Vo1.11,1992
757
Table 3: In vitro aetivity of vermisporin against beta-hemolytic streptococci in Mueller-Hinton (MH) blood agar (Mueller-Hinton medium plus 5 % sheep blood) and in Haemophilus Test Medium (HTM) agar. Organism
(n)
Streptococcuspyogenes
Medium
MIC 0ag/ml) Range
MICS0
MIC90
(18)
MH blood agar HTMagar
2- 8 0.25- 1
4 1
8 1
Streptococcusagalactiae (13)
MH blood agar HTM agar
2- 8 0.25 - 2
8 1
8 2
Streptococcus group C (10)
MH blood agar HTMagar
2 - 16 1- 1
Streptococcus group G (12)
MH blood agar HTM agar
0.5 - 16 0.25 - 1
T h e r e was a m a r k e d increase in MBCs for staphylococci, the m e a n vermisporin MIC90 for Staphylococcus aureus being 0.27 lag/ml and the m e a n MBC90 7 ~g/ml. The mean vermisporin MIC90 for Staphylococcus epidermidis was 0.31/ag/ml, and the MBC90 5.3 pg/ml. T h e s e studies demonstrate that the new antibiotic, vermisporin has excellent activity against anaerobic species such as Bacteroides and Clostridium spp., inhibiting the majority of isolates at < 1 lag/ml. Blood inhibits the activity of vermisporin against streptococcal and staphylococcal species, and there is a 16- to 32-fold difference in MICs and MBCs for staphylococci. Further research may reveal whether a c o m p o u n d of this type could b e useful against anaerobic organisms and m a y suggest structural aspects which could be explored in other anti-anaerobic agents. It is conceivable that vermisporin could be used as an oral agent against Clostridiurn difficile and thereby decrease the use of oral vancomycin, which may be contributing to a rise in resistant enterococci.
References 1. National Committee for Clinical Laboratory Standards:Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. 2nd edition. Approved Standard MT-A2. NCCLS, Villanova, PA, 1990. 2. Jorgenson JH, Reflding JS, Maher IA, Howell AW: Improved medium for antimicrobial susceptibility testing of Haemophilus influenzae. Journal of Clinical Microbiology 1987, 25: 2105-2113.
4 1 2 0.5
8 1
3. National Committee for Clinical Laboratory Standards: Methods for antimicrobial susceptibility testing of anaerobic bacteria, 2nd edition. Approved Standard Mll-A2. NCCLS, Villanova, PA, 1991. 4. PearsonRD, Steigbigel RT, Davis HT, Chapman SW: Method of reliable determination of minimal lethal antibiotic concentrations. Antimierobial Agents and Chemotherapy 1980, 18: 688--708.
m
,lllllllll
In Vitro Activity of L-627 against Anaerobic Bacteria C.E. N o r d 1'2., A . L i n d m a r k 2, I. P e r s s o n 2
The in vitro activity of L-627 against 370 anaerobic bacterial strains including anaerobic cocci, Propionibacterium aches, Clostridlura
perfringens, Clostridium difficile, Bacteroldes fragilis, o t h e r Bacteroides spp. and fusobacteria was determined by the agar dilution method. This activity was compared with that of plperaeillin, cefoxitin, imipenem, meropenem, clindamycin, metronidazole and chloramphenicol. L-627, im. ipenem, meropenem, clindamycin, metronidazole and chloramphenicol were the most active agents tested. L-627 had in vitro activity similar to that of the other carbapenems tested. 1Department of Microbiology, Huddinge University Hospital, Karolinska Institute, 141 86 Huddinge, Sweden. 2National Bacteriological Laboratory, 105 21 Stockholm.
