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Infectious Diseases and Therapy Jun 2024Methicillin-resistant Staphylococcus aureus (MRSA) infections are a serious threat to public health. Vancomycin (VAN) remains the primary treatment for these infections,...
Characterizing Day 1 Area Under the Curve Following Vancomycin Loading Dose Administration in Adult Hospitalized Patients Using Non-Trapezoidal Linear Pharmacokinetic Equations: A Retrospective Observational Study.
INTRODUCTION
Methicillin-resistant Staphylococcus aureus (MRSA) infections are a serious threat to public health. Vancomycin (VAN) remains the primary treatment for these infections, and achieving the recommended area under the curve (AUC) target has been linked to improved clinical outcomes. The current VAN therapeutic monitoring guidelines recommend a loading dose (LD) of 20-35 mg/kg to rapidly attain targeted VAN exposures within 24 h of therapy. However, there is a paucity of data describing the impact of VAN LD on day 1 area under the curve (AUC). This study aims to employ pharmacokinetic (PK) equations to calculate and describe the AUC following a VAN LD of 20 mg/kg.
METHODS
This was a retrospective study of adult patients who were loaded with VAN 20 mg/kg, received ≥ 48 h of treatment, and had two consecutive serum VAN levels collected within 24 h. Linear, non-trapezoidal PK equations and two post-infusion VAN levels were used to calculate AUC. Therapeutic AUC was defined as 400-600 mg/l*h.
RESULTS
Among 123 included patients, the median age was 46 years (IQR 36, 62), 54% (67/123) of the patients had a body mass index (BMI) ≥ 30 kg/m and 27% (33/123) were admitted to the intensive care unit (ICU). Following a LD of 20 mg/kg, 50% (61/123) of the patients met the therapeutic AUC, while 22% (27/123) of the patients were subtherapeutic, and 28% (35/123) were supratherapeutic. Compared with patients who achieved therapeutic AUC, patients with subtherapeutic AUC were more likely to be younger (44 vs. 37 years old) and have a BMI ≥ 30 kg/m (67 vs. 52%). In contrast, patients with supratherapeutic AUC were more likely to be older (64 vs. 44 years old) and to have chronic kidney disease diagnosis (23 vs. 7%) when compared to patients who achieved a therapeutic AUC CONCLUSIONS: Only 50% of patients achieve the target AUC following a VAN 20 mg/kg LD, with younger, heavier patients underexposed and older patients with renal impairment overexposed, suggesting that different dosing strategies are needed for these populations.
PubMed: 38922527
DOI: 10.1007/s40121-024-01004-2 -
Biometals : An International Journal on... Jun 2024In the present manuscript, novel macrocyclic Schiff base complexes [Zn(NMacL)Cl-Zn(NMacL)Cl] were synthesized by the reaction of ZnCl and macrocyclic ligands...
Novel tetraaza macrocyclic Schiff base complexes of bivalent zinc: microwave-assisted green synthesis, spectroscopic characterization, density functional theory calculations, molecular docking studies, in vitro antimicrobial and anticancer activities.
In the present manuscript, novel macrocyclic Schiff base complexes [Zn(NMacL)Cl-Zn(NMacL)Cl] were synthesized by the reaction of ZnCl and macrocyclic ligands (NMacL-NMacL) derived from diketone and diamines under microwave irradiation method and conventional method. The structures of the obtained complexes were identified by various spectrometric methods such as Fourier transformation infra-red (FT-IR), nuclear magnetic resonance (NMR), high-resolution mass spectrometry (HR-MS), powder X-ray diffraction, molar conductivity, and UV-vis. The structures of the synthesized compounds were optimized by using the def2-TZV/J and def2-SVP/J Coulomb fitting basis sets at B3LYP level in density functional theory (DFT) calculations. The macrocyclic Schiff base complexes exhibited higher activities against Gram-positive bacteria (Staphylococcus aureus and Bacillus cereus), Gram-negative bacteria (Escherichia coli and Xanthomonas campestris), and fungal strains (Fusarium oxysporum and Candida albicans) in comparison to macrocyclic Schiff base ligands. Furthermore, the newly synthesized macrocyclic compounds were assessed for their anticancer activity against three cell lines: A549 (human alveolar adenocarcinoma epithelial cell line), HT-29 (human colorectal adenocarcinoma cell line), and MCF-7 (human breast adenocarcinoma cell line) using the MTT assay. The obtained results showed that the macrocyclic complex [Zn(NMacL)Cl] displayed the highest cytotoxic activity (2.23 ± 0.25 µM, 6.53 ± 0.28 µM, and 7.40 ± 0.45 µM for A549, HT-29, and MCF-7 cancer cell lines, respectively). Additionally, molecular docking investigations were conducted to elucidate potential molecular interactions between the synthesized macrocyclic compounds and target proteins. The results revealed a consistent agreement between the docking calculations and the experimental data.
