, the P-lctmse enzymes should e neutrlized nd thus the drug used in comintion with the inhiitor should hve n opportunity to inhiit TABLE 5. TABLE 6. Agr dilution susceptiility tests results with neroic control strins No. of times ech MIC ws recorded fore: MIC B. frgilis ATCC B. thetiotomicron (p.g/ml B. frilis ATC 25285ATCC CPER C-S CPER C-S Replicte tests (n = 100) were ccumulted from five lortories. MIC of C-S is expressed s the concentrtion of CPER in the comintion. ` MICs within the proposed control limits re designted with oldfce type. No limits could e defined for the B. frgilis strin tested ginst C-S. Tests with C. perfringens ATCC were lso too vrile to e useful for qulity control purposes (dt not shown). Arevitions: CPER, cefoperzone lone; C-S, cefoperzone nd sulctm comintion. cteril growth. Consequently, the concentrtion of sulctm in the lood of ptients severl hours fter dministrtion of the comintion my e importnt only when the codministered drug fils to inhiit dditionl 1-lctmse production y the microorgnisms. For tht reson, the serum hlf-lives of the drugs my not e s relevnt s the pek tissue levels when selecting pproprite comintions for in vitro testing. One my simply dd concentrtion of inhiitor which would e expected t the site of infection shortly fter intrvenous dministrtion (4.0 or 8.0,ug/ml). Alterntively, one my test fixed rtio which contins the two drugs in the proportions tht re found in the lood of the ptient shortly fter the comintion is dministered. We elected to test 2 prts cefoperzone comined with 1 prt sulctm ecuse tht rtio resemles the expected levels in lood shortly fter dministrtion. The hlf-life of cefoperzone is much longer thn tht of sulctm nd thus the rtios will chnge with time. MICs CPER nd C-S with stndrd control strins tested in five lortories" No. of times ech MIC ws recorded for': MIC A. clcocetucus susp. P. eruginos ATCC E. coli ATCC E. feclis ATCC S. ureus ATCC (p.g/ml) nitrtus ATCC CPER C-S CPER C-S CPER C-S CPER C-S CPER C-S _ i O_ 2_ o_ " Arevitions: CPER, cefoperzone lone; C-S, cefoperzone-sulctm. MIC of C-S is expressed s the concentrtion of CPER in the comintion (2:1 rtio). ' Broken lines represent current control limits for cefoperzone lone (16) or proposed limits for tests with A. clcoceticus susp. nitrtus ATCC

5 VOL. 26, 1988 CRITERIA FOR DISK TESTS WITH CEFOPERAZONE-SULBACTAM 17 In vitro tests with 2:1 rtio did not differ gretly from those with constnt concentrtion of inhiitor (4.0 or 8.0,ug of sulctm per ml) (8). However, sulctm-susceptile species such s the Acinetocter spp. re est tested with fixed 2:1 rtio ecuse excessive mounts of inhiitor re not included with the lower concentrtions of cefoperzone. On the other hnd, when fixed rtio is tested, wells contining >32,ug of cefoperzone per ml might contin phrmcokineticlly unrelistic mounts of sulctm. To control susceptiility tests with drug comintions, it is necessry to monitor the performnce of oth components. For exmple, when monitoring tests with trimethoprimsulfmethoxzole, the comintion is more ctive thn either drug lone nd thus loss of potency of either drug should e detected y the results of stndrd control tests.,-lctmse inhiitors do not ffect the ctivity of the stndrd control strins. For control of clvulnic cid comined with moxicillin or ticrcillin, type TM IPlctmse-producing strin, E. coli ATCC 35218, hs een recommended y the NCCLS (12, 13, 16). The strin my lso e used for controlling tests with the mpicillin-sulctm comintion. Tht strin is resistnt to the penicillins ut susceptile when clvulnic cid or sulctm is dded. Unfortuntely, tht strin of E. coli is susceptile to cefoperzone lone nd cnnot e used for monitoring the cefoperzone-sulctm comintion. A control strin of A. clcoceticus susp. nitrtus ATCC ws selected for monitoring the sulctm portion of tht comintion. The estlished control strins dequtely monitored the cefoperzone portion of the comintion. For neroic dilution tests, B. thetiotomicron ATCC ws the most useful control strin. For monitoring tests with cefoperzone lone, B. frgilis ATCC ws lso useful. Our MIC control limits