Antibiotics-Basel最新文献

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Background: In the US, 120,000 cases of Staphylococcus aureus bacteremia (SAB) occur annually. Apart from mortality, little is known about other unfavorable outcomes (UOs). We developed a multifaceted definition for UOs in SAB and examined their incidence and predictors. Methods: We conducted a multicenter (~300 hospitals) retrospective cohort study between 2020 and 2022 of adult hospitalized patients with at least one blood culture (BC) positive for S. aureus. UOs were any of the following: hospital mortality, antibiotic escalation, persistently positive BCs, prolonged post-infection length of stay (LOS), 30-day readmission, and disease worsening. We compared the group with UOs to favorable outcomes (FOs). Regression models identified predictors of UOs. Results: Among 4080 patients with SAB, 2427 (59.5%) experienced a UO, most commonly 30-day readmission (42.0%) and antibiotic escalation (37.7%). Those with UOs more frequently had septic shock at admission (5.7% vs. 1.2%), requiring the ICU (18.8% vs. 14.7%) and dialysis (4.4% vs. 1.9%) prior to SAB onset. Community-onset SAB predominated in both groups, with more complicated SAB in the UO group (39.8% vs. 22.3%). Vancomycin use was similar, while daptomycin was more common in the UO group (8.5% vs. 3.0%). Variables with the highest odds ratios predicting a UO were septic shock on admission (3.498, 95% CI 2.145, 5.704), empiric daptomycin (2.723, 95% CI 1.943, 3.821), and complicated SAB (2.476, 95% CI 2.047, 2.994). Conclusions: UOs occur frequently in the setting of SAB. A broader perspective exploring issues other than mortality demonstrates the substantial implications of SAB both for patients and healthcare systems. Select clinical variables are associated with UOs, some of which may not be modifiable.

Introduction: The presence of antibiotic residues in the aquatic environment is a likely contributor to the current increase in antibiotic resistance, posing a significant threat to global health. This study investigated the use of a low-cost and sustainable material based on sawdust with the purpose of removing rifampicin residues from water. Methods: The sawdust was pretreated with 2M sulfuric acid and was characterized using Fourier Transform Infrared spectroscopy (FT-IR), a Mastersizer, scanning electron microscopy (SEM), an elemental analyser, and the pH point of zero charge (pH_pzc). The batch adsorption process was conducted using both raw and treated sawdust to determine the effect of contact time, temperature, pH, adsorbent dosage, and the initial concentration of antibiotic dissolved in water. Results and Discussion: The results revealed that the chemical pretreatment of raw sawdust significantly improved its adsorption capacity. The highest removal efficiency of 65% was achieved using an adsorbent dosage of 31.3 g/L. The thermodynamic studies demonstrated that the process was spontaneous and governed by physisorption within the studied temperature range (293.15 K-318.15 K), being more favourable at higher temperatures. The interactions between the functional groups of sawdust and the rifampicin molecules included electrostatic attraction, hydrogen bonding, and π-π interactions. Conclusions: This research highlights the potential of utilizing waste as a valuable and effective adsorbent of residual antibiotics from water, thus contributing to the sustainable practices of solid waste management and water treatment.

Background/Objectives:Pseudomonas aeruginosa (Psa) can circumvent antimicrobial chemotherapy, an ability enhanced by cigarette smoking (CS). This study probed potential benefits of combinations of anti-pseudomonal agents, and potential augmentation by a macrolide, in the absence or presence of cigarette smoke condensate (CSC). Methods: Two susceptible (WT: wild-type and DS: drug-sensitive) and one multidrug-resistant (MDR) strains of Psa were treated with amikacin, cefepime, and ciprofloxacin, individually and in combination, and with and without clarithromycin, followed by the measurement of planktonic growth and biofilm formation by spectrophotometry. Antibiotic interactions were determined using the fractional inhibitory concentration index (FICI) method. Effects on preformed biofilm density were measured following the addition of antibiotics: all procedures were performed in the absence and presence of CSC. Results: The minimal inhibitory concentrations (MICs) of the three agents ranged from 0.125 mg/L to 1 mg/L (WT and DS strains) and 16 mg/L to 64 mg/L (MDR strain), with all resistant to clarithromycin (125 mg/L). MIC values closely correlated with the antibiotic concentrations required to inhibit biofilm formation. FICI revealed synergism between most combinations, with augmentation by clarithromycin. Amikacin had the greatest effect on biofilm density, which was potentiated by combination with the other antibiotics, particularly clarithromycin. Exposure to CSC had variable, albeit modest, effects on bacterial growth and biofilm formation, but low concentrations increased biofilm mass and attenuated synergistic antimicrobial interactions and effects on biofilm density. Conclusions: Amikacin, cefepime, and ciprofloxacin, especially with clarithromycin, exhibit synergistic anti-pseudomonal activity and decrease preformed biofilm density. CSC attenuated these effects, illustrating the pro-infective potential of CS.

