ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, July 1979, p. 109-111 0066-4804/79/07-0109/03$02.00/0
Vol. 16, No. 1
In Vitro Activity of Cefotaxime Against Cephalothin-Resistant Clinical Isolates H. W. VAN LANDUYT* AND M. PYCKAVET A. Z. St. Jan, Brugge, Belgium
Received for publication 13 April 1979
Cefotaxime is more active than six other cephalosporins against 150 cephalothin-resistant Enterobacteriaceae strains and is the only drug which is more active than ampicillin against Haemophilus. It shows a potentially useful activity against Pseudomonas. ference in activity between cefotaxime and the second most active drug for the other species is on the order of between 21 and 98 times. Against non-fi-lactamase-producing Haemophilus strains, cefotaxime is 16 times more active than ampicillin. It is, respectively, 45 and 49 times more active than cefamandole and cefuroxime against all Haemophilus strains together. The increase in resistance among the Enterobacteriaceae against cephalothin (11) and the emergence of ,B-lactamase-producing Haemophilus strains (9) has increased the demand for new antibiotics. Among the newer cephalosporin-like antibiotics, the most promising are cefamandole and cefuroxime with good activity on Haemophilus and most of the Enterobacteriaceae (5, 12) and cefoxitin with good activity on Bacteroides fragilis (13) and on the Enterobacteriaceae, with the exception of Enterobacter (3, 15); finally, cefazaflur was shown to be very active against the Enterobacteriaceae with the exception of Serratia (14). Cefotaxime has several advantages over the other newer cephalosporins. It has been shown by others to be more active than previous cephalosporins, including cefuroxime and cefoxitin, against cephalothin-susceptible strains and Haemophilus influenzae (1, 7). Its stability against ,8-lactamase hydrolysis is comparable to that of cefuroxime and cefoxitin, but cefotaxime is the most active inhibitor of type 1 ,B-lactamase (6). In contrast, it seems to be less active than cefoxitin against Bacteroides fragilis (1). In accordance with these publications, it is was 18 h for the Enterobacteriaceae and Pseu- clear from this study that cefotaxime is also very domonas strains and 24 h for the Haemophilus active against cephalothin-resistant Enterobacteriaceae with an activity that is at least 21 strains (Table 1). Cefotaxime is about 90 times more active than times greater than that of the second most active cefoxitin against the Enterobacteriaceae in to- drug and the only drug with excellent activity tal. It is 98 times more active against Proteus against one of the most resistant species, namely, strains and 42 times more active against Serratia Serratia. It is also at least 45 times more active strains than cefoxitin, which was the second than the other cephalosporins against Haemomost active drug against these species. The dif- philus strains and the only one which is even
Cefotaxime is the sodium salt of 7-[(2-(2amino-4-thiazolyl)-2(z)-methoxy-imino) acetamido] cephalosporanic acid. The antibacterial spectrum of the compound is considerably broader than that of known cephalosporins (8). The activity of this new compound was compared with that of cephalothin, cefamandole, cefaclor, cefuroxime, cefoxitin, and cefazaflur against 150 Enterobacteriaceae strains resistant to cephalothin (minimal inhibitory concentration [MIC] - 16,ug/ml), and in addition it was compared with ampicillin against 39 Haemophilus strains. The activity against 21 Pseudomonas strains was only tested for cefotaxime. Further characteristics of these strains are listed in Table 1. Identification was performed by standard methods described by Edwards and Ewing (2) and Lennette et al. (10). Antibiotic dilutions were performed by the International Collaborative Study Scheme (4). The MICs of the strains were determined by an agar dilution technique, using an automatic multipoint inoculator (Denley, England). For the Enterobacteriaceae and Pseudomonas strains, the test medium was Diagnostic Sensitivity Test agar (Oxoid), and the final inoculation spot contained 2 x 105 to 4 x 105 colonyforming units (CFU). For the Haemophilus strains, Mueller-Hinton medium (Difco Laboratories) was supplemented with 1% hemoglobin (Oxoid) and 1% IsoVitaleX enrichment agar (BBL), and the final inoculation spot contained 104 to 2 x 104 CFU. The incubation time at 370C
109
1 10
ANTIMICROB. AGENTS CHEMOTHF.R.