758
L-627 is a new carbapenem antibiotic which has a triazolium group and a beta-methyl substitution at C-1 on the carbapenem nucleus to reduce the ability of dehydropeptidase 1 to attack the betalactam molecule. In in vitro susceptibility tests the new carbapenem has shown potent antibacterial activity against gram-positive and gram-negative bacteria, except that most methicillin-resistant Staphylococcus aureus strains tested are resistant (1, 2). The present investigation was undertaken to determine the in vitro activity of L-62' against 370 anaerobic bacterial strains recently isolated from human infections. This activity was compared with that of piperacillin, cefoxitin, imipenem, meropenem, clindamycin, metronidazole and chloramphenicol. Materials and Methods. The 370 strains tested were isolated from a variety of clinical specimens submitted to the National Bacteriological Laboratory and the Huddinge University Hospital, Stockholm, Sweden, during 1991-1992. All strains were identified by the criteria of Holdeman et al. (3).The antimicrobial susceptibility tests were performed by the method of Dornbusch et al. (4). The strains were grown in rubberstopped tubes containing prereduced chopped meat broth with glucose. The antimicrobial susceptibility testing was performed by the agar dilution method on PDM-ASM agar (AB Biodisk, Sweden), with addition of 5% defibrinated horse blood. Inocula consisted of 48 h broth cultures diluted 10-2 in prereduced Proteose Peptone broth (Difco Laboratories, USA). This dilution resulted in 105 cfu per spot when the bacteria were applied with a modified Steers replicator to freshly prepared agar plates containing the appropriate antimicrobial agent. An agar plate without an antimicrobial agent was always included as a growth control. The plates were read after 48 h of incubation at 37 °C in anaerobic jars (GasPak; BBL Microbiology Systems, USA). The MIC was defined as the lowest concentration of the drug that inhibited growth. The appearance of a single colony or of a barely visible haze was disregarded. The following antimicrobial agents were obtained from the indicated manufacturers: L-627 and piperacillin, Lederle Laboratories, USA; chloramphenicol, Parke-Davis Pharmaceutical Research Division, USA; cefoxitin and imipenem, Merck Sharp & Dohme, USA; clindamycin, Upjohn, USA; metronidazote, Rh6ne Poulenc Rorer, Sweden; and meropenem, ICI, UK.
Eur. J. Clin. Microbiol. Infect. Dis.
The breakpoints used for the following antimicrobial agents were those recommended by the National Committee for Clinical Laboratory Standards (5): piperacillin 64 mg/1; cefoxitin 32 mg/1; imipenem 8 mg/1; clindamycin 4 mg/l; metronidazole 16 mg/l; and chloramphenicol 16 mg/l. Provisional breakpoints of 8 mg/l were used for meropenem and L-627 based on human pharmacokinetics. Results and Discussion, The in vitro activity of the antimicrobial agents against anaerobic grampositive cocci are shown in Table 1. All strains were susceptible to L-627, imipenem, meropenem, piperacillin and clindamycin. All isolates were also susceptible to cefoxitin, metronidazole and chloramphenicol, but with higher MIC50 and MIC90 values. Table 1 also shows the in vitro activity against Propionibacterium acnes strains. L-627, imipenem, meropenem and clindamycin were more active against the strains than piperacillin, cefoxitin and chloramphenicol. All Propionibacteriurn aches isolates were resistant to metronidazole. All Clostridium perfringens isolates were susceptible to L-627, imipenem, meropenem, piperacillin, cefoxitin, clindamycin, metronidazole and chloramphenicol (Table t). All Clostridiurn difficile strains were susceptible to L-627, imipenem, meropenem, piperacillin, metronidazole and chloramphenicol (Table 1). Ninety percent of the Clostridium difficile isolates were inhibited by 128 mg/1 of cefoxitin and 8 mg/l of clindamycin. Against the Bacteroides fragilis strains L-627, imipenem and meropenem were the most active beta-lactam agents tested (Table 1). Most strains were susceptible to piperacillin, cefoxitin and clindamycin, while all of them were susceptible to metronidazole and chloramphenicol. The other Bacteroides, Prevotella and Porphyromonas species were also more susceptible to L627, imipenem, meropenem and clindamycin (Table 1), Piperacillin, cefoxitin, metronidazole and chloramphenicol were active against all strains tested. All fusobacteria were susceptible to L-627, imipenem, meropenem, piperacillin, cefoxitin, clindamycin, metronidazole and chloramphenicol (Table 1). Thus no significant differences in activity were found between the three carbapenems tested.
