Current Diagnostic Methods for Periprosthetic Joint Infection

Lee, Ji-Young; Park, Heechul; Bae, Jinyoung; Hyun, Hyanglan; Kim, Sung-Hyun

doi:10.15616/bsl.2022.28.1.1

Cited by 8 publications

(4 citation statements)

References 33 publications

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“…Timely determination of the identity and antibiotic susceptibility profile of contaminating organisms can be crucial in making clinical dosing decisions to combat PJI [53][54][55]. Usually, the minimum inhibitory concentration (MIC) of infecting organisms directs the empirical antibiotic treatment regimens [13,56].…”

Section: Discussionmentioning

confidence: 99%

Investigating the translational value of Periprosthetic Joint Infection (PJI) models to determine the risk and severity of Staphylococcal biofilms

Sekar,

Fan,

Tierney

et al. 2024

Preprint

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With the advent of antibiotic-eluting polymeric materials for targeting recalcitrant infections, using preclinical models to study biofilm is crucial for improving the treatment efficacy in periprosthetic joint infections. The stratification of risk and severity of infections is needed to develop an effective clinical dosing framework with better outcomes. Here, using in-vivo and in-vitro implant-associated infection models, we demonstrate that methicillin-sensitive and resistant Staphylococcus aureus (MSSA and MRSA) have model-dependent distinct implant and peri-implant tissue colonization patterns. The maturity of biofilms and the location (implant vs tissue) were found to influence the antibiotic susceptibility evolution profiles of MSSA and MRSA, and the models were able to capture the differing host-microbe interactions in vivo. Gene expression studies revealed the molecular heterogeneity of colonizing bacterial populations. The comparison and stratification of the risk and severity of infection across different preclinical models provided in this study can aid in guiding clinical dosing to effectively prevent or treat PJI.

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Section: Discussionmentioning

confidence: 99%

Investigating the translational value of Periprosthetic Joint Infection (PJI) models to determine the risk and severity of Staphylococcal biofilms

Sekar,

Fan,

Tierney

et al. 2024

Preprint

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“…In ‘chronic’ cases, the clinical manifestation is less clear where the patient may have some pain or discomfort without overt signs [ 8 ]. The current consensus is focused on using thresholds for systemic markers such as C-reactive protein and combining the results of blood tests such as that for leukocyte esterase to guide diagnosis and treatment decisions [ 9 , 10 ]. The gold-standard approach is two-stage revision surgery which removes all implants followed by a period with intravenous (IV) antibiotics and an antibiotic-eluting bone cement spacer protecting the joint space in the meantime.…”

Section: Introductionmentioning

confidence: 99%

Synergistic use of anti-inflammatory ketorolac and gentamicin to target staphylococcal biofilms

Sekar,

Gil,

Tierney

et al. 2024

J Transl Med

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Background While antibiotics remain our primary tools against microbial infection, increasing antibiotic resistance (inherent and acquired) is a major detriment to their efficacy. A practical approach to maintaining or reversing the efficacy of antibiotics is the use of other commonly used therapeutics, which show synergistic antibacterial action with antibiotics. Here, we investigated the extent of antibacterial synergy between the antibiotic gentamicin and the anti-inflammatory ketorolac regarding the dynamics of biofilm growth, the rate of acquired resistance, and the possible mechanism of synergy. Methods Control (ATCC 12600, ATCC 35984) and clinical strains (L1101, L1116) of Staphylococcus aureus and Staphylococcus epidermidis with varying antibiotic susceptibility profiles were used in this study to simulate implant-material associated low-risk and high-risk biofilms in vitro. The synergistic action of gentamicin sulfate (GS) and ketorolac tromethamine (KT), against planktonic staphylococcal strains were determined using the fractional inhibitory concentration measurement assay. Nascent (6 h) and established (24 h) biofilms were grown on 316L stainless steel plates and the synergistic biofilm eradication activity was determined and characterized using adherent bacteria count, minimum biofilm eradication concentration (MBEC) measurement for GS, visualization by live/dead imaging, scanning electron microscopy, gene expression of biofilm-associated genes, and bacterial membrane fluidity assessment. Results Gentamicin-ketorolac (GS-KT) combination demonstrated synergistic antibacterial action against planktonic Staphylococci. Control and clinical strains showed distinct biofilm growth dynamics and an increase in biofilm maturity was shown to confer further resistance to gentamicin for both ‘low-risk’ and ‘high-risk’ biofilms. The addition of ketorolac enhanced the antibiofilm activity of gentamicin against acquired resistance in staphylococcal biofilms. Mechanistic studies revealed that the synergistic action of gentamicin–ketorolac interferes with biofilm morphology and subverts bacterial stress response altering bacterial physiology, membrane dynamics, and biofilm properties. Conclusion The results of this study have a significant impact on the local administration of antibiotics and other therapeutic agents commonly used in the prevention and treatment of orthopaedic infections. Further, these results warrant the study of synergy for the concurrent or sequential administration of non-antibiotic drugs for antimicrobial effect.

