Antibiotics Vancomycin Research Articles

Fecal microbiota transplantation for treatment of refractory or recurrent Clostridioides difficile infection in Taiwan: a cost-effectiveness analysis.

Compared to antibiotic treatment, fecal microbiota transplantation (FMT) is a more effective treatment for refractory or recurrent CDI (rCDI). Patients with inflammatory bowel disease (IBD) have a higher incidence of CDI and worse outcomes. There has been no study from Asia to evaluate the cost-effectiveness of FMT for overall rCDI patients and rCDI patients with IBD. We applied a Markov model with deterministic and probabilistic sensitivity analyses to evaluate the cost and effectiveness of different treatments for rCDI patients with a time horizon of 1 year from the payer's perspective. We compared the cost and clinical outcomes of FMT through colonoscopy to two antibiotics (vancomycin and fidaxomicin) using data from Chang Gung Memorial Hospital, Taoyuan, Taiwan. Compared to vancomycin, FMT was cost-effective in overall rCDI patients as well as IBD patients with rCDI [USD 39356 (NT$1,101,971.98)/quality-adjusted life year (QALY) gained in overall patients; USD65490 (NT$1,833,719.14)/QALY gained in IBD patients]. Compared to fidaxomicin, FMT was only cost-effective in overall rCDI patients [USD20255 (NT$567,133.45)/QALY gained] but slightly increased QALY (0.0018 QALY gained) in IBD patients with rCDI. FMT is cost-effective, compared to vancomycin or fidaxomicin, for the treatment of rCDI in most scenarios from the payers' perspective in Taiwan.

Experimental bacterial dysbiosis with consequent immune alterations increase intrarectal SIV acquisition susceptibility

Variations in the composition of the intestinal bacterial microbiome correlate with acquisition of some sexually transmitted pathogens. To experimentally assess the contribution of intestinal dysbiosis to rectal lentiviral acquisition, we induce dysbiosis in rhesus macaques (RMs) with the antibiotic vancomycin prior to repeated low-dose intrarectal challenge with simian immunodeficiency virus (SIV) SIVmac239X. Vancomycin administration reduces T helper 17 (TH17) and TH22 frequencies, increases expression of host bacterial sensors and antibacterial peptides, and increases numbers of transmitted-founder (T/F) variants detected upon SIV acquisition. We observe that SIV acquisition does not correlate with measures of dysbiosis but rather associates with perturbations in the host antimicrobial program. These findings establish a functional association between the intestinal microbiome and susceptibility to lentiviral acquisition across the rectal epithelial barrier.

Additive manufacturing of a cementless hip stem demonstrator with local drug delivery functionality

Periprosthetic joint infection from implant surface colonization by pathogenic bacteria and subsequent biofilm formation remains a serious complication following total hip arthroplasty. Local delivery of antimicrobial drugs is an effective approach to prevent and treat such infection. This paper presents a prototype development process chain for a cementless hip stem from which an antimicrobial drug can be delivered directly to the implant surface. A systematic approach was followed in which the external surface of the hip stem represents an area requiring antibacterial coverage. Individual features were tested first to determine the zone of inhibition, represented by the two-dimensional area surrounding the drug release source where the pathogen cannot survive. This zone, determined for the antibiotic vancomycin against strains of the pathogen Staphylococcus aureus to be 15 mm in diameter, was simplified geometrically to circles of uniform radius which should cover the necessary implant surface. A freeform internal channel layout was then designed with source points for drug delivery at the centre of each of these circles. The final cementless stem design was manufactured with laser powder bed fusion from Ti6Al4V ELI. Internal features were free from any blockages and ∼3 mL of 15 mg/mL aqueous vancomycin could be loaded into the demonstrator stem without obstruction. Antimicrobial efficacy of the demonstrator was qualitatively evaluated in a custom experimental setup against Staphylococcus aureus Xen 31 incubated for 24 hours with a commercial hip stem as negative control. Qualitative evaluation of the inoculum revealed that surface colonization was prevented, indicating that the effective released vancomycin concentration exceeded the minimum inhibitory concentration of ∼5 µg/mL. The results contribute evidence to the applicability of laser powder bed fusion for implants with local drug delivery functionality. Further development of the concept could increase the efficacy and resource efficiency of periprosthetic joint infection prophylaxis and treatment.

