Aminoglycoside-Associated Nephrotoxicity in the Elderly

Baciewicz, Anne M.; Sokos, Denise R; Cowan, Ronald I

doi:10.1345/1542-6270(2003)37<182:anite>2.0.co;2

Cited by 3 publications

(5 citation statements)

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“…Similarly, aminoglycosides are effective against Gram-negative aerobic bacteria including resistant Enterobacteriaceae [ 60 ]. However, aminoglycosides monotherapies can lead to unfavorable clinical outcomes due to rapid emergence of resistance, and nephrotoxicity among patients with prolonged usage of aminoglycosides [ 61 , 62 ].…”

Section: Resultsmentioning

confidence: 99%

Synergistic Antibacterial Effects of Meropenem in Combination with Aminoglycosides against Carbapenem-Resistant Escherichia coli Harboring blaNDM-1 and blaNDM-5

et al. 2021

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Infections due to carbapenem-resistant Escherichia coli (CREC) are problematic due to limitation in treatment options. Combination therapies of existing antimicrobial agents have become a reliable strategy to control these infections. In this study, the synergistic effects of meropenem in combination with aminoglycosides were assessed by checkerboard and time-kill assays. Of the 35 isolates, 19 isolates (54.3%) were resistant to carbapenems (imipenem and meropenem) with the MIC ranges from 16 to 128 µg/mL. These isolates were resistant to almost all antibiotic classes. Molecular characteristics revealed co-harboring of carbapenemase (blaNDM-1, blaNDM-5 and blaOXA-48) and extended-spectrum β-lactamases (ESBL) genes (blaCTX-M, blaSHV and blaTEM). The checkerboard assay displayed synergistic effects of meropenem and several aminoglycosides against most CREC isolates. Time-kill assays further demonstrated strong synergistic effects of meropenem in combination with either amikacin, gentamicin, kanamycin, streptomycin, and tobramycin. The results suggested that meropenem in combination with aminoglycoside therapy might be an efficient optional treatment for infections cause by CREC.

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Section: Resultsmentioning

confidence: 99%

Synergistic Antibacterial Effects of Meropenem in Combination with Aminoglycosides against Carbapenem-Resistant Escherichia coli Harboring blaNDM-1 and blaNDM-5

et al. 2021

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“…However, 27 studies expressed the absolute risk of organ injury among exposed older adults. Nine studies (14,17,21,22,27,33,34) reported absolute risk of AKI due to aminoglycoside exposure, eight studies (23-26, 28-31, 38) reported absolute risk of AKI due to glycopeptide exposure. Four studies reported the absolute risk of AKI due to macrolide exposure (15,16).…”

Section: Discussionmentioning

confidence: 99%

“…The full selection process is summarised in gure 1. Six of the included studies had data for two or more antimicrobials (12)(13)(14)(15)(16)(17). Each of these data was treated as a separate study, resulting in 34 studies, as shown in table 1 below.…”

Section: Study Identi Cationmentioning

confidence: 99%

“…Sixteen studies were set on single hospitals (13, 14, 16, 17, 21-24, 26-32, 35), four used primary care data (12,13,19,20), two were population-based (15,16), one multicentre hospital-based (14), and one multicentre randomised controlled study (18). Six of the studies were carried in the United Kingdom (12,13,(19)(20)(21)(22), four each for China (23)(24)(25)(26) and the United States (27-30), two each for Canada (15,16) and Japan (31,32), and one each for Australia (33), France (14), Israel (34), Singapore (17), and South Korea (35). The randomised controlled trial (18) was multinational, including nine countries, namely Australia, Benin, Brazil, Canada, Ghana, Guinea, Indonesia, Saudi Arabia, and South Korea.…”

Section: Characteristics Of Included Studiesmentioning

confidence: 99%

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Antimicrobial-associated Organ Injury among the Older Adults: A Systematic Review and Meta-Analysis

