Article

An Evaluation of the Incidence of Nephrotoxicity After a Loading Dose of Vancomycin in Patients With Severe Renal Impairment

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Abstract

Background: Loading doses of vancomycin assist in the rapid achievement of target trough concentrations. Patients with renal dysfunction have been excluded from studies evaluating loading doses. Objective: The purpose of this study was to investigate nephrotoxicity related to initial vancomycin dose in patients with severe renal dysfunction. Methods: A retrospective cohort study was approved by the Institutional Review Board of a large, academic health system. Adults were included if they received intravenous vancomycin in the emergency department and presented with creatinine clearance < 30 mL/min. Chronic dialysis patients were excluded. The primary outcome was incidence of nephrotoxicity after an initial high (>20 mg/kg) vs. low (≤20 mg/kg) dose of vancomycin. Secondary outcomes included dialysis, vancomycin concentrations, length of stay, in-hospital mortality, and a composite outcome of nephrotoxicity or dialysis. Results: Of the 927 patients included in the analysis, nephrotoxicity occurred in 7.2% and 13.8% of patients in the high- and low-dose groups, respectively (p < 0.01). Patients in the high-dose group had a reduced risk of nephrotoxicity (relative risk 0.53; 95% confidence interval 0.35-0.78). The reduction in risk remained after fitting a generalized linear model adjusting for weight, age, sex, initial serum creatinine, diabetes, and chronic kidney disease (relative risk 0.61; 95% confidence interval 0.39-0.93). Limitations of this study include its retrospective design and single-center population. Conclusion: These data suggest that vancomycin loading doses do not increase nephrotoxicity compared with lower doses in patients with severe renal dysfunction. These patients should be included in future studies relating to vancomycin loading doses.

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... In the remaining 82 articles, 13 articles were preclinical studies and 10 epidemiology studies, 29 research papers without an LD group (LDG) and 13 research papers on unrelated topics. Finally, 17 articles, including 2 RCTs [23,24], 11 retrospective cohorts, and 4 other studies, were included [25][26][27][28][29][30][31][32][33][34][35][36][37][38][39]. The PRISMA flow diagram reporting the procedure of selection of studies is shown in Figure 1. ...
... In the remaining 14 studies, 10 were retrospective cohort studies, 1 prospective, 1 concurrent and 2 studies conducted both retrospectively and prospectively in order to compare the results with each other. Six studies were conducted in patients with MRSA infections [25][26][27][28][29][30], while the remaining were conducted in patients with different infectious diseases [23,24,[31][32][33][34][35][36][37][38][39]. The studies included intensive care unit (ICU) patients, patients with severe renal impairment, sepsis patients, hospitalized hemodialysis patients, emergency department patients and MRSA-infected patients. ...
... Results of RCTs also revealed a significantly higher incidence of nephrotoxicity in the LDG. Marvin and his colleagues reported that a high LD of vancomycin does not increase nephrotoxicity when compared to a lower dose in renally impaired patients [31]. However, Demirjian et al. reported that children who received an LD of 30 mg/kg infused over 2 h reported the occurrence of nephrotoxicity and red man syndrome [23]. ...
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Background: The clinical significance of utilizing a vancomycin loading dose in critically ill patients remains unclear. Objective: The main aim of this systematic review is to evaluate the clinical safety and efficacy of the vancomycin loading dose in critically ill patients. Methods: We performed a systematic review using PRISMA guidelines. PubMed, the Web of Science, MEDLINE, Scopus, Google Scholar, the Saudi Digital Library and other databases were searched. Studies that reported clinical outcomes among patients receiving the vancomycin LD were considered eligible. Data for this study were collected using PubMed, the Web of Science, MEDLINE, Scopus, Google Scholar and the Saudi Digital Library using the following terms: "vancomycin", "safety", "efficacy" and "loading dose" combined with the Boolean operator "AND" or "OR". Results: A total of 17 articles, including 2 RCTs, 11 retrospective cohorts and 4 other studies, met the inclusion/exclusion criteria out of a total 1189 studies. Patients had different clinical characteristics representing a heterogenous group, including patients in critical condition, with renal impairment, sepsis, MRSA infection and hospitalized patients for hemodialysis or in the emergency department. Conclusions: The study shows that the target therapeutic level is achieved more easily among patients receiving a weight-based LD as compared to patients received the usual dose without an increased risk of new-onset adverse drug reactions.