A Case of Klebsiella pneumoniae Meningitis Associated with Brain Abscess and Endophthalmitis

Meningitis, brain abscess, and endophthalmitis are rare manifestations of <i>K. pneumoniae</i> infection. We present a case of <i>Klebsiella</i> meningitis associated with a brain abscess and endophthalmitis. A 58-year-old man with alcoholic liver cirrhosis and hepatocellular carcinoma presented with fever, pain in the right eyeball, and vision loss. Endophthalmitis and urinary tract infections were identified through ophthalmologic examination and urine analysis, respectively, and empirical antibiotic therapy was administered. Approximately seven days after treatment, the patient presented with persistent headaches. In the cerebrospinal fluid study, the white blood cell count was 210/mm<sup>3</sup>, the protein level was 540 mg/dL, and the glucose level was 28.6 mg/ dL. Magnetic resonance imaging of the brain revealed diffuse brain abscesses in both hemispheres. <i>Klebsiella pneumoniae</i> was isolated from the blood and urine cultures. After intravenous injection of antibiotics (vancomycin and ceftriaxone) for 2 months, the headache resolved and the results of the cerebrospinal fluid study were normal.

Molecular detection of some Vancomycin Pathogenic bacteria in Basrah Governorate

The current study aimed to study the resistance of some species Bacterial resistance to the antibiotic vancomycin. 121 samples were collected and grown on Chocolate Agar medium for isolating pathogenic bacteria. and then It was grown on Nutrient Agar medium for pure colonies. These bacteria were diagnosed using phenotypic methods, biochemical tests, and 16SrRNA gene. The results reported that 40 (33.3%) resistant strains appeared, of which 13 were males with a percentage of (32.5%), while the number of female samples was 27 with a percentage (67.5%) and the rest were sensitive to this antibiotic. done during the study The current study obtained four types of bacteria resistant to vancomycin: 24 strains (60%) belonging to Pseudomonas aeruginosa bacteria, 11 strains (27.5%) belonging to Proteus mirabilis bacteria, 4 strains (10%) of Staphylococcus aureus bacteria, and one strain (2.5%) for Actinomyces sp. As for the presence of resistance genes, Vancomycin, where the current study recorded the presence of 17 bacterial strains containing both VanA and VanB genes (42.5%), while the VanA gene was present in 8 strains (20%), and the VanB gene was present in 6 strains (15%), and 9 appeared Strains (22.5%) do not possess either of the two genes (VanA and VanB), although they were resistant to vancomycin, and this may be due to their possession of other resistance genes or other mechanisms of resistance to this antibiotic.

Evaluating the iatrogenic effects of polypharmacy and drug interactions in HIV-positive patients admitted to the intensive care unit: a single-center retrospective study

Background. Polypharmacy and drug interactions are of particular concern in people living with HIV/AIDS, especially those who receive antiretroviral therapy (ARVs). Polypharmacy and drug-drug interactions (DDIs) can impact the efficacy and toxicity of HIV treatment. ARVs used in HIV treatment are often prone to drug interactions if administered with other non-ARV drugs because many of them are metabolized through the cytochrome P450 system. The pharmacological management of HIV patients in the intensive care unit (ICU) is usually complex and typically involves the administration of several classes of drugs. This patient group may be at higher risk for potential DDIs due to polypharmacy in the ICU. The main objective of this study was to assess the iatrogenic effects of polypharmacy in HIV patients treated in the ICU and to describe the DDI profile between ARVs and other non-ARV medications prescribed in the ICU. Methods and materials. Between 2018 and 2020, we conducted a single-center, retrospective study evaluating the medical records of 59 HIV patients admitted to the ICU for more than 24 hours at the Infectious Disease Clinical Hospital No. 2, Moscow, Russia. We evaluated the impact of polypharmacy on renal, hepatic and haemopoietic function. The Liverpool HIV Drug Interaction database was used to identify DDIs in ART-treated HIV patients. Results. All patients received more than 5 different medications matching the definition of polypharmacy. The average number of concurrent medications prescribed was 156.713 (maximum 40, minimum 6). All drug interactions recorded were between ARVs and antibiotics: 30 cases of potential interactions in 65.5% patients who received ARV. Of such patients, 94% were exposed to at least two potential interactions. Tenofovir (TDF) and the antibiotic vancomycin underlaid the most common potential interaction (49.2%), followed by lopinavir ritonavir (LPV/RTV) and ciprofloxacin (30.3%). A significant difference in average creatinine levels was found in patients with TDF/vancomycin potential interactions (p 0.05). Conclusion. This study demonstrated that potential DDIs frequently occur in ICU patients in line with previous investigations. It is necessary to implement collaborations among clinical pharmacologists and infectious disease/HIV specialists, as well as frequent clinical and laboratory monitoring, aimed at developing effective and actionable strategies that could reduce potential DDIs in HIV patients in the ICU.