Vol. 11, 1992
759
Table 1: In vitro activity of L-627 and other antimicrobialagents against anaerobic bacteria. Species
Antimierobial agent
MIC (rag/l) Range
MIC90
0.032 0.032 0.032 0.125 1.0
0.064 0.064 0.064 0.25 4.0
L-627 Imipenem Meropenem Piperacillin Cefoxitin Clindamycm Metronidazole Chloramphenicol
0.0080.0160.0080.0160.064-
L-627 Imipenem Meropenem Piperacillin Cefoxitin Clindamycm Metronidazole Chloramphenicol
0.0160.0320.0160.1250.1250.01632.0 1.0
Clostridium perfringens
L-627 Imipenem Meropenem Piperacillin Cefoxitin Clindamycm Metronidazole Chloramphenicol
0.0080.016 0.0080.160.50.0081.04.0-
Clostridium difficile
L-627 Imipenem Meropenem Piperaeillin Cefoxitin Clindamycm Metronidazole Chloramphenicol
2 . 0 - 4,0 8.0 0.064- 2.0 0.125- 8.0 64.0- 128 0 . 5 - 128 0.125- 0.25 0.125- 4.0
L-627 Imipenem Meropenem Piperacillin Cefoxitin Clindamycm Metronidazole Chloramphenicol
0.0640.0640.0641.02.00.0160.250.5-
0.5 0,25 2.0 128 32 8.0 2.0 4.0
0.125 0.064 0.064 4.0 8.0 0.5 0.5 4.0
0.125 32 16 2.0 1.0 4.0
L-627 Imipenem Meropenem Piperacillin Cefoxitin Clindamycm Metronidazole Chloramphenicol
0.0080.0160.0160.0640.1250.0160.0644.0
0.5 0,25 0.064 8,0 1,0 0.25 4.0
0.125 0.032 0.032 1.0 0.5 0.016 1.0 4.0
0.5 0.25 0,032 8.0 1,0 0.016 4.0 4.0
L-627 Imipenem Meropenem Piperacillin Cefoxitin Clindamycm Metronidazole Chloramphenicol
0.0080.0080.0080.0320.0640.016 0.250.016-
0.5 0.064 0.064 1.0 16
0.016 0.032 0.032 0.064 0.5 0.016 4.0 4.0
0.25 0.064 0.064 0.064 0.5 0.016 4.0 4.0
Anaerobic gram-positive cocci
(n 50) =
Propionibacterium acnes (n=30)
(n = 50)
(n = 50)
Bacteroides fragilis (n = 100)
Other Bacteroides, Prevotella and Porphyromonas spp.
(n 50) =
Fusobacterium spp. (n=40)
0,25 0,064 0.125 2.0 8.0
MIC50
0.016- 1.0
0.064
0.064
0.125- 8.0 0.25- 8.0
4.0 4.0
4.0 8.0
0.25 0.064 0.064 0,25 1.0 0,064 ::'64
0.064 0.032 0.064 0.25 0.125 0.016 __>64 1.0
0.25 0,032 0.064 0,25 0,25 0.032 > 64 1.0
0.064 0.5 0.125 2.0 1.0 1.0 4.0 8.0
0.032 0.25 0.008 0.064 0.5 0.125 1.0 4.0
0.064 0.5 0.008 1.0 1.0 1.0 1.0 4.0
4.0 4.0
4.0 8.0 1.0 4.0 64 4.0 0.125 4.0
4.0 8.0 1.0 4.0 128 8.0 0,25 4.0 0.25 0.125
760
T h e in vitro results o b t a i n e d in this and o t h e r
studies (2; U. Ueno et al., 31st ICAAC, 1991, Abstract no. 815) indicate that L-627 is a promising new carbapenem which may be useful in the treatment of anaerobic infections.
References
1. Yoshida M, Milsuhashi S: In vitro antibacterial activity and beta-lactamase stability of the new carbapenem LJC 10,627. European Journal of Clinical Microbiology & Infectious Diseases 1990, 9: 625-629.
Eur. J. Clin. Microbiol. Infect. Dis.
2. Ubukata K, Hiklda M, Yoshida M, Nishiki K, Furukawa Y, Tashiro K, Konno M, Mitsuhashi S: In vitro activity of LJC 10,627, a new carbapenem antibiotic with high stability to dehydropeptidase I. Antimicrobial Agents and Chemotherapy 1990, 34: 994-
10~. 3. Hoideman LV, Cato EP, Moore WEC: Anaerobe laboratory manual. 4th edition. Virginia Polytechnic Institute and State University, Blacksburg, VA, 1977, p. 1-156. 4. Dornbusch K, Nord CE, Olsson-Liljequlst B: Antibiotic susceptibility of anaerobic bacteria with special reference to Bacteroidesfragitis. Scandinavian Journal of Infectious Diseases 1979, 19: 17-25. 5. National Committee for Clinical Laboratory Standards: Methods for antimicrobial susceptibility testing of anaerobic bacteria. 2nd edition. NCCLS Document Mll'-A2. NCCLS, Villanova, PA, 1990.