PubMed: 38922505
DOI: 10.1007/s10534-024-00616-y -
International Ophthalmology Jun 2024To provide a comprehensive microbiological profile of bacterial dacryocystitis in South Australia. By identifying the specific microorganism and antibiotic...
PURPOSE
To provide a comprehensive microbiological profile of bacterial dacryocystitis in South Australia. By identifying the specific microorganism and antibiotic susceptibility, this study intends to aid ophthalmologists in choosing appropriate empirical antibiotic therapies and development of evidence-based clinical guidelines.
METHOD
A retrospective study was conducted at the Royal Adelaide Hospital (RAH) over five years (2018-2023) of patients with acute dacryocystitis. The study included 43 patients, and data encompassed demographic information, clinical presentation, microbiological analysis, management, and outcomes. Patients with chronic dacryocystitis were excluded.
RESULTS
Among the 43 patients included in the study (female 28 (65%), mean age: 64 years old), the most common clinical features were pain (74%) and swelling (70%). Organisms were identified in 49% of patients, with the predominant bacteria being Staphylococcus aureus (42%), Streptococcus species (19%), and Escherichia coli (8%). Aggregatibacter species (8%), Morganella morganii (4%), Enterobacter cloaceae (4%), Hafnia alvei (4%), mixed anaerobes (4%), E coliforms (4%) and Pseudomonas aeruginosa (4%) were also identified. The most frequently prescribed empirical antibiotics were amoxicillin-clavulanic acid (50%), flucloxacillin (33%) and cefalexin (18%).
CONCLUSION
The microbiological trends of acute dacryocystitis have largely remained consistent, with a predominance of Gram positive organisms. This is the most recent profile analysis of acute dacryocystitis in South Australia and will help form evidence-based clinical guidelines.
Topics: Humans; Female; Middle Aged; Dacryocystitis; Male; Eye Infections, Bacterial; Retrospective Studies; South Australia; Acute Disease; Anti-Bacterial Agents; Aged; Tertiary Care Centers; Adult; Bacteria; Microbial Sensitivity Tests; Aged, 80 and over
PubMed: 38922457
DOI: 10.1007/s10792-024-03236-0 -
Biomacromolecules Jun 2024Polymeric drugs containing up to 60% by weight of the antibiotic vancomycin were synthesized based on dextran carriers activated with epichlorohydrin. Vancomycin was...
Polymeric drugs containing up to 60% by weight of the antibiotic vancomycin were synthesized based on dextran carriers activated with epichlorohydrin. Vancomycin was covalently bound, involving the primary amino group of the molecule through the hydroxypropyl radical to the C6 position of the anhydroglucose units of the dextran main chain. Covalent binding is necessary to prevent spontaneous release of the antibiotic from the gel, thereby reducing the risk of bacterial multiresistance. Antibacterial depot gels were obtained from those polymers, containing up to 17.5% by weight of polysaccharide with a cross-linking density of = 3-5 nodes per macromolecule for the deposition of another type of drugs not covalently bound to the polymer gel. They were used to coat the surface of the internal pores of biocomposite bone implants based on bovine cancellous bone used in orthopedics. The chemical structure of the polymer was studied using C NMR spectroscopy and matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry. The stiffness of the gels was evaluated by the values of the accumulation modulus ' = 170-270 kPa and the loss modulus ″ = 3.7-4.2 kPa determined on a rheometer. Their values are close to those typical for materials used to replace soft tissue in plastic surgery. The minimum inhibitory concentration of the gels against depends on the antibiotic content in the polymer. It equals 2.5 mg/L for vancomycin we used and 100 mg/L for a polymer containing 50% by weight of covalently bound antibiotic. The cytotoxic concentration measured with cell culture exceeds 1200 mg/L in 24 h exposure. The release dynamics of drugs not covalently bound to dextran from the depot gel were studied using fluorescein as a model. The release time is independent of the gel density and lasts up to 6 days for a 2 mm thick layer. Both the gel and the bone implants impregnated with it maintained consistently high antibacterial activity throughout the experiment, up to its completion after 168 h, with the local concentration of the released antibiotic at the site of bacterial attack exceeding the therapeutic level by 200 times.
