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Synergistic activity of aminoglycoside-beta-lactam combinations against Pseudomonas aeruginosa with an unusual aminoglycoside antibiogram

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Abstract

The bactericidal activity of aminoglycosides alone and in combination with various beta-lactams was studied by the time-kill technique against ten Pseudomonas aeruginosa isolates with an unusual antibiogram (amikacin-resistant, gentamicin-resistant, tobramycin-susceptible [ArGrTs]). Previous studies have indicated that ArGrTs isolates are moderately resistant to all aminoglycosides and many are multiply resistant to beta-lactams. Aminoglycoside-beta-lactam combinations showed infrequent synergistic (16%) or enhanced killing (12%) against the ArGrTs isolates. Synergistic activity, when present, was more likely to occur with tobramycin and amikacin than with gentamicin, even though these differences were not statistically significant. Antibiotic resistance patterns were not predictive of synergy or enhanced killing. Systemic infections produced by ArGrTs isolates that are multiply resistant to the beta-lactams may not respond to combination therapy with an aminoglycoside and beta-lactam. Alternative treatment with polymyxin B or a quinolone may be required for these infections.

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References

  1. Anderson EL, Gramling PK, Vestal PR, Farrar WE JR (1975) Susceptibility of Pseudomonas aeruginosa to gentamicin alone and combined with carbenicillin. Antimicrob Agents Chemother 8:300–304

    Google Scholar 

  2. Bustamante CI, Drusano GL, Wharton RC, Wade JC (1987) Synergism of the combinations of imipenem plus ciprofloxacin and imipenem plus amikacin against Pseudomonas aeruginosa and other bacterial pathogens. Antimicrob Agents Chemother 31:632–634

    Google Scholar 

  3. Chan EL, Zabransky RJ (1987) Determination of synergy by two methods with eight antimicrobial combinations against tobramycin-susceptible and tobramycin-resistant strains of Pseudomonas. Diagn Microbiol Infect Dis 6:157–164

    Google Scholar 

  4. Chanbusarakum P, Murray PR (1978) Analysis of piperacillin, ticarcillin, or carbenicillin and aminoglycoside antibiotics. Antimicrob Agents Chemother 14:505–506

    Google Scholar 

  5. Clark RB, Sanders CC, Pakiz CB, Hostetter MK (1988) Aminoglycoside resistance among Pseudomonas aeruginosa isolates with an unusual disk diffusion antibiogram. Antimicrob Agents Chemother 32:689–692

    Google Scholar 

  6. Clark RB, Hu DH, Janda JM, Hostetter MK (1986) Increased susceptibility of gentamicin-resistant Pseudomonas aeruginosa to human sera. Curr Microbiol 13:159–162

    Google Scholar 

  7. Clark RB, Janda JM, Bottone EJ (1984) Phenotypic factors correlated with the absence of virulence among gentamicin-resistant Pseudomonas aeruginosa strains. J Clin Microbiol 20:235–238

    Google Scholar 

  8. Comber KR, Basker MJ, Osborne CD, Sutherland R (1977) Synergy between ticarcillin and tobramycin against Pseudomonas aeruginosa and Enterobacteriaceae in vitro and in vivo. Antimicrob Agents Chemother 11:956–964

    Google Scholar 

  9. Downs JT, Andriole VT, Ryan JL (1986) Synergism of azlocillin, mezlocillin, piperacillin, in combination against Klebsiella and Pseudomonas. Yale J Biol Med 59:11–16

    Google Scholar 

  10. Eliopoulos GM, Eliopoulos CT (1988) Antibiotic combinations: should they be tested? Clin Microbiol Rev 1:139–156

    Google Scholar 

  11. Fass RJ (1982) Comparative in vitro activities of beta-lactam-tobramycin combinations against Pseudomonas aeruginosa and multi-drug resistant gram negative enteric bacilli. Antimicrob Agents Chemother 21:1003–1006

    Google Scholar 

  12. Gimarellou H, Petrikkos G (1987) Ciprofloxacin interactions with imipenem and amikacin against multiresistant Pseudomonas aeruginosa. Antimicrob Agents Chemother 31:959–961

    Google Scholar 

  13. Glew RH, Pavuk RA (1983) Early synergistic interaction between semisynthetic penicillins and aminoglycoside aminocyclitols against Enterobacteriaceae. Antimicrob Agents Chemother 23:902–906

    Google Scholar 

  14. Gombert ME, Aulicino TE (1986) Amikacin synergism with beta-lactams against selected nosocomial pathogens. J Antimicrob Chemother 17:323–326

    Google Scholar 

  15. Hallander HO, Dornbusch K, Gezelins L, Jacobson K, Karsson I (1982) Synergism between aminoglycosides and cephalosporins with antipseudomonal activity: interaction index and killing curve method. Antimicrob Agents Chemother 22:743–752

    Google Scholar 

  16. Heineman HS, Lofton WM (1978) Unpredictable response of Pseudomonas aeruginosa to synergistic antibiotic combinations. Antimicrob Agents Chemother 13:827–831

    Google Scholar 

  17. Hooton TM, Blair AD, Turck M, Counts GW (1984) Synergism at clinically attainable concentrations of aminoglycoside and beta-lactam antibiotics. Antimicrob Agents Chemother 26:535–538

