Aminoglycoside-Induced Nephrotoxicity—A Focus on Monitoring

2014 ◽  
Vol 27 (6) ◽  
pp. 562-566 ◽  
Author(s):  
Christopher J. Destache

The use of aminoglycoside (AG) antibiotics has declined over the past 15 years primarily due to comparable potency of other antimicrobials and the nephrotoxicity potential of AG drugs. However, resurgence in the use of AG antimicrobials is occurring due to multidrug-resistant gram-negative nosocomial infections. Multidrug-resistant Pseudomonas and Acinetobacter isolates as well as extended-spectrum beta-lactamase–producing Enterobacteriaceae continue to force clinicians to consider AG therapy for nosocomial infections in hospitalized patients and enterococcal endocarditis. Additionally, AGs are still indicated in the treatment of pulmonary exacerbations of cystic fibrosis. Along with the use of AG antibiotics is the associated renal insufficiency complication. This review discusses the mechanism for AG-induced nephrotoxicity. Patient- and drug-related risk factors are discussed to help identify patients at increased risk. The issue of serum-level monitoring is discussed relative to the development of nephrotoxicity.

2015 ◽  
Vol 20 (5) ◽  
pp. 373-377
Author(s):  
Lisa A. Degnan ◽  
Aaron M. Milstone ◽  
Marie Diener-West ◽  
Carlton K. K. Lee

OBJECTIVES: Multidrug-resistant Gram-negative bacteria, including extended-spectrum beta-lactamase (ESBL)–producing organisms, are a growing problem. The primary objective of this study was to describe the proportion of children with ESBL-producing urinary isolates at a tertiary medical center as well as these organisms' susceptibility patterns. The secondary objective was to identify the risk factors for acquiring ESBL urinary pathogens. METHODS: This retrospective study evaluated a cohort of children with ESBL urinary isolates, admitted to a tertiary children's hospital during a 6-year period. The proportion of patients with an ESBL-producing urinary isolate among all patients who grew a Gram-negative isolate is described together with the organism's susceptibility pattern. Patients with non-ESBL Gram-negative urinary organisms were used as a control group for identifying patient risk factors for ESBL. RESULTS: A total of 7.8% (29 of 370) of patients in our cohort grew Gram-negative urinary isolates with an ESBL strain. Most of the ESBL organisms isolated were sensitive to carbapenems (100% of ESBL organisms susceptible to ertapenem and 93.8% susceptible to meropenem) and amikacin (92.3% of ESBL organisms susceptible). Patients with longer hospitalization, recent antibiotic use, and recent intensive care unit admission were found to be at increased risk for ESBL organisms in the urine. CONCLUSIONS: When selecting empiric antibiotic therapy for suspected urinary tract infection in children, it may be prudent to consider the risk factors identified for acquiring an ESBL urinary pathogen.


2020 ◽  
Vol 14 (3) ◽  
pp. 2027-2032
Author(s):  
Mita D. Wadekar ◽  
J.V. Sathish ◽  
C. Pooja ◽  
S. Jayashree

Resistance to beta lactam antibiotics is the most common cause for beta-lactamase production. Increasing number of extended spectrum beta-lactamase (ESBL) producers has reduced the treatment options which resulted in emergence of multidrug resistant strains, treatment failure and hence increased mortality. To detect phenotypically, ESBL producers in Gram negative isolates from different samples and to know their susceptibility pattern. A retrospective study of Gram negative isolates was conducted. Total of 521 isolates were isolated from various samples. They were processed and identified by standard procedures. The antibiotic susceptibility testing was performed by Kirby- Bauer disc diffusion method using CLSI guidelines. ESBL was detected by combination disk test. A total of 521 Gram negative isolates were isolated which included E. coli, Klebsiella pneumoniae, Citrobacter spp., Enterobacter spp., Proteus spp. and Acinetobacter spp. Pseudomonas aeruginosa. Of 521 isolates tested, ESBL was detected in 329 (63.1%) isolates. These isolates showed maximum susceptibility to piperacillin- tazobactam (86%) followed by imipenem (78.4%), amikacin (63.5%), cotrimoxazole (54.4%), ciprofloxacin (51%), amoxi-clav (44.9%), cefepime (44.1%), gentamicin (38.9%), cefoxitin (34.9%) and ampicillin (19.1%). ESBL producers which are resistant to beta lactam antibiotics have become a major problem. Detection of these beta-lactamase enzymes by simple disk method and its reporting will help clinicians in prescribing proper antibiotics.


2011 ◽  
Vol 45 (11) ◽  
pp. 1338-1345 ◽  
Author(s):  
Brett H Heintz ◽  
George R Thompson ◽  
William E Dager

