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1.
PLoS One ; 19(5): e0303039, 2024.
Article in English | MEDLINE | ID: mdl-38701045

ABSTRACT

The complexity of chronic wounds creates difficulty in effective treatments, leading to prolonged care and significant morbidity. Additionally, these wounds are incredibly prone to bacterial biofilm development, further complicating treatment. The current standard treatment of colonized superficial wounds, debridement with intermittent systemic antibiotics, can lead to systemic side-effects and often fails to directly target the bacterial biofilm. Furthermore, standard of care dressings do not directly provide adequate antimicrobial properties. This study aims to assess the capacity of human-derived collagen hydrogel to provide sustained antibiotic release to disrupt bacterial biofilms and decrease bacterial load while maintaining host cell viability and scaffold integrity. Human collagen harvested from flexor tendons underwent processing to yield a gellable liquid, and subsequently was combined with varying concentrations of gentamicin (50-500 mg/L) or clindamycin (10-100 mg/L). The elution kinetics of antibiotics from the hydrogel were analyzed using liquid chromatography-mass spectrometry. The gel was used to topically treat Methicillin-resistant Staphylococcus aureus (MRSA) and Clostridium perfringens in established Kirby-Bauer and Crystal Violet models to assess the efficacy of bacterial inhibition. 2D mammalian cell monolayers were topically treated, and cell death was quantified to assess cytotoxicity. Bacteria-enhanced in vitro scratch assays were treated with antibiotic-embedded hydrogel and imaged over time to assess cell death and mobility. Collagen hydrogel embedded with antibiotics (cHG+abx) demonstrated sustained antibiotic release for up to 48 hours with successful inhibition of both MRSA and C. perfringens biofilms, while remaining bioactive up to 72 hours. Administration of cHG+abx with antibiotic concentrations up to 100X minimum inhibitory concentration was found to be non-toxic and facilitated mammalian cell migration in an in vitro scratch model. Collagen hydrogel is a promising pharmaceutical delivery vehicle that allows for safe, precise bacterial targeting for effective bacterial inhibition in a pro-regenerative scaffold.


Subject(s)
Anti-Bacterial Agents , Biofilms , Collagen , Hydrogels , Methicillin-Resistant Staphylococcus aureus , Biofilms/drug effects , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/administration & dosage , Humans , Collagen/chemistry , Hydrogels/chemistry , Methicillin-Resistant Staphylococcus aureus/drug effects , Clindamycin/pharmacology , Clindamycin/administration & dosage , Microbial Sensitivity Tests , Administration, Topical , Gentamicins/pharmacology , Gentamicins/administration & dosage
2.
Sci Rep ; 14(1): 10196, 2024 05 03.
Article in English | MEDLINE | ID: mdl-38702355

ABSTRACT

Urinary tract infections (UTIs) are the most common bacterial infections and uropathogenic Escherichia coli (UPEC) is the main etiological agent of UTIs. UPEC can persist in bladder cells protected by immunological defenses and antibiotics and intracellular behavior leads to difficulty in eradicating the infection. The aim of this paper is to design, prepare and characterize surfactant-based nanocarriers (niosomes) able to entrap antimicrobial drug and potentially to delivery and release antibiotics into UPEC-infected cells. In order to validate the proposed drug delivery system, gentamicin, was chosen as "active model drug" due to its poor cellular penetration. The niosomes physical-chemical characterization was performed combining different techniques: Dynamic Light Scattering Fluorescence Spectroscopy, Transmission Electron Microscopy. Empty and loaded niosomes were characterized in terms of size, ζ-potential, bilayer features and stability. Moreover, Gentamicin entrapped amount was evaluated, and the release study was also carried out. In addition, the effect of empty and loaded niosomes was studied on the invasion ability of UPEC strains in T24 bladder cell monolayers by Gentamicin Protection Assay and Confocal Microscopy. The observed decrease in UPEC invasion rate leads us to hypothesize a release of antibiotic from niosomes inside the cells. The optimization of the proposed drug delivery system could represent a promising strategy to significatively enhance the internalization of antimicrobial drugs.


Subject(s)
Anti-Bacterial Agents , Gentamicins , Liposomes , Uropathogenic Escherichia coli , Gentamicins/pharmacology , Uropathogenic Escherichia coli/drug effects , Humans , Anti-Bacterial Agents/pharmacology , Drug Carriers/chemistry , Urinary Tract Infections/microbiology , Urinary Tract Infections/drug therapy , Escherichia coli Infections/microbiology , Escherichia coli Infections/drug therapy , Drug Delivery Systems , Microbial Sensitivity Tests
3.
ACS Sens ; 9(5): 2622-2633, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38700898

ABSTRACT

Early diagnosis of drug-induced kidney injury (DIKI) is essential for clinical treatment and intervention. However, developing a reliable method to trace kidney injury origins through retrospective studies remains a challenge. In this study, we designed ordered fried-bun-shaped Au nanocone arrays (FBS NCAs) to create microarray chips as a surface-enhanced Raman scattering (SERS) analysis platform. Subsequently, the principal component analysis (PCA)-two-layer nearest neighbor (TLNN) model was constructed to identify and analyze the SERS spectra of exosomes from renal injury induced by cisplatin and gentamycin. The established PCA-TLNN model successfully differentiated the SERS spectra of exosomes from renal injury at different stages and causes, capturing the most significant spectral features for distinguishing these variations. For the SERS spectra of exosomes from renal injury at different induction times, the accuracy of PCA-TLNN reached 97.8% (cisplatin) and 93.3% (gentamicin). For the SERS spectra of exosomes from renal injury caused by different agents, the accuracy of PCA-TLNN reached 100% (7 days) and 96.7% (14 days). This study demonstrates that the combination of label-free exosome SERS and machine learning could serve as an innovative strategy for medical diagnosis and therapeutic intervention.


