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1.
Front Biosci (Landmark Ed) ; 28(1): 14, 2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36722262

RESUMO

BACKGROUND: Kidneys are among the vital organs of the human body; therefore, damage from any exogenous/endogenous agent may put human life at risk. Arachis hypogaea (AH) contains different free radical scavenging flavonoids, stilbenes, and tannins. This research aimed to elucidate the possible nephroprotective mechanism of AH methanolic crude extract (AHcr) and n-hexane oil fraction (AHO) against gentamycin-induced nephrotoxicity. METHODS: After the extraction of the crude oil of the plant, they were tested against a Gentamycin (GM)-treated group of Swiss Albino mice for their nephroprotective action. Animals were divided into six (6) equal groups with five (5) animals in each group. These groups were: control group (0.5 mL normal saline via intraperitoneal -i.p), gentamycin group (gentamycin 100 mg/kg i.p), Silymarin + gentamycin group (Silymarin 50 mg/kg and gentamycin 100 mg/kg i.p), plant extract (AHcr1) and gentamycin group (AHcr1 250 mg/kg and gentamycin 100 mg/kg i.p), AHcr2 + gentamycin group (AHcr2; 500 mg/kg and gentamycin 100 mg/kg i.p) and the hexane oil fraction (AHO) + gentamycin (AHO 1 mL/kg and GM 100 mg/kg i.p). After completion of doses, animals were sacrificed for the collection of blood to further investigate biochemical changes and histopathological changes in kidney tissues. RESULTS: Serum creatinine, urea, and blood urea nitrogen significantly increased (p < 0.001) in the gentamycin-treated group as compared to the control group. The elevated level of serum creatinine, urea, and blood urea nitrogen was decreased significantly (p < 0.001) in groups treated with AHcr and AHO compared to the gentamycin group. Similarly, the histopathological study of kidney tissues from the gentamycin group showed tubular necrosis, vacuolation, and fibrosis. CONCLUSIONS: The effect of crude extract and hexane soluble fraction of AH caused a significant reversal of gentamycin-induced nephrotoxicity.


Assuntos
Arachis , Hexanos , Camundongos , Animais , Humanos , Creatinina , Desenvolvimento de Medicamentos , Gentamicinas , Substâncias Protetoras/farmacologia
2.
Braz J Biol ; 83: e269317, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36722663

RESUMO

Bacteria may be the initial cause of certain pathologies as well as a secondary agent responsible for the development of complications such as pressure ulcer infections. Pressure ulcers are a persistent health problem, especially in immunocompromised patients, and associated with infection by opportunistic microorganisms with antimicrobial resistance, such as Klebsiella pneumoniae, highlight the need for the development of new antimicrobial approaches. Thus, the aim of this study was to evaluate the antibacterial and anti-adherent activity of Origanum vulgare L. (oregano) essential oil against Klebsiella pneumoniae strains, as well as the effect of its association with synthetic antimicrobials. To this end, the Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) analyses were performed on microdilution plates. The assay of the Minimum Inhibitory Adherence Concentration (MIAC), with test tubes. As well as, the association study through the infusion disc method containing ampicillin (AMP), gentamicin (GEN), ciprofloxacin (CIP) and ceftriaxone (CEF). Therefore, it was possible to obtain that the essential oil of oregano presents antimicrobial and bactericidal activity, with MIC ranging between 128µg/mL and 256 µg/mL and MBC between 256 µg/mL and 512 µg/mL, on the tested K. pneumoniae strains. When used in association with ampicillin and gentamicin, oregano essential oil showed synergistic effect for some strains. Therefore, it is observed that the tested essential oil can act as a promising antibacterial in the treatment of diseases caused by K. pneumoniae.


Assuntos
Óleos Voláteis , Origanum , Humanos , Klebsiella pneumoniae , Antibacterianos/farmacologia , Ampicilina , Gentamicinas , Óleos Voláteis/farmacologia
3.
Sci Rep ; 13(1): 449, 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36624272

RESUMO

Whole genome sequencing (WGS) enables detailed characterization of bacteria at single nucleotide resolution. It provides data about acquired resistance genes and mutations leading to resistance. Although WGS is becoming an essential tool to predict resistance patterns accurately, comparing genotype to phenotype with WGS is still in its infancy. Additional data and validation are needed. In this retrospective study, we analysed 234 E. coli isolates from positive blood cultures using WGS as well as microdilution for 11 clinically relevant antibiotics, to compare the two techniques. We performed whole genome sequencing analyses on 234 blood culture isolates (genotype) to detect acquired antibiotic resistance. Minimal inhibitory concentrations (MIC) for E. coli were performed for amoxicillin, cefepime, cefotaxime, ceftazidime, meropenem, amoxicillin/clavulanic acid, piperacillin/tazobactam, amikacin, gentamicin, tobramycin, and ciprofloxacin, using the ISO 20776-1 standard broth microdilution method as recommended by EUCAST (phenotype). We then compared the two methods for statistical 'agreement'. A perfect (100%) categorical agreement between genotype and phenotype was observed for gentamicin and meropenem. However, no resistance to meropenem was observed. A high categorical agreement (> 95%) was observed for amoxicillin, cefepime, cefotaxime, ceftazidime, amikacin, and tobramycin. A categorical agreement lower than 95% was observed for amoxicillin/clavulanic acid, piperacillin/tazobactam, and ciprofloxacin. Most discrepancies occurred in isolates with MICs within ± 1 doubling dilution of the breakpoint and 22.73% of the major errors were samples that tested phenotypically susceptible at higher antibiotic exposure and were therefore considered as 'not resistant'. This study shows that WGS can be used as a valuable tool to predict phenotypic resistance against most of the clinically relevant antibiotics used for the treatment of E. coli bloodstream infections.