757
Table 3: In vitro aetivity of vermisporin against beta-hemolytic streptococci in Mueller-Hinton (MH) blood agar (Mueller-Hinton medium plus 5 % sheep blood) and in Haemophilus Test Medium (HTM) agar. Organism
(n)
Streptococcuspyogenes
Medium
MIC 0ag/ml) Range
MICS0
MIC90
(18)
MH blood agar HTMagar
2- 8 0.25- 1
4 1
8 1
Streptococcusagalactiae (13)
MH blood agar HTM agar
2- 8 0.25 - 2
8 1
8 2
Streptococcus group C (10)
MH blood agar HTMagar
2 - 16 1- 1
Streptococcus group G (12)
MH blood agar HTM agar
0.5 - 16 0.25 - 1
T h e r e was a m a r k e d increase in MBCs for staphylococci, the m e a n vermisporin MIC90 for Staphylococcus aureus being 0.27 lag/ml and the m e a n MBC90 7 ~g/ml. The mean vermisporin MIC90 for Staphylococcus epidermidis was 0.31/ag/ml, and the MBC90 5.3 pg/ml. T h e s e studies demonstrate that the new antibiotic, vermisporin has excellent activity against anaerobic species such as Bacteroides and Clostridium spp., inhibiting the majority of isolates at < 1 lag/ml. Blood inhibits the activity of vermisporin against streptococcal and staphylococcal species, and there is a 16- to 32-fold difference in MICs and MBCs for staphylococci. Further research may reveal whether a c o m p o u n d of this type could b e useful against anaerobic organisms and m a y suggest structural aspects which could be explored in other anti-anaerobic agents. It is conceivable that vermisporin could be used as an oral agent against Clostridiurn difficile and thereby decrease the use of oral vancomycin, which may be contributing to a rise in resistant enterococci.
References 1. National Committee for Clinical Laboratory Standards:Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. 2nd edition. Approved Standard MT-A2. NCCLS, Villanova, PA, 1990. 2. Jorgenson JH, Reflding JS, Maher IA, Howell AW: Improved medium for antimicrobial susceptibility testing of Haemophilus influenzae. Journal of Clinical Microbiology 1987, 25: 2105-2113.
4 1 2 0.5
8 1
3. National Committee for Clinical Laboratory Standards: Methods for antimicrobial susceptibility testing of anaerobic bacteria, 2nd edition. Approved Standard Mll-A2. NCCLS, Villanova, PA, 1991. 4. PearsonRD, Steigbigel RT, Davis HT, Chapman SW: Method of reliable determination of minimal lethal antibiotic concentrations. Antimierobial Agents and Chemotherapy 1980, 18: 688--708.
m
,lllllllll
In Vitro Activity of L-627 against Anaerobic Bacteria C.E. N o r d 1'2., A . L i n d m a r k 2, I. P e r s s o n 2
The in vitro activity of L-627 against 370 anaerobic bacterial strains including anaerobic cocci, Propionibacterium aches, Clostridlura
perfringens, Clostridium difficile, Bacteroldes fragilis, o t h e r Bacteroides spp. and fusobacteria was determined by the agar dilution method. This activity was compared with that of plperaeillin, cefoxitin, imipenem, meropenem, clindamycin, metronidazole and chloramphenicol. L-627, im. ipenem, meropenem, clindamycin, metronidazole and chloramphenicol were the most active agents tested. L-627 had in vitro activity similar to that of the other carbapenems tested. 1Department of Microbiology, Huddinge University Hospital, Karolinska Institute, 141 86 Huddinge, Sweden. 2National Bacteriological Laboratory, 105 21 Stockholm.
