ArTiMIctoIBAL AGoNT8 AND CHumOrHzRAPY, Oct. 1976, p. 736-752 Copyright 0 1976 Americn Society for Microbiology Vol. 10, No. 4 Printed in U.S.A. Susceptibility of Anerobic to 23 Antimicrobil Agents VERA L. SUTTER* AND SYDNEY M. FINEGOLD Reserch nd Medicl Services, Veterns Administrtion Wdsworth Hospitl Center, Los Angeles, Cliforni 90073,* nd Deprtment ofmedicine, UCLA School ofmedicine, Los Angeles, Cliforni 90024 Received for publiction 23 June 1976 The ntimicrobil susceptibility of 492 nerobic bcteri, the mjority of which were. recent clinicl isoltes, ws determined by the gr dilution technique. Penicillin G ws ctive ginst most of the tested t 32 U or less/ ml, but only 72% ofbcteroides frgilis were susceptible t this level nd 9% required 256 U or more/ml. Ampicillin ws effective ginst most of the except B. frgilis t 16 ug or less/ml. Amoxicillin ws ctive ginst only 31% of B. frgilis, 76% of other Bcteroides species, nd 67% of Fusobcterium species t 8,ug/ml. Two new penicillins, mezlocillin nd zlocillin, were similr to mpicillin in their ctivity. Crbenicillin nd ticrcillin inhibited ll but few t 128,ug or less/ml. BLP 1654 ws somewht more ctive thn penicillin G ginst B. frgilis but hd similr ctivity ginst other nerobes. Cephlothin ws inctive ginst B. frgilis, nd only 65% of other Bcteroides species were inhibited by 32 ug or less/ml. It ws effective ginst ll other nerobes t tht level. Cefmndole showed somewht greter ctivity thn cephlothin ginst B. frgilis but generlly less ctivity ginst grm-positive orgnisms. Cefzflur (SKF 59962) ws comprble to cephlothin ginst B. firgilis. Cefoxitin ws distinctly more ctive thn cephlothin ginst B. frgilis. These ltter two gents were less ctive thn cephlothin ginst the grm-positive nerobes. Chlormphenicol remins ctive ginst nerobic bcteri t 16,ug or less/ml, with rre exceptions. Thimphenicol ws similr to chlormphenicol in its ctivity. Clindmycin ws very ctive ginst most ofthe nerobes t 8,ug or less/ml. Erythromycin nd josmycin were lso tested, with josmycin showing greter ctivity ginst B. frgilis thn either erythromycin or clindmycin. A new oligoscchride, everninomicin B, ws less ctive thn clindmycin ginst B. frgilis but more ctive ginst clostridi nd some of the other tested. Most of the groups of bcteri tested demonstrted trend towrd resistnce to tetrcycline. Doxycyline nd minocycline were somewht more ctive thn ws tetrcycline. Metronidzole ws ctive ginst the mjority of the nerobes tested; resistnce ws demonstrted by some of the grm-positive cocci nd grm-positive, non-sporeforming bcilli. It hs been generlly ccepted by investigtors nd clinicins knowledgeble in the dignosis nd therpy of nerobic infections tht rpid, routine susceptibility testing of individul isoltes of nerobic bcteri is imprcticl. Anerobic infections re frequently polymicrobic nd cultures require reltively long periods of time for growth nd isoltion, so tht timely results of susceptibility tests re not fesible. It hs been suggested tht centers with the cpbility for testing on survey bsis do so periodiclly to monitor chnging ptterns of resistnce to commonly recommended gents nd to determine the possible effectiveness of newer gents. The purpose of the present study ws to ssy the in vitro effect of severl drugs currently in 736 use for therpy of nerobic infections nd to determine the ctivity of severl newer gents ginst nerobic bcteri recently isolted from clinicl mteril. MATERIALS AND METHODS l. A totl of 492 of nerobic bcteri ws used throughout the study. All but few were isolted from vriety of clinicl specimens received by the Wdsworth Anerobic Bcteriology Reserch Lbortory from ptients on specil studies nd from ptients seen in consulttion by the Infectious Disese Section during the period of September 1972 to June 1975. Exceptions were 21 of Bcteroides melninogeni, 5 of which were reference nd 16 of which were norml orl or fecl isoltes. Tble 1 gives the specific iden-
VOL. 10, 1976 ANTIMICROBIAL SUSCEPTIBILITY OF ANAEROBES 737 TABLE 1. Identitv of bcteril tested tested in Orgnism studies Orgnism Prt I Prt II Totl i It 34 76 Microerophilic nd n- Bcteroides frgilis 42 subsp. distsonis 8 subsp. frgilis 18 subsp. ovtus 1 subsp. thetiotomicron 9 subsp. vulgtus 4 Other 2 Bcteroides melninogen- 60 i subsp. scchrolyti 21 subsp. intermedius 29 subsp. melninogeni 10 Other 0 Other Bcteroides nd Se- 21 lenomons B. cpillosus 0 B. clostridiiformis 0 subsp. clostridiiformis" B. clostridiiformis 0 subsp. girnsb B. corrodens 2 B. orlis 4 B. pneumosintes 2 B. putredinis 1 B. ruminicol subsp. 0 ruminicol B. ruminicol subsp. 1 brevis B. splnchnic 1 Bcteroides group I 0 Bcteroides group PS 0 Bcteroides sp. 10 Selenomons sp. 0 Fusobcterium nucletum 8 Other Fusobcterium 12 F. gonidiformns 2 F. mortiferum 2 F. nviforme 1 F. necrophorum 1 F. russii 1 Fusobcterium sp. 5 Peptococ nd Gff y 17 P. scchrolyti 2 P. mgnus 4 P. prevotii 6 P. scchrolyti 0 P. vribilis 4 Peptococ sp. 1 Gffky nerobius 0 Peptostreptococ 15 P. nerobius 9 P. micros " 5 Peptostreptococ sp. 1 3 11 erobic Streptococ I12 30 S. constelltus 2 3 S. intermedius I12 21 S. morbillorum 4 8 Grm-negtive cocci 1 3 Acidminococ fer- I11 71 mentns Veillonell lclescens 1 22 V. prvul 6 35 Eubcterium 2 12 E. erofciens 2 2 E. contortum I IL51 72 E. Ientum E. limosum 3 3 E. moniliforme 2 2 Eubcterium sp. Archni propionic Propionibcterium 1 1 P. cnes P. vidum 0 2 Propionibcterium sp. 6 10 Actinomyces 3 5 A. isrelii 1 2 A. neslundii 1 1 A. viscosus Actinomyces sp. 3 4 Bifidobcterium B. dolescentis vr. B 0 1 B. infntis 6 6 Bifidobcterium sp. 8 8 Lctobcillus 16 26 L. cidophilus 1 1 L. ctenforme to 18 L. fermentum 4 16 L. minutis 2 4 L. plntrum 0 2 Lctobcillus sp. 1 2 Clostridiumperfringens 0 1 Other Clostridium 0 1 C. bifermentns 1 6 C. butyricum 2 59 C. difficile 2 1 23 C. glycolicum 6 10 C. innocuum 8 14 C. prperfringens 2 2 C. plgrum 4 8 C. putrificum 0 1 C. rmosum 1 1 C. sphenoides L4 29 C sporogenes 9 18 C. tertium 4 9 Clostridium sp. 1 2 tested in tested in studies Prt I Prt II Totl 6 4 10 0 2 2 4 2 6 2 0 2 7 19 26 2 1 3 2 6 8 3 12 15 8 9 17 0 1 1 0 1 1 4 4 8 2 0 2 1 3 4 2 1 3 4 8 12 4 5 9 0 2 2 0 1 1 16 0 16 5 0 5 9 0 9 0 5 5 0 2 2 0 1 1 0 2 2 10 9 19 0 2 2 2 1 3 0 1 1 1 2 3 2 1 3 5 2 7 8 1 9 27 7 34 2 0 2 2 0 2 5 3 8 7 3 10 0 1 1 4 0 4 It hs recently been proposed tht orgnisms recognized s subspecies of B. frgilis be reinstted to species rnk (7). Strins hving phenotypic chrcteristics similr to these hve recently been found to hve spores nd to be geneticlly similr to Clostridium. It hs been proposed tht they be considered s C. clostridiiformis (15) or C. clostridiiforme (8). Spores hve not been demonstrted in the in the present study. c A new Bcteroides species described by Werner et l. (48).
