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Frontiers in Immunology 2023Drug-induced acute kidney damage (DI-AKI) is a clinical phenomenon of rapid loss of kidney function over a brief period of time as a consequence of the using of...
BACKGROUND
Drug-induced acute kidney damage (DI-AKI) is a clinical phenomenon of rapid loss of kidney function over a brief period of time as a consequence of the using of medicines. The lack of a specialized treatment and the instability of traditional kidney injury markers to detect DI-AKI frequently result in the development of chronic kidney disease. Thus, it is crucial to continue screening for DI-AKI hub genes and specific biomarkers.
METHODS
Differentially expressed genes (DEGs) of group iohexol, cisplatin, and vancomycin's were analyzed using Limma package, and the intersection was calculated. DEGs were then put into String database to create a network of protein-protein interactions (PPI). Ten algorithms are used in the Cytohubba plugin to find the common hub genes. Three DI-AKI models' hub gene expression was verified and using PCR and western blot. To investigate the hub gene's potential as a biomarker, protein levels of mouse serum and urine were measured by ELISA kits. The UUO, IRI and aristolochic acid I-induced nephrotoxicity (AAN) datasets in the GEO database were utilized for external data verification by WGCNA and Limma package. Finally, the Elisa kit was used to identify DI-AKI patient samples.
RESULTS
95 up-regulated common DEGs and 32 down-regulated common DEGs were obtained using Limma package. A PPI network with 84 nodes and 24 edges was built with confidence >0.4. Four hub genes were obtained by Algorithms of Cytohubba plugin, including TLR4, AOC3, IRF4 and TNFAIP6. Then, we discovered that the protein and mRNA levels of four hub genes were significantly changed in the DI-AKI model and . External data validation revealed that only the AAN model, which also belonged to DI-AKI model, had significant difference in these hub genes, whereas IRI and UUO did not. Finally, we found that plasma TLR4 levels were higher in patients with DI-AKI, especially in vancomycin-induced AKI.
CONCLUSION
The immune system and inflammation are key factors in DI-AKI. We discovered the immunological and inflammatory-related genes TLR4, AOC3, IRF4, and TNFAIP6, which may be promising specific biomarkers and essential hub genes for the prevention and identification of DI-AKI.
Topics: Animals; Mice; Toll-Like Receptor 4; Transcriptome; Vancomycin; Acute Kidney Injury
PubMed: 37063876
DOI: 10.3389/fimmu.2023.1126348 -
Antimicrobial Agents and Chemotherapy Feb 2013In an effort to maximize outcomes, recent expert guidelines recommend more-intensive vancomycin dosing schedules to maintain vancomycin troughs between 15 and 20... (Meta-Analysis)
Meta-Analysis Review
In an effort to maximize outcomes, recent expert guidelines recommend more-intensive vancomycin dosing schedules to maintain vancomycin troughs between 15 and 20 mg/liter. The widespread use of these more-intensive regimens has been associated with an increase in vancomycin-induced nephrotoxicity reports. The purpose of this systematic literature review is to determine the nephrotoxicity potential of maintaining higher troughs in clinical practice. All studies pertaining to vancomycin-induced nephrotoxicity between 1996 and April 2012 were identified from PubMed, Embase, Cochrane Controlled Trial Registry, and Medline databases and analyzed according to Cochrane guidelines. Of the initial 240 studies identified, 38 were reviewed, and 15 studies met the inclusion criteria. Overall, higher troughs (≥ 15 mg/liter) were associated with increased odds of nephrotoxicity (odds ratio [OR], 2.67; 95% confidence interval [CI], 1.95 to 3.65) relative to lower troughs of <15 mg/liter. The relationship between a trough of ≥ 15 mg/liter and nephrotoxicity persisted when the analysis was restricted to studies that examined only initial trough concentrations (OR, 3.12; 95% CI, 1.81 to 5.37). The relationship between troughs of ≥ 15 mg/liter and nephrotoxicity persisted after adjustment for covariates known to independently increase the risk of a nephrotoxicity event. An incremental increase in nephrotoxicity was also observed with longer durations of vancomycin administration. Vancomycin-induced nephrotoxicity was reversible in the majority of cases, with short-term dialysis required only in 3% of nephrotoxic episodes. The collective literature indicates that an exposure-nephrotoxicity relationship for vancomycin exists. The probability of a nephrotoxic event increased as a function of the trough concentration and duration of therapy.
Topics: Acute Kidney Injury; Anti-Bacterial Agents; Humans; Kidney; Renal Dialysis; Vancomycin
PubMed: 23165462
DOI: 10.1128/AAC.01568-12 -
Microbiology Spectrum Feb 2023Enterococci can cause various infectious diseases, including urinary tract infection, wound infection, and life-threatening endocarditis and meningitis. The emergence...
