Clostridial prosthetic joint infections: A series of 16 cases and literature review.

OBJECTIVES: Prosthetic joint infections (PJIs) due to the Clostridium species have not been widely investigated. We aimed to characterize these uncommon infections. METHODS: We conducted a retrospective study between 2003 and 2020 in six French hospitals combined with a review of the literature. RESULTS: The main conclusions obtained from the 16 patients included were reinforced by the literature analysis: (i) Clostridium perfringens was the most frequently involved species, (ii) patients presented an advanced age at the time of prosthesis placement and infection, (iii) most of the infections were early- or delayed-onset, (iv) the prognosis for these PJIs remains poor, (v) when performed (n = 5), DAIR with 12-week antimicrobial therapy led to a favorable outcome in 80% of cases. CONCLUSIONS: Given the low incidence of this infection, our work represents the largest series of clostridial PJIs reported to date and highlights some specificities of these infections. Further prospective studies are needed to confirm these results.

[Knowledge, practices and expectations in the management of overactive bladder in general practice and gynecology in France]. / Connaissances, pratiques et attentes pour la prise en charge de l'hyperactivité vésicale en France.

INTRODUCTION: Overactive bladder (OAB) is a clinical syndrome characterized by urgency to urinate, with or without urinary incontinence, often associated with nycturia and pollakiuria. The aim of this practice survey is to identify diagnostic modalities and treatment circuits according to the patient's clinical profile and to practitioner's specialty. MATERIAL AND METHODS: A cross-sectional survey was conducted among 262 physicians practicing in France: 181 general practitioners (GPs) and 81 gynecologists. RESULTS: Urinary disorders were more easily addressed with patients by gynecologists than GPs. Behavioral therapy was the most widely used therapeutic measure, however half of the patients abandoned it. In oldest women and men of all ages, drugs were commonly prescribed, nevertheless only 4 out of 10 patients continued the treatment beyond 6months, according to the physicians. Incontinence was the symptom for which patients were in most need of relief. GPs and gynecologists expressed a need for training, practical tools and recommendations related to OAB. CONCLUSION: Patients and doctors are reluctant to talk about urinary disorders. Non-urologist physicians such as GPs and gynecologists, as health professionals best placed to detect and diagnose OAB, are in demand for training, practical tools and recommendations. LEVEL OF EVIDENCE: 3.

Bacteroides fragilis prevents Salmonella Heidelberg translocation in co-culture model mimicking intestinal epithelium.

Salmonella Heidelberg is one of the most common serovar causing foodborne illnesses. To limit the development of digestive bacterial infection, food supplements containing probiotic bacteria can be proposed. Commensal non-toxigenic Bacteroides fragilis has recently been suggested as a next-generation probiotic candidate. By using an original triple co-culture model including Caco-2 cells (representing human enterocytes), HT29-MTX (representing mucus-secreting goblet cells), and M cells differentiated from Caco-2 by addition of Raji B lymphocytes, bacterial translocation was evaluated. The data showed that S. Heidelberg could translocate in the triple co-culture model with high efficiency, whereas for B. fragilis a weak translocation was obtained. When cells were exposed to both bacteria, S. Heidelberg translocation was inhibited. The cell-free supernatant of B. fragilis also inhibited S. Heidelberg translocation without impacting epithelial barrier integrity. This supernatant did not affect the growth of S. Heidelberg. The non-toxigenic B. fragilis confers health benefits to the host by reducting bacterial translocation. These results suggested that the multicellular model provides an efficient in vitro model to evaluate the translocation of pathogens and to screen for probiotics that have a potential inhibitory effect on this translocation.

Moxifloxacin-rifampicin combination for the treatment of non-staphylococcal Gram-positive orthopedic implant-related infections.