738 SUTTER AND FINEGOLD ANTIMICROB. AGZNTS CHZMOTHEit. tifiction of the bcteri used in ech prt of the study. These bcteri were identified ccording to the criteri of the Wdsworth Anerobic Bcteriology Mnul (40) nd the Virgini Polytechnic Institute Anerobe Lbortory Mnul (13). It hs recently been proposed tht orgnisms recognized s subspecies of Bcteroides frgilis be given species sttus (7). We re in greement with this, but since little or no difference hs been found in the susceptibility of these orgnisms to the ntimicrobil gents in the present study nd in reports of others (2, 14), we will refer to B. frgilis s group including the five species. The subspecies of B. melninogeni re lso referred to s group, bee no differences were observed in their susceptibility to ntimicrobil gents. Six hd the chrcteristics of Bcteroides group 1 nd eight hd the chrcteristics ofbcteroides group PS. These ltter two groups hve recently been recognized s distinct from other Bcteroides species (L. V. Holdemn, personl communiction). Antimicrobil gents. Lbortory-stndrd powders were kindly supplied s follows: penicillin G, cephlothin, cefmndole lithium, nd erythromycin from Eli Lilly & Co., Indinpolis, Ind.; mpicillin trihydrte nd BLP 1654 from Bristol Lbortories, Syre, N.Y.; crbenicillin from Roerig, New York, N.Y.; moxicillin trihydrte nd ticrcillin sodium from Beechm-Mssengill Phrmceuticls, Bristol, Tenn.; mezlocillin nd zlocillin from Delby Phrmceuticls, Inc., Bloomfield, N.J.; sodium cefoxitin from Merck, Shrp nd Dohme, Rhwy, N.J.; cefzflur (SKF 59962) from Smith, Kline nd French Lbortories, Phildelphi, P.; chlormphenicol from Prke-Dvis & Co., Detroit, Mich.; thimphenicol nd thimphenicol glycinte from Zmbon, S.p.A., Bresso, Milno, Itly; clindmycin from The Upjohn Co., Klmzoo, Mich.; everninomicin B from Schering Corp., Bloomfield, N.J.; josmycin from E. I. Dupont de Nemours & Co., Newrk, Del.; tetrcycline nd doxycycline from Pfizer Lbortories, New York, N.Y.; minocycline from Lederle Lbortories, Perl River, N.Y.; nd metronidzole from G. D. Serle & Co., Chicgo, Ill. Procedures. Antimicrobil susceptibility testing ws performed by the gr dilution technique s previously described (40). Sets of three lked blood gr pltes contining no ntibiotic were inoculted before ech series of ntibiotic-contining pltes nd incubted nerobiclly, in 10% CO2 in ir, nd erobiclly, to serve s growth nd contmintion controls. Dt were deleted if poor or no growth occurred on the nerobic growth control plte or if contmintion ws evident. Throughout the study, the following ntimicrobil gents were included: penicillin G, crbenicillin, BLP 1654, chlormphenicol, clindmycin, tetrcycline, doxycycline, minocycline, nd metronidzole. During the first prt of the study, moxicillin, ticrcillin, cefoxitin, cefzflur, thimphenicol, thimphenicol glycinte, nd everninomicin B were included to determine their possible effectiveness ginst nerobes or for comprison of their ctivity with other drugs. During the second prt of the study, the following gents were included: mpicillin, mezlocillin, zlocillin, cephlothin, cefmndole, erythromycin, nd josmycin. RESULTS AND DISCUSSION Penicillins. The ctivity of penicillin G ginst the nerobes tested is shown in Tble 2. An inhibitory concentrtion of 32 U/ml is considered n cceptble level of susceptibility TABLE 2. Activity ofpenicillin G ginst nerobic bcteri Cumultive % susceptible to indicted concn (U/ml) tested r0.1 0.5 1.0 2.0 4.0 8.0 16.0 32.0 64.0 128.0-256 Bcteroides frgilis 76 1 3 5 7 13 42 72 91 Bcteroides melnino- 66 68 79 83 86 89 94 97 geni Other Bcteroides nd 72 24 49 51 56 63 71 75 82 93 96 Selenomons Fusobcterium nucletum 18 72 83 94 Other Fusobcterium 16 50 75 88 94 Peptococ nd Gt ky 59 49 Peptostreptococ 29 55 86 90 97 Anerobic nd microero- 10 50 90 Grm-negtive cocci 26 15 69 85 89 92 Eubcterium 17 18 47 59 77 94 Archni propionic 3 67 o Propionibcterium 12 75 92 Actinomyces 16 69 Bifidobcterium 5 20 Lctobcillus 18 28 89 Clostridium perfringens 9 33 Other Clostridium 34 3 53 71 82 97 Includes ll identified s subspecies of B. frgilis.