Assuntos
Infecções por Escherichia coli , Escherichia coli , Humanos , Escherichia coli/genética , Meropeném , Amicacina/farmacologia , Cefepima , Ceftazidima , Estudos Retrospectivos , Antibacterianos/farmacologia , Cefotaxima , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/microbiologia , Ciprofloxacina/farmacologia , Testes de Sensibilidade Microbiana , Genótipo , Fenótipo , Piperacilina , Tazobactam , Sequenciamento Completo do Genoma , Tobramicina , Amoxicilina , Gentamicinas , Ácido Clavulânico
4.
BMC Pediatr ; 23(1): 24, 2023 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-36647065

RESUMO

BACKGROUND: Gentamicin and amikacin are aminoglycoside antibiotics which are renally excreted and known to be nephrotoxic. Estimate of glomerular filtration rate (eGFR) per body surface area is lower in neonates than in adults and exposure to these drugs could lead to more suppression in kidney function. The aim of this study was to determine maximum and minimum plasma concentrations (Cmax and Cmin), time to reach Cmin levels of gentamicin and amikacin, and to assess eGFR in preterm and term neonates. METHODS: Two groups of patients were recruited, 44 neonates receiving gentamicin (5 mg/kg/24 h) and 35 neonates receiving amikacin (15 mg/kg/24 h) by slow intravenous injection. Patients on amikacin had been on gentamicin before being switched to amikacin. Two blood samples were drawn for the determination of the maximum and minimum plasma concentration. Primary outcomes were determination of Cmax, Cmin, and the time it took to clear the aminoglycoside to a plasma concentration below the toxicity threshold (gentamicin: < 1 mcg/mL; amikacin: < 5 mcg/mL. RESULTS: Therapeutic range for Cmax of gentamicin (15-25 mcg/mL) or amikacin (30-40 mcg/mL) was achieved in only 27.3 and 2.9% of neonates, respectively. Percentage of neonates reaching plasma concentrations below the toxicity threshold within the 24-hour dosing interval was 72.7% for gentamicin and 97.1% for amikacin. Positive correlation between gentamicin clearance and postnatal age borderline statistical significance (p = 0.007), while the correlation between amikacin clearance and postnatal age was poor and not statistically significant (r2 = - 0.30, p = 0.971). CONCLUSION: Although eGFR decreased significantly as a function of postnatal age in neonates receiving amikacin, the majority (91.4%) of these neonates were able to clear the drug to < 5 mcg/mL within a 24-hour dosing interval.


Assuntos
Amicacina , Gentamicinas , Recém-Nascido , Adulto , Humanos , Taxa de Filtração Glomerular , Antibacterianos , Aminoglicosídeos
5.
Tidsskr Nor Laegeforen ; 143(1)2023 Jan 17.
Artigo em Inglês, Norueguês | MEDLINE | ID: mdl-36655955

RESUMO

BACKGROUND: Gentamicin is often used to treat serious paediatric infections. It has been standard practice in Norway to measure the serum concentration of gentamicin immediately prior to the second or third dose (pre-dose [trough] concentration) to assess the risk of toxicity. The clinical significance of such measurements in children has not previously been evaluated in Norway. MATERIAL AND METHOD: This is a retrospective study of routine pre-dose samples obtained for the measurement of serum gentamicin in paediatric patients aged 1 month to 17 years at four hospitals in Norway. Clinical data were extracted from electronic medical records from two of the hospitals. All children received treatment with intravenous gentamicin at a dose of 7 mg/kg once daily in accordance with Norwegian guidelines. RESULTS: The most common indications for treatment were febrile urinary tract infection, febrile neutropenia, and suspected or confirmed sepsis. The median (interquartile range) duration of treatment in 353 episodes at two of the hospitals was 4 (3-5) days. Serum gentamicin pre-dose samples were analysed for 1,288 treatment episodes across four hospitals. In 1,223 episodes (95 %), the pre-dose sample showed a serum gentamicin concentration of less than 0.6 mg/L. In 7 episodes (0.5 %), the pre-dose sample showed an elevated gentamicin concentration, defined as greater than 1.0 mg/L. INTERPRETATION: An in most cases mildly elevated serum gentamicin concentration was found in the pre-dose sample in 7 of 1,288 treatment episodes. Routine measurement of serum gentamicin via a pre-dose sample should in future be reserved for children receiving long-term gentamicin treatment, those with impaired kidney function, or those who are also receiving nephro- or ototoxic drugs.


