activities of ceftizoxime, ceftriaxone, moxalactam, methicihlin, and ampicillin. The spectrum of SK&F 88070 is similar to that of ceftizoxime. Over the past several ...
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Aug. 1985, p. 343-346
Vol. 28, No. 2
0066-4804/85/080343-04$02.00/0 Copyright C 1985, American Society for Microbiology
NOTES In Vitro Antibacterial Activity of SK&F 88070 Against Aerobic Gram-Positive and Gram-Negative Cocci and Haemophilus
influenzae W. MANFORD GOOCH 1111,2* AND JUDY A. DALY' Departments of Pathology' and Pediatrics,2 Primary Children's Medical Center, University of Utah School of Medicine, Salt Lake City, Utah 84103 Received 12 March 1985/Accepted 1 May 1985
The inhibitory activity of SK&F 88070, a cephalosporin whose kinetic characteristics in animals suggest the possibility of once-daily doses, was determined against 345 clinical isolates, and results were compared with the activities of ceftizoxime, ceftriaxone, moxalactam, methicihlin, and ampicillin. The spectrum of SK&F 88070 is similar to that of ceftizoxime.
Over the past several years, new beta-lactamase-stable cephalosporins with extended spectra of activity have been introduced (4, 5), and the pharmacokinetic characteristics of some of these antimicrobial agents have allowed prolonged dosing intervals (5). SK&F 88070 (7-[[(2-amino-4 - thiazolyl)(methoxyimino)acetyl]amino] - 3 - [[[1 - (2 - sulfaminoethyl) - 1H - tetrazol - 5 - yl]thio]methyl] - 3 - cephem - 4 carboxylic acid) is a new parenteral cephalosporin whose pharmacokinetic characteristics in animals suggest the feasibility of once-daily doses (1). The drug is structurally related to cefotaxime and ceftriaxone, and it has a broad spectrum of activity which includes members of the family Enterobacteriaceae, Staphylococcus aureus, and Staphylococcus epidermidis. The current study examines the activity of SK&F 88070 against aerobic gram-positive cocci exhibiting a spectrum of penicillin and methicillin susceptibility and against strains of Hqemophilus influenzae and members of the family Neisseriaceae. Reference standard SK&F 88070 and ceftizoxime were supplied by Smith Kline & French Laboratories, Philadelphia, Pa. The other antimicrobial agents were supplied by the following pharmaceutical firms: methicillin and ampicillin by Beecham Laboratories, Bristol, Tenn.; moxalactam by Eli Lilly Research Laboratories, Indianapolis, Ind.; ceftriaxone by Hoffmann-La Roche Inc., Nutley, N.J. The 236 recent clinical isolates collected by the microbiology staff of Primary Children's Medical Center (Salt Lake City, Utah) included the following: 12 penicillin-resistant, methicillin-susceptible strains of Staphylococcus aureus; 21 penicillin-susceptible, methicillin-susceptible strains of Staphylococcus epidermidis; 25 penicillin-resistant, methicillin-susceptible strains of S. epidermidis; 18 penicillin-resistant, methicillin-resistant strains of S. epidermidis; 30 strains of Streptococcus pyogenes; 20 strains of Streptococcus agalactiae; 32 strains of Streptococcus pneumoniae; 16 strains of Streptococcus faecalis; 21 beta-lactamasepositive strains of Haemophilus influenzae; 20-beta-