... This population was decidedly more severely ill than our study population, as over 40% of patients in both cohorts were eventually transferred to the ICU. 19 A larger retrospective study by Rosini et al, 2016 examined loading-dose vancomycin and AKI rate in septic patients. Like the aforementioned study, the loading dose cohort had a significantly lower rate of nephrotoxicity (5.8% versus 11.1%) with an adjusted RR of 0.60; 95% confidence interval = 0.44 to 0.82. ...
... Further, current definitions of AKI rely on changes in creatinine and urine output cutoffs, proxies for renal function that do not always capture renal injury. 17 However, the previous study duration in similar loading dose studies has been historically between 36 hours and 5 days, 19,[21][22][23][24] so this study has a chance to capture more potential AKIs. As discussed previously, however, there is stronger evidence of an association between duration of vancomycin exposure and AKI. ...
Article
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Background Infectious Disease Society of America (IDSA) guidelines recommend the usage of a loading dose when using vancomycin for seriously ill patients. While the relationship between vancomycin and nephrotoxicity is the focus of many studies, few studies have examined the relationship between vancomycin loading doses and nephrotoxicity. Methods We performed a retrospective cohort study examining vancomycin dosing for internal medicine teaching services’ patients over the 2014–15 academic year at one academic medical center. We generated a list of all hospitalized patients aged 18–85 who received vancomycin and were admitted to a teaching service. Nephrotoxicity was determined by 7-day acute kidney injury (AKI) rate. Patients in the loading dose cohort were compared with those in the standard-dose cohort. Primary modeling used multivariable logistic regression with AKI as our outcome of interest. Results Four hundred and thirty-eight patients were included for analysis. The loading dose (n = 365, 83%) and standard dosing (n = 73, 17%) cohorts were not significantly different regarding demographics, GFR, nephrotoxic drug exposure, total vancomycin received, trough levels, or comorbidities and were only significantly different regarding body mass index (BMI). The 7-day AKI rate was not significantly different between the two arms (6.3% in the standard dosing arm and 8.2% in the loading dose arm, p = 0.6). Conclusion Few studies have examined the relationship between nephrotoxicity and vancomycin loading doses. The results of this study provide evidence that the use of loading doses is not significantly associated with increased 7-day AKI rate.
... ese side effects limit its administration and efficacy [2]. Nephrotoxicity duo to VAN therapy was reported in 5-30% of patients [3], while this can increase to 20-35% when combined with an aminoglycoside antibiotic [2,4]. On average, nephrotoxicity developed between 4 and 17 days after VAN therapy [5]. ...
... On average, nephrotoxicity developed between 4 and 17 days after VAN therapy [5]. Although the exact mechanism of VAN-induced nephrotoxicity is not well understood, studies have suggested that oxidative stress [4,6], inflammatory process, and apoptosis may be involved in the pathogenesis of renal toxicity of VAN [2]. As mentioned in the literature, oxidative damage is the consequence of unevenness amongst reactive oxygen species (ROSs) and antioxidants leading to cellular harm [7]. ...
