Gentamicin Treatment Research Articles

Effect of calcium acetate and quercetin on gentamicin-induced nephrotoxicity in rat

Objective: The present work was conducted to evaluate the possible renoprotective effect of both calcium acetate and quercetin against gentamicin-induced nephrotoxicity in rat. Design: Controlled study. Animals: Seven groups of male albino rats. Procedures: Seventy, apparently healthy, male albino rats were haphazardlydivided into seven equal groups. Group 1: injected I.P with normal saline (control), Group 2: received gentamicin (80 mg/kg/d, I.P for 7 consecutive days), Group 3: received gentamicin plus lower dose of calcium acetate (75 mg/kg/d, orally for 7 consecutive days) simultaneously, Group 4: received gentamicin plus higher dose of calcium acetate (200 mg/kg/d, orally for 7 consecutive days) simultaneously, Group 5: received gentamicin; afterwards, rats were treated with quercetin (50 mg/kg/d, orally for 7 consecutive days, Group 6: received quercetin; afterwards, rats were simultaneously treated with gentamicin plus quercetin with the same doses, and Group 7: received gentamicin, calcium acetate (lower dose), and quercetin simultaneously. Results: The study demonstrated the nephrotoxic impacts of gentamicin biochemically and histopathologically. Gentamicin treatment induced a significant increase in blood urea nitrogen (BUN) and serum creatinine levels besides a significant elevation in C-reactive protein (CRP) level. The significant increase in the tissue malondialdehyde(MDA) level and the significant reduction in the tissue superoxide dismutase(SOD) and glutathione(GSH) levels demonstrated that gentamicin-induced nephrotoxicity was mediated through oxidative stress reactions. Gentamicin-induced degenerative changes in renal tubules and glomeruli were also reported. Conclusion and clinical relevance: The use of both calcium acetate (lower and higher doses) or quercetin (therapeutically and prophylactically) in combination with gentamicin significantly minimized its nephrotoxicity as revealed from decreasing BUN, serum creatinine, CRP levels, oxidative stress reactions, and histopathological alterations with better protective effect of quercetin than Ca acetate. Co-administration of both calcium acetate and quercetin with gentamicin could prevent gentamicin-induced nephrotoxicity.

Effect of fermented milk from Lactococcus lactis ssp. cremoris strain JFR1 on Salmonella invasion of intestinal epithelial cells

The process of fermentation contributes to the organoleptic properties, preservation, and nutritional benefits of food. Fermented food may interfere with pathogen infections through a variety of mechanisms, including competitive exclusion or improving intestinal barrier integrity. In this study, the effect of milk fermented with Lactococcus lactis ssp. cremoris JFR1 on Salmonella invasion of intestinal epithelial cell cultures was investigated. Epithelial cells (HT29-MTX, Caco-2, and cocultures of the 2) were treated for 1 h with Lactococcus lactis ssp. cremoris JFR1 fermented milk before infection with Salmonella enterica ssp. enterica Typhimurium. Treatment with fermented milk resulted in increased transepithelial electrical resistance, which remained constant for the duration of infection (up to 3 h), illustrating a protective effect. After gentamicin treatment to remove adhered bacterial cells, enumeration revealed a reduction in numbers of intracellular Salmonella. Quantitative reverse-transcription PCR data indicated a downregulation of Salmonella virulence genes hilA, invA, and sopD after treatment with fermented milk. Fermented milk treatment of epithelial cells also exhibited an immunomodulatory effect reducing the production of proinflammatory IL-8. In contrast, chemically acidified milk (glucono delta-lactone) failed to show the same effect on monolayer integrity, Salmonella Typhimurium invasion, and gene expression as well as immune modulation. Furthermore, an oppA knockout mutant of Salmonella Typhimurium infecting treated epithelial cells did not show suppressed virulence gene expression. Collectively, these results suggest that milk fermented with Lactococcus lactis ssp. cremoris JFR1 is effective in vitro in the reduction of Salmonella invasion into intestinal epithelial cells. A functional OppA permease in Salmonella is required to obtain the antivirulence effect of fermented milk.

