Susceptibility study of common bacterial isolates in periprosthetic joint infection to manually-mixed fosfomycin compared with gentamicin pre-mixed PMMA bone cement
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Published:
Aug 17, 2019
Keywords:
Susceptibility study fosfomycin gentamicin antibiotic bone cement periprosthetic joint infection
Main Article Content
Abstract
Objective: This study aimed to compare in vitro susceptibility of S. aureus and S. epidermidis, which are common isolates in periprosthetic joint infection, o manually-mixed fosfomycin with, the more commonly used, gentamicin pre-mixed bone cement.
Materials and Methods: Modified disk diffusion technique was performed.Two clinical and 1 laboratory strains of S. aureus and 3 laboratory strains of S. epidermidis were cultured on agar plates. Manually-mixed fosfomycin (4 g fosfomycin in 40 g PMMA) and gentamicin pre-mixed (0.5 g gentamicin in 40.8 g PMMA) bone cement were prepared by using standard sterile mixing technique to produce 6 mm- spherical cement beads. The susceptibility of all bacteria on agar plates were tested against these cement beads. After incubation, the zone of inhibition was measured.
Results: Disk diffusion susceptibility test demonstrated that all 3 strains of standardized S. aureus and S. epidermidis are more susceptible to manually-mixed fosfomycin cement beads than gentamicin pre-mixed beads as shown by the wider inhibition zone of each cement bead on agar plate. The mean difference of inhibition zone of both types of cement beads for S. aureus strain 1, 2 and 3 are 4.65 (3.24, 6.06), 17.33 (16.71, 17.94) and 9.44 (8.63, 10.25), for S. epidermidis strain 1, 2 and 3 are 12.39 (11.74, 13.03), 12.95 (12.93, 12.97) and 11.62 (11.26, 11.98), which are all statistically significant (p<0.01).
Conclusions: The susceptibility of S. aureus and S. epidermidis to manually-mixed fosfomycin cement beads (4 g of fosfomycin in 40 g PMMA) are significantly more than to pre-mixed gentamicin beads (0.5 g gentamicin in 40.8 g PMMA) as demonstrated by in vitro disk diffusion study.
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References
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27. Arciola CR, An YH, Campoccia D, Donati ME, Montanaro L. Etiology of implant orthopedic infections: a survey on 1027 clinical isolates. Int J Artif Organs. 2005; 28(11): 1091-100.
28. Von Eiff C, Arciola CR, Montanaro L, Becker K, Campoccia D. Emerging Staphylococcus species as new pathogens in implant infections. Int J Artif Organs. 2006; 29(4): 360-7.
29. Kaplan JB. Antibiotic-induced biofilm formation. Int J Artif Organs. 2011; 34(9): 737-51.
30. Durbhakula SM, Czajka J, Fuchs MD, Uhl RL. Antibiotic-loaded articulating cement spacer in the 2-stage exchange of infected total knee arthroplasty. J Arthroplasty. 2004; 19: 768-74.
31. Hanssen AD, Spangehl MJ. Practical applications of antibiotic-loaded bone cement for treatment of infected joint replacements. Clin Orthop Relat Res. 2004; 427: 79-85.
32. Springer BD, Lee GC, Osmon D, Haidukewych GJ, Hanssen AD, Jacofsky DJ. Systemic safety of high-dose antibiotic-loaded cement spacers after resection of an infected total knee arthroplasty. Clin Orthop Relat Res. 2004; 427: 47-51.
33. Larikov D, Demian H, Rubin D, Alexander J, Nambiar S. Choice and doses of antibacterial agents for cement spacers in treatment of prosthetic joint infections: review of published studies. Clin Infect Dis. 2012; 55(11): 1474–80.
34. Chang Y, Tai CL, Hsieh PH, Ueng SWN. Gentamicin in bone cement: a potentially more effective prophylactic measure of infection in joint arthroplasty. Bone Joint Res. 2013; 2: 220–6.
35. Sharma D, Douglas J, Coulter C, Weinrauch P, Crawford R. Microbiology of infected arthroplasty: implications for empiric perioperative antibiotic. J Orthop Surg. 2008; 16(3): 339-42.
