Antibiotic resistance rates in hypervirulent Klebsiella pneumoniae strains: a systematic review and meta-analysis.

OBJECTIVES: In response to the growing global concerns regarding antibiotic resistance, we conducted a meta-analysis to assess the prevalence of antibiotic resistance in hypervirulent Klebsiella pneumoniae (hvKp) strains. METHODS: We conducted a meta-analysis of antibiotic resistance in the hvKp strains. Eligible studies published in English until April 10, 2023, were identified through a systematic search of various databases. After removing duplicates, two authors independently assessed and analyzed the relevant publications, and a third author resolved any discrepancies. Data extraction included publication details and key information on antibiotic resistance. Data synthesis employed a random-effects model to account for heterogeneity, and various statistical analyses were conducted using R and the metafor package. RESULTS: This meta-analysis of 77 studies from 17 countries revealed the prevalence of antibiotic resistance in hvKp strains. A high resistance rates have been observed against various classes of antibiotics. Ampicillin-sulbactam faced 45.3% resistance, respectively, rendering them largely ineffective. The first-generation cephalosporin cefazolin exhibited a resistance rate of 38.1%, whereas second-generation cefuroxime displayed 26.7% resistance. Third-generation cephalosporins, cefotaxime (65.8%) and ceftazidime (57.1%), and fourth-generation cephalosporins, cefepime (51.3%), showed substantial resistance. The last-resort carbapenems, imipenem (45.7%), meropenem (51.0%), and ertapenem (40.6%), were not spared. Conclusion CONCLUSION: This study emphasizes the growing issue of antibiotic resistance in hvKp strains, with notable resistance to both older and newer antibiotics, increasing resistance over time, regional disparities, and methodological variations. Effective responses should involve international cooperation, standardized testing, and tailored regional interventions.

A novel Enterococcus faecium phage EF-M80: unveiling the effects of hydrogel-encapsulated phage on wound infection healing.

Background: Enterococcus faecium is one of the members of ESKAPE pathogens. Due to its resistance to antimicrobial agents, treating this bacterium has become challenging. The development of innovative approaches to combat antibiotic resistance is necessary. Phage therapy has emerged as a promising method for curing antibiotic-resistant bacteria. Methods: In this study, E. faecium phages were isolated from wastewater. Phage properties were characterized through in vitro assays (e.g. morphological studies, and physicochemical properties). In addition, whole genome sequencing was performed. A hydrogel-based encapsulated phage was obtained and its structure characteristics were evaluated. Wound healing activity of the hydrogel-based phage was assessed in a wound mice model. Results: The purified phage showed remarkable properties including broad host range, tolerance to high temperature and pH and biofilm degradation feature as a stable and reliable therapeutic agent. Whole genome sequencing revealed that the genome of the EF-M80 phage had a length of 40,434 bp and harbored 65 open reading frames (ORFs) with a GC content of 34.9% (GenBank accession number is OR767211). Hydrogel-based encapsulated phage represented an optimized structure. Phage-loaded hydrogel-treated mice showed that the counting of neutrophils, fibroblasts, blood vessels, hair follicles and percentage of collagen growth were in favor of the wound healing process in the mice model. Conclusion: These findings collectively suggest the promising capability of this phage-based therapeutic strategy for the treatment of infections associated with the antibiotic-resistant E. faecium. In the near future, we hope to expect the presence of bacteriophages in the list of antibacterial compounds used in the clinical settings.

Insights into the novel Enterococcus faecalis phage: A comprehensive genome analysis.

Enterococcus faecalis, a Gram-positive bacterium, poses a significant clinical challenge owing to its intrinsic resistance to a broad spectrum of antibiotics, warranting urgent exploration of innovative therapeutic strategies. This study investigated the viability of phage therapy as an alternative intervention for antibiotic-resistant E. faecalis, with a specific emphasis on the comprehensive genomic analysis of bacteriophage SAM-E.f 12. The investigation involved whole-genome sequencing of SAM-E.f 12 using Illumina technology, resulting in a robust dataset for detailed genomic characterization. Bioinformatics analyses were employed to predict genes and assign functional annotations. The bacteriophage SAM-E.f 12, which belongs to the Siphoviridae family, exhibited substantial potential, with a burst size of 5.7 PFU/infected cells and a latent period of 20 min. Host range determination experiments demonstrated its effectiveness against clinical E. faecalis strains, positioning SAM-E.f 12 as a precise therapeutic agent. Stability assays underscore resilience across diverse environmental conditions. This study provides a comprehensive understanding of SAM-E.f 12 genomic composition, lytic lifecycle parameters, and practical applications, particularly its efficacy in murine wound models. These results emphasize the promising role of phage therapy, specifically its targeted approach against antibiotic-resistant E. faecalis strains. The nuanced insights derived from this research will contribute to the ongoing pursuit of efficacious phage therapies and offer valuable implications for addressing the clinical challenges associated with E. faecalis infections.

Repurposing of Compounds from Streptomyces spp. as Potential Inhibitors of Aminoacyltransferase FemA: An Essential Drug Target against Drug-resistant Staphylococcus aureus.

BACKGROUND: Drug-resistant Staphylococcus aureus represents a substantial healthcare challenge worldwide, and its range of available therapeutic options continues to diminish progressively. Thus, this study aimed to identify potential inhibitors against FemA, a crucial protein involved in the cell wall biosynthesis of S. aureus. MATERIALS AND METHODS: The screening process involved a comprehensive structure-based virtual screening on the StreptomDB database to identify ligands with potential inhibitory effects on FemA using AutoDock Vina. The most desirable ligands with the highest binding affinity and pharmacokinetic properties were selected. Two ligands with the highest number of hydrogen bonds and hydrophobic interactions were further analyzed by molecular dynamics (MD) using the GROMACS version 2018 simulation package. RESULTS: Six H-donor conserved residues were selected as protein active sites, including Arg- 220, Tyr-38, Gln-154, Asn-73, Arg-74, and Thr-24. Through virtual screening, a total of nine compounds with the highest binding affinity to the FemA protein were identified. Frigocyclinone and C21H21N3O4 exhibited the highest binding affinity and demonstrated favorable pharmacokinetic properties. Molecular dynamics analysis of the FemA-ligand complexes further indicated desirable stability and reliability of complexes, reinforcing the potential efficacy of these ligands as inhibitors of FemA protein. CONCLUSION: Our findings suggest that Frigocyclinone and C21H21N3O4 are promising inhibitors of FemA in S. aureus. To further validate these computational results, experimental studies are planned to confirm the inhibitory effects of these compounds on various S. aureus strains. Combining computational screening with experimental validation contributes valuable insights to the field of drug discovery in comparison to the classical drug discovery approaches.