BWC0977, a broad-spectrum antibacterial clinical candidate to treat multidrug resistant infections.

The global crisis of antimicrobial resistance (AMR) necessitates the development of broad-spectrum antibacterial drugs effective against multi-drug resistant (MDR) pathogens. BWC0977, a Novel Bacterial Topoisomerase Inhibitor (NBTI) selectively inhibits bacterial DNA replication via inhibition of DNA gyrase and topoisomerase IV. BWC0977 exhibited a minimum inhibitory concentration (MIC90) of 0.03-2 µg/mL against a global panel of MDR Gram-negative bacteria including Enterobacterales and non-fermenters, Gram-positive bacteria, anaerobes and biothreat pathogens. BWC0977 retains activity against isolates resistant to fluoroquinolones (FQs), carbapenems and colistin and demonstrates efficacy against multiple pathogens in two rodent species with significantly higher drug levels in the epithelial lining fluid of infected lungs. In healthy volunteers, single-ascending doses of BWC0977 administered intravenously ( https://clinicaltrials.gov/study/NCT05088421 ) was found to be safe, well tolerated (primary endpoint) and achieved dose-proportional exposures (secondary endpoint) consistent with modelled data from preclinical studies. Here, we show that BWC0977 has the potential to treat a range of critical-care infections including MDR bacterial pneumonias.

Retrospective evaluation of rapid genotypic ID and phenotypic AST systems on positive blood culture turnaround time and simulated potential impacts on bloodstream infection management.

BACKGROUND: Bloodstream infections are linked to heightened morbidity and mortality rates. The consequences of delayed antibiotic treatment can be detrimental. Effective management of bacteraemia hinges on rapid antimicrobial susceptibility testing. OBJECTIVES: This retrospective study examined the influence of the VITEK® REVEAL™ Rapid AST system on positive blood culture (PBC) management in a French tertiary hospital. MATERIALS AND METHODS: Between November 2021 and March 2022, 79 Gram-negative monomicrobial PBC cases underwent testing with both VITEK®REVEAL™ and VITEK®2 systems. RESULTS: The study found that VITEK®REVEAL™ yielded better results than the standard of care, significantly shortening the time to result (7.0 h compared to 9.6 h) as well as the turnaround time (15 h compared to 31.1 h) when applied for all isolates. CONCLUSIONS: This study implies that the use of VITEK®REVEAL™ enables swift adaptations of antibiotic treatment strategies. By considerably minimizing the turnaround time, healthcare professionals can promptly make necessary adjustments to therapeutic regimens. Notably, these findings underscore the potential of VITEK®REVEAL™ in expediting appropriate antibiotic interventions, even in less ideal conditions. Further studies in varied laboratory contexts are required to validate these encouraging outcomes.

In treacherous waters: detection of colistin-resistant bacteria in water and plastic litter from a recreational estuary.

Colistin resistance poses a major therapeutic challenge and resistant strains have now been reported worldwide. However, the occurrence of such bacteria in aquatic environments is considerably less understood. This study aimed to isolate and characterize colistin-resistant strains from water and plastic litter collected in an urban recreational estuary. Altogether, 64 strains with acquired colistin resistance were identified, mainly Acinetobacter spp. and Enterobacter spp. From these, 40.6% were positive for at least one mcr variant (1-9), 26.5% harbored, extended-spectrum beta-lactamases, 23.4% harbored, sulfonamide resistance genes, and 9.3% harbored, quinolone resistance genes. merA, encoding mercury resistance, was detected in 10.5% of these strains, most of which were also strong biofilm producers. The minimum inhibitory concentration toward colistin was determined for the mcr-positive strains and ranged from 2 to ≥512 µg ml-1. Our findings suggest that Gram-negative bacteria highly resistant to a last-resort antimicrobial can be found in recreational waters and plastic litter, thereby evidencing the urgency of the One Health approach to mitigate the antimicrobial resistance crisis.

Optimizing antimicrobial synergy: Green synthesis of silver nanoparticles from Calotropis gigantea leaves enhanced by patchouli oil.

