ANTMICROBIL AGENT8 AND CHEMOTHERAPY, Aug. 1977, p. 290-292 Copyright © 1977 American Society for Microbiology
Vol. 12, No. 2 Printed in U.S.A.
In Vitro Susceptibility Studies with Cefaclor and Cephalexin W. MICHAEL SCHELD, OKSANA M. KORZENIOWSKI, AND MERLE A. SANDE* Department ofInternal Medicine, University of Virginia School ofMedicine, Charlottesville, Virginia 22901
Received for publication 17 January 1977
The in vitro activity of cefaclor and cephalexin against clinical isolates of four bacterial genera was compared. Both agents had a similar range of activity, but cefaclor was significantly more active by weight than cephalexin for most isolates tested.
Cefaclor, 3-chloro-7-D-(2-phenyglycinamido)3-cephem-4-carboxylic acid, is a new oral semisynthetic cephalosporin antibiotic derived from cephalexin. Preliminary reports indicate a greater in vitro activity against most strains susceptible to the parent compound (1; N. J. Bill and J. A. Washington, Prog. Abstr. Intersci. Conf. Antimicrob. Agents Chemother. 16th, Chicago, Ill., Abstr. no. 356, 1976; D. A. Preston, Prog. Abstr. Intersci. Conf. Antimicrob. Agents Chemother. 16th, Chicago, Ill., Abstr. no. 352, 1976). It is well absorbed by the oral route, cleared primarily by renal mechanisms, and well tolerated (3; H. R. Black, K. S. Israel, G. H. Brier, and J. D. Wolny, Prog. Abstr. Intersci. Conf Antimicrob. Agents Chemother. 16th, Chicago, Ill., Abstr. no. 354, 1976). In this study, the in vitro susceptibilities of Escherichia coli, Enterobacter sp., Klebsiella sp., Proteus mirabilis, and indole-positive Proteus sp. to cefaclor and cephalexin were compared. All test strains were clinical isolates obtained from the microbiology laboratory at the University of Virginia Hospital. Those strains isolated in 1971 and 1975 are denoted by the designations 71 and 75, respectively. The minimum inhibitory concentrations (MICs) of cefaclor and cephalexin for all isolates were determined by a microtiter broth dilution method (4). Serial twofold dilutions of freshly prepared stock solutions of both antibiotics (supplied by Eli Lilly and Co., Indianapolis, Ind.) were made in heart infusion broth (Difco), using a semiautomatic multimicrodiluter (Cooke Engineering Co., Alexandria, Va.) and microdilution plates (Linbro Chemical Co., IS-MRC-96, New Haven, Conn.). Each well was inoculated with 105 colony-forming units obtained from dilution of an overnight culture. The MIC was defined as the lowest concentration preventing the appearance of visible turbidity after an 18-h incubation at 35°C. Cefaclor was more active than, cephalexin
against all strains, with a median MIC of .2 ,ug/ml for all strains except the recent Enterobacter sp. isolates (Fig. 1). The geometric median MIC of cephalexin was 3 to 16 times greater than that of cefaclor for all except the latter isolates. At 4 ,ug/ml, a level easily achievable in serum (H. R. Black, K. S. Israel, G. L. Brier, and J. D. Wolny, Prog. Abstr. Intersci. Conf. Antimicrob. Agents Chemother. 16th, Chicago, Ill., Abstr. no. 354, 1976), cefaclor inhibited 80 and 87% of strains of E. coli 71 and 75; 63 and 17% of strains of Enterobacter sp. 71 and 75; 79 and 73% of strains of Klebsiella sp. 71 and 75; 91 and 92% of strains of P. mirabilis 71 and 75; and 90% of strains of Proteus sp. 75. To achieve similar levels of activity, 16 p.g of cephalexin per ml was required. The only significant change in the in vitro spectrum of these two antibiotics that occurred over the 4year period was the recent increase in the number of resistant enterobacter strains; 63% were inhibited by cefaclor at 4 ,ug/ml in 1971, whereas only 17% were inhibited in 1975. At the present time, there are two oral cephalosporins available, cephalexin and cephradine. Cephaloglycin, the first oral cephalosporin, has been replaced by these two agents due to the low serum concentrations obtained. Cephradine is slightly less active in vitro than is cephalexin (1, 2, 5, 7), which has a wide spectrum of activity (6, 8). In this study, the majority of enterobacteriaceae tested were inhibited by a lower concentration of cefaclor than cephalexin. Preston (Prog. Abstr. Intersci. Conf. Antimicrob. Agents Chemother. 16th, Chicago, Ill., Abstr. no. 352, 1976) has shown the median MIC of cephalexin to be 2 to 8 times greater than that of cefaclor for Streptococcus pneumoniae. In addition, Bill and Washington (1) observed the same results with staphylococci, streptococci, gonococci, meningococci, haemophilus, E. coli, Klebsiella pneumoniae, Citrobacter diversus, P. mirabilis, salmonellae, and 290
NOTES
V'OL. 12, '1977
291
Ecoli 75 (31)
Ecoli 71 (25) 100 80 60 40 20
Enterobacter 71 (16)
-.