36. Streuli JC, Exner GU, Reize CL, Merkofer C, Scott CP, Zbinden R. In Vitro Inhibition of Coagulase-Negative Staphylococci by Vancomycin/Aminoglycoside- Loaded Cement Spacers. Infection 2006; 34: 81– 6.
37. Hendlin D, Stapley EO, Jackson M, Wallick H, Miller AK, Wolf FJ, et al. Phosphonomycin. A new antibiotic produced by strains of Streptomyces. Science 1969; 166: 122–3.
38. Michalopoulos AS, Livaditis IG, Gougoutas V. The revival of fosfomycin. Int J of Infect Dis. 2011; 15: e732– 9.
39. Rodrı´guez-Martı´nez JM, Ballesta S, Pascual A. Activity and penetration of fosfomycin, ciprofloxacin, amoxicillin/clavulanic acid and co-trimoxazole in Escherichia coli and Pseudomonas aeruginosa biofilms. Int J Antimicrob Agents 2007; 30: 366–8.
40. Monden K, Ando E, Iida M, Kumon H. Role of fosfomycin in a synergistic combination with ofloxacin against Pseudomonas aeruginosa growing in a biofilm. J Infect Chemother 2002; 8: 218–26.
41. Cai Y, Fan Y, Wang R, An MM, Liang BB. Synergistic effects of aminoglycosides and fosfomycin on Pseudomonas aeruginosa in vitro and biofilm infections in a rat model. J Antimicrob Chemother 2009; 64: 563–6.
42. Masri BA, Duncan CP, Beauchamp CP, Paris NJ, Arntorp J. Effect of varying surface patterns on antibiotic elution from antibiotic-loaded bone cement. J Arthroplasty. 1995; 10(4): 453-9.
43. McLaren AC, Nugent M, Economopoulos K, Kaul H, Vernon BL, McLemore R. Hand-mixed and premixed antibiotic-loaded bone cement have similar homogeneity. Clin Orthop Relat Res. 2009; 467(7): 1693-8.
44. Keuchle DK, Landon GC, Musher DM, Noble PC. Elution of vancomycin, daptomycin and amikacin from acrylic bone cement. Clin Orthop Relat Res. 1991; 264: 302- 8.
45. Adams K, Couch L, Cierny G, Calhoun J, Mader JT. In vitro and in vivo evaluation of antibiotic diffusion from antibiotic-impregnated polymethylmethacrylate beads. Clin Orthop Relat Res. 1992; 278: 244-52.
2. Springer BD, Cahue S, Etkin CD, Lewallen DG, BJMG. Infection burden in total hip and knee arthroplasties: an international registry based perspective. Arthroplasty Today. 2017; 3: 137–40.
3. Bozic KJ, Kamath AF, Ong K, Lau E, Kurtz S, Chan V, et al. Comparative epidemiology of revision arthroplasty: failed THA poses greater clinical and economic burdens than failed TKA. Clin Orthop Relat Res. 2015; 473: 2131–8.
4. Badarudeen S, Shu AC, Ong KL, Baykal D, Lau E, Malkani AL. Complications after revision total hip arthroplasty in the Medicare population. J Arthroplast. 2017; 32: 1954–8.
5. Pulido L, Ghanem E, Joshi A, Purtill JJ, Parvizi J. Periprosthetic joint infection: the incidence, timing, and predisposing factors. Clin Orthop Relat Res. 2008; 466: 1710– 5.
6. Fulkerson E, Della CJ, Wise B, Walsh M, Preston C, Di Cesare PE. Antibiotic susceptibility of bacteria infecting total joint arthroplasty sites. J Bone Joint Surg. 2006; 88A: 1231-7.
7. Arciola CR, An YH, Campoccia D, Donati ME, Montanaro L. Etiology of implant orthopedic infections: a survey on 1027 clinical isolates. Int J Artif Organs. 2005; 28(11):1091–100.
8. Matthews PC, Berendt AR, McNally MA, Byren I. Diagnosis and management of prosthetic joint infection. BMJ. 2009; 338: b1773.
9. Kapadia BH, Berg RA, Daley JA, Fritz J, Bhave A, Mont MA. Periprosthetic joint infection. Lancet. 2016; 387: 386-94.
10. Jaeblon T. Polymethylmethacrylate: properties and contemporary uses in orthopaedics. J Am Acad Orthop Surg. 2010; 18(5): 297-305.
