In Vitro Activities of Ro 17-2301 and Aztreonam Comparedwith. Those of Other New P-Lactam Antibiotics Against Clinical Isolates of Pseudomonas aeruginosa.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, May 1985, p. 872-873 0066-4804/85/050872-02$02.00/0 Copyright 0 1985, American Society for Microbiology
Vol. 27, No. S
NOTES In Vitro Activities of Ro 17-2301 and Aztreonam Compared with Those of Other New P-Lactam Antibiotics Against Clinical Isolates of Pseudomonas aeruginosa WILSON W. S. NG,l* P. Y. CHAU,2 Y. K. LEUNG,2 AND D. M. LIVERMORE3 Departments ofExtra-Mural Studiesl* and Microbiology, University of Hong Kong, Hong Kong, and Department of
Medical Microbiology, London Hospital Medical College, London, United Kingdom3 Received 19 November 1984/Accepted 30 January 1985
The in vitro activities of Ro 17-2301 and aztreonam against 191 Pseudomonas aeruginosa Isolates were compared with those of five other 1-lactam antibiotics. Both compounds showed activities comparable to that of ceftazidime and were bactericidal. They were as effective against gentamicin- or carbenicilin-resistant isolates as against susceptible ones.
A number of 1-lactam antibiotics active against Pseudomonas aeruginosa have been developed in recent years. However, the high mortality rate of infections caused by P. aeruginosa remains a serious clinical problem. A further problem is posed by the increasingly frequent isolation of carbenicillin- and gentamicin-resistant strains in various localities including Hong Kong. Monocyclic lB-lactam antibiotics such as aztreonam and Ro 17-2301, the latter a relatively new monobactam, have been reported to be active against P. aeruginosa and many other gram-negative bacteria (1; P. Angehrn, Proc. 13th Int. Congr. Chemother., p. 4.2/15-4.2/18, 1983). In this study, the in vitro activities of aztreonam and Ro 17-2301 against 191 clinical isolates of P. aeruginosa from the Queen Mary Hospital, Hong Kong, were compared with those of other new 1-lactam antibiotics. Of the 191 clinical isolates tested, 85 were from blood and 106 from pus, wounds, urine, and other clinical specimens. In addition to aztreonam (E. R. Squibb & Sons, Princeton, N.J.) and Ro 17-2301 (Hoffmann-La Roche, Inc., Nutley, N.J.), the antibiotics tested in this study included ceftazidime (Glaxo Pharmaceuticals, Ltd., Greenford, United Kingdom) cefoperazone (Pfizer Inc., New York, N.Y.), cefpiramide (Wyeth Laboratories, Philadelphia, Penn.), piperacillin (Lederle Laboratories, Pearl River, N.Y.), apalcillin (Wyeth), and carbenicillin and gentamicin. The MICs were determined by the agar dilution method on unsupplemented Mueller-Hinton agar (Oxoid Ltd., Basingstoke, England). A final inoculum of 10o CFU per spot, prepared by dilution of overnight broth cultures, was applied in duplicate by a multipoint inoculator to freshly prepared agar plates containing the antibiotic. The MIC was determined as the lowest concentration of antibiotic that inhibited all growth after overnight incubation. The MICs and MBCs of Ro 17-2301, aztreonam, and ceftazidime for 32 randomly selected P. aeruginosa isolates were compared by the brothtube dilution method. Mueller-Hinton broths containing the appropriate antibiotic were inoculated with P. aeruginosa at 1.5 x 106 CFU/ml. After overnight incubation, 0.01-mi portions of clear broth were plated onto nutrient agar. The *