Ultra-Short Cyclized β-Boomerang Peptides: Structures, Interactions with Lipopolysaccharide, Antibiotic Potentiator and Wound Healing.

Many antibiotics are ineffective in killing Gram-negative bacteria due to the permeability barrier of the outer-membrane LPS. Infections caused by multi-drug-resistant Gram-negative pathogens require new antibiotics, which are often difficult to develop. Antibiotic potentiators disrupt outer-membrane LPS and can assist the entry of large-scaffold antibiotics to the bacterial targets. In this work, we designed a backbone-cyclized ultra-short, six-amino-acid-long (WKRKRY) peptide, termed cWY6 from LPS binding motif of β-boomerang bactericidal peptides. The cWY6 peptide does not exhibit any antimicrobial activity; however, it is able to permeabilize the LPS outer membrane. Our results demonstrate the antibiotic potentiator activity in the designed cWY6 peptide for several conventional antibiotics (vancomycin, rifampicin, erythromycin, novobiocin and azithromycin). Remarkably, the short cWY6 peptide exhibits wound-healing activity in in vitro assays. NMR, computational docking and biophysical studies describe the atomic-resolution structure of the peptide in complex with LPS and mode of action in disrupting the outer membrane. The dual activities of cWY6 peptide hold high promise for further translation to therapeutics.

662. In vitro antibacterial activity of contezolid compared to linezolid and vancomycin in clinical isolates from China

Abstract Background Linezolid and vancomycin are insufficient in the treatment of drug-resistant Gram-positive bacteria due to adverse drug reactions and drug resistance, and new antibiotics are needed, especially for patients with myelosuppression and vancomycin-resistant Enteroccocus (VRE) infection. Contezolid (CZD) is a novel oral oxazolidinone with potent activity against Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) and VRE. We evaluate the in vitro antibacterial activity of contezolid compared to linezolid and vancomycin in Gram-positive clinical isolates. Methods 176 clinical isolates were obtained from 176 sterile body fluids from patients at 3 tertiary care hospitals in China, and the minimal inhibitory concentrations (MICs) of contezolid, linezolid and vancomycin determined by broth microdilution assay. Results Contezolid exhibits excellent antibacterial activity against prevalent Gram-positive bacteria, Staphylococcus spp. and Enterococcus spp., including methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant and coagulase-negative Staphylococcus (MRCNS), and vancomycin-resistant Enterococcus (VRE). MIC90 values of contezolid were 2 mg/L for all MRSA and VRE isolates and 1 mg/L for MRCNS isolates. The antibacterial activity of contezolid against Staphylococcus spp., including S. aureus, was essentially similar to linezolid, and slightly higher than or similar to vancomycin. Antibacterial activity of contezolid against Enterococcus, including VRE, was similar to linezolid, while being slightly lower than for vancomycin in vancomycin-susceptible isolates. Consistent with the shared antibacterial mode of action, bacterial strains resistant to linezolid were cross-resistant to contezolid. Table 1.Antimicrobial susceptibility testing results of clinical bacterial strains (MICs, mg/L) Conclusion Contezolid, a novel oxazolidinone drug, exhibits potent in vitro antibacterial activity against clinical isolates of common Gram-positive pathogens, including multidrug-resistant (MDR) Gram-positive bacteria, MRSA, MRCNS, and VRE. Contezolid has antibacterial activity similar to standard-of-care antibiotics linezolid and vancomycin. Results suggest that contezolid can play an important role in treatment of MDR Gram-positive bacterial infections. Figure 1.Distribution of MICs of CZD or LZD against 48 strains of MRSAFigure 2.Distribution of MICs of CZD or LZD against 29 strains of MRCNSFigure 3.Distribution of MICs of CZD or LZD against 17 strains of VRE Disclosures All Authors: No reported disclosures.

