Relationship Between Initial Vancomycin Trough Levels and Early-Onset Vancomycin-Associated Nephrotoxicity in Critically Ill Patients

Abstract BackgroundVancomycin is a commonly used antibiotic in critically ill patients for various indications. Critical illness imposes pharmacokinetic-pharmacodynamics challenges which makes optimizing vancomycin in this population cumbersome. Data are scarce on the clinical impact of time to therapeutic trough levels of vancomycin in critically ill patients. Objective (s)The aim of this study to evaluate the timing to achieve therapeutic trough level vancomycin on 30-day mortality in critically ill patients.SettingAdult critically ill patients admitted to intensive care units (ICUs) between January 1st, 2017 and December 31st, 2018 at a tertiary teaching hospital.MethodA retrospective cohort study for all adult critically ill patients aged 18 years or older with confirmed gram-positive infection and received vancomycin. We compared early (<48 hours) versus late (≥ 48 hours) attainment of vancomycin therapeutic trough levels. Main outcomesPrimary outcome was the 30-day mortality in critically ill patients. Secondary outcomes were development of resistant organisms, eradicating microorganisms within 4-5 days of vancomycin initiation, vancomycin-induced acute kidney injury (AKI), and ICU LOS. ResultsTwo hundred and nine patients were included. No significant differences between comparative groups in baseline characteristics. Achieving therapeutic levels were associated with better survival at 30 days (OR: 0.48; 95% CI [0.26-0.87]; p<0.01). Additionally, patients who achieved therapeutic levels of vancomycin early were less likely to develop resistant organisms (OR=0.08; 95% CI [0.01-0.59]; p=0.01). Acute kidney injury (AKI) and ICU length of stay (LOS) were not significant between the two groups.ConclusionEarly attainment of vancomycin therapeutic levels was associated with possible survival benefit.

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Association of early-onset constipation and diarrhea with patient outcomes in critically ill ventilated patients: a retrospective observational cohort study

10.21203/rs.3.rs-966931/v1 ◽

2021 ◽

Author(s):

Gen Aikawa ◽

Akira Ouchi ◽

Hideaki Sakuramoto ◽

Tetsuya Hoshino ◽

Yuki Enomoto ◽

...

Keyword(s):

Critically Ill ◽

Critically Ill Patients ◽

Early Onset ◽

Multivariable Analysis ◽

Icu Admission ◽

Icu Stay ◽

Normal Defecation ◽

Poor Outcomes ◽

Length Of Icu Stay ◽

Ventilated Patients

Abstract Constipation and diarrhea are both associated with poor outcomes in critically ill patients. Although constipation and diarrhea are closely related, few studies have examined them simultaneously. The purpose of this study was to describe patient defecation status after intensive care unit (ICU) admission and determine the association of early-onset constipation and diarrhea after ICU admission with outcomes for critically ill ventilated patients. Critically ill patients were retrospectively investigated and their defecation status was assessed during the first week after admission. The patients were divided into three groups: normal defecation, constipation, and diarrhea, and multiple comparison tests were performed. Additionally, multivariable analysis was performed for mortality and length of stay. Of the 85 critically ill ventilated patients, 47 (55%) experienced constipation, and 12 (14%) experienced diarrhea during the first week of ICU admission. Patients with normal defecation and diarrhea increased from the fourth and fifth day of ICU admission. Diarrhea was significantly associated with the length of ICU stay (B=7.534, 95% confidence interval: 0.116-14.951). Early-onset constipation and diarrhea were common in critically ill ventilated patients, and early-onset diarrhea was associated with the length of ICU stay. Prevention of constipation and diarrhea before the fifth day of ICU admission is essential.

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Vancomycin-Associated Acute Kidney Injury in Critically Ill Adolescent and Young Adult Patients

Journal of Pharmacy Practice ◽

10.1177/0897190019829652 ◽

2019 ◽

Vol 33 (6) ◽

pp. 749-753 ◽

Cited By ~ 2

Author(s):

William B. Hays ◽

Emma Tillman

Keyword(s):

