With the aging of population, the number of indications for total joint replacement is continuously increasing. However, prosthesis loosening can happen and is related to two major mechanisms: (1) ...aseptic loosening due to prosthesis micromotion and/or corrosion and release of wear particles from the different components of the implanted material and (2) septic loosening due to chronic prosthetic joint infection (PJI). The "aseptic" character of prosthesis loosening has been challenged over the years, especially considering that bacteria can persist in biofilms and be overlooked during diagnosis. Histological studies on periprosthetic tissue samples reported that macrophages are the principle cells associated with aseptic loosening due to wear debris. They produce cytokines and favor an inflammatory environment that induces formation and activation of osteoclasts, leading to bone resorption and periprosthetic osteolysis. In PJIs, the presence of infiltrates of polymorphonuclear neutrophils is a major criterion for histological diagnosis. Neutrophils are colocalized with osteoclasts and zones of osteolysis. A similar inflammatory environment also develops, leading to bone resorption through osteoclasts.
,
, and
are the main staphylococci observed in PJIs. They share the common feature to form biofilm. For
and
, the interaction between biofilm and immunes cells (macrophages and polymorphonuclear neutrophils) differs regarding the species. Indeed, the composition of extracellular matrix of biofilm seems to impact the interaction with immune cells. Recent papers also reported the major role of myeloid-derived suppressor cells in biofilm-associated PJIs with
. These cells prevent lymphocyte infiltration and facilitate biofilm persistence. Moreover, the role of T lymphocytes is still unclear and potentially underestimates. In this review, after introducing the cellular mechanism of aseptic and septic loosening, we will focus on the interrelationships between staphylococcal biofilm, immune cells, and bone cells.
Actinomycosis is a rare chronic disease caused by Actinomyces spp., anaerobic Gram-positive bacteria that normally colonize the human mouth and digestive and genital tracts. Physicians must be aware ...of typical clinical presentations (such as cervicofacial actinomycosis following dental focus of infection, pelvic actinomycosis in women with an intrauterine device, and pulmonary actinomycosis in smokers with poor dental hygiene), but also that actinomycosis may mimic the malignancy process in various anatomical sites. Bacterial cultures and pathology are the cornerstone of diagnosis, but particular conditions are required in order to get the correct diagnosis. Prolonged bacterial cultures in anaerobic conditions are necessary to identify the bacterium and typical microscopic findings include necrosis with yellowish sulfur granules and filamentous Gram-positive fungal-like pathogens. Patients with actinomycosis require prolonged (6- to 12-month) high doses (to facilitate the drug penetration in abscess and in infected tissues) of penicillin G or amoxicillin, but the duration of antimicrobial therapy could probably be shortened to 3 months in patients in whom optimal surgical resection of infected tissues has been performed. Preventive measures, such as reduction of alcohol abuse and improvement of dental hygiene, may limit occurrence of pulmonary, cervicofacial, and central nervous system actinomycosis. In women, intrauterine devices must be changed every 5 years in order to limit the occurrence of pelvic actinomycosis.
Small colony variants (SCV) of
have been reported as implicated in chronic infections. Here, we investigated the genomic and transcriptomic changes involved in the evolution from a wild-type to a SCV ...from in a patient with prosthetic joint infection relapse. The SCV presented a stable phenotype with no classical auxotrophy and the emergence of rifampicin resistance. Whole Genome Sequencing (WGS) analysis showed only the loss of a 42.5 kb phage and 3 deletions, among which one targeting the
gene, known to be the target of rifampicin and to be associated to SCV formation in the context of a constitutively active stringent response. Transcriptomic analysis highlighted a specific signature in the SCV strain including a complex, multi-level strategy of survival and adaptation to chronicity within the host including a protection from the inflammatory response, an evasion of the immune response, a constitutively activated stringent response and a scavenging of iron sources.
Biofilm formation is a critical virulence factor responsible for treatment failure and chronicity in orthopaedic device-related infections (ODIs) caused by Staphylococcus aureus. Clonal lineages ...differ in terms of their biofilm forming capacities. The aim of this study was to investigate the correlation between the clonal complex (CC) affiliation and biofilm phenotype of 30 clinical S. aureus isolates responsible of ODI based on i) early biofilm formation using BioFilm Ring Test® and mature biofilm formation using crystal violet assays, ii) biofilm composition using DNase and proteinase K activity, and iii) prevention of biofilm formation by cloxacillin, teicoplanin and vancomycin using Antibiofilmogram® (biofilm minimal inhibitory concentration-bMIC). In terms of early biofilm formation, the CC30 strains were significantly slower than the CC5, CC15 and CC45 strains. CC45 strains produced significantly more mature biofilm than other group of strains did. The formation of biofilms was highly dependent on the presence of extracellular DNA in the CC5, CC15 and CC30 strains whereas it was mostly dependent on the presence of proteins in CC45. Finally, the CC30 group highlighted higher proportion of susceptible (bMIC < breakpoints of EUCAST guidelines) for cloxacillin, teicoplanin and vancomycin compared to the other CCs. These results demonstrate that the biofilm phenotype of clinical S. aureus isolates from ODIs is strongly related to their respective CC affiliation.
Allogeneic hematopoietic stem cell transplantation (HSCT) is a major curative treatment option for malignant and non-malignant hematological diseases, but is associated with an increased risk for ...infections, of which some are preventable by vaccination. Vaccination guidelines recommend repeated doses of most inactivated vaccines to achieve long-lasting immune responses. However, the efficacy of immunization is often hampered by graft-versus-host disease or severe opportunistic infections.
This review summarizes the vaccine recommendations for adult allogeneic HSCT recipients and discusses the challenges and future directions regarding vaccine immunization in these patients.