566. The Impact of a Clinical Practice Guideline and Educational Interventions on the Management of Children Hospitalized with Uncomplicated Community Acquired Pneumonia

Abstract Background The 2011 guidelines for management of pediatric uncomplicated community acquired pneumonia (CAP) recommend the use of ampicillin or penicillin first line. We sought to evaluate improvement in adherence to these guidelines through antimicrobial stewardship interventions at a single institution to minimize unnecessary broad antimicrobials. Methods A retrospective chart review was conducted of admitted patients aged 2 months - 21 years old with uncomplicated CAP. The pre-intervention phase was September 1, 2019-February 29, 2020 and the post-intervention phase included September 1-February 28 of 2021 and 2022. Antimicrobial stewardship interventions included the incorporation of clinical practice guidelines (CPG) into a new institutional CAP pathway (approved in June 2020) and subsequent education to ordering providers in the spring of 2020. Patients with complicated pneumonia or with comorbidities including sickle cell disease, chronic lung disease, neurologic conditions, congenital heart disease or patients who were immunocompromised were excluded. The prescribing patterns of specific physicians were recorded and adherence to CPG recommendations were assessed. The primary endpoint was to measure the reduction of broad spectrum antibiotics (vancomycin, clindamycin, ceftriaxone, levofloxacin and cefdinir) to narrow spectrum antibiotics (ampicillin, amoxicillin, and amoxicillin-clavulanate). Results A total of 114 patients were included in the study; 72 pre-intervention and 42 post-intervention. Mean age was 5.4 years pre- and 6.5 years post-intervention. A significant reduction in broad spectrum antibiotic use was noted in the ED (p=< 0.0001), during the first 24 hours of admission (p=0.0034) and for discharge antibiotics (p=0.0003) (Figures 1-3) between the pre- and post-intervention groups. Guideline adherence was 78.5%. No change in length of stay or treatment failure were observed. Antibiotic Prescriptions in the Emergency Department After the implementation of the CPG guideline there was a 17% reduction in the number of times a combination of antibiotics were used, a 7.2% reduction of broad spectrum antibiotics and a 24% increase in the utilization of narrow spectrum antibiotics, p-value= <0.0001. Antibiotic Utilization 24 hours After Hospital Admission After the implementation of the CPG guideline there was a 20% reduction in the number of times a broad spectrum antibiotic was prescribed, p-value =0.0034. Discharge Antibiotic Prescriptions After the implementation of the CPG guideline there was a 18% reduction of broad spectrum antibiotics and a 34% increase in the utilization of narrow spectrum antibiotics, p=0.0003. Conclusion The CPG and educational interventions had a positive impact on the antibiotic management of children hospitalized, with an overall 4.7% reduction of broad spectrum antibiotics and a 28% increase in the utilization of narrow spectrum antibiotics. Continued education may improve CPG adherence. Disclosures All Authors: No reported disclosures.

2008. Real-World Experience of Administration of Bezlotoxumab in an Outpatient Infusion Center Upon Discharge in Recurrent Clostridioides difficile patients

Abstract Background Bezlotoxumab is a humanized monoclonal antibody administered as single IV infusion that binds to Clostridioides difficile toxin B. It is currently recommended as a co-intervention in the updated 2021 IDSA guidelines for patients with recurrent C. difficile infection (CDI) in the last 6 months in addition to standard of care (SOC) antibiotics (vancomycin or fidaxomicin) to decrease CDI recurrence. Due to logistical issues and cost restrictions, administration is difficult as part of the inpatient stay. This case series evaluated a novel practice of discharging patients to receive bezlotoxumab immediately upon discharge from our not-for-profit community health system. Methods This was a retrospective chart review of all adult patients who received an outpatient infusion of bezlotoxumab after discharge between June 2019 and January 2022 for recurrent CDI. CDI was defined as ≥ 3 loose stools within 24 hours and a positive stool test for toxigenic C. difficile. The primary objectives were to evaluate the safety of bezlotoxumab in the outpatient setting and the rate of recurrent CDI at 12 weeks and 1 year. Recurrent CDI was defined using the same parameters as initial infection. Results Ten patients received bezlotoxumab in the outpatient setting after discharge and were included. Of the 10 patients, 2 were immunocompromised, 6 had at least stage 2 chronic kidney disease, and 4 required dialysis. All patients had > 1 previous CDI in the past 6 months, ranging between 1-6 with the average being 2.4. The average time to infusion was 9.8 days after starting SOC antibiotics and 80% of patients received treatment within 24 hours of discharge. No patients reported adverse reactions during treatment. One patient with a previous diagnosis of heart failure was readmitted for a heart failure exacerbation 69 days after receiving bezlotoxumab. Two patients and 4 patients experienced CDI recurrence within 12 weeks and 1 year of infusion, respectively. Conclusion Discharging patients to receive bezlotoxumab as an outpatient infusion is a safe and effective way to treat recurrent CDI logistically and may offer a financial advantage to institutions to shift costs to an outpatient payment model. Recurrence rates compared to phase III trials of bezlotoxumab were similar at 12 weeks (20% vs. 16%). Disclosures Christopher M. Bland, PharmD, FCCP, FIDSA, BCPS, biomerieux, Inc.: Honoraria|Merck Pharmaceuticals: Advisor/Consultant|Merck Pharmaceuticals: Honoraria Bruce M. Jones, Pharm.D., FIDSA, BCPS, AbbVie: Advisor/Consultant|AbbVie: Honoraria|La Jolla: Honoraria|Melinta: Advisor/Consultant|Paratek: Honoraria|Regeneron: Honoraria.

