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CURRENT STATUS OF IN VITRO ANTIBACTERIAL ACTIVITIES OF AND ELEVEN OTHER β-LACTAMS AGAINST RECENT CLINICALLY SIGNIFICANT PATHOGENS

SATOSHI NAKASHIO and MASAO NAKAMURA Department of Laboratory Medicine, St. Marianna University School of Medicine, Kawasaki 213, Japan

(Received January 22, 1987)

The present in vitro antibacterial activity of five third- generation (cefo- taxime, , , cefpiramide, ), four first- and second- generation agents (, , , ) and eight other anti- microbial agents were simultaneously compared against 384 strains of Gram- positive cocci, 595 strains of Enterobacteriaceae, 240 strains of non- fermenters and 143 strains of anaero- bic bacteria and others. The agar dilution method was used to measure the minimum inhibitory concentration (MIC) and the results were expressed as MIC range, MIC 50%and MIC90%. AmongƒÀ- lactams, cefotaxime and latamoxef exhibited the highest activity against a wide variety of Gram- positive and Gram- negative bacteria. Cefpiramide and cefoperazone were generally less active than these two agents, although cefpiramide showed

good activity against P. aeruginosa strains. Ofloxacin, a new pyridone carboxylic acid derivative, inhibited the growth of over 80% of strains in all species tested, except C. difficile strains, at a concentration of 3.13ƒÊg/ ml. All the strains were tested forƒÀ- lacta- mase production by the Cefinase disc method and susceptibility toƒÀ- latams evaluated in each of the species. We hope to have demonstrated the need for periodic susceptibility testing to provide guidance for empiric chemotherapy.

INTRODUCTION study, we chose cefotaxime as the standard with Some new third- generation cephalosporins have which other agents were compared, because it is become available in the last few years. These the pioneer of the third-generation agents and is agents have potentially greater clinical usefulness now available in over 90 countries. In addition, because they possess:(a) a wider spectrum of the total net world consumption of cefotaxime ac- antibacterial activity than do the older (first- and counts for more than 10% of all cephalosporins. second- generation) cephalosporins and (b) lower Cefotaxime, cefoperazone and latamoxef were in- toxicity than the aminoglycosides 1). Since patterns troduced in Japan in 1981, and cefmenoxime and of resistance in a wide variety of patho- cefpiramide in 1983 and 1985. Despite increasing genic organisms may vary over even short periods consumption of third- generation agents, little has and according to hospital environment, periodic been published documenting their antibacterial ac- evaluation of antibacterial activity is necessary for tivity against recently significant pathogens freshly up- to- date information. The group isolated from clinical specimens. is large and still growing, and it is impossible to It is important to investigate whether the isola- simultaneously evaluate all available agents in any tion frequencies of resistant organisms against these one test. We therefore limited our comparative agents have increased after several years of use. studies to a few establishedƒÀ- lactams or to the We compared their present antibacterial activities latest developments in the field. In the present with the results evaluated when they were first 676 CHEMOTHERAPY SEPT. 1987 introduced in Japan 2•`6), and with those of other In vitro susceptibility testing. The mini- groups of drugs, including G, , mum inhibitory concentrations (MICs) were deter- , gentamicin, tobramycin, minocyc- mined by the agar dilution method as defined by line, lincomycin and ofloxacin. the Japanese Society of Chemotherapy 11). Over-

β- lactamase (EC 3.5. 2.6) production is one of night cultures of test- organisms were diluted to the major mechanisms by which organisms resist a density of approximately 104 colony- forming units