Silver nanoparticles (AgNPs) synthesized from plant extracts have gained attention for their potential applications in biomedicine. Calotropis gigantea has been utilized to synthesize AgNPs, called AgNPs-LCg, and exhibit antibacterial activities against both Gram-positive and Gram-negative bacteria as well as antifungal. However, further enhancement of their antimicrobial properties is needed. The aim of this study was to synthesize AgNPs-LCg and to enhance their antimicrobial and antifungal activities through a hybrid green synthesis reaction using patchouli oil (PO), as well as to characterize the synthesized AgNPs-LCg. Optimization was conducted using the response surface method (RSM) with a central composite design (CCD). AgNPs-LCg were synthesized under optimal conditions and hybridized with different forms of PO-crude, distillation wastewater (hydrolate), and heavy and light fractions-resulting in PO-AgNPs-LCg, PH-AgNPs-LCg, LP-AgNPs-LCg, and HP-AgNPs-LCg, respectively. The samples were then tested for their antibacterial (both Gram-positive and Gram-negative bacteria) and antifungal activities. Our data indicated that all samples, including those with distillation wastewater, had enhanced antimicrobial activity. HP-AgNPs-LCg, however, had the highest efficacy; therefore, only HP-AgNPs-LCg proceeded to the characterization stage for comparison with AgNPs-LCg. UV-Vis spectrophotometry indicated surface plasmon resonance (SPR) peaks at 400 nm for AgNPs-LCg and 360 nm for HP-AgNPs-LCg. The Fourier-transform infrared spectroscopy (FTIR) analysis confirmed the presence of O-H, N-H, and C-H groups in C. gigantea extract and AgNP samples. The smallest AgNPs-LCg were 56 nm, indicating successful RSM optimization. Scanning electron microscopy (SEM) analysis revealed spherical AgNPs-LCg and primarily cubic HP-AgNPs-LCg, with energy-dispersive X-ray spectroscopy (EDX) confirming silver's predominance. This study demonstrated that PO in any form significantly enhances the antimicrobial properties of AgNPs-LCg. The findings pave the way for the exploration of enhanced and environmentally sustainable antimicrobial agents, capitalizing on the natural resources found in Aceh Province, Indonesia.

Examining the prevalence and antimicrobial resistance profiles of multidrug-resistant bacterial isolates in wound infections from Indonesian patients.

The emergence of multidrug-resistant (MDR) infections in wounds is a significant public health issue. The aim of this study was to investigate the prevalence and antimicrobial resistance profiles of MDR bacterial isolates in wound infections. Through a cross-sectional study, 1,035 bacterial isolates were collected from wound infection patients at Tugurejo Hospital in Semarang, Indonesia, over a three-year period (from January 2020 to December 2022). Initial identification involved Gram staining and colony morphology assessment, followed by biochemical assays and antimicrobial susceptibility testing using the VITEK®2 Compact system. Gram-negative bacteria constituted the majority of isolates (60.77%, n=629). The predominant strains included were Staphylococcus spp. (30.92%, n=320), Escherichia coli (18.45%, n=191), and Klebsiella pneumoniae (13.04%, n=135). Notably, Gram-negative bacteria exhibited a significantly higher likelihood of MDR development compared to their Gram-positive counterparts (p<0.001), with Gram-negative bacteria having a 2.05 times higher probability of acquiring MDR. These findings underscore the urgent need for comprehensive surveillance of antimicrobial resistance patterns and the implementation of tailored antimicrobial stewardship programs to address the pressing public health challenge of MDR wound infections. Further research is warranted to elucidate the complex interplay of factors contributing to MDR development in wound infections, thereby informing targeted intervention strategies and improving patient outcomes.

Prevalence and antimicrobial resistance of bacterial meningitis in China from 2017 to 2021: a multicenter retrospective study.

