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International Journal of Biological... Jun 2024Conventional wound dressings are monolithically designed to cover the injured areas as well as absorb the exudates at injured site. Furthermore, antibacterial drugs and...
Conventional wound dressings are monolithically designed to cover the injured areas as well as absorb the exudates at injured site. Furthermore, antibacterial drugs and growth prompting factors are additionally appended to realize sensible and omnibearing wound management, exhibiting long and tedious treatment process in practice. Consequently, the creation of multifunctional wound dressings that combines wound repair enhancement with antibacterial properties turns out to be significant for simplifying wound managements. In our investigation, electronegative human epidermal growth factor (hEGF) was combined with the positively charged ZnAl layered double hydroxides (ZnAl LDHs) via electrostatic interaction while the obtained hEGF/LDH was integrated with sodium hyaluronate hydrogel (SH) hydrogel, forming a composite hydrogel with synergistic benefits for wound management. The innovative hEGF/LDH@SH hydrogel equipped with fine biocompatibility was designed to optimize wound healing in which hEGF stimulates epithelial cell growth while LDH released antibacterial factor Zn against Methicillin-resistant staphylococcus aureus (MRSA) and Escherichia coli (E.coli) under acidic wound environment. Additionally, the SH hydrogel constructed a three-dimensional structure that not only safeguarded the wound area but also maintained a moist environment conducive to recovery. The synthesized hEGF/LDH was confirmed via fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and thermo-gravimetry (TG) measurements. The release of Zn from ZnAl LDH under acid circumstance was detected via inductively coupled plasma (ICP) and the in vitro bactericidal experiments endowed the antibacterial property of hEGF/LDH@SH hydrogel. In vitro drug release experiments illustrated the controlled-release of hEGF from hEGF/LDH which promoted the long-term affect of hEGF at wound site. In vitro cell experiments verified that the hEGF/LDH@SH hydrogel motivated the promotion on cell proliferation and migration without cytotoxicity. An in vivo study of the repairing of MRSA-infected wound in mice indicated that hEGF/LDH@SH hydrogel serves as a simple and novel, innoxious and efficient wound healing approach. This brand new hydrogel possesses properties of promoting the regeneration of skin tissue, achieving antimicrobial therapy without any accessional antibacterial drugs as well as realizing controlled release of hEGF.
PubMed: 38942404
DOI: 10.1016/j.ijbiomac.2024.133423 -
Scientific Reports Jun 2024Methicillin-resistant Staphylococcus (MRS) has been associated with neonatal infections, with colonization of the anovaginal tract being the main source of vertical...
Methicillin-resistant Staphylococcus (MRS) has been associated with neonatal infections, with colonization of the anovaginal tract being the main source of vertical transmission. The COVID-19 pandemic has altered the frequency of antibiotic usage, potentially contributing to changes in the dynamics of bacterial agents colonizing humans. Here we determined MRS colonization rates among pregnant individuals attending a single maternity in Rio de Janeiro, Brazil before (January 2019-March 2020) and during (May 2020-March 2021) the COVID-19 pandemic. Anovaginal samples (n = 806 [521 samples before and 285 during the pandemic]) were streaked onto chromogenic media. Colonies were identified by MALDI-TOF MS. Detection of mecA gene and SCCmec typing were assessed by PCR and antimicrobial susceptibility testing was done according to CLSI guidelines. After the onset of the pandemic, MRS colonization rates increased significantly (p < 0.05) from 8.6% (45) to 54.7% (156). Overall, 215 (26.6%) MRS isolates were detected, of which S. haemolyticus was the most prevalent species (MRSH, 84.2%; 181 isolates). SCCmec type V was the most frequent among MRS (63.3%; 136), and 31.6% (68) of MRS strains had a non-typeable SCCmec, due to new combinations of ccr and mecA complexes. Among MRS strains, 41.9% (90) were resistant to at least 3 different classes of antimicrobial agents, and 60% (54) of them were S. haemolyticus harboring SCCmec V. MRS colonization rates and the emergence of multidrug-resistant variants detected in this study indicate the need for continuing surveillance of this important pathogen within maternal and child populations.
