A spacer infection by Candida albicans secondary to a Staphylococcus capitis prosthetic joint infection: a case report.

BACKGROUND: Prosthetic joint infection (PJI) is one of the most feared complications following total arthroplasty surgeries. Gram-positive bacteria are the most common microorganisms implicated in PJIs, while infections mediated by fungi only account for 1% of cases. When dealing with PJIs, a two-stage revision arthroplasty is widely used. Briefly, a spacer is introduced until re-implantation of the definitive prosthesis to provide skeleton stabilization while delivering antibiotics in the site of the infection. Sometimes, antimicrobial therapy may fail, but the isolation of a second microorganism from the spacer is uncommon and even less frequent that of a yeast. CASE PRESENTATION: Here is described a case of a 75-year-old woman who underwent two-stage revision surgery of the left hip prosthesis secondary to a Staphylococcus capitis infection, whose spacer was found to be infected by Candida albicans at a later time. Briefly, the patient underwent revision surgery of the hip prosthesis for a suspected PJI. After the debridement of the infected tissue, an antibiotic-loaded spacer was implanted. The microbiological analysis of the periprosthetic tissues and the implant depicted a S. capitis infection that was treated according to the antimicrobial susceptibility profile of the clinical isolate. Three months later, the patient was admitted to the emergency room due to local inflammatory signs. Synovial fluid was sent to the laboratory for culture. No evidence of S. capitis was detected, however, a yeast was identified as Candida albicans. Fifteen days later, the patient was hospitalized for the removal of the infected spacer. Microbiological cultures confirmed the results of the synovial fluid analysis. According to the susceptibility profile, the patient was treated with fluconazole (400 mg/day) for 6 months. Seven months later, the patient underwent second-stage surgery. The microbiological tests on the spacer were all negative. After 12 months of follow-up, the patient has fully recovered and no radiological signs of infection have been detected. CONCLUSIONS: Given the exceptionality of this complication, it is important to report these events to better understand the clinical outcomes after the selected therapeutic options to prevent and forestall the development of either bacterial or fungal spacer infections.

Superior Osteo-Inductive and Osteo-Conductive Properties of Trabecular Titanium vs. PEEK Scaffolds on Human Mesenchymal Stem Cells: A Proof of Concept for the Use of Fusion Cages.

Fusion cages composed of titanium and its alloys are emerging as valuable alternative to standard polyetheretherketone (PEEK) ones routinely used in cervical and lumbar spine surgery. Aim of this study was to evaluate osteo-inductive and osteo-conductive ability of an innovative trabecular titanium (T-Ti) scaffold on human mesenchymal stem cells (hMSCs), in both absence and presence of biochemical osteogenic stimuli. Same abilities were assessed on PEEK and standard 2D plastic surface, the latter meant as gold-standard for in vitro differentiation studies. hMSCs adhered and colonized both T-Ti and PEEK scaffolds. In absence of osteogenic factors, T-Ti triggered osteogenic induction of MSCs, as demonstrated by alkaline phosphatase activity and calcium deposition increments, while PEEK and standard 2D did not. Addition of osteogenic stimuli reinforced osteogenic differentiation of hMSCs cultured on T-Ti in a significantly higher manner with respect to standard 2D plastic culture surfaces, whereas PEEK almost completely abolished the process. T-Ti driven differentiation towards osteoblasts was confirmed by gene and marker expression analyses, even in absence of osteogenic stimuli. These results clearly indicate superior in vitro osteo-inductive and osteo-conductive capacity of T-Ti compared to PEEK, and make ground for further studies supporting the use of T-Ti cages to improve bone fusion.

In Vitro Evaluation of Gentamicin or Vancomycin Containing Bone Graft Substitute in the Prevention of Orthopedic Implant-Related Infections.

