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Abstract: It was recently observed that a glucose-enriched diet activates the insulin-like pathway in Caenorhabditis elegans, resulting in an inhibition of the FOXO transcription factor DAF-16. Because this signalling pathway is highly conserved from invertebrates to mammals and DAF-16 is a key player in innate immunity, we wondered whether a high-glucose diet, resembling the hyperglycaemic conditions in diabetic patients, would affect the susceptibility of C. elegans to bacterial pathogens isolated from different clinical situations (urinary tract or diabetic foot infections). We confirmed previous reports showing that such a diet decreases the lifespan of C. elegans fed with an avirulent Escherichia coli strain. However, glucose-fed nematodes appeared to be more resistant to most clinical isolates tested, showing that this invertebrate model does not mimic infections encountered in human diabetes, where patients show increased susceptibility to bacterial infections. This study also suggests that modulation of innate immunity in C. elegans, upon activation of the IGF1/insulin-like pathway by glucose, is not exclusively mediated by DAF-16, but also involves an additional factor that requires DAF-16 activity. [Copyright &y& Elsevier]

Abstract: Imipenem (IPM) is a carbapenem antibiotic frequently used in severe hospital infections. Several reports have mentioned the emergence of resistant isolates exhibiting membrane modifications. A study was conducted between September 2005 and August 2007 to survey infections due to Enterobacter aerogenes in patients hospitalised in a French university hospital. Resistant E. aerogenes clinical isolates obtained from patients treated with IPM and collected during the 3 months following initiation of treatment were phenotypically and molecularly characterised for β-lactamases, efflux pumps activity and outer membrane proteins. Among the 339 patients infected with E. aerogenes during the study period, 41 isolates (12.1%) were resistant to extended-spectrum cephalosporins and 17 patients (5.0%) were treated with IPM. The isolates from these 17 patients presented TEM-24 and basal efflux expression. Following IPM treatment, an IPM-intermediate-susceptible (IPM-I) isolate emerged in 11 patients and an IPM-resistant (IPM-R) isolate in 6 patients. A change in the porin balance (Omp35/Omp36) was observed in IPM-I isolates exhibiting ertapenem resistance. Finally, a porin deficiency (Omp35 and Omp36 absence) was detected in IPM-R isolates associated with efflux pump expression. This study indicates that the alteration in porin expression, including the shift of porin expression and lack of porins, contribute to the E. aerogenes adaptive response to IPM treatment. [Copyright &y& Elsevier]

Abstract: Salmonella enterica serovar Typhimurium (S. Typhimurium) and certain Escherichia coli are human pathogens that have evolved through the acquisition of multiple virulence determinants by horizontal gene transfer. Similar genetic elements, as pathogenicity islands and virulence plasmids, have driven molecular evolution of virulence in both species. In addition, the contribution of prophages has been recently highlighted as a reservoir for pathogenic diversity. Characterization of horizontally acquired virulence genes has several clinical implications. First, identification of virulence determinants that have a sporadic distribution and are specifically associated with a pathotype and/or a pathology can be useful markers for risk assessment and diagnosis. Secondly, virulence factors widely distributed in pathogenic strains, but absent from non-pathogenic bacteria, are interesting targets for the development of novel antimicrobial chemotherapies and vaccines. Here, we summarize the horizontally acquired virulence factors of S. Typhimurium, enterohemorrhagic E. coli O157:H7 and uropathogenic E. coli, and we describe their use in novel therapeutic approaches. [Copyright &y& Elsevier]

Escherichia coli (E. coli) is the most frequent bacterium implicated in community-acquired infection as well as in nosocomial infections. This bacterium is characterised by numerous possibilities to acquire resistance mechanisms, even during antibiotic treatment. The main mechanism of resistance is the production of beta-lactamines, enzymes hydrolysing beta-lactam ring. This paper describes enzymatic mechanisms of resistance of E. coli to beta-lactam and indicates the necessity of a good knowledge of the risk factors for resistance to have an adapted good clinical practice in using antibiotics. [Copyright &y& Elsevier]