Topics: Humans; Female; Pregnancy; COVID-19; Staphylococcal Infections; Methicillin-Resistant Staphylococcus aureus; Adult; Brazil; Pregnancy Complications, Infectious; Anti-Bacterial Agents; SARS-CoV-2; Microbial Sensitivity Tests; Pandemics; Vagina
PubMed: 38942787
DOI: 10.1038/s41598-024-64422-9 -
Journal of Microbiology, Immunology,... Jun 2024The increasing prevalence of drug-resistant pathogens leads to delays in adequate antimicrobial treatment in intensive care units (ICU). The real-world influence of the...
The real-world impact of the BioFire FilmArray blood culture identification 2 panel on antimicrobial stewardship among patients with bloodstream infections in intensive care units with a high burden of drug-resistant pathogens.
BACKGROUND
The increasing prevalence of drug-resistant pathogens leads to delays in adequate antimicrobial treatment in intensive care units (ICU). The real-world influence of the BioFire FilmArray Blood Culture Identification 2 (BCID2) panel on pathogen identification, diagnostic concordance with conventional culture methods, and antimicrobial stewardship in the ICU remains unexplored.
METHODS
This retrospective observational study, conducted from July 2021 to August 2023, involved adult ICU patients with positive blood cultures who underwent BCID2 testing. The concordance between BCID2 and conventional culture results was examined, and its impact on antimicrobial stewardship was assessed through a comprehensive retrospective review of patient records by intensivists.
RESULTS
A total of 129 blood specimens from 113 patients were analysed. Among these patients, a high proportion of drug-resistant strains were noted, including carbapenem-resistant Klebsiella pneumoniae (CRKP) (57.1%), carbapenem-resistant Acinetobacter calcoaceticus-baumannii complex (100%), methicillin-resistant Staphylococcus aureus (MRSA) (70%), and vancomycin-resistant Enterococcus faecium (VRE) (100%). The time from blood culture collection to obtaining BCID2 results was significantly shorter than conventional culture (46.2 h vs. 86.9 h, p < 0.001). BCID2 demonstrated 100% concordance in genotype-phenotype correlation in antimicrobial resistance (AMR) for CRKP, carbapenem-resistant Escherichia coli, MRSA, and VRE. A total of 40.5% of patients received inadequate empirical antimicrobial treatment. The antimicrobial regimen was adjusted or confirmed in 55.4% of patients following the BCID2 results.
CONCLUSIONS
In the context of a high burden of drug-resistant pathogens, BCID2 demonstrated rapid pathogen and AMR detection, with a noticeable impact on antimicrobial stewardship in BSI in the ICU.
PubMed: 38942661
DOI: 10.1016/j.jmii.2024.06.004 -
PloS One 2024A growing increase in the number of serious infections caused by multidrug resistant bacteria (MDR) is challenging our society. Despite efforts to discover novel...
A growing increase in the number of serious infections caused by multidrug resistant bacteria (MDR) is challenging our society. Despite efforts to discover novel therapeutic options, few antibiotics targeting MDR have been approved by the Food and Drug Administration (FDA). Lactic acid bacteria have emerged as a promising therapeutic alternative due to their demonstrated ability to combat MDR pathogens in vitro. Our previous co-culture studies showed Lacticaseibacillus rhamnosus CRL 2244 as having a potent killing effect against carbapenem-resistant Acinetobacter baumannii (CRAB) strains. Here we report that cell-free conditioned media (CFCM) samples obtained from Lcb. rhamnosus CRL 2244 cultures incubated at different times display antimicrobial activity against 43 different pathogens, including CRAB, methicillin-resistant Staphylococcus aureus (MRSA) and carbapenemase Klebsiella pneumoniae (KPC)-positive strains. Furthermore, transwell and ultrafiltration analyses together with physical and chemical/biochemical tests showed that Lcb. rhamnosus CRL 2244 secretes a <3 kDa metabolite(s) whose antimicrobial activity is not significantly impaired by mild changes in pH, temperature and various enzymatic treatments. Furthermore, sensitivity and time-kill assays showed that the bactericidal activity of the Lcb. rhamnosus CRL 2244 metabolite(s) enhances the activity of some current FDA approved antibiotics. We hypothesize that this observation could be due to the effects of Lcb. rhamnosus CRL 2244 metabolite(s) on cell morphology and the enhanced transcriptional expression of genes coding for the phenylacetate (PAA) and histidine catabolic Hut pathways, metal acquisition and biofilm formation, all of which are associated with bacterial virulence. Interestingly, the extracellular presence of Lcb. rhamnosus CRL 2244 induced the transcription of the gene coding for the CidA/LgrA protein, which is involved in programmed cell death in some bacteria. Overall, the findings presented in this report underscore the promising potential of the compound(s) released by Lcb. rhamnosus CRL2244 as an alternative and/or complementary option to treat infections caused by A. baumannii as well as other MDR bacterial pathogens.