PubMed: 38922325
DOI: 10.1021/acs.biomac.4c00268 -
Veterinary Sciences Jun 2024Ischemic teat necrosis (ITN) is a growing problem in the dairy industry characterized by teat lesions, necrosis, pruritus and automutilation. Despite the economic and...
Ischemic teat necrosis (ITN) is a growing problem in the dairy industry characterized by teat lesions, necrosis, pruritus and automutilation. Despite the economic and welfare consequences, there is no treatment, and the etiology of the disease remains poorly understood. The aim of this study was to investigate ITN by analyzing its clinical presentation, potential risk factors and microbial involvement. Methods included collection of milk and swab samples from affected cows over a period of one-and-a-half years and completion of questionnaires by veterinarians and farmers. Microbial testing included PCR testing for spp. and cultural testing by anaerobic and aerobic incubation on blood agar. The results showed a high and significant prevalence of spp. and in affected teats compared to non-ITN-affected control teats, indicating their potential role in the development of ITN. Other factors such as edema and milking practices also appear to contribute to the tissue damage. First-lactation and early-lactation heifers are particularly at risk. In conclusion, ITN appears to have a multifactorial etiology with both infectious and non-infectious factors playing a role. Further research is needed to better understand the complex interplay of these factors and to develop effective prevention and management strategies.
PubMed: 38922018
DOI: 10.3390/vetsci11060271 -
Veterinary Sciences Jun 2024Traditionally, non- staphylococci and mammaliicocci (NASM) were not considered significant players in bovine mastitis. This study investigated the involvement of NASM (...
Traditionally, non- staphylococci and mammaliicocci (NASM) were not considered significant players in bovine mastitis. This study investigated the involvement of NASM ( and ) and lactic acid bacteria (LAB) strains () through bovine neutrophil responses. Bovine neutrophils displayed minimal apoptosis upon NASM and LAB challenge. Neutrophils expressed high TLR2 after challenge, but TLR6 expression varied and remained low in NASM pathogen recognition. Bovine neutrophils effectively engulfed and killed LAB, but their activity was significantly impaired against NASM. This was evident in , where reduced TLR6 recognition and a weakened phagocytic response likely contributed to a lower bactericidal effect. Regardless of the bacteria encountered, intracellular ROS production remained high. -challenged neutrophils displayed upregulation in genes for pathogen recognition (TLRs), ROS production, and both pro- and anti-apoptotic pathways. This response mirrored that of . except for and , suggesting these bacteria have divergent roles in triggering cell death. Our findings suggest that manipulates bovine neutrophil defenses through coordinated changes in functional responses and gene expression, while LAB strains have a weaker influence on apoptosis.
PubMed: 38922009
DOI: 10.3390/vetsci11060262 -
Veterinary Sciences May 2024Bovine mastitis is an important and costly disease to dairy cattle. Diagnostic methods usually performed in Brazil are somatic cell counts (SCC) and milk microbiology....
Bovine mastitis is an important and costly disease to dairy cattle. Diagnostic methods usually performed in Brazil are somatic cell counts (SCC) and milk microbiology. Low bacteria shedding in milk implies no colony growth in microbiological tests and false negative results. and are principal pathogens of mixed mastitis. However, has a higher bacterial release from the mammary gland than , affecting microbiological sensitivity to diagnose . This study aimed to estimate the SCC and total bacterial count (TBC) from cows according to pathogen isolated in milk and to evaluate variation in diagnosis by a microbiological test during treatment, which is called blitz therapy. Both and presented high SCC means, although showed shedding of bacteria 2.3 times greater than . Microbiological sensitivity to increased for 5 months during treatment. The prevalence of fell after 5 months of therapeutic procedures. The prevalence of increased to 39.0. The results showed that due to high sensitivity, the polymerase chain reaction (PCR) could be used at the beginning of blitz therapy with the goal of eradication from the dairy herd.