VOL. 10, 1976 if high prenterl dosge is given. Most of the bcteri were inhibited by this concentrtion or less. However, only 72% of B. frgilis, 82% of Bcteroides species other thn B. frgilis nd B. melninogeni, nd 88% offusobcterium species other thn Fusobcterium nucletum were inhibited by 32 U/ml. Nine percent, or seven ofthe in the B. frgilis group (six B. frgilis nd one Bcteroides vulgtus), 4% or three of other Bcteroides species, nd one Fusobcterium species required 256 U or more/ml for inhibition. The B. frgilis included in this study pper to hve bout the sme susceptibility s those tested in prior study in which hd been isolted from vriety of sources, including humn feces, over period of severl yers (39). There ws no difference in susceptibility of tested in the two prts of the study, with pproximtely equl proportions of the resistnt ppering in ech segment. The present results with B. frgilis nd other nerobes tested re lso similr to those reported by others (2, 14, 16, 21, 34, 43, 51), nd greter resistnce to penicillin does not pper to be emerging. The ctivity of mpicillin ginst the tested in the second prt of the study is shown in Tble 3. With prenterl dosge, levels of t lest 16,ug/ml re chievble. Ampicillin inhibited most of the nerobes tested t concentrtions of 16,ug or less/ml but ws effective ginst only 56% of B. frgilis t this level. The results with B. frgilis re similr to ANTIMICROBIAL SUSCEPTIBILITY OF ANAEROBES those reported by Kislk (16) nd overll results show higher minimum inhibitory concentrtions (MICs) thn those ileported by Rotilie et l. (32), who used microdilution technique for determintion of susceptibility. Amoxicillin, n orl, brod-spectrum penicillin, chieves serum levels of up to 8,ug/ml (24). The ctivity of this ntibiotic ginst nerobes ws determined during the first prt of the study. Amoxicillin ws ctive ginst mny of the tested (Tble 4), but only 31% of B. frgilis, 76% of other Bcteroides species, nd 67% offusobcterium species were inhibited by 8,ug or less/ml. One strin ech ofpeptostreptococ nerobius nd Streptococ intermedius required 16 ug/ml nd one strin of Clostridium perfringens required 32,ug/ml for inhibition. These studies would indicte tht moxicillin would be less useful in serious nerobic infections thn either penicillin G or mpicillin İn the second prt of the study two new semisynthetic cylureido penicillins, mezlocillin nd zlocillin, were tested. Results re shown in Tbles 5 nd 6. These compounds hve similr in vitro effectiveness ginst the nerobes tested nd, on the bsis of weight, re similr to mpicillin in their ctivity. Phrmcologicl dt on these two compounds re not yet vilble. The susceptibility of nerobes to crbenicillin ws tested throughout the study, nd results re shown in Tble 7. Crbenicillin inhibited ll nerobes tested t level of 128,ug/ TABLE 3. Activity of mpicillin ginst nerobic bcteri Cumultive % susceptible to indicted concn (j,g/ml) tested <0.1 0.5 1.0 2.0 4.0 8.0 16.0 32.0 64.0 128.0.256 Bcteroides frgilis 34 6 15 56 82 91 Bcteroides melninogeni- 9 22 67 78 Other Bcteroides nd Se- 50 26 44 48 54 60 72 92 94 98 lenomons Fusobcterium nucletum 10 70 80 90 Other Fusobcterium 4 25 50 75 Peptococ nd Gffky 41 39 93 Peptostreptococ 13 23 85 92 Anerobic nd microero- 4 25 Grm-negtive cocci 19 16 79 90 95 Eubcterium 9 22 67 78 Archni propionic 1 Propionibcterium 7 29 Bifidobcterium 5 Lctobcillus 8 13 75 88 Clostridium perfringens 1 Other Clostridium 7 14 71 86 Includes ll identified s subspecies of B. frgilis. 739
740 SUTTER AND FINEGOLD ANTiMICROB. AGZNTS CHZMOTHER. TABLE 4. Activity of moxicillin ginst nerobic bcteri Cumultive % susceptible to indicted concn (Ag/ml) tested s0.1 0.5 1.0 2.0 4.0 8.0 16.0 32.0 64.0 128.0.256 Bcteroides frgilis 42 2 5 10 17 26 31 52 83 91 93 Bcteroides melninogeni- 59 71 83 86 90 95 Other Bcteroides nd Se- 21 43 57 62 67 76 86 95 lenomons Fusobcterium nucletum 8 63 88 Other Fusobcterium 12 42 67 75 83 92 Peptococ nd Gffky 19 42 90 95 Peptostreptococ 15 53 87 93 Anerobic nd microero- 6 67 83 Grm-negtive cocci 7 57 86 Eubcterium 7 57 Archni propionic 2 Propionibcterium 4 25 75 Actinomyces 16 63 Lctobcillus 10 60 90 Clostridium perfringens 8 75 88 Other Clostridium 26 8 77 92 96 Includes ll identified s subspecies of B. frgilis. TABLE 5. Activity of meziocillin ginst nerobic bcteri Cumultive % susceptible to indicted concn (yg/ml) tested 50.1 0.5 1.0 2.0 4.0 8.0 16.0 32.0 64.0 128.0 256.0 2512 Bcteroides frgilis 34 6 27 62 82 91 Bcteroides melni- 9 67 78 89 nogeni Other Bcteroides 50 10 28 40 50 62 80 88 94 98 nd Selenomons Fusobcterium nu- 10 60 90 cletum Other Fusobcterium 4 25 50 75 Peptococ nd Gff- 42 48 95 ky Peptostreptococ 13 70 77 85 Anerobic nd mi- 4 50 75 croero Grm-negtive cocci 19 11 26 47 68 74 84 90 Eubcterium 9 22 44 78 Archni propionic 1 Propionibcterium 7 29 86 Bifidobcterium 5 20 80 Lctobcillus 8 13 63 88 Clostridium perfrin- 1 gens Other Clostridium 7 29 43 86 Includes ll identified s subspecies of B. frgilis. ml, with the exception of four of B. ers (51) but re pprecibly lower thn those of frgilis, Bcteroides species, Bcteroides Blzevic nd Mtsen (3) nd Tlly et l. (43). corrodens, Bcteroides clostridiiformis Both of the ltter studies utilized prereduced subsp. clostridiiformis, nd Fusobcterium medi contining cysteine in determining susspecies. The MICs of in the present ceptibility; this might ccount for some loss of study re similr to those of our previous stud- crbenicillin ctivity. ies (36) nd to those of Kislk (16), Stneck nd The ctivity of ticrcillin ginst the Wshington (34), nd Zbrnsky nd co-work- tested in the second prt of the study is shown