β-lactams. The contribution ofƒÀ- lactamase may per ml in Mueller- Hinton broth (Difco, Michigan, be qualitative and/ or quantitative 7). An awarenenss USA) for facultative anaerobes and GAM broth of the prevalence ofƒÀ- lactamase in a specie, is (Nissui) for anaerobes and applied by means of a valuable not only for physicians in choosing anti- multiple inocula replicotor (Sakuma, Tokyo) to biotics but also for manufactures in anessing the the surface of modified Mueller- Hinton agar plates relative merits of new agents. A novel cephalo- (Nissui) containing two- fold dilutions of antibac- sporin nitrocefin, for example, has been reported terial agents. For streptococci, modified Mueller- as being very sensitive to hydrolysis by a wide Hinton agar supplemented with 5% horse blood was variety ofƒÀ- lactemases 6). The present study was used, and for Haemophilus, modified Mueller- Hin- also designed to evaluate the relationship between ton agar supplemented with 2% Filde's Enrichment susceptibility againstƒÀ- lactams andƒÀ- lactamase (Difco). Streptococcus, Neisseria and Haemophi- production in each species tested. lus strains were incubated in 5% CO2. For Cans- MATERIALS AND METHODS pylobacter, modified Mueller- Hinton agar supple- Strains tested. The organisms used were all mented with 5% defibrinated sheep blood and 0.1% recent clinical isolates in St. Marianna University vitamin K- hemin (Difco) was used. Control Plates Hospital and were routinely identified by the clini- without an antibacterial agent were also inoculated cal microbiology laboratory. Species and numbers before and after each series of plates. Staphylococ- of strains tested are shown in Table 1. The iden- cus aureus ATCC 25923, Escherichia coli ATCC tification was confirmed by the API 20E microtube 25922 and ATCC 27853 system (Analytab Products, Plainview, New York, were included as control strains in all susceptibility USA) and Enteogram System 9) (Terumo, Tokyo) tests. The MICs were determined as the lowest for Enterobacteriaceae, the Nonfergram system 10) concentrations inhibiting growth after overnight (Terumo) for non- fermenters and the SP- 18 sys- incubation at 37•Ž. A few slow growing strains tem (Nissui, Tokyo) for staphylococci. Isolates were incubated for 48 hr. Results were expressed were stored in 20% skim milk and kept frozen at as the range of MIC (ƒÊg/ ml), MIC50. and MIC90. - 80℃ until use. Before testing, the isolates were β- lactamase detection. Production ofƒÀ- lacta- subcultured onto blood agar plates for facultative mase was determined by testing 18- 24hr- old cul- anaerobes and GAM agar plates (Nissui) for anaer- tures by the Cefinase disc (BBL Microbiology Sys- obes. tent) method 12). The characteristic ofƒÀ- lactamase

Antibacterial agents. A total of 17 antibac- production of a species was evaluated as "+","-" terial agents were tested. They were kindly sup- or "d", according to the description in Bergey's plied by the following organizations: carbenicillin, Manual of Systematic Bacteriology 12). The mean- cefoperazone and gentamicin (Pfizer Teito, To- ings of symbols are:+, 90% or more of the strains kyo); latamoxef, cefamandole and tobramycin positive;-, 90% or more of the strains negative: (Shionogi, Osaka); penicillin G and ampicillin(Mei- d, 11- 89% of the strains positive. ji Seiko, Tokyo); cefotiam and cefmenoxime (Ta- RESULTS keda, Osaka); lincomycin and cefpiramide (Japan The MIC range, MIC50 and MICE90 of nineƒÀ- Upjohn, Tokyo); cefmetazole (Sankyo, Tokyo); lactams and eight other antibacterial agents are cefazolin (Fujisawa, Osaka); cefotaxime (Roussel shown in Table 1. The reproducibility of the

Medico, Tokyo); minocycline (Japan Lederle, To- MIC determinations against control organisms was kyo); offoxacin (Daiichi, Tokyo). Solutions of excellent for all agents and varied only within one antibacterial agents were freshly prepared for each two- fold dilution in separate measurements. A- test. gainst staphylococci, allƒÀ- lactams were relatively VOL.35 NO.9 CHEMOTHERAPY 677