Assuntos
Sepse , Infecções Urinárias , Humanos , Criança , Gentamicinas/efeitos adversos , Antibacterianos/efeitos adversos , Estudos Retrospectivos , Infecções Urinárias/tratamento farmacológico , Sepse/tratamento farmacológico
6.
Surg Infect (Larchmt) ; 24(1): 82-90, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36706256

RESUMO

Background: Fibrin sealants are used as antimicrobial-releasing carriers for preventing surgical site infections; however, it is important to determine the release kinetics and antimicrobial effects of drugs added to fibrin sealants and the effects of drugs on clot/clotting properties. Materials and Methods: The antimicrobial and antibiofilm activity of cefazolin, colistin, gentamicin, oxacillin, tobramycin, and silver nitrate released from fibrin sealant were characterized using in vitro and ex vivo assays against bacteria commonly found on the skin. The effects of antimicrobial agents on the physical structure of the fibrin sealant were assessed with scanning electron microscopy (SEM) and on the clotting rate and strength of fibrin clots using run-off tests and rheology. Results: Generally, antibiotic agents were released gradually from fibrin sealant and were stable after release, with antimicrobial effects evident up to three days. Cefazolin, gentamicin, and oxacillin prevented biofilm formation of Staphylococcus aureus in porcine skin explants; gentamicin and colistin prevented biofilm formation of Pseudomonas aeruginosa. Gentamicin, cefazolin, colistin, and tobramycin did not affect the structural integrity or viscoelastic properties of fibrin sealant; changes were observed with oxacillin (SEM) and particularly silver nitrate (SEM and rheology). No antimicrobial agents caused deterioration of clotting time (run-off tests). Conclusions: From the antimicrobial agents tested, gentamicin and cefazolin showed prolonged release from fibrin sealant, sustained antimicrobial activity, and biofilm prevention properties against Staphylococcus aureus; similar results were observed for gentamicin and colistin against Pseudomonas aeruginosa. For each of these findings, the physical structure of the fibrin sealant, clotting rate, and strength of fibrin clots were unaffected.


Assuntos
Adesivo Tecidual de Fibrina , Infecções Estafilocócicas , Animais , Suínos , Adesivo Tecidual de Fibrina/farmacologia , Adesivo Tecidual de Fibrina/química , Cefazolina , Colistina , Nitrato de Prata , Antibacterianos/uso terapêutico , Gentamicinas/farmacologia , Oxacilina , Tobramicina , Infecções Estafilocócicas/tratamento farmacológico
7.
Int J Antimicrob Agents ; 61(1): 106702, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36476965

RESUMO

BACKGROUND: Optimal treatment of carbapenemase-producing Enterobacterales (CPE) bone infections is poorly defined. This study evaluated the efficacy of the novel beta-lactam-beta-lactamase inhibitor-ceftazidime-avibactam (CAZ-AVI)-with different antibiotic combinations in an experimental model of CPE osteomyelitis. METHODS: KPC-99YC is a clinical strain of Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae with intermediate susceptibility to meropenem (MIC 4 mg/L), gentamicin (MIC 0.25 mg/L), colistin (MIC 0.25 mg/L), fosfomycin (MIC 4 mg/L) and ceftazidime-avibactam (MIC 1 mg/L). Time-kill curves were performed at 4x MIC. Osteomyelitis was induced in rabbits by tibial injection of 2×108 CFU of KPC-99YC. Six groups started treatment 14 days later for 7 days: control, colistin, CAZ-AVI, CAZ-AVI plus gentamicin, CAZ-AVI plus colistin and CAZ-AVI plus fosfomycin. Antibiotic dosages were selected to simulate plasma concentrations obtained in humans. Treatment was evaluated according to bone cultures quantified in log10 CFU. RESULTS: In vitro, CAZ-AVI plus colistin or gentamicin were rapidly bactericidal in contrast with CAZ-AVI plus fosfomycin. In vivo, compared with controls, colistin alone (P = 0.045) and CAZ-AVI alone or in combination significantly lowered bone bacterial counts (P < 0.001). Bone sterilisation was achieved in 67% and 100% of animals with combinations of CAZ-AVI plus colistin or gentamicin (P = 0.001 and P < 0.001, respectively) whereas other treatments were no different from controls. CAZ-AVI plus gentamicin provided greater bone bacterial reduction than CAZ-AVI plus colistin (P = 0.033). No CAZ-AVI-resistant strains emerged in treated rabbits, regardless of combination. CONCLUSIONS: CAZ-AVI plus gentamicin was the best effective combination therapy. Combinations with CAZ-AVI appear to be a promising treatment of KPC-producing Klebsiella pneumoniae osteomyelitis.


Assuntos
Fosfomicina , Infecções por Klebsiella , Osteomielite , Humanos , Animais , Coelhos , Klebsiella pneumoniae , Colistina/uso terapêutico , Colistina/farmacologia , Fosfomicina/uso terapêutico , Fosfomicina/farmacologia , Klebsiella , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/microbiologia , Ceftazidima/uso terapêutico , Ceftazidima/farmacologia , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , beta-Lactamases/farmacologia , Compostos Azabicíclicos/uso terapêutico , Compostos Azabicíclicos/farmacologia , Combinação de Medicamentos , Inibidores de beta-Lactamases/uso terapêutico , Gentamicinas/uso terapêutico , Osteomielite/tratamento farmacológico , Testes de Sensibilidade Microbiana
8.
Microb Pathog ; 174: 105906, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36494020

RESUMO

The bacteriophage vB8388 can lyse multi-drug resistant Klebsiella oxytoca strain FK-8388 and maintain stability in a wide range of temperatures (from 4 °C to 80 °C) and pHs (3-11). Bioinformatics analysis showed that vB8388 is a linear double-stranded DNA virus that is 39,750 long with 50.65% G + C content and 44 putative open reading frames (ORFs). Phage vB8388 belongs to the family Autographviridae and possesses a non-contractile tail. The latency period of vB8388 was approximately 20 min. The combination of phage vB8388 and gentamicin, amikacin, or tobramycin could effectively inhibit the growth of K. oxytoca strain FK-8388, with a decrease of more than 4 log units within 12 h in vitro. Phage vB8388 showed a strong synergistic effect with gentamicin that could enhance the anti-biofilm effect of vB8388. The phage + gentamicin combination also showed synergy in vivo in the larval infection model of Galleria mellonella. In conclusion, the findings of this study suggest the potential of phage + antibiotic combination therapy to be used as an alternative therapeutic approach for treating infectious diseases caused by multidrug-resistant bacteria.