Enterococci can cause various infectious diseases, including urinary tract infection, wound infection, and life-threatening endocarditis and meningitis. The emergence and transmission of vancomycin-resistant enterococci (VRE) have presented a challenge to clinical treatment. There is an urgent need to develop new strategies to fight against this pathogen. This study investigated the antibacterial and anti-biofilm activity of celastrol (CEL), a natural product originating from against enterococci, and its adjuvant capacity of restoring the susceptibility of VRE to vancomycin and . CEL inhibited all enterococcus strains tested, with MICs ranging from 0.5 to 4 μg/mL. More than 50% of biofilm was eliminated by CEL at 16 μg/mL after 24 h of exposure. The combination of CEL and vancomycin showed a synergistic effect against all 23 strains tested in checkerboard assays. The combination of sub-MIC levels of CEL and vancomycin showed a synergistic effect in a time-kill assay and exhibited significant protective efficacy in Galleria mellonella larval infection model compared with either drug used alone. The underlying mechanisms of CEL were explored by conducting biomolecular binding interactions and an enzyme inhibition assay of CEL on bacterial cell-division protein FtsZ. CEL presented strong binding and suppression ability to FtsZ, with K and IC values of 2.454 μM and 1.04 ± 0.17 μg/mL, respectively. CEL exhibits a significant antibacterial and synergic activity against VRE and and has the potential to be a new antibacterial agent or adjuvant to vancomycin as a therapeutic option in combating VRE. The emergence and transmission of VRE pose a significant medical and public health challenge. CEL, well-known for a wide range of biological activities, has not previously been investigated for its synergistic effect with vancomycin against VRE. In the present study, CEL exhibited antibacterial activity against enterococci, including VRE strains, and restored the activity of vancomycin against VRE and . Hence, CEL has the potential to be a new antibacterial adjuvant to vancomycin and could provide a promising therapeutic option in combating VRE.
Topics: Vancomycin; Anti-Bacterial Agents; Pentacyclic Triterpenes; Vancomycin-Resistant Enterococci; Microbial Sensitivity Tests
PubMed: 36622182
DOI: 10.1128/spectrum.03699-22 -
International Journal of Environmental... Feb 2022Under the Japanese health insurance system, medicines undergoing therapeutic drug monitoring (TDM) can be billed for medical fees if they meet the specified... (Review)
Review
Under the Japanese health insurance system, medicines undergoing therapeutic drug monitoring (TDM) can be billed for medical fees if they meet the specified requirements. In Japan, TDM of vancomycin, teicoplanin, aminoglycosides, and voriconazole, which are used for the treatment of infectious diseases, is common practice. This means the levels of antibiotics are measured in-house using chromatography or other methods. In some facilities, the blood and/or tissue concentrations of other non-TDM drugs are measured by HPLC and are applied to treatment, which is necessary for personalized medicine. This review describes personalized medicine based on the use of chromatography as a result of the current situation in Japan.
Topics: Anti-Bacterial Agents; Drug Monitoring; Insurance; Japan; Vancomycin
PubMed: 35270215
DOI: 10.3390/ijerph19052516 -
Revista Latino-americana de Enfermagem 2022to verify the stability of vancomycin hydrochloride in antimicrobial seal solutions with and without association of heparin sodium according to temperature and...
OBJECTIVE
to verify the stability of vancomycin hydrochloride in antimicrobial seal solutions with and without association of heparin sodium according to temperature and association time.
METHOD
an experimental study designed for the analysis of hydrogenionic potential and concentration by means of high-efficiency liquid chromatography of vancomycin hydrochloride (n=06) and vancomycin hydrochloride and heparin sodium (n=06). The solutions studied were submitted to absence of light, as well as to 22°C and 37°C. Analyses in triplicate (n=192) were performed at the initial moment (T0) and three (T3), eight (T8) and 24 hours (T24) after preparation. The data were submitted to analysis of variance (p≤0.05).
RESULTS
concentration of the antimicrobial at 22°C presented a reduction (T0-T8) and a subsequent increase (T24); hydrogenionic potential decreased significantly over time. At 37°C, the concentration increased up to T3 and decreased at T24, with a reduction of hydrogenionic potential up to 24 hours. Concentration of the vancomycin hydrochloride and heparin sodium solutions varied with a reduction at 22°C, accompanied by increased hydrogenionic potential. Precipitate formation was observed by visual inspection of the vancomycin hydrochloride-heparin sodium association (T3).
CONCLUSION
pharmacological stability of vancomycin hydrochloride (5 mg/mL) and physical incompatibility with heparin sodium (100 IU/mL) were evidenced after three hours of association in the antimicrobial seal solutions studied.