Topics: Lacticaseibacillus rhamnosus; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Microbial Sensitivity Tests; Acinetobacter baumannii; Drug Synergism; Methicillin-Resistant Staphylococcus aureus; Culture Media, Conditioned; Bacterial Proteins
PubMed: 38941324
DOI: 10.1371/journal.pone.0306273 -
Personalized Medicine Jun 2024Compare two vancomycin dosing strategies in critical patients with methicillin-resistant (MRSA) infections, considering the heterogeneity of the dosing regimens...
Compare two vancomycin dosing strategies in critical patients with methicillin-resistant (MRSA) infections, considering the heterogeneity of the dosing regimens administered and their implications for toxicity and efficacy. Longitudinal retrospective observational study in two patient cohorts (standard dosing vs dosing via Bayesian algorithms). The group of Bayesian algorithms received substantially higher and significantly heterogeneous doses, with an absence of nephrotoxicity. The speed of decrease observed in CRP and PCT was greater for the Bayesian strategy (p = 0.045 and 0.0009, respectively). Applying Bayesian algorithms to vancomycin dosage individualization allows for administering much higher doses than with standard regimens, facilitating a quicker clinical response in the absence of nephrotoxicity.
PubMed: 38940364
DOI: 10.1080/17410541.2024.2365616 -
Acta Medica Philippina 2024Based on the 2017-2020 annual report of the Department of Health-Antimicrobial Resistance Surveillance Program, significant resistance patterns have been observed for...
BACKGROUND
Based on the 2017-2020 annual report of the Department of Health-Antimicrobial Resistance Surveillance Program, significant resistance patterns have been observed for common disease-causing pathogens. In the hospital setting, antimicrobial stewardship programs have been implemented to optimize the use of antimicrobials. Drug utilization review studies provide essential feedback to improve prescribing and use of medications.
OBJECTIVES
This study aimed to review drug utilization of monitored parenteral antimicrobials among patients admitted from January to December 2019.
METHODS
The study employed a retrospective, cross-sectional, descriptive research design. A retrospective chart review of drugs administered to patients was conducted.
RESULTS
A total of 821 patients charts met the inclusion criteria. The patients' ages ranged from 18 to 98 years old and 52% were females. General Internal Medicine practitioners (28%) were the top prescribers of monitored parenteral antimicrobials primarily for the management of moderate-risk community-acquired pneumonia (39%). They were mostly indicated for empirical treatment of infections (94%) and were given for an average of 5.73 days.Only 58% of the total cases had orders for culture and sensitivity testing. Of which, principally 47% had colony cultures. Blood (29%) and sputum (27%) were the most common specimens taken for culture and sensitivity testing. The microorganisms often isolated were (19%), (18%), and (9%). In addition, extended-spectrum beta lactamase-producing gram-negative pathogens (4%) and methicillin-resistant (1%) were also isolated. All the microorganisms isolated showed most resistance to ampicillin (81%) and most susceptibility to colistin (100%). There were drug therapy-related problems encountered. There was one case of an adverse drug reaction (0.1%) and two cases of contraindications (0.2%). Therapeutic duplication was also observed in 5% of the cases. Moreover, 39% had instances of drug-drug interactions.Piperacillin-tazobactam had the highest consumption (79.50 defined daily doses/1,000-patient days) among the monitored parenteral antimicrobials.Some prescriptions were deemed inappropriate upon evaluation. 12% of cases were inappropriate based on the justification indicator. As for the critical indicators, duration of therapy (78%) was the main reason. Only four components of the DUE criteria indicators have met or exceeded the established threshold level.The cost analysis indicated that the total actual cost of therapy with the monitored parenteral antimicrobials amounted to ₱17,645,601.73. Considering Department of Health National Antibiotic Guidelines recommendations, ideal total cost of treatment was ₱14,917,214.29. Potential cumulative cost savings of ₱2,728,387.44 could have been achieved for patients admitted last 2019.