lactamase-negative strains of H. influenzae; 21 betalactamase-negative strains of Neisseria gonorrhoeae. An additional 109 stock strains included 33-beta-lactamasepositive strains of Neisseria gonorrhoeae; 30 strains of Neisseria meningitidis; 15 penicillin-resistant, methicillinresistant strains of Staphylococcus aureus; 19 penicillinsusceptible, methicillin-susceptible strains of S. aureus; 12 strains of viridans group streptococci. Stock strains were passed through at least three log phases of growth before susceptibility testing. All isolates were identified by standard methods (2). MICs were determined by broth microdilution in MuellerHinton broth (for staphylococci), Todd-Hewitt broth (for streptococci other than S. pneumoniae), Mueller-Hinton broth supplemented with 5% defibrinated sheep blood (for S. pneumoniae), and Mueller-Hinton broth supplemented (1:1, vol/vol) with Shaedler broth (for H. influenzae), or by agar dilution in GC agar supplemented with Kellogg supplements I and II (for N. gonorrhoeae and N. meningitidis). Methods were those recommended by the National Committee for Clinical Laboratory Standards (3) with a final inoculum of ca. 5 x 105 CFU/ml, appropriate quality control strains, and purity, inoculum, and growth controls. The MIC was defined as the lowest antimicrobial concentration completely inhibiting bacterial growth in broth or inhibiting 99.9% CFU on agar after 16 to 20 h of incubation at 350C. Staphylococcal penicillin resistance was defined as an MIC of .0.12 pg/ml, and methicillin resistance was defined as an MIC of >8.0 ,ug/ml. Beta-lactamase production was determined with a chromogenic cephalosporin substrate (Cefinase; BBL Microbiology Systems, Cockeysville, Md.). Comparative activity against the 345 strains is shown in Table 1. In general, the activity of SK&F 88070 was most similar to that of ceftizoxime among the drugs tested. The drug was slightly less active against S. pyogenes than were ceftriaxone and ampicillin, and it was considerably more active than either methicillin or moxalactam. Also, the activity of SK&F 88070 against S. agalactiae was greater than that of any of the other agents except ceftizoxime. Isolates of S. faecalis were uniformly resistant to all drugs
* Corresponding author.
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GOOCH AND DALY
TABLE 1. Comparative activity of SK&F 88070 and other compounds Microorganism (no. of strains)
Antibiotic
MIC (,ug/tnl)'
50Oo
90%o
SK&F 88070 Ceftizoxime Ceftriaxone Moxalactam Methicillin Ampicillin
8.0 4.0 16.0 8.0 16.0 64.0
>64.0 >64.0 64.0 >64.0 16.0 64.0
8.0->64.0 2.0->64.0 2.0->64.0 8.0->64.0 16.0->64.0 >64.0
Penicillin-resistant, methicillinsusceptible (12)
SK&F 88070 Ceftizoxime Ceftriaxone Moxalactam Methicillin Ampicillin
32.0 >64.0 8.0 64.0 4.0 32.0
>64.0 >64.0 16.0 >64.0 4.0 64.0
2.0->64.0 2.0->64.0 2.0-16.0 4.0->64.0 2.0-4.0 2.0-64.0
Penicillin-susceptible, methicillinsusceptible (19)
SK&F 88070 Ceftizoxime Ceftriaxone Moxalactam Methicillin Ampicillin
32.0 >64.0 4.0 16.0 2.0 0.5
2.0-64.0 0.5->64.0 2.0-4.0 4.0-16.0 0.5-2.0 -0.0625-2.0
Staphylococcus aureus Penicillin-resistant, methicillinresistant (15)
Staphylococcus epidermidis Penicillin-resistant, methicillinresistant (18)
Penicillin-resistant, methicillinsusceptible (25)
Penicillin-susceptible, methicillinsusceptible (21)
8.0 2.0 4.0 8.0 2.0 0.125
Range
SK&F 88070 Ceftizoxime Ceftriaxone Moxalactam Methicillin Ampicillin
64.0 32.0 64.0 64.0 64.0 32.0
64.0 64.0 64.0 64.0 64.0 64.0
4.0-64.0 0.5->64.0 0.5-64.0 16.0->64.0 16.0-64.0 1.0-64.0
SK&F 88070 Ceftizoxime Ceftriaxone Moxalactam Methicillin Ampicillin
16.0 1.0 4.0
64.0 16.0 32.0
32.0 4.0 2.0
64.0 4.0 16.0
4.0->64.0 0.5->64.0 1.0-32.0 2.0-32.0 2.0-4.0 0.25-64.0
8.0 0.5 1.0 8.0 1.0 0.125
32.0 2.0 8.0 16.0 2.0 0.25
2.0-32.0 .0.0625-64.0 0.25-16.0 2.0-16.0 .0.0625-8.0 64.0 32.0->64.0 1.0-64.0