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“…In ‘chronic’ cases, the clinical manifestation is less clear where the patient may have some pain or discomfort without overt signs. The current consensus is focused on using thresholds for systemic markers such as C-reactive protein and combining the results of blood tests such as that for leukocyte esterase to guide diagnosis and treatment decisions( 8 , 9 ). The gold-standard approach is two-stage revision surgery which removes all implants followed by a period with intravenous (IV) antibiotics and an antibiotic-eluting bone cement spacer protecting the joint space in the meantime.…”

Section: Introductionmentioning

confidence: 99%

Synergistic use of anti-inflammatory ketorolac and gentamicin to target staphylococcal biofilms

Sekar,

Gil,

Tierney

et al. 2023

Preprint

View full text Add to dashboard Cite

Background While antibiotics remain our primary tools against microbial infection, increasing antibiotic resistance (inherent and acquired) is a major detriment to their efficacy. A practical approach to maintaining or reversing the efficacy of antibiotics is the use of other commonly used therapeutics, which show synergistic antibacterial action with antibiotics. Here, we investigated the extent of antibacterial synergy between the antibiotic gentamicin and the anti-inflammatory ketorolac regarding the dynamics of biofilm growth, the rate of acquired resistance, and the possible mechanism of synergy. Methods Control (ATCC 12600, ATCC 35984) and clinical strains (L1101, L1116) of S. aureus and S. epidermidis with varying antibiotic susceptibility profiles were used in this study to simulate implant-material associated low-risk and high-risk biofilms in vitro. The synergistic action of gentamicin sulfate (GS) and ketorolac tromethamine (KT), against planktonic staphylococcal strains were determined using the fractional inhibitory concentration measurement assay. Nascent (6hr) and established (24hr) biofilms were grown on 316 stainless steel plates and the synergistic biofilm eradication activity was determined and characterized using adherent bacteria count, MBEC measurement for GS, gene expression of biofilm-associated genes, visualization by live/dead imaging, scanning electron microscopy, and bacterial membrane fluidity assessment. Results Gentamicin-ketorolac combination demonstrated synergistic antibacterial action against planktonic Staphylococci. Control and clinical strains showed distinct biofilm growth dynamics and an increase in biofilm maturity was shown to confer further resistance to gentamicin for both ‘low-risk’ and ‘high-risk’ biofilms. The addition of ketorolac enhanced the antibiofilm activity of gentamicin against acquired resistance in staphylococcal biofilms. Mechanistic studies revealed that the synergistic action of gentamicin-ketorolac interferes with biofilm morphology and subverts bacterial stress response altering bacterial physiology, membrane dynamics, and biofilm properties. Conclusion The results of this study have a significant impact on the local administration of antibiotics and other therapeutic agents commonly used in the prevention and treatment of orthopaedic infections. Further, these results warrant the study of synergy for the concurrent or sequential administration of non-antibiotic drugs for antimicrobial effect.

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Current Diagnostic Methods for Periprosthetic Joint Infection

Cited by 8 publications

References 33 publications

Investigating the translational value of Periprosthetic Joint Infection (PJI) models to determine the risk and severity of Staphylococcal biofilms

Investigating the translational value of Periprosthetic Joint Infection (PJI) models to determine the risk and severity of Staphylococcal biofilms

Synergistic use of anti-inflammatory ketorolac and gentamicin to target staphylococcal biofilms

Synergistic use of anti-inflammatory ketorolac and gentamicin to target staphylococcal biofilms

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