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Vancomycin-induced nephrotoxicity (VIN) has been reported to occur in 5–35% of recipient patients. The aims of the study were to evaluate protective effects of Rosa canina (RC) on VIN in rats. Rats were randomly divided into five groups as follows: control group I, group II (received VAN 400 mg/kg/day, every 12 h at doses of 200 mg/kg/day, for 7 consecutive days), group III (VAN + RC 250 mg/kg/day, for 7 consecutive days), group IV (VAN + RC 500 mg/kg/day, for consecutive days), and group V (received RC 500 mg/kg/day, for consecutive 7 days). On the eighth day after anesthetizing the animals, blood samples were taken from the heart, and then, the kidneys were removed to investigate kidney function, oxidative stress, and histopathological marker. Also, the chemical composition of RC extract was identified by GC-MS analysis. Oral dose of 500 mg/kg RC extract significantly reduced the serum levels of blood urea nitrogen (BUN), creatinine (Cr), malondialdehyde (MDA), and nitric oxide (NO) and also the kidney tissue MDA, protein carbonyl, and NO metabolites (nitrite) levels compared to the VAN-treated group (P
... We observe that a supratherapeutic AUC occurred when the loading dose was 1500 mg or 2000 mg, and in one case at 1000 mg with a low BMI. In a study of patients with severe renal impairment (creatinine clearance < 30 mL/min), without hemodialysis and a loading dose of 25-30-mg/kg of vancomycin, nephrotoxicity occurred in 7.2% of patients in the high-dose group [15]. ...
Article
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Background/Objectives: Vancomycin is a reserve antibiotic that is frequently prescribed for central venous catheter (CVC)-associated infections in hemodialysis patients. Hemodialysis patients are very fragile patients and the presence of CVCs increases the risk of sepsis. We conducted a prospective study, evaluating the needs of changes in vancomycin dosing for treatment based on the use of the new 2020 vancomycin dosing guidelines, to increase drug safety (preventing subtherapeutic or supratherapeutic doses and offering therapeutic concentrations of the drug) in a particular group of patients with sepsis caused by catheter infections and being on intermittent hemodialysis. Methods: This prospective study included patients with sepsis caused by catheter infections and being on intermittent hemodialysis, treated with vancomycin, admitted in the nephrology department and intensive care unit (ICU). Vancomycin levels were adjusted according to the 2020 vancomycin guidelines. Results: In our study, nine (45%) patients had a vancomycin AUC between 400 and 600 mcg × h/mL, five (25%) patients had a subtherapeutic AUC, and six (30%) patients had a supratherapeutic AUC. It is important to mention that in 10 (50%) of the patients included in the study, the loading and maintenance doses mentioned in the protocol were respected, but 50% of them had a supratherapeutic AUC. We observed that a supratherapeutic AUC occurred when the loading dose was 1500 mg or 2000 mg, and in one case at 1000 mg with a low BMI. Conclusions: a therapeutic level of vancomycin can often be difficult to achieve because of different reasons, mainly in hemodialysis patients.
... Although studies suggests that oxidative stress 22,23 , inflammation, and apoptosis may play a role in the pathology of vancomycin induced renal toxicity 2 , the exact mechanism of vancomycin-induced nephrotoxicity is not fully understood. In many countries, in addition to chemical drugs, the use of natural antioxidants, which reduce complications with fewer side effects, low toxicity, and affordable prices, are being investigated. ...
Article
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Purpose: The aim of the study explores probable toxic effects of vancomycin on kidney and analysis of the probable protective effects of melatonin. Materials and Methods: In this study, rats were randomly divided into 4 groups: the control group; the melatonin (10 mg/kg/day) group; the vancomycin-treated (200 mg/kg) group; and the vancomycin (200 mg/kg) + melatonin (10 mg/kg/day) group. Rats in the treatment group were given two doses of vancomycin a day with an interval of seven consecutive days and melatonin (10 mg/kg/day) once daily for seven consecutive days. The experiment was continued for 15 days. In each group, seven rats were grouped together. 15 days after the experiment, the rats were sacrificed under anesthesia and among all groups. Kidney tissues were collected and processed for further TNF- expression analysis, as well as histological analyses such as hematoxylin and eosin (H&E), Masson's tricrom, and Periodic acid schiff (PAS) staining to assess pathological severity. In addition, a terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was performed to evaluate apoptosis. Results: While vancomycin upregulated TNF-α expression, melatonin reduced levels of TNF-α immunoreactivity intensity and clearly improved pathological severity in rat kidneys. Further, melatonin significantly inhibited vancomycin-induced TUNEL-positive cell numbers. Conclusion: Melatonin has protective activity against vancomycin-induced pro-inflammatory and proapoptotic effects in kidneys during organ preservation time and improves kidney function.