NOTlsE
TABLE 1. Comparative activity of cephalosporin antibiotics against gram-negative bacilli MIC (pg/ml of medium) For 0 o r f mean Species (no. of strains For 50% of For 90% of mean teste) Raxue tested)II...ig*
strains
CLT CMD CFU CFO CFZ CCL CTX
16 to >128 0.5 to >128 2 to 32 1 to 64 1 to >128 4 to >128 0.04 to 2
32 16
Kiebsiella (22)
CLT CMD CFU CFO CFZ CCL CTX
16 to >128 8 to >128 2 to >128 1 to 16 2 to 128 4 to >128 cO.02 to 1
Enterobacter (25)
CLT CMD
strains
1
53.81 12.49 6.72 6.24 8.61 30.45 0.11
32 16 4 2 4 16 0.04
128 64 16 8 32 64 0.32
36.29 23.35 4.83 3.20 7.27 14.10 0.05
CFO CFZ CCL CTX
32 to >128 1 to >128 1 to 128 40.25 to >128 2 to >128 8 to >128 0.04 to 16
>128 2 4 128 16 64 0.16
>128 128 8 >128 >128 >128 0.32
178.52 3.58 4.99 82.13 16.44 67.64 0.17
Serratia (27)
CLT CMD CFU CFO CFZ CCL CTX
>128 8 to >128 16 to >128 8 to 128 16 to >128 128 to >128 0.16 to4
>128 >128 64 16 >128 >128 0.64
>128 >128 >128 32 >128 >128 0.64
255.99 183.35 109.72 20.15 225.16 249.51 0.48
Proteus (39)
CLT CMD CFU CFO CFZ CCL CTX
64 to >128 40.25 to >128 0.50 to >128 1 to 16 '0.25 to >128 64 to >128 40.02 to 0.32
>128 64 64 4 >128 >128 0.04
>128 >128 >128 8 >128 >128 0.08
226.05 28.25 55.51 3.92 132.63 226.05 0.04
Citrobacter (4)
CLT CMD CFU CFO CFZ CCL CTX
64 to >128 0.5 to 128 2 to 16 64 to 128 4 to 128 64 to >128 0.08 to 0.32
64 1 4
>128 128 16 128 128 >128 0.32
128.00 3.36 4.75 90.50 13.45 127.99 0.13
CLT
128 to >128 0.5 to 32 1 to 4 1 to 4 32 to 128 128 40.02 to 0.16
>128 32 4 4 128 128 0.16
222.86 6.06 2.29 1.74
E. coli (28)
CFU
Providencia (4)
CMD CFU CFO CFZ CCL CTX
4
8 4 16 0.08
64 4 128 0.08
>128 16 2 2 64 128
0.04
>128 128 32 32 >128 >128
63.99 128.00 0.06
Pseudomonas (21)
CTX
4to64
16
32
16.00
f-lactamase
CLT
1 to 16
8
16
6.10
VOL. 16, 1979
NOTES
111
TABLE 1-Continued MIC
Species (no. of strains tested)
Haemophilus (18)
Druga rgRange CMD CFU
CFO CFZ CCL CTX AMP Non-,B-lactamase Haemophilus (21)
CLT CMD CFU
CFO CFZ CCL CTX AMP
(jtg/ml of medium) For 50% of strains
For 90% of
0.5 to 4 0.5 to4 2to8 1 to 8 4 to 32 -0.02 to 1 4 to 128
1 1 8 8 16
Vol. 16, No. 1
In Vitro Activity of Cefotaxime Against Cephalothin-Resistant Clinical Isolates H. W. VAN LANDUYT* AND M. PYCKAVET A. Z. St. Jan, Brugge, Belgium
Received for publication 13 April 1979
Cefotaxime is more active than six other cephalosporins against 150 cephalothin-resistant Enterobacteriaceae strains and is the only drug which is more active than ampicillin against Haemophilus. It shows a potentially useful activity against Pseudomonas. ference in activity between cefotaxime and the second most active drug for the other species is on the order of between 21 and 98 times. Against non-fi-lactamase-producing Haemophilus strains, cefotaxime is 16 times more active than ampicillin. It is, respectively, 45 and 49 times more active than cefamandole and cefuroxime against all Haemophilus strains together. The increase in resistance among the Enterobacteriaceae against cephalothin (11) and the emergence of ,B-lactamase-producing Haemophilus strains (9) has increased the demand for new antibiotics. Among the newer cephalosporin-like antibiotics, the most promising are cefamandole and cefuroxime with good activity on Haemophilus and most of the Enterobacteriaceae (5, 12) and cefoxitin with good activity on Bacteroides fragilis (13) and on the Enterobacteriaceae, with the exception of Enterobacter (3, 15); finally, cefazaflur was shown to be very active against the Enterobacteriaceae with the exception of Serratia (14). Cefotaxime has several advantages over the other newer cephalosporins. It has been shown by others to be more active than previous cephalosporins, including cefuroxime and cefoxitin, against cephalothin-susceptible strains and Haemophilus influenzae (1, 7). Its stability against ,8-lactamase hydrolysis is comparable to that of cefuroxime and cefoxitin, but cefotaxime is the most active inhibitor of type 1 ,B-lactamase (6). In contrast, it seems to be less active than cefoxitin against Bacteroides fragilis (1). In accordance with these publications, it is was 18 h for the Enterobacteriaceae and Pseu- clear from this study that cefotaxime is also very domonas strains and 24 h for the Haemophilus active against