OBJECTIVE: We aimed to describe the effectiveness and safety of the moxifloxacin-rifampicin combination in non-staphylococcal Gram-positive orthopedic implant-related infections. METHODS: Patients treated with the moxifloxacin-rifampicin combination for an implant-related infection from November 2014 to November 2016 were retrospectively identified from the database of the referral centers for bone and joint infections in Western France. RESULTS: Twenty-three cases of infection due to Streptococcus spp. (n=12), Cutibacteriumacnes (n=6), and Enterococcus faecalis (n=5) were included. Ten patients with hip prosthesis were included. Infection was polymicrobial in 11 cases. According to the MIC, moxifloxacin was 1.5 to 11.7 times as active as levofloxacin against non-staphylococcal Gram-positive bacteria. We reported an 81.8% success rate, and no severe adverse effect. CONCLUSION: The moxifloxacin-rifampicin combination is a valuable alternative for the treatment of non-staphylococcal Gram-positive implant-related infections because of the good activity of moxifloxacin against these bacteria and the potential activity on the biofilm.

Broad-range 16 s rDNA PCR in synovial fluid does not improve the diagnostic performance of septic arthritis in native joints in adults: cross-sectional single-center study in 95 patients.

OBJECTIVE: To evaluate the diagnostic performance of bacterial identification by broad-range polymerase chain reaction (PCR) of ribosomal DNA (rDNA) 16 s (16S rDNA PCR) for the diagnosis of septic arthritis on native joints. METHODS: Patients with acute mono or oligoarthritis who underwent synovial fluid puncture and prospective follow-up allowing definitive diagnosis (septic arthritis, crystal related disease, chronic inflammatory arthritis, undifferentiated arthritis) were recruited in this single-center study. Systematic analysis of synovial fluid included leukocytes count, search for urate and pyrophosphate crystals with polarized light microscopy, direct bacteriological examination (gram staining), bacteriological culture, and 16S rDNA PCR. RESULTS: Ninety-five patients were included, 34 of which (35.8%) had septic arthritis. Nineteen (20.0%) patients had received probabilistic antibiotic therapy prior to joint puncture. Gram + cocci infection accounted for 79.4% of septic arthritis, of which nearly half (47.1%) was caused by Staphylococcus aureus. Eight (23.5%) septic arthritis patients had a 16S rDNA PCR positive in the synovial fluid with an AUC of 0.618 (95% CI, 0.493-0.742), a sensitivity of 0.24 (95% CI, 0.12-0.40), and a specificity of 1.00 (95% CI 0.94-1.00). The diagnostic performance of 16S rDNA PCR was lower than that of direct examination (AUC at 0.691, CI 95%, 0.570-0.812), blood cultures (AUC at 0.727, CI 95%, 0.610-0.844), and culture (0.925, CI 95%, 0.856-0.994) for the diagnosis of septic arthritis. There was no difference in the positivity of 16S rDNA PCR according to previous exposure to antibiotics. CONCLUSIONS: 16 s rDNA PCR in the synovial fluid does not improve the diagnostic performance of septic arthritis on native adult joints, particularly for Gram-positive cocci infections.

Assessment of the automated multiplex-PCR Unyvero i60 ITI® cartridge system to diagnose prosthetic joint infection: a multicentre study.

OBJECTIVES: Prosthetic joint infections (PJI) are responsible for significant morbidity and mortality and their number continues to rise. Their management remains complex, especially the microbiological diagnosis. Besides 'homemade' tests developed by several teams, new molecular biology methods are now available with different analytical performance and usability. METHODS: We studied the performances of one of these tests: ITI® multiplex PCR (mPCR) by the Curetis® company and compared it to either 'optimized' culture or 16S rRNA PCR. We performed a retrospective multicentre study to assess the contributions of mPCR in the diagnosis of PJI. We randomly selected 484 intraoperative specimens among 1252 of various types (biopsy, bone, tissue around the prosthesis, synovial fluid) from 251 patients in seven different hospitals. Each sample was treated according to the recommendations of the manufacturer. RESULTS: In all, 154 out of 164 (93.9%) samples negative in culture were negative with the mPCR. Among the 276 positive samples in culture, 251 (90.9%) were monomicrobial, of which 119 (47.4%) were positive with the mPCR, and 25 (9.1%) were polymicrobial, of which 12 (48%) were positive with the mPCR. The concordance rate of mPCR with culture was 58.1% (53.6%-62.7%) and the concordance rate with 16S rRNA PCR was 70.1% (65.5%-74.6%). CONCLUSION: This new standardized molecular test showed a lack of detection when the bacterial inoculum was low (number of positive media per sample and number of colonies per media) but can be useful when patients have received antibiotic therapy previously.