CONCLUSION
Consumption of piperacillin-tazobactam was relatively high as compared to the other monitored parenteral antimicrobials covered in this study. Physicians at the study site seldom prescribe monitored parenteral antimicrobials as recommended by the National Antibiotic Guidelines. This is evidenced in the incidence of inappropriate therapy regimens, with inapt duration of therapy as the leading explanation.From the patient's perspective, the main economic implication was on the direct medical costs, particularly the increased cost of the actual antimicrobial therapy prescribed to manage various infections. Adherence of physicians to the established guidelines and selection of the most cost-effective therapy could have resulted in considerable cost savings.
PubMed: 38939423
DOI: 10.47895/amp.vi0.7249 -
Chemical Science Jun 2024Antimicrobial resistance (AMR) is a growing threat to health globally, with the potential to render numerous medical procedures so dangerous as to be impractical. There...
Antimicrobial resistance (AMR) is a growing threat to health globally, with the potential to render numerous medical procedures so dangerous as to be impractical. There is therefore an urgent need for new molecules that function through novel mechanisms of action to combat AMR. The bacterial DNA-repair and SOS-response pathways promote survival of pathogens in infection settings and also activate hypermutation and resistance mechanisms, making these pathways attractive targets for new therapeutics. Small molecules, such as IMP-1700, potentiate DNA damage and inhibit the SOS response in methicillin-resistant ; however, understanding of the structure-activity relationship (SAR) of this series is lacking. We report here the first comprehensive SAR study of the IMP-1700 scaffold, identifying key pharmacophoric groups and delivering the most potent analogue reported to date, OXF-077. Furthermore, we demonstrate that as a potent inhibitor of the mutagenic SOS response, OXF-077 suppresses the rate of ciprofloxacin resistance emergence in . This work supports SOS-response inhibitors as a novel means to combat AMR, and delivers OXF-077 as a tool molecule for future development.
PubMed: 38939155
DOI: 10.1039/d4sc00995a -
The Journal of Dermatological Treatment Dec 2024Cutaneous infection in epidermolysis bullosa (EB) can cause significant morbidity, mortality, and dangerous sequelae. This review article aims to delve into the known... (Review)
Review
Cutaneous infection in epidermolysis bullosa (EB) can cause significant morbidity, mortality, and dangerous sequelae. This review article aims to delve into the known epidemiology of EB, highlight the disease's primary causative agents and their antimicrobial resistance spectrum. A thorough literature search was conducted using Medline, EMBASE, JBI and PubMed to gather data on the microbial landscape of EB wounds. The focus was on identifying the most common bacteria associated with EB infections and assessing their antimicrobial resistance profiles. The analysis revealed that is the most frequently identified bacterium in EB wounds, with a notable prevalence of methicillin-resistant strains (MRSA). Specific studies on mupirocin resistance further indicated rising rates of mupirocin-resistant , with one study reporting rates as high as 16.07%. Additionally, high resistance to other antibiotics, such as levofloxacin and trimethoprim/sulfamethoxazole, was observed in MRSA isolates. The findings highlight the critical need for regular resistance surveillance and the prudent use of mupirocin to manage infections effectively in EB. The multi-drug resistant nature of pathogens in EB presents a significant challenge in treatment, highlighting the importance of antimicrobial stewardship. Ultimately, given the sparse literature and the rarity of large-scale studies, further longitudinal research on the antimicrobial resistance profile of bacteria isolated from EB wounds is essential.