Effect Of Calcium Acetate And QuercetinOn Gentamicin‐Induced Nephrotoxicity In Rat

The present work was conducted to evaluate the possible renoprotective effect of both calcium acetate and quercetin against gentamicin-induced nephrotoxicity in rat. Seventy, apparently healthy, male albino rats were haphazardlydivided into seven equal groups. group 1: injected I.P with normal saline (control), group 2: received gentamicin (80 mg/kg/d, I.P for 7 consecutive days), group 3: received gentamicin plus lower dose of calcium acetate (75 mg/kg/d, orally for 7 consecutive days) simultaneously, group 4: received gentamicin plus higher dose of calcium acetate (200 mg/kg/d, orally for 7 consecutive days) simultaneously, group 5: received gentamicin; afterwards, rats were treated with quercetin (50 mg/kg/d, orally for 7 consecutive days, group 6: received quercetin; afterwards, rats were simultaneously treated with gentamicin plus quercetin with the same doses, and group 7: received gentamicin, calcium acetate (lower dose), and quercetin simultaneously. The study demonstrated the nephrotoxic impacts of gentamicin biochemically and histopathologically. Gentamicin treatment induced a significant increase in blood urea nitrogen (BUN) and serum creatinine levels besides a significant elevation in C-reactive protein (CRP) level. The significant increase in the tissue malondialdehyde(MDA) level and the significant reduction in the tissue superoxide dismutase(SOD) and glutathione(GSH) levels demonstrated that gentamicin-induced nephrotoxicity was mediated through oxidative stress reactions. Gentamicin-induced degenerative changes in renal tubules and glomeruli were also reported. The use of both calcium acetate (lower and higher doses) or quercetin (therapeutically and prophylactically) in combination with gentamicin significantly minimized its nephrotoxicity as revealed from decreasing BUN, serum creatinine, CRP levels, oxidative stress reactions, and histopathological alterations with better protective effect of quercetin than Ca acetate. Co-administration of both calcium acetate and quercetin with gentamicin could prevent gentamicin-induced nephrotoxicity.

Use of antibiotics to control endophytic bacterial growth migration onto culture medium in Eucalyptus cloeziana F.Muell.: a micropropagation approach

The natural endophytic bacterial growth migration onto a culture medium is commonly associated with unnecessary microplant discards. In micropropagation procedures, some bacteria can exude from the internal tissues of plants to colonize the culture medium and compete with the plants for nutrients, which may lead to a reduction in plant development. To find an efficient antibiotic protocol to control this bacterial growth migration onto the culture medium without affecting plant development, Eucalyptus cloeziana F.Muell. microstumps were subjected to four antibiotic treatments for 30 d. They were treated with gentamicin, ciprofloxacin, rifampicin, or Timentin®, in addition to the control treatment (antibiotic free). The effects of the antibiotics were monitored weekly, and the endophytic bacterial community structures were evaluated in two periods of plant development (15 d and 30 d).The denaturing gradient gel electrophoresis (DGGE) technique was used to compare the control and post-antibiotic treatment plant microbiological composition, to determine if the antibiotic treatment played a specific role on the endophytic bacterial community structure. The gentamicin treatment was composed of a distinct community from the control treatment. Nonetheless, the plants treated with ciprofloxacin and rifampicin manifested similar endophytic community structures compared to the control. In contrast, plants treated with Timentin® showed a specific bacterial community composition and a higher plant dry mass, number of shoots, and nutritional content. These results suggested that Timentin® treatment could be applied for 30 days to control endophytic bacterial growth migration onto the culture medium, without affecting the homeostatic balance between the bacteria and plants.