Subject(s)
Cisplatin , Gold , Machine Learning , Principal Component Analysis , Spectrum Analysis, Raman , Spectrum Analysis, Raman/methods , Animals , Gold/chemistry , Exosomes/chemistry , Gentamicins/analysis , Metal Nanoparticles/chemistry
4.
Mol Biol Rep ; 51(1): 655, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38739285

ABSTRACT

BACKGROUND: There is limited data regarding the hazardous effect of gentamicin (GM) on the uterus and whether or not vinpocetine (Vinpo) ameliorates it. The present study aimed to identify the possible protective effect of Vinpo in GM-induced uterine injury in rats. METHODS: Female rats were assorted in control-group, Vinpo-group, GM-group, and Vinpo plus GM group. Serum and uterine GM concentration were measured. Uterine oxidative stress parameters besides inflammatory and apoptotic biomarkers were evaluated. Uterine histopathological examination and interlukin-1beta (IL-1ß) immune-histochemical study were detected. RESULTS: GM significantly increased uterine oxidative stress, inflammatory and apoptotic biomarkers. Histopathological picture of uterine damage and increased IL-1ß immunoexpression were detected. Vinpo significantly ameliorated the distributed GM concentration, oxidative stress, inflammatory and apoptotic biomarkers with a prompt improvement in histopathological picture and a decrease in IL-1ß immunoexpression. CONCLUSION: Vinpo protective effect against GM-induced uterine injury involves modulation of inflammasome/caspase-1/IL-1ß signaling pathway.


Subject(s)
Caspase 1 , Gentamicins , Inflammasomes , Interleukin-1beta , Oxidative Stress , Signal Transduction , Uterus , Vinca Alkaloids , Animals , Female , Interleukin-1beta/metabolism , Vinca Alkaloids/pharmacology , Rats , Caspase 1/metabolism , Gentamicins/adverse effects , Inflammasomes/metabolism , Inflammasomes/drug effects , Uterus/drug effects , Uterus/metabolism , Uterus/pathology , Oxidative Stress/drug effects , Signal Transduction/drug effects , Apoptosis/drug effects
5.
Braz J Microbiol ; 55(2): 1189-1203, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38705960

ABSTRACT

Alginate is a major extra polymeric substance in the biofilm formed by mucoid Pseudomonas aeruginosa. It is the main proven perpetrator of lung infections in patients suffering from cystic fibrosis. Alginate lyases are very important in the treatment of cystic fibrosis. This study evaluated the role of standalone and in conjugation, effect of alginate lyase of SG4 + isolated from Paenibacillus lautus in enhancing in vitro bactericidal activity of gentamicin and amikacin on mucoid P. aeruginosa. Using Response Surface Methodology (RSM) alginate lyase SG4 + production was optimized in shake flask and there 8.49-fold enhancement in enzyme production. In fermenter, maximum growth (10.15 mg/ml) and alginate lyase (1.46 International Units) production, 1.71-fold was increased using Central Composite Design (CCD). Further, fermentation time was reduced from 48 to 20 h. To the best of our knowledge this is the first report in which CCD was used for fermenter studies to optimize alginate lyase production. The Km and Vmax of purified enzyme were found to be 2.7 mg/ml and 0.84 mol/ml-min, respectively. The half-life (t 1/2) of purified alginate lyase SG4 + at 37 °C was 180 min. Alginate lyase SG4 + in combination with gentamicin and amikacin eradiated 48.4- 52.3% and 58- 64.6%, alginate biofilm formed by P. aeruginosa strains, respectively. The study proves that alginate lyase SG4 + has excellent exopolysaccharide disintegrating ability and may be useful in development of potent therapeutic agent to treat P. aeruginosa biofilms.


Subject(s)
Anti-Bacterial Agents , Biofilms , Paenibacillus , Polysaccharide-Lyases , Pseudomonas aeruginosa , Pseudomonas aeruginosa/drug effects , Pseudomonas aeruginosa/enzymology , Pseudomonas aeruginosa/genetics , Biofilms/drug effects , Biofilms/growth & development , Polysaccharide-Lyases/metabolism , Polysaccharide-Lyases/genetics , Anti-Bacterial Agents/pharmacology , Paenibacillus/genetics , Paenibacillus/enzymology , Paenibacillus/drug effects , Gentamicins/pharmacology , Amikacin/pharmacology , Fermentation , Microbial Sensitivity Tests , Bacterial Proteins/metabolism , Bacterial Proteins/genetics , Alginates/metabolism
6.
Microbiology (Reading) ; 170(5)2024 May.
Article in English | MEDLINE | ID: mdl-38739119

