Case Report: Arthroscopic "Debridement Antibiotics and Implant Retention" With Local Injection of Personalized Phage Therapy to Salvage a Relapsing Pseudomonas Aeruginosa Prosthetic Knee Infection

Bacteriophages are viruses that specifically target bacteria. They are considered to have a high potential in patients with prosthetic joint infection (PJI), as they have a synergistic anti-biofilm activity with antibiotics. We report here the case of an 88-year-old man (63 kg) with relapsing Pseudomonas aeruginosa prosthetic knee infection. The patient had severe alteration of the general status and was bedridden with congestive heart failure. As prosthesis explantation and/or exchange was not feasible, we proposed to this patient the use of phage therapy to try to control the disease in accordance with the local ethics committee and the French National Agency for Medicines and Health Products Safety (ANSM). Three phages, targeting P. aeruginosa, were selected based on their lytic activity on the patient's strain (phagogram). Hospital pharmacist mixed extemporaneously the active phages (initial concentration 1 ml of 1 × 1010 PFU/ml for each phage) to obtain a cocktail of phages in a suspension form (final dilution 1 × 109 PFU/ml for both phages). Conventional arthroscopy was performed and 30 cc of the magistral preparation was injected through the arthroscope (PhagoDAIR procedure). The patient received intravenous ceftazidime and then oral ciprofloxacin as suppressive antimicrobial therapy. Under this treatment, the patient rapidly improved with disappearance of signs of heart failure and pain of the left knee. During the follow-up of 1 year, the local status of the left knee was normal, and its motion and walking were unpainful. The present case suggests that the PhagoDAIR procedure by arthroscopy has the potential to be used as salvage therapy for patients with P. aeruginosa relapsing PJI, in combination with suppressive antimicrobial therapy. A Phase II clinical study deserves to be performed to confirm this hypothesis

Adaptation of Staphylococcus aureus in a Medium Mimicking a Diabetic Foot Environment

International audienceStaphylococcus aureus is the most prevalent pathogen isolated from diabetic foot infections (DFIs). The purpose of this study was to evaluate its behavior in an in vitro model mimicking the conditions encountered in DFI. Four clinical S. aureus strains were cultivated for 16 weeks in a specific environment based on the wound-like medium biofilm model. The adaptation of isolates was evaluated as follows: by Caenorhabditis elegans model (to evaluate virulence); by quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) (to evaluate expression of the main virulence genes); and by Biofilm Ring test® (to assess the biofilm formation). After 16 weeks, the four S. aureus had adapted their metabolism, with the development of small colony variants and the loss of β-hemolysin expression. The in vivo nematode model suggested a decrease of virulence, confirmed by qRT-PCRs, showing a significant decrease of expression of the main staphylococcal virulence genes tested, notably the toxin-encoding genes. An increased expression of genes involved in adhesion and biofilm was noted. Our data based on an in vitro model confirm the impact of environment on the adaptation switch of S. aureus to prolonged stress environmental conditions. These results contribute to explore and characterize the virulence of S. aureus in chronic wounds

Unexpected categories at risk of S. aureus nasal carriage among hospital workers

Objectives: Thirty percent of the general population are Staphylococcus aureus nasal carriers. It has been shown that this increases with repeated contact with patients, but it is not known whether all categories of healthcare workers are at equal risk of carriage. We aimed to explore S. aureus nasal carriage among healthcare professionals.Methods: Prospective study conducted in two French university hospitals in 2014 and 2016. Volunteers were screened for S. aureus nasal carriage. Profession and hygiene habits were collected. Based on the results of this initial study, a second study focused on semi-skilled workers and biomedical equipment technicians (BETs) only; participants were given education on the basic rules of hygiene, then re-screened three months later.Results: In the initial study, 38.8% of the 436 participants were detected as nasal carriers. There was a significant difference in nasal carriage according to professional category (p < 0.0001); the lowest was found among administrative agents (17.3%), followed by healthcare providers (37.4%), laboratory technicians (37.6%). The greatest proportion was found among semi-skilled workers and BETs (52.9%). Spa-typing ruled out the hypothesis of a single clone dissemination among colleagues. After the three-month hygiene awareness campaign, all re-screened individuals remained positive, and with their respective initial strain.Conclusions: To the best of our knowledge we report here for the first time that semi-skilled workers and BETs are specifically more at risk of S. aureus nasal colonisation. This striking finding urges hospital hygiene departments to evaluate this specific professional category and implement strategies to improve hygiene awareness

