Vol. 36, No. 3
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Mar. 1992, p. 684-686 0066-4804/92/030684-03$02.00/0 Copyright © 1992, American Society for Microbiology
In Vitro Activity of E1040 against Imipenem-Resistant Pseudomonas
Strains
aeruginosa MASATO
WATANABE,"* EIKO INOUE,1 KANEMASA KATSU,1 SHIZUKO IYOBE,2
AND SUSUMU MITSUHASHI1 Episome Institute, Fujimi-mura, Seta-gun, 1 and Laboratory of Drug Resistance in Bacteria, Gunma University School of Medicine, Maebashi, Gunma-ken, Japan
Received 2 August 1991/Accepted 31 December 1991
E1040 showed the most potent activity (MIC for 90o of strains, 6.25 iLg/ml) among 13-lactams tested against 70 strains of imipenem-resistant Pseudomonas aeruginosa. Two strains showed high-level resistance to E1040; one strain produced a type II oxyiminocephalosporin-hydrolyzing P-lactamase (group 3), and the other produced an enzyme similar to a type II penicillinase (OXA-1). Both "-lactamases contributed to resistance to E1040. maximum rate of hydrolysis (relative VmD) were determined a Lineweaver-Burk plot. 3-Lactamase activity (1 U) was expressed as 1 ,umol of substrate hydrolyzed per min at
E1040 is a novel 3-lactam antibiotic which shows activity against a broad spectrum of organisms, including Pseudomonas aeruginosa (4, 9, 19). Imipenem-resistant strains of P. aeruginosa were reported recently (1, 7, 12, 18). We investigated the antibacterial activity of E1040 against imipenem-resistant P. aeruginosa (MIC, .12.5 ,ug/ml).
with
30°C in 50 mM phosphate buffer. The pI, molecular weight, and protein concentration were determined as previously described (18). Plasmid DNA was isolated by the method of
TABLE 1. Susceptibility of 70 imipenem-resistant P. aeruginosa strains to ,-lactam antibiotics Cumulative % of strains inhibited by the following MIC (,ug/ml): Drug
E1040 Ceftazidime
0.39
0.78
1.56
3.13
6.25
10.0
30.0 2.9
47.1 15.7 11.4
87.1 25.7 21.4 15.7 5.7 20.0 15.7
95.7
21.4 21.4 18.6 5.7
32.9 32.9 60.0 50.0
Cefsulodin Cefoperazone Cefpirome Cefepime Piperacillin Carbenicillin Aztreonam Carumonam Gentamicin Amikacin Imipenem
8.6 2.9 11.4 2.9 1.4
32.9 37.1 18.6
17.1 45.7 21.4
54.3 51.4 22.9 31.4 74.3 25.7 54.3 42.9 80.0 80.0 64.3
25
50
100
97.1 62.9 80.0 37.1 52.9 95.7 37.1 7.1 90.0
98.6 95.7 92.9 52.9 87.1 97.1 55.7 34.3 98.6
100 98.6 95.7 84.3 97.1
57.1
95.7 82.9 97.1 100
92.9 97.1
65.7 52.9 100 100 84.3
> 100
100 100 100 100 100 100 100 100 100
Kado and Liu (6) or Sasakawa et al. (14), and conjugation and transformation were carried out as previously reported
The strains used were collected between 1988 and 1989 from several hospitals throughout Japan (18). Antibacterial susceptibility was measured by an agar dilution method with sensitivity disk agar (Nissui, Tokyo, Japan) (17). The antimicrobial agents used were as follows: E1040 (Eisai); imipenem and amikacin (Banyu Pharmaceutical); aztreonam (Squibb); cephaloridine and cephalothin (Shionogi); cefotaxime and cefpirome (Hoechst Japan); cefsulodin and carumonam (Takeda Chemical Industries); ceftazidime (Nippon Glaxo); cefepime (Bristol Meyers Squibb); piperacillin and cefoperazone (Toyama Chemicals); penicillin G, ampicillin, and cloxacillin (Meiji Seika Kaisha); carbenicillin (SmithKline Beecham Seiyaku); and gentamicin (Schering-Plough).
(18). The antibacterial activity of E1040 against imipenemresistant P. aeruginosa is shown in Table 1. E1040 inhibited 90% of the strains at