INTRODUCTION: This study aims to investigate the changing epidemiology and antimicrobial susceptibility of bacteria isolated from cerebrospinal fluid (CSF) in the Shandong region. METHODOLOGY: We conducted a retrospective analysis of bacterial distribution and resistance patterns in CSF samples, utilizing data from the SPARSS network and analyzed with WHONET 5.6 software. RESULTS: A total of 3968 pathogenic bacterial strains were isolated, consisting of 70.6% Gram-positive bacteria, 27.2% Gram-negative bacteria, and 0.2% fungi. The six most commonly detected bacteria were coagulase-negative staphylococcus, Acinetobacter baumannii, Klebsiella pneumoniae, Streptococcus pneumoniae, Escherichia coli, and staphylococcus aureus. Analysis revealed gender and seasonal variations in the distribution of CSF pathogens, with a higher incidence observed in males and during autumn compared to other seasons. The susceptibility profiles of these bacterial species varied significantly, with many exhibiting multidrug resistances. A. baumannii showed a high resistance rate to cephalosporins and carbapenems but was sensitive to tigecycline and polymyxins. For treating multidrug-resistant A. baumannii infections, polymyxin-based combinations with tigecycline or sulbactam are recommended for adults, while tigecycline combined with meropenem is suggested for children. Enterobacteriaceae species were generally sensitive to carbapenems, such as meropenem and other carbapenems that can penetrate the blood-brain barrier can be recommended. Linezolid and vancomycin are the first choice for treating common gram-positive bacterial infections. CONCLUSIONS: The high resistance rates observed among common CSF isolates and their varied distributions across different demographics highlight the necessity for customized treatment strategies.

[Cefiderocol: a first and novel class of siderophore cephalosporin for Carbapenem-resistant Gram-negative infection].

Antimicrobial resistance is currently recognized as an urgent concern against public health in worldwide. Carbapenem-resistant (CR) Gram-negative bacteria, such as Enterobacterales, Pseudomonas aeruginosa and Acinetobacter baumannii are listed as critical pathogens which are widely spread and can cause severe and often deadly infections in WHO guidance. Cefiderocol (Fetroja®), a novel and first siderophore cephalosporin, was approved for the infections caused by these problematic CR Gram-negative bacteria in Japan on November 30, 2023. Cefiderocol has unique mechanisms to be incorporated into bacterial cells using bacterial iron transportation system and to be highly stable against most ß-lactamases, which lead to promising antibacterial activity against these Gram-negative bacteria including CR strains in vitro. In CREDIBLE-CR Ph3 trial, cefiderocol showed the good efficacy and safety for patients with CR Gram-negative bacteria. In APEKS-cUTI and APEKS-NP trials, cefiderocol showed non-inferiority and suggested superiority to imipenem/cilastatin in complicated urinary tract infection (cUTI) patients, and non-inferiority to high dose of meropemen in pneumonia patients, respectively. Cefiderocol is expected to be an optimal treatment for CR Gram-negative infections with limited treatment options and would be an important drug to combat the threat of CR bacteria.

[Importance and prevalence of multidrug-resistant gram-negative bacteria in Germany]. / Gramnegative Erreger (3MRGN/4MRGN): Häufigkeit und Besonderheiten.

Infections with multidrug-resistant gram-negative bacterial species are a great concern in clinics in Germany. By limiting therapeutic options dramatically, these bacteria pose a significant threat to patient health and cause extensive pressure on hygiene systems and patient management. In Germany, the recommendations on how to deal with these bacteria are called MRGN classification, using the terms 3MRGN and 4MRGN for bacteria resistant to three or four major classes of antibiotics. To be resistant to this large number of antibiotics and become classified as 3MRGN or 4MRGN, bacterial strains need to acquire multiple resistance mechanisms with beta-lactamases, especially carbapenemases, being the most important ones. According to established surveillance systems like national reporting systems, KISS or the National Reference Centre, multidrug-resistant bacteria are constantly on the rise in Germany. Although several novel therapeutic options have been approved recently, these bacteria represent a constant challenge and it may be necessary to discuss if the present hygiene recommendations need an update for an efficient and targeted prevention of transmission.

Evaluating the accuracy of the MBT Lipid Xtract Kit for assessing colistin resistance in comparison to broth microdilution.