VOL. 10, 1976 ANTIMICROBIAL SUSCEPTIBILITY OF ANAEROBES 741 TABLE 6. Activity of ziocillin ginst nerobic bcteri Cumultive % susceptible to indicted concn (Ig/ml) tested s0.1 0.5 1.0 2.0 4.0 8.0 16.0 32.0 64.0 128.0 256.0.512 Bcteroides frgilis 34 6 32 65 91 97 Bcteroides melni- 9 11 56 67 89 nogeni Other Bcteroides 50 12 38 42 50 54 70 80 88 94 98 nd Selenomons Fusobcterium nu- 10 60 90 cletum Other Fusobcterium 4 25 50 75 Peptococ nd Gff- 42 33 95 ky Peptostreptococ 13 69 77 85 Anerobic nd mi- 4 25 croero Grm-negtive cocci 19 5 37 63 79 84 95 Eubcterium 9 11 33 44 78 Archni propionic 1 Propionibcterium 7 29 Bifidobcterium 5 80 Lctobcillus 8 63 88 Clostridium perfrin- 1 gens Other Clostridium 7 57 86 Includes ll identified s subspecies of B. frgilis. TABLE 7. Activity of crbenicillin ginst nerobic bcteri Cumultive % susceptible to indicted concn (yg/ml) tested 50.1 0.5 1.0 2.0 4.0 8.0 16.0 32.0 64.0 128.0 256.0.512 Bcteroides figilis 76 1 3 5 8 21 25 38 47 80 95 Bcteroides melni- 67 42 85 90 94 97 nogeni Other Bcteroides 72 7 47 53 68 76 81 88 92 96 nd Selenomons Fusobcterium nu- 18 39 83 94 cletum Other Fusobcterium 16 25 44 50 81 88 94 Peptococ nd Gff- 59 25 73 88 98 ky Peptostreptococ 29 10 45 69 83 90 93 97 Anerobic nd mi- 10 20 40 50 80 90 croero Grm-negtive cocci 26 23 42 65 81 89 92 96 Eubcterium 17 12 18 24 47 53 65 88 Archni propionic 3 67 Propionibcterium 12 17 83 92 Actinomyces 16 69 Bifidobcterium 5 20 40 60 Lctobcillus 18 17 33 50 89 94 Clostridium perfrin- 9 gens Other Clostridium 33 9 21 36 49 61 76 94 Includes ll identified s subspecies of B. frgilis. in Tble 8. With high prenterl dosge sched- effective ginst ll tested t 128,tg or ules, blood levels of ticrcillin re similr to less/ml, with the exception of two of B. those of crbenicillin (26). The in vitro ctivity frgilis nd one strin ech of Fusobcterium ginst nerobes is lso quite similr. It ws species nd Fusobcterium gonidiformns.
742 SUTTER AND FINEGOLD ANTIMICROB. AGENTS CHEMOTHER. Tble 9 indictes the ctivity of BLP 1654 in Tble 10. All of B. frgilis were reginst the nerobic bcteri tested through- sistnt to cephlothin, requiring t lest 64,ug/ out the study. Orgnisms with MICs of 32,ug or ml for inhibition. Only 65% of other Bcteroides less/ml re considered susceptible to this gent species were inhibited by 32,g/ml. Previous (4). Unfortuntely, bee of its nephrotoxic- studies indicted 6 to 11% ofb. frgilis nd ll ity, further evlution of BLP 1654 hs been of other Bcteroides species to be indiscontinued. hibited by this concentrtion (36, 42). All other Cephlosporins nd similr drugs. The sus- groups tested in the present study were inceptibility of the nerobic bcteri from the hibited by 32,ug or less/ml. Most of the grmsecond prt of the study to cephlothin is shown positive nerobes were inhibited by 8 ug or TABLE 8. Activity of ticrcillin ginst nerobic bcteri Cumultive % susceptible to indicted concn (.tg/ml) tested so.1 0.5 1.0 2.0 4.0 8.0 16.0 32.0 64.0 128.0-256 Bcteroides frgilis 42 2 5 12 14 24 33 50 76 95 Bcteroides melninogeni- 59 41 85 87 90 95 98 Other Bcteroides nd Se- 21 24 48 62 67 71 lenomons Fusobcterium nucletum 8 38 88 Other Fusobcterium 12 25 42 50 58 67 Peptococ nd Gffky 15 20 60 93 Peptostreptococ 15 13 53 80 93 Anerobic nd microero- 6 50 83 Grm-negtive cocci 7 29 57 71 Eubcterium 7 14 29 43 Archni propionic 2 50 Propionibcterium 4 75 Actinomyces 16 13 81 Lctobcillus 10 10 60 70 80 Clostridium perfringens 8 88 Other Clostridium 26 8 15 31 54 Includes ll identified s subspecies of B. frgilis. 75 83 86 95 86 57 86 90 85 96 TABLE 9. Activity ofblp 1654 ginst nerobic bcteri Cumultive % susceptible to indicted concn (pg/ml) tested -0.1 0.5 1.0 2.0 4.0 8.0 16.0 32.0 64.0 128.0-256 Bcteroides frgilis 76 1 3 4 5 8 32 63 90 91 93 Bcteroides melninogeni- 68 50 81 85 87 93 99 c.u Other Bcteroides nd Se- 70 20 46 51 53 56 64 79 93 94 96 lenomons Fusobcterium nucletum 18 72 78 83 89 Other Fusobcterium 16 31 56 81 88 Peptococ nd Gffky 59 39 95 Peptostreptococ 28 54 89 93 96 Anerobic nd microero- 10 30 70 90 Grm-negtive cocci 26 8 39 58 73 89 92 96 Eubcterium 16 19 50 63 75 Archni propionic 3 67 Propionibcterium 11 46 91 Actinomyces 16 25 Bifldobcterium 5 Lctobcillus 18 39 83 94 Clostridium perfringens 9 22 Other Clostridium 33 33 70 82 94 Includes ll identified s subspecies of B. frgilis.