PubMed: 38921980
DOI: 10.3390/vetsci11060233 -
Nanomaterials (Basel, Switzerland) Jun 2024Tetrahedral amorphous carbon (taC) is a hydrogen-free carbon with extensive properties such as hardness, optical transparency, and chemical inertness. taC coatings have...
Tetrahedral amorphous carbon (taC) is a hydrogen-free carbon with extensive properties such as hardness, optical transparency, and chemical inertness. taC coatings have attracted much attention in recent times, as have coatings doped with a noble metal. A known antimicrobial metal agent, silver (Ag), has been used as a dopant in taC, with different Ag concentrations on the Ti64 coupons using a hybrid filtered cathodic vacuum arc (FCVA) and magnetron sputtering system. The physiochemical properties of the coated surface were investigated using spectroscopic and electron microscopy techniques. A doping effect of Ag-taC on biofilm formation was investigated and found to have a significant effect on the bacterial-biofilm-forming bacteria and depending on the concentration of Ag. Further, the effect of coated and uncoated Ag-taC films on a pathogenic bacterium was examined using SEM. The result revealed that the Ag-taC coatings inhibited the biofilm formation of . Therefore, this study demonstrated the possible use of Ag-taC coatings against biofilm-related complications on medical devices and infections from pathogenic bacteria.
PubMed: 38921893
DOI: 10.3390/nano14121017 -
Pathogens (Basel, Switzerland) Jun 2024Sternal bursitis, a common inflammatory condition in poultry, poses significant challenges to both animal welfare and public health. This study aimed to investigate the...
Sternal bursitis, a common inflammatory condition in poultry, poses significant challenges to both animal welfare and public health. This study aimed to investigate the prevalence, antimicrobial resistance, and genetic characteristics of isolates associated with sternal bursitis in chickens. Ninety-eight samples were collected from affected chickens, and 24 isolates were identified. Antimicrobial susceptibility testing revealed resistance to multiple agents, with a notable prevalence of aminoglycoside resistance genes. Whole genome sequencing elucidated the genetic diversity and virulence profiles of the isolates, highlighting the predominance of clonal complex 5 (CC5) strains. Additionally, biofilm formation assays demonstrated moderate biofilm production capacity among the isolates. These findings underscore the importance of vigilant monitoring and targeted interventions to mitigate the impact of sternal bursitis in poultry production systems.
PubMed: 38921816
DOI: 10.3390/pathogens13060519 -
Pathogens (Basel, Switzerland) May 2024alpha toxin (CPA), which causes yellow lamb disease in sheep and gas gangrene and food poisoning in humans, is produced by all types of and is the major virulence...
alpha toxin (CPA), which causes yellow lamb disease in sheep and gas gangrene and food poisoning in humans, is produced by all types of and is the major virulence determinant of type A. CPA induces hemolysis in many species, including humans, murines, sheep and rabbits, through its enzymatic activity, which dissolves the cell membrane. Recent studies have shown that some pore-forming toxins cause hemolysis, which is achieved by the activation of purinergic receptors (P2). However, the relationship between P2 receptors and non-pore-forming toxin hemolysis has not been investigated. In the present study, we examined the function of P2 receptors in CPA toxin hemolysis and found that CPA-induced hemolysis was dependent on P2 receptor activation, and this was also true for β-Hemolysin, another non-pore-forming toxin. Furthermore, we use selective P2 receptor antagonists to demonstrate that P2X1 and P2X7 play important roles in the hemolysis of human and murine erythrocytes. In addition, we found that redox metabolism was mainly involved in CPA-induced hemolysis using metabolomic analysis. We further demonstrate that CPA activates P2 receptors and then activates NADPH oxidase through the PI3K/Akt and MEK1/ERK1 pathways, followed by the production of active oxygen to induce hemolysis. These findings contribute to our understanding of the pathological effects of CPA, clarify the relationship between P2 activation and non-pore-forming toxin-induced hemolysis, and provide new insights into CPA-induced hemolysis.
PubMed: 38921752
DOI: 10.3390/pathogens13060454