Qualified presumption of safety (QPS) was developed to provide a generic safety evaluation for biological agents to support EFSA's Scientific Panels. The taxonomic identity, body of knowledge, safety concerns and antimicrobial resistance are assessed. Safety concerns identified for a taxonomic unit (TU) are where possible to be confirmed at strain or product level, reflected by 'qualifications'. No new information was found that would change the previously recommended QPS TUs and their qualifications. The list of microorganisms notified to EFSA was updated with 54 biological agents, received between April and September 2019; 23 already had QPS status, 14 were excluded from the QPS exercise (7 filamentous fungi, 6 Escherichia coli, Sphingomonas paucimobilis which was already evaluated). Seventeen, corresponding to 16 TUs, were evaluated for possible QPS status, fourteen of these for the first time, and Protaminobacter rubrum, evaluated previously, was excluded because it is not a valid species. Eight TUs are recommended for QPS status. Lactobacillus parafarraginis and Zygosaccharomyces rouxii are recommended to be included in the QPS list. Parageobacillus thermoglucosidasius and Paenibacillus illinoisensis can be recommended for the QPS list with the qualification 'for production purposes only' and absence of toxigenic potential. Bacillus velezensis can be recommended for the QPS list with the qualification 'absence of toxigenic potential and the absence of aminoglycoside production ability'. Cupriavidus necator, Aurantiochytrium limacinum and Tetraselmis chuii can be recommended for the QPS list with the qualification 'production purposes only'. Pantoea ananatis is not recommended for the QPS list due to lack of body of knowledge in relation to its pathogenicity potential for plants. Corynebacterium stationis, Hamamotoa singularis, Rhodococcus aetherivorans and Rhodococcus ruber cannot be recommended for the QPS list due to lack of body of knowledge. Kodamaea ohmeri cannot be recommended for the QPS list due to safety concerns.

https://efsa.onlinelibrary.wiley.com/doi/pdf/10.2903/j.efsa.2020.5965

Update of the list of QPS-recommended biological agents intentionally added to food or feed as notified to EFSA 13: suitability of taxonomic units notified to EFSA until September 2020.

Objective: To describe the contemporary features of coagulase-negative staphylococcal (CoNS) prosthetic valve endocarditis (PVE). Design: Observational study of prospectively collected data from a multinational cohort of patients with infective endocarditis. Patients with CoNS PVE were compared to patients with Staphylococcus aureus and viridans streptococcal (VGS) PVE. Setting: The International Collaboration on Endocarditis-Prospective Cohort Study (ICE-PCS) is a contemporary cohort of patients with infective endocarditis from 61 centres in 28 countries. Patients: Adult patients in the ICE-PCS with definite PVE and no history of injecting drug use from June 2000 to August 2005 were included. Interventions: None. Main outcome measures: Heart failure, intracardiac abscess, death. Results: CoNS caused 16% (n = 86) of 537 cases of definite non-injecting drug use-associated PVE. Nearly one-half (n = 33/69, 48%) of patients with CoNS PVE presented between 60 days and 365 days of valve implantation. The rate of intracardiac abscess was significantly higher in patients with CoNS PVE (38%) than in patients with either S aureus (23%, p = 0.03) or VGS (20%, p = 0.05) PVE. The rate of abscess was particularly high in early (50%) and intermediate (52%) CoNS PVE. In-hospital mortality was 24% for CoNS PVE, 36% for S aureus PVE (p = 0.09) and 9.1% for VGS PVE (p = 0.08). Meticillin resistance was present in 68% of CoNS strains. Conclusions: Nearly one-half of CoNS PVE cases occur between 60 days and 365 days of prosthetic valve implantation. CoNS PVE is associated with a high rate of meticillin resistance and significant valvular complications.

Coagulase-negative Staphylococcal Prosthetic Valve Endocarditis: A Contemporary Update Based on the International Collaboration on Endocarditis - Prospective Cohort Study (ICE-PCS)

Extracellular polymeric substances (EPS) hold infectious biofilms together and limit antimicrobial penetration and clinical infection control. Here, we present zwitterionic micelles as a previously unexplored, synthetic self-targeting dispersant. First, a pH-responsive poly(e-caprolactone)-block-poly(quaternary-amino-ester) was synthesized and self-assembled with poly(ethylene glycol)-block-poly(e-caprolactone) to form zwitterionic, mixed-shell polymeric micelles (ZW-MSPMs). In the acidic environment of staphylococcal biofilms, ZW-MSPMs became positively charged because of conversion of the zwitterionic poly(quaternary-amino-ester) to a cationic lactone ring. This allowed ZW-MSPMs to self-target, penetrate, and accumulate in staphylococcal biofilms in vitro. In vivo biofilm targeting by ZW-MSPMs was confirmed for staphylococcal biofilms grown underneath an implanted abdominal imaging window through direct imaging in living mice. ZW-MSPMs interacted strongly with important EPS components such as eDNA and protein to disperse biofilm and enhance ciprofloxacin efficacy toward remaining biofilm, both in vitro and in vivo. Zwitterionic micellar dispersants may aid infection control and enhance efficacy of existing antibiotics against remaining biofilm.

/pdf/self-targeting-zwitterionic-micellar-dispersants-enhance-3k8rvod79f.pdf

Self-targeting, zwitterionic micellar dispersants enhance antibiotic killing of infectious biofilms-An intravital imaging study in mice.

Can β-Lactam Antibiotics Be Resurrected to Combat MRSA?

