OBJECTIVES:Perioperative antibiotic prophylaxis is crucial for preventing detrimental postoperative prosthetic joint infections (PJIs). Guidelines aim to prevent infection with methicillin-susceptible staphylococci-in Sweden through administering cloxacillin, at fixed doses with minimal consideration to kidney function or patient weight. Over- and under-dosing could have adverse effects, negative effects on the microbiome, or increase the risk of PJI. We aimed primarily to evaluate whether the current uniform prophylactic regimen of cloxacillin in hip and knee arthroplasty is adequate. PATIENTS AND METHODS:Patients subjected to elective prosthetic joint surgery (N = 204) were included in a prospective study. Free plasma concentrations of cloxacillin were measured on three occasions throughout arthroplasty surgery. Samples were analysed using a validated HPLC-MS/MS method. A free concentration of <2 mg/L was deemed a theoretically appropriate concentration to suppress growth of methicillin-susceptible staphylococci in bone. A sensitivity analysis with values of 1 and 4 mg/L was included. RESULTS:Potentially subtherapeutic concentrations (≤2 mg/L) at the end of surgery were found in 31 cases (15%). The corresponding numbers for 1 and 4 mg/L were 3 and 88 (1% and 43%). In multivariable logistic regression analysis, an ASA (American Association of Anesthesiologists physical status) score of I (relatively healthy patients), estimated glomerular filtration rate >90 mL/min/1.73 m2, body weight >100 kg and long duration of surgery significantly predicted suboptimal concentrations. CONCLUSIONS:Current cloxacillin dosing in hip and knee arthroplasty surgery results in a risk for subtherapeutic levels in patients with high body weight and preserved renal function. Therefore, dosing guidelines for cloxacillin prophylaxis in arthroplasty should be reviewed.

BACKGROUND AND OBJECTIVES:Dalbavancin, a lipoglycopeptide with a half-life of 150-200 h, is a promising treatment option for prosthetic joint infections (PJIs) and other orthopaedic implant-associated infections (IAIs) caused by multidrug-resistant staphylococci. However, in vitro studies have shown that when exposed to low concentrations of dalbavancin, staphylococcal strains resistant to dalbavancin can emerge, potentially affecting its effectiveness in cases of recurrent infection. To investigate whether dalbavancin-resistant staphylococci emerge in vivo following long-term dalbavancin treatment for PJIs or orthopaedic IAIs. PATIENTS AND METHODS:Nineteen patients who had received long-term dalbavancin treatment (≥12 weeks) following PJI or orthopaedic IAI and 25 control patients scheduled for elective prosthetic joint surgery were sampled from the nares and perineum. Each sample was subcultured on Mueller-Hinton II agar plates containing various concentrations of dalbavancin (0.0, 0.125, 0.5, and 2.0 mg/L). The growth of staphylococcal colonies was analysed using MALDI-TOF, and the MIC values of dalbavancin were determined using the gradient test method. RESULTS:Among dalbavancin-treated patients, 4 out of 19 displayed staphylococcal species resistant to dalbavancin (MIC value >0.25 mg/L according to EUCAST breakpoint tables). These four were all Staphylococcus epidermidis isolates, three from the nares and one from the perineum, and displayed MIC values of 0.38, 0.38, 0.5, and 0.75 mg/L. No resistant staphylococci were detected in the samples from the control group (P = 0.029, Fisher's exact test). CONCLUSIONS:The present study demonstrated the emergence of dalbavancin-resistant staphylococci following long-term treatment.

Background Staphylococcus epidermidis is a ubiquitous member of the healthy skin and mucous microbiota but is also an opportunistic pathogen responsible for various infections, often treated with antibiotics like rifampicin. Resistance to rifampicin in S. epidermidis arises primarily through nonsynonymous mutations in the rpoB gene. Objectives To investigate the prevalence of rpoB mutations and their association with phenotypic rifampicin resistance in clinical S. epidermidis isolates from Denmark, France, and Sweden. Methods All clinical isolates (N = 942) were whole-genome sequenced to identify mutations in rpoB and subsequently linked to phenotypic rifampicin resistance based on antimicrobial susceptibility testing. Results A total of 64 (6.8%) isolates were resistant to rifampicin. They carried all mutational changes in the rifampicin resistance-determining region (RRDR). Among 12 identified nonsynonymous mutations, 11 were exclusively observed in resistant strains, including novel mutations not previously described in S. epidermidis. Conclusions This study highlights the diverse genetic variants of rpoB associated with rifampicin resistance in clinical S. epidermidis isolates, including novel mutations. The strong correlation between mutational changes in RRDR and phenotypic resistance reinforces the role of rpoB mutations as a primary mechanism of resistance in clinical isolates.