Table 1-1 Antibacterial activity of seventeen antimicrobial agents 678 CHEMOTHERAPY SEPT. 1987

Table 1-2 Antibacterial activity of seventeen antimicrobial agents VOL.35 NO.9 CHEMOTHERAPY 679

Table 1- 3 Antibacterial activity of seventeen antimicrobial agents 680 CHEMOTHERAPY SEPT. 1987

Table 1-4 Antibacterial activity of seventeen antimicrobial agents CHEMOTHERAPY VOL.35 NO.9 681

Table 1- 5 Antibacterial activity of seventeen antimicrobial agents 682 CHEMOTHERAPY SEPT. 1987

Table 1- 6 Antibacterlal activity of seventeen antimicrobial agents VOL.35 NO.9 CHEMOTHERAPY 683

Table 1-7 Antibacterial activity of seventeen antimicrobial agents 684 CHEMOTHERAPY SEPT. 1587

Table 1- 8 Antibacterial activity of seventeen andmlcroblial agents VOL.35 NO.9 CHEMOTHERAPY 685

Table 1- 9 Antibacterial nedvity of aeventaen antimicrobial agents 686 CHEMOTHERAPY SEPT. 1987

Table 1-10 Antibacterial acdvity of seventeen antimicrobial agents VOL.35 No.9 CHEMOTHERAPY 687

Table 1- 11 Antibacterial activity of seventeen antimicrobial agents CHEMOTHERAPY SEPT. 1987 688

Table 1-12 Antibacterial acdvity of aeventem antimicrobial agents VOL.35 NO.9 CHEMOTHERAPY 689

Table 1- 13 Antibacterial activity of seventeen antimicrobial agents SEPT. 1987 690 CHEMOTHERAPY

Table 1- 14 Antibecterial activie of seventeen andedcrobial agents VOL.35 NO.9 CHEMOTHERAPY 691

Table 1-15 Antibacterial activity of seventeen antimicrobial agents 692 CHEMOTHERAPY SEPT. 1987

Table 1- 16 Antibacterial acdvity of seventeen antimicrobial agents VOL.35 NO.9 CHEMOTHERAPY 693

Table 1- 17 Antibacterial activity of seventeen antimicrobial agents

a. Number in parentheses indicates number of strains tested. 694 CHEMOTHERAPY SEPT. 1987

Table 2 Antibacterial activity of five third- generation cepheme

a MIC80varies considerably. dependins on the ceohern involved. b Coagulase- negative. mannitol- nonfermentative staohylococci. c Coagulase- negative. mannitol- fermentative staohylococci. inactive, the MICs. being 25ƒÊg /ml or more. A- in susceptibility to was observed, how- gainst coagulase- negative staphylococci (CNS), a ever, between strains of E. faecalis and of E. faeci- significant difference in susceptibility ',vas observed um and E. avium. MICs90 of ampicillin and car- between mannitol- fermentative CNS and mannitol- benicillin against E. faecalis strains were 1.56 and nonfermentative CNS. The former group consist- 3.13ƒÊg/ml respectively, whereas those against E. ed mainly of S. haemolyticus and a small number faecium and E. avium strains were 25ƒÊg/ml or of S. sciuri, S. capitis and S. cohnii. The latter more. group consisted mainly of S. epidermidis and a few Against Enterobacteriaceae, the third-generation S. hominis. In general, all cephalosporins were agents were MOre effective than the older ones, inactive against the latter group, with MICs90 of especiagainst C. freundii,C. diversus, E.aero-