Topics: Anti-Bacterial Agents; Central Venous Catheters; Drug Stability; Heparin; Humans; Vancomycin
PubMed: 35920542
DOI: 10.1590/1518-8345.5869.3620 -
Journal of Veterinary Internal Medicine Jan 2019Vancomycin is commonly used to treat resistant bacterial infections in people. Reported adverse effects of vancomycin in people include acute kidney injury (AKI),...
BACKGROUND
Vancomycin is commonly used to treat resistant bacterial infections in people. Reported adverse effects of vancomycin in people include acute kidney injury (AKI), neutropenia, and systemic allergic reaction. Given the increased incidence of vancomycin-resistant bacterial infections in people, support is growing for restriction of vancomycin.
OBJECTIVES
To evaluate the use of intravenous (IV) vancomycin in a university teaching hospital and to describe potential adverse effects.
ANIMALS
Twenty-nine dogs and 7 cats.
METHODS
Medical records of dogs and cats treated with IV vancomycin at the Foster Hospital for Small Animals between January 2003 and October 2017 were reviewed. Information recorded included signalment, infection source, vancomycin dosing, potential adverse effects, and outcome.
RESULTS
Vancomycin was used to treat infections from a range of sources with a variety of dosing intervals. The most common bacterial isolates susceptible to vancomycin included Enterococcus sp. (11/36, 30.6%), methicillin-resistant Staphylococcus aureus (8/36, 22.2%), and methicillin-resistant Staphylococcus pseudintermedius (2/36, 5.6%). AKI occurred in 6 of 36 patients (16.7%) during vancomycin treatment but could not definitively be attributed to vancomycin treatment in any patients because of illness severity, additional nephrotoxic treatments, or both. Neutropenia or allergic reaction was not documented in any animal. In 2 of 36 patients (5.6%), susceptibility data documented an infection that was only susceptible to vancomycin. Most patients survived to discharge (25/36, 69.4%).
CONCLUSIONS AND CLINICAL IMPORTANCE
Adverse effects attributable to vancomycin were infrequent in dogs and cats. In most cases, there were potential alternative effective antimicrobials or lack of susceptibility data to support vancomycin treatment.
Topics: Animals; Anti-Bacterial Agents; Bacterial Infections; Cat Diseases; Cats; Dog Diseases; Dogs; Female; Injections, Intravenous; Male; Retrospective Studies; Vancomycin
PubMed: 30499215
DOI: 10.1111/jvim.15357 -
Journal of Orthopaedic Research :... Feb 2019Revisions TKAs are being completed with uncemented constructs more frequently. We hypothesized that tantalum cones could be an efficient carrier of antibiotics in... (Comparative Study)
Comparative Study
Revisions TKAs are being completed with uncemented constructs more frequently. We hypothesized that tantalum cones could be an efficient carrier of antibiotics in uncemented procedures. We aimed to compare the release of vancomycin between (i) tantalum and smooth stainless cylinders; (ii) different concentrations of vancomycin; and (iii) different durations of bathing. Specifically designed tantalum cylinders were bathed in a vancomycin solution with various durations of baths. We investigated rinses between each interval as well as the dose of vancomycin. Vancomycin concentrations were determined in each group by fluorescence polarization immunoassay at different intervals (1 h, days 1, 2, 3, 5). At 1 h, the mean vancomycin concentration for the 1-hour soaking group was 3,172 μg/ml, whereas mean concentration for the smooth stainless steel group was 39.37 μg/ml (p < 0.001). The rinsing group showed a significantly lower concentration at 1 h and 1 day (p < 0.05). The 2-gram vancomycin group showed no difference at days 1, 2, and 3 compared to the 1-hour group. The 5, 15, and 30-minute bathing groups showed significantly lower vancomycin concentrations at all-time points. All vancomycin concentrations at day 3 were superior to the minimal inhibitory concentration of Staphyloccocus aureus. The mean concentration of vancomycin depends on the material, duration of bathing, the rinsing effect, and the drug dose. Our in-vitro study is the first to show that porous tantalum cylinders allow antibiotic carriage and progressive release. If appearing in vivo, in a similar extent, this intrinsic property might be useful to prevent and/or treat peri-prosthetic joint infection. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:308-312, 2019.
Topics: Anti-Bacterial Agents; Arthroplasty, Replacement; Humans; Kinetics; Prosthesis-Related Infections; Reoperation; Tantalum; Vancomycin
PubMed: 30325073
DOI: 10.1002/jor.24160 -
Journal of Mass Spectrometry : JMS Mar 2021Suboptimal antibiotic dosing has been identified as one of the key drivers in the development of multidrug-resistant (MDR) bacteria that have become a global health...
