Empiric guideline-recommended weight-based vancomycin dosing and nephrotoxicity rates in patients with methicillin-resistant Staphylococcus aureus bacteremia: a retrospective cohort study

Hall, Ronald G.; Hazlewood, Kathleen A.; Brouse, Sara D.; Giuliano, Christopher; Haase, Krystal K.; Frei, Christopher R.; Forcade, Nicolas A.; Bell, Todd; Bedimo, Roger; Álvarez, Carlos A.

doi:10.1186/2050-6511-14-12

Cited by 43 publications

(42 citation statements)

References 24 publications

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“…A multicenter prospective clinical trial, including 288 adult patients (70), and a recent meta-analysis (71) have reaffirmed the high probability of nephrotoxicity with vancomycin trough levels of Ͼ15 mg/liter. This threshold is not uniform in all studies, and other authors have found that recommended dosages of vancomycin with target troughs of 15 to 20 mg/liter are not an independent risk factor for nephrotoxicity (72). Davies et al (73) found that vancomycin was related to a rise in creatinine levels only with trough levels of Ͼ20 mg/liter.…”

Section: Vancomycin Toxicitymentioning

confidence: 94%

Optimizing the Clinical Use of Vancomycin

Álvarez

López-Cortés

Molina

et al. 2016

Antimicrob Agents Chemother

195

124

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Pharmacists published specific guidelines about vancomycin dosage and monitoring. However, these guidelines have not been updated in the past 6 years. This review analyzes the new available information about vancomycin published in recent years regarding pharmacokinetics and pharmacodynamics, serum concentration monitoring, and optimal vancomycin dosing in special situations (obese people, burn patients, renal replacement therapy, among others). Vancomycin efficacy is linked to a correct dosage which should aim to reach an area under the curve (AUC)/MIC ratio of >400; serum trough levels of 15 to 20 mg/liter are considered a surrogate marker of an AUC/MIC ratio of >400 for a MIC of <1 mg/liter. For Staphylococcus aureus strains presenting with a MIC >1 mg/liter, an alternative agent should be considered. Vancomycin doses must be adjusted according to body weight and the plasma trough levels of the drug. Nephrotoxicity has been associated with target vancomycin trough levels above 15 mg/liter. Continuous infusion is an option, especially for patients at high risk of renal impairment or unstable vancomycin clearance. In such cases, vancomycin plasma steady-state level and creatinine monitoring are strongly indicated. Vancomycin has traditionally been used as a first-line agent for treating methicillin-resistant Staphylococcus aureus (MRSA) and other Gram-positive beta-lactam-resistant bacteria (1), which are frequent etiologies of severe health-related infections (2, 3).Although the effectiveness of vancomycin is supported by more than 5 decades of use and multiple studies, the clinical and microbiological scenario in which it is used is always changing. Attaining an appropriate dosage of vancomycin for S. aureus infections might be difficult due to the clinical impact of the creep in the MIC of vancomycin and heteroresistance among MRSA strains, or due to complex pharmacokinetic and pharmacodynamic (PK/PD) situations. In this context, the American Society of Health-System Pharmacists (ASHP), the Infectious Diseases Society of America (IDSA), and the Society of Infectious Diseases Pharmacists (SIDP) introduced a practice guideline in 2009 (4), marking a milestone in vancomycin therapy. However, several questions, such as the optimal dosing in some special clinical situations (e.g., with renal replacement therapies or in burn patients or obese patients), the role of continuous infusion, or the renal toxicity when the suggested vancomycin serum levels are achieved, remain unanswered. The present review mainly focuses on these issues. VANCOMYCIN PHARMACODYNAMICS AND ITS IMPLICATIONS FOR DRUG MONITORINGThe killing effect of vancomycin is characterized by a slow mode of action and is further hampered by a large bacterial inoculum, a stationary growth phase, and anaerobic conditions (5, 6). Although several pharmacodynamic parameters have been proposed to determine vancomycin activity, data from experimental and clinical studies have selected the area under the curve (AUC)/ MIC ratio as the best parameter to predict the...