-. .C
100 80 60 40 20
Enterobacter 75 (18)
-~~~~~ r,
Vol. 12, No. 2 Printed in U.S.A.
In Vitro Susceptibility Studies with Cefaclor and Cephalexin W. MICHAEL SCHELD, OKSANA M. KORZENIOWSKI, AND MERLE A. SANDE* Department ofInternal Medicine, University of Virginia School ofMedicine, Charlottesville, Virginia 22901
Received for publication 17 January 1977
The in vitro activity of cefaclor and cephalexin against clinical isolates of four bacterial genera was compared. Both agents had a similar range of activity, but cefaclor was significantly more active by weight than cephalexin for most isolates tested.
Cefaclor, 3-chloro-7-D-(2-phenyglycinamido)3-cephem-4-carboxylic acid, is a new oral semisynthetic cephalosporin antibiotic derived from cephalexin. Preliminary reports indicate a greater in vitro activity against most strains susceptible to the parent compound (1; N. J. Bill and J. A. Washington, Prog. Abstr. Intersci. Conf. Antimicrob. Agents Chemother. 16th, Chicago, Ill., Abstr. no. 356, 1976; D. A. Preston, Prog. Abstr. Intersci. Conf. Antimicrob. Agents Chemother. 16th, Chicago, Ill., Abstr. no. 352, 1976). It is well absorbed by the oral route, cleared primarily by renal mechanisms, and well tolerated (3; H. R. Black, K. S. Israel, G. H. Brier, and J. D. Wolny, Prog. Abstr. Intersci. Conf Antimicrob. Agents Chemother. 16th, Chicago, Ill., Abstr. no. 354, 1976). In this study, the in vitro susceptibilities of Escherichia coli, Enterobacter sp., Klebsiella sp., Proteus mirabilis, and indole-positive Proteus sp. to cefaclor and cephalexin were compared. All test strains were clinical isolates obtained from the microbiology laboratory at the University of Virginia Hospital. Those strains isolated in 1971 and 1975 are denoted by the designations 71 and 75, respectively. The minimum inhibitory concentrations (MICs) of cefaclor and cephalexin for all isolates were determined by a microtiter broth dilution method (4). Serial twofold dilutions of freshly prepared stock solutions of both antibiotics (supplied by Eli Lilly and Co., Indianapolis, Ind.) were made in heart infusion broth (Difco), using a semiautomatic multimicrodiluter (Cooke Engineering Co., Alexandria, Va.) and microdilution plates (Linbro Chemical Co., IS-MRC-96, New Haven, Conn.). Each well was inoculated with 105 colony-forming units obtained from dilution of an overnight culture. The MIC was defined as the lowest concentration preventing the appearance of visible turbidity after an 18-h incubation at 35°C. Cefaclor was more active than, cephalexin
against all strains, with a median MIC of .2 ,ug/ml for all strains except the recent Enterobacter sp. isolates (Fig. 1). The geometric median MIC of cephalexin was 3 to 16 times greater than that of cefaclor for all except the latter isolates. At 4 ,ug/ml, a level easily achievable in serum (H. R. Black, K. S. Israel, G. L. Brier, and J. D. Wolny, Prog. Abstr. Intersci. Conf. Antimicrob. Agents Chemother. 16th, Chicago, Ill., Abstr. no. 354, 1976), cefaclor inhibited 80 and 87% of strains of E. coli 71 and 75; 63 and 17% of strains of Enterobacter sp. 71 and 75; 79 and 73% of strains of Klebsiella sp. 71 and 75; 91 and 92% of strains of P. mirabilis 71 and 75; and 90% of strains of Proteus sp. 75. To achieve similar levels of activity, 16 p.g of cephalexin per ml was required. The only significant change in the in vitro spectrum of these two antibiotics that occurred over the 4year period was the recent increase in the number of resistant enterobacter strains; 63% were inhibited by cefaclor at 4 ,ug/ml in 1971, whereas only 17% were inhibited in 1975. At the present time, there are two oral cephalosporins available, cephalexin and cephradine. Cephaloglycin, the first oral cephalosporin, has been replaced by these two agents due to the low serum concentrations obtained. Cephradine is slightly less active in vitro than is cephalexin (1, 2, 5, 7), which has a wide spectrum of activity (6, 8). In this study, the majority of enterobacteriaceae tested were inhibited by a lower concentration of cefaclor than cephalexin. Preston (Prog. Abstr. Intersci. Conf. Antimicrob. Agents Chemother. 16th, Chicago, Ill., Abstr. no. 352, 1976) has shown the median MIC of cephalexin to be 2 to 8 times greater than that of cefaclor for Streptococcus pneumoniae. In addition, Bill and Washington (1) observed the same results with staphylococci, streptococci, gonococci, meningococci, haemophilus, E. coli, Klebsiella pneumoniae, Citrobacter diversus, P. mirabilis, salmonellae, and 290
NOTES
V'OL. 12, '1977
291
Ecoli 75 (31)
Ecoli 71 (25) 100 80 60 40 20
Enterobacter 71 (16)
-.
-. .C
100 80 60 40 20
Enterobacter 75 (18)
-~~~~~ r,