758
L-627 is a new carbapenem antibiotic which has a triazolium group and a beta-methyl substitution at C-1 on the carbapenem nucleus to reduce the ability of dehydropeptidase 1 to attack the betalactam molecule. In in vitro susceptibility tests the new carbapenem has shown potent antibacterial activity against gram-positive and gram-negative bacteria, except that most methicillin-resistant Staphylococcus aureus strains tested are resistant (1, 2). The present investigation was undertaken to determine the in vitro activity of L-62' against 370 anaerobic bacterial strains recently isolated from human infections. This activity was compared with that of piperacillin, cefoxitin, imipenem, meropenem, clindamycin, metronidazole and chloramphenicol. Materials and Methods. The 370 strains tested were isolated from a variety of clinical specimens submitted to the National Bacteriological Laboratory and the Huddinge University Hospital, Stockholm, Sweden, during 1991-1992. All strains were identified by the criteria of Holdeman et al. (3).The antimicrobial susceptibility tests were performed by the method of Dornbusch et al. (4). The strains were grown in rubberstopped tubes containing prereduced chopped meat broth with glucose. The antimicrobial susceptibility testing was performed by the agar dilution method on PDM-ASM agar (AB Biodisk, Sweden), with addition of 5% defibrinated horse blood. Inocula consisted of 48 h broth cultures diluted 10-2 in prereduced Proteose Peptone broth (Difco Laboratories, USA). This dilution resulted in 105 cfu per spot when the bacteria were applied with a modified Steers replicator to freshly prepared agar plates containing the appropriate antimicrobial agent. An agar plate without an antimicrobial agent was always included as a growth control. The plates were read after 48 h of incubation at 37 °C in anaerobic jars (GasPak; BBL Microbiology Systems, USA). The MIC was defined as the lowest concentration of the drug that inhibited growth. The appearance of a single colony or of a barely visible haze was disregarded. The following antimicrobial agents were obtained from the indicated manufacturers: L-627 and piperacillin, Lederle Laboratories, USA; chloramphenicol, Parke-Davis Pharmaceutical Research Division, USA; cefoxitin and imipenem, Merck Sharp & Dohme, USA; clindamycin, Upjohn, USA; metronidazote, Rh6ne Poulenc Rorer, Sweden; and meropenem, ICI, UK.
Eur. J. Clin. Microbiol. Infect. Dis.
The breakpoints used for the following antimicrobial agents were those recommended by the National Committee for Clinical Laboratory Standards (5): piperacillin 64 mg/1; cefoxitin 32 mg/1; imipenem 8 mg/1; clindamycin 4 mg/l; metronidazole 16 mg/l; and chloramphenicol 16 mg/l. Provisional breakpoints of 8 mg/l were used for meropenem and L-627 based on human pharmacokinetics. Results and Discussion, The in vitro activity of the antimicrobial agents against anaerobic grampositive cocci are shown in Table 1. All strains were susceptible to L-627, imipenem, meropenem, piperacillin and clindamycin. All isolates were also susceptible to cefoxitin, metronidazole and chloramphenicol, but with higher MIC50 and MIC90 values. Table 1 also shows the in vitro activity against Propionibacterium acnes strains. L-627, imipenem, meropenem and clindamycin were more active against the strains than piperacillin, cefoxitin and chloramphenicol. All Propionibacteriurn aches isolates were resistant to metronidazole. All Clostridium perfringens isolates were susceptible to L-627, imipenem, meropenem, piperacillin, cefoxitin, clindamycin, metronidazole and chloramphenicol (Table t). All Clostridiurn difficile strains were susceptible to L-627, imipenem, meropenem, piperacillin, metronidazole and chloramphenicol (Table 1). Ninety percent of the Clostridium difficile isolates were inhibited by 128 mg/1 of cefoxitin and 8 mg/l of clindamycin. Against the Bacteroides fragilis strains L-627, imipenem and meropenem were the most active beta-lactam agents tested (Table 1). Most strains were susceptible to piperacillin, cefoxitin and clindamycin, while all of them were susceptible to metronidazole and chloramphenicol. The other Bacteroides, Prevotella and Porphyromonas species were also more susceptible to L627, imipenem, meropenem and clindamycin (Table 1), Piperacillin, cefoxitin, metronidazole and chloramphenicol were active against all strains tested. All fusobacteria were susceptible to L-627, imipenem, meropenem, piperacillin, cefoxitin, clindamycin, metronidazole and chloramphenicol (Table 1). Thus no significant differences in activity were found between the three carbapenems tested.