Colistin resistance testing methods such as broth microdilution (BMD) are time-consuming and labour intensive for clinical laboratories. MBT Lipid Xtract Kit on MALDI Biotyper Sirius System (Bruker, Billerica, MA, USA) utilizes lipidomic analysis to identify specific cell wall modifications associated with colistin resistance. We compared MBT to BMD (ComASP Colistin, Liofilchem) across 36 Gram-negative isolates (non-resistant MIC ≤2 µg ml-1, resistant MIC ≥4 µg ml-1). All samples were tested twice on MBT with discrepant results repeated before assessing categorical agreement between MBT and BMD. 44.4% (16/36) of isolates were colistin resistant via BMD. MBT Lipid Xtract had 80.6% agreement (29/36) with BMD, with 5/7 discrepancies corrected to match upon repeat testing. There was 100% agreement for Escherichia coli isolates (n=16). The whole-genome sequencing was completed on the two discrepant Klebsiella pneumoniae isolates, with variants within colistin resistance-associated loci identified (MIC 0.5 µg ml-1: arnC S30T, pmrB T246A, lapB N212T, lpxM S253G, crrB Q287K and MIC >16 µg ml-1: arnC S30T, pmrB R90insRN, pmrB T246A, pmrA E57G, lpxM S253G). Further evaluation, particularly for non-E. coli, of MBT is required prior to implementation in clinical laboratories.

Valnemulin restores colistin sensitivity against multidrug-resistant gram-negative pathogens.

Colistin is one of the last-resort antibiotics in treating infections caused by multidrug-resistant (MDR) pathogens. Unfortunately, the emergence of colistin-resistant gram-negative strains limit its clinical application. Here, we identify an FDA-approved drug, valnemulin (Val), exhibit a synergistic effect with colistin in eradicating both colistin-resistant and colistin-susceptible gram-negative pathogens both in vitro and in the mouse infection model. Furthermore, Val acts synergistically with colistin in eliminating intracellular bacteria in vitro. Functional studies and transcriptional analysis confirm that the combinational use of Val and colistin could cause membrane permeabilization, proton motive force dissipation, reduction in intracellular ATP level, and suppression in bacterial motility, which result in bacterial membrane disruption and finally cell death. Our findings reveal the potential of Val as a colistin adjuvant to combat MDR bacterial pathogens and treat recalcitrant infections.

Antimicrobial resistance profile and associated factors of hospital-acquired gram-negative bacterial pathogens among hospitalized patients in northeast Ethiopia.

BACKGROUND: Antimicrobial resistance is a major global public health issue. Infections caused by resistant species are associated with higher mortality rates, longer hospital stays, medication failure, and rising medical costs. The World Health Organisation has declared multidrug resistance-associated infections as an epidemic of public health concern. OBJECTIVE: This study aimed to evaluate the antimicrobial resistance profile and associated factors of hospital-acquired Gram-negative bacterial pathogens among hospitalized patients in Northeast Ethiopia. MATERIALS AND METHODS: A health facility-based cross-sectional study was conducted among hospitalized patients from March 2021 to February 2022. About 810 clinical specimens were collected, transported, and processed from admitted patients following the standard bacteriological procedures. The clinical samples were inoculated onto blood agar, MacConkey agar, and chocolate agar. Furthermore, the species identification was done using gram reactions, colony morphology, and color and biochemical tests. Antimicrobial susceptibility tests, extended-spectrum beta-lactamase, and carbapenemase production were performed as per the clinical laboratory standard institute guidelines. For analysis, the information was entered into Epi-data and exported to SPSS. A P value of < 0.05 with a 95% confidence interval was considered as a statistically significant association. RESULTS: Out of 810 clinical specimens, 285/810 (35.2%) developed bacterial infections. From the isolated bacteria, E. coli was the predominant bacteria accounting for 78/285 (27.4%) followed by K. pneumoniae, 69/285(24.42%), whereas P. vulgaris accounted for the least, 7/285 (2.5%). Overall, 132/285 (46.3%) and 99/285 (34.7%) of culture-positive patients were infected by extended-spectrum beta-lactamase and carbapenemase-producing bacteria. The overall multidrug resistance rate of the isolated bacteria was 89.4%. The highest antibiotic resistance rates were detected for doxycycline (92.9%), amoxicillin-clavulanic acid (83.9%), and ampicillin (93%). The least antibiotic resistance rate was observed for meropenem at 41.1% and amikacin at 1.7%, respectively. CONCLUSIONS AND RECOMMENDATIONS: In the study area, significant health concerns include a range of hospital-acquired bacterial infections associated with elevated rates of multidrug resistance, Extended-spectrum beta-lactamase (ESBL), and carbapenemase-producing bacterial pathogens. Consequently, it is recommended to conduct drug-susceptibility testing of isolates and molecular detection at a national level to optimize antibiotic usage for treating prevalent bacterial infections in this area.