Intestinal IL-17R signaling controls liver inflammation by constraining microbiome induced TLR9 signaling and IL-18 production

Abstract Th17 cells and the intestinal microbiome have been linked to liver diseases such as autoimmune and viral hepatitis. Patients exhibit intestinal dysbiosis and increased bacterial translocation. In a mouse model of T cell mediated liver inflammation, concanavalin A (Con A) hepatitis, global Il17ra deficiency and gentamicin treatment are protective. Yet, it is unknown if IL-17 contributes to microbial dysbiosis and bacterial translocation in hepatitis, and how these factors together affect disease. To study this, we generated intestinal epithelial-specific IL-17RA deficient mice (Il17rafl/flx villin cre+ mice). Absence of enteric IL-17R signaling induced commensal dysbiosis and increased intestinal Th17 cells and Il18. These mice were more susceptible to Con A, exhibiting worsened liver damage and lethality. Single cell RNA sequencing partnered with protein-based assays revealed elevated liver IL-18, IFNγ, and FasL in Il17rafl/flx villin cre+ mice, while cohousing and antibiotic studies implicated the microbiome in disease exacerbation. Il17rafl/flx villin cre+ mice also had increased liver CpG levels, which induced IL-18. Moreover, anti-IL18 ameliorated Con A hepatitis. We propose that disrupted enteric IL-17 signaling promotes intestinal dysbiosis and translocation of CpG to the liver, stimulating TLR9 and IL-18 production. IL-18 then induces hepatic lymphocyte activation and cell death to worsen inflammation. Understanding the mechanism underlying exacerbated disease in Il17rafl/flx villin cre+ mice will elucidate the role of enteric Th17 and the microbiome in hepatitis, with broader implications on the effects of impaired intestinal immunity and subsequent release of microbial products seen in other diseases.

Downregulated UCHL1 Accelerates Gentamicin-Induced Auditory Cell Death via Autophagy.

The clinical use of aminoglycoside antibiotics is partly limited by their ototoxicity. The pathogenesis of aminoglycoside-induced ototoxicity still remains unknown. Here, RNA-sequencing was conducted to identify differentially expressed genes in rat cochlear organotypic cultures treated with gentamicin (GM), and 232 and 43 genes were commonly up- and downregulated, respectively, at day 1 and 2 after exposure. Ubiquitin carboxyl-terminal hydrolase isozyme L1 (Uchl1) was one of the downregulated genes whose expression was prominent in spiral ganglion cells (SGCs), lateral walls, as well as efferent nerve terminal and nerve fibers. We further investigated if a deficit of Uchl1 in organotypic cochlea and the House Ear Institute-Organ of Corti 1 (HEI-OC1) cells accelerates ototoxicity. We found that a deficit in Uchl1 accelerated GM-induced ototoxicity by showing a decreased number of SGCs and nerve fibers in organotypic cochlear cultures and HEI-OC1 cells. Furthermore, Uchl1-depleted HEI-OC1 cells revealed an increased number of autophagosomes accompanied by decreased lysosomal fusion. These data indicate that the downregulation of Uchl1 following GM treatment is deleterious to auditory cell survival, which results from the impaired autophagic flux. Our results provide evidence that UCHL1-dependent autophagic flux may have a potential as an otoprotective target for the treatment of GM-induced auditory cell death.

Baicalin attenuates gentamicin-induced cochlear hair cell ototoxicity.

