Shoulder arthroplasty infections - is implant coating effective?

Is Implant Coating With Tyrosol- and Antibiotic-loaded Hydrogel Effective in Reducing Cutibacterium (Propionibacterium) acnes Biofilm Formation? A Preliminary In Vitro Study

Tyrosol is a quorum-sensing molecule (that is, a molecule that regulates cell-to-cell communication) present in olive oil and produced by Candida albicans. It is an inexpensive natural phenolic compound with substantial antimicrobial/antibiofilm activity against multiple aerobic microorganisms. The authors suggest that this molecule has low cytotoxicity.

These authors examined the in vitro effectiveness of Tyrosol (alone or in combination with antibiotics) in inhibiting Cutibacterium acnes planktonic growth and in reducing C. acnes biofilm formation on roughened titanium alloy disks.

The rationale behind the use of titanium alloy was that this particular biomaterial presents a higher affinity for C. acnes adhesion when compared with stainless steel and cobalt chromium. There is evidence of a correlation between roughness of biomaterials and degree of bacterial attachment.

They found that

(1) Tyrosol was effective in inhibiting C. acnes planktonic (free-floating) growth and that there was synergy with rifampicin.
(2) A hydrogel coating with Tyrosol showed no difference in the inhibition of free-floating (planktonic) C. acnes over control. 

(3) Loaded hydrogel with tyrosol was no more effective than control in reducing C. acnes biofilm formation.
(4) Soluble Tyrosol inhibited biofilm formation compared to control.

They concluded that although the implant coating with hydrogel (either pure or supplemented with antimicrobial agents) did not diminish C. acnes biofilm development in vitro, soluble tyrosol at 597 mg/mL (1 M) exceeded the meaningful biofilm inhibition threshold of 80%.

It is of interest to see the resistance of C. acnes to Clindamycin and Cipro

Comment: The titanium alloy from which most humeral implants are made are known to encourage the formation of Cutibacterium biofilms. The concept of coating implants to prevent these biofilms is of great interest. However, at present an effective coating has yet to be identified.
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Can a 'smart' coating on titanium reduce the risk of infection?

In Vivo Efficacy of a "Smart" Antimicrobial Implant Coating.


These authors explored the use of a "smart" implant coating that combines passive elution of antibiotic with an active-release mechanism that "targets" bacteria in an in vivo mouse model of post-arthroplasty infection.

They designed a biodegradable coating using branched poly(ethylene glycol)-poly(propylene sulfide) (PEG-PPS) polymer to deliver antibiotics both passively and actively. This  PEG-PPS polymer coating can be covalently linked to metal implants.

They used high-performance liquid chromatography (HPLC) quantification to study in vitro release kinetics in conditions representing (a) the physiologic environment and (b) the more oxidative, hyperinflammatory environment of periprosthetic infection. 

They tested the in vivo efficacy of the PEG-PPS coating delivering vancomycin and tigecycline using an established mouse model of post-arthroplasty infection consisting of a medical-grade, 0.8-mm-diameter titanium Kirschner-wire implant, precoated with PEG-PPS, PEG-PPS encapsulating vancomycin, or PEG-PPS encapsulating tigecycline, was surgically placed into the distal aspect of the right femur of the mice, and the joint was challenged with bioluminescent S. aureus Xen36 strain.

They used noninvasive bioluminescence imaging to quantify the bacterial burden; radiography to assess osseointegration and bone resorption; and implant sonication for colony counts.

In vitro-release kinetics confirmed passive elution above the minimum inhibitory concentration (MIC). A rapid release of antibiotic was noted when challenged with an oxidative environment (p < 0.05), confirming a "smart" active-release mechanism. 

The PEG-PPS coating with tigecycline significantly lowered the infection burden on all days, whereas PEG-PPS-vancomycin decreased infection on postoperative day (POD) 1, 3, 5, and 7 (p < 0.05). 

A mean of 0, 9, and 2.6 × 10(2) colony-forming units (CFUs) grew on culture from the implants treated with tigecycline, vancomycin, and PEG-PPS alone, respectively, and a mean of 1.2 × 10(2), 4.3 × 10(3), and 5.9 × 10(4) CFUs, respectively, on culture of the surrounding tissue (p < 0.05).

Implants coated with PEG-PPS alone showed a dramatic degree of periprosthetic osteolysis that became evident by POD 7 and progressed over time. In contrast, antibiotic encapsulated  PEG-PPS implants showed no detectable radiographic periprosthetic osteolysis. 

At 28 days, the control PEG-PPS coated implant was surrounded by osteolytic bone

 in contrast to the implants with tigecycline containing coating

They concluded that PEG-PPS coating provides a promising approach to preventing periprosthetic infection. This polymer is novel in that it combines both passive and active antibiotic-release mechanisms. The tigecycline-based coating outperformed the vancomycin-based coating in this study.

Comment: These authors emphasize the importance of preventing bacteria-containing biofilms on the surfaces of implants. They point to the short-lived effects of topical antibiotics as well as the disadvantages of antibiotic-impregnated cement (polymethylmethacrylate [PMMA]) with a poorly regulated erratic antibiotic release leaving an inert permanent surface for colonization. As an alternative, they pursued a completely biodegradable polymer coating that delivered antibiotics passively and actively stimulated by the reactive oxygen cased initiated by the presence of bacteria.

The authors remind us that at this point their studies have been limited to infection with S. Aureus and not against our 'favorite' bug, Propionibacterium.

Nevertheless they are addressing the key issue of hitting the bacteria before they have a chance to form a biofilm on titanium implants as discussed in this recent post:

Infections with Propionibacterium - the necessity of a surgical implant

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