Background:: A resurgence of aminoglycoside use has followed the recent increase of multidrug-resistant gram-negative pathogens and is often needed even in the treatment of dialysis-dependent patients; however, studies evaluating the treatment of gram-negative infections with aminoglycosides, including the optimal dose, in the setting of dialysis are limited. Objective: To evaluate the current patterns of aminoglycoside use, including microbiologic and clinical indications, and identify risk factors associated with mortality in dialysis-dependent patients receiving aminoglycosides. Methods: Utilization, clinical, and microbiologic data were collected retrospectively over a 2-year period (July 2008-June 2010) for adults with a diagnosis of renal failure requiring dialysis and aminoglycoside therapy. Binary logistic and multivariate regression analyses were performed to identify risk factors for alt-cause 30-day mortality. Results: Ninety-five consecutive aminoglycoside courses in 88 patients met inclusion criteria for evaluation. A wide variety of clinical and microbiologic indications were documented. The average duration of aminoglycoside therapy was 5.2 days (range 1-42), the average duration of antimicrobial therapy was 13.5 days (1-60), and the all-cause 30-day mortality rate was 36.5%. Factors associated with all-cause 30-day mortality were gram-negative rod (GNR) bacteremia (OR 28.6; p = 0.035), advanced age (OR 8.5; p = 0.030), recent admission (OR 33.4; p = 0.038). and inadequate empiric therapy (OR 14.9; p = 0.024). Intravenous catheter removal was protective of all-cause 30-day mortality (OR 0.01; p = 0.005). A first pre-dialysis plasma concentration relative to the minimum inhibitory concentration (Cp:MIC) <6 mg/L (gentamicin/tobramycin) was associated with an increased risk of mortality (p = 0.026) upon subgroup analysis of dialysis-dependent patients with GNR bloodstream infections. Conclusions: Outcomes among dialysis-dependent patients who received aminoglycosides were below expectations. Various risk factors for mortality were identified, including retention of the catheter, inadequate empiric therapy, and a Cp:MIC <6 mg/L. Improved approaches to dosing of aminoglycosides in dialysis-dependent patients, including more aggressive dosing practices, should be urgently explored in attempts to maximize favorable patient outcomes.


2017 ◽  
Vol 4 (2) ◽  
pp. 135
Author(s):  
Afifah Afifah ◽  
Tunggul Adi Purwonegoro ◽  
IDSAP Peramiarti

Resistant Gram-negative bacteria, particularly Klebsiella sp., has become a serious problem in hospitals as one of the main causes of nosocomial infections spread through urine catheterization. Infections of Klebsiella sp. producing extended-spectrum beta-lactamase (ESBL) can lead to significant economic and clinical negative outcome. This study was aimed to determine the sensitivity of ESBL Klebsiella sp. against meropenem as a cause of nosocomial infections in Prof. Dr. Margono Soekarjo hospital. This research obtained urine samples from the urinary catheter of patients hospitalized for at least two days in the surgical ward and intensive care unit. ESBL examination conducted by the initial screen test, meanwhile, sensitivity test to meropenem done by using disk diffusion test. Among the 40 patients examined in this study 7.5% isolates were Klebsiella sp-positive. This research identified five percent of the total patients as ESBL positive with the level of sensitivity against meropenem was revealed as resistant.


2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S567-S568
Author(s):  
Alyssa Ammazzalorso ◽  
Jennifer Han ◽  
Ebbing Lautenbach ◽  
Pranita Tamma ◽  
Pranita Tamma ◽  
...  

Abstract Background Multidrug-resistant (MDR) Gram-negative (GN) bloodstream infections (BSI) are a major cause of morbidity and mortality among solid organ transplant recipients (SOTR). We determined risk factors associated with subsequent MDR-GN BSI following an initial Enterobacterales (EB) BSI among SOTRs. Methods A retrospective cohort study was performed. All SOTR with an EB BSI at the Hospital of the University of Pennsylvania and University of Maryland Medical Center between 1 Jan 2007 and 30 June 2018 and The Johns Hopkins Hospital between 1 Jan 2005 and 31 Dec 2015 were included. The primary outcome was any MDR-GN BSI within 60 days of the EB BSI, including MDR-EB (defined by ceftriaxone MIC ≥8μg/mL), and MDR-Pseudomonas and Acinetobacter (defined by resistance to three or more antibiotic classes). Unadjusted analyses were performed to identify possible risk factors, using a Fisher’s exact or χ 2 test for categorical and Student’s t-test for continuous variables. Results Of 988 SOTR with an EB BSI, 138 (14%) had a MDR-GN BSI within 60 days. In unadjusted analyses, possible risk factors for a subsequent MDR-GN BSI (Table 1) included: (1) an index BSI due to extended-spectrum beta-lactamase (ESBL)-producing EB (compared to a susceptible index EB BSI); (2) a carbapenem-resistant EB (CRE) index BSI (compared to a susceptible index EB BSI); (3) exposure to piperacillin-tazobactam or carbapenems in the 6 months prior to the index EB BSI; (4) prior liver transplantation; and (5) need for reoperation within four weeks of the original transplantation. There was no significant association between recurrent MDR-GN BSI and immunosuppression at time of infection, induction immunosuppression history, acute rejection history, or primary graft dysfunction. Table 1. Risk factors for subsequent MDR-GN BSI following EB BSI among SOTR. Data are presented as numbers (percentages) except where noted. Abbreviations: BSI, bloodstream infection; CRE, carbapenem-resistant Enterobacterales; EB, Enterobacterales; ESBL, extended-spectrum beta-lactamase; GN, Gram-negative; IQR, interquartile range; MDR, multidrug-resistant Conclusion This study shows that liver transplantation, reoperation following transplantation, an index ESBL-EB or CRE BSI, and recent exposure to broad-spectrum beta-lactam antibiotics are associated with an increased odds of subsequent MDR-GN BSI in SOTR, and underscores the need for future studies aimed at preventing emergence of MDR-GN infections in this vulnerable population. Disclosures Jennifer Han, MD, MSCE, GlaxoSmithKline (Employee, Shareholder) Ebbing Lautenbach, MD, MPH, MSCE, Merck (Other Financial or Material Support, Member of Data and Safety Monitoring Board (DSMB)) Pranita Tamma, MD, MHS, Nothing to disclose Emily Blumberg, MD, Amplyx (Other Financial or Material Support, Member of Data and Safety Monitoring Board (DSMB))Hologic (Research Grant or Support)Merck (Grant/Research Support, Other Financial or Material Support, Member of Scientific Advisory Committee)Takeda (Research Grant or Support, Other Financial or Material Support, Member of Scientific Advisory Committee) Judith A. Anesi, MD, MSCE, Nothing to disclose


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