VOL. 10, 1976 ANTIMICROBIAL SUSCEPTIBILITY OF ANAEROBES 743 TABLE 10. Activity of cephlothin ginst nerobic bcteri Cumultive % susceptible to indicted concn (,&g/ml) tested <0.1 0.5 1.0 2.0 4.0 8.0 16.0 32.0 64.0 128.0 256.0 512 Bcteroides frgilis 34 15 50 53 Bcteroides melni- 9 44 56 67 78 nogeni Other Bcteroides 51 2 24 39 41 43 45 51 65 78 92 nd Selenomons Fusobcterium nu- 10 60 90 cletum Other Fusobcterium 4 50 Peptococ nd Gff- 42 14 74 95 98 ky Peptostreptococ 14 14 79 93 Anerobic nd mi- 4 25 croero Grm-negtive cocci 19 68 84 90 Eubcterium 9 11 33 44 67 Archni propionic 1 Propionibcterium 8 88 Bifidobcterium 5 20 40 60 Lctobcillus 8 13 Clostridium perfrin- 1 gens Other Clostridium 7 14 29 Includes ll identified s subspecies of B. frgilis. less/ml. These dt re in greement with those of our erlier study, except tht resistnt clostridi hve not been found s yet. The ctivity of cefmndole (7-D-mndelmido-3- [1-methyl-lH-tetrzol-5-ylthiomethyl]-3- cephem-4-crboxylic cid) ws compred with tht of cephlothin. Cefmndole is new cephlosporin which hs been shown to hve brod spectrum of ctivity ginst fculttive bcteri (5, 22, 25). It hs been shown to be resistnt to penicillinse nd cephlosporinses derived from fculttive bcteri (25, 49). The results of the studies on the ctivity of cefmndole re shown in Tble 11. Since cefmndole is resistnt to /8-lctmses, the of B. frgilis tested were more resistnt to this gent thn would be expected, with only 9% of the susceptible to 32 ug/ml. B. frgilis (3- lctmses hve been shown to be different from those produced by Enterobctericee (29). It is possible tht cefmndole is not resistnt to the cephlosporinse produced by these. Our results with B. frgilis re in disgreement with those recently published by Ernst et l. (12), who found tht 57% of their were inhibited by 32 ug of cefmndole per ml. This discrepncy could be due to n inoculum effect, since our inoculum is t lest 10-fold greter thn tht used by Ernst nd coworkers, or it could be due to crryover of lrger mount of cephlosporinse with the inoculum. The studies of Olsson nd co-workers (29) showed tht the mount of f-lctmse produced by their of B. frgilis ws medium dependent, nd it is possible tht greter mounts of the enzyme re produced in the thioglycolte medium used in our studies. Further investigtion is necessry to determine the significnce of this phenomenon. Cefmndole ws more ctive ginst B. melninogeni nd other Bcteroides species thn ws cephlothin, hd similr ctivity ginst Fusobcterium species, nd ws less ctive ginst the grm-positive nerobes. Prior studies with cefzolin indicted tht it my be slightly more ctive thn cefmndole ginst B. frgilis, the nerobic cocci, nd clostridi (36). The ctivities of cefzflur (7-trifluoromethylthiocetmido - 3 - [1- methyl - 1H-tetrzol-5- ylthiomethyll-3-cephem-4-crboxylic cid) nd sodium cefoxitin were compred. Cefoxitin is cephmycin, clss of compounds closely relted to the cephlosporins. Results re shown in Tbles 12 nd 13. Cefzflur ws less ctive thn cefoxitin ginst B. frgilis nd other grm-negtive nerobes, ws similr in ctivity ginst grm-positive, non-sporeforming nerobes, nd ws somewht more ctive ginst Clostridium species other thn C. perfringens. Phrmcologicl studies with nimls indicte tht serum levels with cefzflur re similr to those obtined with cephlothin
744 SUTTER AND FINEGOLD ANTiMICItOB. AGZNTS CHZMOTHZR. TABLE 11. Activity of cefmndole ginst nerobic bcteri Cumultive % susceptible to indicted concn (,ug/ml) tested s0.1 0.5 1.0 2.0 4.0 8.0 16.0 32.0 64.0 128.0 256.0 2512 Bcteroides frgilis 34 9 29 56 71 Bcteroides melni- 9 11 56 67 89 nogeni Other Bcteroides 51 8 24 35 51 55 67 76 90 94 98 nd Selenomons Fusobcterium nu- 10 80 cletum Other Fusobcterium 4 75 Peptococ nd Gff- 42 17 57 83 88 93 98 ky Peptostreptococ 14 7 71 79 86 93 Anerobic nd mi- 4 25 croero Grm-negtive cocci 19 11 84 95 Eubcterium 9 11 56 78 89 Archni propionic 1 Propionibcterium 8 13 Bifidobcterium 5 20 60 Lctobcillus 8 13 75 88 Clostridium perfrin- 1 gens Other Clostridium 7 14 57 71 86 Includes ll identified s subspecies of B. frgilis. TABLE 12. Activity of cefzflur ginst nerobic bcteri Cumultive % susceptible to indicted concn (,ug/ml) tested -..1 0.5 1.0 2.0 4.0 8.0 16.0 32.0 64.0 128.0 2256 Bcteroides frgilis 41 2 5 10 12 42 Bcteroides melninogeni- 59 46 81 85 88 93 95 98 Other Bcteroides nd Se- 21 14 43 52 62 67 76 86 91 lenomons Fusobcterium nucletum 8 75 Other Fusobcterium 12 25 42 50 58 67 75 Peptococ nd Gffky 17 24 94 Peptostreptococ 15 27 87 93 Anerobic nd microero- 6 17 67 83 Grm-negtive cocci 7 86 Eubcterium 7 14 43 57 71 86 Archni propionic 2 Propionibcterium 4 75 Actinomyces 16 31 Lctobcillus 10 50 80 90 Clostridium perfringens 8 38 50 88 Other Clostridium 26 4 8 15 23 65 73 85 92 Includes ll identified s subspecies of B. frgilis. (1); therefore, orgnisms with MICs of 64 Ag or the groups of bcteri pper to be more resistmore/ml would be considered resistnt. Results nt thn those reported in previous study with cefoxitin ginst the nerobes indicte (36). At tht time, ll B. frgilis were tht the mjority of re inhibited t n inhibited by 32 ug/ml, wheres only 85% of chievble level of 32,ug/ml. However, some of recent isoltes re susceptible to tht level.