    Google Scholar 

  18. Kluge RM, Standiford HC, Tatem B, Young VM, Schimpff SC, Greene WH, Calia FM, Hornick RB (1974) The carbenicillin-gentamicin combination against Pseudomonas aeruginosa. Correlation of effect with gentamicin sensitivity. Ann Intern Med 81:584–587

    Google Scholar 

  19. Kragstad DJ, Moellering RC Jr (1986) Antimicrobial combinations. In: Lorian V (ed) Antibiotics in laboratory medicine. Williams and Wilkins, Baltimore, pp 537–595

    Google Scholar 

  20. Kurtz TO, Winston DJ, Bruckner DA, Martin WJ (1981) Comparative in vitro synergistic activity of new beta-lactam antimicrobial agents and amikacin against Pseudomonas aeruginosa and Serratia marcescens. Antimicrob Agents Chemother 20:239–243

    Google Scholar 

  21. Lydon MD, Smith KR, Saag MS, Cloud BA, Cobbs CG (1986) In vitro activity of piperacillin, ticarcillin, and mezlocillin alone and in combination with aminoglycosides against Pseudomonas aeruginosa. Antimicrob Agents Chemother 30:25–30

    Google Scholar 

  22. Marks MI, Hammerberg S, Greenstone G, Silver B (1977) Activity of newer aminoglycosides and carbenicillin, alone and in combination, against gentamicin-resistant Pseudomonas aeruginosa. Antimicrob Agents Chemother 10:399–401

    Google Scholar 

  23. Mintz L, Drew WL (1981) Comparative synergistic activity of cefoperazone, cefotaxime, moxalactam, and carbenicillin, combined with tobramycin, against Pseudomonas aeruginosa. Antimicrob Agents Chemother 19:332–334

    Google Scholar 

  24. Moellering RC, Wennesten C, Medrek T, Weinberg AN (1971) Prevalence of high-level resistance to aminoglycosides in clinical isolates of enterococci. Antimicrob Agents Chemother 1970:335–340

    Google Scholar 

  25. National Committee for Clinical Laboratory Standards (1984) Performance standards for antimicrobial disk susceptibility tests-third edition, National Committee for Laboratory Standards, Villanova, PA

    Google Scholar 

  26. National Committee for Clinical Laboratory Standards (1985) Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. National Committee for Laboratory Standards, Villanova, PA

    Google Scholar 

  27. Neu HC Fu KP (1978) Synergy of azlocillin and mezlocillin combined with aminoglycoside antibiotics and cephalosporins. Antimicrob Agents Chemother 13:813–819

    Google Scholar 

  28. Norden CW, Wentzel H, Keleti E (1979) Comparison of techniques for measurement of in vitro antibiotic synergism. J Infect Dis 140:629–633

    Google Scholar 

  29. Scribner RK, Marks MI, Weber AH, Tarpay MM, Welch DF (1982) Activities of various beta-lactams and aminoglycosides, alone and in combination, against isolates of Pseudomonas aeruginosa from patients with cystic fibrosis. Antimicrob Agents Chemother 21:939–943

    Google Scholar 

  30. Smith CB, Dans PE, Wilfert JN, Finland M (1969) Use of gentamicin in combinations with other antibiotics. J Infect Dis 119:370–377

    Google Scholar 

  31. Spitzer PG, Dliopoulos GM, Karchmer AW, Moellering RW Jr (1988) Synergistic activity between vancomycin or teicoplanin and gentamicin or tobramycin against pathogenic diptheroids. Antimicrob Agents Chemother 1968:286–291

    Google Scholar 

  32. Standiford HC, Kind AC, Kirby WMM (1968) Laboratory and clinical studies of carbenicillin against Gram-negative bacilli. Antimicob Agents Chemother 1968:286–291

    Google Scholar 

  33. Wald ER, Sandiford HC, Tatem BA, Calia FM, Hornick RB (1975) BL-P1654, ticarcillin, and carbenicillin: in vitro comparison alone and in combination with gentamicin against Pseudomonas aeruginosa. Antimicrob Agents Chemother 1968:286–291

    Google Scholar 

  34. Watanakunakorn C (1986) Effects of inoculum size on the activity of carboxy-and ureido-penicillins and effect of combinations of ureido-penicillins with aminoglycosides against resistant Pseudomonas aeruginosa J Antimicrob Chemother 17:91–95

    Google Scholar 

  35. Young LS (1971) Gentamicin: clinical use with carbenicillin and in vitro studies with recent isolates of Pseudomonas aeruginosa J Infect Dis 124:S202-S206

    Google Scholar 

  36. Yu PKW, Edson RS, Washington JA, Hermans PE (1983) Bactericidal and synergistic activity of moxalactam alone and in combination against Pseudomonas aeruginosa. Antimicrob Agents Chemother 23:179–181

    Google Scholar 

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Clark, R.B., Pakiz, C.B. & Hostetter, M.K. Synergistic activity of aminoglycoside-beta-lactam combinations against Pseudomonas aeruginosa with an unusual aminoglycoside antibiogram. Med Microbiol Immunol 179, 77–86 (1990). https://doi.org/10.1007/BF00198528

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  • DOI: https://doi.org/10.1007/BF00198528

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