To assess the performance of the rapid syndromic BioFire® Joint Infection Panel (BF-JIP) to detect bacterial and fungal pathogens, as well as antibiotic resistance genes, directly in synovial fluid specimens collected from patients with acute arthritis. The study was conducted in six French bacteriological laboratories. To assess the performances of BF-JIP, results were compared with those of synovial fluid 14-day culture and, in case of discrepancy, with those of complementary molecular methods and intraoperative samples. A total of 308 synovial fluid specimens were tested after collection from 308 adults and children presenting with clinical and biological suspicion of acute arthritis; patients presenting with acute periprosthetic joint infection were included according to the European Bone and Joint Infection Society 2021 criteria. Only one specimen failed (no result). On the basis of the consolidated data, the BF-JIP was concordant with the 14-day culture in 280 (91.2%) of the 307 specimens finally included in the study. The positive percentage agreement was 84.9% (95% CI, 78.8–89.8%) and the negative percentage agreement was 100% (95% CI, 97.2–100%). The positive predictive value was extremely high (100%; 95% CI, 97.6–100%), whereas the negative predictive value was lower (82.6%; 95% CI, 75.7–88.2%), partially explained by the missing target species in the panel. The BF-JIP showed high performances to detect pathogens involved in acute arthritis. [ABSTRACT FROM AUTHOR]

Abstract We propose a new approach combining the principles and advantages of stir bar sorptive extraction (SBSE) and headspace sorptive extraction (HSSE). Stir bars have so far never been used for the extraction of volatile/semi-volatile bacterial compounds. The effectiveness of two stir bars with polydimethylsiloxane (PDMS) or ethylene glycol/silicone (EGS) as sorbent was tested by performing sample extraction directly in gas chromatography (GC) vials containing bacterial cultures. Several combinations of desorption and extraction were tested at different growth times. When the extraction was carried out simultaneously with the EGS stir bar in headspace and the PDMS in the bacterial culture, the number of extracted compounds was significantly increased. Using both twisters increased the polarity range of the compounds found, and extraction at the end of the exponential phase of growth generated the best yields. This method was successfully applied to determine the production of 17 molecules by a strain of Staphylococcus aureus. In conclusion, this study paves the way for a new method for determining the volatile metabolite profile of bacteria, which can provide a promising innovative alternative in the identification of biomarkers. Graphical abstract fx1 Highlights • Assessment of stir bar sorptive extraction in bacterial identification. • Two coatings with different properties (EGS and PDMS) were tested. • Simultaneous extraction allows higher recovery of bacterial volatile compounds. • This method provides a novel method of chemical analysis of bacterial metabolites. [ABSTRACT FROM AUTHOR]

Abstract: One of the most critical post-surgical complications is mesh-related infection. This paper describes how a commercially available polypropylene (PP) mesh was modified to minimize the risk of post-implantation infection. A dual drug-release coating was created around mesh filaments using an airbrush spray system. This coating was composed of three layers containing ofloxacin and rifampicin dispersed in a degradable polymer reservoir made up of [poly(ε-caprolactone) (PCL) and poly(dl-lactic acid) (PLA)]. Drug release kinetics were managed by varying the structure of the degradable polymer and the multilayer coating. In vitro, this new drug delivery polymer system was seen to be more rapidly invaded by fibroblasts than was the initial PP mesh. Active mesh showed excellent antibacterial properties with regard to microorganism adhesion, biofilm formation and the periprosthetic inhibition of bacterial growth. Sustained release of the two antibiotics from the coated mesh prevented mesh contamination for at least 72h. This triple-layer coating technology is potentially of great interest for it can be easily extrapolated to other medical devices and drug combinations for the prevention or treatment of other diseases. [Copyright &y& Elsevier]