Gentamicin can lead to cochlear hair cells associated ototoxicity by inducing apoptosis and oxidative stress, which can be alleviated by baicalin, one flavonoid extracted from the root of Scutellaria baicalensis. The role of baicalin in protecting gentamicin-induced hearing loss is unclear. Interference with oxidative stress was investigated in this study using House Ear Institute-Organ of Corti1 (HEI-OC1) cells, which were simultaneously treated with baicalin (0-400μm) and gentamicin (0.2 or 1mm). MTT was used to assay cell viability and apoptosis was detected with Annexin V-fluorescein isothiocyanate staining. The production of reactive oxygen species was indicated by 2,7-dichlorofluorescein diacetate fluorescence intensity and mitochondrial depolarization was assayed by JC1-mitochondrial membrane potential assay. Poly(ADP-ribose) polymerase (PARP), cleaved-caspase 3 and cleaved-PARP expression were analyzed with western blot. Baicalin improved the viability of HEI-OC1 cells and significantly reduced the oxidative stress and mitochondrial depolarization compared with the gentamicin treatment group. Gentamicin treatment increased the activation of PARP and caspase-3, while such an increase could be downregulated by baicalin. Baicalin attenuates gentamicin-induced cochlear hair cells ototoxicity, and such inhibition may be mediated by the regulation of reactive oxygen species production, mitochondrial depolarization, and caspase-3 and PARP activation.

Nephroprotective properties of the methanol stem extract of Abrus precatorius on gentamicin‐induced renal damage through suppression of NF‐κB/CRP and enhancement of Bcl‐2 signaling pathways

The nephroprotective properties of methanol stem bark extract of Abrus precatorius against gentamicin‐induced renal damage in rats was evaluated in this study. Thirty (30) male Wistar rats were divided into five equal groups. Group A was the negative control group while B was the positive control group which received gentamicin 100 mg/kg intra‐peritoneally for six days. Group C were pretreated with 100 mg/kg extract for the three days and then concurrently with gentamicin 100 mg/kg for three days and group D were pretreated with 200 mg/kg extract for three days and then concurrently with gentamicin 100mg/kg for three days. Group E received gentamicin intraperitoneally for six days followed by administration of 200 mg/kg of the extract for 3 days. Blood samples, kidneys and kidney homogenates were collected for haematological, biochemical, histopathological and immunohistochemical analysis. The results showed that no significant haematological changes were noted. The groups treated with extract exhibited significant increase in body weight gain. While group B significantly exhibited focal areas of inflammation, fatty degeneration, congestion of vessels, tubular necrosis and glomerular atrophy, the lesions were mild with the treated groups. Treated groups exhibited a dose dependent significant decrease in serum creatinine, urea, XO, NO and Myeloperoxidase, AOPP, Protein carbonyl, H2O2, MDA levels when compared with gentamicin treatment group. There were significant dose dependent improvements in SOD, GST, GSH, Protein thiol, and non‐protein thiol levels in the treated groups when compared with group B. In immunohistochemistry, gentamicin treatment group exhibited over expression of CRP and NF‐κB levels, and marked reduction in expression of Bcl‐2 while the reverse was seen in the groups treated with methanol extracts of Abrus precatorius.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Adjunctive gentamicin did not improve outcome of enterococcal bacteraemia in neutropenic patients: a propensity scored matched study

Background: Patients with haematologic malignancies receiving chemotherapy have a high risk of developing febrile neutropenia and bloodstream infections. The benefit of adjunctive gentamicin treatment for enterococcal bloodstream infections is debated. In this study, we compare the treatment outcome of a cell wall-active antibiotic with and without gentamicin for enterococcal bacteraemia in patients with neutropenia.Methods: The observational study was performed from 1999 through 2016. Patients with bacteraemia due to non-high level gentamicin-resistant enterococci were included. Analyses were performed in two data sets of episodes with enterococcal bacteraemia. One data set consisting of all included episodes (full cohort, n = 154) and one with propensity score-matched episodes (n = 96). The primary endpoint was death within 30 days, and the secondary outcomes were defervescence and persistence of enterococcal bloodstream infection after initiation of anti-enterococcal therapy.Results: Episodes with gentamicin treatment (n = 82, full cohort; n = 48, propensity score-matched cohort) were comparable with episodes without gentamicin treatment (n = 72, full cohort; n = 48, propensity score-matched cohort) with regard to patient- and disease-related characteristics. Enterococcus faecium (40.9%) was the most frequently isolated organism. In the propensity score-matched cohort, there was no difference in 30-days mortality (14.6% in episodes with gentamicin versus 16.7% in episodes without gentamicin, p = 1), median time to defervescence (1 versus 2 days, p = .37) or persistence of enterococcal bloodstream infection for ≥72 h (9.4% versus 7.5%, p = 1).Conclusions: In our study with neutropenic patients, treatment with a cell wall-active antibiotic without adjunctive gentamicin for episodes with enterococcal bloodstream infection was as effective as combination therapy with gentamicin.

