Formation of Propionibacterium acnes biofilms on orthopaedic biomaterials and their susceptibility to antimicrobials

doi:10.1016/S0142-9612(03)00173-X

Biomaterials

Volume 24, Issue 19, August 2003, Pages 3221-3227

https://doi.org/10.1016/S0142-9612(03)00173-X Get rights and content

Abstract

Failure to treat and eradicate prosthetic hip infection with systemic antibiotic regimens is usually due to the fact that the infection is associated with biofilm formation and that bacterial cells growing within a biofilm exhibit increased resistance to antimicrobial agents. In this in vitro study, we investigated the susceptibility of prosthetic hip Propionibacterium acnes and Staphylococcus spp. isolates growing within biofilms on polymethylmethacrylate (PMMA) bone cement to a range of antibiotics. All P. acnes isolates in the biofilm mode of growth demonstrated considerably greater resistance to cefamandole, ciprofloxacin and vancomycin. In contrast, only four of the eight P. acnes isolates demonstrated an increase in resistance to gentamicin. All ten Staphylococcus spp. isolates in the biofilm mode of growth exhibited large increases in resistance to gentamicin and cefamandole with eight of the ten isolates also exhibiting an increase in resistance to vancomycin. However, only three of the ten Staphylococcus spp. isolates exhibited an increase in resistance to ciprofloxacin. Biofilms were also formed on three different titanium alloys and on PMMA bone cement using P. acnes, Staphylococcus epidermidis and Staphylococcus aureus strains to determine if the underlying biomaterial surface had an effect on biofilm formation and the antimicrobial susceptibility of the bacteria growing within biofilms. Although differences in the rate at which the three strains adhered to the different biomaterials were apparent, no differences in biofilm antibiotic resistance between the biomaterials were observed. In the light of these results, it is important that the efficacy of other antibiotics against P. acnes and Staphylococcus spp. prosthetic hip isolates growing within biofilms on orthopaedic biomaterials be determined to ensure optimal treatment of orthopaedic implant infection.

Introduction

Although total hip replacement has become commonplace in recent years, bacterial infection remains a significant complication following this procedure. In a recent study, in which we combined mild ultrasonication to dislodge the bacteria growing within adherent biofilms on the surface of the removed prosthesis with the use of strict anaerobic techniques, we cultured bacteria from 26 of 120 (22%) retrieved prostheses [1]. Sixteen of the 26 implants (62%) were infected by the anaerobic bacterium, Propionibacterium acnes, either as the single infecting organism (12 implants) or in combination with a Gram-positive coccus (four implants). The results of our study demonstrated for the first time that P. acnes, which when previously isolated had been disregarded as a skin contaminant, is associated with chronic low-grade infection of implanted biomaterials as frequently as Staphylococcus spp.

Attempts to treat prosthetic hip infections using systemic antibiotics usually fail as the infecting bacteria grow predominantly within a confluent biofilm on the surface of the prosthesis, rendering them resistant to currently employed antibiotics. Although previous studies have examined the antimicrobial susceptibility of Staphylococcus epidermidis [2], [3] and Staphylococcus aureus [2], [4], [5] biofilms formed on orthopaedic biomaterials and determined the antimicrobial susceptibility of planktonically grown P. acnes strains isolated from retrieved orthopaedic implants [6], there is a lack of detail with regard to P. acnes biofilm formation. To date, no studies have examined either the formation of P. acnes biofilms on orthopaedic biomaterials or determined the antimicrobial susceptibility of P. acnes strains growing within biofilms.

In this study we investigated P. acnes and Staphylococcus spp. biofilm formation on polymethylmethacrylate (PMMA) bone cement and titanium alloys and determined the susceptibility of these biofilms to a range of antimicrobial agents.

Section snippets

Bacterial strains

Fourteen of the 18 clinical prosthetic hip isolates used in this study (HJ1 to HJ14, Table 2) were isolated as described previously [1], with a further four P. acnes strains (L671, L149, L1958, CK77) which had also been isolated from prosthetic joints kindly supplied by Dr. Carl Kamme, University of Lund, Sweden.

Antimicrobial agents

The following antimicrobial agents were used: Gentamicin sulphate (Sigma Chemical Co. Dorset, UK); cefamandole naftate as Kefadol^® (Dista Products Ltd, Basingstoke, UK); ciprofloxacin

Results

Adherence of the three selected prosthetic hip isolates to the four different biomaterials are shown in Fig. 1. Analysis of variance of the results obtained showed that both biomaterial surface and time exerted a significant effect on adherence of the isolates to the biomaterials. Significant differences were observed in the adherence of P. acnes to each of the biomaterials. P. acnes adherence to TA1 was greater than to the other three biomaterials during the initial 3 h period. However, at 4

Discussion

This study is the first to describe the formation of P. acnes biofilm on different orthopaedic biomaterials and to determine the susceptibility of biofilm-grown P. acnes to a range of antimicrobial agents. The three titanium alloys compared were of the same chemical composition, but all possessed a different surface finish and, therefore, a different surface roughness. The differences in surface finish of the alloys were based on different regions of the femoral component of a prosthetic hip,

Acknowledgments

M.M. Tunney and the work were funded by the Arthritis Research Campaign of the United Kingdom (Project Grant Number P0522); G. Ramage was funded by a Department of Education for Northern Ireland Research Studentship.

The technical assistance of Stef McGrath, School of Pharmacy, The Queen's University of Belfast, is gratefully acknowledged.

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Citation Excerpt :
In contrast to the conventional understanding of infection, whereby bacteria are in a planktonic and metabolically active state, the formation of a biofilm consists of sessile bacterium embedded in an extracellular matrix attached to the surface of a foreign body.3 In vitro, C acnes has been demonstrated to form a mature biofilm within 18-96 hours, and once in this state are significantly less susceptible to antimicrobial agents.58 There is clinical significance associated with C acnes's ability to form a biofilm.
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¹: Current address: Department of Biological Sciences, University of Calgary, 2500 University Drive, NW, Calgary, Alberta, T2N 1N4, UK.

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Biomaterials

Abstract

Introduction

Section snippets

Bacterial strains

Antimicrobial agents

Results

Discussion

Acknowledgments

References (18)

Staphylococcus aureus biofilm formation on different gentamicin-loaded polymethylmethacrylate bone cements

Biomaterials

Surgical biomaterials and differential colonization by Staphylococcus epidermidis

Biomaterials

In vitro bactericidal activities of beta-lactamases, amikacin, and fluoroquinolones against Pseudomonas aeruginosa biofilm in artificial urine

Urology

Pseudomonas aeruginosa biofilms are more susceptible to ciprofloxacin than tobramycin

Int J Antimicrob Agents

Improved detection of infection in hip replacements—a currently underestimated problem

J Bone Jt Surg

Microbial adherence on poly(methyl methacrylate) (PMMA) surfaces

J Biomed Mater Res

Local antibacterial therapy for the management of orthopaedic infections. Pharmacokinetic considerations

Clin Pharmacokinet

Gentamicin release from polymethylmethacrylate bone cements and Staphylococcus aureus biofilm formation

Acta Orthop Scand

Antimicrobial susceptibility of bacteria isolated from orthopedic implants following revision hip surgery

Antimicrob Agents Chemother

Cited by (191)

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Cutibacterium acnes: An emerging pathogen in culture negative bacterial prosthetic valve infective endocarditis (IE)

Bone marrow mesenchymal stem cells offer an immune-privileged niche to Cutibacterium acnes in case of implant-associated osteomyelitis

Cutibacterium acnes in shoulder surgery: a scoping review of strategies for prevention, diagnosis, and treatment