Topics: Humans; Epidermolysis Bullosa; Anti-Bacterial Agents; Methicillin-Resistant Staphylococcus aureus; Drug Resistance, Multiple, Bacterial; Microbial Sensitivity Tests; Wound Infection; Mupirocin; Drug Resistance, Bacterial
PubMed: 38936964
DOI: 10.1080/09546634.2024.2370424 -
International Journal of Biological... Jun 2024Targeting delivery to the infection site and good affinity of vehicle to the bacterial are two main concerns in therapy of bacterial infection, and on-demand release of...
Targeting delivery to the infection site and good affinity of vehicle to the bacterial are two main concerns in therapy of bacterial infection, and on-demand release of drug is another important issue. In this work, a liposome drug delivery system (HA/P/BAI-lip) incorporated with baicalein and modified by PHMG and HA was prepared. Several characterizations were conducted to examine the physical properties of liposome. Then it was applied to treatments of MRSA induced dorsal subcutaneous abscess model and the thigh muscle infected model. The presence of guanidine group in HA/P/BAI-lip rendered the liposome satisfactory bacterial target ability and good pH sensitive properties. The lipase secreted by bacterial could promote the hydrolysis of soybean phosphatidylcholine (SPC) in liposome. The modification of HA in HA/P/BAI-lip could lead the drug system to the exact infected site where CD44 was abundant because of inflammation. The low pH microenvironment characteristic of bacterial infection could induce the swelling of liposome following by degradation. Taken together, baicalein could be released selectively at the infected site to exert antibacterial capacity. HA/P/BAI-lip showed impressive antibacterial ability and dramatically decrease the bacterial burden of infection site and alleviate the infiltration of inflammatory cells, facilitating the recovery of infection.
PubMed: 38936579
DOI: 10.1016/j.ijbiomac.2024.133432 -
Bioorganic Chemistry Jun 2024Di-branched and tetra-branched versions of a previously reported analogue of the lipopeptide battacin were successfully synthesised using thiol-maleimide click and 1, 2,...
Di-branched and tetra-branched versions of a previously reported analogue of the lipopeptide battacin were successfully synthesised using thiol-maleimide click and 1, 2, 3-triazole click chemistry. Antimicrobial studies against drug resistant clinical isolates of Escherichia coli (ESBL E. coli Ctx-M14), Pseudomonas aeruginosa (P. aeruginosa Q502), and Methicillin resistant Staphylococcus aureus (MRSA ATCC 33593), as well as clinically isolated Acinetobacter baumannii (A. baumannii ATCC 19606), and P. aeruginosa (ATCC 27853), revealed that the dendrimeric peptides have antimicrobial activity in the low micromolar range (0.5 -- 4 μM) which was 10 times more potent than the monomer peptides. Under high salt concentrations (150 mM NaCl, 2 mM MgCl, and 2.5 mM CaCl) the di-branched lipopeptides retained their antimicrobial activity while the monomer peptides were not active (>100 μM). The di-branched triazole click lipopeptide, Peptide 12, was membrane lytic, showed faster killing kinetics, and exhibited antibiofilm activity against A. baumannii and MRSA and eradicated > 85 % preformed biofilms at low micromolar concentrations. The di-branched analogues were > 30-fold potent than the monomers against Candida albicans. Peptide 12 was not haemolytic (HC10 = 932.12 μM) and showed up to 40-fold higher selectivity against bacteria and fungi than the monomer peptide. Peptide 12 exhibited strong proteolytic stability (>80 % not degraded) in rat serum over 24 h whereas > 95 % of the thiol-maleimide analogue (Peptide 10) was degraded. The tetra-branched peptides showed comparable antibacterial potency to the di-branched analogues. These findings indicate that dual branching using triazole click chemistry is a promising strategy to improve the antimicrobial activity and proteolytic stability of battacin based lipopeptides. The information gathered can be used to build effective antimicrobial dendrimeric peptides as new peptide antibiotics.
PubMed: 38936047
DOI: 10.1016/j.bioorg.2024.107567