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Section: Vancomycin Toxicitymentioning

confidence: 94%

Optimizing the Clinical Use of Vancomycin

Álvarez

López-Cortés

Molina

et al. 2016

Antimicrob Agents Chemother

195

124

View full text Add to dashboard Cite

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“…Our patients had several risk factors that are typically associated with vancomycin nephrotoxicity: high trough concentrations, 9,10 obesity, 11 concomitant administration of piperacillin-tazobactam, and in a few patients, aminoglycosides. 12, 13 A recent study has suggested that piperacillin-tazobactam increases vancomycin-induced nephrotoxicity, but we failed to reproduce this finding experimentally in mice.…”

Section: Introductionmentioning

confidence: 99%

Vancomycin-Associated Cast Nephropathy

Luque

Louis

Jouanneau

et al. 2017

JASN

124

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Vancomycin is a widely prescribed antibiotic, but the exact nature of vancomycin-associated nephrotoxicity is unclear, in particular when considering the frequent coadministration of aminoglycosides. We describe here the initial case of a 56-year-old woman with normal renal function developing unexplained ARF without hypovolemia after administration of vancomycin without coadministration of aminoglycosides. Studying the patient’s renal biopsy specimen, we ascertained that obstructive tubular casts composed of noncrystal nanospheric vancomycin aggregates entangled with uromodulin explained the vancomycin-associated ARF. We developed in parallel a new immunohistologic staining technique to detect vancomycin in renal tissue and confirmed retrospectively that deleterious vancomycin-associated casts existed in eight additional patients with acute tubular necrosis in the absence of hypovolemia. Concomitant high vancomycin trough plasma levels had been observed in each patient. We also reproduced experimentally the toxic and obstructive nature of vancomycin-associated cast nephropathy in mice, which we detected using different in vivo imaging techniques. In conclusion, the interaction of uromodulin with nanospheric vancomycin aggregates represents a new mode of tubular cast formation, revealing the hitherto unsuspected mechanism of vancomycin-associated renal injury.

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“…The association between VT or vancomycin total daily dose and AKI has been described in several studies [4,5,[8][9][10][11][12][13][14] . However, some studies demonstrated that higher VT level of 15-20 is not more associated with AKI than lower levels [7,15,16] .…”

Section: Discussionmentioning

confidence: 99%

Vancomycin Trough and Acute Kidney Injury: A Large Retrospective, Cohort Study

Hammoud

Brimacombe

et al. 2016

Am J Nephrol

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Background: The association between vancomycin trough (VT) and acute kidney injury (AKI) at the recommended doses remains controversial. Methods: The authors conducted a retrospective, observational cohort study of 500 adult patients who received vancomycin for ≥72 h. Data collected included 2 main predictors: average VT (including only VTs before the occurrence of AKI), first VT and other possible risk factors for AKI. The baseline characteristics/variables between patients with AKI and patients with no AKI were compared. Logistic regression models were used to develop multivariate models. The authors divided the patients into 4 subgroups: (1) VT <10, (2) 10 ≤ VT < 15, (3) 15 ≤ VT < 20 and (4) VT ≥20 µg/ml. All subgroups were compared to subgroup 2 (reference group). Results: AKI occurred in 12.85% of patients while on vancomycin. The incidence of AKI in subgroups 1-4 was 8.02, 13.61, 13.70 and 31.82%, respectively, using the first VT, that is significantly higher in subgroup 4. Using average VT, AKI incidence was 5, 10.38, 19.01 and 25.58%, respectively, that is significantly higher in subgroups 3 and 4. On multivariate logistic regression, average VT, first VT, average VT >15, first VT >15, methicillin-resistant Staphylococcus aureus infection and morbid obesity were significantly associated with increased incidence of AKI. Conclusion: Clinicians should be careful when aiming for a VT >15 μg/ml as this is associated with increased incidence of AKI.

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Empiric guideline-recommended weight-based vancomycin dosing and nephrotoxicity rates in patients with methicillin-resistant Staphylococcus aureus bacteremia: a retrospective cohort study

Cited by 43 publications

References 24 publications

Optimizing the Clinical Use of Vancomycin

Optimizing the Clinical Use of Vancomycin

Vancomycin-Associated Cast Nephropathy

Vancomycin Trough and Acute Kidney Injury: A Large Retrospective, Cohort Study

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