... 5,6 Nephrotoxicity is characterized by the decrease in glomerular filtration rate (GFR), which is clinically evaluated from increased serum creatinine (SCr) and decreased creatinine clearance (CrCl) below 60mL/min/1.73 m 2 . 7 A study carried out in Poland found out that nephrotoxicity was a major clinical problem among cancer patients who received chemotherapy. 8 Chemotherapy regimens containing platinum agents (cisplatin, carboplatin or oxaliplatin) have the most nephrotoxic effects. ...
Article
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Background Nephrotoxicity is common among cancer patients, yet some anti-cancer drugs, for example, platinum derivatives, are nephrotoxic and have narrow therapeutic indices. If nephrotoxicity is not managed, it can progress to kidney injury, which results in unregulated blood pressure, hormonal imbalance, electrolyte imbalance, body fluid imbalance and death. However, the burden of nephrotoxicity among adult cancer patients in Uganda is not documented in the literature. Objective This study assessed the prevalence and risk factors of nephrotoxicity among cancer patients receiving chemotherapy at Mbarara Regional Referral Hospital Cancer Unit (MRRHCU). Methods The study was a cross-sectional study carried out at the MRRHCU, Uganda. All the 206 adult cancer patients who received at least three cycles of chemotherapy and fulfilled the inclusion criteria were included. A data collection form was used to collect data, which was recorded into Microsoft Excel version 2013. Data were analyzed using Stata version 12.1. Results Of the 206 participants, 74 (35.9%) developed nephrotoxicity with majority in stage 1 (n = 83, 40.3%) and stage 2 (n = 55, 26.7%). In the multivariate logistic regression of risk factors for nephrotoxicity, age >50 years old (aOR: 1.80, 95% CI: 1.06, 1.91; p > 0.001), hypertension (aOR: 1.71, 95% CI: 1.74, 1.94; p = 0.011) and use of platinum agents (aOR: 2.04, 95% CI: 1.82, 3.34; p = 0.002) were significant independent risk factors of nephrotoxicity. Conclusion About one-third (1/3) of the adult cancer patients at MRRHCU develop nephrotoxicity, which indicates a high burden of nephrotoxicity. The prevention of progression of nephrotoxicity from grades 0, 1 or 2 to grade 3 or 4 is therefore necessary, especially among the patients with risk factors, such as hypertension and age >50 years old and use of platinum agents.
... Although prolonged exposure to elevated C min causes nephrotoxicity, a temporary increase in the C min with an initial loading dose might not cause nephrotoxicity. Marvin et al. [29] reported that a loading dose > 20 mg/kg was not associated with increased nephrotoxicity in patients with a CL cr < 30 mL/min compared with a standard dosing regimen. ...
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Background Vancomycin therapeutic guidelines suggest a loading dose of 25–30 mg/kg for seriously ill patients. However, high-quality data to guide the use of loading dose are lacking. Evaluate whether a loading dose 1) achieves a target trough concentration (Cmin) at steady state and 2) improves early clinical responses. Methods Patients with an estimated glomerular filtration rate ≥90 mL/min/1.73 m2 were included. A loading dose of 25 mg/kg vancomycin followed by 15 mg/kg twice daily was compared with traditional dosing. A Cmin sample was obtained before the fifth dose. An early clinical response 48–72 h after the start of therapy and clinical success at end of therapy (EOT) was evaluated in patients with methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant coagulase-negative Staphylococci, or Enterococcus faecium. Results There was no significant difference in Cmin between the regimen with and without a loading dose (median: 10.4 µg/mL and 10.2 µg/mL, P=0.538). Proportions of patients achieving 10–20 µg/mL and 15–20 µg/mL were 56.9% and 5.6%, respectively, in patients with a loading dose. Although there was no significant difference in success rate at EOT between groups, loading dose was associated with increased early clinical responses for all infections [adjusted odds ratio (OR): 4.829, 95% confidence interval (CI): 1.441–16.188] and MRSA infections (OR: 10.851, 95% CI: 1.701–69.233). Increased adverse events were not observed with the loading dose. Study limitations included no Cmin measurements within 24 hours, and the inclusion of less critically ill patients. Conclusions Although the loading dose did not achieve optimal Cmin at steady state, a higher early clinical response was obtained compared with traditional dosing.