ABSTRACT

Introduction. Bacterial keratitis, particularly caused by Pseudomonas aeruginosa, is challenging to treat because of multi-drug tolerance, often associated with the formation of biofilms. Antibiotics in development are typically evaluated against planktonic bacteria in a culture medium, which may not accurately represent the complexity of infections in vivo.Hypothesis/Gap Statement. Developing a reliable, economic ex vivo keratitis model that replicates some complexity of tissue infections could facilitate a deeper understanding of antibiotic efficacy, thus aiding in the optimization of treatment strategies for bacterial keratitis.Methodology. Here we investigated the efficacy of three commonly used antibiotics (gentamicin, ciprofloxacin and meropenem) against Pseudomonas aeruginosa cytotoxic strain PA14 and invasive strain PA01 using an ex vivo porcine keratitis model.Results. Both strains of P. aeruginosa were susceptible to the MIC of the three tested antibiotics. However, significantly higher concentrations were necessary to inhibit bacterial growth in the minimum biofilm eradication concentration (MBEC) assay, with both strains tolerating concentrations greater than 512 mg l-1 of meropenem. When MIC and higher concentrations than MBEC (1024 mg l-1) of antibiotics were applied, ciprofloxacin exhibited the highest potency against both P. aeruginosa strains, followed by meropenem, while gentamicin showed the least potency. Despite this, none of the antibiotic concentrations used effectively cleared the infection, even after 18 h of continuous exposure.Conclusions. Further exploration of antibiotic concentrations and aligning dosing with clinical studies to validate the model is needed. Nonetheless, our ex vivo porcine keratitis model could be a valuable tool for assessing antibiotic efficacy.


Subject(s)
Anti-Bacterial Agents , Biofilms , Ciprofloxacin , Disease Models, Animal , Keratitis , Microbial Sensitivity Tests , Pseudomonas Infections , Pseudomonas aeruginosa , Animals , Pseudomonas aeruginosa/drug effects , Pseudomonas aeruginosa/growth & development , Anti-Bacterial Agents/pharmacology , Swine , Pseudomonas Infections/drug therapy , Pseudomonas Infections/microbiology , Biofilms/drug effects , Keratitis/microbiology , Keratitis/drug therapy , Ciprofloxacin/pharmacology , Gentamicins/pharmacology , Meropenem/pharmacology
7.
Int Immunopharmacol ; 133: 112170, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38691919

ABSTRACT

Acute kidney injury (AKI) is characterized by a sudden decline in renal function. Traditional Chinese medicine has employed Fuzi for kidney diseases; however, concerns about neurotoxicity and cardiotoxicity have constrained its clinical use. This study explored mesaconine, derived from processed Fuzi, as a promising low-toxicity alternative for AKI treatment. In this study, we assessed the protective effects of mesaconine in gentamicin (GM)-induced NRK-52E cells and AKI rat models in vitro and in vivo, respectively. Mesaconine promotes the proliferation of damaged NRK-52E cells and down-regulates intracellular transforming growth factor ß1 (TGF-ß1) and kidney injury molecule 1 (KIM-1) to promote renal cell repair. Concurrently, mesaconine restored mitochondrial morphology and permeability transition pores, reversed the decrease in mitochondrial membrane potential, mitigated mitochondrial dysfunction, decreased ATP production, inhibited inflammatory factor release, and reduced early apoptosis rates. In vivo, GM-induced AKI rat models exhibited elevated AKI biomarkers, in which mesaconine was effectively reduced, indicating improved renal function. Mesaconine enhanced superoxide dismutase activity, reduced malondialdehyde content, alleviated inflammatory infiltrate, mitigated tubular and glomerular lesions, and downregulated NF-κB (nuclear factor-κb) p65 expression, leading to decreased tumor necrosis factor-α (TNF-α) and IL-1ß (interleukin-1ß) levels in GM-induced AKI animals. Furthermore, mesaconine inhibited the expression of renal pro-apoptotic proteins (Bax, cytochrome c, cleaved-caspase 9, and cleaved-caspase 3) and induced the release of the anti-apoptotic protein bcl-2, further suppressing apoptosis. This study highlighted the therapeutic potential of mesaconine in GM-induced AKI. Its multifaceted mechanisms, including the restoration of mitochondrial dysfunction, anti-inflammatory and antioxidant effects, and apoptosis mitigation, make mesaconine a promising candidate for further exploration in AKI management.


Subject(s)
Aconitum , Acute Kidney Injury , Apoptosis , Kidney , Mitochondria , Rats, Sprague-Dawley , Animals , Acute Kidney Injury/drug therapy , Acute Kidney Injury/chemically induced , Acute Kidney Injury/pathology , Apoptosis/drug effects , Aconitum/chemistry , Mitochondria/drug effects , Mitochondria/metabolism , Male , Rats , Cell Line , Kidney/drug effects , Kidney/pathology , Gentamicins/toxicity , Drugs, Chinese Herbal/therapeutic use , Drugs, Chinese Herbal/pharmacology , Aconitine/analogs & derivatives , Aconitine/pharmacology , Aconitine/therapeutic use , Disease Models, Animal , Membrane Potential, Mitochondrial/drug effects , Humans , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Diterpenes
8.
Redox Rep ; 29(1): 2332038, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38563333

ABSTRACT

OBJECTIVES: Gentamicin is one of the most common ototoxic drugs that can lower patients' quality of life. Oxidative stress is a key factors inducing sensory hair cell death during gentamicin administration. So far, there are no effective drugs to prevent or treat gentamicin- induced hearing loss. A recent study found cystic fibrosis transmembrane conductance regulator (CFTR) as a new target to modulate cellular oxidative balance. The objective of this study was to estimate the effect of the CFTR activator ivacaftor on gentamicin-induced ototoxicity and determine its mechanism. METHODS: The hair cell count was analyzed by Myosin 7a staining. Apoptosis was analyzed by TUNEL Apoptosis Kit. Cellular reactive oxygen species (ROS) level was detected by DCFH-DA probes. The Nrf2 related proteins expression levels were analyzed by western blot. RESULTS: An in vitro cochlear explant model showed that gentamicin caused ROS accumulation in sensory hair cells and induced apoptosis, and this effect was alleviated by pretreatment with ivacaftor. Western blotting showed that ivacaftor administration markedly increased the protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO1), and NAD(P)H:quinone oxidoreductase 1 (NQO1). The protective effect of ivacaftor was abolished by the Nrf2 inhibitor ML385. DISCUSSION: Our results indicate the protective role of the CFTR-Nrf2-HO1/NQO1 pathway in gentamicin-induced ototoxicity. Ivacaftor may be repositioned or repurposed towards aminoglycosides-induced hearing loss.