Hematogenous prosthetic joint infections (PJIs) are primarily associated with Staphylococcus aureus, and there is a 30%-40% risk of contracting a hematogenous PJI following an S. aureus bacteremia. The aim of this study was to investigate whether identical strains of S. aureus were present in each patient from a cohort with both bacteremia and PJI and to explore the genomic differences between paired isolates obtained from blood cultures and tissue biopsies. All patients with a PJI and a temporally concomitant bacteremia due to S. aureus from 2005 to 2020 were included. Paired isolates of S. aureus from tissue biopsies and blood cultures were subjected to whole-genome sequencing. Twenty-four episodes of PJI were identified in 23 patients. All pairwise isolates from individual patients belonged to the same multilocus sequence type, clonal complex, and core genome multilocus sequence typing (cgMLST) complex type. The median number of single nucleotide polymorphisms (SNPs) in the conserved core genomes between the pairwise isolates was 3. In conclusion, identical cgMLST complex types and low levels of SNP differences between paired isolates of S. aureus from blood cultures and tissue biopsies suggest hematogenous seeding in all cases of PJI in this cohort.

BACKGROUND:Recent studies have reported an increasing prevalence of penicillin-susceptible Staphylococcus aureus (PSSA) worldwide. The reliability of disc diffusion testing for detecting penicillin-resistance has been questioned, and the molecular epidemiology of PSSA has not been studied to the same extent as that of MRSA strains. OBJECTIVES:To investigate the reliability of the disc diffusion method for detecting penicillin-resistance in S. aureus, and to examine the prevalence and molecular epidemiology of PSSA in bloodstream infections. METHODS:A total of 258 bacteraemic isolates obtained from one geographic region in Sweden during 2018-2019 were analysed using the disc diffusion test to detect penicillin-resistance, and genome sequenced to examine the prevalence of the blaZ gene and the molecular epidemiology of PSSA. RESULTS:Phenotypic susceptibility to penicillin correlated strongly with the absence of the blaZ gene, with nearly 98% concordance. The prevalence of PSSA among patients with bacteraemia was 35.1%, highlighting the need for penicillin-susceptibility testing. Additionally, population structure analyses revealed substantial genetic diversity, underscoring the complexity of the PSSA epidemiology. The PSSA belonged to diverse clonal lineages, with CC5 and CC45 dominating our cohort, similar to findings in Spain, Australia, and other parts of Sweden. However, our study revealed a higher prevalence of CC12 compared with other regions, underscoring the importance of local epidemiological surveillance. CONCLUSIONS:These findings validate the reliability of EUCAST's disc diffusion method, showing a high prevalence of PSSA, and provide insight into the genetic underpinnings of penicillin-susceptibility in S. aureus.

Corynebacterium is a widespread and abundant bacterial genus on human skin. Occasionally, corynebacteria are isolated from clinical specimens associated with infection. In this study, 56 bacterial isolates were examined. These isolates were obtained from 52 patients with diverse infections such as keratitis, osteitis/osteomyelitis, mastitis, (suspected) foreign body associated infections (spine, prosthetic joint), suspected meningitis, post-operative infections, among others. These isolates were identified as corynebacteria by MALDI-TOF mass spectrometry but could not be reliably assigned to a specific species. To resolve this issue, the isolates were genome-sequenced, and species identification was done with different approaches, including digital DNA–DNA hybridization, phylogenomic tree placement and Average Nucleotide Identity (ANI) calculations. A subset of 34 strains was further investigated by biochemical characterization and antimicrobial susceptibility testing (AST). The 56 isolates belonged to 28 distinct corynebacterial species. Species identification was particularly ambiguous for 13 isolates as the ANIs were below 95