Assuntos
Aminoglicosídeos , Bacteriófagos , Animais , Aminoglicosídeos/farmacologia , Bacteriófagos/genética , Klebsiella oxytoca , Antibacterianos/farmacologia , Gentamicinas/farmacologia , Klebsiella pneumoniae
9.
Int J Biol Macromol ; 228: 773-782, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36577473

RESUMO

The current research includes the synthesis, improvement of NaCMC-cl-DMAA/AAc hydrogel and in-situ controlled release of gentamicin within various pH environments. The prepared hydrogel was then modified using boron nitride nanosheets aiming to enhancement in the adsorption rate. The prepared hydrogels were investigated by FTIR, XRD, FESEM, TGA/DSC, swelling and cell viability analysis. Cytotoxicity study indicated that prepared sample has a cytocompatibility nature towards healthy normal human cell line (FR2 cells). By changing the pH environment, the drug release properties of the hydrogels can be controlled. The cumulative rate of release for NaCMC-cl-DMAA/AAc hydrogel was 76.5 % at pH = 2.2 and 87.5 % at pH = 7.4. Whereas drug release rate for NaCMC-cl-DMAA/AAc-BNNSs hydrogel composite was 78.6 % at pH = 2.2 and 97.3 % at pH = 7.4 within 4320 min. Gentamicin release kinetics have been determined using the Korsemeyar-Peppas model, which confirms the drug release mechanism.


Assuntos
Carboximetilcelulose Sódica , Hidrogéis , Humanos , Hidrogéis/química , Carboximetilcelulose Sódica/química , Portadores de Fármacos/química , Gentamicinas/farmacologia , Liberação Controlada de Fármacos , Colo , Concentração de Íons de Hidrogênio
10.
Int J Pediatr Otorhinolaryngol ; 164: 111405, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36481814

RESUMO

OBJECTIVE: Aminoglycosides are relatively potent antibiotics used against some life-threatening infections but contribute to ototoxicity. Although the beneficial effects of high-dose nigella sativa oil (NSO) on ototoxicity in the form of intratympanic or oral use have been demonstrated, no variable-dose studies have been conducted on this subject. We aimed to investigate the potential protective effect of different doses of intraperitoneal (i.p.) NSO on Gentamicin (GM)-induced ototoxicity with auditory brainstem responses (ABR) testing. METHODS: Thirty adult male Sprague-Dawley rats (300-400 gr) were used in this study. Rats were randomly divided into 5 groups, with six animals in each group: All the groups received GM (120 mg/kg i.p) for ten days. Group 1: 0.9% saline solution (0.3 ml/kg i.p.), Group 2: NSOL (low dose 0.1 ml/kg i.p.), Group 3: NSOM (median dose 0.3 ml/kg i.p.), Group 4: NSOH (high dose 3 ml/kg i.p.), Group 5: NSOML (late onset median dose 0.3 ml/kg i.p) were given for fifteen days. But death occurred in 3 rats in group 4 and they were excluded from the study. The pretreatment and posttreatment ABR testings were performed. RESULTS: The posttreatment ABR results were compared with the pretreatment values. A significant difference was found in group 1 (p:0,002), group 2 (p: 0,040), and group 4 (p: 0,027). When the posttreatment tests were compared with each other, there was a significant difference between groups 1 and 2 (p < 0,001), groups 1 and 3 (p < 0,001), and groups 1 and 5 (p < 0,001). CONCLUSIONS: The administration of 0.1 ml/kg and 3 ml/kg dose of NSO does not prevent ototoxicity. The 0.3 ml/kg dose of NSO effectively prevents GM-induced ototoxicity within both prophylactic and therapeutic use.


Assuntos
Gentamicinas , Ototoxicidade , Ratos , Masculino , Animais , Ratos Sprague-Dawley , Gentamicinas/toxicidade , Ototoxicidade/etiologia , Ototoxicidade/prevenção & controle , Óleos Vegetais/farmacologia , Antibacterianos/toxicidade
11.
Int Immunopharmacol ; 114: 109578, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36525794

