The Nephrotoxicity of Vancomycin.
TL;DR: This work critically examines available data in adult patients pertinent to this question, and reviews the pharmacokinetics/pharmacodynamics of vancomycin metabolism, effectiveness and safety data, as well as investigating the potential synergistic nephrotoxicity of van comycin and piperacillin‐tazobactam.
Abstract: Vancomycin use is often associated with nephrotoxicity. It remains uncertain, however, to what extent vancomycin is directly responsible, as numerous potential risk factors for acute kidney injury frequently coexist. Herein, we critically examine available data in adult patients pertinent to this question. We review the pharmacokinetics/pharmacodynamics of vancomycin metabolism. Efficacy and safety data are discussed. The pathophysiology of vancomycin nephrotoxicity is considered. Risk factors for nephrotoxicity are enumerated, including the potential synergistic nephrotoxicity of vancomycin and piperacillin-tazobactam. Suggestions for clinical practice and future research are given.
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01 Sep 2008
TL;DR: The Methodology used to Prepare the Guideline Epidemiology Incidence Etiology and Recommendations for Assessing Response to Therapy Suggested Performance Indicators is summarized.
Abstract: Executive Summary Introduction Methodology Used to Prepare the Guideline Epidemiology Incidence Etiology Major Epidemiologic Points Pathogenesis Major Points for Pathogenesis Modifiable Risk Factors Intubation and Mechanical Ventilation Aspiration, Body Position, and Enteral Feeding Modulation of Colonization: Oral Antiseptics and Antibiotics Stress Bleeding Prophylaxis, Transfusion, and Glucose Control Major Points and Recommendations for Modifiable Risk Factors Diagnostic Testing Major Points and Recommendations for Diagnosis Diagnostic Strategies and Approaches Clinical Strategy Bacteriologic Strategy Recommended Diagnostic Strategy Major Points and Recommendations for Comparing Diagnostic Strategies Antibiotic Treatment of Hospital-acquired Pneumonia General Approach Initial Empiric Antibiotic Therapy Appropriate Antibiotic Selection and Adequate Dosing Local Instillation and Aerosolized Antibiotics Combination versus Monotherapy Duration of Therapy Major Points and Recommendations for Optimal Antibiotic Therapy Specific Antibiotic Regimens Antibiotic Heterogeneity and Antibiotic Cycling Response to Therapy Modification of Empiric Antibiotic Regimens Defining the Normal Pattern of Resolution Reasons for Deterioration or Nonresolution Evaluation of the Nonresponding Patient Major Points and Recommendations for Assessing Response to Therapy Suggested Performance Indicators
2,961 citations
TL;DR: The association of type and duration of prophylaxis with surgical site infection, acute kidney injury, and Clostridium difficile infection, and SSI was characterized and increasing duration of anti-infection efforts was associated with higher odds of AKI and C difficiles infection.
Abstract: Importance The benefits of antimicrobial prophylaxis are limited to the first 24 hours postoperatively. Little is known about the harms associated with continuing antimicrobial prophylaxis after skin closure. Objective To characterize the association of type and duration of prophylaxis with surgical site infection (SSI), acute kidney injury (AKI), andClostridium difficileinfection. Design, Setting, and Participants In this multicenter, national retrospective cohort study, all patients within the national Veterans Affairs health care system who underwent cardiac, orthopedic total joint replacement, colorectal, and vascular procedures and who received planned manual review by a trained nurse reviewer for type and duration of surgical prophylaxis and for SSI from October 1, 2008, to September 30, 2013, were included. Data were analyzed using multivariable logistic regression, with adjustments for covariates determined a priori to be associated with the outcomes of interest. Data were analyzed from December 2016 to December 2018. Exposures Duration of postoperative antimicrobial prophylaxis ( Main Outcomes and Measures Surgical site infection, AKI, andC difficileinfection. Results Of the 79 058 included patients, 76 109 (96.3%) were men, and the mean (SD) age was 64.8 (9.4) years. Among 79 058 surgical procedures in the cohort, all had SSI andC difficileoutcome data available; 71 344 (90.2%) had AKI outcome data. After stratification by type of surgery and adjustment for age, sex, race, diabetes, smoking, American Society of Anesthesiologists score greater than 2, methicillin-resistantStaphylococcus aureuscolonization, mupirocin, type of prophylaxis, and facility factors, SSI was not associated with duration of prophylaxis. Adjusted odds of AKI increased with each additional day of prophylaxis (cardiac procedure: 24- Conclusions and Relevance Increasing duration of antimicrobial prophylaxis was associated with higher odds of AKI andC difficileinfection in a duration-dependent fashion; extended duration did not lead to additional SSI reduction. These findings highlight the notion that every day matters and suggest that stewardship efforts to limit duration of prophylaxis have the potential to reduce adverse events without increasing SSI.
191 citations
TL;DR: AUCs measured in the first or second 24 hours and lower than ~650 mg*h/L may result in a decreased risk of AKI, and vancomycin AUC monitoring strategy mayresult in less vancomYcin-associated AKI.