To describe the clinical characteristics of exogenous episodes of endophthalmitis from which Staphylococcus epidermidis was isolated by vitreous cultures. We also explored the genomic traits of these S. epidermidis isolates and their relatedness to S. epidermidis originating from carriers and from prosthetic joint infections in the same geographical region. S. epidermidis isolated from cases of exogenous endophthalmitis (n = 33) were genome sequenced. Clinical features were retrospectively collected from medical records. The isolates were compared with previously sequenced S. epidermidis isolates from the nares of healthy individuals (n = 151) and from prosthetic joint infections (n = 138). The most common ophthalmological procedure preceding the endophthalmitis was a posterior segment surgery (76

BACKGROUND AND OBJECTIVES:Staphylococcus epidermidis is a major cause of prosthetic joint infections (PJIs). Multidrug resistant (MDR), hospital-adapted clones constitute most cases globally, though regional differences in lineage dissemination likely exist. The aim was to explore the population structure of S. epidermidis from PJIs in Sweden and France, with a focus on the presence of antimicrobial resistance (AMR). METHODS:This study included genome sequence data from 191 clinical S. epidermidis isolates collected from patients with PJI in central Sweden (2007-16; n = 138) and the Lyon region in France (2015-20; n = 53). RESULTS:Hospital-adapted lineages with a high burden of AMR dominated the cases in both countries. However, the ST2 lineage was significantly more prevalent in Sweden (43% versus 11% in France), while ST5 and ST87 were more common in France (55% versus 10% in Sweden). ST215 was only present in Sweden (25%). A significantly higher prevalence of streptogramin resistance genes [vat(B), vga(A), vga(B)] was found in French (26%) versus Swedish (2%) isolates. These genes were present in all ST87 isolates and in 20% of the French ST5 isolates. The erm(C) gene (resistance to streptogramin A, macrolides and lincosamides) was also more common in the French isolates (77% versus 55% of Swedish isolates), and so was the fusidic acid resistance gene fusB (France: 66%, Sweden: 39%). CONCLUSIONS:This study highlights significant regional differences in S. epidermidis variants causing PJI. Despite similar MDR levels, certain AMR genes, particularly those related to streptogramin resistance, were significantly more prevalent among French isolates. This suggests that S. epidermidis undergoes local adaptation to region-specific antibiotic usage.

International guidelines for Staphylococcus aureus vertebral osteomyelitis recommend 6 weeks of treatment, including oral follow-up using antibiotics with high bioavailability such as a fluoroquinolone/rifampicin combination. Oral flucloxacillin is not recommended due to low bioavailability and scarce evidence. However, flucloxacillin as oral follow-up treatment is common practice in Sweden based on favourable clinical experience, good tolerability, few interactions, and low ecological impact. Our aim was to review a single-centre experience of S. aureus vertebral osteomyelitis, with focus on flucloxacillin treatment. A single-centre retrospective cohort of patients with Staphylococcus aureus vertebral osteomyelitis (n = 40) was identified between 2010 and 2016. Patients were further stratified by antibiotic treatment strategy with focus on oral flucloxacillin therapy (n = 24). Primary outcomes were relapse or death within 12 months of treatment initiation, and antibiotic-related adverse effects during treatment. Methicillin-susceptible S. aureus (MSSA) caused 38 of the infections (95

