The Clinical Outcome of Early Periprosthetic Joint Infections Caused by Staphylococcus epidermidis and Managed by Surgical Debridement in an Era of Increasing Resistance

Shabana, Nada S.; Seeber, Gesine H; Soriano, Álex; Jutte, Paul C.; Westermann, Silvia; Mithoe, Glenn; Pirii, Loredana; Siebers, Théke; Have, Bas ten; Zijlstra, Wierd P; Lazovic, Djordje; Wouthuyzen-Bakker, Marjan

doi:10.3390/antibiotics12010040

Cited by 10 publications

(7 citation statements)

References 26 publications

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“…Resistance is also a major concern in the treatment of CoNS and varies in its prevalence, even when comparing similar populations [34]. Shabana et al highlight the possible need for adjustments in treatments when facing PJIs caused by resistant CoNS [35]. One-third of all CoNS included in this study were resistant to rifampicin, which is in line with previous findings [36].…”

Section: Discussionsupporting

confidence: 85%

Incidence of Rifampicin Resistance in Periprosthetic Joint Infection: A Single-Centre Cohort Study on 238 Patients

Lazarinis,

Hailer,

Järhult

et al. 2023

Antibiotics

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Background. Rifampicin is a pillar in the treatment of periprosthetic joint infection (PJI). However, rifampicin resistance is an increasing threat to PJI treatment. This study explores the incidence of rifampicin-resistant bacteria over time in a Swedish tertiary referral centre and the association of rifampicin resistance with infection-free survival after PJI. Methods. The study included 238 staphylococcal PJIs treated between 2001 and 2020 for which susceptibility data for rifampicin were available. Data on causative bacteria, rifampicin resistance, treatment, and outcome were obtained. Kaplan–Meier survival analysis and Cox regression modelling estimated the infection-free cumulative survival and adjusted hazard ratios (HRs) for the risk of treatment failure. Results. Rifampicin-resistant causative bacteria were identified in 40 cases (17%). The proportion of rifampicin-resistant agents decreased from 24% in 2010–2015 to 12% in 2016–2020. The 2-year infection-free survival rates were 78.6% (95% CI, 66.4–93.1%) for the rifampicin-resistant group and 90.0% (95% CI, 85.8–94.4%) for the rifampicin-sensitive group. Patients with PJI caused by rifampicin-resistant bacteria had an increased risk of treatment failure (adjusted HR, 4.2; 95% CI, 1.7–10.3). Conclusions. The incidence of PJI caused by rifampicin-resistant bacteria did not increase over the past 20 years. The risk of treatment failure in PJI caused by rifampicin-resistant bacteria is more than four times that caused by rifampicin-sensitive bacteria, highlighting the importance of limiting the development of rifampicin resistance.

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Section: Discussionsupporting

confidence: 85%

Incidence of Rifampicin Resistance in Periprosthetic Joint Infection: A Single-Centre Cohort Study on 238 Patients

Lazarinis,

Hailer,

Järhult

et al. 2023

Antibiotics

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“…While some bacteria produce toxins and several other virulence factors, the commensal skin bacterium Staphylococcus epidermidis (S. epidermidis) relies primarily on biofilm formation to support its existence in the human body. Thanks to its ability to form biofilm, S. epidermidis is a major cause of catheter-related bloodstream infections (2) and serious implant-associated infections such as prosthetic valve endocarditis (3), cardiac implantable electronic device infection (4) and prosthetic joint infection (5,6). Due to high rates of resistance to several classes of antimicrobials, treatment failure is high in prosthetic joint infections (6).…”

Section: Introductionmentioning

confidence: 99%

“…Thanks to its ability to form biofilm, S. epidermidis is a major cause of catheter-related bloodstream infections (2) and serious implant-associated infections such as prosthetic valve endocarditis (3), cardiac implantable electronic device infection (4) and prosthetic joint infection (5,6). Due to high rates of resistance to several classes of antimicrobials, treatment failure is high in prosthetic joint infections (6).…”

Section: Introductionmentioning

confidence: 99%

Extracellular G-quadruplex and Z-DNA protect biofilms from DNase I and forms a DNAzyme with peroxidase activity