25ƒÊg/ ml or more; but active against the former, genes, E. cloacae, indole- positive Proteus (includ- with MICsao ranging 0.78ƒÊg/m l (cefotiam) to 12.5 ing P.vulgaris, M. morganii and P. rettgeri), and μg/ ml (latamoxef). The significance of the dif- S. marcescens. The Enterobacteriaceae were rough- ference in susceptibility of CNS necessiates accurate ly divided into two groups according to their identification of species and precise testing in a susceptibility to the third-generation agents (Table clinical microbiology laboratory. The third- gener- 2). The Group 1, which included strains of E. ation agents had less activity than the older agents coli, C. freundii, C. diversus, K. pneumoniae ssp. against mannitol- nonfermentative CNS. Against pneumoniae, K. pneumoniae ssp. oxaenae, H. alvei, streptococci, all ƒÀ- Itams showed good activity P. mirabilis and Salmonella species, was normally and MIC. of these agents vvere 1.56ƒÊg/ ml or less. sensitive to these agents. Amounts ranging from No significant difference in susceptibility to /3-lac- 0.025- 6.25ƒÊg/ml of these agents were sufficient to tams was observed among S. pneumoniae, S. pyo- inhibit 80% of strains of all species in this group. gene s and S. agalactiae strains. Against enterococ- Group 2, however, which included strains of E. ci, all cephalosporins were inactive and MICs.. aerogenes, E. cloacae, K. oxytoca, P.vulgaris, M. were more than 100ƒÊg/ ml. A significant difference morganii, P. rettgeri and S. marcescens, showed VOL.35 NO.9 CHEMOTHERAPY 695

Table 3 Detection of ƒÀ- lactamase by Nitrocefin disc

*+ : more than 90% strains positive. -: more than 90% strains negative. d : 11-89% strains positive. b Coagulase- negative. mannitol- nonfermentatiye staphylococci. c Coagulase- nesative. mannitol- fermentative staphylococci. d Pentococci and pentostranococci.