... Finally, 2 RCTs (158 patients) and 7 other studies (2658 patients) were included in the systematic review and meta-analysis. [14][15][16][17][18][19][20][21][22] The literature search and study selection process are shown in Figure 1. ...
Article
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Background: The clinical significance of using vancomycin loading dose remains controversial. A systematic review and meta-analysis were performed to assess the clinical efficacy and safety of vancomycin loading dose in the treatment of infections. Methods: The Pubmed, Embase, Web of Science, and Cochrane Library databases were searched from their inception up to 5 May 2019. Randomized controlled trials (RCTs) and other observational studies were included if they provided clinical outcomes or trough concentrations of vancomycin loading dose (20-30 mg/kg) and conventional-dose (10-20 mg/kg) in the treatment of infections. Achievement of therapeutic concentration (serum trough concentrations of vancomycin reached 15-20 mg/L before the second dose), clinical response (clinical improvement or culture-negative), nephrotoxicity (serum creatinine increase ≥0.5 mg/dL or ≥50% increasing from the baseline), other adverse events (including pruritus, flushing, rash, and/or red man syndrome), and mortality were analyzed. Heterogeneity was identified using the Cochrane I statistic, and P-value <.10 or I-values >50% indicated significant heterogeneity. Pooled estimates of the intervention effects were determined by the odds ratios (ORs) and 95% confidence intervals (CIs) in Review Manager program, version 5.3.5. Results: Two RCTs and 7 cohort studies including 2816 infected patients were selected for the analysis, in which serum trough concentrations of vancomycin following the use of vancomycin loading dose or other outcomes were available. Loading dose group had a significantly higher compliance rate of serum trough concentration of 15 to 20 mg/L (OR = 3.06; 95% CI = 1.15-8.15; P = .03) and significantly lower incidence of nephrotoxicity (OR = 0.59, 95% CI = 0.40-0.87; P = .008; I = 29%) compared with control group. No significant difference was noted between loading dose group and control group in terms of other adverse events and clinical response (OR = 1.98, 95% CI = 0.80-4.93; P = .14; I = 0%). The use of vancomycin loading doses in patients can indeed increase the achievement of therapeutic concentration. Conclusion: Vancomycin loading dose increases the achievement of therapeutic concentration without bringing extra risk of nephrotoxicity. However, well-designed large-scale RCTs remain needed to validate the clinical efficacy of vancomycin loading dose and to further evaluate other adverse reactions and mortality.PROSPERO registration number CRD42018093927.
Chapter
Appraisal of available literature published from January 2019 to April 2020 yielded a total of 98 studies, 14 of which pertained to aminoglycosides, 26 to fluoroquinolones, 23 to glycopeptides, 3 to clindamycin, 13 to macrolides, 7 to oxazolidinones, 4 to polymyxins, 5 to trimethoprim/sulfamethoxazole, 2 to daptomycin, 1 to nitrofurantoin, 1 to fosfomycin, and 1 to lefamulin. Our search yielded no pertinent literature for tedizolid and for trimethoprim alone.
