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Antimicrob Agents Chemother. 1995 June; 39(6): 1281–1286.
PMCID: PMC162727

Effects of ciprofloxacin and protamine sulfate combinations against catheter-associated Pseudomonas aeruginosa biofilms.


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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Selected References

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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. [PubMed]
  • Anwar H, Dasgupta MK, Costerton JW. Testing the susceptibility of bacteria in biofilms to antibacterial agents. Antimicrob Agents Chemother. 1990 Nov;34(11):2043–2046. [PMC free article] [PubMed]
  • Anwar H, Strap JL, Costerton JW. Eradication of biofilm cells of Staphylococcus aureus with tobramycin and cephalexin. Can J Microbiol. 1992 Jul;38(7):618–625. [PubMed]
  • Anwar H, Strap JL, Costerton JW. Establishment of aging biofilms: possible mechanism of bacterial resistance to antimicrobial therapy. Antimicrob Agents Chemother. 1992 Jul;36(7):1347–1351. [PMC free article] [PubMed]
  • Costerton JW, Khoury AE, Ward KH, Anwar H. Practical measures to control device-related bacterial infections. Int J Artif Organs. 1993 Nov;16(11):765–770. [PubMed]
  • Farber BF, Kaplan MH, Clogston AG. Staphylococcus epidermidis extracted slime inhibits the antimicrobial action of glycopeptide antibiotics. J Infect Dis. 1990 Jan;161(1):37–40. [PubMed]
  • 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. [PubMed]
  • Giwercman B, Jensen ET, Høiby N, Kharazmi A, Costerton JW. Induction of beta-lactamase production in Pseudomonas aeruginosa biofilm. Antimicrob Agents Chemother. 1991 May;35(5):1008–1010. [PMC free article] [PubMed]
  • Gristina AG. Biomaterial-centered infection: microbial adhesion versus tissue integration. Science. 1987 Sep 25;237(4822):1588–1595. [PubMed]
  • Hooper DC, Wolfson JS. Fluoroquinolone antimicrobial agents. N Engl J Med. 1991 Feb 7;324(6):384–394. [PubMed]
  • Hoyle BD, Alcantara J, Costerton JW. Pseudomonas aeruginosa biofilm as a diffusion barrier to piperacillin. Antimicrob Agents Chemother. 1992 Sep;36(9):2054–2056. [PMC free article] [PubMed]
  • Nickel JC, Ruseska I, Wright JB, Costerton JW. Tobramycin resistance of Pseudomonas aeruginosa cells growing as a biofilm on urinary catheter material. Antimicrob Agents Chemother. 1985 Apr;27(4):619–624. [PMC free article] [PubMed]
  • Parsons CL, Stauffer C, Schmidt JD. Impairment of antibacterial effect of bladder surface mucin by protamine sulfate. J Infect Dis. 1981 Aug;144(2):180–180. [PubMed]
  • Selan L, Berlutti F, Passariello C, Comodi-Ballanti MR, Thaller MC. Proteolytic enzymes: a new treatment strategy for prosthetic infections? Antimicrob Agents Chemother. 1993 Dec;37(12):2618–2621. [PMC free article] [PubMed]
  • Shand GH, Anwar H, Kadurugamuwa J, Brown MR, Silverman SH, Melling J. In vivo evidence that bacteria in urinary tract infection grow under iron-restricted conditions. Infect Immun. 1985 Apr;48(1):35–39. [PMC free article] [PubMed]
  • Suci PA, Mittelman MW, Yu FP, Geesey GG. Investigation of ciprofloxacin penetration into Pseudomonas aeruginosa biofilms. Antimicrob Agents Chemother. 1994 Sep;38(9):2125–2133. [PMC free article] [PubMed]
  • Teichman JM, Abraham VE, Stein PC, Parsons CL. Protamine sulfate and vancomycin are synergistic against Staphylococcus epidermidis prosthesis infection in vivo. J Urol. 1994 Jul;152(1):213–216. [PubMed]

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