Opportunistic bacteria from the genus
can cause life-threatening infections such as pneumonia, endocarditis, bone and joint infections, and sepsis. This pathogenicity is closely related to their ...capacity to bind directly to the extracellular matrix or to host cells. Adhesion is indeed the first step in the formation of biofilm or the invasion of host cells, which protect the bacteria from the host immune system and facilitate chronic infection. Adhesion relies on the expression of a repertoire of surface proteins called adhesins, notably microbial surface components recognizing adhesive matrix molecules. In this short review, we discuss the main pathway (FnBP-Fn-α5β1 integrin), as well as alternatives, through which
adheres to and then invades non-professional phagocytic cells. We then examine the corresponding mechanisms for coagulase negative staphylococci. There is currently a little understanding of the molecular mechanisms that lead to internalization. Filling this gap in the literature would therefore be an important step toward limiting the duration of staphylococci infections in clinical practice.
Abstract
Background
While the treatment of ESBL-producing Enterobacterales osteomyelitis relies on carbapenems, the optimal regimen for OXA48 types remains unclear. We evaluated the efficacy of ...ceftazidime/avibactam in different combinations in an experimental model of OXA-48-/ESBL-producing Escherichia coli osteomyelitis.
Methods
E. coli pACYC184 is a clinical strain harbouring blaOXA-48 and blaCTX-M-15 inserts, with ‘increased exposure susceptibility’ to imipenem (MIC, 2 mg/L), gentamicin (MIC, 0.5 mg/L), colistin (MIC, 0.25 mg/L), ceftazidime/avibactam (MIC, 0.094 mg/L) and fosfomycin (MIC, 1 mg/L), and resistance to ceftazidime (MIC, 16 mg/L). Osteomyelitis was induced in rabbits by tibial injection of 2 × 108 cfu of OXA-48/ESBL E. coli. Treatment started 14 days later for 7 days in six groups: (1) control, (2) colistin 150.000 IU/kg subcutaneously (SC) q8h, (3) ceftazidime/avibactam 100/25 mg/kg SC q8h, (4) ceftazidime/avibactam + colistin, (5) ceftazidime/avibactam + fosfomycin 150 mg/kg SC q12h, (6) ceftazidime/avibactam + gentamicin 15 mg/kg intramuscularly (IM) q24h. Treatment was evaluated at Day 24 according to bone cultures.
Results
In vitro, time–kill curves of ceftazidime/avibactam in combination showed a synergistic effect. In vivo, compared with controls, rabbits treated with colistin alone had similar bone bacterial density (P = 0.50), whereas ceftazidime/avibactam alone or in combinations significantly decreased bone bacterial densities (P = 0.004 and P < 0.0002, respectively). Bone sterilization was achieved using ceftazidime/avibactam in combination with colistin (91%) or fosfomycin (100%) or gentamicin (100%) (P < 0.0001), whereas single therapies were not different from controls. No ceftazidime/avibactam-resistant strains emerged in rabbits treated, regardless of the combination.
Conclusions
In our model of E. coli OXA-48/ESBL osteomyelitis, ceftazidime/avibactam in combination was more effective than any single therapy, whatever the companion drug used (gentamicin or colistin or fosfomycin).
is responsible for difficult-to-treat bone and joint infections (BJIs). This is related to its ability to form biofilm and to be internalized and persist inside osteoblasts. Recently, bacteriophage ...therapy has emerged as a promising option to improve treatment of such infections, but data on its activity against the specific bacterial lifestyles presented above remain scarce. We evaluated the activity of a combination of three bacteriophages, recently used for compassionate treatment in France, against
HG001 in a model of staphylococcal biofilm and a model of osteoblasts infection, alone or in association with vancomycin or rifampin. The activity of bacteriophages against biofilm-embedded
was dose dependent. In addition, synergistic effects were observed when bacteriophages were combined with antibiotics used at the lowest concentrations. Phage penetration into osteoblasts was observed only when the cells were infected, suggesting a
-dependent Trojan horse mechanism for internalization. The intracellular bacterial count of bacteria in infected osteoblasts treated with bacteriophages as well as with vancomycin was significantly higher than in cells treated with lysostaphin, used as a control condition, owing to the absence of intracellular activity and the rapid killing of bacteria released after the death of infected cells. These results suggest that bacteriophages are both inactive in the intracellular compartment after being internalized in infected osteoblasts and present a delayed killing effect on bacteria released after cell lysis into the extracellular compartment, which avoids preventing them from infecting other osteoblasts. The combination of bacteriophages tested was highly active against
embedded in biofilm but showed no activity against intracellular bacteria in the cell model used.