TABLE 1. In vitro activity of Ro 17-2301 and six other 1-lactam antibiotics against P. aeruginosa MIC (mg/liter) for: Antibiotic 85 blood isolates 106 nonblood isolates Range MIC,0 MIC90 Range MIC,o MIC,0 Ro 17-2301 0.5-8.0 2.0 4.0 0.5-64 2.0 4.0 Aztreonam 1.0-16 2.0 8.0 2.0-128 2.0 4.0 Ceftazidime 0.5-8.0 1.0 4.0 0.5-32 1.0 4.0 Cefoperazone 0.5-64 4.0 16 0.5->128 4.0 64 Cefpiramide 1.0-64 2.0 4.0 1.0->128 2.0 16 Apalciflin 1.0-64 1.0 4.0 0.5->128 2.0 32 Piperacillin 1.0-128 2.0 8.0 1.0->128 4.0 64
MBC was defined as the lowest concentration of antibiotic at which no growth occurred on solid medium after a further incubation of 24 h at 370C. Table 1 shows that all seven ,B-lactam antibiotics were active against the 85 blood isolates of P. aeruginosa. Ceftazidime, Ro 17-2301, and aztreonam showed a narrower MIC range, and none of the strains tested required an MIC of >16 mg/liter for inhibition. In comparison, the MICs of cefoperazone, cefpiramide, apalcillin, and piperacillin for a few P. aeruginosa isolates were .32 mg/liter. These differences, however, were not apparent when the MIC for 50% of TABLE 2. Effect of inoculum size on the in vitro activity of Ro 17-2301, aztreonam, and ceftazidime on 32 P. aerugionosa isolates Inoculumr Antibiotic size spot MICgo MIC50 (range) (rne per spot) Ro 17-2301 1 x 104 1.0-64 2.0 8.0 1.5 x 106 4.0 1.064 16
Corresponding author. 872
Aztreonam
1 x 104 1.5 x 106
2.0-128 2.0-64
2.0 4.0
8.0 16
Ceftazidime
1 x 104 1.5 x 106
1.0-8.0 2.0-32
2.0 4.0
4.0 8.0
NOTES
VOL. 27, 1985
the isolates (MIC50) and MIC90 were compared. Strains of P. aeruginosa isolated from other clinical specimens were found as a group to be more resistant than blood isolates. Against these strains, ceftazidime, Ro 17-2301, and aztreonam showed the greatest activity. They inhibited all 106 of the nonblood isolates at the following concentrations: ceftazidime, 32 mg/liter; Ro 17-2301, 64 mg/liter; and aztreonam, 128 mg/liter. A number of the isolates showed resistance to the other four P-lactam antibiotics which had MICs of >128 mg/liter. There was no significant increase in the MICs of Ro 17-2301, aztreonam, and ceftazidime for the isolates when they showed an increasing resistance to carbenicillin (MICs TAB3LE 3. MICs and MBCs of Ro 17-2301, aztreonam, and ceftazidime for 32 P. aeruginosa isolates tested by the broth dilution method Antibiotic
Ro 17-2301 Aztreonam Ceftazidime
MIC (mg/liter) Range MIC50 MIC¶0
1.0-64 2.0-64 2.0-32
4.0 4.0 4.0
16 16 8.0
MBC (mg/liter) Range MBC50 MBC9O
2.0-64 4.0-128 4.0-32
4.0 4.0 4.0
16 32 16
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-128 mg/liter; 50 strains) and gentamicin (MICs .16 mg/liter; 42 strains). The in vitro activities of Ro 17-2301, aztreonam, and ceftazidime were not appreciably affected by an increase in the inoculum size of the isolates (Table 2) or by the presence of plasmid-mediated P-lactamases (PSE-1, PSE-2, PSE-3, PSE-4, OXA-1, OXA-3, and TEM-2) in the strains tested. When tested against 32 randomly selected P. aeruginosa isolates, Ro 17-2301, aztreonam, and ceftazidime were all found to be bactericidal; the MBCs were equal to or two times greater than the MICs (Table 3). These data indicated that Ro 17-2301, aztreonam, and ceftazidime were comparable to each other in activity against our clinical isolates of P. aeruginosa. All three antibiotics were bactericidal, and their activities were unaffected by an increase in the inoculum size. Furthermore, they were as effective against gentamicin- or carbenicillin-resistant isolates as against sensitive ones and appeared to be stable to plasmid-mediated lactamases. LITERATURE CITED 1. Sykes, R. B., D. P. Bonner, K. Bush, and N. H. Georgopapadakou. 1982. Azthreonam (SQ 26,776), a synthetic monobactam specifically active against aerobic gram-negative bacteria. Antimicrob. Agents Chemother. 21:85-92.