were more consistent with the originl recommendtions of the NCCLS (15), rther thn the roder 4-dilution rnge tht ws recommended in the 1986 supplement (16). For the disk diffusion test, we hve previously recommended use of 75/15-,ug disks, ut 75/30-ptg disks were not evluted (9). In this study, we expnded our previous oservtions to evlute oth types of disks nd concluded tht either disk could e used stisfctorily. However, the 75/30-,ug disks provided fewer discrepncies with MIC (2:1 rtio) ctegories. Qulity control limits for tests with 75/30-,ug disks re proposed in this report. LITERATURE CITED 1. Appelum, P. C., M. R. Jcos, S. K. Spngler, nd S. Yme Comprtive ctivity of,-lctmse inhiitors YTR 830, clvulnte, nd sulctm comined with,b-lctms ginst P-lctmse-producing neroes. Antimicro. Agents Chemother. 30: Brry, A. L., T. L. Gvn, R. N. Jones, L. W. Ayers, P. C. Fuchs, E. H. Gerlch, nd C. Thornserry Qulity control limits for microdilution susceptiility tests with ztreonm, imipenem, ceftrixone, ceftzidime, ceftizoxime, cefuroxime, nd cefonicid. Dign. Microiol. Infect. Dis. 7: Brry, A. L., R. N. Jones, nd R. R. Pcker In vitro susceptiility of the Bcteroides frgilis group to cefoperzone, mpicillin, ticrcillin nd moxycillin comined with P-lctmse inhiitors. J. Antimicro. Chemother. 17: Crosy, M. A., nd D. W. Gump Activity of cefoperzone nd two P-lctmse inhiitors, sulctm nd clvulnic cid, ginst Bcteroides spp. correlted with P-lctmse production. Antimicro. Agents Chemother. 22: English, A. R., J. A. Retsem, A. E. Girrd, J. E. Lynch, nd W. E. Brth CP-45,899, P-lctmse inhiitor tht extends the nticteril spectrum of P-lctms: initil cteriologicl chrcteriztion. Antimicro. Agents Chemother. 14: Fu, K. P., nd H. C. Neu Synergistic ctivity of cefoperzone in comintion with,b-lctmse inhiitors. J. Antimicro. Chemother. 7: Gvn, T. L., R. N. Jones, A. L. Brry, P. C. Fuchs, E. H. Gerlch, J. M. Mtsen, L. B. Reller, C. Thornserry, nd L. D. Thrupp Qulity control limits for mpicillin, crenicillin, mezlocillin, nd pipercillin disk diffusion susceptiility tests: collortive study. J. Clin. Microiol. 14: Jones, R. N., A. L. Brry, R. R. Pcker, W. W. Gregory, nd C. Thornserry In vitro ntimicroil spectrum, occurrence of synergy, nd recommendtions for dilution susceptiility testing concentrtions of the cefoperzone-sulctm comintion. J. Clin. Microiol. 25: Jones, R. N., A. L. Brry, C. Thornserry, nd H. W. Wilson The cefoperzone-sulctm comintion: in vitro qulities including et-lctmse stility, ntimicroil ctivity, nd interpretive criteri for disk diffusion tests. Am. J. Clin. Pthol. 84: Jones, R. N., T. L. Gvn, A. L. Brry, C. Thornserry, nd D. L. Gis Cefoperzone disk diffusion susceptiility test: confirmtion of the tenttive interpretive criteri, Pseudomons eruginos cross-resistnce, nd determintion of qulity control performnce limits. J. Clin. Microiol. 15: Jones, R. N., H. W. Wilson, C. Thornserry, nd A. L. Brry In vitro ntimicroil ctivity of cefoperzone-sulctm comintions ginst 554 clinicl isoltes including review nd,3-lctmse studies. Dign. Microiol. Infect. Dis. 3: Ntionl Committee for Clinicl Lortory Stndrds Performnce stndrd for ntimicroil disk susceptiility tests. Approved stndrd, M2-A3. Ntionl Committee for Clinicl Lortory Stndrds, Villnov, P. 13. Ntionl Committee for Clinicl Lortory Stndrds Stndrd methods for dilution ntimicroil susceptiility tests for cteri which grow eroiclly. Approved stndrd, M7-A. Ntionl Committee for Clinicl Lortory Stndrds, Villnov, P. 14. Ntionl Committee for Clinicl Lortory Stndrds Alterntive methods for ntimicroil susceptiility testing of neroic cteri. Proposed guideline, M17-P. Ntionl Committee for Clinicl Lortory Stndrds, Villnov, P. 15. Ntionl Committee for Clinicl Lortory Stndrds Reference gr dilution procedure for ntimicroil susceptiility testing of neroic cteri. Approved stndrd, Mil-A. Ntionl Committee for Clinicl Lortory Stndrds, Villnov, P. 16. Ntionl Committee for Clinicl Lortory Stndrds Performnce stndrds for ntimicroil susceptiility testing. First informtionl supplement, M100-S. Ntionl Committee for Clinicl Lortory Stndrds, Villnov, P.