Abstract
Stenotrophomonas (Xanthomonas) maltophilia is inherently resistant to multiple antimicrobial agents. In order to investigate the in vitro potential of combinations of antimicrobial agents, we obtained 230 epidemiologically unrelated clinical isolates from seven hospitals across Canada and from Northwestern Memorial Hospital in Chicago. Ticarcillin-clavulanate combined with ciprofloxacin or trimethoprim-sulfamethoxazole were assayed for synergy against 31 ticarcillin-resistant strains of S. maltophilia by using microtiter checkerboard panels and against 20 strains by using time-kill methodology. The combination of ciprofloxacin with ceftazidime was also evaluated by time-kill studies. Ticarcillin-clavulanate plus trimethoprim-sulfamethoxazole demonstrated synergy by checkerboard panels, with fractional inhibitory concentration indices ranging from 0.033 to 0.49, and by time-kill studies for all 20 strains tested. Synergy between ticarcillin-clavulanate plus ciprofloxacin was found by the checkerboard method for 24 of 31 strains (77%), with fractional inhibitory concentration indices ranging from 0.188 to 0.75. A correlation between synergy by the checkerboard method and the reference time-kill study method was not observed for ticarcillin-clavulanate plus ciprofloxacin, with results for 3 of 10 strains being nonconcordant. Synergy with both ticarcillin-clavulanate plus ciprofloxacin and ceftazidime plus ciprofloxacin by the time-kill method was found to correlate with ciprofloxacin MICs of <32 micrograms/ml and zone diameters of >15 mm on Mueller-Hinton agar. Evaluation of these combinations in vivo may be warranted.
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Selected References
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- Akova M., Bonfiglio G., Livermore D. M. Susceptibility to beta-lactam antibiotics of mutant strains of Xanthomonas maltophilia with high- and low-level constitutive expression of L1 and L2 beta-lactamases. J Med Microbiol. 1991 Oct;35(4):208–213. doi: 10.1099/00222615-35-4-208. [DOI] [PubMed] [Google Scholar]
- Baker C. N., Thornsberry C., Facklam R. R. Synergism, killing kinetics, and antimicrobial susceptibility of group A and B streptococci. Antimicrob Agents Chemother. 1981 May;19(5):716–725. doi: 10.1128/aac.19.5.716. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bamberger D. M., Peterson L. R., Gerding D. N., Moody J. A., Fasching C. E. Ciprofloxacin, azlocillin, ceftizoxime and amikacin alone and in combination against gram-negative bacilli in an infected chamber model. J Antimicrob Chemother. 1986 Jul;18(1):51–63. doi: 10.1093/jac/18.1.51. [DOI] [PubMed] [Google Scholar]
- Bayer A. S., Morrison J. O. Disparity between timed-kill and checkerboard methods for determination of in vitro bactericidal interactions of vancomycin plus rifampin versus methicillin-susceptible and -resistant Staphylococcus aureus. Antimicrob Agents Chemother. 1984 Aug;26(2):220–223. doi: 10.1128/aac.26.2.220. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bayer A. S., Morrison J. O., Kim K. S. Experimental group B streptococcal endocarditis treated with penicillin G versus ceftizoxime. In vitro-in vivo disparity. Chemotherapy. 1983;29(5):352–361. doi: 10.1159/000238219. [DOI] [PubMed] [Google Scholar]
- Bonfiglio G., Livermore D. M. Effect of media composition on the susceptibility of Xanthomonas maltophilia to beta-lactam antibiotics. J Antimicrob Chemother. 1991 Dec;28(6):837–842. doi: 10.1093/jac/28.6.837. [DOI] [PubMed] [Google Scholar]