varying susceptibility to each of the five third- strains. The third- generation agents, however, generation agents. A significant difference in showed equally good activity against indole- nega- species susceptibility to the older agents, however, tive and- positive Proteus strains. was observed between indole- positive and- negative Against non- fermenters, the relative activities Proteus strains. P. mirabilis strains were sensitive of ƒÀ-•@lactams varied by species tested. Strains of to the first- and second- generation agents with P. aeruginosa, P. cepacia, P. putida, Flavobacter- MICs90 ranging from 0.78- 6.25 ƒÊg/ml. However, ium species and Acinetobacter species were resistant indole- positive strains were generally resistant to to cephalosporins, whereas strains of A. faecalis the older agents and MICs 90 ranged from 6. 25 ƒÊg/ were normally sensitive, the MICs90, of cefotaxime ml(cefmetazole) to more than 100 ƒÊg/ml (cefazo- and latamoxef being 0.78 and 0.39 ƒÊg/ml respec- lin). MIC s90 of the older agents to indole- positive tively. Strains of X. maltophilia(formerly P. mat. Proteus strains were 4 (cefmetazole) to 128 (cefo- tophilia) were generally highly resistant to cepha- tiam)- times higher than those to P. mirabilis losporins, despite their lack of ƒÀ-•@lactamase produc- 696 CHEMOTHERAPY SEPT. 1987 tion. Against Haemophilus and Neisseria species, isolates, cefotaxime and latamoxef appear to be the cephalosporins were generally highly effective. most widely active against Enterobacteriaceae, They were inactive against 'trains of Campylo- some non- fermenters and Gram- positive cocci. bacter, although some penicillin. showed good activ- Although there was a slight difference in activity ity. Against anaerobic bacteria, the relative activ- against some species, this difference seems to be ities of ƒÀ- lactams varied by species tested. Again. clinically irrelevant when the low MICs are con- Gram- positive cocci (peptococci and peptostrepto- sidered. Their insufficient activity in comparison cocci) and Fusobacterium, all ƒÀ- lectems showed with cefpiramide against P. aeruginosa may consti- good activity, their MICs90 being 0.78 ƒÊg/ml or tute a slight handicap in clinical infections if less. Against Bacteroides (mainly B. fragilis) and microbiological diagnosis has not excluded a P. C. difficile strain., cephalosporins were generally aeruginosa infection 14). Nevertheless, it should be ineffective. Ofloxacin, one of the newer pyridone noted that cefpiramide is definitely less active than carboxylic acid derivatives, inhibited growth of cefotaxime and latamoxef against a wide variety over 80% of strains in all species tested except C. of species. Cefopernone and cefmenoxime were difficile strains, at a concentration of 3. 13 ƒÊg/ml. less active than cefotaxime and latamoxef against An apparently close relationship between suscep- Enterobacteriaceae in vitro. Cefotiam and cefa- tibility to ƒÀ- lactams and ƒÀ- lactarnase production mandole were generally less active than the third- was observed in Proteus species (Table 3). Strains generation agents, and might become obsolete as of indole- positive Proteus produced ƒÀ- lactamase and soon as the latter becomes generally more availa- were resistant to the older cephalosporins, whereas ble. strains of P. mirabilis did not produce ƒÀ- lactamase Our results were compared with those previously and were susceptible to the older cephalosporins. evaluated when the third- generation agents were Both groups of Proteus strains, however, were first introduced in Japan 2•`6), and are in general equally susceptible to the third- generation cepha- agreement with the previously reported suscepti- losporins which are generally ƒÀ- lactamase resistant. bilities of a wide variety of clinical isolates. No On the other hand, a controversial relationship was significant increase in resistant organisms to any of observed in Klebsiella species: although K. pneu- the agents was observed in the species tested, al- moniae ssp. pneumoniae produced ƒÀ- lactamase, though continued increase in the resistance of or- whereas K. pneumoniae ssp. ozaenae did not, the ganisms to the older cephalosporins has been susceptibility profiles of both species were quite demonstrated 14). There were, however, some differ- similar. These results indicate that ƒÀ- lactamase ences between the present results and those re- production is not an absolute determinant of sus- Ported from other researchers 15•`19) in the suscepti- ceptibility to ƒÀ- lactams, so that alternative mecha- bility patterns of bacterial isolates. Regional varia- nism (s) of resistance should be considered in each tions, origins of strains tested, and extent of con- case. sumption of antibacterial agents may account for DISCUSSION some of these differences. The antibacterial activity of cephalosporins was No apparently close relationship was observed summarized in a recent paper 1).. Enormous pro- between ƒÀ- lactamase production and resistance to gress in cephalosporins has been effected of late by β-lactams in Klebsiella species or the Pseudomo- the development of a large number of potent semi- nas- Xanthomonas group. We demonstrated that synthetic derivatives. The pioneer of the newer, β- lactmmase production w. not an absolute predic- third-generation cephalosporins is cefotaxime, tor of susceptibility, as some of the ƒÀ- lactamase which combines high ƒÀ- lactamase stability with a producing strains were susceptible to cefaxolin and, markedly improved intrinsic bactericidal activity contrariwise, some of the ƒÀ- lactamase nonproduc- and extends the antibacterial spectrum to almost ing strains were resistant to cefazolin and cefotaxi- all species of Enterobacteriaceae and also to some me. In these cases, alternative mechanism (s) of

Gram- positive and Gram- negative organisms. resistance, for example, the existence of a per-

From the present in vitro comparison of activities meability barrier in the outer membrane or altera- of third- generation agents against recent clinical tion of the properties of the target enzymes, should VOL.35 NO.9 CHEMOTHERAPY 697