Subject(s)
Aminophenols , Hearing Loss , Ototoxicity , Quinolones , Humans , Gentamicins/toxicity , Reactive Oxygen Species/metabolism , NF-E2-Related Factor 2/metabolism , Cystic Fibrosis Transmembrane Conductance Regulator/metabolism , Cystic Fibrosis Transmembrane Conductance Regulator/pharmacology , Heme Oxygenase-1/metabolism , Heme Oxygenase-1/pharmacology , Quality of Life , Oxidative Stress , Apoptosis , NAD(P)H Dehydrogenase (Quinone)/metabolism , NAD(P)H Dehydrogenase (Quinone)/pharmacology
9.
Planta Med ; 90(6): 469-481, 2024 May.
Article in English | MEDLINE | ID: mdl-38580306

ABSTRACT

Methylrhodomelol (1: ) is a bromophenol from the red alga Vertebrata lanosa that has been associated with antimicrobial properties. The aim of the current study was, therefore, to assess the antimicrobial potential of this compound in more detail against the gram-negative pathogen Pseudomonas aeruginosa. 1: exerted weak bacteriostatic activity against different strains when grown in minimal medium, whereas other phenolics were inactive. In addition, 1: (35 and 10 µg/mL) markedly enhanced the susceptibility of multidrug-resistant P. aeruginosa toward the aminoglycoside gentamicin, while it did not affect the viability of Vero kidney cells up to 100 µM. Finally, pyoverdine release was reduced in bacteria treated at sub-inhibitory concentration, but no effect on other virulence factors was observed. Transcriptome analysis of treated versus untreated P. aeruginosa indicated an interference of 1: with bacterial carbon and energy metabolism, which was corroborated by RT-qPCR and decreased ATP-levels in treated bacteria. In summary, the current study characterized the antibacterial properties of methylrhodomelol, revealed its potential as an adjuvant to standard antibiotics, and generated a hypothesis on its mode of action.


Subject(s)
Anti-Bacterial Agents , Microbial Sensitivity Tests , Pseudomonas aeruginosa , Rhodophyta , Pseudomonas aeruginosa/drug effects , Anti-Bacterial Agents/pharmacology , Animals , Rhodophyta/chemistry , Vero Cells , Phenols/pharmacology , Chlorocebus aethiops , Gentamicins/pharmacology
10.
Sci Rep ; 14(1): 9690, 2024 04 27.
Article in English | MEDLINE | ID: mdl-38678140

ABSTRACT

Despite evidence suggesting the benefit of prophylactic regional antibiotic delivery (RAD) to sternal edges during cardiac surgery, it is seldom performed in clinical practice. The value of topical vancomycin and gentamicin for sternal wound infections (SWI) prophylaxis was further questioned by recent studies including randomized controlled trials (RCTs). The aim of this systematic review and meta-analysis was to comprehensively assess the safety and effectiveness of RAD to reduce the risk of SWI.We screened multiple databases for RCTs assessing the effectiveness of RAD (vancomycin, gentamicin) in SWI prophylaxis. Random effects meta-analysis was performed. The primary endpoint was any SWI; other wound complications were also analysed. Odds Ratios served as the primary statistical analyses. Trial sequential analysis (TSA) was performed.Thirteen RCTs (N = 7,719 patients) were included. The odds of any SWI were significantly reduced by over 50% with any RAD: OR (95%CIs): 0.49 (0.35-0.68); p < 0.001 and consistently reduced in vancomycin (0.34 [0.18-0.64]; p < 0.001) and gentamicin (0.58 [0.39-0.86]; p = 0.007) groups (psubgroup = 0.15). Similarly, RAD reduced the odds of SWI in diabetic and non-diabetic patients (0.46 [0.32-0.65]; p < 0.001 and 0.60 [0.44-0.83]; p = 0.002 respectively). Cumulative Z-curve passed the TSA-adjusted boundary for SWIs suggesting adequate power has been met and no further trials are needed. RAD significantly reduced deep (0.60 [0.43-0.83]; p = 0.003) and superficial SWIs (0.54 [0.32-0.91]; p = 0.02). No differences were seen in mediastinitis and mortality, however, limited number of studies assessed these endpoints. There was no evidence of systemic toxicity, sternal dehiscence and resistant strains emergence. Both vancomycin and gentamicin reduced the odds of cultures outside their respective serum concentrations' activity: vancomycin against gram-negative strains: 0.20 (0.01-4.18) and gentamicin against gram-positive strains: 0.42 (0.28-0.62); P < 0.001. Regional antibiotic delivery is safe and effectively reduces the risk of SWI in cardiac surgery patients.