Treponema, Iron and Neurodegeneration.

Spirochetes are suspected to be linked to the genesis of neurological diseases, including neurosyphillis or neurodegeneration (ND). Impaired iron homeostasis has been implicated in loss of function in several enzymes requiring iron as a cofactor, formation of toxic oxidative species, inflammation and elevated production of beta-amyloid proteins. This review proposes to discuss the link that may exist between the involvement of Treponema spp. in the genesis or worsening of ND, and iron dyshomeostasis. Proteins secreted by Treponema can act directly on iron metabolism, with hemin binding ability (HbpA and HbpB) and iron reductase able to reduce the central ferric iron of hemin, iron-containing proteins (rubredoxin, neelaredoxin, desulfoferrodoxin metalloproteins, bacterioferritins etc). Treponema can also interact with cellular compounds, especially plasma proteins involved in iron metabolism, contributing to the virulence of the syphilis spirochetes (e.g. treponemal motility and survival). Fibronectin, transferrin and lactoferrin were also shown to be receptors for treponemal adherence to host cells and extracellular matrix. Association between Treponema and iron binding proteins results in iron accumulation and sequestration by Treponema from host macromolecules during systemic and mucosal infections.

MALDI-TOF MS performance compared to direct examination, culture, and 16S rDNA PCR for the rapid diagnosis of bone and joint infections.

The rapid identification of bacterial species involved in bone and joint infections (BJI) is an important element to optimize the diagnosis and care of patients. The aim of this study was to evaluate the usefulness of matrix-assisted laser desorption ionization mass spectrometry (MALDI-TOF MS) for the rapid diagnosis of bone infections, directly on synovial fluid (SF) or on crushed osteoarticular samples (CS). From January to October 2013, we prospectively analyzed 111 osteoarticular samples (bone and joint samples, BJS) from 78 patients in care at the University Hospital of Rennes, France. The diagnosis procedure leading to the sample collection was linked to a suspicion of infection, inflammatory disease, arthritis, or for any bone or joint abnormalities. Standard bacteriological diagnosis and molecular biology analysis [16S rRNA polymerase chain reaction (PCR) and sequencing] were conducted. In addition, analysis by MALDI-TOF MS was performed directly on the osteoarticular samples, as soon as the amount allowed. Culture, which remains the gold standard for the diagnosis of BJI, has the highest sensitivity (85.9 %) and remains necessary to test antimicrobial susceptibility. The 16S rDNA PCR results were positive in the group with positive BJI (28.6 %) and negative in the group without infection. Direct examination remains insensitive (31.7 %) but more effective than MALDI-TOF MS directly on the sample (6.3 %). The specificity was 100 % in all cases, except for culture (74.5 %). Bacterial culture remains the gold standard, especially enrichment in blood bottles. Direct analysis of bone samples with MALDI-TOF MS is not useful, possibly due to the low inoculum of BJS.

Predictors of failure for prosthetic joint infections treated with debridement.

OBJECTIVE: Prosthetic joint infections (PJI) may be cured in selected patients with debridement and prosthesis retention. We aimed to identify predictors of failure to better target patients most likely to benefit from this conservative strategy. METHODS: Observational study of patients presenting with PJI initially treated at our hospital with debridement between 2008 and 2011, with>6 months of post-treatment follow-up. RESULTS: Sixty consecutive patients presenting with PJI (hip, n=34; knee, n=26) fulfilled the inclusion criteria. Failures (n=20, 33%), predefined as persistence of PJI signs or relapses, were managed with additional surgery (n=17) and/or lifelong suppressive antibiotic treatment (n=6). Variables independently associated with failure: previous surgery on the prosthetic joint (OR: 6.3 [1.8-22.3]), Staphylococcus aureus PJI (OR: 9.4 [1.6-53.9]), post-debridement antibiotic treatment for <3 months (OR: 20.0 [2.2-200]). CONCLUSION: Previous surgery, S. aureus PJI, and short duration antibiotic treatment are associated with an increased risk of failure after debridement.