be considered. 6) MIWATANI, T. et al.: The antibacterial activi- Staphylococci and streptococci are Gram- positive ty of new against clinical bacteria which play important roles in infectious isolate.. A comparison of the antibacterial activity of cefotaxime with other antibiotics. diseases. Gram- positive cocci are notoriously sus- Jap. J. Antibiotics XXXVI: 260•`276, 1983 ceptible to ƒÀ- lactams. Enterococci, however, are 7) MITSUHASHI, S.; M. INOUE & S. MASUYOSHI: an exception to this rule, showing susceptibility Antibacterial activity of cefotaxime. J. An- to some penicillins but usually high resistance to timicrob. Chemother. 6 (Suppl) :37•`47,1980 cephalosporins. This differential susceptibility sug- 8) BOURGAULT, A- M.& J. E. ROSENBLATT: Charac- gests that streptococci and enterococci may possess terisation of anaerobic Gram-negative bacil- different penicillin- binding proteins. li by using rapid slide tests for ƒÀ-•@lactamase β-lactams have been thought to be more reliable production. J. Clin. Microbiol. 9: 654•`656, and safe than other groups of antibacterial agents. 1979 9) NAKASHIO, S.; I. KIKUGAWA, M. NAKAMURA, I. Nevertheless, serious problems have emerged with HARASAWA, T. MIYAMOTO, H. OURA, C. IRo- wide use of some of third- generation agents. La- KAWA & S. SAKAMA: Evaluation of "Enteo- tamoxef and cefoperazone, both of which have a gram" system for rapid identification of methyltetrazolethiol side chain, have been reported the Enterobacteriaceae. Clin. Microbiol. 12: tooause coagulation abnormalities, clinical bleeding 605•`610, 1985 and disulfiram- like reactions. In addition, an 10) NAKASHIO, S.; Y. INAJIMA, M. NAKAMURA, I. unusually high incidence of diarrhea has been as- HARASAWA, H. OURA, C. IROKAWA, T. MIYA- MOTO & T. SAKAI.: Evaluation of "Nonfer- sociated with administration of cefoperazone. Ce- fotaxime, however, does not have this side chain gram" system for rapid identification of glu- cose- nonfermentative Gram- negative rods. and has not caused the symptoms described above 17). Clin. Microbiol. 13: 373•`380, 1986 In conclusion, their broad spectrum and highly 11) GOTO. S.; T. KAWAKITA, N. KOZAKAI, S. MITSU- potent in vitro activity and other in vivo charac- HASHI, T. NisHIN0, N. OSAWA, & H. TANANG: teristics make cefotaxime and some other third- Methods for determination of minimum in- generation agents potentially useful therapeutic hibitory concentration (MIC). Chemotherapy agents; but continued periodic evaluation of their 29; 76•`79, 1981 12) MONTGOMERY, K.; L. RAYMUNDO, JR. & W. L. in vitro activity and in vivo therapeutic efficacy is DREW: Chromogenic cephalosporin spot test necessary. to detect ƒÀ- lactamase in clinically significant References bacteria. J. Clin. Microbiol. 9: 205•`207, 1) ROLINSON, G. N. ƒÀ-•@ lactam antibiotics. J. An- 1979 timicrob. Chemother. 17: 5•`36, 1986 13) KRIEG, N. R. & J. G. HOLT: In Bergey's 2) NAKASHIO, S.; I. KOINUMA, S. NARIKAWA, M. Manual of Systematic Bacteriology, vol. 1. NAKAMURA & I. HARASAWA: Antimicrobial ac- WILLIAMS& WILKINS, Baltimore, USA 1984 tivity of cefmetazole against various clinical 14) NAKASHIO, S.; I. KIKUGAWA, M. NAKAMURA, I. pathogens. Prog. in Med. 2: 1330•`4334, HARASAWA, C. YANAGAWA, Y. TANAKA, K. 1982 ASHIKAWA & N. MAEDA : Serotype and anti- 3) NAKASHIO, S.; I. KOINUMA, S. NARIKAWA, M. biotic susceptibility of Staphylococcus aureus NAKAMURA & I. HARASAWA: Antimicrobial ac- and Pseudomonas aeruginosa isolated from tivity of cefotaxime against various clinical burned patients, with the special reference pathogens. J. New Remed. Clin. 31: 849•` to hospital infection. J. Jap. Assoc. Infect. 853, 1982 Die. 60: 222•`230, 1986 4) NAKASHIO, S.; I. KOINUMA, S. NARIKAWA, M. 15) KURTZ, T. O.; D. S. WINSTON, J. A. HINDER, L. NAKAMURA & I. HARASAWA: Antimicrobial ac- S. YOUNG, W. L. HEWITT & W. J. MARTIN: tivity of cefoperazone against various clinical Comparative in vitro activity of moxalactam, pathogens. J. New Remed. Clin. 31: 1027•` cefotaxime, cefoperazone, and 1031, 1982 aminoglycosides against Gram- negative ba- 5) NAKASHIO, S.; I. KIKUGAWA, Y. INAJIMA, I. HARA- cilli. Antimicrob. Agents Chemother. 18: SAWA & M. NAKAMURA: Antimicrobial ac- 645•`648. 1980 tivity of ofloxacin, a new pyridone carboxy- 16) LANG,S. D. R.; D. J. EDWARDS & D. T. DUR- lic acid, against various clinical pathogens. ACK: Comparison of cefoperasone, cefotaxi- Prog. in Med. 6: 565•`572, 1986 me, and moxalactam (LY 127935) against 698 CHEMOTHERAPY SEPT. 1987