Background/Objectives: New drugs are urgently needed for the treatment of neglected tropical diseases including leishmaniasis and eumycetoma, as well as globally occurring parasitic diseases such as toxoplasmosis. Fragrances, both natural and synthetic, were shown to be a rich source for the development of new anti-infectives and warrant deeper investigations. Exemplarily, we synthetically optimized the fragrance 4-(4,8-dimethyl-3,7-nonadienyl)-pyridine, a.k.a. Maritima, a pyridine derivative with marine odor. Methods: A new cationic N-cetyl-modified derivative of Maritima (dubbed Cetyl-Maritima), obtained by alkylation of Maritima, was tested for its activity against Madurella mycetomatis (M. mycetomatis) fungi, as well as against Toxoplasma gondii (T. gondii) and Leishmania major (L. major) protozoal parasites. Results: Cetyl-Maritima was found to be more strongly antifungal than the parent Maritima and a known antibiotic cetylpyridinium salt. Cetyl-Maritima also showed a similar activity against T. gondii parasites and, most notably, exhibited sub-micromolar activity against L. major amastigotes. Conclusions: The considerable antileishmanial activity of Cetyl-Maritima might lead to the development of a new potent and cost-effective drug candidate for the therapy of leishmaniasis and other infectious diseases caused by kinetoplastid parasites.

Background/Objectives: As probiotics gain prominence in the prevention and treatment of intestinal diseases, their protective effects against pathogens and influence on host health have drawn significant attention. This study investigates the genomic characteristics and functional potential of Pediococcus acidilactici XJ-24 (XJ-24) in the prevention of Listeria monocytogenes (LM) infection in mice. Methods/Results: Whole-genome analysis confirmed the safety and probiotic properties of XJ-24, including acid and bile salt tolerance, antimicrobial activity, and safety. In vivo, C57BL/6 mice challenges indicated that XJ-24 significantly reduced LM colonization, suppressed pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, IFN-γ), alleviated colon and spleen tissue damage, and maintained intestinal barrier integrity by upregulating tight junction proteins (Occludin, Claudin-1, ZO-1). Moreover, XJ-24 modulated gut microbiota composition by increasing beneficial taxa while reducing harmful bacteria. Correlation analysis highlighted a positive association between Lachnospiraceae and tight junction proteins. Conclusions: These findings demonstrate the potential of XJ-24 as a functional probiotic for preventing LM infection and provide a basis for further clinical exploration.

Background/Objectives: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is an important pathogen associated with high mortality and treatment failure rates. We aimed to assess the susceptibility of CRPA to antipseudomonal agents, identify its resistance mechanisms, and evaluate clinical outcomes in a sample of CRPA isolates. Methods: This was an in vitro study of a clinical isolate of CRPA from hospitalized patients with CRPA infection and a retrospective observational study of these patients, who were diagnosed between 14 February 2021 and 10 August 2023 at Songklanagarind Hospital in Songkhla, Thailand. In vitro experiments were conducted to determine the minimum inhibitory concentrations (MICs) of the antipseudomonal agents using the broth microdilution method. Resistance mechanisms were assessed using the modified carbapenem inactivation method, combined disk tests, and quantitative real-time reverse transcription polymerase chain reaction. Results: A total of 140 CRPA isolates were analyzed. Both traditional and novel β-lactams had high MICs. The most common resistance mechanism was the upregulation of the MexAB-OprM efflux pump (81.3%), followed by the downregulation of the OprD porin (48.9%) and metallo-β-lactamase (MBL) production (45.0%), and the overexpression of bla_AmpC (41.0%). The 30-day all-cause mortality rate was 30.5%. The risk factors associated with 30-day mortality included a Charlson Comorbidity Index of ≥5 (OR: 3.43; 95% CI: 1.07-10.99; p = 0.03), sepsis (OR: 10.62; 95% CI: 1.26-89.44; p = 0.03), and septic shock (OR: 4.39; 95% CI: 1.67-11.55; p < 0.01). In contrast, receiving active documented therapy was significantly associated with reduced mortality (OR: 0.17; 95% CI: 0.04-0.74; p = 0.01). Conclusions: This study revealed higher MIC values of all β-lactams for CRPA, while colistin and amikacin remained effective. The resistance mechanisms included MexAB-OprM overexpression, OprD downregulation, MBL production, and bla_AmpC overexpression, with a higher prevalence of MBL than in other regions of Thailand. High 30-day mortality was associated with comorbidities, sepsis, and septic shock, but active therapy reduced mortality.