INTRODUCTION:Dalbavancin is a lipoglycopeptide with an exceptionally long half-life that allows simplified administration, which may be of value in long-term treatment of bone and joint infections, such as prosthetic joint infections (PJIs). The objective was to determine trough (Cmin) values of dalbavancin during long-term PJI treatment according to the recommendation of the Swedish National Guidelines for Bone and Joint Infections: a loading dose of 1,500 mg on day 1 and another 1,500 mg on days 8-14, followed by day 28 administration of 1,000 mg every two weeks or 500 mg per week. PATIENTS/METHODS:Twelve patients with PJI treated with at least six doses of dalbavancin were prospectively followed up, serum samples were collected, and renal function was investigated. Dalbavancin concentrations were measured using ultra-high pressure liquid chromatography coupled with unispray tandem mass spectrometry (UHPLC-MS/MS). RESULTS:The median serum concentration (Cmin) 14 days after the first 1,500 mg dose was 36.3 mg/L (range: 6.6-62.4 mg/L). The median trough value at the date of the last given dose (1,000 mg) after a total of 6-7 doses was 53.6 mg/L (range: 32.0-97.5 mg/L). Three patients showed a tendency towards successive accumulation of dalbavancin during treatment. None of the patients showed any significant impairment in renal function. CONCLUSIONS:Therapeutic drug monitoring during long-term dalbavancin treatment is recommended to avoid the risk of accumulation and unnecessarily high trough levels. In many cases, such monitoring can allow the dosing interval to be extended.

Surgical site infection (SSI) and antimicrobial resistance are a worldwide problem affecting patient safety. It is lacking randomised controlled trials (RCT) regarding how the number of personnel in the operating room (OR) affects the air quality. We aimed to investigate the effect the number of personnel in the OR have on bacterial air contamination during the preparation of sterile surgical goods, to identify the species and antibiotic susceptibility of the bacteria isolated, and to describe the number of SSIs together with causative microorganisms. This RCT used an intervention group in which two individuals prepared the surgical goods and a control group in which five individuals prepared the goods. Bacteria were isolated on aerobic and anaerobic plates, and bacterial growth was measured as colony forming units (CFU). All isolates were typed, and types known to cause SSI were tested for susceptibility to eight antibiotics. Data were analysed with the Mann-Whitney U test, the chi-square test, or Fisher’s exact test. Results were based on 69 open-heart surgeries and 414 plates. When sterile surgical goods were prepared with two personnel, the median CFU was 2 with an IQR of 2, compared with five personnel, the median CFU was 5, with an IQR of 5 (p < 0.001). The 272 CFU represented 45 different bacterial species, with 38 species isolated in the control group and 21 in the intervention group. The most frequently isolated bacteria were Cutibacterium acnes (82/272, 30 ClinicalTrials.Gov (NCT05597072).

Background CoNS constitute a significant part of the human microbiota of skin and mucous membranes. They can cause nosocomial infections, and have shown decreased susceptibility to several antibiotics. The few remaining treatment options include (lipo)glycopeptides such as dalbavancin. However, there is a lack of knowledge concerning whether susceptibility to lipoglycopeptides varies between different species of CoNS. Objectives To determine the susceptibility to dalbavancin in different species of CoNS. Methods We investigated 480 bacterial isolates from 10 CoNS species: Staphylococcus epidermidis, Staphylococcus capitis, Staphylococcus caprae, Staphylococcus haemolyticus, Staphylococcus lugdunensis, Staphylococcus warneri, Staphylococcus pettenkoferi, Staphylococcus hominis, Staphylococcus sciuri and Staphylococcus simulans. The isolates were randomly selected from different sources of infection, including blood isolates, as well as deep and superficial infections. Antibiotic susceptibility was tested with the gradient test method. Results There was a statistically significant difference (ANOVA; P < 0.0001) in the MIC distribution for dalbavancin between different CoNS species. S. sciuri was the least susceptible species, with 90% of the isolates having an MIC value for dalbavancin above the EUCAST breakpoint of 0.125 mg/L. The lowest MIC90 values were seen for S. capitis, S. simulans and S. caprae (all 0.032 mg/L). Conclusions This study demonstrated a difference in dalbavancin susceptibility between different CoNS species, suggesting that species-specific breakpoints for CoNS should be further investigated.