RESUMO

Acute kidney injury (AKI) is a challenging side effect which may clinically impede the use of gentamicin (GM). The present study explored the impact of liraglutide (Lir) on GM-induced kidney injury in rats. Lir (0.2 and 0.4 mg/kg, s.c) was given for 10 days (a dose/day) starting 3 days before giving GM (100 mg/kg, i.p) once daily for 7 days. Interestingly, Lir notably ameliorated GM-induced elevated levels of renal injury markers; urea and creatinine. Moreover, Lir remarkably mitigated malondialdehyde (MDA) level and elevated glutathione (GSH) level as well as superoxide dismutase (SOD) activity. Also, Lir pre-treatment notably diminished inflammatory markers levels; interleukin-1ß (IL-1ß), tumor necrosis factor alpha (TNF-α), vascular cell adhesion molecule (VCAM), monocyte chemoattractant protein 1 (MCP-1) and interferon gamma (INF-γ). In addition, Lir significantly replenished expression of Peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1α), Protein kinase A (PKA), cAMP response element-binding protein (CREB), nuclear Nuclear factor erythroid 2-related factor 2 (Nrf2), heme Oxygenase-1 (HO-1), B-cell lymphoma 2 (Bcl-2), and remarkably attenuated expression of Notch homolog 1 (Notch1), Hairy and enhancer of split-1 (Hes-1), Bcl-2-associated X (Bax), cleaved caspase 3 and nuclear Nuclear factor Kappa B (NF-κB (p65)). The nephroprotective activity of Lir was further confirmed by histopathological examination as well as transmission electron microscopy (TEM). In conclusion Lir achieved its nephroprotective effects through the amelioration of oxidative stress, inflammatory and apoptotic manifestations. It is worth-mentioning that the current study is the first to focus on the involvement of mitochondrial biogenesis and its upstream regulators, PKA/CREB and Notch/Hes-1 signaling pathways in the nephroprotective potentials of Lir. The attenuation of the aforementioned injurious aspects is partially attributed to the improvement of the mitochondrial status as demonstrated by elevated PGC-1α expression via acceleration of PKA/CREB and abatement of Notch/Hes-1 signaling pathways.


Assuntos
Injúria Renal Aguda , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico , Ratos , Animais , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Liraglutida/farmacologia , Liraglutida/uso terapêutico , Gentamicinas , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Biogênese de Organelas , Transdução de Sinais , NF-kappa B/metabolismo , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
12.
Life Sci ; 313: 121267, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36481167

RESUMO

AIMS: This study scrutinized α-Terpineol (α-T) for its anti-virulence and anti-fouling potential against P. aeruginosa PAO1 in conjunction with gentamicin (GeN) using in-vitro, in-silico, and in-vivo approaches. MAIN METHODS: The quorum quenching (QQ) potential of the drug combination was studied using a quorum sensing (QS) biosensor strain and tested for synergy using chequerboard and time-kill kinetics assays. The effect of α-T and GeN on bacterial motility, QS-regulated virulence factor production, and biofilm formation was assessed in P. aeruginosa PAO1 along with molecular docking analysis. The protective effects of α-T-GeN combination were also examined in a Caenorhabditis elegans infection model through slow-killing (SK) assays. KEY FINDINGS: The drug combination displayed synergy, enhanced QQ activity, and suppressed AHL production in PAO1. At sub-inhibitory concentrations, the drug combination suppressed the expression of genes regulating QS and pseudomonal virulence, thereby inhibiting the production of virulence factors in PAO1. The drug combination compromised all forms of pseudomonal motility, strongly inhibited biofilm formation, and successfully eradicated preformed biofilms. Based on these findings, it is concluded that GeN (alone) does not harbor any QQ properties, but enhances the QQ potential of α-T. Moreover, combinational treatment protected C. elegans from pseudomonal infection and improved survival rates by 73 % at 96 h. SIGNIFICANCE: For the first time, the molecular mechanism responsible for the anti-QS activity of α-T was unraveled through a comprehensive investigation, thereby asserting its potential as an anti-virulent drug against P. aeruginosa.


Assuntos
Infecções por Pseudomonas , Percepção de Quorum , Animais , Caenorhabditis elegans/metabolismo , Gentamicinas/farmacologia , Simulação de Acoplamento Molecular , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Biofilmes , Fatores de Virulência/genética , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Pseudomonas aeruginosa
13.
Biomed Res Int ; 2022: 1373160, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36467883

RESUMO

Convolvulus arvensis L. is rich in phenolic compounds and traditionally used to treat wounds, skin ulcer, and inflammation. The current study is aimed at scientifically potentiating its traditional wound healing use. The methanolic extract of C. arvensis stem (CaME) was analyzed for HPLC and GC-MS analyses. The binding modes of active compounds were investigated against protein targets glycogen synthase kinase-3ß (GSK-3ß), transforming growth factor-beta (TGF-ß), c-myc, and ß-catenin by molecular docking followed by molecular dynamic simulations which revealed some conserved mode of binding as reported in crystal structures. The antioxidant potential of CaME was evaluated by in vitro methods such as 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, hydrogen peroxide scavenging, and ferric reducing power assays. Ointment formulations of 10 and 20% CaME were applied topically and evaluated for wound healing potency against the excisional wound on the skin of Wistar rats. Gentamycin (0.1%) served as standard therapy. The healing process was observed for 20 days in the form of wound size and epithelialization followed by histopathological evaluation of the wound area. Chemical characterization showed the presence of 7-hexadecenoic acid, 2-hexadecylicosan-1-ol, quercetin, gallic acid, ferulic acid, and other compounds. The plant extract exhibited significant in vitro antioxidant activity. The animals treated with 10% ointment showed moderate healing, whereas the treatment with 20% CaME revealed healing potential comparable to the standard 0.1% gentamycin as coevidenced from histopathological evaluation of skin. The study corroborates promising potential of C. arvensis on the healing of wounds, which possibly will be attributed to its antioxidant activity, fatty acids, quercetin, and gallic and caffeic acids, and binding potential of its phytoconstituents (phenolic acids) with wound healing targets.