Time to blood culture positivity an independent predictor of infective endocarditis and mortality in patients with Staphylococcus aureus bacteraemia

International audienceObjectives - Time to blood culture positivity (TTP), a routinely available parameter in automated blood culture systems, may be a proxy for infectious burden in patients with bloodstream infections. We aimed to study the association between TTP and infective endocarditis (IE), or death, in patients with Staphylococcus aureus bacteraemia. Methods - VIRSTA is a multicenter prospective cohort study that included all adult patients with S. aureus bacteraemia in eight university hospitals in France (2009-2011). We analyzed data from four centers which collected data on TTP. Regression models were used to study the association between TTP and definite IE (Duke-Li criteria), and 30 day-mortality. Results - We included 587 patients with S. aureus bacteraemia: mean age was 65.3±16.3 years, 420/587 patients (71.6%) were male, 121/587 (20.6%) died, and 42/587 (7.2%) had definite IE. Median TTP of first positive blood culture was 13.7 h (interquartile range, 9.9-18). On multivariate analysis, 30-day mortality was associated with TTP≤13.7 h (74/295 (25.1%) vs 47/292 (16.1%), P=0.02), as well as old age, McCabe score, methicillin resistance, stroke, pneumonia, and C-Reactive Protein. TTP was also independently associated with IE, but with a U-shape curve: IE was more common in the first (TTP18 h, 8/146, 5.5%) quartiles of TTP, P=0.002. Conclusions - TTP provides reliable information in patients with S. aureus bacteraemia, on the risk of IE, and prognosis, with short TTP being an independent predictor of death. This data readily available at no cost may be used to identify patients who require specific attention

Demographic fluctuation of community-acquired antibiotic-resistant Staphylococcus aureus lineages: potential role of flimsy antibiotic exposure

International audienceCommunity-acquired (CA)-~as opposed to hospital acquired- methicillin-resistant Staphylococcus aureus (MRSA) lineages arose worldwide during the 1990s. To determine which factors, including selective antibiotic pressure, govern the expansion of two major lineages of CA-MRSA, namely "USA300" in Northern America and "European ST80" in North Africa, Europe and Middle-East, we explored virulence factor expression, and fitness levels with or without antibiotics. The sampled strains were collected in a temporal window representing various steps of the epidemics, reflecting predicted changes in effective population size as inferred from whole-genome analysis. In addition to slight variations in virulence factor expression and biofilm production that might influence the ecological niches of theses lineages, competitive fitness experiments revealed that the biological cost of resistance to methicillin, fusidic acid and fluoroquinolones is totally reversed in the presence of trace amount of antibiotics. Our results suggest that low-level antibiotics exposure in human and animal environments contributed to the expansion of both European ST80 and USA300 lineages in community settings. This surge was likely driven by antibiotic (ab)use promoting the accumulation of antibiotics as environmental pollutants. The current results provide a novel link between effective population size increase of a pathogen and a selective advantage conferred by antibiotic resistance

Author Correction: Complex ecological interactions of Staphylococcus aureus in tampons during menstruation

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Complex ecological interactions of Staphylococcus aureus in tampons during menstruation

International audienceMenstrual toxic shock syndrome (mTSS) is a severe disease that occurs in healthy women vaginally colonized by Staphylococcus aureus producing toxic shock toxin 1 and who use tampons. The aim of the present study was to determine the impact of the composition of vaginal microbial communities on tampon colonisation by S. aureus during menses. We analysed the microbiota in menstrual fluids extracted from tampons from 108 healthy women and 7 mTSS cases. Using culture, S. aureus was detected in menstrual fluids of 40% of healthy volunteers and 100% of mTSS patients. Between class analysis of culturomic and 16S rRNA gene metabarcoding data indicated that the composition of the tampons' microbiota differs according to the presence or absence of S. aureus and identify discriminating genera. However, the bacterial communities of tampon fluid positive for S. aureus did not cluster together. No difference in tampon microbiome richness, diversity, and ecological distance was observed between tampon vaginal fluids with or without S. aureus, and between healthy donors carrying S. aureus and mTSS patients. Our results show that the vagina is a major niche of. S. aureus in tampon users and the composition of the tampon microbiota control its virulence though more complex interactions than simple inhibition by lactic acid-producing bacterial species