Abstract
Infection is a common complication associated with the use of transcutaneous and implanted medical devices. These infections are generally difficult to treat and frequently require removal of the biomaterial before the infection can be completely eradicated. The presence of a bacterial biofilm recalcitrant to treatment often mediates these infections. We studied the influence of a polycationic protein, protamine sulfate, on the efficacy of the fluoroquinolone ciprofloxacin against a clinical isolate of Pseudomonas aeruginosa. A P. aeruginosa biofilm was developed on 1-cm sections of red rubber catheter material and then treated with various combinations of protamine sulfate and ciprofloxacin. The present work demonstrated that ciprofloxacin in combination with protamine was more effective against biofilms than was ciprofloxacin alone. Protamine sulfate at 50 micrograms/ml combined with antibiotic at 0.5 microgram/ml reduced the number of viable cells by an average of 98.97%, while protamine sulfate at 50 micrograms/ml alone resulted in an average 107.8% increase and antibiotic alone resulted in an average 58.6% reduction after 24 h. Furthermore, protamine sulfate, in combination with ciprofloxacin, inhibited P. aeruginosa in a dose-dependent fashion. It was further observed that treatment with the combination of protamine sulfate and ciprofloxacin had a more drastic effect on planktonic organisms as compared with the P. aeruginosa biofilms; the MBC was reduced to < 0.05 microgram/ml in the presence of 25 micrograms of protamine sulfate per ml. These findings were substantiated by ultrastructure studies of treated cells using scanning and transmission electron microscopy. The synergism between ciprofloxacin and protamine sulfate significantly enhanced the efficacy of ciprofloxacin against planktonic and biofilm P. aeruginosa.
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- Antohi S., Popescu A. Lethal effect of protamine and histone on competent Bacillus subtilis cells. Inhibition of genetic transformation by protamine in sublethal concentration. Mol Gen Genet. 1979 Mar 5;170(3):345–349. doi: 10.1007/BF00267068. [DOI] [PubMed] [Google Scholar]
- Anwar H., Dasgupta M. K., Costerton J. W. Testing the susceptibility of bacteria in biofilms to antibacterial agents. Antimicrob Agents Chemother. 1990 Nov;34(11):2043–2046. doi: 10.1128/aac.34.11.2043. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Anwar H., Strap J. L., Costerton J. W. Eradication of biofilm cells of Staphylococcus aureus with tobramycin and cephalexin. Can J Microbiol. 1992 Jul;38(7):618–625. doi: 10.1139/m92-102. [DOI] [PubMed] [Google Scholar]
- Anwar H., Strap J. L., Costerton J. W. Establishment of aging biofilms: possible mechanism of bacterial resistance to antimicrobial therapy. Antimicrob Agents Chemother. 1992 Jul;36(7):1347–1351. doi: 10.1128/aac.36.7.1347. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Costerton J. W., Khoury A. E., Ward K. H., Anwar H. Practical measures to control device-related bacterial infections. Int J Artif Organs. 1993 Nov;16(11):765–770. [PubMed] [Google Scholar]
- Farber B. F., Kaplan M. H., Clogston A. G. Staphylococcus epidermidis extracted slime inhibits the antimicrobial action of glycopeptide antibiotics. J Infect Dis. 1990 Jan;161(1):37–40. doi: 10.1093/infdis/161.1.37. [DOI] [PubMed] [Google Scholar]
- Furusawa T., Uete T., Kawada T., Kuwahara M., Okuma A. Resistance to cefsulodin and gentamicin in Pseudomonas aeruginosa strains in five areas of Japan between 1980 and 1983. J Antimicrob Chemother. 1986 Jun;17(6):755–762. doi: 10.1093/jac/17.6.755. [DOI] [PubMed] [Google Scholar]
- Giwercman B., Jensen E. T., Høiby N., Kharazmi A., Costerton J. W. Induction of beta-lactamase production in Pseudomonas aeruginosa biofilm. Antimicrob Agents Chemother. 1991 May;35(5):1008–1010. doi: 10.1128/aac.35.5.1008. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gristina A. G. Biomaterial-centered infection: microbial adhesion versus tissue integration. Science. 1987 Sep 25;237(4822):1588–1595. doi: 10.1126/science.3629258. [DOI] [PubMed] [Google Scholar]
- Hooper D. C., Wolfson J. S. Fluoroquinolone antimicrobial agents. N Engl J Med. 1991 Feb 7;324(6):384–394. doi: 10.1056/NEJM199102073240606. [DOI] [PubMed] [Google Scholar]
- Hoyle B. D., Alcantara J., Costerton J. W. Pseudomonas aeruginosa biofilm as a diffusion barrier to piperacillin. Antimicrob Agents Chemother. 1992 Sep;36(9):2054–2056. doi: 10.1128/aac.36.9.2054. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nickel J. C., Ruseska I., Wright J. B., Costerton J. W. Tobramycin resistance of Pseudomonas aeruginosa cells growing as a biofilm on urinary catheter material. Antimicrob Agents Chemother. 1985 Apr;27(4):619–624. doi: 10.1128/aac.27.4.619. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Parsons C. L., Stauffer C., Schmidt J. D. Impairment of antibacterial effect of bladder surface mucin by protamine sulfate. J Infect Dis. 1981 Aug;144(2):180–180. doi: 10.1093/infdis/144.2.180. [DOI] [PubMed] [Google Scholar]
- Selan L., Berlutti F., Passariello C., Comodi-Ballanti M. R., Thaller M. C. Proteolytic enzymes: a new treatment strategy for prosthetic infections? Antimicrob Agents Chemother. 1993 Dec;37(12):2618–2621. doi: 10.1128/aac.37.12.2618. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shand G. H., Anwar H., Kadurugamuwa J., Brown M. R., Silverman S. H., Melling J. In vivo evidence that bacteria in urinary tract infection grow under iron-restricted conditions. Infect Immun. 1985 Apr;48(1):35–39. doi: 10.1128/iai.48.1.35-39.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Suci P. A., Mittelman M. W., Yu F. P., Geesey G. G. Investigation of ciprofloxacin penetration into Pseudomonas aeruginosa biofilms. Antimicrob Agents Chemother. 1994 Sep;38(9):2125–2133. doi: 10.1128/aac.38.9.2125. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Teichman J. M., Abraham V. E., Stein P. C., Parsons C. L. Protamine sulfate and vancomycin are synergistic against Staphylococcus epidermidis prosthesis infection in vivo. J Urol. 1994 Jul;152(1):213–216. doi: 10.1016/s0022-5347(17)32864-1. [DOI] [PubMed] [Google Scholar]