Background/Objectives: The deterioration of food quality and safety is often linked to the presence of pathogenic and spoilage microorganisms. Postbiotics, including organic acids, enzymes, and bacteriocins produced by lactic acid bacteria (LAB), have emerged as promising next-generation food preservatives. This study investigates the biological and physicochemical properties of several postbiotic-based extracts (PBEs) comprising cell-free supernatant (CFS) and exopolysaccharide (EPS) fractions derived from three native probiotic strains: Lactiplantibacillus plantarum UTNGt2, Lactococcus lactis UTNGt28, and Weissella cibaria UTNGt21O. Methods: The antibacterial activity of these PBEs was assessed against multidrug-resistant Escherichia coli L1PEag1. Moreover, the antioxidant capacity and cytotoxicity along with the characterization of these formulations was assessed. Results: FU6 (CFS UTNGt28: EPS UTNGt2) and FU13 (CFS UTNGt21O) were found as the most potent formulations. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) confirmed dose- and time-dependent damage to the bacterial membrane and cell wall. FU6 exhibited superior antioxidant activity and lacked hemolytic effects, whereas both FU6 and FU13 induced cell-specific responses in HEK293 (human kidney) and HT-29 (intestinal mucus-producing) cell lines. Furthermore, attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy identified characteristic absorption bands corresponding to proteins, lipids, carbohydrates, and nucleic acids, while proton nuclear magnetic resonance (¹H-NMR) spectroscopy revealed key monosaccharides, amino acids, and metabolites such as lactate and acetate within the extracts. Conclusions: FU6 and FU13 demonstrate potential as safe and effective postbiotic formulations at non-concentrated doses. However, further research is required to elucidate their molecular composition comprehensively and evaluate their applicability for broader and long-term use in food preservation and pharmaceutical development.

Background/Objectives: The aim of the present study is to report an outbreak of bloodstream infections caused by Serratia marcescens in patients undergoing postoperational procedures in the Cardiothoracic Department and to describe the epidemiological investigations and control measures undertaken. A cluster of bacteremia due to Serratia marcescens was identified in blood cultures from postoperative patients in the Cardiothoracic Surgery Department in November 2023. Methods: Active surveillance by the hospital's prevention and control team was initiated. Interviews with nurses and sanitary personnel and reviews of the most common procedures, such as hand washing, bladder catheterization, and intravenous catheter care, were performed. Culturing samples from hospital personnel, postoperative patients, and the environment, including pressure transducers, tap water, soap, therapeutic solutions, antiseptics, respirators, and various intravenous preparations, were drawn up. Overall, 225 samples were collected, including 149 blood cultures, and these were all sent to the Hospital's Microbiology Laboratory. Results: Twenty-three out of forty-seven postoperative patients had positive blood cultures for Serratia marcescens. All the postoperative patients involved in the outbreak received cefepime according to antimicrobial susceptibility testing. Three pre-prepared flushing syringes were found to be positive for Serratia marcescens as well. The Cardiothoracic Department was kept under surveillance with hand hygiene measures, infusion preparation, medical device use, and cleaning procedures reviewed by the infection's prevention and control team. Conclusions: Undoubtedly, nosocomial outbreaks represent an important health issue regarding morbidity, mortality, and costs. Timely interventions by the hospital's infection prevention and control team may be life-saving under these circumstances.

Background: Phosphoinositide 3-kinase is a potent target for cancer therapy due to its significant role in the regulation of cellular growth and proliferation. Dysregulation of the PI3k signaling cascade can constitutively activate growth pathways to trigger the progression of cancer, resulting in the development of multiple inhibitors as cancer therapeutics. Objectives: The wide array of cells expressing PI3k also include immune cells, and the inhibition of these receptors has shown promise in combating inflammation and infectious disease, a relationship we sought to examine further. Methods: We infected wild-type and PI3kγ knockout murine macrophages as well as PI3kγ inhibitor-treated THP-1 human macrophage-like cells with Staphylococcus aureus and quantified inflammation through gene expression analysis, protein secretion assays, and immunofluorescence imaging. Results: We observed that knockout of PI3kγ in murine macrophages alongside pharmacological inhibition through IPI549 treatment in THP-1 cells led to an NF-κB-driven suppression in transcription and release of inflammatory cytokines upon infection with methicillin-resistant Staphylococcus aureus. We were also able to confirm that this suppression of NF-κB translocation and subsequent decrease in inflammatory cytokine release did not compromise and even slightly boosted the bacterial killing ability. Conclusion: PI3k is primarily targeted for cancer therapies, but further exploration can also be carried out on its potential roles in treating bacterial infection.