Assuntos
Convolvulus , Ratos , Animais , Ratos Wistar , Metanol , Pomadas , Quercetina , Antioxidantes/farmacologia , Glicogênio Sintase Quinase 3 beta , Simulação de Acoplamento Molecular , Cicatrização , Emolientes , Extratos Vegetais/farmacologia , Gentamicinas
14.
West Afr J Med ; 39(11): 1148-1155, 2022 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-36453526

RESUMO

BACKGROUND: Staphylococcus aureus is a cosmopolitan and pathogenic microorganism associated with various diseases spectra and antimicrobial resistance of public health importance. AIM: This study determined the phenotypic characteristics of S. aureus isolated from patients in healthcare institutions in Zaria metropolis. STUDY DESIGN: A cross-sectional hospital-based study was carried out in 5 healthcare institutions. Four hundred and twenty clinical samples were collected and analyzed. RESULTS: Majority of the patients (54.3%) were within the age range 21-40 years and mean age of 26.04 ± 12 years. Approximately, 70% of the respondents had history of antibiotic use prior to consultation in the hospitals and were self-prescribed, and 91.2% were outpatients. The most commonly abused antibiotics were ampicillin-cloxacillin (19.5%) and cotrimoxazole (10.0%), and the mean duration of their use was 3.5 ± 1.3 days. The detection rate for S. aureus was 10% and 5.2% for MRSA. The S. aureus isolates showed the highest frequency of resistance against ampicillin 42 (100%), followed by penicillin G 39 (92.9%) and least was to gentamicin 5 (11.9%). The frequency of resistance for the MRSA were ampicillin 22 (100%), penicillin G 21(95.5%) and least was to gentamicin 2 (9.1%). The minimum inhibitory concentrations of oxacillin were greater than 128 µg /ml. CONCLUSION: The detection rate of S. aureus and MRSA strains are of great public health concern which requires continuous health education on rational use of antibiotics among others.


CONTEXTE: Staphylococcus aureus est un micro-organisme cosmopolite et pathogène associé à divers spectres de maladies et à une résistance aux antimicrobiens d'importance pour la santé publique. OBJECTIF: Cette étude a permis de déterminer les caractéristiques phénotypiques de S. aureus isolé chez des patients dans des établissements de santé de la métropole de Zaria. PLAN DE L'ÉTUDE: Une étude transversale en milieu hospitalier a été menée dans 5 établissements de santé. Quatre cent vingt échantillons cliniques ont été recueillis et analysés. RÉSULTATS: La majorité des patients (54,3 %) étaient âgés de 21 à 40 ans et l'âge moyen était de 26,04 ± 12 ans. Environ 70 % des répondants avaient des antécédents d'utilisation d'antibiotiques avant la consultation dans les hôpitaux et étaient auto-prescrits, et 91,2 % étaient des patients externes. Les antibiotiques les plus fréquemment utilisés étaient l'ampicillinecloxacilline (19,5 %) et le cotrimoxazole (10,0 %), et la durée moyenne de leur utilisation était de 3,5 ± 1,3 jours. Le taux de détection de S. aureus était de 10 % et de 5,2 % pour le SARM. Les isolats de S. aureus ont montré la plus grande fréquence de résistance à l'ampicilline 42 (100%), suivie de la pénicilline G 39 (92,9%) et la plus faible à la gentamicine 5 (11,9%). La fréquence de résistance pour le SARM était de 22 (100%) pour l'ampicilline, 21 (95,5%) pour la pénicilline G et 2 (9,1%) pour la gentamicine. Les concentrations minimales inhibitrices de l'oxacilline étaient supérieures à 128 µg /ml. CONCLUSION: Le taux de détection des souches de S. aureus et de SARM est un grand problème de santé publique qui nécessite une éducation sanitaire continue sur l'utilisation rationnelle des antibiotiques entre autres. Mots clés: S. aureus, MRSA, phénotype, résistance aux antimicrobiens, patients d'hôpitaux, Nigeria.


Assuntos
Infecções Estafilocócicas , Staphylococcus aureus , Humanos , Adolescente , Adulto Jovem , Adulto , Nigéria/epidemiologia , Estudos Transversais , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/epidemiologia , Oxacilina/farmacologia , Ampicilina , Antibacterianos/farmacologia , Gentamicinas , Atenção à Saúde
15.
Artigo em Inglês | MEDLINE | ID: mdl-36529133

RESUMO

Abstract: From 1 January to 31 December 2021, forty-eight institutions around Australia participated in the Australian Staphylococcus aureus Surveillance Outcome Programme (ASSOP). The aim of ASSOP 2021 was to determine the proportion of Staphylococcus aureus bacteraemia (SAB) isolates in Australia that were antimicrobial resistant, with particular emphasis on susceptibility to methicillin and on characterisation of the molecular epidemiology of the methicillin-resistant isolates. A total of 2,928 SAB episodes were reported, of which 78.4% were community-onset. Overall, 16.9% of S. aureus isolates were methicillin resistant. The 30-day all-cause mortality associated with methicillin-resistant SAB was 15.0%, which was not significantly different from the 14.4% all-cause mortality associated with methicillin-susceptible SAB (p = 0.7). With the exception of the ß-lactams and erythromycin, antimicrobial resistance in methicillin-susceptible S. aureus was rare. However, in addition to the ß-lactams, approximately 36% of methicillin-resistant S. aureus (MRSA) were resistant to ciprofloxacin; 30% to erythromycin; 15% to tetracycline; 16% to gentamicin; and 3% to co-trimoxazole. When applying the European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints, teicoplanin resistance was detected in three S. aureus isolates. Resistance to vancomycin or linezolid was not detected. Resistance to non-ß-lactam antimicrobials was largely attributable to the healthcare-associated MRSA (HA-MRSA) clone ST22-IV [2B] (EMRSA-15), and the community-associated MRSA (CA-MRSA) clone ST45-V [5C2&5] which has acquired multiple antimicrobial resistance determinants including ciprofloxacin, erythromycin, clindamycin, gentamicin and tetracycline. The ST22-IV [2B] (EMRSA-15) clone is the predominant HA-MRSA clone in Australia. Nonetheless, 85% of methicillin-resistant SAB episodes were due to CA-MRSA clones. Although polyclonal, approximately 68% of CA-MRSA clones were characterised as ST93-IV [2B] (Queensland clone); ST45-V [5C2&5]; ST5-IV [2B]; ST1-IV [2B]; ST30-IV [2B]; and ST97-IV [2B]. As CA-MRSA is well established in the Australian community, it is important to monitor antimicrobial resistance patterns in community- and healthcare-associated SAB as this information will guide therapeutic practices in treating S. aureus bacteraemia.