Knowledge, attitudes, and readiness about critical antimicrobial resistant organisms among healthcare workers at colonial war memorial hospital in Fiji: a pre and post intervention study.

BACKGROUND: Gram-negative bacteria resistant to carbapenems are also known as critical antimicrobial resistant organisms. Their emergence at Colonial War Memorial Hospital (CWMH), the largest hospital in Fiji, is a major clinical concern. This study was conducted to determine the knowledge, attitudes, and readiness of healthcare workers (HCW) at CWMH regarding management of patients with infections caused by critical antimicrobial resistant organisms. METHODS: A questionnaire was designed using a Likert scale to assess knowledge, attitudes, and readiness. Two cross-sectional studies were conducted, before and after the implementation of targeted educational activities which were informed by the pre-intervention study findings. RESULTS: A total of 393 and 420 HCW participated in the pre- and post-intervention studies, respectively. The majority of respondents were female (77.3%) and 18-34 years of age (67%). HCW professional roles included nurses (56.3%), doctors (31.6%), and laboratory personnel (12.2%). In the post-intervention study, significantly more HCW reported having received infection prevention and control (IPC) and antimicrobial resistance education and training (26.8% in pre to 45.5% in post intervention, p < 0.001). The majority of nurses and doctors (> 85% to ≥ 95%) were aware of how AMR organisms spread in healthcare settings and knew the IPC measures to prevent transmission of AMR infections including hand hygiene, standard and transmission-based precautions. Attitudes towards AMR were positive, with 84.2% pre intervention and 84.8% of HCW post intervention expressing their willingness to change their work environment to assist with AMR prevention. Perceived readiness to address the problem showed mixed results. Improvements in laboratory AMR surveillance data availability were noted (29.4-52.4%, p < 0001). Modest improvement in the hospital's capacity for outbreak response (44-51.9%, p = 0.01), and treatment of AMR infections (38.9-44.4%, p = 0.01) was reported. CONCLUSIONS: Our data revealed high levels of staff awareness and knowledge about AMR and IPC. However, readiness for outbreak response and treatment of critical AMR infections requires more attention. Improving AMR prevention and containment in CWMH will likely require sustained and multisectoral interventions with strong administrative commitment.

Inhalable SPRAY nanoparticles by modular peptide assemblies reverse alveolar inflammation in lethal Gram-negative bacteria infection.

Current pharmacotherapy remains futile in acute alveolar inflammation induced by Gram-negative bacteria (GNB), eliciting consequent respiratory failure. The release of lipid polysaccharides after antibiotic treatment and subsequent progress of proinflammatory cascade highlights the necessity to apply effective inflammation management simultaneously. This work describes modular self-assembling peptides for rapid anti-inflammatory programming (SPRAY) to form nanoparticles targeting macrophage specifically, having anti-inflammation and bactericidal functions synchronously. SPRAY nanoparticles accelerate the self-delivery process in macrophages via lysosomal membrane permeabilization, maintaining anti-inflammatory programming in macrophages with efficacy close to T helper 2 cytokines. By pulmonary deposition, SPRAY nanoparticles effectively suppress inflammatory infiltration and promote alveoli regeneration in murine aseptic acute lung injury. Moreover, SPRAY nanoparticles efficiently eradicate multidrug-resistant GNB in alveoli by disrupting bacterial membrane. The universal molecular design of SPRAY nanoparticles provides a robust and clinically unseen local strategy in reverse acute inflammation featured by a high accumulation of proinflammatory cellularity and drug-resistant bacteria.

The effect of combinations of a glyphosate-based herbicide with various clinically used antibiotics on phenotypic traits of Gram-negative species from the ESKAPEE group.