11. Hendriksa JGE, van Hornb JR, van der Meia HC, Busschera HJ. Backgrounds of antibiotic-loaded bone cement and prosthesis-related infection. Biomaterials. 2004; 25: 545–56.
12. Tan HL, Lin WT, Tang TT. The use of antimicrobial-impregnated PMMA to manage periprosthetic infections: controversial issues and the latest developments. Int J Artif Organs. 2012; 35 (10): 832- 9.
13. Anguita-Alonso P, Hanssen AD, Osmon DR, Trampuz A, Steckelberg JM, Patel R. High rate of aminoglycoside resistance among staphylococci causing prosthetic joint infection. Clin Orthop Relat Res. 2005; 439:43–7.
14. Moran E, Masters S, Berendt AR, McLardy-Smith P, Byren I, Atkins BL. Guiding empirical antibiotic therapy in orthopaedics: the microbiology of prosthetic joint infection managed by debridement, irrigation and prosthesis retention. J Infect 2007; 55:1–7.
15. Whittaker JP, Warren RE, Jones RS, Gregson PA. Is prolonged systemic antibiotic treatment essential in two-stage revision hip replacement for chronic Gram-positive infection? J Bone Joint Surg Br. 2009; 91: 44–51.
16. Thornes B, Murray P, Bouchier-Hayes D. Development of resistant strains of Staphylococcus epidermidis on gentamicin-loaded bone cement in vivo. J Bone Joint Surg Br. 2002; 84(5): 758-60.
17. Michalopoulos AS, Livaditis LG, Gougoutas V. The revival of fosfomycin. Int J of Infectious Dis. 2011; 15: e732– 9.
18. Gilbert DN, Chambers HF, Eliopoulos GM, Saag MS, Pana AT. The Sanford guide to antimicrobial therapy, 46th edition. Antimicrobial Therapy, Inc., Sperryville, Virginia. 2016: p76-8.
19. Ribes S, Taberner F, Domenech A, Cabellos C, Tubau F, Lin˜ares J, et al. Evaluation of fosfomycin alone and in combination with ceftriaxone or vancomycin in an experimental model of meningitis caused by two strains of cephalosporin resistant Streptococcus pneumoniae. J Antimicrob Chemother. 2006; 57: 931–6.
20. Banon Arias R, Garcia Lopez M, Pinedo Sanchez A. Time-kill evaluation of antimicrobial regimens against clinical isolates of penicillin-resistant Streptococcus pneumoniae. J Chemother. 2001; 13: 535–40.
21. Allerberger F, Klare I. In-vitro activity of fosfomycin against vancomycin resistant enterococci. J Antimicrob Chemother 1999; 43: 211– 7.
22. Bauer AW, Kirby WMM, Sherris JC, Turck M. Antibiotic susceptibility testing by a standardized single disk method. Am J Clin Pathol. 1966; 45: 493-6.
23. Kuper KM, Boles DM, Mohr JF, Wanger A. Antimicrobial susceptibility testing: A primer for clinicians. Pharmacotherapy. 2009; 29(11): 1326– 43.
24. Bozic KJ, Kurtz SM, Lau E, Ong K, Chiu V, Vail TP, et al. The epidemiology of revision total knee arthroplasty in the United States. Clin Orthop Relat Res. 2010; 468: 45-51.
25. Jafari SM, Coyle C, Mortazavi SM, Sharkey PF, Parvizi J. Revision hip arthroplasty: infection is the most common cause of failure. Clin Orthop Relat Res. 2010; 468: 2046-51.
26. Arciola CR, Campoccia D, Speziale P, Montanaro L, Costerton JW. Biofilm formation in Staphylococcus implant infections. A review of molecular mechanisms and implications for biofilm-resistant materials. Biomaterials. 2012; 33(26): 5967-82.
27. Arciola CR, An YH, Campoccia D, Donati ME, Montanaro L. Etiology of implant orthopedic infections: a survey on 1027 clinical isolates. Int J Artif Organs. 2005; 28(11): 1091-100.