Background There are limited treatment options for prosthetic joint infections (PJI) due to multidrug-resistant Staphylococcus epidermidis (MDRSE). Fosfomycin (FOF) has gained attention as a potential therapy, but there is a paucity of information on the phenotypic and genotypic susceptibility amongst S. epidermidis, including MDRSE. Objectives To investigate phenotypical and genotypical susceptibility to FOF in S. epidermidis isolates prospectively collected from PJIs in Sweden. Methods MIC determination was performed using in-house agar dilution (AD) and a commercial AD panel. Genes and gene variants associated with FOF resistance were analysed. Results Multidrug resistance was common [74/89 (83%) isolates were MDRSE]. FOF inhibited all isolates except one, which had an MIC > 256 mg/L. The commercial AD panel demonstrated good overall performance but tended to overestimate the MIC, resulting in 84% essential agreement with the gold standard. Genomic analysis with publically available tools for whole-genome sequencing (WGS) data suggested genotypic FOF resistance in all isolates, but in-depth analysis revealed that fosB, associated with FOF resistance, was only present in the phenotypically resistant isolate. No other genes or gene variants associated with FOF resistance were detected. Results Multidrug resistance was common [74/89 (83%) isolates were MDRSE]. FOF inhibited all isolates except one, which had an MIC > 256 mg/L. The commercial AD panel demonstrated good overall performance but tended to overestimate the MIC, resulting in 84% essential agreement with the gold standard. Genomic analysis with publically available tools for whole-genome sequencing (WGS) data suggested genotypic FOF resistance in all isolates, but in-depth analysis revealed that fosB, associated with FOF resistance, was only present in the phenotypically resistant isolate. No other genes or gene variants associated with FOF resistance were detected. Conclusions Phenotypic resistance to FOF and presence of fosB were rare in this collection, indicating FOF's potential as a treatment option for S. epidermidis. The commercial AD panel demonstrated high reproducibility, but EA with the reference method was less than optimal. Findings of genotypic FOF resistance using common tools for WGS data should be critically evaluated and appropriately verified with relevant fosB references for S. epidermidis.

ABSTRACT Cutibacterium acnes is a major skin commensal that may act as an opportunistic pathogen. It is difficult to interpret findings of C. acnes in tissue cultures obtained during arthroplasty revision surgery, since they may represent true infection or contamination. This study investigated whether C. acnes obtained from prosthetic joint infections (PJIs) were related and shared common genomic traits that might correlate with clinical courses and patient outcomes. C. acnes isolates from revision surgery of patients with PJIs of the hip, shoulder, and knee were characterized using molecular methods to determine the sequence type (ST) and the presence of possible virulence determinants (Christie–Atkins–Munch-Peterson factors, dermatan sulfate-binding adhesion 1, hyaluronidase lyase, and linear plasmid). A standardized review of the patients’ medical charts was performed. The study included 37 patients with C. acnes culture-positive tissue samples where multiple isolates of C. acnes belonged to the same ST. Most of the isolates belonged to phylotype IA 1 . Phylogenetic analysis of virulence determinants revealed no shared pattern among PJI isolates. Seven patients had a polymicrobial infection. Exchange revision was performed in 70% of the patients, and >50% of all patients received antibiotic treatment for ≥3 months. Failure was noted in seven patients. No specific ST or any identifiable unique feature among virulence determinants were found among C. acnes isolated from PJIs of hips and shoulders. The majority of patients had low inflammatory markers and were treated successfully, even polymicrobial infections. However, failure was more common among shoulder infections compared with hip infections. IMPORTANCE Prosthetic joint infection (PJI) is a rare complication after arthroplasty surgery. The infection seldom resolves without a combination of both surgical and antibiotic treatment and can cause significant suffering among affected patients. Cutibacterium acnes is a common skin bacterium that is most often found in shoulder PJIs but can also infect other prostheses. In this study, we conducted a review of patients with previously verified PJIs involving C. acnes in hip or shoulder prostheses, along with a genomic analysis of the bacteria causing the infections. The majority of patients had successful outcomes. We did not identify any specific phylogenetic lineage or specific molecular signature of virulence factors among these PJI-associated C. acnes isolates that seemed to be associated with increased potential to cause infection among this species. This indicates that C. acnes isolated from PJIs originates from the patients’ own skin microbiome and is inoculated during the arthroplasty surgery.