The emission of glyphosate and antibiotic residues from human activities threatens the diversity and functioning of the microbial community. This study examines the impact of a glyphosate-based herbicide (GBH) and common antibiotics on Gram-negative bacteria within the ESKAPEE group (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp. and Escherichia coli). Ten strains, including type and multidrug-resistant strains for each species were analysed and eight antibiotics (cefotaxime, meropenem, aztreonam, ciprofloxacin, gentamicin, tigecycline, sulfamethoxazole-trimethoprim, and colistin) were combined with the GBH. While most combinations yielded additive or indifferent effects in 70 associations, antagonistic effects were observed with ciprofloxacin and gentamicin in five strains. GBH notably decreased the minimum inhibitory concentration of colistin in eight strains and displayed synergistic activity with meropenem against metallo-ß-lactamase (MBL)-producing strains. Investigation into the effect of GBH properties on outer membrane permeability involved exposing strains to a combination of this GBH and vancomycin. Results indicated that GBH rendered strains sensitive to vancomycin, which is typically ineffective against Gram-negative bacteria. Furthermore, we examined the impact of GBH in combination with three carbapenem agents on 14 strains exhibiting varying carbapenem-resistance mechanisms to assess its effect on carbapenemase activity. The GBH efficiently inhibited MBL activity, demonstrating similar effects to EDTA (ethylenediaminetetraacetic acid). Chelating effect of GBH may have multifaceted impacts on bacterial cells, potentially by increasing outer membrane permeability and inactivating metalloenzyme activity.

Increasing trends of antibiotic resistance in Uganda: analysis of the national antimicrobial resistance surveillance data, 2018-2021.

BACKGROUND: Continuous monitoring of antimicrobial resistance (AMR) in Uganda involves testing bacterial isolates from clinical samples at national and regional hospitals. Although the National Microbiology Reference Laboratory (NMRL) analyzes these isolates for official AMR surveillance data, there's limited integration into public health planning. To enhance the utilization of NMRL data to better inform drug selection and public health strategies in combating antibiotic resistance, we evaluated the trends and spatial distribution of AMR to common antibiotics used in Uganda. METHODS: We analyzed data from pathogenic bacterial isolates from blood, cerebrospinal, peritoneal, and pleural fluid from AMR surveillance data for 2018-2021. We calculated the proportions of isolates that were resistant to common antimicrobial classes. We used the chi-square test for trends to evaluate changes in AMR resistance over the study period. RESULTS: Out of 537 isolates with 15 pathogenic bacteria, 478 (89%) were from blood, 34 (6.3%) were from pleural fluid, 21 (4%) were from cerebrospinal fluid, and 4 (0.7%) were from peritoneal fluid. The most common pathogen was Staphylococcus aureus (20.1%), followed by Salmonella species (18.8%). The overall change in resistance over the four years was 63-84% for sulfonamides, fluoroquinolones macrolides (46-76%), phenicols (48-71%), penicillins (42-97%), ß-lactamase inhibitors (20-92%), aminoglycosides (17-53%), cephalosporins (8.3-90%), carbapenems (5.3-26%), and glycopeptides (0-20%). There was a fluctuation in resistance of Staphylococcus aureus to methicillin (60%-45%) (using cefoxitin resistance as a surrogate for oxacillin resistance) Among gram-negative organisms, there were increases in resistance to tetracycline (29-78% p < 0.001), ciprofloxacin (17-43%, p = 0.004), ceftriaxone (8-72%, p = 0.003), imipenem (6-26%, p = 0.004), and meropenem (7-18%, p = 0.03). CONCLUSION: The study highlights a concerning increase in antibiotic resistance rates over four years, with significant increase in resistance observed across different classes of antibiotics for both gram-positive and gram-negative organisms. This increased antibiotic resistance, particularly to commonly used antibiotics like ceftriaxone and ciprofloxacin, makes adhering to the WHO's Access, Watch, and Reserve (AWaRe) category even more critical. It also emphasizes how important it is to guard against the growing threat of antibiotic resistance by appropriately using medicines, especially those that are marked for "Watch" or "Reserve."

Self-Assembling and Pore-Forming Peptoids as Antimicrobial Biomaterials.