Article
What is known and objective Vancomycin therapeutic guidelines suggest a loading dose of 25‐30 mg/kg for seriously ill patients. However, high‐quality data to guide the use of loading doses are lacking. We aimed to evaluate whether a loading dose (a) achieved a target trough concentration at steady state and (b) improved early clinical response. Methods Patients with an estimated glomerular filtration rate ≥ 90 mL/min/1.73 m² were included. A loading dose of 25 mg/kg vancomycin followed by 15 mg/kg twice daily was compared with traditional dosing. A Cmin sample was obtained before the fifth dose. An early clinical response 48‐72 hours after the start of therapy and clinical success at end of therapy (EOT) was evaluated in patients with methicillin‐resistant Staphylococcus aureus (MRSA), methicillin‐resistant coagulase‐negative Staphylococci or Enterococcus faecium. Results There was no significant difference in Cmin between the regimen with and without a loading dose (median: 10.4 and 10.2 µg/mL, P = .54). Proportions of patients achieving 10‐20 and 15‐20 µg/mL were 56.9% and 5.6%, respectively, in patients with a loading dose. Although there was no significant difference in success rate at EOT between groups, a loading dose was associated with increased early clinical response for all infections (adjusted odds ratio [OR]: 4.588, 95% confidence interval [CI]: 1.373‐15.330) and MRSA infections (OR: 12.065, 95% CI: 1.821‐79.959). Study limitations included no Cmin measurements within 24 hours and the inclusion of less critically ill patients. What is new and conclusion A loading dose of 25 mg/kg followed by 15 mg/kg twice daily did not achieve the optimal Cmin at steady state in patients with normal renal function. However, more early clinical responses were obtained with a loading dose compared with traditional dosing, possibly because of a prompt albeit temporary achievement of a more effective concentration.
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Vancomycin is a glycopeptide antibiotic that has been in clinical use for nearly 50 years as a penicillin alternative to treat penicillinaseproducing strains of Staphylococcus aureus. It is one of the most widely used antibiotics in the United States for the treatment of serious gram-positive infections involving methicillin-resistant S. aureus (MRSA). 1 Early use of vancomycin was associated with a number of adverse effects, including infusionrelated toxicities, nephrotoxicity, and possible ototoxicity. Upon further
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Evidence-based guidelines for implementation and measurement of antibiotic stewardship interventions in inpatient populations including long-term care were prepared by a multidisciplinary expert panel of the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. The panel included clinicians and investigators representing internal medicine, emergency medicine, microbiology, critical care, surgery, epidemiology, pharmacy, and adult and pediatric infectious diseases specialties. These recommendations address the best approaches for antibiotic stewardship programs to influence the optimal use of antibiotics.
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Objective: Vancomycin loading doses are recommended, however, the risk of nephrotoxicity with these doses is unknown. The primary objective of this study was to compare nephrotoxicity in emergency department (ED) sepsis patients who received vancomycin at high doses (>20 mg/kg) versus lower doses (≤20 mg/kg). Methods: A retrospective cohort study was performed in three academic EDs. Inclusion criteria: age ≥ 18 years, IV vancomycin order, and hospital admission. Exclusion criteria: no documented weight, hemodialysis-dependent, inadequate serum creatinine (SCr) values for the measured outcome. Analyses compared the incidence of nephrotoxicity for patients who received vancomycin at high dose (>20 mg/kg) vs. low dose (≤20 mg/kg). Results: A total of 2,131 consecutive patients prescribed vancomycin over 6 months were identified. Of these, 1,330 patients had three SCr values assessed for the primary outcome. High dose initial vancomycin was associated with a significantly lower rate of nephrotoxicity (5.8% vs 11.1%). After adjusting for age, gender, and initial SCr, the risk of high dose vancomycin compared to low dose was decreased for the development of nephrotoxicity (RR=0.60; 95% CI: 0.44, 0.82). Conclusion: Initial dosing of vancomycin >20 mg/kg, was not associated with an increased rate of nephrotoxicity compared with lower doses. Findings from this study support compliance with initial weight-based vancomycin loading doses. This article is protected by copyright. All rights reserved.