Assuntos
Anti-Infecciosos , Bacteriemia , Infecção Hospitalar , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Humanos , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus , Bacteriemia/epidemiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Ágar/uso terapêutico , Austrália/epidemiologia , Meticilina/uso terapêutico , Testes de Sensibilidade Microbiana , Infecção Hospitalar/tratamento farmacológico , Farmacorresistência Bacteriana , Gentamicinas/uso terapêutico , Eritromicina/uso terapêutico , Ciprofloxacina/uso terapêutico , Tetraciclina/uso terapêutico
16.
PLoS One ; 17(12): e0277522, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36480529

RESUMO

The repair of infected bone defects remains a clinical challenge. Staphylococcus aureus is a common pathogenic micro-organism associated with such infections. Gentamycin (GM) is a broad spectrum antibiotic that can kill S. aureus in a dose-dependent manner. However, the systemic administration of antibiotics may lead to drug resistance and gut dysbiosis. In this work, we constructed ß-tricalcium phosphate/gelatin composite scaffolds incorporated with gentamycin-loaded chitosan microspheres (CMs(GM)-ß-TCP/gelatin composite scaffolds), which helped optimize the local GM release in the infected defect areas and enhance bone regeneration. The cumulative release curves showed that both microspheres and composite scaffolds reached a sustained slow-release phase after the initial rapid release, and the latter further stabilized the initial drug release rate. The release curve of CMs(GM)-ß-TCP/gelatin composite scaffolds reached a plateau after 24 h, and the cumulative release reached 41.86% during this period. Moreover, the combination of ß-TCP and gelatin mimicked bone composition and were able to provide the requisite mechanical strength (0.82 ± 0.05 MPa) during the first phase of bone generation. The inner structure of the scaffold was arranged in the shape of interconnected pores, and presented a porosity level of 16%. The apertures were uniform in size, which was beneficial for cell proliferation and material transportation. Macroscopic observation and histological analysis showed that CMs(GM)-ß-TCP/gelatin composite scaffolds fused with bone tissues, and new tissues were formed in defect areas without any infection. This new composite scaffold may be a promising repair material for treating infected bone defects.


Assuntos
Quitosana , Gelatina , Gentamicinas/uso terapêutico , Staphylococcus aureus
17.
World J Microbiol Biotechnol ; 39(2): 45, 2022 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-36534183

RESUMO

To tackling antibiotic resistance and the appearance of multidrug-resistant (MDR) strains, one current approach is the combined use of biosurfactants with antibiotics to increase their efficacy. The antimicrobial ability of biosurfactant produced by Shewanella algae strain B12 was examined using the agar well diffusion method versus some resistant Gram-negative and Gram-positive bacteria. The Minimum Inhibitory Concentration (MIC) of Glycolipid-Biosurfactant of B12 (GBB12) was performed by the broth dilution technique. The inhibition of biofilm formation, disruption of biofilm, and reducing the population of viable cells in biofilm were evaluated by the microtiter plate method. Finally, Scanning Electron Microscopy (SEM) analysis was used to confirm the disruption of the cell membrane by GBB12. In all experiments, when GBB12 was added to antibiotics (except Amikacin), the antimicrobial activity was increased. The synergistic effects of GBB12 and antibiotics (Ciprofloxacin and Gentamycin) against Methicillin-Resistant Staphylococcus aureus (MRSA) and Acinetobacter baumannii were confirmed by the Fractional Inhibitory Concentration Index (FICI). GBB12-Gentamycin mixture almost completely inhibits the formation of A. baumannii biofilm, reaching 99.8% inhibition. Also, the rate of MRSA biofilm inhibition treated with GBB12-Ciprofloxacin mixture was found to be 99.4%. biosurfactant-antibiotic mixture could be adequate replacements for traditional antibiotics in the near future. This study shows the potential of GBB12 as antimicrobial and antibiofilm agent.