Bone and joint infections (BJI) are severe infections that require a tailored and protracted antibiotic treatment. Yet, the diagnostic based on culturing samples lacks sensitivity, especially for ...hardly culturable bacteria. Metagenomic sequencing could potentially address those limitations. Here, we assessed the performances of metagenomic sequencing on 24 BJI samples for the identification of pathogens and the prediction of their antibiotic susceptibility. For monomicrobial samples in culture (n = 8), the presence of the pathogen was confirmed by metagenomics in all cases. For polymicrobial samples (n = 16), 32/55 bacteria (58.2%) were found at the species level (and 41/55 74.5% at the genus level). Conversely, 273 bacteria not found in culture were identified, 182 being possible pathogens and 91 contaminants. A correct antibiotic susceptibility could be inferred in 94.1% and 76.5% cases for monomicrobial and polymicrobial samples, respectively. Altogether, we found that clinical metagenomics applied to BJI samples is a potential tool to support conventional culture.
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.
We report a systematic prospective multicenter nationwide study of clinical Aeromonas infections in France. During 6 months (May to October 2006), 78 cases of aeromonosis were reviewed for risk ...factors and clinical, microbiological, and antimicrobial susceptibility data. They included wound infections (44%), bacteremia (26%), enteritis (19%), respiratory tract infections (6%), and miscellaneous (5%) infections.
•Chitosan-coated alginate fibers were achieved by a wet spinning technique.•The alginate/chitosan fibers contain about 10 % of chitosan by an external coating.•Mechanical and absorbency properties of ...alginate fibers are preserved after coating.•These fibers present an antibacterial activity against Gram-negative Escherichia coli.•These fibers present an antibacterial activity against some Staphylococcus (MRSA).
The preparation of chitosan-coated alginate fibers by a wet spin process is presented and the characterization of the antibacterial activities of these fibers is discussed. Preformed calcium alginate fibers were passed in chitosan acetate solutions. The coagulation method of the coating consisted in the immersion of fibers in a bath of calcium dihydroxide solution (0.1 M). The antibacterial evaluation was achieved by a CFU (Colony-Forming Units) counting method after 6 h of incubation at 37 °C. The incorporation of chitosan on calcium alginate fibers brings antibacterial activities against Staphylococcus epidermidis, Escherichia coli and various Staphylococcus aureus strains namely MSSA (Methicillin Sensitive Staphylococcus aureus), CA-MRSA (Community Associated Methicillin Resistant Staphylococcus aureus) and HA-MRSA (Healthcare Associated Methicillin Resistant Staphylococcus aureus) which make these chitosan-coated fibers potential candidates for wound dressing materials. Developing a wound dressing with the haemostatic and healing properties of alginate combined with antibacterial properties of chitosan is envisioned for fighting against the infections and more particularly nosocomial diseases.
We report the strategy leading to the first detection of variant of concern 202012/01 (VOC) in France (21 December 2020). First, the spike (S) deletion H69-V70 (ΔH69/ΔV70), identified in certain ...SARS-CoV-2 variants including VOC, is screened for. This deletion is associated with a S-gene target failure (SGTF) in the three-target RT-PCR assay (TaqPath kit). Subsequently, SGTF samples are whole genome sequenced. This approach revealed mutations co-occurring with ΔH69/ΔV70 including S:N501Y in the VOC.
Infective endocarditis is a rare condition in humans and is associated with high illness and death rates. We describe a case of infective endocarditis caused by Staphylococcus succinus bacteria in ...France. We used several techniques for susceptibility testing for this case to determine the oxacillin profile.
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.
PDF