ОСОБЕННОСТИ ТЕЧЕНИЯ ОСТРЫХ ОДОНТОГЕННЫХ ВОСПАЛИТЕЛЬНЫХ ПРОЦЕССОВ ЧЕЛЮСТЕЙ ВДЕТСКОМ ВОЗРАСТЕ

The goal.Studying the clinical course’s features of acute odontogenic inflammatory processes of the jaws in children, describing species composition of pathogens, determination sensitivity to antibiotics of various groups in acute odontogenic inflammatory processes of the jaws in childhood. Materials and methods.The case histories of 900 patients were analyzed, microbiological research methods were carried out (microscopic examination of clinical samples with Gram staining, culture method, determination of the sensitivity of theisolated pathogen to antimicrobial drugs).Results.The most common odontogenic inflammatory processes of the jaws were observed in children aged 4–5 years. In48,85 % of cases in a milk bite and in 67,92 % of cases in a permanent bite, the cause of the development of an odontogenic inflammatory process was complicated caries of the mandibular molars. 56% of children had a general condition. The leading causative agent of the inflammatory process of the jaws was in 65,6 % of cases hemolytic streptococcus. In other cases, Streptococcus Viridans(6,1 %), pneumococci (4,3 %), candida (3 %), Staphylococcus aureus(2,8 %), Moraxella cataralis(1,2 %), etc. were detected in the mixed microflora of purulent exudate. The drugs of choice for empirical antibiotic therapy for odontogenic inflammatory process caused by beta-hemolytic streptococcus group A are vancomycin (antibiotic sensitivity –99 %), fluoroquinolones (antibiotic sensitivity –98 %), beta-lactams (antibiotic sensitivity –91 %). The highest percentage of resistance of this microflora was noted to macrolides (41 %), and to clindamycin (33 %). The rapid spread of the purulent-inflammatory process in the maxillofacial region in acute odontogenic processes in children, the resistant microflora of the odontogenic purulent focus require a competent approach when providing emergency care.Conclusions.The obtained has great practical importance for the choice of rational antibiotic therapy.

Antibiotic Sensitivity Against Klebsiella spp. in the Post Debridement Culture an Open Fracture in Emergency Department of dr. Soebandi Hospital Jember

Surgical site infection (SSI) in open fracture is often caused by bacterial contamination in the management of open fracture. Because of that, one of the most important thing in handling open fracture is debridement. Prophylactic antibiotics given are Cephalosporin and Aminoglycosides. Post-debridement culture is important in predicting the incidence of infection. One of the bacteria that is often found in post-debridement culture is Klebsiella spp. which can produce ESBL to fight β-lactam class of antibiotics. The purpose of this study was to determine antibiotic sensitivity against Klebsiella spp. in the post-debridement culture of cases of open fractures in the emergency department of dr. Soebandi hospital Jember. This study uses a laboratory exploratory research design. The sample of this study was the isolate of Klebsiella spp. which amounts to 5 from post debridement culture of open fracture patients in the emergency department of dr. Soebandi hospital Jember from March to May 2019.The method used is diffusion (Kirby Baurer) by matching using the CLSI standard table to determine sensitive, intermediate, or resistant. The results of this study showed that most antibiotics had resistance to Klebsiella spp., including β-lactam antibiotics, such as Amoxicillin, Ceftriaxone, Cefixime, Penicilin, Meropenem, and Cefadroxil. Vancomycin antibiotics are still sensitive to Klebsiella spp. in all patients. Gentamicin, Ciprofloxacin, Tetracycline, and Chloramphenicol antibiotics were sensitive in 1 patient. Erythromycin intermediates antibiotics against Klebsiella spp.. The conclusion of this study is that all β-lactam group antibiotics are resistant to Klebsiella spp while the most sensitive antibiotic is Vancomycin.

Comparative biofilm-forming ability between Clostridioides difficile strains isolated in Latin America and the epidemic NAP1/027 strain.