Abstract: Background This study analyzed the relationship between vancomycin area under the concentration-time curve (AUC) and acute kidney injury (AKI) reported across recent studies. Methods A systematic review of PubMed, Medline, Scopus, and compiled references was conducted. We included randomized cohort and case-control studies that reported vancomycin AUCs and risk of AKI (from 1990 to 2018). The primary outcome was AKI, defined as an increase in serum creatinine of ≥0.5 mg/L or a 50% increase from baseline on ≥2 consecutive measurements. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Primary analyses compared the impact of AUC cutpoint (greater than ~650 mg × hour/L) and AKI. Additional analysis compared AUC vs trough-guided monitoring on AKI incidence. Results Eight observational studies met inclusion/exclusion criteria with data for 2491 patients. Five studies reported first-24-hour AUCs (AUC0-24) and AKI, 2 studies reported 24- to 48-hour AUCs (AUC24-48) and AKI, and 2 studies reported AKI associated with AUC- vs trough-guided monitoring. AUC less than approximately 650 mg × hour/L was associated with decreased AKI for AUC0-24 (OR, 0.36 [95% CI, .23-.56]) as well as AUC24-48 (OR, 0.45 [95% CI, .27-.75]). AKI associated with the AUC monitoring strategy was significantly lower than trough-guided monitoring (OR, 0.68 [95% CI, .46-.99]). Conclusions AUCs measured in the first or second 24 hours and lower than approximately 650 mg × hour/L may result in a decreased risk of AKI. Vancomycin AUC monitoring strategy may result in less vancomycin-associated AKI. Additional investigations are warranted.
117 citations
TL;DR: This study shows that formulations of existing antibiotics in nanocarrier systems can improve their therapeutic efficiency, indicating that combination therapy with drug-loaded silica nanoparticles may provide a better treatment outcome for infections that require high concentrations of multiple drugs.
76 citations
TL;DR: The place in therapy, mechanism of action, pharmacokinetic, pharmacodynamic, and other pharmacologic considerations encountered when prescribing commonly used antibiotics in patients with chronic kidney disease or ESKD are discussed.
Abstract: Antimicrobial pharmacology and its effect on prescribing is quite complex. Selecting an antibiotic that will optimally treat an infection while minimizing adverse effects and the development of resistance is only the first step, as one must also consider the patient’s individual pharmacokinetic alterations and the pharmacodynamic properties of the drug when prescribing it as well. Patients with CKD may have alterations in their protein binding, volumes of distribution, kidney clearance, and nonrenal clearance that necessitates antibiotic dose adjustments to prevent the development of toxicity. Knowledge of a drug’s pharmacodynamics, defined as the relationship between drug exposure and antibacterial efficacy, provides some guidance regarding the optimal way to make dose adjustments. Different pharmacodynamic goals, such as maximizing the time that free (unbound) drug concentrations spend above the minimum inhibitory concentration (MIC) for time dependent drugs (e.g., β-lactams) or maximizing the free peak-to-MIC ratio for concentration-dependent antibiotics (e.g., aminoglycosides), require different adjustment strategies; for instance, decreasing the dose while maintaining normal dosing frequency or giving normal (or even larger) doses less frequently, respectively. Patients receiving hemodialysis have other important prescribing considerations as well. The nephrologist or patient may prefer to receive antibiotics that can be administered intravenously toward the end of a dialysis session. Additionally, newer dialysis technologies and filters can increase drug removal more than originally reported. This review will discuss the place in therapy, mechanism of action, pharmacokinetic, pharmacodynamic, and other pharmacologic considerations encountered when prescribing commonly used antibiotics in patients with chronic kidney disease or ESKD.
68 citations
References
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TL;DR: These guidelines discuss the management of a variety of clinical syndromes associated with MRSA disease, including skin and soft tissue infections (SSTI), bacteremia and endocarditis, pneumonia, bone and joint infections, and central nervous system infections.
Abstract: Evidence-based guidelines for the management of patients with methicillin-resistant Staphylococcus aureus (MRSA) infections were prepared by an Expert Panel of the Infectious Diseases Society of America (IDSA). The guidelines are intended for use by health care providers who care for adult and pediatric patients with MRSA infections. The guidelines discuss the management of a variety of clinical syndromes associated with MRSA disease, including skin and soft tissue infections (SSTI), bacteremia and endocarditis, pneumonia, bone and joint infections, and central nervous system (CNS) infections. Recommendations are provided regarding vancomycin dosing and monitoring, management of infections due to MRSA strains with reduced susceptibility to vancomycin, and vancomycin treatment failures.
3,370 citations
"The Nephrotoxicity of Vancomycin." refers background in this paper
...The 2009 Guidelines recommend considering alternative therapy,(8) but the IDSA 2011 guidelines state vancomycin should be continued irrespective of the MIC unless lack of response occurs.(1) Determining an AUC, and hence the AUC/MIC, is impractical under normal clinical circumstances due to the large number of blood draws required after a single dose....
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01 Sep 2008
TL;DR: The Methodology used to Prepare the Guideline Epidemiology Incidence Etiology and Recommendations for Assessing Response to Therapy Suggested Performance Indicators is summarized.