Clinical features and management of Meniere's disease patients with drop attacks.

The aims of the present study are to investigate the variations in clinical features, including medical history, hearing function, vestibular function, and degree of endolymphatic hydrops (EH), in Meniere's disease (MD) patients with and without drop attacks (DAs), and to examine the efficacy of intratympanic gentamicin (ITG) treatment in alleviating DAs. In total, 177 unilateral definite MD patients, including 16 patients with DAs and 161 patients without DAs, were enrolled. The results of hearing test, vestibular-evoked myogenic potentials (VEMPs), and magnetic resonance imaging (MRI) were analyzed. Thirteen patients with DAs received a single ITG treatment and were followed up. The disease course of MD in the DA group was significantly longer than that in the control group (p = 0.007). MD patients with DAs had significantly greater hearing loss and worse EH than MD patients without DAs (p < 0.05). However, there was no between-group difference in vestibular function. In the study, 92.31% of refractory definite MD patients with DAs achieved satisfactory control of DAs after ITG treatment. MD patients with DAs tend to suffer from severe hearing loss and a significant degree of EH in the inner ear. However, the vestibular function of MD patients with DAs may not be completely abolished, but be sensitive to stimulating signals. ITG treatment, which helps to decrease vestibular sensitivity, was an effective treatment to control DAs.

Delayed Effect and Gain Restoration After Intratympanic Gentamicin for Menière's Disease

This study aimed to evaluate the changes in the VOR gain after intratympanic gentamicin therapy and to correlate them with the mid-term effects on the control of vertigo, in a population of Menière's disease patients. The study design was a prospective "Outcomes research." Tertiary referral center. This study included 20 patients with unilateral Menière's disease refractory to medical therapy for at least 1 year, and treated with an on demand intratympanic gentamicin protocol. Therapeutic. Audiometry, caloric testing, and a vHIT before beginning the protocol were performed. Patients underwent weekly vHIT assessments until a significant gain reduction was observed. Subsequently we performed vHIT tests 1 month after the therapy completion, and then every 3 months for at least 1 year. Complete vertigo control (class A) was achieved in 14 patients at the 12-month follow-up assessment. We observed a significant reduction in VOR gain values at the 3-week follow-up assessment. We found a significant correlation between the 1-month posttreatment ipsilateral hVOR gain and the rate of vertigo recurrence after the first IT gentamicin treatment (p = 0.012; r = 0.400). At the mid-term assessment, 10 patients exhibited a significant partial recovery of the hVOR gain. The delayed effect of intratympanic gentamicin and the subsequent gain restoration are factors that may influence the patients' outcome. The feasibility of the vHIT system makes it a useful tool to monitorize the VOR changes.

Surface‐Enhanced Raman Spectroscopy for the Detection of a Metabolic Product in the Headspace Above Live Bacterial Cultures

AbstractIn situ surface‐enhanced Raman spectra of the headspace above cultures of six bacterial species showed strong characteristic bands from chemisorbed methyl sulfide. This marker compound is created by dissociation of dimethyl disulfide (DMDS), a fermentative metabolite of bacteria, on the surface of the enhancing Au or Ag nanoparticle films. Kinetic binding plots of media spiked with DMDS and of live cultures showed that the Au‐based substrates were more suitable for the rapid detection of bacteria than Ag‐based substrates. For E. coli DH5α, the sensitivity limit for headspace SERS detection was 1.5×107 CFU mL−1, which corresponded to detection 15 min after inoculation of the growth medium. Since the metabolites are only produced by viable bacteria, antibiotic (gentamicin) treatment stopped the normal signal growth of the marker peak. This work is a promising step towards rapid bedside detection of bacterial infections and rapid screening of antibiotics against bacteria.