[Screening for carriage of Staphylococcus aureus prior to mammary reconstruction in the prevention of surgical site infection]. / En reconstruction mammaire: intérêt du dépistage du portage de Staphylococcus aureus dans la prévention de l'infection du site opératoire.

The incidence of prosthesis infections after breast reconstruction is of the order of 4% to 13% according to the literature. In surgical patients, Staphylococcus aureus (S. aureus) is the bacterial species most often responsible for surgical site infections. In cardiac surgery, screening for carriage of S. aureus and preoperative decontamination are carried out routinely before prosthetic surgery. We retrospectively reviewed data from patients at our institution between January 2011 and December 2013. Our series showed that the prosthesis infection rates were in the range of 5.92% in 2008 with an ISO rate of S. aureus 3.61%. Routine screening for prosthetic reconstructions was performed to assess the impact of preoperative decontamination patients in carriers of S. aureus. This screening was done in 381 patients: 17.8% of patients were carriers of S. aureus ; 11 patients have an ISO (or an incidence rate of 2.88%) ; 5 patients have an ISO S. aureus (an incidence of S. aureus ISO 1.3%). The introduction of the screening process, allowed a drop of 5.92% ISO rate at 1.46% with a passage of S. aureus SSI rates of 3, 60% to 0.72%. In the near future, studies are needed to confirm these encouraging results, to demonstrate the efficacy of preoperative decontamination in carriers of S. aureus patients before laying prosthesis.

Antibiotic content of selective culture media for isolation of Capnocytophaga species from oral polymicrobial samples.

UNLABELLED: In oral microbiome, because of the abundance of commensal competitive flora, selective media with antibiotics are necessary for the recovery of fastidious Capnocytophaga species. The performances of six culture media (blood agar, chocolate blood agar, VCAT medium, CAPE medium, bacitracin chocolate blood agar and VK medium) were compared with literature data concerning five other media (FAA, LB, TSBV, CapR and TBBP media). To understand variable growth on selective media, the MICs of each antimicrobial agent contained in this different media (colistin, kanamycin, trimethoprim, trimethoprim-sulfamethoxazole, vancomycin, aztreonam and bacitracin) were determined for all Capnocytophaga species. Overall, VCAT medium (Columbia, 10% cooked horse blood, polyvitaminic supplement, 3·75 mg l(-1) of colistin, 1·5 mg l(-1) of trimethoprim, 1 mg l(-1) of vancomycin and 0·5 mg l(-1) of amphotericin B, Oxoid, France) was the more efficient selective medium, with regard to the detection of Capnocytophaga species from oral samples (P < 0·001) and the elimination of commensal clinical species (P < 0·001). The demonstrated superiority of VCAT medium, related to its antibiotic content, made its use indispensable for the optimal isolation of Capnocytophaga species from polymicrobial samples. SIGNIFICANCE AND IMPACT OF THE STUDY: Isolation of Capnocytophaga species is important for the proper diagnosis and treatment of the systemic infections they cause and for epidemiological studies of periodontal flora. We showed that in pure culture, a simple blood agar allowed the growth of all Capnocytophaga species. Nonetheless, in oral samples, because of the abundance of commensal competitive flora, selective media with antibiotics are necessary for the recovery of Capnocytophaga species. The demonstrated superiority of VCAT medium made its use essential for the optimal detection of this bacterial genus. This work showed that extreme caution should be exercised when reporting the isolation of Capnocytophaga species from oral polymicrobial samples, because the culture medium is a determining factor.

[Present and future strategies for women at risk, or suffering from premature ovarian failure (POF)]. / Quelles solutions d'avenir pour les femmes à risque, ou souffrant d'une insuffisance ovarienne précoce (IOP)?