Bacterial infections have been a serious threat to mankind throughout history. Natural antimicrobial peptides (AMPs) and their membrane disruption mechanism have generated immense interest in the design and development of synthetic mimetics that could overcome the intrinsic drawbacks of AMPs, such as their susceptibility to proteolytic degradation and low bioavailability. Herein, by exploiting the self-assembly and pore-forming capabilities of sequence-defined peptoids, we discovered a family of low-molecular weight peptoid antibiotics that exhibit excellent broad-spectrum activity and high selectivity toward a panel of clinically significant Gram-positive and Gram-negative bacterial strains, including vancomycin-resistant Enterococcus faecalis (VREF), methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epidermidis (MRSE), Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae. Tuning the peptoid side chain chemistry and structure enabled us to tune the efficacy of antimicrobial activity. Mechanistic studies using transmission electron microscopy (TEM), bacterial membrane depolarization and lysis, and time-kill kinetics assays along with molecular dynamics simulations reveal that these peptoids kill both Gram-positive and Gram-negative bacteria through a membrane disruption mechanism. These robust and biocompatible peptoid-based antibiotics can provide a valuable tool for combating emerging drug resistance.

Effect of multifunctional cationic polymer coatings on mitigation of broad microbial pathogens.

Infection control measures to prevent viral and bacterial infection spread are critical to maintaining a healthy environment. Pathogens such as viruses and pyogenic bacteria can cause infectious complications. Viruses such as SARS-CoV-2 are known to spread through the aerosol route and on fomite surfaces, lasting for a prolonged time in the environment. Developing technologies to mitigate the spread of pathogens through airborne routes and on surfaces is critical, especially for patients at high risk for infectious complications. Multifunctional coatings with a broad capacity to bind pathogens that result in inactivation can disrupt infectious spread through aerosol and inanimate surface spread. This study uses C-POLAR, a proprietary cationic, polyamine, organic polymer with a charged, dielectric property coated onto air filtration material and textiles. Using both SARS-CoV-2 live viral particles and bovine coronavirus models, C-POLAR-treated material shows a dramatic 2-log reduction in circulating viral inoculum. This reduction is consistent in a static room model, indicating simple airflow through a static C-POLAR hanging can capture significant airborne particles. Finally, Gram-positive and Gram-negative bacteria are applied to C-POLAR textiles using a viability indicator to demonstrate eradication on fomite surfaces. These data suggest that a cationic polymer surface can capture and eradicate human pathogens, potentially interrupting the infectious spread for a more resilient environment. IMPORTANCE: Infection control is critical for maintaining a healthy home, work, and hospital environment. We test a cationic polymer capable of capturing and eradicating viral and bacterial pathogens by applying the polymer to the air filtration material and textiles. The data suggest that the simple addition of cationic material can result in the improvement of an infectious resilient environment against viral and bacterial pathogens.

Microbiological characterization of neuropathic diabetic foot infection: a retrospective study at a Portuguese tertiary hospital.

Diabetic foot infection imposes a significant burden and is the major cause of nontraumatic limb amputation. Adequate patient management with effective antibiotic therapy is crucial.This retrospective cohort study aimed to characterize the microbiology and resistance patterns of moderate to severe neuropathic diabetic foot infection in patients hospitalized at a tertiary referral hospital between January 2020 and June 2023. Deep tissue specimens from ulcers were collected for culture.Sixty inpatients were included (62% male, mean age 59.1 ± 11.5 years). Osteomyelitis was present in 90% of the patients. Among 102 microorganisms (average of 1.91 ± 1.25 pathogens per patient), 60.8% were gram-positive bacteria, 31.4% were gram-negative, 3.92% were anaerobic bacteria, and 3.92% were fungi. Staphylococcus aureus (19%) and Enterococcus faecium (17%) were the most common. Pseudomonas aeruginosa (8%) and bacteria of the Enterobacterales family (24%) accounted for all the isolated gram-negative bacteria. Sixteen percent of Staphylococcus aureus and 67% of coagulase-negative Staphylococci were resistant to methicillin. Resistance to ampicillin was found in 11% of Enterococci. All Pseudomonas aeruginosa isolates were sensitive to piperacillin-tazobactam, ceftazidime, or cefepime. Among the Enterobacterales, resistance rates were 35% for piperacillin-tazobactam, 38% for ceftazidime, 21% for cefepime, and 13% for carbapenems.Although the prevalence of methicillin-resistant staphylococci was lower than that in other studies, carbapenem resistance among gram-negative bacteria warrants attention. This study highlights the importance of understanding local epidemiology for effective diabetic foot infection management and resistance mitigation.