Targeted polymer-based antibiotic delivery system: A promising option for treating bacterial infections via macromolecular approaches

Methicillin-resistant Staphylococcus aureus (MRSA) is a medical concern. Here, we show that branched polyethylenimine (BPEI), a nontoxic, cationic polymer, restores MRSA’s susceptibility to β-lactam antibiotics. Checkerboard assays with MRSA demonstrated synergy between BPEI and β-lactam antibiotics. A time-killing curve showed BPEI to be bactericidal in combination with oxacillin. BPEI did not potentiate efficacy with vancomycin, chloramphenicol, or linezolid. When exposed to BPEI, MRSA increased in size and had difficulty forming septa. BPEI electrostatically binds to wall teichoic acid (WTA), a cell wall anionic polymer of Gram-positive bacteria that is important for localization of certain cell wall proteins. Lack of potentiation in a WTA knockout mutant supports the WTA-based mechanism. These data suggest that BPEI may prevent proper localization of cell wall machinery by binding to WTA; leading to cell death when administered in combination with β-lactam antibiotics. Negligible in vitro toxicity sug...

Targeting Wall Teichoic Acid in Situ with Branched Polyethylenimine Potentiates β-Lactam Efficacy against MRSA

Staphylococcus epidermidis is one of the most prevalent prokaryotic species on human skin and mucosal membranes that constitute the commensal flora S epidermidis has become one of the most common causes of primary bacteremia Infections are difficult to diagnose because the pathogen has natural niches on human skin and the ability to adhere to inanimate surfaces via biofilms Alarmingly, S epidermidis has acquired resistance to many antibiotics, which presents a danger to human health Known as methicillin-resistant S epidermidis (MRSE), most clinical isolates of MRSE in North America exhibit β-lactam resistance primarily due to the presence of mecA, a gene that bestows β-lactam antibiotic resistance in a manner similar to methicillin-resistant Staphylococcus aureus (MRSA) MecA encodes for expression of penicillin-binding protein 2a (PBP2a), which is absent in β-lactam susceptible strains of S epidermidis We can disable this resistance factor in MRSE with 600-Da branched polyethylenimine (BPEI) Cationic BPEI targets anionic wall teichoic acid (WTA), an essential cofactor for proper functioning of PBP2a We found that BPEI synergizes the activity of β-lactam antibiotics against MRSE Growth curves suggest that the combination of BPEI and oxacillin is bactericidal Electron micrographs indicate abnormalities in the cellular septa and cell walls of treated samples Therefore, first-line clinical treatments can be effective against MRSE when used in combination with BPEI

/pdf/cationic-branched-polyethylenimine-bpei-disables-antibiotic-4pm1a2kexu.pdf

Cationic Branched Polyethylenimine (BPEI) Disables Antibiotic Resistance in Methicillin-Resistant Staphylococcus epidermidis (MRSE).

Clinicians prescribe hundreds of millions of β-lactam antibiotics to treat the majority of patients presenting with bacterial infections. Patient outcomes are positive unless resistant bacteria, su...

/pdf/overcoming-multidrug-resistance-and-biofilms-of-pseudomonas-2jo1yqvwpo.pdf

Overcoming Multidrug Resistance and Biofilms of Pseudomonas aeruginosa with a Single Dual-Function Potentiator of β-Lactams.

With its high morbidity rate and increasing resistance to treatment, methicillin-resistant Staphylococcus aureus (MRSA) is a grave concern in the medical field. In methicillin-susceptible strains, β-lactam antibiotics disable the penicillin binding proteins (PBPs) that cross-link the bacterial cell wall. However, methicillin-resistant strains have PBP2a and PBP4, which continue enzymatic activity in the presence of β-lactam antibiotics. The activity of PBP2a and PBP4 is linked to the presence of wall teichoic acid (WTA); thus, WTA has emerged as a target for antibiotic drug discovery. In this work, we disable WTA in situ using its anionic phosphodiester backbone to attract cationic branched polyethylenimine (BPEI). Data show that BPEI removes β-lactam resistance in common MRSA strains and clinical isolates. Fluorescence microscopy was used to investigate this mechanism of action. The results indicate that BPEI prevents the localization of PBP4 to the cell division septum, thereby changing the cellular morphology and inhibiting cell division. Although PBP4 is not required for septum formation, proper cell division and morphology require WTA; BPEI prevents this essential function. The combination of BPEI and β-lactams is bactericidal and synergistic. Because BPEI allows us to study the role of WTA in the cell wall without genetic mutation or altered translocation of biomolecules and/or their precursors, this approach can help revise existing paradigms regarding the role of WTA in prokaryotic biochemistry at every growth stage.

/pdf/bpei-induced-delocalization-of-pbp4-potentiates-b-lactams-jtx3al1vti.pdf

Erika L. Moen

Papers

Targeting Wall Teichoic Acid in Situ with Branched Polyethylenimine Potentiates β-Lactam Efficacy against MRSA

Cationic Branched Polyethylenimine (BPEI) Disables Antibiotic Resistance in Methicillin-Resistant Staphylococcus epidermidis (MRSE).

Overcoming Multidrug Resistance and Biofilms of Pseudomonas aeruginosa with a Single Dual-Function Potentiator of β-Lactams.

BPEI-Induced Delocalization of PBP4 Potentiates β-lactams Against MRSA.

Antibiofilm Synergy of β-Lactams and Branched Polyethylenimine against Methicillin-Resistant Staphylococcus epidermidis.