One of the challenges in treating Clostridioides difficile infection (CDI) is that the bacterium forms biofilms, a critical virulence mechanism known to promote antibiotic resistance and, as a result, consequently, a higher recurrence of the disease. The goal of this study was to compare the ability of three MLST Clade 2 strains to form a biofilm in vitro: ICC-45 (ribotype SLO231/UK[CE]821), a ST41 toxinotype IXb isolated in Brazil; and two epidemic NAP1/027/ST01 strains: NAP1/027/ST01 (LIBA5756), isolated during a 2010 outbreak in Costa Rica and the reference epidemic strain NAP1/027/ST01 (R20291); and ATCC700057, a non-toxigenic strain. The ability of strains to form biofilm was evaluated using crystal violet staining. In addition, samples were stained with the Film Tracer biofilm matrix (Invitrogen®) and the biofilm matrix thickness was measured using confocal microscopy. The matrix architecture was determined using Scanning electron microscop. Confocal microscopy was used to detect the presence of toxin A (tcdA) using an anti-Clostridioides difficile TcdA antibody. The expression of virulence genes (tcdA, tcdB, tcdC, cdtB, spo0A, slpA, cwp66 and cwp84) was examined, as well as the effect of antibiotics metronidazole (MTZ) and vancomycin (VAN) on biofilm growth. All of the strains tested formed a moderate biofilm with 1.1 <DO570nm>3.5. After 72h, biofilm biomass of the NAP1/027/ST01 epidemic strains (LIBA5756 and R20291) was significantly higher than ICC-45 and ATCC 700057 biofilms, as confirmed by electron and confocal microscopy. At 120h, the LIBA5756 biofilm biomass decreased compared to other strains. The toxigenic strains R20291 or LIBA 5756 had higher expression of genes tcdA, tcdB, tcdC, cdtA, slpA and spo0A than ICC-45, but there were no significant differences in the expression levels of cdtB, cwp66 and cwp84. In epidemic strains, VAN and MTZ inhibited biofilm formation; however, in the ICC-45 strain, MIC concentrations of VAN and MIC and 4MIC of MTZ did not inhibit biofilm formation. The three MLST Clade 2 isolated from different rybotipes, two of which were isolated from Latin America, are competent biofilm-forming bacteria, indicating their ability to induce C. difficile infection recurrence, making treatment difficult.

Impregnating graphene oxide into polyvinylsulphonic acid–sterculia gum hydrogels to modulate antibiotic drug vancomycin interactions for controlled drug delivery applications

Recently, graphene oxide (GO) has been well explored for biomedical applications due to its stability, biocompatibility and large surface area. Herein this research, GO incorporated sterculia gum-poly(VSA) hydrogels were designed by encapsulating vancomycin antibiotic drug for use in colon specific drug delivery.

UV-VUV Photofragmentation Spectroscopy of Isolated Neutral Fragile Macromolecules: A Proof-of-Principle Based on a Deprotonated Vancomycin-Peptide Noncovalent Complex.

The gas phase offers the possibility to analyze organic molecules by ultraviolet-vacuum ultraviolet (UV-VUV) spectroscopy without any solvent effect or limitation in terms of spectral range due to absorption by the solvent. Up to now, the size and chemical composition of neutral molecular systems under study have been limited by the use of vaporization methods based on thermal heating. Soft sources of gas-phase thermolabile molecular systems such as electrospray or matrix-assisted laser desorption ionization are appealing alternatives to heating-based techniques, but they lead to the production of ions. In such cases, UV-VUV action spectroscopy is then the method of choice to study the electronic structure and corresponding photodynamics of these gas-phase molecular ions. However, previous investigations have shown that the UV-VUV action spectrum of a given molecular ion depends on the charge state, which in many cases might be a caveat. Here, by means of synchrotron radiation coupled to mass spectrometry and through the test case of the glycopeptide antibiotic vancomycin noncovalently bound to a deprotonated small peptide, we show that the UV-VUV photofragmentation spectrum of neutral thermally fragile organic molecules can be obtained via charge-tagging action spectroscopy.

Antimicrobial Applications of Green Synthesized Bimetallic Nanoparticles from Ocimum basilicum.