Subject(s)
Anti-Bacterial Agents , Antibiotic Prophylaxis , Gentamicins , Randomized Controlled Trials as Topic , Surgical Wound Infection , Vancomycin , Humans , Surgical Wound Infection/prevention & control , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/therapeutic use , Antibiotic Prophylaxis/methods , Vancomycin/administration & dosage , Gentamicins/administration & dosage , Gentamicins/therapeutic use , Sternum/surgery , Sternum/microbiology , Cardiac Surgical Procedures/adverse effects
11.
Microb Drug Resist ; 30(5): 196-202, 2024 May.
Article in English | MEDLINE | ID: mdl-38579161

ABSTRACT

Staphylococcus aureus, the principal causative agent of osteomyelitis, can be internalized by osteoblasts and thereby escape from immune phagocytes and many kinds of antibiotics. To deliver antibiotics into osteoblasts to kill S. aureus in the intracellular environment, we developed gentamicin-loaded chitosan nanoparticles and evaluated their intracellular bactericidal effect. We found decreased numbers of S. aureus cells in infected osteoblasts treated with gentamicin-loaded chitosan nanoparticles. The cytotoxicity of the nanoparticles was evaluated by CCK-8 assay. There was no significant viability decrease at all tested concentrations. In conclusion, our results provide evidence for the potential use of gentamicin-loaded chitosan nanoparticles to enhance the delivery of gentamicin into cells and for their antibacterial effect against internalized S. aureus in the intracellular environment of osteoblasts.


Subject(s)
Anti-Bacterial Agents , Chitosan , Gentamicins , Nanoparticles , Osteoblasts , Staphylococcus aureus , Gentamicins/pharmacology , Chitosan/pharmacology , Chitosan/chemistry , Staphylococcus aureus/drug effects , Osteoblasts/drug effects , Anti-Bacterial Agents/pharmacology , Nanoparticles/chemistry , Animals , Microbial Sensitivity Tests , Staphylococcal Infections/drug therapy , Staphylococcal Infections/microbiology , Humans , Cell Survival/drug effects , Mice
12.
Open Vet J ; 14(1): 438-448, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38633178

ABSTRACT

Background: Nowadays veterinarians and poultry producers use antibiotics to increase growth rates, bird health, and feed efficiency, egg production, for preventative and therapeutic purposes, and to lessen the prevalence of poultry diseases. Most poultry producers have used a variety of antibiotics, either with or without veterinarian instruction. Although antibiotics are beneficial for the majority of their uses, their unauthorized use has resulted in residues accumulated in poultry products intended for human consumption which represents a serious risk to the general public that could be toxicological, microbiological, or immunological. Aim: This study aimed to the estimation of the residues of three major antimicrobials used in the intensive chicken-rearing systems in Egypt, namely Oxytetracycline (OTC), Gentamicin, and Ciprofloxacin. Moreover, the effect of cooking on such residues was investigated. Methods: A total of 100 chicken meat samples (breast, thigh, gizzard, liver, 25 each) were examined for detection of the aforementioned antimicrobials using the microbial inhibition assay and high-performance liquid chromatography (HPLC). Besides, samples containing the highest antimicrobial residues were examined for the effect of boiling for 30 minutes on such residues. Results: The obtained results revealed that 23%, 21%, and 17% of the examined samples were positive for OTC, gentamicin, and ciprofloxacin residues , respectively . Cooking (boiling) for 30 minutes showed a reduction of the antibiotic residue by 88.2%, 95.2%, and 31.3%, respectively. Conclusion: Antimicrobial residues were detected in the chicken meat parts retailed in Egypt. Cooking can reduce the antimicrobial residues at least in part.


Subject(s)
Anti-Infective Agents , Oxytetracycline , Animals , Humans , Anti-Bacterial Agents/pharmacology , Chickens , Poultry/microbiology , Ciprofloxacin , Gentamicins
13.
J Appl Microbiol ; 135(4)2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38587823

ABSTRACT

AIM: In this study, it was aimed to examine the antibacterial activity of the essential oil components (EOCs), carvacrol (CAR), cinnamaldehyde (CIN), thymol (TH), alpha pinene (α-PN), eucalyptol (EU), limonene (LIM), and the antibiotics, linezolid (LZD), vancomycin (VAN), gentamicin (GEN), ciprofloxacin (CIP), clindamycin (CLN), and penicillin (PEN) against 50 multidrug resistant Corynebacterium striatum strains, and the synergistic interactions of CAR and CIN with the antibiotics against 10 randomly selected Coryne. striatum strains to explore synergistic interactions to determine if their combined use could enhance antibiotic activity and potentially reduce resistance. METHODS AND RESULTS: The activity of the EOCs and the antibiotics against Coryne. striatum strains isolated from clinical specimens, was examined by broth microdilution method. The synergistic interactions of the EOCs with the antibiotics against 10 randomly selected Coryne. striatum strains were determined by checkerboard method. EOCs, CIN, and CAR and antibiotics, LZD, VAN, GEN, CIP, and CLN were detected to have antibacterial activity against Coryne. striatum strains alone and either synergistic interactions were observed in combinations of the antibiotics with EOCs. CONCLUSIONS: All Coryne. striatum strains were determined to be susceptible to VAN and LZD and resistant to GEN, PEN, CIP, and CLN. Synergistic interactions were observed in all combinations of antibiotics tested with CAR and CIN.