Chinzowu

Roy

Nishtala

2021

Preprint

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Background: Older adults (aged 65 years and above) constitute the fastest growing population cohort in the western world. There is increasing evidence that the burden of infections disproportionately affects older adults, and hence this vulnerable population is frequently exposed to antimicrobials. There is currently no systematic review summarising the evidence for organ injury risk among older adults following antimicrobial exposure. This systematic review and meta-analysis examined the relationship between antimicrobial exposure and organ injury in older adults. Methodology: We searched for Psych INFO, PubMed, and EMBASE databases for relevant articles using MeSH terms where applicable. After removing duplicates, articles were screened for inclusion into or exclusion from the study by two reviewers. The Newcastle-Ottawa scale was used to assess the risk of bias for cohort and case-control studies. The Cochrane collaboration's tool for risk of bias (version 2) was used to assess the risk of bias for randomised control trials. We explored the heterogeneity of the included studies using the Q test and I2 test and the publication bias using the funnel plot and Egger's test. Results: The overall absolute risks of acute kidney injury among older adults prescribed aminoglycosides, glycopeptides, and macrolides were 15.1%, 19.1%, and 0.3%, respectively. Only 3 studies reported antimicrobial associated drug-induced liver injury. Studies reporting on the association of organ injury and antimicrobial exposure by age or duration of treatment were too few to meta-analyse. The funnel plot and Egger's tests did not indicate evidence of publication bias.Conclusion: Older adults have a significantly higher risk of sustaining acute kidney injury when compared to the general adult population. Older adults prescribed aminoglycosides have a similar risk of acute kidney injury to the general adult population.

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“…Balardi and colleagues have shown that elderly patients (≥65 years) had ten times the incidence rate Elderly patients who developed AKI on a background of CKD are less likely to recover from AKI and more likely to progress to more advanced stage or even ESKD which contributes to the higher mortality rate 83,84 .The hazard ratio of developing ESKD for patients with both AKI and CKD is 13.0 relative to those only with AKI 85 . The two-year mortality rate is higher for those with to aminoglycosides in combination an ACE inhibitor in elderly patients has been reported[94][95][96] . While contrast-induced nephropathy (CIN) is a significant cause of AKI in hospitalized elderly patients89,97 , age per se may not be an independent predictor of contrast nephropathy 98 .…”

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confidence: 96%

The role of the age-dependent loss of alpha(E)-catenin in increased acute kidney injury

Wang¹

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The aging kidney undergoes structural and functional alterations which make it more susceptible to acute kidney injury (AKI). Previous studies in our laboratory have shown that the aging kidney has a marked loss of alpha(E)-catenin in proximal tubular epithelium. alpha-Catenin, a key regulator of actin cytoskeleton, interacts with a variety of actin-binding proteins. Fascin 2 is an actin bundling protein that interacts with adhesion molecules and F-actin. In this work, we hypothesized that loss of alpha(E)-catenin leads to disruption of actin cytoskeleton which increases cisplatin-induced injury in aged kidney. A stable shRNA knock-down of alpha(E)-catenin was generated in NRK-52E cells (C2 cells); NT3 cells are the non-targeted control. We demonstrated that age-dependent loss of alpah(E)-catenin in renal tubule epithelial cells facilitates the Fas-mediated apoptotic signaling pathway in response to cisplatin-induced AKI injury. In addition, a cisplatin-induced loss of fascin 2 was observed in aged kidney. Overexpression of Fscn2 abolished increased cisplatin-induced apoptosis, mitochondrial dysfunction and oxidative stress in C2 cells compared with NT3 cells. In conclusion, this dissertation projects novel insight into understanding the increased incidence of AKI in aged kidney and identified a novel role of fascin 2 in renal epithelial cells, which depends on the functional interaction with alpha(E)-catenin and F-actin. These findings may lay the groundwork for new therapeutic approaches to AKI in aged patients in the future.

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Aminoglycoside-Associated Nephrotoxicity in the Elderly

Cited by 3 publications

References 0 publications

Synergistic Antibacterial Effects of Meropenem in Combination with Aminoglycosides against Carbapenem-Resistant Escherichia coli Harboring blaNDM-1 and blaNDM-5

Synergistic Antibacterial Effects of Meropenem in Combination with Aminoglycosides against Carbapenem-Resistant Escherichia coli Harboring blaNDM-1 and blaNDM-5

Antimicrobial-associated Organ Injury among the Older Adults: A Systematic Review and Meta-Analysis

The role of the age-dependent loss of alpha(E)-catenin in increased acute kidney injury

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