Minero,

Møllebjerg,

Thiesen

et al. 2023

Preprint

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Many bacteria form biofilms to protect themselves from predators or stressful environmental conditions. In the biofilm, bacteria are embedded in a protective extracellular matrix composed of polysaccharides, proteins and extracellular DNA (eDNA). eDNA most often arises from lysed cells, and it is the only matrix component most biofilms appear to have in common. However, little is known about the form DNA takes in the extracellular space, and how different non-canonical DNA structures such as Z-DNA or G-quadruplex formation might contribute to its function in the biofilm. The aim of this study was to determine if non-canonical DNA structures form in eDNA-rich staphylococcal biofilms, and if these structures protect the biofilm from degradation by nucleases. We grew Staphylococcus epidermidis biofilms in laboratory media amended with hemin and NaCl to stabilize secondary DNA structures and visualized their location by immunolabelling and fluorescence microscopy. We furthermore visualized the macroscopic biofilm structure by optical coherence tomography. We developed assays to quantify degradation of Z-DNA and G-quadruplex DNA oligos by different nucleases, and subsequently investigated how these enzymes affected eDNA in the biofilms. Z-DNA and G-quadruplex DNA were abundant in the biofilm matrix, and were often present in a web-like structure in biofilms grown in vitro and in vivo using a murine implant-associated osteomyelitis model. In vitro, the structures did not form in the absence of NaCl or mechanical shaking during biofilm growth, or in bacterial strains deficient in eDNA or exopolysaccharide production. We thus infer that eDNA and polysaccharides interact, leading to non-canonical DNA structures under mechanical stress when stabilized by salt, and we confirmed that G-quadruplex DNA and Z-DNA was also present in biofilms from infected implants. Mammalian DNase I lacked activity against Z-DNA and G-quadruplex DNA, while Micrococcal nuclease could degrade G-quadruplex DNA and S1 Aspergillus nuclease could degrade Z-DNA. Micrococcal nuclease, which originates from Staphylococcus aureus, may thus be key for dispersal of biofilm in staphylococci. In addition to its structural role, we show for the first time that the eDNA in biofilms forms a DNAzyme with peroxidase-like activity in the presence of hemin. While peroxidases are part of host defenses against pathogens, we now show that biofilms can possess intrinsic peroxidase activity in the extracellular matrix.

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“…While some bacteria produce toxins and several other virulence factors, the commensal skin bacterium Staphylococcus epidermidis relies primarily on biofilm formation to support its existence in the human body. Thanks to its ability to form a biofilm, S. epidermidis is a major cause of catheter-related bloodstream infections ( 2 ) and serious implant-associated infections such as prosthetic valve endocarditis ( 3 ), cardiac implantable electronic device infection ( 4 ) and prosthetic joint infection ( 5 , 6 ). Due to high rates of resistance to several classes of antimicrobials, treatment failure is high in prosthetic joint infections ( 6 ).…”

Section: Introductionmentioning

confidence: 99%

Extracellular G-quadruplexes and Z-DNA protect biofilms from DNase I, and G-quadruplexes form a DNAzyme with peroxidase activity

Minero,

Møllebjerg,

Thiesen

et al. 2024

Nucleic Acids Research

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Many bacteria form biofilms to protect themselves from predators or stressful environmental conditions. In the biofilm, bacteria are embedded in a protective extracellular matrix composed of polysaccharides, proteins and extracellular DNA (eDNA). eDNA most often is released from lysed bacteria or host mammalian cells, and it is the only matrix component most biofilms appear to have in common. However, little is known about the form DNA takes in the extracellular space, and how different non-canonical DNA structures such as Z-DNA or G-quadruplexes might contribute to its function in the biofilm. The aim of this study was to determine if non-canonical DNA structures form in eDNA-rich staphylococcal biofilms, and if these structures protect the biofilm from degradation by nucleases. We grew Staphylococcus epidermidis biofilms in laboratory media supplemented with hemin and NaCl to stabilize secondary DNA structures and visualized their location by immunolabelling and fluorescence microscopy. We furthermore visualized the macroscopic biofilm structure by optical coherence tomography. We developed assays to quantify degradation of Z-DNA and G-quadruplex DNA oligos by different nucleases, and subsequently investigated how these enzymes affected eDNA in the biofilms. Z-DNA and G-quadruplex DNA were abundant in the biofilm matrix, and were often present in a web-like structures. In vitro, the structures did not form in the absence of NaCl or mechanical shaking during biofilm growth, or in bacterial strains deficient in eDNA or exopolysaccharide production. We thus infer that eDNA and polysaccharides interact, leading to non-canonical DNA structures under mechanical stress when stabilized by salt. We also confirmed that G-quadruplex DNA and Z-DNA was present in biofilms from infected implants in a murine implant-associated osteomyelitis model. Mammalian DNase I lacked activity against Z-DNA and G-quadruplex DNA, while Micrococcal nuclease could degrade G-quadruplex DNA and S1 Aspergillus nuclease could degrade Z-DNA. Micrococcal nuclease, which originates from Staphylococcus aureus, may thus be key for dispersal of biofilm in staphylococci. In addition to its structural role, we show for the first time that the eDNA in biofilms forms a DNAzyme with peroxidase-like activity in the presence of hemin. While peroxidases are part of host defenses against pathogens, we now show that biofilms can possess intrinsic peroxidase activity in the extracellular matrix.

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The Clinical Outcome of Early Periprosthetic Joint Infections Caused by Staphylococcus epidermidis and Managed by Surgical Debridement in an Era of Increasing Resistance

Cited by 10 publications

References 26 publications

Incidence of Rifampicin Resistance in Periprosthetic Joint Infection: A Single-Centre Cohort Study on 238 Patients

Incidence of Rifampicin Resistance in Periprosthetic Joint Infection: A Single-Centre Cohort Study on 238 Patients

Extracellular G-quadruplex and Z-DNA protect biofilms from DNase I and forms a DNAzyme with peroxidase activity

Extracellular G-quadruplexes and Z-DNA protect biofilms from DNase I, and G-quadruplexes form a DNAzyme with peroxidase activity

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