BackgroundMethicillin-resistant Staphylococcus aureus (MRSA) has been an issue in healthcare since the 1960s. It was initially found only in healthcare facilities, but in the late 1990s it began to be seen with no healthcare connexion. The mechanisms of intercontinental and national spread are not fully understood, as sometimes novel outbreaks occur without any identifiable source or connexion to locally dominant clonal clusters.MethodsThis study investigated the epidemiology and genomics of community-associated MRSA in Region Örebro County, Sweden, through 330 isolates collected between 2000 and 2019.ResultsA shift in the dominant sequence type (ST) from ST80 to ST22 occurred in 2011–2019, along with an increase in the prevalence of STs belonging to clonal complexes CC5 and CC22. Both ST8 and ST80 isolates seemed to give way to emerging ST22 isolates, also indicated by the declining presence of the USA300 clone. The staphylococcal chromosomal cassette mec (SCCmec) type IV Remained dominant.ConclusionsThe SCCmec type IV characteristic appears to be relatively geographically stable, possibly due to its low fitness cost and transductal capabilities. This warrants further studies of SCCmec type IV variant's survival mechanics as well as the effects of migratory flow on local epidemiology, in preparation for future possible outbreaks.

BACKGROUND:There is limited knowledge regarding how long prepared sterile goods can wait before becoming contaminated. We investigated whether surgical goods could be prepared the day before surgery and kept sterile overnight in the operating room, if protected by sterile covers. METHODS:Sterile surgical goods for open-heart surgeries (n=70) were randomized to preparation on the morning of the operation or on the previous evening. Exposure time was the total time between preparation and use. Primary outcome was bacterial growth reported as colony forming units (cfu), isolated on 840 agar plates. The protocol was registered with ClinicalTrials.gov (NCT05597072). RESULTS:When the agar plates were protected with sterile covers, exposure time had no impact (intervention group: 7 cfu, control group: 17 cfu). Without protection, longer exposure time was associated with more cfu (P=.016). A total of 499 cfu were isolated, displaying 59 different types of bacteria including 13 resistant Staphylococcus epidermidis, 6 (46%) of which were multidrug resistant. CONCLUSIONS:Sterile goods could wait in the operating room for at least 15 hours before use without increased risk of bacterial air contamination, if protected with sterile covers. However, if the goods were not covered, bacterial air contamination occurred over time.

ABSTRACT Local delivery of antibiotics as prophylaxis for prosthetic joint infections (PJIs) is frequently used during total hip replacement surgery. Morselized bone allograft impregnated with vancomycin and tobramycin ( TobraVanc ) could provide effective prophylaxis against bacteria commonly associated with PJIs. In this study, the concentrations of antibiotics released by bone allograft impregnated with TobraVanc were determined by using an in vitro bioassay system entailing measuring inhibition zone diameters caused by antibiotic-impregnated bone chips cast in agar against standard curves. The concentrations were determined in samples of TobraVanc -impregnated bone graft taken before and after the application of the bone graft in the patients undergoing acetabular revision surgery. Antibiotic-impregnated bone grafts, sampled prior to application in the patient, delivered antibiotics in the concentration ranges of 730–9,800 mg/L for tobramycin and 1,300–11,000 mg/L for vancomycin. Samples taken after application in the patient released lower concentrations of tobramycin (490–1,900 mg/L; P < 0.01) and vancomycin (3,000–5,100 mg/L; P < 0.05); however, these concentrations remained well above the tobramycin minimum inhibitory concentrations (MICs) for investigated, highly tobramycin-resistant Staphylococcus epidermidis strains (MICs > 256 mg/L). At the tested concentrations, bone graft material mixed with TobraVanc delivered antibiotics in potent concentrations above the MICs for bacteria causing PJIs. Clinical trials are needed to evaluate the efficacy and risk of TobraVanc -impregnated bone graft as a prophylactic agent for patients undergoing hip replacement surgery. IMPORTANCE Antibiotic prophylaxis is the cornerstone of successful joint replacement surgery, reducing the risk for the dreaded complication of prosthetic joint infection (PJI) to roughly 0.5%–2% in standard total hip replacement (THR). In addition to systemic antibiotics, antibiotics added locally have the potential to reduce the PJI risk even further, because of the high concentrations that can be achieved in the joint with limited risk for systemic toxicity. The results in the current study show that bone chips impregnated with a combination of tobramycin and vancomycin ( TobraVanc ) release antibiotics in concentrations that are potent against common bacteria causing PJIs. Especially in high-risk patients, our results support the prophylactic use of TobraVanc in hip replacement surgery requiring the use of a bone graft. A clinical study testing the efficacy of TobraVanc -impregnated bone graft in reducing the incidence of PJI in hip replacement surgery is currently ongoing (EudraCT: 2021-001708-14).