The purpose of this review is to present the strategies for fertility preservation that are currently proposed to patients at risk from premature ovarian failure (POF) due to chemotherapy as well as some future solutions that could allow patients already affected by an IOP to recover their fertility. Today, cryo-preservation of pieces of ovarian cortex followed by orthotopic transplantation as well as in vitro maturation of oocytes (IVM) allow preservation of fertility in patients being to undergo an antitumor treatment. However, although promising results have been obtained, the pregnancy rate remains very low. Improvement of these techniques, but also stimulation of resting follicle activation, in vitro folliculogenesis, and culture of putative oogonia that may be present in the adult ovary, are all future opportunities for patients suffering from an IOP, and are currently the subject of intensive researches.

[Regulation of resting follicle activation]. / Régulation de l'initiation de la croissance folliculaire.

In humans, folliculogenesis starts when some resting follicles leave the ovarian reserve to enter the growing phase. Activation of resting follicles remains poorly understood, however recent data show existence of a balance between activating and repressing factors. Many molecules, comprised KIT ligand, bind a protein kinase receptor and activate the phosphatidylinositol kinase (PI3K) signaling pathway, which contains enzymes and transcription factors that either stimulate or inhibit activation of resting follicles. Some inhibiting (AMH) or activating (activin, BMPs) molecules belong to the TGF-ß super-family, while others can either stimulate (LIF, androgens) or inhibit (estradiol, progesterone, somatostatin) activation of resting follicles. The understanding of molecular mechanisms controlling activation of resting follicles has significant clinical implications in mobilizing resting follicles in patients suffering from infertility due to ovarian dysfunction either spontaneous or resulting from cancer treatments.

Effect of higher minimum inhibitory concentrations of quaternary ammonium compounds in clinical E. coli isolates on antibiotic susceptibilities and clinical outcomes.

Quaternary ammonium compounds (QACs) are cationic surfactants used as preservatives and environmental disinfectants. Limited data are available regarding the effect of QACs in the clinical setting. We performed a prospective cohort study in 153 patients with Escherichia coli bacteraemia from February to September 2008 at University Hospital in Rennes. The minimum inhibitory concentrations (MICs) of antibiotics and QACs alkyldimethylbenzylammonium chloride (ADBAC) and didecyldimethylammonium chloride (DDAC) were determined by the agar dilution method. The capacity of biofilm production was assayed using the Crystal Violet method, and mutation frequencies by measuring the capacity of strains to generate resistance to rifampicin. Logistic regression analysis showed that one of the significant factors related to low MICs for ADBAC (≤16 mg/L) and DDAC (≤8 mg/L), was cotrimoxazole susceptibility (odds ratio: 3.72; 95% confidence interval: 1.22-11.24; P=0.02 and OR: 3.61; 95% CI: 1.56-7.56; P<0.01, respectively). Antibiotic susceptibility to cotrimoxazole was strongly associated with susceptibility to amoxicillin and nalidixic acid (P<0.01). Community-acquired or healthcare-associated bacteraemia, severity of bacteraemia, and patient outcome were independent of the MICs of ADBAC and DDAC. Our findings demonstrate an epidemiological relationship between higher MIC values of QACs in clinical E. coli isolates and antibiotic resistance.

[Is neo-oogenesis in the adult ovary, a realistic paradigm?]. / La néo-ovogenèse spontanée dans l'ovaire adulte est-elle une hypothèse réaliste ?

It is a central dogma of female reproductive biology that oogenesis ceases around the time of birth in mammalian species. In 2004 and 2005, two studies were published by Johnson et al., in which they claimed that in the adult mouse ovary, neo-oogenesis takes place and originates from female germline stem cells that are present in either the ovarian surface epithelium or bone marrow. Following these publications, experiments showed that non-germinal stem cells could generate oocytes. However, in the mouse, ability of extra-ovarian stem cells to refurbish the ovary in new oocytes competent to ovulate, and subsequent existence of a spontaneous neo-oogenesis in the adult ovary in normal physiologic conditions, have been disputed. Morphologic studies performed in the adult mouse ovary showed that atresia of the immature follicle pool was strongly overestimated by Johnson et al., and that no intermediary stages of meiosis were seen. These observations led to the conclusion that adult female mice do not need neo-oogenesis for maintaining a normal reproductive function. However, a recent study have shown that female germline stem cells might be present in the ovarian surface epithelium in mice and humans. When sampled in GFP transgenic mice, cultured for a long period and transplanted into ovaries of sterilized mice, these cells underwent oogenesis and the mice produced offsprings. These new data support the possibility to experimentally restore fertility in women suffering from a premature ovarian failure.