Surface-Enhanced Raman Spectroscopy for the Detection of a Metabolic Product in the Headspace Above Live Bacterial Cultures.

In situ surface-enhanced Raman spectra of the headspace above cultures of six bacterial species showed strong characteristic bands from chemisorbed methyl sulfide. This marker compound is created by dissociation of dimethyl disulfide (DMDS), a fermentative metabolite of bacteria, on the surface of the enhancing Au or Ag nanoparticle films. Kinetic binding plots of media spiked with DMDS and of live cultures showed that the Au-based substrates were more suitable for the rapid detection of bacteria than Ag-based substrates. For E. coli DH5α, the sensitivity limit for headspace SERS detection was 1.5×107 CFU mL-1 , which corresponded to detection 15 min after inoculation of the growth medium. Since the metabolites are only produced by viable bacteria, antibiotic (gentamicin) treatment stopped the normal signal growth of the marker peak. This work is a promising step towards rapid bedside detection of bacterial infections and rapid screening of antibiotics against bacteria.

Ameliorative Effect of Methanol Extract of Hymenocardia acida Leaves on Gentamicin-Induced Renal Toxicity in Rats

Aim: This study evaluated the nephroprotective effect of methanol extract of Hymenocardia acida leaves in rat model of gentamicin induced renal damage.&#x0D; Materials and Methods: Twenty- four (24) Wistar albino rats of either sex weighing 150- 200g were divided into 4 groups of 6 animals each; Group I served as the control and received normal saline, Group II- IV received gentamicin (40 mg/kg, i.p), Groups III and IV also received 200 and 400 mg/kg body wt., p.o methanol extract of Hymenocardia acida leaves respectively for 15 days. Body weight measurement, serum urea, creatinine, electrolytes analyses and histopathological examination of kidney were carried out.&#x0D; Results: Gentamicin treatment caused nephrotoxicity as evidenced by marked elevation in Serum urea, creatinine, decreased sodium and chloride ions, elevated serum level of potassium ion and pathological signs such as congestion, focal areas of inflammation, tubular necrosis, and glomerular atrophy. Administration of the extract at doses of 200 and 400 mg/kg/ body wt significantly (p&lt; 0.05) decreased Creatinine and urea levels, significantly (p&lt; 0.05) increased sodium and chloride ion and significantly (p&lt; 0.05) decreased potassium ion level when compared to the gentamicin- alone- treated group. Histopathological analysis also revealed a gradual reversal of the pathological features caused by gentamicin toxicity.&#x0D; Conclusion: It was concluded that the extract possesses nephroprotective potential.

Candesartan and epigallocatechin-3-gallate ameliorate gentamicin-induced renal damage in rats through p38-MAPK and NF-κB pathways.

This study pointed to estimate the possible protective impacts of candesartan and/or epigallocatechin-3-gallate (EGCG) against gentamicin-induced nephrotoxicity. The current work revealed that gentamicin significantly elevated relative kidney weight and the serum level of creatinine and urea. Also, renal level of malondialdehyde was significantly increased with a concurrent decrease in renal glutathione-S-transferase and superoxide dismutase activities. Moreover, renal levels of nuclear factor-kappa B (NF-κB) and p38 mitogen-activated protein kinase (p38-MAPK) were increased together with the elevation of tumor necrosis factor-alpha and interleukin-1 beta levels after gentamicin treatment. In addition, caspase-3 expression was elevated, and histological examination revealed extreme alterations enlightening inflammation, degeneration, and necrosis. Pretreatments with candesartan and/or EGCG attenuated gentamicin-induced nephrotoxicity. Importantly, the altered expression of p38-MAPK and NF-κB may play a significant role in the protective mechanisms exerted by candesartan and EGCG. Coadministration of candesartan and EGCG exhibited more profound response compared with the monotherapy.

