Dataset Information

A Multicenter Evaluation of Vancomycin-Associated Acute Kidney Injury in Hospitalized Patients with Acute Bacterial Skin and Skin Structure Infections.

ABSTRACT: BACKGROUND:We sought to determine the real-world incidence of and risk factors for vancomycin-associated acute kidney injury (V-AKI) in hospitalized adults with acute bacterial skin and skin structure infections (ABSSSI). METHODS:Retrospective, observational, cohort study at ten U.S. medical centers between 2015 and 2019. Hospitalized patients treated with vancomycin (??72 h) for ABSSSI and ??one baseline AKI risk factor were eligible. Patients with end-stage kidney disease, on renal replacement therapy or AKI at baseline, were excluded. The primary outcome was V-AKI by the vancomycin guidelines criteria. RESULTS:In total, 415 patients were included. V-AKI occurred in 39 (9.4%) patients. Independent risk factors for V-AKI were: chronic alcohol abuse (aOR 4.710, 95% CI 1.929-11.499), no medical insurance (aOR 3.451, 95% CI 1.310-9.090), ICU residence (aOR 4.398, 95% CI 1.676-11.541), Gram-negative coverage (aOR 2.926, 95% CI 1.158-7.392) and vancomycin duration (aOR 1.143, 95% CI 1.037-1.260). Based on infection severity and comorbidities, 34.7% of patients were candidates for oral antibiotics at baseline and 39.3% had non-purulent cellulitis which could have been more appropriately treated with a beta-lactam. Patients with V-AKI had significantly longer hospital lengths of stay (9 vs. 6 days, p?=?0.001), higher 30-day readmission rates (30.8 vs. 9.0%, p?

SUBMITTER: Jorgensen SCJ

PROVIDER: S-EPMC7054514 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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A Multicenter Evaluation of Vancomycin-Associated Acute Kidney Injury in Hospitalized Patients with Acute Bacterial Skin and Skin Structure Infections.

Jorgensen Sarah C J SCJ Murray Kyle P KP Lagnf Abdalhamid M AM Melvin Sarah S Bhatia Sahil S Shamim Muhammad-Daniayl MD Smith Jordan R JR Brade Karrine D KD Simon Samuel P SP Nagel Jerod J Williams Karen S KS Ortwine Jessica K JK Veve Michael P MP Truong James J Huang David B DB Davis Susan L SL Rybak Michael J MJ

Infectious diseases and therapy 20200125 1

<h4>Background</h4>We sought to determine the real-world incidence of and risk factors for vancomycin-associated acute kidney injury (V-AKI) in hospitalized adults with acute bacterial skin and skin structure infections (ABSSSI).<h4>Methods</h4>Retrospective, observational, cohort study at ten U.S. medical centers between 2015 and 2019. Hospitalized patients treated with vancomycin (≥ 72 h) for ABSSSI and ≥ one baseline AKI risk factor were eligible. Patients with end-stage kidney disease, on re ...[more]

PMID: 31983021

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Project description:BackgroundOmadacycline is an oral and intravenous (IV) once-daily aminomethylcycline antibiotic that was recently approved by the US Food and Drug Administration for the treatment of patients with acute bacterial skin and skin structure infections (ABSSSI). In 2 phase 3 clinical trials, IV-to-oral switch and oral-only administration of omadacycline achieved the primary end points of noninferiority compared with linezolid in treating patients with ABSSSI.ObjectiveTo estimate the potential cost-savings with bioequivalent IV-to-oral antibiotics, such as omadacycline, compared with the standard of care with IV vancomycin by avoiding hospitalizations and reducing hospital stays in patients presenting from the emergency department for ABSSSI treatment.MethodsWe used hospital avoidance models to examine the potential cost-savings of managing patients with ABSSSI and no or limited comorbidities and without life-threatening conditions by using omadacycline in the outpatient setting compared with the current standard of care. Early hospital discharge models were used to evaluate the hospital stay reduction that would be required to be achieved with omadacycline treatment relative to IV vancomycin to confer cost-savings compared with standard of care among patients with ABSSSI and ?2 comorbidities but no life-threatening conditions.ResultsIn the hospital stay avoidance models, cost-savings may be realized by using therapeutically bioequivalent IV-to-oral antibiotics, such as omadacycline, compared with inpatient treatment with IV vancomycin. Based on a sensitivity analysis, further savings could be possible with outpatient administration of omadacycline, even if 20% of omadacycline outpatients were subsequently admitted and incurred the full inpatient cost, with no reimbursement penalties. Of more than 300 patients, only 1 was admitted to the hospital after a full course of omadacycline in the oral-only clinical trial. In the early hospital discharge models, the maximum cost-minimizing daily expense of omadacycline varied from $173 to $936, depending on the presence of active comorbidities or systemic symptoms, hospital stay reduction, and model perspective.ConclusionThese results suggest that the targeted use of antibiotics with bioequivalent IV-to-oral formulations, such as omadacycline, for select patients with ABSSSI may lead to cost-savings compared with inpatient IV vancomycin treatment by shifting care to the outpatient setting or by facilitating earlier hospital discharge among hospitalized patients.