Assuntos
Acinetobacter baumannii , Anti-Infecciosos , Staphylococcus aureus Resistente à Meticilina , Antibacterianos/farmacologia , Plâncton , Anti-Infecciosos/farmacologia , Ciprofloxacina/farmacologia , Biofilmes , Gentamicinas/farmacologia , Testes de Sensibilidade Microbiana
18.
Molecules ; 27(23)2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36500657

RESUMO

Gentamicin (GEN) is a kind of aminoglycoside antibiotic with the adverse effect of nephrotoxicity. Currently, no effective measures against the nephrotoxicity have been approved. In the present study, epigallocatechin gallate (EG), a useful ingredient in green tea, was used to attenuate its nephrotoxicity. EG was shown to largely attenuate the renal damage and the increase of malondialdehyde (MDA) and the decrease of glutathione (GSH) in GEN-injected rats. In NRK-52E cells, GEN increased the cellular ROS in the early treatment phase and ROS remained continuously high from 1.5 H to 24 H. Moreover, EG alleviated the increase of ROS and MDA and the decrease of GSH caused by GEN. Furthermore, EG activated the protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). After the treatment of GEN, the protein level of cleaved-caspase-3, the flow cytometry analysis and the JC-1 staining, the protein levels of glutathione peroxidase 4 (GPX4) and SLC7A11, were greatly changed, indicating the occurrence of both apoptosis and ferroptosis, whereas EG can reduce these changes. However, when Nrf2 was knocked down by siRNA, the above protective effects of EG were weakened. In summary, EG attenuated GEN-induced nephrotoxicity by suppressing apoptosis and ferroptosis.


Assuntos
Gentamicinas , Fator 2 Relacionado a NF-E2 , Ratos , Animais , Gentamicinas/efeitos adversos , Fator 2 Relacionado a NF-E2/metabolismo , Apoptose , Rim , Malondialdeído/metabolismo , Glutationa/metabolismo
19.
BMC Vet Res ; 18(1): 452, 2022 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-36572871

RESUMO

BACKGROUND: The Prototheca algae have recently emerged as an important cause of bovine mastitis globally. Isolates from bovine mastitis in several countries were nearly all identified as P. bovis, suggesting that it was the main causative agent of bovine protothecal mastitis. The aim of the present study was to evaluate the presence and isolation of Prototheca spp. in dairy farms, detect the genetic diversity among strains, determine the capacity of producing biofilm and their resistance to antifungal and antimicrobial drugs. RESULTS: A total of 48 Prototheca isolates from four different farms were randomly selected to be investigated. Multiplex PCR showed all isolated colonies were Prototheca bovis. Performing RAPD-PCR by using OPA-4 primer, it was revealed that there was a clear amplification pattern. Different levels of biofilm production were observed among strains. Among 48 isolates, only 4 of them (8.33%) showed strong biofilm production. By using E-test strips, amphotericin B was able to inhibit the growth of all the strains tested. Disc diffusion method used for antimicrobial sensitivity test showed that the highest activity was demonstrated by gentamicin and colistin with 95.83% (46/48) and 89.58% (43/48) of sensitive strains, respectively. CONCLUSIONS: The present study showed that RAPD-PCR was a rapid tool for discriminating P. bovis strains. Also, gentamicin and colistin can be considered as potential antimicrobial drugs which can prevent the growth of the mentioned strains in vitro, although there is no effective clinical treatment yet. Further studies are needed in order to detect an effective clinical therapy considering biofilm production by Prototheca spp. and their probable role in Prototheca pathogenicity.


Assuntos
Anti-Infecciosos , Doenças dos Bovinos , Mastite Bovina , Prototheca , Bovinos , Feminino , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Prototheca/genética , Técnica de Amplificação ao Acaso de DNA Polimórfico/veterinária , Mastite Bovina/tratamento farmacológico , Mastite Bovina/microbiologia , Colistina/farmacologia , Farmacorresistência Bacteriana/genética , Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêutico , Biofilmes , Gentamicinas/farmacologia
20.
Urogynecology (Hagerstown) ; 28(12): 825-833, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36409639

RESUMO

IMPORTANCE: Currently available evidence for efficacy of postoperative antibiotics to prevent postoperative urinary tract infection (UTI) conflicts. Oral antibiotics rely on patient adherence and can cause unwanted systemic effects. Gentamicin is a broad-spectrum antibiotic with rapid bactericidal activity and, when administered intravesically, has no systemic absorption through intact urothelium. OBJECTIVE: We aimed to determine whether a single intravesical instillation of gentamicin at the conclusion of urogynecologic surgery would reduce the proportion of women treated for UTI within 6 weeks postoperatively compared with sham instillation. STUDY DESIGN: This was a multicenter, randomized (stratified by study site, route of prolapse repair ±suburethral sling, with balanced 1:1 randomization), participant-masked, sham-controlled, study. The primary outcome was the proportion of participants treated with antibiotics for UTI within 6 weeks postoperatively. An adjusted multivariable logistic regression model was constructed to determine predictors of postoperative UTI treatment. RESULTS: Three hundred seventy participants were randomized (gentamicin, 185; sham, 185), and data from 363 participants were analyzed (gentamicin, 183; sham, 180). Nineteen women in the gentamicin group and 20 women in the sham group were treated for UTI within 6 weeks postoperatively (10.4% vs 11.1%, P = 0.87). There were no adverse events related to the instillations. Increasing age (odds ratio, 1.028 [1.000-1.057]) and number of intraoperative transurethral instrumentations (odds ratio, 1.342 [1.080-1.668]) were independent predictors of postoperative UTI treatment. CONCLUSIONS: In women undergoing urogynecologic surgery, postoperative intravesical gentamicin did not reduce the incidence of postoperative UTI. The number of intraoperative transurethral instrumentations is an important, potentially modifiable risk factor for postoperative UTI treatment.


Assuntos
Slings Suburetrais , Infecções Urinárias , Humanos , Feminino , Gentamicinas/efeitos adversos , Administração Intravesical , Infecções Urinárias/epidemiologia , Slings Suburetrais/efeitos adversos , Antibacterianos/efeitos adversos
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