VOL. 10, 1976 ANTIMICROBIAL SUSCEPTIBILITY OF ANAEROBES 745 Nonetheless, cefoxitin is distinctly more ctive Clostridium species pper slightly more susthn ny of the cephlosporins ginst B. fr- ceptible thn those reported by Tlly et l. (42). gilis. Other Fusobcterium species, grm-posi- Chlormphenicol. The ctivity of chlormtive cocci, nd grm-positive, non-sporeforming phenicol ginst the nerobes tested is shown bcilli lso re demonstrting higher inhibitory in Tble 14. A level of 16 ug/ml is redily end points. The B. frgilis in the cur- chievble, nd ll but two of the bcteri were rent study pper to be less susceptible to cefox- inhibited t this concentrtion. Only one strin itin thn those reported by others (6, 28, 42), in the B. frgilis group (B. frgilis subsp. thebut the reminder of nerobes other thn tiotomicron or Bcteroides thetiotomicron) TABLE 13. Activity of sodium cefoxitin ginst nerobic bcteri Cumultive % susceptible to indicted concn (pg/ml) tested s0.1 0.5 1.0 2.0 4.0 8.0 16.0 32.0 64.0 128.0-256 Bcteroides frgilis Bcteroides melninogeni- 40 55 20 3 89 5 93 8 98 15 40 65 85 98 Other Bcteroides nd Se- 21 43 48 62 71 81 86 91 lenomons Fusobcterium nucletum 8 25 75 88 Other Fusobcterium 12 8 33 42 50 75 83 Peptococ nd Gffky 17 29 82 88 94 Peptostreptococ 15 60 73 87 93 Anerobic nd microero- 6 33 50 83 Grm-negtive cocci 7 14 43 Eubcterium 7 14 43 57 71 86 Archni propionic 2 Propionibcterium 4 75 Actinomyces 16 38 88 94 Lctobcillus 10 40 60 70 80 90 Clostridium perfringens 8 13 50 75 Other Clostridium 26 4 19 46 54 58 62 77 Includes ll identified s subspecies of B. frgilis. TABLE 14. Activity of chlormphenicol ginst nerobic bcteri Cumultive % susceptible to indicted concn (pg/ml) tested <0.1 0.5 1.0 2.0 4.0 8.0 16.0 32.0 64.0 128.0 Bcteroides frgilis 76 1 5 30 86 99 Bcteroides melninogeni 68 10 25 56 91 Other Bcteroides nd Seleno- 72 1 8 38 65 86 96 99 mons Fusobcterium nucletum 18 72 94 Other Fusobcterium 16 50 88 Peptococ nd Gffky 59 2 3 42 88 98 Peptostreptococ 29 3 21 66 97 Anerobic nd microerophilic 10 40 80 streptococci Grm-negtive cocci 25 32 68 96 Eubcterium 17 6 24 65 Archni propionic 3 33 67 Propionibcterium 12 50 75 92 Actinomyces 16 19 81 88 94 Bifidobcterium 5 20 60 Lctobcillus 18 17 44 83 94 Clostridium perfringens 9 22 Other Clostridium 34 3 6 27 68 91 Includes ll identified s subspecies of B. frgilis.
746 SUTTER AND FINEGOLD required 32,ug/ml for inhibition, nd one strin of B. clostridiiformis subsp. clostrid4iformis ws inhibited by 128 yg/ml. These results re similr to previous reports from this lbortory nd to those of others (2, 16, 18, 21, 32, 33, 39, 41, 46, 51). Thimphenicol, n nlogue of chlormphenicol, with substitution of the p-nitro group by methylsulfonyl moiety, nd its prenterl form, thimphenicol glycinte, were tested during the first prt of this study. These compounds produce serum levels equivlent to those of chlormphenicol nd hve been found to produce less serious side effects thn does chlormphenicol (46). Results obtined with thimphenicol re given in Tble 15. Thimphenicol glycinte ws equivlent to thimphenicol in ctivity. Thimphenicol ws similr in ctivity to chlormphenicol, with most of the tested inhibited by 16 ug or less/ml. The orgnisms tht required 32,ug or more/ml for inhibition were one strin ech of Bcteroides species, B. corrodens, Lctobcillus plntrum, nd Clostridium difficile. Mcrolides nd similr drugs. Clindmycin ws very ctive ginst most of the nerobes t 8,Mg or less/ml (Tble 16). All B. frgilis were inhibited t this level. Strins tht required 16,Mg or more/ml for inhibition were three of the Bcteroides species, nine of the Peptococ species, Lctobcillus ctenforme, nd four of the Clostridium species. For most of the groups of nerobes tested, results re in greement with previously published studies (2, 17, 18, 21, 32-34, 39, 41, 47, 50, ANTiMICROB. AGENTS CHZMOTHZR. 51). With regrd to resistnce mong the Peptococ, it ws not observed by Werner nd B6hm (47) but ws observed by Mrtin et l. (21) nd in our own erlier studies (18). This my be n importnt considertion in nerobic pleuropulmonry infections nd in certin other nerobic infections where clindmycin my be recommended when penicillin cnnot be used. Resistnce mong Clostridium species other thn C. perfringens hs been noted previously (34, 41, 50). However, despite the widespred use of this compound over the pst few yers, resistnce does not pper to be emerging mong nerobes previously susceptible to it. The ctivity of erythromycin ginst the nerobes tested in the second prt of the study is indicted in Tble 17. These results show tht the B. frgilis, nd the nerobic nd microero, showed more resistnce to erythromycin, wheres the fusobcteri nd Clostridium species were more susceptible thn used in the first prt of the study. These results were the subject of previous publiction (37). These disprities were not observed with clindmycin in the two prts of the study. Erythromycin ws much less ctive thn clindmycin ginst B. frgilis, the fusobcteri, nd the grm-negtive cocci. It showed greter ctivity ginst the nerobic streptococci nd clostridi nd hd similr ctivity ginst the reminder of the tested. Josmycin, mcrolide structurlly similr to erythromycin nd with similr in vitro ctivity ginst fculttive bcteri, does not induce TABLz 15. Activity of thimphenicol ginst nerobic bcteri Cumultive % susceptible to indicted concn (,tg/ml) tested <0.1 0.5 1.0 2.0 4.0 8.0 16.0 32.0 64.0 128.0 Bcteroides frgilis 42 5 21 71 Bcteroides melninogeni 59 9 24 51 90 Other Bcteroides nd Seleno- 21 19 24 57 76 86 91 95 mons Fusobcterium nucletum 8 Other Fusobcterium 12 42 92 Peptococ nd Gfftky 17 35 71 Peptostreptococ 15 33 47 93 Anerobic nd microerophilic 6 50 83 streptococci Grm-negtive cocci 7 43 86 Eubcterium 7 43 57 Archni propionic 2 50 Propionibcterium 4 50 75 Actinomyces 16 25 56 94 Lctobcillus 10 10 30 50 90 Clostridium perfringens 8 Other Clostridium 27 4 22 63 78 96 Includes ll identified s subspecies of B. frgilis.