Antibiotic resistance is an important and emerging alarm for public health that requires development of new potential antibacterial strategies. In recent years, nanoscale materials have emerged as an alternative way to fight pathogens. Many researchers have shown great interest in nanoparticles (NPs) using noble metals, such as silver, gold, and platinum, even though numerous nanomaterials have shown toxicity. To overcome the problem of toxicity, nanotechnology merged with green chemistry to synthesize nature-friendly nanoparticles from plants. Here, we describe the synthesis of NPs using silver (AgNPs) and platinum (PtNPs) alone or in combination (AgPtNPs) in the presence of Ocimum basilicum (O. basilicum) leaf extract. O. basilicum is a well-known medicinal plant with antibacterial compounds. A preliminary chemical-physical characterization of the extract was conducted. The size, shape and elemental analysis were carried out using UV-Visible spectroscopy, dynamic light scattering (DLS), and zeta potential. Transmission electron microscopy (TEM) confirmed polydisperse NPs with spherical shape. The size of the particles was approximately 59 nm, confirmed by DLS analysis, and the polydisperse index was 0.159. Fourier transform infrared (FTIR) demonstrated an effective and selective capping of the phytoconstituents on the NPs. The cytotoxic activities of AgNPs, PtNPs and AgPtNPs were assessed on different epithelial cell models, using the 3-[4.5-dimethylthiazol-2-yl]-2.5-diphenyltetrazolium bromide (MTT) cell proliferation assay, and discovered low toxicity, with a cell viability of 80%. The antibacterial potential of the NPs was evaluated against Escherichia coli (E. coli), Enterococcus faecalis (E. faecalis), Klebsiella pneumonia (K. pneumoniae), and Staphylococcus aureus (S. aureus) strains. Minimum inhibitory concentration (MIC) assays showed AgPtNP activity till the least concentration of NPs (3.15-1.56 µg/mL) against ATCC, MS, and MDR E. coli, E. faecalis, and S. aureus and the Kirby-Bauer method showed that AgPtNPs gave a zone of inhibition for Gram-positive and Gram-negative bacteria in a range of 9-25 mm. In addition, we obtained AgPtNP synergistic activity in combination with vancomycin or ampicillin antibiotics. Taken together, these results indicate that bimetallic nanoparticles, synthesized from O. basilicum leaf extract, could represent a natural, ecofriendly, cheap, and safe method to produce alternative antibacterial strategies with low cytotoxicity.

Novel Alligator Cathelicidin As-CATH8 Demonstrates Anti-Infective Activity against Clinically Relevant and Crocodylian Bacterial Pathogens

Host defense peptides (HDPs) represent an alternative way to address the emergence of antibiotic resistance. Crocodylians are interesting species for the study of these molecules because of their potent immune system, which confers high resistance to infection. Profile hidden Markov models were used to screen the genomes of four crocodylian species for encoded cathelicidins and eighteen novel sequences were identified. Synthetic cathelicidins showed broad spectrum antimicrobial and antibiofilm activity against several clinically important antibiotic-resistant bacteria. In particular, the As-CATH8 cathelicidin showed potent in vitro activity profiles similar to the last-resort antibiotics vancomycin and polymyxin B. In addition, As-CATH8 demonstrated rapid killing of planktonic and biofilm cells, which correlated with its ability to cause cytoplasmic membrane depolarization and permeabilization as well as binding to DNA. As-CATH8 displayed greater antibiofilm activity than the human cathelicidin LL-37 against methicillin-resistant Staphylococcus aureus in a human organoid model of biofilm skin infection. Furthermore, As-CATH8 demonstrated strong antibacterial effects in a murine abscess model of high-density bacterial infections against clinical isolates of S. aureus and Acinetobacter baumannii, two of the most common bacterial species causing skin infections globally. Overall, this work expands the repertoire of cathelicidin peptides known in crocodylians, including one with considerable therapeutic promise for treating common skin infections.

Abstract 14460: Aortic Valve Infective Endocarditis Complicated by Complete Heart Block and Gerbode’s Defect