28. Von Eiff C, Arciola CR, Montanaro L, Becker K, Campoccia D. Emerging Staphylococcus species as new pathogens in implant infections. Int J Artif Organs. 2006; 29(4): 360-7.
29. Kaplan JB. Antibiotic-induced biofilm formation. Int J Artif Organs. 2011; 34(9): 737-51.
30. Durbhakula SM, Czajka J, Fuchs MD, Uhl RL. Antibiotic-loaded articulating cement spacer in the 2-stage exchange of infected total knee arthroplasty. J Arthroplasty. 2004; 19: 768-74.
31. Hanssen AD, Spangehl MJ. Practical applications of antibiotic-loaded bone cement for treatment of infected joint replacements. Clin Orthop Relat Res. 2004; 427: 79-85.
32. Springer BD, Lee GC, Osmon D, Haidukewych GJ, Hanssen AD, Jacofsky DJ. Systemic safety of high-dose antibiotic-loaded cement spacers after resection of an infected total knee arthroplasty. Clin Orthop Relat Res. 2004; 427: 47-51.
33. Larikov D, Demian H, Rubin D, Alexander J, Nambiar S. Choice and doses of antibacterial agents for cement spacers in treatment of prosthetic joint infections: review of published studies. Clin Infect Dis. 2012; 55(11): 1474–80.
34. Chang Y, Tai CL, Hsieh PH, Ueng SWN. Gentamicin in bone cement: a potentially more effective prophylactic measure of infection in joint arthroplasty. Bone Joint Res. 2013; 2: 220–6.
35. Sharma D, Douglas J, Coulter C, Weinrauch P, Crawford R. Microbiology of infected arthroplasty: implications for empiric perioperative antibiotic. J Orthop Surg. 2008; 16(3): 339-42.
36. Streuli JC, Exner GU, Reize CL, Merkofer C, Scott CP, Zbinden R. In Vitro Inhibition of Coagulase-Negative Staphylococci by Vancomycin/Aminoglycoside- Loaded Cement Spacers. Infection 2006; 34: 81– 6.
37. Hendlin D, Stapley EO, Jackson M, Wallick H, Miller AK, Wolf FJ, et al. Phosphonomycin. A new antibiotic produced by strains of Streptomyces. Science 1969; 166: 122–3.
38. Michalopoulos AS, Livaditis IG, Gougoutas V. The revival of fosfomycin. Int J of Infect Dis. 2011; 15: e732– 9.
39. Rodrı´guez-Martı´nez JM, Ballesta S, Pascual A. Activity and penetration of fosfomycin, ciprofloxacin, amoxicillin/clavulanic acid and co-trimoxazole in Escherichia coli and Pseudomonas aeruginosa biofilms. Int J Antimicrob Agents 2007; 30: 366–8.
40. Monden K, Ando E, Iida M, Kumon H. Role of fosfomycin in a synergistic combination with ofloxacin against Pseudomonas aeruginosa growing in a biofilm. J Infect Chemother 2002; 8: 218–26.
41. Cai Y, Fan Y, Wang R, An MM, Liang BB. Synergistic effects of aminoglycosides and fosfomycin on Pseudomonas aeruginosa in vitro and biofilm infections in a rat model. J Antimicrob Chemother 2009; 64: 563–6.
42. Masri BA, Duncan CP, Beauchamp CP, Paris NJ, Arntorp J. Effect of varying surface patterns on antibiotic elution from antibiotic-loaded bone cement. J Arthroplasty. 1995; 10(4): 453-9.
43. McLaren AC, Nugent M, Economopoulos K, Kaul H, Vernon BL, McLemore R. Hand-mixed and premixed antibiotic-loaded bone cement have similar homogeneity. Clin Orthop Relat Res. 2009; 467(7): 1693-8.
44. Keuchle DK, Landon GC, Musher DM, Noble PC. Elution of vancomycin, daptomycin and amikacin from acrylic bone cement. Clin Orthop Relat Res. 1991; 264: 302- 8.
45. Adams K, Couch L, Cierny G, Calhoun J, Mader JT. In vitro and in vivo evaluation of antibiotic diffusion from antibiotic-impregnated polymethylmethacrylate beads. Clin Orthop Relat Res. 1992; 278: 244-52.