Vaccination is a well-tolerated therapeutic intervention to prevent infections after allogeneic HSCT. Allogeneic HSCT recipients could benefit from experience regarding vaccine efficacy capitalized through specific data registries. An individualized immunization approach, modulating inception and intensity of vaccination schedule according to transplant characteristics, transplant-related complications and immune recovery status, might help to improve vaccine efficacy in this specific population. Identification of surrogate markers of the immune status and of vaccine efficacy, beyond antibody testing, as well as development of new vaccines are exciting fields of future research.
is an emerging species responsible for infections comparable to those induced by
. It has been involved in few chronic or persistent infections so far. In this study, we described a case of a ...persistent prosthetic-joint infection (PJI) affecting a young woman. We investigated in vitro the virulence traits of the incriminated
strain (bone cell invasion, biofilm formation and induction of inflammation) and analyzed its genome, in comparison with two other strains of
and two
isolates. It appeared that this
PJI strain combined biofilm formation, osteoblast invasion and intracellular persistence abilities together with genes potentially involved in the escape of the host immune defenses, which might explain the chronicization of the infection.
Although Staphylococcus aureus persistence in osteoblasts, partly as small-colony variants (SCVs), can contribute to bone and joint infection (BJI) relapses, the intracellular activity of ...antimicrobials is not currently considered in the choice of treatment strategies for BJI. Here, antistaphylococcal antimicrobials were evaluated for their intraosteoblastic activity and their impact on the intracellular emergence of SCVs in an ex vivo osteoblast infection model. Osteoblastic MG63 cells were infected for 2 h with HG001 S. aureus. After killing the remaining extracellular bacteria with lysostaphin, infected cells were incubated for 24 h with antimicrobials at the intraosseous concentrations reached with standard therapeutic doses. Intracellular bacteria and SCVs were then quantified by plating cell lysates. A bactericidal effect was observed with fosfomycin, linezolid, tigecycline, oxacillin, rifampin, ofloxacin, and clindamycin, with reductions in the intracellular inocula of -2.5, -3.1, -3.9, -4.2, -4.9, -4.9, and -5.2 log10 CFU/100,000 cells, respectively (P < 10(-4)). Conversely, a bacteriostatic effect was observed with ceftaroline and teicoplanin, whereas vancomycin and daptomycin had no significant impact on intracellular bacterial growth. Ofloxacin, daptomycin, and vancomycin significantly limited intracellular SCV emergence. Overall, ofloxacin was the only molecule to combine an excellent intracellular activity while limiting the emergence of SCVs. These data provide a basis for refining the choice of antibiotics to prioritise in the management of BJI, justifying the combination of a fluoroquinolone for its intracellular activity with an anti-biofilm molecule, such as rifampin.
Pseudomonas aeruginosa is one of the main causes of healthcare-associated infection in Europe that increases patient morbidity and mortality. Multi-resistant pathogens are a major public health issue ...in burn centers. Mortality increases when the initial antibiotic treatment is inappropriate, especially if the patient is infected with P. aeruginosa strains that are resistant to many antibiotics. Phage therapy is an emerging option to treat severe P. aeruginosa infections. It involves using natural viruses called bacteriophages, which have the ability to infect, replicate, and, theoretically, destroy the P. aeruginosa population in an infected patient. We report here the case of a severely burned patient who experienced relapsing ventilator-associated pneumonia associated with skin graft infection and bacteremia due to extensively drug-resistant P. aeruginosa. The patient was successfully treated with personalized nebulized and intravenous phage therapy in combination with immunostimulation (interferon-γ) and last-resort antimicrobial therapy (imipenem-relebactam).
•Post-cranioplasty bone flap infection is associated with a high risk of treatment failure.•Main implicated pathogens are staphylococci, Cutibacterium acnes, and gram-negative bacilli.•Extensive ...surgical debridement, including curettage of bone edges, is necessary.•These difficult-to-treat infections require dedicated multidisciplinary management.
We aimed to describe diagnostic, management, and outcome of bone flap-related osteomyelitis after cranioplasty.
Patients followed up in our tertiary care hospital for bone flap-related osteomyelitis after cranioplasty were included in a retrospective cohort (2008-2021). Determinants of treatment failure were assessed using logistic regression and Kaplan-Meier curves analysis.
The 144 included patients (81 56.3% males; median age 53.4 interquartile range IQR, 42.6-62.5 years) mostly presented wound abnormalities (n = 115, 79.9%). All infections were documented, the main pathogens being Staphylococcus aureus (n = 64, 44.4%), Cutibacterium acnes (n = 57, 39.6%), gram-negative bacilli (n = 40, 27.8%) and/or non-aureus staphylococci (n = 34, 23.6%). Surgery was performed in 140 (97.2%) cases, for bone flap removal (n = 102, 72.9%) or debridement with flap retention (n = 31, 22.1%), along with 12.7 (IQR, 8.0-14.0) weeks of antimicrobial therapy. After a follow-up of 117.1 (IQR, 62.5-235.5) weeks, 37 (26.1%) failures were observed: 16 (43.2%) infection persistence, three (8.1%) relapses, 22 (59.5%) superinfections and/or two (1.7%) infection-related deaths. Excluding superinfections, determinants of the 19 (13.4%) specific failures were an index craniectomy for brain tumor (odds ratio = 4.038, P = 0.033) and curettage of bone edges (odds ratio = 0.342, P = 0.048).
Post-craniectomy bone flap osteomyelitis are difficult-to-treat infection, necessitating prolonged antimicrobial therapy with appropriate surgical debridement, and advocating for multidisciplinary management in dedicated reference centers.
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