- Bush K. Classification of beta-lactamases: groups 2c, 2d, 2e, 3, and 4. Antimicrob Agents Chemother. 1989 Mar;33(3):271–276. doi: 10.1128/aac.33.3.271. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chow A. W., Wong J., Bartlett K. H. Synergistic interactions of ciprofloxacin and extended-spectrum beta-lactams or aminoglycosides against multiply drug-resistant Pseudomonas maltophilia. Antimicrob Agents Chemother. 1988 May;32(5):782–784. doi: 10.1128/aac.32.5.782. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cullmann W. Antibiotic susceptibility and outer membrane proteins of clinical Xanthomonas maltophilia isolates. Chemotherapy. 1991;37(4):246–250. doi: 10.1159/000238862. [DOI] [PubMed] [Google Scholar]
- Cullmann W., Dick W. Heterogeneity of beta-lactamase production in Pseudomonas maltophilia, a nosocomial pathogen. Chemotherapy. 1990;36(2):117–126. doi: 10.1159/000238757. [DOI] [PubMed] [Google Scholar]
- Elting L. S., Khardori N., Bodey G. P., Fainstein V. Nosocomial infection caused by Xanthomonas maltophilia: a case-control study of predisposing factors. Infect Control Hosp Epidemiol. 1990 Mar;11(3):134–138. doi: 10.1086/646136. [DOI] [PubMed] [Google Scholar]
- Felegie T. P., Yu V. L., Rumans L. W., Yee R. B. Susceptibility of Pseudomonas maltophilia to antimicrobial agents, singly and in combination. Antimicrob Agents Chemother. 1979 Dec;16(6):833–837. doi: 10.1128/aac.16.6.833. [DOI] [PMC free article] [PubMed] [Google Scholar]
- García-Rodríguez J. A., García Sánchez J. E., García García M. I., García Sánchez E., Muñoz Bellido J. L. Antibiotic susceptibility profile of Xanthomonas maltophilia. In vitro activity of beta-lactam/beta-lactamase inhibitor combinations. Diagn Microbiol Infect Dis. 1991 May-Jun;14(3):239–243. doi: 10.1016/0732-8893(91)90038-h. [DOI] [PubMed] [Google Scholar]
- García-Rodríguez J. A., García Sánchez J. E., Muñoz Bellido J. L., García García M. I., García Sánchez E. Kinetics of antimicrobial activity of aztreonam/clavulanic acid (2:1) against Xanthomonas maltophilia. J Antimicrob Chemother. 1991 Apr;27(4):552–554. doi: 10.1093/jac/27.4.552. [DOI] [PubMed] [Google Scholar]
- Hawkey P. M., Birkenhead D., Kerr K. G., Newton K. E., Hyde W. A. Effect of divalent cations in bacteriological media on the susceptibility of Xanthomonas maltophilia to imipenem, with special reference to zinc ions. J Antimicrob Chemother. 1993 Jan;31(1):47–55. doi: 10.1093/jac/31.1.47. [DOI] [PubMed] [Google Scholar]
- Hohl P., Frei R., Aubry P. In vitro susceptibility of 33 clinical case isolates of Xanthomonas maltophilia. Inconsistent correlation of agar dilution and of disk diffusion test results. Diagn Microbiol Infect Dis. 1991 Sep-Oct;14(5):447–450. doi: 10.1016/0732-8893(91)90072-n. [DOI] [PubMed] [Google Scholar]
- Khardori N., Elting L., Wong E., Schable B., Bodey G. P. Nosocomial infections due to Xanthomonas maltophilia (Pseudomonas maltophilia) in patients with cancer. Rev Infect Dis. 1990 Nov-Dec;12(6):997–1003. doi: 10.1093/clinids/12.6.997. [DOI] [PubMed] [Google Scholar]
- Khardori N., Reuben A., Rosenbaum B., Rolston K., Bodey G. P. In vitro susceptibility of Xanthomonas (Pseudomonas) maltophilia to newer antimicrobial agents. Antimicrob Agents Chemother. 1990 Aug;34(8):1609–1610. doi: 10.1128/aac.34.8.1609. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Marshall W. F., Keating M. R., Anhalt J. P., Steckelberg J. M. Xanthomonas maltophilia: an emerging nosocomial pathogen. Mayo Clin Proc. 1989 Sep;64(9):1097–1104. doi: 10.1016/s0025-6196(12)64979-9. [DOI] [PubMed] [Google Scholar]