Introduction: Aortic root abscess with complete heart block is a rare complication of infective endocarditis (IE). Early diagnosis and prompt surgical management are necessary to prevent fatal outcomes. Case Presentation: A 45-year-old male with past medical history of uncontrolled diabetes mellitus was referred to our cardiac intensive care unit for management of complete heart block. His symptoms including exertional dyspnea, hiccups, and dry cough started two weeks prior to presentation. The patient was bradycardic, hypoxic, and hypotensive on examination. Labs were significant for marked leukocytosis 21,000/ul with a neutrophilic predominance. Blood cultures were obtained, and the patient was started on empiric antibiotics vancomycin and piperacillin-tazobactam. Electrocardiogram (ECG) showed evidence of complete heart block and a temporary transvenous pacemaker was placed. A transthoracic echocardiogram was obtained that showed evidence of severe aortic regurgitation and aortic valve vegetations. Due to high clinical suspicion, a transesophageal echocardiogram was immediately performed that revealed aortic root abscess. Patient underwent successful debridement of aortic valve vegetations and aortic valve replacement. Intraoperative findings also included a subaortic left ventricular to right atrial (LV-RA) shunt also known as Gerbode’s defect that was repaired with pericardial patch. Blood cultures and intraoperative tissue cultures confirmed a Staphylococcus lugdunensis infection. He received six weeks of intravenous antibiotics. At 2-month follow-up, the patient reported doing well. Conclusion: New complete heart block may be a manifestation of aortic root abscess. This case illustrates the need to maintain a high level of suspicion for complicated infective endocarditis in patients with sepsis and complete heart block. Timely diagnosis with imaging and early surgical repair results in favorable outcomes.

Can heavy metal pollution induce soil bacterial community resistance to antibiotics in boreal forests?

Abstract The emergence of microbial antibiotic resistance is a central threat to global health, food security, and development. It has been shown that heavy metal pollution can give rise to microbial resistance to antibiotics, but how wide‐spread this phenomenon is remains an open question that urgently needs filling to enable appropriate environmental risk assessments. Here, we determined whether long‐term differences in heavy metal pollution in boreal forests had affected soil microbial communities such that they had increased microbial resistance to antibiotics. First, we assessed variation in metal concentrations in samples collected across a distance trajectory from the pollution source, and also the microbial rates and levels of bacterial community resistance to the heavy metal Cu and the antibiotics tetracycline and vancomycin in those samples. Second, we tested if the exposure to Cu or tetracycline could increase bacterial community resistance to Cu and to antibiotics in soils with high versus low background levels of metal contamination. Metal pollution had affected microbial community structures and suppressed decomposer functioning. Importantly, bacterial community Cu resistance increased with higher metal concentrations, which coincided with an induced bacterial community resistance to tetracycline, but not to vancomycin. Laboratory experiments revealed that bacterial community Cu resistance could be further induced in both the low and high end of the pollution gradient, but also that these short‐term inductions of community metal tolerance did not coincide with enhanced antibiotic resistance. This yielded a surprising negative correlation between long‐term and short‐term effects by metals on microbial metal and antibiotic resistances. One mechanism that could provide protection against both metal cations and tetracycline is the small multidrug resistance (SMR) family, which is an energy demanding physiological mechanism that may take time to confer protection. This may explain the different microbial responses to long‐term gradients and metal addition experiments. Policy implications. We show that metal pollution in boreal forests will promote soil bacterial antibiotic resistance, revealing a so far unrecognized reservoir of microbial antibiotic resistance. We recommend that environmental risk assessments for any activity giving rise to increased soil metal concentrations need to also consider the induction of microbial antibiotic resistance.

Membrane Vesicles Derived from Gut Microbiota and Probiotics: Cutting-Edge Therapeutic Approaches for Multidrug-Resistant Superbugs Linked to Neurological Anomalies.

Multidrug-resistant (MDR) superbugs can breach the blood-brain barrier (BBB), leading to a continuous barrage of pro-inflammatory modulators and induction of severe infection-related pathologies, including meningitis and brain abscess. Both broad-spectrum or species-specific antibiotics (β-lactamase inhibitors, polymyxins, vancomycin, meropenem, plazomicin, and sarecycline) and biocompatible poly (lactic-co-glycolic acid) (PLGA) nanoparticles have been used to treat these infections. However, new therapeutic platforms with a broad impact that do not exert off-target deleterious effects are needed. Membrane vesicles or extracellular vesicles (EVs) are lipid bilayer-enclosed particles with therapeutic potential owing to their ability to circumvent BBB constraints. Bacteria-derived EVs (bEVs) from gut microbiota are efficient transporters that can penetrate the central nervous system. In fact, bEVs can be remodeled via surface modification and CRISPR/Cas editing and, thus, represent a novel platform for conferring protection against infections breaching the BBB. Here, we discuss the latest scientific research related to gut microbiota- and probiotic-derived bEVs, and their therapeutic modifications, in terms of regulating neurotransmitters and inhibiting quorum sensing, for the treatment of neurodegenerative diseases, such as Parkinson's and Alzheimer's diseases. We also emphasize the benefits of probiotic-derived bEVs to human health and propose a novel direction for the development of innovative heterologous expression systems to combat BBB-crossing pathogens.