Intravesical gentamicin treatment for recurrent urinary tract infections caused by multidrug-resistant bacteria

PurposeAntimicrobial resistance leads to complications in the management of recurrent urinary tract infections (rUTIs). In some rUTI patients with limited treatment options, intravenous therapy with reserve antibiotics is often required. In this study we aimed to assess the effectiveness, safety, and feasibility of prophylactic treatment with intravesical gentamicin in patients with refractory rUTI caused by multidrug-resistant (MDR) microorganisms. Materials and MethodsProspective trial of 63 adults with rUTI caused by MDR pathogens, enrolled at one academic and one general hospital in the Netherlands between 2014 and 2017. Interventionovernight intravesical instillations of gentamicin for 6 months.The primary outcome was the recurrence rate of UTIs compared to that in the preceding 6 months. Secondary objectives included the assessment of the safety of intravesical gentamicin instillation and its influence on the development of antibiotic resistance in uropathogens. ResultsThe mean number of UTIs reduced from 4.8 to 1.0 during intravesical treatment. The resistance rate of the uropathogens dropped from 78% to 23%. No systemic absorption or clinically relevant side-effects were observed. ConclusionsIntravesical gentamicin instillation reduced the number of UTI episodes and the degree of antimicrobial resistance.

The effect of short-course gentamicin therapy on kidney function in patients with bacteraemia-a retrospective cohort study.

The nephrotoxic potential of aminoglycosides is primarily correlated to the duration of therapy. However, there are discrepancies between previous studies regarding the effect of short course treatment. The aim of this study was to compare renal function, renal recovery and mortality in a large cohort of patients with bacteraemia, who were empirically treated with regimens with and without a short course (≤ 3days) of once daily dosing of gentamicin. This was a retrospective propensity score-matched cohort study based on all patients with bacteraemia in a Danish hospital in the period 2010-2013. We included 702 patients who received gentamicin, and 702 who did not receive gentamicin. To determine the impact of gentamicin on renal function, we used a modified version of the Kidney Disease: Improving Global Outcomes (KDIGO) criteria for acute kidney injury (AKI), and the resulting data were analyzed by logistic regression. We used Cox regression analysis to compare the adjusted mortality rates between the two groups. According to the KDIGO criteria, we found no significant difference in the occurrence of AKI between the two groups (odds ratio (OR) 0.90 (95% CI 0.68-1.20)). We found that recovery of renal function was similar in the two groups, OR 1.00 (95% CI 0.63-1.60). The hazard ratio for 90-day all-cause mortality was 1.02 (95% CI 0.84-1.25). Short-course empirical gentamicin treatment of patients with bacteraemia was not associated with an increased incidence of AKI nor all-cause mortality in this study, and we observed similar reversibility of renal function.

STK33 alleviates gentamicin-induced ototoxicity in cochlear hair cells and House Ear Institute-Organ of Corti 1 cells.