Suboptimal antibiotic dosing has been identified as one of the key drivers in the development of multidrug-resistant (MDR) bacteria that have become a global health concern. Aminoglycosides and vancomycin are broad-spectrum antibiotics used to treat critically ill patients infected by a variety of MDR bacterial species. Resistance to these antibiotics is becoming more prevalent. In order to design proper antibiotic regimens that maximize efficacy and minimize the development of resistance, it is pivotal to obtain the in situ pharmacokinetic-pharmacodynamic profiles at the sites of infection. Mass spectrometry imaging (MSI) is the ideal technique to achieve this. Aminoglycosides, due to their structure, suffer from poor ionization efficiency. Additionally, ion suppression effects by endogenous molecules greatly inhibit the detection of aminoglycosides and vancomycin at therapeutic levels. In the current study, an optimized method was developed that enabled the detection of these antibiotics by MSI. Tissue spotting experiments demonstrated a 5-, 15-, 35-, and 54-fold increase in detection sensitivity in the washed samples for kanamycin, amikacin, streptomycin, and vancomycin, respectively. Tissue mimetic models were utilized to optimize the washing time and matrix additive concentration. These studies determined the improved limit of detection was 40 to 5 μg/g of tissue for vancomycin and streptomycin, and 40 to 10 μg/g of tissue for kanamycin and amikacin. The optimized protocol was applied to lung sections from mice dosed with therapeutic levels of kanamycin and vancomycin. The washing protocol enabled the first drug distribution investigations of aminoglycosides and vancomycin by MSI, paving the way for site-of-disease antibiotic penetration studies.
Topics: Aminoglycosides; Animals; Anti-Bacterial Agents; Female; Mice; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Tissue Distribution; Vancomycin
PubMed: 33586279
DOI: 10.1002/jms.4708 -
Cell Host & Microbe May 2023Clostridioides difficile infections (CDIs) remain a healthcare problem due to high rates of relapsing/recurrent CDIs (rCDIs). Breakdown of colonization resistance...
Clostridioides difficile infections (CDIs) remain a healthcare problem due to high rates of relapsing/recurrent CDIs (rCDIs). Breakdown of colonization resistance promoted by broad-spectrum antibiotics and the persistence of spores contribute to rCDI. Here, we demonstrate antimicrobial activity of the natural product class of chlorotonils against C. difficile. In contrast to vancomycin, chlorotonil A (ChA) efficiently inhibits disease and prevents rCDI in mice. Notably, ChA affects the murine and porcine microbiota to a lesser extent than vancomycin, largely preserving microbiota composition and minimally impacting the intestinal metabolome. Correspondingly, ChA treatment does not break colonization resistance against C. difficile and is linked to faster recovery of the microbiota after CDI. Additionally, ChA accumulates in the spore and inhibits outgrowth of C. difficile spores, thus potentially contributing to lower rates of rCDI. We conclude that chlorotonils have unique antimicrobial properties targeting critical steps in the infection cycle of C. difficile.
Topics: Animals; Mice; Swine; Vancomycin; Clostridioides difficile; Anti-Bacterial Agents; Clostridium Infections
PubMed: 37098342
DOI: 10.1016/j.chom.2023.04.003 -
ACS Infectious Diseases Jul 2023Traditional antibacterial screens rely on growing bacteria in nutrient-replete conditions which are not representative of the natural environment or sites of infection....
Traditional antibacterial screens rely on growing bacteria in nutrient-replete conditions which are not representative of the natural environment or sites of infection. Instead, screening in more physiologically relevant conditions may reveal novel activity for existing antibiotics. Here, we screened a panel of antibiotics reported to lack activity against the opportunistic Gram-negative bacterium, , under low-nutrient and low-iron conditions, and discovered that the glycopeptide vancomycin inhibited the growth of at low micromolar concentrations through its canonical mechanism of action, disruption of peptidoglycan crosslinking. Spontaneous vancomycin-resistant mutants underwent activating mutations in the sensor kinase of the two-component CpxSR system, which induced cross-resistance to almost all classes of β-lactams, including the siderophore antibiotic cefiderocol. Other mutations that conferred vancomycin resistance mapped to WapR, an α-1,3-rhamnosyltransferase involved in lipopolysaccharide core biosynthesis. A WapR P164T mutant had a modified LPS profile compared to wild type that was accompanied by increased susceptibility to select bacteriophages. We conclude that screening in nutrient-limited conditions can reveal novel activity for existing antibiotics and lead to discovery of new and impactful resistance mechanisms.
Topics: Vancomycin; Pseudomonas aeruginosa; Anti-Bacterial Agents; Glycopeptides; Nutrients
PubMed: 37279282
DOI: 10.1021/acsinfecdis.3c00167