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To systematically assess the literature to ascertain the pharmacokinetics, pharmacodynamics, and clinical efficacy and safety associated with administration of a vancomycin loading dose (LD). MEDLINE (1948-December 31, 2014), EMBASE (1980-December 31, 2014), Cochrane Central Register of Controlled Trials, International Pharmaceutical Abstracts (1970-December 31, 2014), Google and Google Scholar, and International Clinical Trials Registry Platform were searched using the following terms: vancomycin, glycopeptides, loading dose, dose-response relationship. Pharmacokinetic, pharmacodynamic, and clinical efficacy studies using vancomycin LDs to achieve trough concentrations of 15 to 20 mg/L were included. Nonhuman, non-English, oral vancomycin, and dialysis patient studies were excluded. Abstracts were included. Study quality was ranked using US Preventative Services Task Force 1996 classification system. Data on study design, baseline characteristics, exclusion criteria, dosing, study outcomes, and conclusions were extracted. A total of 8 studies (5 manuscripts [2 level I, 3 level II-3] and 3 abstracts) were cited. Of 6 adult studies, 4 concluded that administration of vancomycin LDs resulted in significantly more patients achieving troughs of 15 to 20 mg/L. Studies in children found that LDs did not lead to rapid attainment of vancomycin levels ≥15 mg/L. No studies assessed clinical or microbiological outcomes. Limitations included heterogeneity and inconsistent timing of concentration measurements. High-quality data to guide the use of vancomycin LDs are lacking. LDs may more rapidly attain vancomycin troughs of 15 to 20 mg/L in adults, but information in pediatrics, obesity, and renal impairment is limited. Further studies are required to determine benefit of LDs on clinical and microbiological outcomes. © The Author(s) 2015.
Article
Objective To assess the impact of a computer physician order entry (CPOE) electronic order set on appropriate vancomycin dosing in the Emergency Department (ED). Methods We conducted a retrospective study examining ED dosing of vancomycin before and after the implementation of an electronic weight-based vancomycin order set. Pre- and post-implementation patient records were analyzed between the dates of June 1st and August 31st 2010 for the Pre-CPOE group and January 1st – March 31st 2013 for the Post-CPOE group. Statistical analysis: Chi square analysis, Fisher’s Exact Test, and t-tests were performed with a two-sided p-value < 0.05 denoting statistical significance, where appropriate. Results A total of 597 patients were included in the study, with 220 in the Pre-CPOE group and 377 in the Post-CPOE group. The use of the electronic order set resulted in a 21.9% increase (p < 0.05) in appropriate dosing with 67.4% (254/377) of Post-CPOE vancomycin doses considered appropriate versus 45.5% (100/220) in the Pre-CPOE group. In critically ill patients, there was a 16.3% increase in appropriate dosing with 44.7% (38/85) in the Post-CPOE group compared to 28.4% (19/67) in the Pre-CPOE group Conclusion The implementation of an electronic order set increased the percentage of ED patients receiving appropriate initial vancomycin doses.. The impact of increasing compliance to vancomycin guidelines is in accordance with stewardship principles that promote optimization of antimicrobial dosing based on individual patient characteristics. More studies are needed to assess the relationship between appropriate vancomycin loading doses in the ED and therapeutic outcomes.
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To describe the implementation of vancomycin dosing and monitoring practices recommended by the consensus guidelines in a diverse sample of hospitals, and to identify needs for quality improvement and research. Cross-sectional study using an online survey instrument. Making a Difference in Infectious Diseases Pharmacotherapy (MAD-ID) Research Network. A total of 163 respondents from MAD-ID who work in antimicrobial stewardship and represent unique hospitals. The survey population represented a wide range of patient populations (96% adult, 49% pediatric, and 23% long-term care) and settings (52% not-for-profit nonuniversity, 31% university based, and 11% for profit). Automatic consultation of pharmacy services for all vancomycin dosing was reported in 51% of the institutions. Among the dosing and monitoring practices endorsed by the consensus guidelines, participant institutions commonly followed these recommendations: use of trough concentrations without peak concentrations, maintenance of trough concentration higher than 10 mg/L, and target trough concentrations of 15-20 mg/L for complicated infections. In contrast, there was less consistent application of appropriate timing of trough concentrations, use of loading doses, and use of actual body weight. The remaining challenges and controversies surrounding vancomycin dosing are discussed. Despite the availability of consensus guideline recommendations, practices for dosing and monitoring of vancomycin are not universally applied. The findings of this survey highlight many opportunities for future research and quality improvement strategies.