aerobic Gram- negative bacilli. Antimicrob. of eight ƒÀ- lactamase- stable cephalosporins Agents Chemother. 17: 488•`498, 1980 against ƒÀ- lactamase- producing Gram- nega- 17) PARKER, R. H. & S-•@Y. PARK: S•@afety of cefo- tive bacilli. Antimicrob. Agents. Chem. taxime and other new beta- lactam antibio- thee. 19: 407•`418, 1981 tics. J. Antimicrob. Chemother. 14 (Suppl) Acknowledgement B : 331•`335, 1984 The authors would like to thank I. Hareems, 18) SCHRINNER, E.; M. LIRRERT, L. PENASSE & A. LUTZ: Antibacterial activity of cefotaxime Y. Bayern., C. Irokawa, T. Miyamoto, S. Saksma and other newer cephalosporins. J. Antimi- and M. Iwamatsu for their excellent technical as- crob. Chemother. 6 (Suppl) A : 25•`30, 1980 sistance and helpful advice. 19) VERBIST, L.: Comparison of in vitro activities

新鮮臨床分離菌 に対す るCefotaximeお よび8種 の β－ラクタム系薬 剤の抗菌力の検討

中 塩 哲 士*中 村 正 夫 聖マリアンナ医科大学臨床検査医学教室

'臨 床材料から分離された グラム陽性球菌384株 ,腸 内細菌科菌群595株,ブ ドウ糖非発酵菌240株,嫌 気性菌 その他143株 を用いて,第3世 代セ フエム 系 薬 剤5種(Cofotaxime,Latamoxef,Cefmenoxime,Cefpira- mide,Cefoerazone).第1,第2世 代セ フェム系 薬 剤4種(Cefazolin,Cefotiam,Cefme励1馬C¢f鋤 dole)お よび他の8種 の抗菌性物質の`n"」'70抗 菌力を検討した。化 療標 準法 によりMICを 測定 し,MIC range,MICso,MICg0で 表示した。β一ラクタム剤の中でCefotaximeとLatamoxefは 広範な菌種に対し最も 優れた抗菌力を示した。CefpiramideとCefoperazoneは 前二者よ り抗菌力は劣った。OfloxacinはC.dilffcile を除いて,全 菌種において3.13μg/mlの 濃度で80%以 上の菌株の増殖を阻害した。Cefinseデ イスク法によ り全菌株の β-1actamase産 生能を測定 し,β-ラ クタム剤 に対す る感受性 との関連を検討した。有効な化学療法 を実施するために,新 鮮 分離菌株に対する抗菌活性を定期 的に検討 し把握 してお くこ とが必要である。