cephalothin-resistant Enterobacteriaceae with an activity that is at least 21 strains (Table 1). Cefotaxime is about 90 times more active than times greater than that of the second most active cefoxitin against the Enterobacteriaceae in to- drug and the only drug with excellent activity tal. It is 98 times more active against Proteus against one of the most resistant species, namely, strains and 42 times more active against Serratia Serratia. It is also at least 45 times more active strains than cefoxitin, which was the second than the other cephalosporins against Haemomost active drug against these species. The dif- philus strains and the only one which is even
Cefotaxime is the sodium salt of 7-[(2-(2amino-4-thiazolyl)-2(z)-methoxy-imino) acetamido] cephalosporanic acid. The antibacterial spectrum of the compound is considerably broader than that of known cephalosporins (8). The activity of this new compound was compared with that of cephalothin, cefamandole, cefaclor, cefuroxime, cefoxitin, and cefazaflur against 150 Enterobacteriaceae strains resistant to cephalothin (minimal inhibitory concentration [MIC] - 16,ug/ml), and in addition it was compared with ampicillin against 39 Haemophilus strains. The activity against 21 Pseudomonas strains was only tested for cefotaxime. Further characteristics of these strains are listed in Table 1. Identification was performed by standard methods described by Edwards and Ewing (2) and Lennette et al. (10). Antibiotic dilutions were performed by the International Collaborative Study Scheme (4). The MICs of the strains were determined by an agar dilution technique, using an automatic multipoint inoculator (Denley, England). For the Enterobacteriaceae and Pseudomonas strains, the test medium was Diagnostic Sensitivity Test agar (Oxoid), and the final inoculation spot contained 2 x 105 to 4 x 105 colonyforming units (CFU). For the Haemophilus strains, Mueller-Hinton medium (Difco Laboratories) was supplemented with 1% hemoglobin (Oxoid) and 1% IsoVitaleX enrichment agar (BBL), and the final inoculation spot contained 104 to 2 x 104 CFU. The incubation time at 370C
109
1 10
ANTIMICROB. AGENTS CHEMOTHF.R.
NOTlsE
TABLE 1. Comparative activity of cephalosporin antibiotics against gram-negative bacilli MIC (pg/ml of medium) For 0 o r f mean Species (no. of strains For 50% of For 90% of mean teste) Raxue tested)II...ig*
strains
CLT CMD CFU CFO CFZ CCL CTX
16 to >128 0.5 to >128 2 to 32 1 to 64 1 to >128 4 to >128 0.04 to 2
32 16
Kiebsiella (22)
CLT CMD CFU CFO CFZ CCL CTX
16 to >128 8 to >128 2 to >128 1 to 16 2 to 128 4 to >128 cO.02 to 1
Enterobacter (25)
CLT CMD
strains
1
53.81 12.49 6.72 6.24 8.61 30.45 0.11
32 16 4 2 4 16 0.04
128 64 16 8 32 64 0.32
36.29 23.35 4.83 3.20 7.27 14.10 0.05
CFO CFZ CCL CTX
32 to >128 1 to >128 1 to 128 40.25 to >128 2 to >128 8 to >128 0.04 to 16
>128 2 4 128 16 64 0.16
>128 128 8 >128 >128 >128 0.32
178.52 3.58 4.99 82.13 16.44 67.64 0.17
Serratia (27)
CLT CMD CFU CFO CFZ CCL CTX
>128 8 to >128 16 to >128 8 to 128 16 to >128 128 to >128 0.16 to4
>128 >128 64 16 >128 >128 0.64
>128 >128 >128 32 >128 >128 0.64
255.99 183.35 109.72 20.15 225.16 249.51 0.48
Proteus (39)
CLT CMD CFU CFO CFZ CCL CTX
64 to >128 40.25 to >128 0.50 to >128 1 to 16 '0.25 to >128 64 to >128 40.02 to 0.32
>128 64 64 4 >128 >128 0.04
>128 >128 >128 8 >128 >128 0.08
226.05 28.25 55.51 3.92 132.63 226.05 0.04
Citrobacter (4)
CLT CMD CFU CFO CFZ CCL CTX
64 to >128 0.5 to 128 2 to 16 64 to 128 4 to 128 64 to >128 0.08 to 0.32
64 1 4
>128 128 16 128 128 >128 0.32
128.00 3.36 4.75 90.50 13.45 127.99 0.13
CLT
128 to >128 0.5 to 32 1 to 4 1 to 4 32 to 128 128 40.02 to 0.16
>128 32 4 4 128 128 0.16
222.86 6.06 2.29 1.74
E. coli (28)
CFU
Providencia (4)
CMD CFU CFO CFZ CCL CTX
4
8 4 16 0.08
64 4 128 0.08
>128 16 2 2 64 128
0.04
>128 128 32 32 >128 >128
63.99 128.00 0.06
Pseudomonas (21)
CTX
4to64
16
32
16.00
f-lactamase
CLT
1 to 16
8
16
6.10
VOL. 16, 1979
NOTES
111
TABLE 1-Continued MIC
Species (no. of strains tested)
Haemophilus (18)
Druga rgRange CMD CFU
CFO CFZ CCL CTX AMP Non-,B-lactamase Haemophilus (21)
CLT CMD CFU
CFO CFZ CCL CTX AMP
(jtg/ml of medium) For 50% of strains
For 90% of
0.5 to 4 0.5 to4 2to8 1 to 8 4 to 32 -0.02 to 1 4 to 128
1 1 8 8 16