To evaluate performances of the rapid multiplex PCR assay BioFire FilmArray Pneumonia Panel (FA-PP) for detection of bacterial pathogens and antibiotic resistance genes in sputum, endotracheal aspirate (ETA) and bronchoalveolar lavage (BAL) specimens. This prospective observational study was conducted in 11 French university hospitals (July to December 2018) and assessed performance of FA-PP by comparison with routine conventional methods. A total of 515 respiratory specimens were studied, including 58 sputa, 217 ETA and 240 BAL. The FA-PP detected at least one pathogen in 384 specimens, yielding an overall positivity rate of 74.6% (384/515). Of them, 353 (68.5%) specimens were positive for typical bacteria while eight atypical bacteria and 42 resistance genes were found. While identifying most bacterial pathogens isolated by culture (374/396, 94.4%), the FA-PP detected 294 additional species in 37.7% (194/515) of specimens. The FA-PP demonstrated positive percentage agreement and negative percentage agreement values of 94.4% (95% CI 91.7%–96.5%) and 96.0% (95% CI 95.5%–96.4%), respectively, when compared with culture. Of FA-PP false-negative results, 67.6% (46/68) corresponded to bacterial species not included in the panel. At the same semi-quantification level (in DNA copies/mL for FA-PP versus in CFU/mL for culture), the concordance rate was 43.4% (142/327) for culture-positive specimens with FA-PP reporting higher semi-quantification of ≥1 log 10 in 48.6% (159/327) of cases. Interestingly, 90.1% of detected bacteria with ≥106 DNA copies/mL grew significantly in culture. FA-PP is a simple and rapid molecular test that could complement routine conventional methods for improvement of diagnosis accuracy of pneumonia. [ABSTRACT FROM AUTHOR]

The 2019 Nîmes International Symposium in Antibiotic Therapy Optimisation aimed at determining the best approaches of a number of the antibiotic management strategies for critically ill patients. Experts reviewed the latest literature relating to requirements for an optimal antibiotic stewardship program, risks of sub-therapeutic dosing of antibiotics in critically ill patients, persisting issues about efficiency of combination therapy and the value of de-escalation, new perspectives of pharmacokinetics, drug toxicities including collateral damages-associated with antibiotics, the place of nebulisation of antibiotics, management of patients receiving extracorporeal therapies and the place of new antibiotics. In this paper, each of these issues is discussed with key messages presented after a brief review of evidence. [ABSTRACT FROM AUTHOR]

• Resistance to fluoroquinolones and cephalosporins in Escherichia coli was mainly correlated with fluoroquinolone consumption. • Resistance to fluoroquinolones and cephalosporins in E. coli was negatively correlated with anti-pseudomonal activity penicillin with beta-lactamase inhibitors consumption. • The predictive abilities of dynamic regression models are moderate. • The results should be used with caution for the implementation of antimicrobial stewardship programs. The aim of this study was to determine the correlation between antimicrobial consumption (AMC) and antimicrobial resistance (AMR) in Escherichia coli at a hospital level, and assess the capacity of dynamic regression (DR) models to predict AMR for their use in deployment of antimicrobial stewardship programs (ASPs). A retrospective epidemiological study was conducted in a French tertiary hospital between 2014 and 2019. DR models were used to assess the correlation between AMC and AMR from 2014 to 2018. The predictive abilities of the models were estimated by comparing the predicted data with those observed in 2019. Rates of fluoroquinolone and cephalosporin resistance decreased. AMC increased overall but decreased for fluoroquinolone. DR models highlighted that the decrease in use of fluoroquinolone and the increase in use of anti-pseudomonal activity penicillin with beta-lactamase inhibitor (AAPBI) explained 54% of the decrease in fluoroquinolone resistance and 15% of the decrease in cephalosporin resistance. In addition, penicillin/beta-lactamase inhibitor (PBI) consumption explained 53% of PBI resistance, and beta-lactam use explained 36% of penicillin resistance, with both remaining stable over time. DR models had predictive capabilities with margins of error from 8% to 34%. Over a six-year period in a French tertiary hospital, decreasing rates of resistance to fluoroquinolones and cephalosporins were correlated with decreasing use of fluoroquinolone and increasing use of AAPBI, whereas rates of resistance to penicillin remained high and stable. The results indicate that DR models should be used with caution for AMR forecasting and ASP implementation. [ABSTRACT FROM AUTHOR]

Few reports described infections with CC398 methicillin-susceptible Staphylococcus aureus (MSSA). We compared the genetic background of CC398 MSSA strains from nasal carriage and knee arthroplasty infection. DNA microarray analysis shows acquisition of particular adhesin, iron capture system and immune defense evasion mechanisms. These characteristics could explain pathogenesis in this type of infection. [ABSTRACT FROM AUTHOR]