Characterization and application of LysSGF2 and HolSGF2 as potential biocontrol agents against planktonic and biofilm cells of common pathogenic bacteria.

Antimicrobial resistance represents a global health emergency, necessitating the introduction of novel antimicrobial agents. In the present study, lysozyme and holin from Shigella flexneri 1.1868 phage SGF2, named LysSGF2 and HolSGF2, respectively, were cloned, expressed, and characterized. LysSGF2 and HolSGF2 showed lytic activities against S. flexneri 1.1868 cells at 4-55 °C and pH 3.1-10.3. LysSGF2 exhibited antimicrobial activity against five gram-negative and two gram-positive bacteria. HolSGF2 showed antimicrobial activity against four gram-negative and one gram-positive species. The antibacterial activities of LysSGF2 and HolSGF2 were determined in liquid beverages, including bottled water and milk. The relative lytic activity of LysSGF2 combined with HolSGF2 against the tested bacteria was approximately 46-77 % in water. Furthermore, the combination markedly decreased the viable counts of tested bacteria by approximately 3-5 log CFU/mL. LysSGF2 and HolSGF2 could efficiently remove biofilms on polystyrene, glass, and stainless-steel. The efficacy of the LysSGF2 and HolSGF2 combination against the tested bacteria on polystyrene was 58-71 %. Combination treatment effectively killed biofilm cells formed on stainless-steel and glass by 1-4 log CFU/mL. ese results indicate that LysSGF2 and HolSGF2 can successfully control both the planktonic and biofilm cells of common pathogenic bacteria, suggesting that the combined or single use of LysSGF2 and HolSGF2 may be of great value in food processing.

Retrospective ANalysis of multi-drug resistant Gram-nEgative bacteRia on veno-venous extracorporeal membrane oxygenation. The multicenter RANGER STUDY.

BACKGROUND: Veno-venous extracorporeal membrane oxygenation (V-V ECMO) is a rapidly expanding life-support technique worldwide. The most common indications are severe hypoxemia and/or hypercapnia, unresponsive to conventional treatments, primarily in cases of acute respiratory distress syndrome. Concerning potential contraindications, there is no mention of microbiological history, especially related to multi-drug resistant (MDR) bacteria isolated before V-V ECMO placement. Our study aims to investigate: (i) the prevalence and incidence of MDR Gram-negative (GN) bacteria in a cohort of V-V ECMOs; (ii) the risk of 1-year mortality, especially in the case of predetected MDR GN bacteria; and (iii) the impact of annual hospital V-V ECMO volume on the probability of acquiring MDR GN bacteria. METHODS: All consecutive adults admitted to the Intensive Care Units of 5 Italian university-affiliated hospitals and requiring V-V ECMO were screened. Exclusion criteria were age < 18 years, pregnancy, veno-arterial or mixed ECMO-configuration, incomplete records, survival < 24 h after V-V ECMO. A standard protocol of microbiological surveillance was applied and MDR profiles were identified using in vitro susceptibility tests. Cox-proportional hazards models were applied for investigating mortality. RESULTS: Two hundred and seventy-nine V-V ECMO patients (72% male) were enrolled. The overall MDR GN bacteria percentage was 50%: 21% (n.59) detected before and 29% (n.80) after V-V ECMO placement. The overall 1-year mortality was 42%, with a higher risk observed in predetected patients (aHR 2.14 [1.33-3.47], p value 0.002), while not in 'V-V ECMO-acquired MDR GN bacteria' group (aHR 1.51 [0.94-2.42], p value 0.090), as compared to 'non-MDR GN bacteria' group (reference). Same findings were found considering only infections. A larger annual hospital V-V ECMO volume was associated with a lower probability of acquiring MDR GN bacteria during V-V ECMO course (aOR 0.91 [0.86-0.97], p value 0.002). CONCLUSIONS: 21% of MDR GN bacteria were detected before; while 29% after V-V ECMO connection. A history of MDR GN bacteria, isolated before V-V ECMO, was an independent risk factor for mortality. The annual hospital V-V ECMO volume affected the probability of acquiring MDR GN bacteria. Trial Registration ClinicalTrial.gov Registration Number NCTNCT06199141, date 12.26.2023.