Project description:Importanceβ-Lactam antibiotics are often coadministered with intravenous (IV) vancomycin hydrochloride for children with suspected serious infections. For adults, the combination of IV vancomycin plus piperacillin sodium/tazobactam sodium is associated with a higher risk of acute kidney injury (AKI) compared with vancomycin plus 1 other β-lactam antibiotic. However, few studies have evaluated the safety of this combination for children.ObjectiveTo assess the risk of AKI in children during concomitant therapy with vancomycin and 1 antipseudomonal β-lactam antibiotic throughout the first week of hospitalization.Design, setting, and participantsThis retrospective cohort study focused on children hospitalized for 3 or more days who received IV vancomycin plus 1 other antipseudomonal β-lactam combination therapy at 1 of 6 large children's hospitals from January 1, 2007, through December 31, 2012. The study used the Pediatric Health Information System Plus database, which contains administrative and laboratory data from 6 pediatric hospitals in the United States. Patients with underlying kidney disease or abnormal serum creatinine levels on hospital days 0 to 2 were among those excluded. Patients 6 months to 18 years of age who were admitted through the emergency department of the hospital were included. Data were collected from July 2015 to March 2016. Data analysis took place from April 2016 through July 2017. (Exact dates are not available because the data collection and analysis processes were iterative.).Main outcomes and measuresThe primary outcome was AKI on hospital days 3 to 7 and within 2 days of receiving combination therapy. Acute kidney injury was defined using KDIGO criteria and was based on changes in serum creatinine level from hospital days 0 to 2 through hospital days 3 to 7. Multiple logistic regression was performed using a discrete-time failure model to test the association between AKI and receipt of IV vancomycin plus piperacillin/tazobactam or vancomycin plus 1 other antipseudomonal β-lactam antibiotic.ResultsA total of 1915 hospitalized children who received combination therapy were identified. Of the 1915 patients, a total of 866 (45.2%) were female and 1049 (54.8%) were male, 1049 (54.8%) were identified as white in race/ethnicity, and the median (interquartile range) age was 5.6 (2.1-12.7) years. Among the cohort who received IV vancomycin plus 1 other antipseudomonal β-lactam antibiotic, 157 patients (8.2%) had antibiotic-associated AKI. This number included 117 of 1009 patients (11.7%) who received IV vancomycin plus piperacillin/tazobactam combination therapy. After adjustment for age, intensive care unit level of care, receipt of nephrotoxins, and hospital, IV vancomycin plus piperacillin/tazobactam combination therapy was associated with higher odds of AKI each hospital day compared with vancomycin plus 1 other antipseudomonal β-lactam antibiotic combination (adjusted odds ratio, 3.40; 95% CI, 2.26-5.14).Conclusions and relevanceCoadministration of IV vancomycin and piperacillin/tazobactam may increase the risk of AKI in hospitalized children. Pediatricians must be cognizant of the potential added risk of this combination therapy when making empirical antibiotic choices.