Patients with atopic dermatitis (AD) are more likely than healthy individuals to harbour Staphylococcus aureus on their skin. Superantigens (SAgs) produced by specific S. aureus strains may contribute to AD-associated skin inflammation. The present study compared the prevalence and types of SAg-encoding genes between S. aureus isolated from patients with AD and from controls, and within the AD group between isolates from different sampling sites (lesional skin, non-lesional skin, and nares). This retrospective case-control study extracted data from 2 previous studies that examined S. aureus using whole-genome sequencing. The 138 S. aureus isolates obtained from 71 AD patients contained 349 SAg-encoding genes; 22 (6.3%) were found in isolates from nares (0.4 ± 0.6 genes per isolate), 99 (28.4%) in isolates from non-lesional skin (3.7 ± 3.9), and 228 (65.3%) in isolates from lesional skin (4.2 ± 4.5). S. aureus (n = 101) from the control group contained 594 SAg-encoding genes (5.9 ± 4.2). Of the S. aureus isolated from lesional AD skin, 69% carried at least 1 gene encoding SAg compared with 33% of AD nasal isolates. SAg could be a factor in the pathogenesis of a subset of AD patients.

Cutibacterium avidum has recently been reported as a rare cause of prosthetic joint infections (PJIs), contrary to Cutibacterium acnes, which is well established as a cause of PJIs, especially in shoulder arthroplasties. Two specific risk factors for PJI due to C. avidum have been reported: obesity and the skin incision approach. Here, we report four cases of hip PJIs caused by C. avidum admitted over a 30-month period at a single center. Whole-genome sequencing revealed that the four C. avidum strains were all individual strains and did not originate from a common source, such as an outbreak. Antibiotic susceptibility tests showed that the isolates were fully susceptible, and none carried known antibiotic resistance genes. In conclusion, the occurrence of four cases of PJI caused by C. avidum over a limited time at a single center may indicate that this pathogen is underestimated and is either emerging or more common than previously recognized. The patients presented overt signs of infection during surgery, indicating that C. avidum is a virulent pathogen. None of the previously reported risk factors for C. avidum PJI applied to these patients as only one was obese and none were operated on using a direct anterior skin incision approach.

PLNC8 αβ is a cationic antimicrobial peptide that previously has been reported to express both antibacterial and antiviral properties. This study aimed to further elucidate the antiviral effects of PLNC8 αβ and its impact on virus-induced cytotoxicity and inflammatory signaling in human alveolar epithelial cells (A549) infected with the flavivirus Kunjin. Complementary in silico analyses using molecular dynamics (MD) simulation were conducted to investigate the mechanism of action of PLNC8 αβ by studying the interaction of PLNC8 α and β with models of a flavivirus membrane and a eukaryotic plasma membrane, respectively. Our findings demonstrated that PLNC8 αβ significantly reduces both extracellular and intracellular viral loads, as confirmed by plaque reduction assays and RT-PCR. The peptide also mitigated virus-induced cytotoxicity and inflammation. Notably, PLNC8 αβ modulated the virus-induced dysregulation of key signaling and inflammatory genes, such as TLR9, TLR3, NOD2, FOS, JUN, IL6, and CXCL8. MD simulation revealed that PLNC8 αβ exhibits higher binding affinity for a flavivirus membrane model compared to a model of the plasma membrane, likely due to stronger electrostatic interactions with anionic phospholipids. This selective interaction possibly accounts for a potent antiviral activity of PLNC8 αβ combined with a minimal cytotoxicity toward human cells. Overall, PLNC8 αβ shows significant promise as an antiviral agent against flavivirus infections and warrants further exploration for peptide-based antiviral therapies.