Abstract
A total of 101 Acinetobacter genospecies (77 Acinetobacter baumannii strains and 24 non-A. baumannii strains) were tested for their susceptibilities to levofloxacin, ofloxacin, and ciprofloxacin and for synergy between the quinolones and amikacin by checkerboard titration and time-kill analyses. The MICs at which 50% of the isolates are inhibited (MIC50)/MIC90s for the 101 strains were as follows (in micrograms per milliliter): levofloxacin, 0.25/16.0; ofloxacin, 0.5/32.0; ciprofloxacin, 0.25/> 64.0; and amikacin, 1.0/> 32.0. At empiric breakpoints of < or = 2.0 microg/ml, 61% of the strains were susceptible to all three quinolones. At a breakpoint of < or = 16.0 microg/ml, 84% of the strains were susceptible to amikacin. Checkerboard titrations yielded synergistic fractional inhibitory concentration (FIC) indices (< or = 0.5) for one strain with levofloxacin and amikacin and for two strains with ofloxacin and amikacin. Indices of > 0.5 to 1.0 were seen for 57, 54, and 55 strains with levofloxacin plus amikacin, ofloxacin plus amikacin, and ciprofloxacin plus amikacin, respectively, and indices of > 1.0 in 43, 45, and 46 strains, respectively, were found with the above three combinations. No strains yielded antagonistic FIC indices (> 4.0). Most FIC results of > 1.0 occurred in strains for which the quinolone MICs were > 2.0 microg/ml and for which the amikacin MICs were > or = 32.0 microg/ml. By contrast, synergy (defined as > or = 2 log10 decrease compared to the more active compound alone by time-kill analysis) was found in all seven strains tested for which the quinolone MICs were < or = 2.0 microg/ml. For eight other strains for which the quinolone MICs were > 2.0 microg/ml as determined by time-kill analysis, quinolone and amikacin concentrations in combination were usually too high to permit clinical use. Time-kill analysis was found to be more sensitive in detecting synergy than was the checkerboard method.
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- Appelbaum P. C., Spangler S. K., Sollenberger L. Susceptibility of non-fermentative gram-negative bacteria to ciprofloxacin, norfloxacin, amifloxacin, pefloxacin and cefpirome. J Antimicrob Chemother. 1986 Dec;18(6):675–679. doi: 10.1093/jac/18.6.675. [DOI] [PubMed] [Google Scholar]
- Appelbaum P. C., Spangler S. K., Tamarree T. Susceptibility of 310 nonfermentative gram-negative bacteria to aztreonam, carumonam, ciprofloxacin, ofloxacin and fleroxacin. Chemotherapy. 1988;34(1):40–45. doi: 10.1159/000238546. [DOI] [PubMed] [Google Scholar]
- Appelbaum P. C., Tamim J., Pankuch G. A., Aber R. C. Susceptibility of 324 nonfermentative gram-negative rods to 6 cephalosporins and azthreonam. Chemotherapy. 1983;29(5):337–344. doi: 10.1159/000238217. [DOI] [PubMed] [Google Scholar]
- Bajaksouzian S., Visalli M. A., Jacobs M. R., Appelbaum P. C. Antipneumococcal activities of cefpirome and cefotaxime, alone and in combination with vancomycin and teicoplanin, determined by checkerboard and time-kill methods. Antimicrob Agents Chemother. 1996 Sep;40(9):1973–1976. doi: 10.1128/aac.40.9.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Barry A. L., Fuchs P. C. In vitro activities of sparfloxacin, tosufloxacin, ciprofloxacin, and fleroxacin. Antimicrob Agents Chemother. 1991 May;35(5):955–960. doi: 10.1128/aac.35.5.955. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bergogne-Berezin E., Joly-Guillou M. L. Comparative activity of imipenem, ceftazidime and cefotaxime against Acinetobacter calcoaceticus. J Antimicrob Chemother. 1986 Dec;18 (Suppl E):35–39. doi: 10.1093/jac/18.supplement_e.35. [DOI] [PubMed] [Google Scholar]
- Braveny I. In vitro activity of imipenem--a review. Eur J Clin Microbiol. 1984 Oct;3(5):456–462. doi: 10.1007/BF02017375. [DOI] [PubMed] [Google Scholar]
- Cantón E., Pemán J., Jimenez M. T., Ramón M. S., Gobernado M. In vitro activity of sparfloxacin compared with those of five other quinolones. Antimicrob Agents Chemother. 1992 Mar;36(3):558–565. doi: 10.1128/aac.36.3.558. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cappelletty D. M., Rybak M. J. Comparison of methodologies for synergism testing of drug combinations against resistant strains of Pseudomonas aeruginosa. Antimicrob Agents Chemother. 1996 Mar;40(3):677–683. doi: 10.1128/aac.40.3.677. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chin N. X., Gu J. W., Yu K. W., Zhang Y. X., Neu H. C. In vitro activity of sparfloxacin. Antimicrob Agents Chemother. 1991 Mar;35(3):567–571. doi: 10.1128/aac.35.3.567. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dholakia N., Rolston K. V., Ho D. H., LeBlanc B., Bodey G. P. Susceptibilities of bacterial isolates from patients with cancer to levofloxacin and other quinolones. Antimicrob Agents Chemother. 1994 Apr;38(4):848–852. doi: 10.1128/aac.38.4.848. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fu K. P., Lafredo S. C., Foleno B., Isaacson D. M., Barrett J. F., Tobia A. J., Rosenthale M. E. In vitro and in vivo antibacterial activities of levofloxacin (l-ofloxacin), an optically active ofloxacin. Antimicrob Agents Chemother. 1992 Apr;36(4):860–866. doi: 10.1128/aac.36.4.860. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hoban D. J., Jones R. N., Yamane N., Frei R., Trilla A., Pignatari A. C. In vitro activity of three carbapenem antibiotics. Comparative studies with biapenem (L-627), imipenem, and meropenem against aerobic pathogens isolated worldwide. Diagn Microbiol Infect Dis. 1993 Nov-Dec;17(4):299–305. doi: 10.1016/0732-8893(93)90039-a. [DOI] [PubMed] [Google Scholar]
- Husson M. O., Izard D., Bouillet L., Leclerc H. Comparative in-vitro activity of ciprofloxacin against non-fermenters. J Antimicrob Chemother. 1985 Apr;15(4):457–462. doi: 10.1093/jac/15.4.457. [DOI] [PubMed] [Google Scholar]
- Joly-Guillou M. L., Bergogne-Bérézin E. In-vitro activity of sparfloxacin, pefloxacin, ciprofloxacin and temafloxacin against clinical isolates of Acinetobacter spp. J Antimicrob Chemother. 1992 Apr;29(4):466–468. doi: 10.1093/jac/29.4.466. [DOI] [PubMed] [Google Scholar]
- Kuah B. G., Kumarasinghe G., Doran J., Chang H. R. Antimicrobial susceptibilities of clinical isolates of Acinetobacter baumannii from Singapore. Antimicrob Agents Chemother. 1994 Oct;38(10):2502–2503. doi: 10.1128/aac.38.10.2502. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Neu H. C., Chin N. X. In vitro activity of S-ofloxacin. Antimicrob Agents Chemother. 1989 Jul;33(7):1105–1107. doi: 10.1128/aac.33.7.1105. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pfaller M. A., Barry A. L., Fuchs P. C. Levofloxacin disk potency and tentative interpretive criteria for susceptibility tests. J Clin Microbiol. 1993 Jul;31(7):1924–1926. doi: 10.1128/jcm.31.7.1924-1926.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rolston K. V., Bodey G. P. In vitro susceptibility of Acinetobacter species to various antimicrobial agents. Antimicrob Agents Chemother. 1986 Nov;30(5):769–770. doi: 10.1128/aac.30.5.769. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Seifert H., Baginski R., Schulze A., Pulverer G. Antimicrobial susceptibility of Acinetobacter species. Antimicrob Agents Chemother. 1993 Apr;37(4):750–753. doi: 10.1128/aac.37.4.750. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shalit I., Dan M., Gutman R., Gorea A., Berger S. A. Cross resistance to ciprofloxacin and other antimicrobial agents among clinical isolates of Acinetobacter calcoaceticus biovar anitratus. Antimicrob Agents Chemother. 1990 Mar;34(3):494–495. doi: 10.1128/aac.34.3.494. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Simor A. E., Louie L., Louie M. In vitro susceptibility of Acinetobacter baumannii to biapenem, piperacillin/tazobactam and thirteen other antimicrobial agents. Eur J Clin Microbiol Infect Dis. 1994 Jun;13(6):521–523. doi: 10.1007/BF01974651. [DOI] [PubMed] [Google Scholar]
- Spangler S. K., Visalli M. A., Jacobs M. R., Appelbaum P. C. Susceptibilities of non-Pseudomonas aeruginosa gram-negative nonfermentative rods to ciprofloxacin, ofloxacin, levofloxacin, D-ofloxacin, sparfloxacin, ceftazidime, piperacillin, piperacillin-tazobactam, trimethoprim-sulfamethoxazole, and imipenem. Antimicrob Agents Chemother. 1996 Mar;40(3):772–775. doi: 10.1128/aac.40.3.772. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tanaka M., Otsuki M., Une T., Nishino T. In-vitro and in-vivo activity of DR-3355, an optically active isomer of ofloxacin. J Antimicrob Chemother. 1990 Nov;26(5):659–666. doi: 10.1093/jac/26.5.659. [DOI] [PubMed] [Google Scholar]
- Visser M. R., Rozenberg-Arska M., Beumer H., Hoepelman I. M., Verhoef J. Comparative in vitro antibacterial activity of sparfloxacin (AT-4140; RP 64206), a new quinolone. Antimicrob Agents Chemother. 1991 May;35(5):858–868. doi: 10.1128/aac.35.5.858. [DOI] [PMC free article] [PubMed] [Google Scholar]
- von Graevenitz A., Bucher C. The effect of N-formimidoyl thienamycin, ceftazidime, cefotiam, ceftriaxone and cefotaxime on non-fermentative Gram-negative rods, Aeromonas, Plesiomonas and Enterobacter agglomerans. Infection. 1982 Sep-Oct;10(5):293–298. doi: 10.1007/BF01640878. [DOI] [PubMed] [Google Scholar]