Abstract: Executive Summary Introduction Methodology Used to Prepare the Guideline Epidemiology Incidence Etiology Major Epidemiologic Points Pathogenesis Major Points for Pathogenesis Modifiable Risk Factors Intubation and Mechanical Ventilation Aspiration, Body Position, and Enteral Feeding Modulation of Colonization: Oral Antiseptics and Antibiotics Stress Bleeding Prophylaxis, Transfusion, and Glucose Control Major Points and Recommendations for Modifiable Risk Factors Diagnostic Testing Major Points and Recommendations for Diagnosis Diagnostic Strategies and Approaches Clinical Strategy Bacteriologic Strategy Recommended Diagnostic Strategy Major Points and Recommendations for Comparing Diagnostic Strategies Antibiotic Treatment of Hospital-acquired Pneumonia General Approach Initial Empiric Antibiotic Therapy Appropriate Antibiotic Selection and Adequate Dosing Local Instillation and Aerosolized Antibiotics Combination versus Monotherapy Duration of Therapy Major Points and Recommendations for Optimal Antibiotic Therapy Specific Antibiotic Regimens Antibiotic Heterogeneity and Antibiotic Cycling Response to Therapy Modification of Empiric Antibiotic Regimens Defining the Normal Pattern of Resolution Reasons for Deterioration or Nonresolution Evaluation of the Nonresponding Patient Major Points and Recommendations for Assessing Response to Therapy Suggested Performance Indicators
2,961 citations
TL;DR: Vancomycin is a glycopeptide antibiotic that is one of the most widely used antibiotics in the United States for the treatment of serious gram-positive streptococcus aureus infections.
Abstract: Vancomycin is a glycopeptide antibiotic that has been in clinical use for nearly 50 years as a penicillin alternative to treat penicillinase-producing strains of Staphylococcus aureus . It is one of the most widely used antibiotics in the United States for the treatment of serious gram-positive
1,608 citations
TL;DR: High prevalence of clinical MRSA strains with elevated vancomycin MIC (2 microg/mL) requires aggressive empirical vancomYcin dosing to achieve a trough greater than 15 microg /mL, and Combination or alternative therapy should be considered for invasive infections caused by these strains.
Abstract: Background Vancomycin hydrochloride treatment failure for infections caused by susceptible methicillin-resistant Staphylococcus aureus (MRSA) strains with high minimum inhibitory concentration (MIC) has prompted recent guidelines to recommend a higher vancomycin target trough of 15 to 20 μg/mL. Methods A prospective cohort study of adult patients infected with MRSA was performed to determine the distribution of vancomycin MIC and treatment outcomes with vancomycin doses targeting an unbound trough of at least 4 times the MIC. The microbiology laboratory computer records were used to identify all patients from whom MRSA was isolated from August 1, 2004, through June 30, 2005. Primary outcome measures were clinical response, mortality, and nephrotoxicity. Patients were placed into subgroups based on target trough attainment and high vs low vancomycin MIC (≥2 vs Results Of the 95 patients in the study, 51 (54%) were infected with high-MIC strains and had pneumonia (77%) and/or bacteremia. An initial response rate of 74% was achieved if the target trough was attained irrespective of MIC. However, despite achieving the target trough, the high-MIC group had lower end-of-treatment responses (24/39 [62%] vs 34/40 [85%]; P = .02) and higher infection-related mortality (11/51 [24%] vs 4/44 [10%]; P =.16) compared with the low-MIC group. High MIC ( P = .03) and Acute Physiology and Chronic Health Evaluation II score ( P = .009) were independent predictors of poor response in multivariate analysis. Nephrotoxicity occurred only in the high-trough group (11/63 [12%]), significantly predicted by concomitant therapy with other nephrotoxic agents. Conclusions High prevalence of clinical MRSA strains with elevated vancomycin MIC (2 μg/mL) requires aggressive empirical vancomycin dosing to achieve a trough greater than 15 μg/mL. Combination or alternative therapy should be considered for invasive infections caused by these strains.
845 citations
TL;DR: The safety and efficacy of daptomycin were comparable with conventional therapy, and the frequency and distribution of adverse events were similar among both treatment groups.
Abstract: Daptomycin is the first available agent from a new class of antibiotics, the cyclic lipopeptides, that has activity against a broad range of gram-positive pathogens, including organisms that are resistant to methicillin, vancomycin, and other currently available agents. Daptomycin (4 mg/kg intravenously [iv] every 24 h for 7-14 days) was compared with conventional antibiotics (penicillinase-resistant penicillins [4-12 g iv per day] or vancomycin [1 g iv every 12 h]) in 2 randomized, international trials involving 1092 patients with complicated skin and skin-structure infections. Among 902 clinically evaluable patients, clinical success rates were 83.4% and 84.2% for the daptomycin- and comparator-treated groups, respectively (95% confidence interval, -4.0 to 5.6). Among patients successfully treated with iv daptomycin, 63% required only 4-7 days of therapy, compared with 33% of comparator-treated patients (P<.0001). The frequency and distribution of adverse events were similar among both treatment groups. Overall, the safety and efficacy of daptomycin were comparable with conventional therapy.
657 citations