Antibiotic-loaded bone graft substitutes are attractive clinical options and have been used for years either for prophylaxis or therapy for periprosthetic and fracture-related infections. Calcium sulfate and hydroxyapatite can be combined in an injectable and moldable bone graft substitute that provides dead space management with local release of high concentrations of antibiotics in a one-stage approach. With the aim to test preventive strategies against bone infections, a commercial hydroxyapatite/calcium sulfate bone graft substitute containing either gentamicin or vancomycin was tested against Staphylococcus aureus, Staphylococcus epidermidis and Pseudomonas aeruginosa, harboring different resistance determinants. The prevention of bacterial colonization and biofilm development by selected microorganisms was investigated along with the capability of the eluted antibiotics to select for antibiotic resistance. The addition of antibiotics drastically affected the ability of the selected strains to adhere to the tested compound. Furthermore, both the antibiotics eluted by the bone graft substitutes were able to negatively impair the biofilm maturation of all the staphylococcal strains. As expected, P. aeruginosa was significantly affected only by the gentamicin containing bone graft substitutes. Finally, the prolonged exposure to antibiotic-containing sulfate/hydroxyapatite discs did not lead to any stable or transient adaptations in either of the tested bacterial strains. No signs of the development of antibiotic resistance were found, which confirms the safety of this strategy for the prevention of infection in orthopedic surgery.

Ability of adhesion and biofilm formation of pathogens of periprosthetic joint infections on titanium-niobium nitride (TiNbN) ceramic coatings.

BACKGROUND: Orthopedic metal implants are notoriously associated with release of metallic ions able to cause biological adverse reactions which might lead to implant loosening and failure. To limit any possible adverse reactions, ceramic coatings for orthopedic metal implants have been introduced. However, information regarding the interaction of these coatings with microbes responsible for periprosthetic joint infections (PJIs) is lacking. Hence, the aim of the present in vitro study is to assess the microbial affinity to a titanium-niobium nitride (TiNbN) coating. METHODS: Adhesion and biofilm formation of clinical isolates of Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Cutibacterium acnes were assessed on TiNbN-coated titanium discs in comparison with uncoated titanium and cobalt-chrome alloys discs, with either smooth or rough surfaces. Bacterial adhesion was performed by counting adhered bacteria in the first hours of incubation, and the biofilm formation was performed by means of a spectrophotometric assay and by confocal laser scan microscopy after 72 hours of incubation. RESULTS: Overall, Staphylococcus aureus and Staphylococcus epidermidis, among the most common bacteria responsible for PJIs, displayed a significantly decreased attachment in the first hours of contact and, when cultured in presence of TiNbN coating, in comparison with CoCrMo. Biofilm formation of the four tested strains was comparable on all alloys. CONCLUSIONS: Although the onset of a PJI is more complex than in an in vitro scenario, these findings suggest that TiNbN-coated orthopedic implants do not increase PJIs risk while ameliorating tribological and surface properties could represent a valid choice to limit possible complications such as metal hypersensitivity.

A non-linear deterministic model for regulation of diauxic lag on cellobiose by the pneumococcal multidomain transcriptional regulator CelR.

When grown on glucose and beta-glucosides, S. pneumoniae shows sequential use of sugars resulting in diauxic growth with variable time extent of the lag phase separating the biphasic growth curve. The pneumococcal beta-glucoside uptake locus containing the PTS transporter spr0276-82, is regulated by a multi-domain transcriptional regulator CelR. In this work, we address the contribution of phosphorylation of the phosphorylable cysteine in the EIIB domain of CelR to diauxic lag. Utilising site-directed mutagenesis of the phosphorylable amino acids in the EIIB and EIIA domains of CelR, we show that the EIIB domain activation is linked to the duration of the lag phase. Analysis of mutants for other PTS systems indicates that a second beta-glucoside PTS (spr0505), not able to support growth on cellobiose, is responsible for the lag during diauxic growth. A mathematical model of the process is devised together with a nonlinear identification procedure which provides model parameter estimates characterizing the single phases of bacterial growth. Parameter identification performed on data recorded in appropriate experiments on mutants allows for establishing a relationship between a specific model parameter, the EIIB domain and the time extent of the diauxic lag. The experimental results and the related insights provided by the mathematical model provide evidence that the conflicting activation of the CelR regulator is at the origin of the lag phase during sequential growth on glucose and cellobiose. This data is the first description of diauxic lag regulation involving two PTS and a multidomain regulator and could serve as a promising approach for studying the S. pneumoniae growth process on complex carbon sources as possibly encountered in the human host.