VOL. 10, 1976 ANTIMICROBIAL SUSCEPTIBILITY OF ANAEROBES 747 TABLz 16. Activity of clindmycin ginst nerobic bcteri Cumultive % susceptible to indicted concn (ug/ml) tested 0.1 0.5 1.0 2.0 4.0 8.0 16.0 32.0 64.0 128.0-256 Bcteroides frgilis 76 17 46 67 84 96 Bcteroides melninogeni- 64 97 Other Bcteroides nd Se- 72 76 90 93 94 96 99 lenomons Fusobcterium nucletum 18 94 Other Fusobcterium 16 81 Peptococ nd Gffky 59 41 76 80 81 83 86 93 Peptostreptococ 29 52 97 Anerobic nd microero- 10 40 70 80 90 Grm-negtive cocci 25 88 Eubcterium 17 41 77 88 Archni propionic 3 33 Propionibcterium 12 67 Actinomyces 16 56 Bifidobcterium 5 80 Lctobcillus 18 56 83 89 94 Clostridium perfringens 9 33 57 89 Other Clostridium 34 9 41 53 62 79 88 91 Includes ll identified s subspecies of B. frgilis. TABLE 17. Activity of erythromycin ginst nerobic bcteri Cumultive % susceptible to indicted concn (jag/ml) tested co.1 0.5 1.0 2.0 4.0 8.0 16.0 32.0 64.0 128.0-256 Bcteroides frgilis 34 3 6 15 24 47 71 88 94 Bcteroides melninogeni- 9 44 89 Other Bcteroides nd Se- 51 10 45 78 86 96 98 lenomons Fusobcterium nucletum 10 30 70 90 Other Fusobcterium 4 25 50 75 Peptococ nd Gffky 42 5 36 71 83 Peptostreptococ 13 77 85 92 Anerobic nd microero- 4 Grm-negtive cocci 19 5 32 58 79 90 Eubcterium 9 44 Archni propionic 1 Propionibcterium 8 88 Bifidobcterium 5 60 Lctobcillus 8 63 88 Clostridium perfringens 1 Other Clostridium 7 14 71 Includes ll identified s subspecies of B. frgilis. mcrolide resistnce mong stphylococci (30). ctive thn clindmycin ginst the clostridi It hs been shown to be ctive ginst B. fr- but ws less ctive thn clindmycin ginst gilis nd other nerobic bcteri (17, 20, 27, the fusobcteri. It ppers to be s ctive s 35). The susceptibility of the nerobes from rosmicin ginst B. frgilis (37) nd other the second prt of the study is given in Tble nerobes. However, direct comprison with 18. On weight bsis, josmycin ws more the sme ws not mde. ctive thn erythromycin or clindmycin A new oligoscchride, everninomicin B, ws ginst B. frgilis nd showed ctivity similr tested nd the results re shown in Tble 19. to tht of erythromycin with the reminder of Phrmcologicl dt re not yet vilble, but the nerobes. It, like erythromycin, ws more on weight bsis everninomicin is less ctive
748 SUTTER AND FINEGOLD ANTiMICROB. AGENTS CHZMOTHZR. TABLE 18. Activity ofjosmycin ginst nerobic bcteri Cumultive 9 susceptible to indicted concn (,tg/ml) tested S0.1 0.5 1.0 2.0 4.0 8.0 16.0 32.0 64.0 128.0-256 Bcteroides frgilis 34 29 53 77 Bcteroides melninogeni- 9 56 Other Bcteroides nd Se- 51 12 90 92 98 lenomons Fusobcterium nucletum 10 30 80 Other Fusobcterium 4 25 50 75 Peptococ nd Gfthy 44 43 82 84 87 93 98 Peptostreptococ 13 31 85 92 Anerobic nd microero- 4 50 75 Grm-negtive cocci 19 5 32 42 68 84 95 Eubcterium 9 33 78 Archni propionic 1 Propionibcterium 8 38 Bifidobcterium 5 Lctobcillus 8 38 75 88 Clostridium perfringens 1 Other Clostridium 7 14 71 Includes ll identified s subspecies of B. frgilis. TABLE 19. Activity of everninomicin B ginst nerobic bcteri Cumultive % susceptible to indicted concn (Ag/ml) tested O0.1 0.5 1.0 2.0 4.0 8.0 16.0 32.0 64.0 128.0.256 Bcteroides frgilis Bcteroides melninogeni- 36 58 9 64 3 78 6 85 14 97 25 42 69 94 97 Other Bcteroides nd Se- 20 15 40 45 55 65 70 95 lenomons Fusobcterium nucletum 8 50 88 Other Fusobcterium 10 40 50 Peptococ nd Gffky 13 69 92 Peptostreptococ 12 50 Anerobic nd microero- 5 80 Grm-negtive cocci 6 33 67 83 Eubcterium 7 43 86 Archni propionic 2 50 Propionibcterium 4 25 Actinomyces 16 69 94 Lctobcillus 7 86 Clostridium perfringens 7 43 71 86 Other Clostridium 23 13 83 91 Includes ll identified s subspecies of B. frgilis. thn clindmycin ginst B. frgilis nd other grm-negtive nerobes nd more ctive ginst the clostridi, including resistnt to clindmycin. It ws lso more ctive thn ws clindmycin ginst grm-positive, non-sporeforming bcteri, with the exception of the few. of Archni, Propionibcterium, nd Actinomyces tested. Tetrcyclines. The ctivities of tetrcycline, doxycycline, nd minocycline were determined throughout the study. Results re shown in Tbles 20 through 22. Only 42% of in the B. frgilis group remin susceptible to tetrcycline t 4,ug or less/ml nd 46% t 8,ug or less/ ml. Other groups of nerobes lso exhibited less suceptibility to tetrcycline thn in prior reports (16, 33, 38). The current results re similr to other recently published dt (2, 9, 21, 32, 41, 51). Doxycycline remins more ctive thn tetrcycline ginst nerobes but is
VOL. 10, 1976 ANTIMICROBIAL SUSCEPTIBILITY OF ANAEROBES 749 TABLE 20. Activity of tetrcycline ginst nerobic bcteri Cumultive % susceptible to indicted concn (gg/ml) tested -0.1 0.5 1.0 2.0 4.0 8.0 16.0 32.0 64.0 128.0 Bcteroides frgilis 76 25 40 42 46 68 93 99 Bcteroides melninogeni 67 51 75 76 79 87 94 96 99 Other Bcteroides nd Seleno- 72 8 33 35 43 50 60 75 93 99 mons Fusohcterium nucletum 18 33 Other Fusobcterium 16 19 88 94 Peptococ nd Gfftky 59 2 25 29 36 37 61 92 Peptostreptococ 29 28 38 41 48 52 72 86 97 Anerobic nd microerophilic 10 50 60 70 90 streptococci Grm-negtive cocci 26 8 54 69 73 85 92 Eubcterium 17 6 24 59 65 77 82 94 Archni propionic 3 67 Propionibcterium 12 58 75 83 Actinomyces 16 56 69 94 Bifidobcterium 5 60 Lctobcillus 17 6 24 53 59 65 77 82 Clostridium perfringens 9 11 22 56 67 78 Other Clostridium 33 6 36 46 49 52 61 