Human ovarian follicular development: from activation of resting follicles to preovulatory maturation.

By integrating morphometrical and endocrinological data, as well as biological effects of various molecules synthesized by the human follicle, we propose a dynamic view of the follicle growth within the human ovary. Folliculogenesis starts with entry of resting follicles into the growth phase, a process where the kit system plays a key role. Several months are required for a new growing follicle to reach the preantral stage (0.15mm), then 70 additional days to reach the size of 2mm. Early growing follicle growth is regulated by subtle interactions between follicle-stimulating hormone (FSH) and local factors produced by theca and granulosa cells (GCs), as well as the oocyte. From the time they enter the selectable stage during the late luteal phase, follicles become sensitive to cyclic changes of FSH in terms of granulosa cell proliferation. During the early follicular phase, the early selected follicle grows very quickly and estradiol is present in the follicular fluid. However, the total steroid production remains moderate. From the mid-follicular phase, the preovulatory follicle synthesizes high quantities of estradiol, then after the mid-cycle gonadotropin surge, very large amounts of progesterone. At this stage of development, the responsiveness of the follicle to gonadotropins is maximum, especially to luteinizing hormone (LH) that triggers granulosa wall dissociation and cumulus expansion as well as oocyte nuclear maturation. Thus, as the follicle develops, its responsiveness to gonadotropins progressively increases under the control of local factors acting in an autocrine/paracrine fashion.

Distribution of mutation frequencies among Salmonella enterica isolates from animal and human sources and genetic characterization of a Salmonella Heidelberg hypermutator.

Hypermutation is an important mechanism used by different Salmonella enterica subspecies enterica to regulate genetic stability in adaptation to changing environments, including antimicrobial treatments and industrial processes. Strong hypermutator strains generally contain a mutation in genes of the methyl mismatch repair (MMR) system and have mutation frequencies up to 1000-fold higher than wild type strains. The objectives of this study were to determine the distribution of mutation frequencies from a collection of 209 Salmonella strains, to genetically characterize a strong mutator, and to study MMR mutated protein-DNA binding interactions. Only one strain of S. Heidelberg was determined to have a hypermutator phenotype by virtue of its high mutation rate. Sequencing of genes of the MMR system showed a 12bp deletion in the mutS gene was present. The MMR mutated protein-DNA binding interactions were studied by bioanalysis, using the available crystal structure of a similar MutS protein from Escherichia coli. This analysis showed the small deletion in the Salmonella MutS was localized within the core domain. A retardation assay with MutS from hypermutable and wild type strains showed this mutation has no effect on MutS DNA binding. A better understanding of the genetic mechanisms of hypermutation will help to anticipate the behavior of hypermutator strains in various conditions.

Outbreak of Serratia marcescens in a neonatal intensive care unit: contaminated unmedicated liquid soap and risk factors.

This study describes an outbreak of Serratia marcescens and its investigation and control in a neonatal intensive care unit (NICU). During a three-month period, five infants were colonised or infected by a single strain of S. marcescens. A case-control study, culture surveys and pulse-field gel electrophoresis analysis implicated a bottle soap dispenser as a reservoir of S. marcescens (P=0.032). Infants with S. marcescens colonisation or infection were also more likely to have been exposed to a central or percutaneous venous catheter (P=0.05) and had had longer exposure to endotracheal intubation (P=0.05). Soap dispensers are used in many hospitals and may be an unrecognised source of nosocomial infections. This potential source of infection could be reduced by using 'airless' dispensers which have no air intake for the distribution of soap. Prompt intervention and strict adherence to alcoholic hand disinfection were the key factors that led to the successful control of this outbreak.