Project description:INTRODUCTION:Vancomycin associated acute kidney injury (vAKI) is a well known complication in pediatric patients. Identification and characterization of the incidence and risk factors for vAKI in the pediatric population would assist clinicians in potentially preventing or mitigating vAKI. METHODS AND MATERIALS:A 6 year retrospective cohort study was designed. Patients were included if they were < 19 years of age, received vancomycin as inpatients, and had a baseline SCr and one other SCr drawn during and up to 72 hours after the discontinuation of vancomycin. Data collection included patient demographics, vancomycin doses and length of therapy, vancomycin serum concentrations, and concomitant medications. The Kidney Disease Improving Global Outcomes (KDIGO) criteria were used to characterize acute kidney injury. Descriptive statistical methods were used and ordinal logistic regression was employed to determine variables significantly associated with vAKI. RESULTS:A total of 7,095 patients met study criteria (55.4% male, median age 4.1 years (IQR 0.67-11.2 years)). Mechanical ventilation was used in 7.9% (n = 563) and mortality was 4.9% (n = 344). A total of 153 concomitant medications were identified. A median of 5 (IQR 3-7) SCr values were obtained and median SCr prior to vancomycin was 0.39 (IQR 0.28-0.57) mg/dL (CrCl 134±58 mL/min/1.73m2). Vancomycin was administered for a median of 2 (IQR 1-3) days (14.9±1.6 mg/kg/dose). vAKI was present in 12.2% (n = 862: KDIGO stage 1 (8.30%, n = 589), KDIGO stage 2 (1.94%, n = 138) KDIGO stage 3 (1.89%, n = 134)). Mean vancomycin serum concentration at 6-8 hours after a dose for patients with vAKI (10.7±8.9 mg/L) was significantly, but not clinically different for patients with no vAKI (7.5±6.3 mg/L). (p<0.05) Ordinal logistic regression identified total dose of vancomycin, vancomycin administration in the intensive care unit, and concomitant medication administration as significant for vAKI. In particular, concomitant administration of several different medications, including nafcillin, clindamycin, and acetazolamide, were noted for strong associations with vAKI. (p<0.05). CONCLUSIONS:Moderate to severe acute kidney injury due to vancomycin is infrequent in children and associated with concomitant medication use and total dose of vancomycin. Serum vancomycin concentrations are not useful predictors of vAKI in the pediatric population.

Project description:Vancomycin has been associated with acute kidney injury (AKI). However, the pharmacokinetic/toxicodynamic relationship for AKI is not well defined. Allometrically scaled vancomycin exposures were used to assess the relationship between vancomycin exposure and AKI. Male Sprague-Dawley rats received clinical-grade vancomycin in normal saline (NS) as intraperitoneal (i.p.) injections for 24- to 72-h durations with doses ranging 0 to 200 mg/kg of body weight divided once or twice daily. Urine was collected over the protocol's final 24 h. Renal histopathology was qualitatively scored. Urinary biomarkers (e.g., cystatin C, clusterin, kidney injury molecule 1 [KIM-1], osteopontin, lipocalin 2/neutrophil gelatinase-associated lipocalin 2) were assayed using a Luminex xMAP system. Plasma vancomycin concentrations were assayed by high-performance liquid chromatography with UV detection. A three-compartment vancomycin pharmacokinetic model was fit to the data with the Pmetrics package for R. The exposure-response in the first 24 h was evaluated using Spearman's nonparametric correlation coefficient (rs) values for the area under the concentration-time curve during the first 24 h (AUC0-24), the maximum concentration in plasma during the first 24 h (Cmax0-24 ), and the lowest (minimum) concentration in plasma after the dose closest to 24 h (Cmin0-24 ). A total of 52 rats received vancomycin (n = 42) or NS (n = 10). The strongest exposure-response correlations were observed between AUC0-24 and Cmax0-24 and urinary AKI biomarkers. Exposure-response correlations (rs values) for AUC0-24, Cmax0-24 , and Cmin0-24 were 0.37, 0.39, and 0.22, respectively, for clusterin; 0.42, 0.45, and 0.26, respectively, for KIM-1; and 0.52, 0.55, and 0.42, respectively, for osteopontin. However, no differences in histopathological scores were observed. Optimal sampling times after administration of the i.p. dose were 0.25, 0.75, 2.75, and 8 h for the once-daily dosing schemes and 0.25, 1.25, 14.5, and 17.25 h for the twice-daily dosing schemes. Our observations suggest that AUC0-24 or Cmax0-24 correlates with increases in urinary AKI biomarkers.

Dataset Information

A Multicenter Evaluation of Vancomycin-Associated Acute Kidney Injury in Hospitalized Patients with Acute Bacterial Skin and Skin Structure Infections.

Publications

A Multicenter Evaluation of Vancomycin-Associated Acute Kidney Injury in Hospitalized Patients with Acute Bacterial Skin and Skin Structure Infections.

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