67 76 91 Includes ll identified s subspecies of B. frgilis. TABLE 21. Activity of doxycycline ginst nerobic bcteri Cumultive % susceptible to indicted concn (,ug/ml) tested s0.1 0.5 1.0 2.0 4.0 8.0 16.0 32.0 64.0 128.0 Bcteroides frgilis 76 5 41 42 50 75 88 97 Bcteroides melninogeni 67 66 75 78 90 96 97 99 Other Bcteroides nd Seleno- 72 15 40 43 53 68 79 85 96 99 mons Fusobcterium nucletum 18 44 Other Fusobcterium 16 38 88 Peptococ nd Gffky 60 8 28 35 40 70 93 98 Peptostreptococ 29 31 45 66 79 97 Anerobic nd microerophilic 10 20 70 90 streptococci Grm-negtive cocci 26 4 58 69 73 81 96 Eubcterium 17 12 59 65 77 82 88 Archni propionic 3 67 Propionibcterium 12 17 75 83 92 Actinomyces 16 63 69 94 Bilidobcterium 5 20 40 60 Lctobcillus 17 12 35 59 71 82 94 Clostridium perfringens 9 11 67 78 89 Other Clostridium 33 21 49 52 61 68 82 97 Includes ll identified s subspecies of Bcteroides frgilis. slightly less ctive thn minocycline ginst species, three Streptococ intermedius, two the sme, except for C. perfringens. Eubcterium species, two Archni propion- Metronidzole. The susceptibility of the n- ic, eight Propionibcterium cnes, two Propierobes to metronidzole is shown in Tble 23. onibcterium vidum, eight Actinomyces spe- With the exception of the grm-positive, non- cies, one Actinomyces isrelii, one Actinomyces sporeforming bcilli, the mjority of viscosus, nd one ech of Bifidobcterium spewere inhibited by 16,ug or less/ml. cies, Bifidobcterium dolescentis vr. B, nd requiring MICs of 32,.g or more/ml were two Bifidobcterium infntis. These results gener ofbcteroides pneumosintes, one Pepto- lly gree with those in previous publictions coc scchrolyti, one Peptostreptococ (11, 19, 23, 31, 34, 41, 44, 45). We did not observe
750 SUTTER AND FINEGOLD TABLz 22. Activity of minocycline ginst nerobic bcteri Cumultive % susceptible to indicted concn (,tg/ml) tested :0.1 0.5 1.0 2.0 4.0 8.0 16.0 32.0 Bcteroides frgilis 76 29 49 57 70 82 97 Bcteroides melninogeni 65 71 74 82 89 97 99 Other Bcteroides nd Selenomons 70 29 49 56 70 79 90 96. Fusobcterium nucletum 18 67 Other Fusobcterium 16 69 94 Peptococ nd Gflky 58 19 43 59 74 93 97 Peptostreptococ 28 39 54 75 82 93 Anerobic nd microero 10 40 90 Grm-negtive cocci 25 12 68 72 92 Eubcterium 16 25 69 81 94 Archni propionic 3 33 Propionibcterium 12 42 83 92 Actinomyces 16 88 94 Bifidobcterium 5 40 80 Lctobcillus 17 24 59 71 82 88 Clostridium perfringens 9 22 67 78 Other Clostridium 33 27 58 61 73 76 97 Includes ll identified s subspecies of.b. frgilis. ANTiMICROB. AGZNTS CHZMOTHZR. TABLE 23. Activity of metronidzole ginst nerobic bcteri Cumultive % susceptible to indicted concn (jsg/ml) tested s0.1 0.5 1.0 2.0 4.0 8.0 16.0 32.0 64.0 128.0 2256 Bcteroides frgilis 76 1 12 28 57 86 99 Bcteroides melninogeni- 69 15 81 93 99 Other Bcteroides nd Se- 71 6 42 69 86 94 97 99 lenomons Fusobcterium nucletum 18 56 94 Other Fusobcterium 16 38 94 Peptococ nd Gfthy 58 3 72 88 98 Peptostreptococ 29 21 69 76 83 86 93 97 Anerobic nd microero- 10 30 40 50 Grm-negtive cocci 25 4 60 92 96 Eubcterium 16 6 44 81 88 Archni propionic 3 33 Propionibcterium 12 8 17 Actinomyces 16 13 19 50 56 63 Bifidobcterium 5 20 40 60 80 Lctobcillus 19 11 37 58 68 79 84 90 Clostridium perfringens 9 33 78 Other Clostridium 32 9 53 81 97 Includes ll identified s subspecies of B. frgilis. resistnt of B. frgilis, Fusobcterium non-sporeforming bcilli. However, the mjorspecies, or Clostridium species, s ws reported ity of nerobic bcteri most frequently enby Chow et l. (10). countered in infections remin susceptible to Although ll of the in the current chievble levels of metronidzole. study were defined s nerobes bee on initil isoltion they grew poorly or not t ll in ACKNOWLEDGMENTS the presence of ir, some becme more ero- We grtefully cknowledge the contribution of Godfrey tolernt through subsequent in vitro cultiv- K. M. Hrding for his studies on identifiction of subspecies tion. For the most prt, these were the of the B. melninogeni. We thnk Lubn Afzl showing the gretest resistnce to metronid- Kureshi nd Y. Y. Kwok for their excellent technicl ssistnce nd Edwrd 0. Wrburton nd others t the Biomedizole. They belonged in the genus Streptococ cl Engineering nd Computer Center, Sepulved VA Hosnd in the vrious gener of grm-positive, pitl, for their excellent ssistnce in compiling the dt.
VOL. 10, 1976 These studies were supported by grnts from Beechm- Mssengill Phrmceuticls, Bristol, Tenn., Bristol Lbortories, Syre, N.Y., Delby Phrmceuticls, Inc., Bloomfield, N.J., E. I. Dupont de Nemours nd Co., Newrk, Del., Lederle Lbortories, Perl River, N.Y., Eli Lilly nd Co., Indinpolis, Ind., Pfizer Lbortories, New York, N.Y., Schering Corp., Bloomfield, N.J., G. D. Serle nd Co., Chicgo, Ill., Smith, Kline nd French Lbortories, Phildelphi, P., nd Zmbon, S.p.A., Bresso, Milno, Itly. LITERATURE CITED 1. Actor, P., J. V. Uri, J. R. Gurini, I. Zjc, L. Phillips, C. S. Schs, R. M. De Mrinis, J. R. E. Hoover, nd J. A. Weisbch. 1975. A new prenterl cephlosporin. SK&F 59962: in vitro nd in vivo ntibcteril ctivity nd serum levels in experimentl nimls. J. Antibiot. 28:471-476. 2. Blzevic, D. J. 1976. Antibiotic susceptibility of the subspecies of Bcteroides frgilis. Antimicrob. Agents Chemother. 9:481-484. 3. Blzevic, D. J., nd J. M. Mtsen. 1974. 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