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Antimicrobial pharmacokinetics (PK) and pharmacodynamics (PD) are important considerations, particularly in critically ill patients with severe sepsis and septic shock. The pathophysiologic changes that occur in these conditions can have a major effect on pharmacokinetic parameters, which in turn could result in failure to achieve pharmacodynamic targets for antimicrobials thus adversely affecting clinical outcome. This paper discusses the pathophysiologic changes that occur during severe sepsis and septic shock and the consequent effects on antimicrobial PK and PD. The effect of PK/PD on specific antimicrobial classes is discussed and a rational framework for antimicrobial dosing is provided. Knowledge of PK/PD properties of antimicrobials can be used to personalize dosing regimens not only to maximize antimicrobial activity but also to minimize toxicity and reduce the development of antimicrobial resistance.
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The goal of this investigation was to determine whether more aggressive vancomycin dosing is associated with greater risk for renal toxicity in patients with health care-associated pneumonia (HCAP) attributed to methicillin-resistant Staphylococcus aureus (MRSA). This was a retrospective, single-center, observational cohort study. The following information was obtained for all study patients from automated hospital, microbiology, and pharmacy databases: age, sex, weight, serial serum creatinine (SCr), age- and sex-adjusted creatinine clearance (CrCl) during receipt of vancomycin, vancomycin serum trough concentrations, duration of vancomycin therapy, and Acute Physiology and Chronic Health Evaluation II scores. Renal toxicity was defined as either a 0.5-mg/dL increase from baseline in SCr or a >or=50% increase in SCr based on serial SCr measurements. Data for patients who met the definition of renal toxicity were compared with data for those who did not. Ninety-four patients (mean [SD]age, 59.0 [15.6] years; 59 [62.8%] men; 73 (77.7%) white; mean baseline CrCl, 70.3 [23.0] mL/min) were identified as having MRSA HCAP. Forty (42.6%) patients developed renal toxicity. Patients who developed renal toxicity were significantly more likely than patients who did not develop renal toxicity to have greater mean vancomycin serum trough concentrations (20.8 [9.9] g/mL vs 14.3 [6.7] g/mL, respectively; P < 0.001), vancomycin serum trough concentrations >or=15 g/mL (67.5% vs 40.7%; P = 0.01), and a prolonged duration (>or=14 days) of vancomycin treatment (45.0% vs 20.4%; P = 0.011). Logistic regression analysis identified a maximum vancomycin serum trough concentration of >or=15 g/mL as being independently associated with renal toxicity (adjusted odds ratio = 2.82; 95% CI, 1.02-7.74; P = 0.045). The overall mean change in CrCl for the study population was -13.5 (-16.0) mL/min (range, 0.0 to -62.6 mL/min). Patients with maximum measured vancomycin serum trough concentrations >or=15 g/mL (n = 49) had significantly greater absolute changes in CrCl compared with patients with maximum measured vancomycin serum trough concentrations <15 g/mL (n = 45) (-18.9 [-17.0] vs -7.6 [-12.5] mL/min, respectively; P < 0.001). The results suggest that aggressive vancomycin dosing and prolonged vancomycin administration may be associated with greater risk for renal toxicity in patients with MRSA HCAP. However, this retrospective study cannot establish causation, and a prospective, randomized, double-blind trial is needed.
KDIGO clinical practice guideline for acute kidney injury.