Subject(s)
Acrolein , Acrolein/analogs & derivatives , Anti-Bacterial Agents , Corynebacterium , Drug Resistance, Multiple, Bacterial , Drug Synergism , Microbial Sensitivity Tests , Monoterpenes , Oils, Volatile , Anti-Bacterial Agents/pharmacology , Corynebacterium/drug effects , Oils, Volatile/pharmacology , Drug Resistance, Multiple, Bacterial/drug effects , Acrolein/pharmacology , Monoterpenes/pharmacology , Cymenes/pharmacology , Ciprofloxacin/pharmacology , Gentamicins/pharmacology , Vancomycin/pharmacology , Linezolid/pharmacology , Limonene/pharmacology , Eucalyptol/pharmacology , Thymol/pharmacology , Clindamycin/pharmacology , Humans , Penicillins/pharmacology , Terpenes/pharmacology , Cyclohexenes/pharmacology , Corynebacterium Infections/microbiology
14.
Arch Toxicol ; 98(6): 1827-1842, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38563869

ABSTRACT

Aminoglycosides are commonly used antibiotics for treatment of gram-negative bacterial infections, however, they might act on inner ear, leading to hair-cell death and hearing loss. Currently, there is no targeted therapy for aminoglycoside ototoxicity, since the underlying mechanisms of aminoglycoside-induced hearing impairments are not fully defined. This study aimed to investigate whether the calcium channel blocker verapamil and changes in intracellular & extracellular calcium could ameliorate aminoglycoside-induced ototoxicity in zebrafish. The present findings showed that a significant decreased number of neuromasts in the lateral lines of zebrafish larvae at 5 days' post fertilization after neomycin (20 µM) and gentamicin (20 mg/mL) exposure, which was prevented by verapamil. Moreover, verapamil (10-100 µM) attenuated aminoglycoside-induced toxic response in different external calcium concentrations (33-3300 µM). The increasing extracellular calcium reduced hair cell loss from aminoglycoside exposure, while lower calcium facilitated hair cell death. In contrast, calcium channel activator Bay K8644 (20 µM) enhanced aminoglycoside-induced ototoxicity and reversed the protective action of higher external calcium on hair cell loss. However, neomycin-elicited hair cell death was not altered by caffeine, ryanodine receptor (RyR) agonist, and RyR antagonists, including thapsigargin, ryanodine, and ruthenium red. The uptake of neomycin into hair cells was attenuated by verapamil and under high external calcium concentration. Consistently, the production of reactive oxygen species (ROS) in neuromasts exposed to neomycin was also reduced by verapamil and high external calcium. Significantly, zebrafish larvae when exposed to neomycin exhibited decreased swimming distances in reaction to droplet stimulus when compared to the control group. Verapamil and elevated external calcium effectively protected the impaired swimming ability of zebrafish larvae induced by neomycin. These data imply that prevention of hair cell damage correlated with swimming behavior against aminoglycoside ototoxicity by verapamil and higher external calcium might be associated with inhibition of excessive ROS production and aminoglycoside uptake through cation channels. These findings indicate that calcium channel blocker and higher external calcium could be applied to protect aminoglycoside-induced listening impairments.


Subject(s)
Anti-Bacterial Agents , Calcium Channel Blockers , Calcium , Gentamicins , Hair Cells, Auditory , Neomycin , Verapamil , Zebrafish , Animals , Calcium Channel Blockers/pharmacology , Calcium/metabolism , Verapamil/pharmacology , Neomycin/toxicity , Hair Cells, Auditory/drug effects , Hair Cells, Auditory/metabolism , Gentamicins/toxicity , Anti-Bacterial Agents/toxicity , Reactive Oxygen Species/metabolism , Ototoxicity/prevention & control , Aminoglycosides/toxicity , Lateral Line System/drug effects , Larva/drug effects , Hearing Loss/chemically induced , Hearing Loss/prevention & control
15.
Colloids Surf B Biointerfaces ; 238: 113925, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38657556

ABSTRACT

Antibiotic-loaded calcium phosphate cement (CPC) has emerged as a promising biomaterial for drug delivery in orthopedics. However, there are problems such as the burst release of antibiotics, low cumulative release ratio, inappropriate release cycle, inferior mechanical strength, and poor anti-collapse properties. In this research, montmorillonite-gentamicin (MMT-GS) was fabricated by solution intercalation method and served as the drug release pathways in CPC to avoid burst release of GS, achieving promoted cumulative release ratios and a release cycle matched the time of inflammatory response. The results indicated that the highest cumulative release ratio and release concentration of GS in CPC/MMT-GS was 94.1 ± 2.8 % and 1183.05 µg/mL, and the release cycle was up to 504 h. In addition, the hierarchical GS delivery system was divided into three stages, and the kinetics followed the Korsmeyer-Peppas model, the zero-order model, and the diffusion-dissolution model, respectively. Meanwhile, the compressive strength of CPC/MMT-GS was up to 51.33 ± 3.62 MPa. Antibacterial results demonstrated that CPC/MMT-GS exhibited excellent in vitro long-lasting antibacterial properties to E. coli and S. aureus. Furthermore, CPC/MMT-GS promoted osteoblast proliferation and exhibited excellent in vivo histocompatibility. Therefore, CPC/MMT-GS has favorable application prospects in the treatment of bone defects with bacterial infections and inflammatory reactions.


Subject(s)
Anti-Bacterial Agents , Bentonite , Bone Cements , Calcium Phosphates , Drug Delivery Systems , Drug Liberation , Escherichia coli , Gentamicins , Staphylococcus aureus , Bentonite/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Gentamicins/pharmacology , Gentamicins/chemistry , Gentamicins/administration & dosage , Gentamicins/pharmacokinetics , Calcium Phosphates/chemistry , Bone Cements/chemistry , Bone Cements/pharmacology , Animals , Escherichia coli/drug effects , Mice , Staphylococcus aureus/drug effects , Microbial Sensitivity Tests , Particle Size
16.
J Appl Microbiol ; 135(5)2024 May 01.
Article in English | MEDLINE | ID: mdl-38658191