Serine/threonine kinase 33 (STK33), a member of the calcium/calmodulin‐dependent kinase (CAMK), plays vital roles in a wide spectrum of cell processes. The present study was designed to investigate whether STK33 expressed in the mammalian cochlea and, if so, what effect STK33 exerted on aminoglycoside‐induced ototoxicity in House Ear Institute‐Organ of Corti 1 (HEI‐OC1) cells. Immunofluorescence staining and western blotting were performed to investigate STK33 expression in cochlear hair cells (HCs) and HEI‐OC1 cells with or without gentamicin treatment. CCK8, flow cytometry, immunofluorescence staining and western blotting were employed to detect the effects of STK33 knockdown, and/or U0126, and/or N‐acetyl‐L‐cysteine (NAC) on the sensitivity to gentamicin‐induced ototoxicity in HEI‐OC1 cells. We found that STK33 was expressed in both mice cochlear HCs and HEI‐OC1 cells, and the expression of STK33 was significantly decreased in cochlear HCs and HEI‐OC1 cells after gentamicin exposure. STK33 knockdown resulted in an increase in the cleaved caspase‐3 and Bax expressions as well as cell apoptosis after gentamicin damage in HEI‐OC1 cells. Mechanistic studies revealed that knockdown of STK33 led to activated mitochondrial apoptosis pathway as well as augmented reactive oxygen species (ROS) accumulation after gentamicin damage. Moreover, STK33 was involved in extracellular signal‐regulated kinase 1/2 pathway in primary culture of HCs and HEI‐OC1 cells in response to gentamicin insult. The findings from this work indicate that STK33 decreases the sensitivity to the apoptosis dependent on mitochondrial apoptotic pathway by regulating ROS generation after gentamicin treatment, which provides a new potential target for protection from the aminoglycoside‐induced ototoxicity.

Intratympanic Gentamicin for Small Vestibular Schwannomas With Intractable Vertigo.

To evaluate the objective and subjective effects of intratympanic gentamicin treatment in patients with small vestibular schwannomas who exhibit intractable vertigo. Individuals diagnosed with small vestibular schwannomas who exhibited intractable vertigo were retrospectively reviewed. Intratympanic gentamicin injection. Vertigo control. Eight patients were included in the study. All patients achieved complete or substantial control of vertigo attacks while six patients reported residual imbalance. Three patients experienced significant hearing loss during therapy and follow-up. Only one patient showed a drop from Class B to Class C. Caloric tests and vestibular evoked myogenic potentials showed that all patients exhibited impaired peripheral vestibular function before treatment and that unilateral vestibular deafferentation was achieved during follow-up. Dizziness Handicap Inventory scores decreased over time, indicating an increase in the quality of life. Intratympanic gentamicin could provide an efficient approach to control intractable vertigo caused by small vestibular schwannoma. Before treatment, a complete physical examination, hearing level evaluation, vestibular function evaluation, and appropriate patient expectations are indispensable.

Intra-articular Gentamicin-loaded PLA Microparticle Injection for the Treatment of Septic Arthritis in Rabbits.

Because local delivery of drugs induces high concentrations, it could be helpful to apply these delivery systems to the treatment of septic arthritis by antibiotics. Thus, a gentamicin-loaded polymer was tested in a rabbit model of Staphylococcus aureus septic arthritis. Thirty New Zealand rabbits were split into five groups: A: infection only; B: infection and systemic gentamicin treatment; C: infection and unloaded polymer and systemic gentamicin treatment; D: infection and gentamicin-loaded polymer only; and E: no infection and unloaded polymer. After inducing nonlethal septic arthritis in the knee joint by injecting 10 colony-forming units (CFUs) of a strain of methicillin-sensitive S aureus in groups A, B, C, and D, rabbits were housed for 15 days, and then the joint capsules were removed and the remaining bacteria were counted. Bacterial load was expressed in CFUs per gram of synovial tissue. In group E, capsules were removed, and a pathologic examination was done. At day 15, the bacterial load was 6 × 10, 2 × 10, 1.8 × 10, and 7 × 10 CFU/g of tissue for groups A, B, C, and D, respectively. Compared with the mean of groups A, B, and C, the bacterial load of group D was 4.94 units of log10 CFU/g lower than that of these groups. The bacterial load of group D was statistically significantly lower than that of the other three groups. Noticeably, two animals of group D had a nil bacterial count. In group E animals, a minimal foreign body reaction was observed around the polymer. Gentamicin-containing microparticles were more efficient in reducing bacterial load than systemic injections of gentamicin and thus have an interesting role to play in the treatment of human arthritis. However, inserting microparticles in joints is not easy, and hydrogels might be a good alternative approach.