- Mett H., Rosta S., Schacher B., Frei R. Outer membrane permeability and beta-lactamase content in Pseudomonas maltophilia clinical isolates and laboratory mutants. Rev Infect Dis. 1988 Jul-Aug;10(4):765–769. doi: 10.1093/clinids/10.4.765. [DOI] [PubMed] [Google Scholar]
- Morrison A. J., Jr, Hoffmann K. K., Wenzel R. P. Associated mortality and clinical characteristics of nosocomial Pseudomonas maltophilia in a university hospital. J Clin Microbiol. 1986 Jul;24(1):52–55. doi: 10.1128/jcm.24.1.52-55.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pankuch G. A., Jacobs M. R., Appelbaum P. C. Susceptibilities of 123 Xanthomonas maltophilia strains to clinafloxacin, PD 131628, PD 138312, PD 140248, ciprofloxacin, and ofloxacin. Antimicrob Agents Chemother. 1994 Feb;38(2):369–370. doi: 10.1128/aac.38.2.369. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Paton R., Miles R. S., Amyes S. G. Biochemical properties of inducible beta-lactamases produced from Xanthomonas maltophilia. Antimicrob Agents Chemother. 1994 Sep;38(9):2143–2149. doi: 10.1128/aac.38.9.2143. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Payne D. J., Cramp R., Bateson J. H., Neale J., Knowles D. Rapid identification of metallo- and serine beta-lactamases. Antimicrob Agents Chemother. 1994 May;38(5):991–996. doi: 10.1128/aac.38.5.991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rolston K. V., Messer M., Ho D. H. Comparative in vitro activities of newer quinolones against Pseudomonas species and Xanthomonas maltophilia isolated from patients with cancer. Antimicrob Agents Chemother. 1990 Sep;34(9):1812–1813. doi: 10.1128/aac.34.9.1812. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Saino Y., Inoue M., Mitsuhashi S. Purification and properties of an inducible cephalosporinase from Pseudomonas maltophilia GN12873. Antimicrob Agents Chemother. 1984 Mar;25(3):362–365. doi: 10.1128/aac.25.3.362. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Saino Y., Kobayashi F., Inoue M., Mitsuhashi S. Purification and properties of inducible penicillin beta-lactamase isolated from Pseudomonas maltophilia. Antimicrob Agents Chemother. 1982 Oct;22(4):564–570. doi: 10.1128/aac.22.4.564. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Vartivarian S. E., Papadakis K. A., Palacios J. A., Manning J. T., Jr, Anaissie E. J. Mucocutaneous and soft tissue infections caused by Xanthomonas maltophilia. A new spectrum. Ann Intern Med. 1994 Dec 15;121(12):969–973. doi: 10.7326/0003-4819-121-12-199412150-00011. [DOI] [PubMed] [Google Scholar]
- Vartivarian S., Anaissie E., Bodey G., Sprigg H., Rolston K. A changing pattern of susceptibility of Xanthomonas maltophilia to antimicrobial agents: implications for therapy. Antimicrob Agents Chemother. 1994 Mar;38(3):624–627. doi: 10.1128/aac.38.3.624. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wheat P. F., Winstanley T. G., Spencer R. C. Effect of temperature on antimicrobial susceptibilities of Pseudomonas maltophilia. J Clin Pathol. 1985 Sep;38(9):1055–1058. doi: 10.1136/jcp.38.9.1055. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yamazaki E., Ishii J., Sato K., Nakae T. The barrier function of the outer membrane of Pseudomonas maltophilia in the diffusion of saccharides and beta-lactam antibiotics. FEMS Microbiol Lett. 1989 Jul 1;51(1):85–88. doi: 10.1016/0378-1097(89)90082-7. [DOI] [PubMed] [Google Scholar]
- Yu V. L., Felegie T. P., Yee R. B., Pasculle A. W., Taylor F. H. Synergistic interaction in vitro with use of three antibiotics simultaneously against Pseudomonas maltophilia. J Infect Dis. 1980 Oct;142(4):602–607. doi: 10.1093/infdis/142.4.602. [DOI] [PubMed] [Google Scholar]