ABSTRACT

AIMS: The research aimed to optimize the ultrasound-assisted extraction of secondary metabolites and the antibacterial activity of the plant species Geranium robertianum. The phytochemical profiles of the optimized extracts, as well as their antibacterial and synergistic activity with an antibiotic and their potential mechanisms of action and cytotoxicity, were examined. METHODS AND RESULTS: Response Surface Methodology was used to optimize extraction conditions. Optimized ethanol and acetone extracts were tested via microdilution, checkerboard, time-kill kinetics, and cell membrane permeability methods. The extracts displayed broad antibacterial activity with minimum inhibitory concentrations ranging from 1.25 to 20 mg ml-1. In addition, the extract synergistically reacted with gentamicin against gentamicin-resistant strains of Escherichia coli and Staphylococcus aureus, enhancing the efficacy of the antibiotic up to 32-fold. The extracts demonstrated strain-dependent bactericidal activity in a 24-h time interval. They increase the permeability of the cell membrane, thus disrupting its normal functioning. The cytotoxic concentration (CC50) on human keratinocytes was 1771.24 ± 5.78 µg ml-1 for ethanol extract, and 958.01 ± 6.14 µg ml-1 for acetone extract. Kaempferol, ellagic acid, quercetin, and rutin were recognized as the main components in both extracts. CONCLUSIONS: The findings of this study indicate that the extracts of G. robertianum can be considered as potential natural antibacterial agents in the control of microorganisms.


Subject(s)
Anti-Bacterial Agents , Escherichia coli , Geranium , Microbial Sensitivity Tests , Plant Extracts , Staphylococcus aureus , Anti-Bacterial Agents/pharmacology , Geranium/chemistry , Plant Extracts/pharmacology , Staphylococcus aureus/drug effects , Humans , Escherichia coli/drug effects , Gentamicins/pharmacology , Keratinocytes/drug effects
17.
J Med Case Rep ; 18(1): 180, 2024 Mar 25.
Article in English | MEDLINE | ID: mdl-38523318

ABSTRACT

BACKGROUND: Stenotrophomonas maltophilia is a gram-negative bacteria known for causing opportunistic and nosocomial infections in humans. S. maltophilia is an emerging pathogen of concern due to it's increasing prevalence, diverse disease spectrum, intrinsic multi-drug resistance and high mortality rates in immunocompromised individuals. S. maltophilia is a rare cause of neonatal sepsis associated with significant morbidity and mortality. The bacterium's multi-drug resistance poses a considerable challenge for treatment, with various mechanisms contributing to its resistance. CASE PRESENTATION: We report a case involving a 40-h-old male African neonate who exhibited symptoms of neonatal sepsis. The blood culture revealed Stenotrophomonas maltophilia, which was sensitive to ciprofloxacin and gentamicin but resistant to other antibiotics. Lumbar puncture for CSF could not be done because the father declined. We treated the newborn with the empirical first-line antibiotics as per the national guideline intravenous ampicillin and gentamicin for six days, and the child recovered fully with a repeated negative blood culture. CONCLUSIONS: This report describes a neonatal sepsis case caused by S. maltophilia, a multi-drug resistant bacteria and a rare cause of neonatal sepsis. We report that early detection of the bacterial and antimicrobial management based on local antibiogram data may be essential for successful patient's management.


Subject(s)
Gram-Negative Bacterial Infections , Neonatal Sepsis , Stenotrophomonas maltophilia , Child , Infant, Newborn , Male , Humans , Neonatal Sepsis/diagnosis , Neonatal Sepsis/drug therapy , Gram-Negative Bacterial Infections/diagnosis , Gram-Negative Bacterial Infections/drug therapy , Anti-Bacterial Agents/therapeutic use , Gentamicins/therapeutic use
18.
Sci Rep ; 14(1): 7397, 2024 03 28.
Article in English | MEDLINE | ID: mdl-38548851

ABSTRACT

Urinary tract infections (UTIs) are one of the most prevalent bacterial infections affecting humans, with a higher incidence among women. Pregnant women are at an increased risk of developing UTIs, which can have detrimental consequences for both the mother and fetus. UTIs can be caused by various bacteria, and the prevalence of drug-resistant UTIs in maternity and children's hospitals is a cause for concern due to the potential for severe complications if left untreated. The primary objective of the current study was to determine the distribution of UTI-causing bacteria and investigate the antibiotic sensitivity patterns of isolated cultures obtained from pregnant women with UTIs at the Maternity and Children's Hospital, Bisha, Saudi Arabia. This cross-sectional study was conducted from October 2021 to October 2023, involving the analysis of urine samples collected from 321 participants who acquired UTIs during pregnancy. Using biochemical tests and standard cultures, the urine samples were examined for pathogenic bacteria and their anti-microbial sensitivity patterns. The study analyzed susceptibility results according to the Clinical Laboratory Standards Institute guidelines (M100, 28th Edition, 2018). Bacterial strains demonstrating resistance to three or more antibiotics were classified as multidrug-resistant (MDR). This study revealed the distribution of UTI-causing bacteria to be as follows: Escherichia coli, 57.01%; Klebsiella pneumoniae, 24.61%; Pseudomonas aeruginosa, 4.36%; Proteus mirabilis and Enterobacter cloacae, 3.74%; Streptococcus agalactiae, 3.11%; Enterococcus faecalis, 2.18%; and Staphylococcus aureus, 1.24%. Antimicrobial susceptibility testing varied among gram-positive and gram-negative bacteria. Gentamicin demonstrated the highest sensitivity among both gram-positive and gram-negative bacteria; piperacillin-tazobactam was the second most effective drug against gram-negative bacteria. The bacterial isolates showed varying susceptibility to different antibiotics, with Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa being mainly sensitive to gentamicin, piperacillin-tazobactam, and ciprofloxacin, respectively. The strategies for reducing the risk of UTIs need to be improved to limit the spread of MDR bacteria. These strategies may include promoting hygienic practices and administering appropriate antibiotics to prevent the emergence and spread of drug-resistant bacteria. Further research is required to monitor the trends in antibiotic resistance among UTI-causing bacteria and develop effective strategies for managing this public health menace.