Vol. 11, 1992
759
Table 1: In vitro activity of L-627 and other antimicrobialagents against anaerobic bacteria. Species
Antimierobial agent
MIC (rag/l) Range
MIC90
0.032 0.032 0.032 0.125 1.0
0.064 0.064 0.064 0.25 4.0
L-627 Imipenem Meropenem Piperacillin Cefoxitin Clindamycm Metronidazole Chloramphenicol
0.0080.0160.0080.0160.064-
L-627 Imipenem Meropenem Piperacillin Cefoxitin Clindamycm Metronidazole Chloramphenicol
0.0160.0320.0160.1250.1250.01632.0 1.0
Clostridium perfringens
L-627 Imipenem Meropenem Piperacillin Cefoxitin Clindamycm Metronidazole Chloramphenicol
0.0080.016 0.0080.160.50.0081.04.0-
Clostridium difficile
L-627 Imipenem Meropenem Piperaeillin Cefoxitin Clindamycm Metronidazole Chloramphenicol
2 . 0 - 4,0 8.0 0.064- 2.0 0.125- 8.0 64.0- 128 0 . 5 - 128 0.125- 0.25 0.125- 4.0
L-627 Imipenem Meropenem Piperacillin Cefoxitin Clindamycm Metronidazole Chloramphenicol
0.0640.0640.0641.02.00.0160.250.5-
0.5 0,25 2.0 128 32 8.0 2.0 4.0
0.125 0.064 0.064 4.0 8.0 0.5 0.5 4.0
0.125 32 16 2.0 1.0 4.0
L-627 Imipenem Meropenem Piperacillin Cefoxitin Clindamycm Metronidazole Chloramphenicol
0.0080.0160.0160.0640.1250.0160.0644.0
0.5 0,25 0.064 8,0 1,0 0.25 4.0
0.125 0.032 0.032 1.0 0.5 0.016 1.0 4.0
0.5 0.25 0,032 8.0 1,0 0.016 4.0 4.0
L-627 Imipenem Meropenem Piperacillin Cefoxitin Clindamycm Metronidazole Chloramphenicol
0.0080.0080.0080.0320.0640.016 0.250.016-
0.5 0.064 0.064 1.0 16
0.016 0.032 0.032 0.064 0.5 0.016 4.0 4.0
0.25 0.064 0.064 0.064 0.5 0.016 4.0 4.0
Anaerobic gram-positive cocci
(n 50) =
Propionibacterium acnes (n=30)
(n = 50)
(n = 50)
Bacteroides fragilis (n = 100)
Other Bacteroides, Prevotella and Porphyromonas spp.
(n 50) =
Fusobacterium spp. (n=40)
0,25 0,064 0.125 2.0 8.0
MIC50
0.016- 1.0
0.064
0.064
0.125- 8.0 0.25- 8.0
4.0 4.0
4.0 8.0
0.25 0.064 0.064 0,25 1.0 0,064 ::'64
0.064 0.032 0.064 0.25 0.125 0.016 __>64 1.0
0.25 0,032 0.064 0,25 0,25 0.032 > 64 1.0
0.064 0.5 0.125 2.0 1.0 1.0 4.0 8.0
0.032 0.25 0.008 0.064 0.5 0.125 1.0 4.0
0.064 0.5 0.008 1.0 1.0 1.0 1.0 4.0
4.0 4.0
4.0 8.0 1.0 4.0 64 4.0 0.125 4.0
4.0 8.0 1.0 4.0 128 8.0 0,25 4.0 0.25 0.125
760
T h e in vitro results o b t a i n e d in this and o t h e r
studies (2; U. Ueno et al., 31st ICAAC, 1991, Abstract no. 815) indicate that L-627 is a promising new carbapenem which may be useful in the treatment of anaerobic infections.
References
1. Yoshida M, Milsuhashi S: In vitro antibacterial activity and beta-lactamase stability of the new carbapenem LJC 10,627. European Journal of Clinical Microbiology & Infectious Diseases 1990, 9: 625-629.
Eur. J. Clin. Microbiol. Infect. Dis.
2. Ubukata K, Hiklda M, Yoshida M, Nishiki K, Furukawa Y, Tashiro K, Konno M, Mitsuhashi S: In vitro activity of LJC 10,627, a new carbapenem antibiotic with high stability to dehydropeptidase I. Antimicrobial Agents and Chemotherapy 1990, 34: 994-
10~. 3. Hoideman LV, Cato EP, Moore WEC: Anaerobe laboratory manual. 4th edition. Virginia Polytechnic Institute and State University, Blacksburg, VA, 1977, p. 1-156. 4. Dornbusch K, Nord CE, Olsson-Liljequlst B: Antibiotic susceptibility of anaerobic bacteria with special reference to Bacteroidesfragitis. Scandinavian Journal of Infectious Diseases 1979, 19: 17-25. 5. National Committee for Clinical Laboratory Standards: Methods for antimicrobial susceptibility testing of anaerobic bacteria. 2nd edition. NCCLS Document Mll'-A2. NCCLS, Villanova, PA, 1990.