Subject(s)
Anti-Bacterial Agents , Urinary Tract Infections , Pregnancy , Child , Female , Humans , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Pregnant Women , Saudi Arabia/epidemiology , Cross-Sectional Studies , Gram-Negative Bacteria , Gram-Positive Bacteria , Urinary Tract Infections/drug therapy , Urinary Tract Infections/epidemiology , Urinary Tract Infections/microbiology , Bacteria , Piperacillin, Tazobactam Drug Combination/therapeutic use , Escherichia coli , Gentamicins/pharmacology , Hospitals , Microbial Sensitivity Tests , Drug Resistance, Bacterial
19.
Int Tinnitus J ; 27(2): 211-216, 2024 Mar 21.
Article in English | MEDLINE | ID: mdl-38507637

ABSTRACT

Dental caries are mainly occur owing to the presence and activity of bacterial agents. The present study was done to assess the prevalence and antibiotic resistance of bacterial strains isolated from the cases of dental caries. Fifty patients with approved dental carries were included in the study. Sampling from the site of dental caries was done using the sterile swab. Swabs were transferred to laboratory and subjected to microbial culture. Species identification of bacteria was done using biochemical test. Bacterial isolates were subjected to disk diffusion to assess their antimicrobial resistance. S. aureus (40%) harboured the highest rate of contamination, while S. oralis (16%) and E. aerogenes (10%) harbored the lowest. S. aureus and S. mutans (6%) harbored the highest distribution amongst the cases of mix infections, while S. aureus and S. oralis (2%) harbnored the lowest. S. aureus strains harbored the highest rate of resistance toward tetracycline (90%), penicillin (75%), ampicillin (75%), amoxicillin (60%), and erythromycin (60%). E. coli strains harbored the highest rate of resistance toward tetracycline (90%), gentamicin (80%), ampicillin (70%), and erythromycin (70%). S. mutans strains harbored the highest rate of resistance toward tetracycline (93.33%), ampicillin (86.66%), penicillin (80%), amoxicillin (80%), and erythromycin (80%). S. oralis strains harbored the highest rate of resistance toward tetracycline (100%), ampicillin (75%), penicillin (62.50%), and amoxicillin (62.50%). E. aerogenes strains harbored the highest rate of resistance toward tetracycline (80%), gentamicin (80%), and ampicillin (80%). S. aureus bacteria isolated from dental caries harbored the highest rate of MDR. Distribution of resistance against more than 3 antimicrobial agents amongst the S. aureus, E. coli, S. mutans, S. oralis, and E. aerogenes bacteria isolated from the cases of dental caries was 90%, 60%, 80%, 62.50%, and 80%, respectively. Application of disk diffuin can help practitioners to reduce the rate of resistance in bacteria responsible for dental caries.


Subject(s)
Anti-Bacterial Agents , Dental Caries , Humans , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Staphylococcus aureus , Prevalence , Dental Caries/epidemiology , Dental Caries/drug therapy , Escherichia coli , Drug Resistance, Bacterial , Microbial Sensitivity Tests , Erythromycin , Amoxicillin , Tetracycline , Penicillins , Gentamicins
20.
PLoS One ; 19(3): e0298529, 2024.
Article in English | MEDLINE | ID: mdl-38483863

ABSTRACT

Salidroside (SAL) is a phenol glycoside compound found in plants of the Rhodiola genus which has natural antioxidant and free radical scavenging properties. SAL are able to protect against manganese-induced ototoxicity. However, the molecular mechanism by which SAL reduces levels of reactive oxygen species (ROS) is unclear. Here, we established an in vitro gentamicin (GM) ototoxicity model to observe the protective effect of SAL on GM-induced hair cells (HC) damage. Cochlear explants of postnatal day 4 rats were obtained and randomly divided into six groups: two model groups (treatment with 0.2 mM or 0.4 mM GM for 24 h); two 400 µmol/L SAL-pretreated groups pretreatment with SAL for 3 h followed by GM treatment (0.2 mM or 0.4 mM) for 24 h; 400 µmol/L SAL group (treatment with SAL for 24 h); control group (normal cultured cochlear explants). The protective effects of SAL on GM-induced HC damage, and on mRNA and protein levels of antioxidant enzymes were observed. HC loss occurred after 24 h of GM treatment. Pretreatment with SAL significantly reduced GM-induced OHC loss. In cochlear tissues, mRNA and protein levels of NRF2 and HO-1 were enhanced in the GM alone group compared with the SAL pretreatment GM treatment group. SAL may protect against GM-induced ototoxicity by regulating the antioxidant defense system of cochlear tissues; SAL can activate NRF2/HO-1 signaling, inhibit NF-κB activation, activate AKT, and increase inhibitory phosphorylation of GSK3ß to decrease GSK3 activity, all of which exert antioxidant effects.


Subject(s)
Gentamicins , Glucosides , Ototoxicity , Rats , Animals , Gentamicins/toxicity , Gentamicins/metabolism , NF-kappa B/metabolism , Antioxidants/pharmacology , Antioxidants/metabolism , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/metabolism , Glycogen Synthase Kinase 3 beta/metabolism , Glycogen Synthase Kinase 3/metabolism , Hair Cells, Auditory , Cochlea/metabolism , Phenols/pharmacology , Phenols/metabolism , RNA, Messenger/metabolism
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