Risk Factors ◽

Acute Kidney Injury ◽

Young Adult ◽

Critically Ill ◽

Kidney Injury ◽

Adult Patients ◽

Adolescent And Young Adult ◽

Daily Dose ◽

Vancomycin Trough ◽

Trough Levels

Background: Risk factors for the development of vancomycin-associated acute kidney injury (AKI) have been evaluated in both pediatric and adult populations; however, no previous studies exist evaluating this in the critically ill adolescent and young adult patients. Objective: Identify the incidence of AKI and examine risk factors for the development of AKI in critically ill adolescents and young adults on vancomycin. Methods: This retrospective review evaluated the incidence of AKI in patients 15 to 25 years of age who received vancomycin, while admitted to an intensive care unit. Acute kidney injury in this population was defined as an increase in serum creatinine by 0.5 mg/dL or 50% from baseline. Patients who developed AKI were evaluated for specific risk factors compared to those who did not develop AKI. Results: A total of 50 patients (20 developed AKI) were included in the study. There was no difference in vancomycin daily dose or duration of vancomycin therapy. Maximum vancomycin trough (31.15 mg/dL vs 12.5 mg/dL, P = .006), percentage of patients with concurrent nephrotoxic medication (95% vs 60%, P = .012) and concurrent vasopressor (55% vs 23%, P = .029) were higher in those who developed AKI. Percentage of patients who underwent a procedure while on vancomycin (35% vs 6.7%, P = .021) was also higher within the AKI group. Conclusions: Vancomycin-associated AKI occurred in 40% of critically ill adolescent and young adult patients. These patients may be more likely to develop vancomycin-associated AKI if they had undergone a procedure, as well as in the presence of high vancomycin trough levels, concurrent nephrotoxic agents, and concurrent vasopressor therapy.

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A fixed dose approach to thrombosis chemoprophylaxis may be inadequate in heavier critically ill patients

Critical Care and Resuscitation ◽

10.51893/2021.1.oa9 ◽

2021 ◽

Vol 23 (1) ◽

pp. 94-102

Author(s):

George Yi ◽

◽

Adam M Deane ◽

Melissa Ankravs ◽

Lucy Sharrock ◽

...

Keyword(s):

Critically Ill ◽

Critically Ill Patients ◽

Prescribing Patterns ◽

Fixed Dose ◽

Single Centre ◽

Eligibility Criteria ◽

Once Daily ◽

The Third ◽

Fourth Dose ◽

Trough Levels

Objectives: Overweight patients are at greater risk of venous thromboembolism. We aimed to describe prescribing patterns of thrombosis chemoprophylaxis in critically ill patients weighing ≥ 100 kg and quantify the effectiveness of these regimens using the surrogate biomarker of plasma anti-Xa level. Design, setting and patients: A prospective single-centre cohort study was conducted over a 6-month period. Patients weighing ≥ 100 kg who were prescribed enoxaparin for chemoprophylaxis and expected to remain in the intensive care unit for > 48 hours were eligible. Anti-Xa levels were measured once a patient had received at least three consecutive doses of enoxaparin. Peak levels were measured 4–6 hours after the third dose and trough levels were measured before the fourth dose. Anti-Xa levels were compared with established target ranges for peak and trough anti-Xa levels (0.2–0.5 IU/mL and > 0.1 IU/mL, respectively). Results: Eighty-eight patients met the eligibility criteria, and anti-Xa levels for 42 patients were obtained. Fixed dose chemoprophylaxis approaches varied considerably, with 40 mg once daily (54/88 [61%]) and 40 mg twice daily (20/88 [23%]) being the most frequently prescribed regimens. No patient had a peak anti-Xa level > 0.5 IU/mL. When comparing 40 mg once daily versus twice daily, the once daily regimen had lower median trough levels (0.01 IU/mL [interquartile range (IQR), 0.00–0.04] v 0.09 IU/mL [IQR, 0.05–0.13]; P < 0.001) and greater proportions of patients with levels below the established range (< 0.1 IU/mL) (15/16 [95%] v 7/14 [50%]; P = 0.002) and levels that were undetectable (0.00 IU/mL) (8/16 [50%] v 1/14 [7%]; P = 0.01). Conclusions: At a single centre, thrombosis chemoprophylaxis prescribing patterns for heavier critically ill patients varied considerably. Current fixed dose approaches may be inadequate in this cohort

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The Effect of Hypoalbuminemia on the Therapeutic Concentration and Dosage of Vancomycin in Critically Ill Septic Patients in Low-Resource Countries

Dose-Response ◽

10.1177/1559325819850419 ◽

2019 ◽

Vol 17 (2) ◽

pp. 155932581985041 ◽

Cited By ~ 1

Author(s):

Tijana Kovacevic ◽

Branislava Miljkovic ◽

Momir Mikov ◽

Svjetlana Stojisavljevic Satara ◽

Sasa Dragic ◽

...

Keyword(s):

Critically Ill ◽

High Probability ◽

Serum Levels ◽

Loading Dose ◽

Therapeutic Concentration ◽

Dose Administration ◽

Single Center Study ◽

Vancomycin Trough ◽

Vancomycin Dosage ◽

Trough Levels

Purpose: To determine whether severe hypoalbuminemia (<25 mg/L) has a significant effect on serum levels of vancomycin and whether it can effect vancomycin dosage regimen and the loading dose administration. Material and Methods: Prospective, cohort, and a single-center study included 61 patients whose vancomycin serum levels were measured in steady state. Vancomycin trough levels ( C min) that were in the range 15 to 20 µg/mL were considered therapeutic and trough levels higher than 15 µg/mL were considered potentially nephrotoxic. Results: In the group of patients with severe hypoalbuminemia, C min was significantly higher compared to the those with nonsevere hypoalbuminemia (>25 mg/L; 23.04 [19.14] vs 13.28 [11.28], P = .01). In the group of patients who received the vancomycin loading dose of 2 g, C min was significantly higher in patients with severe hypoalbuminemia compared to the patients with nonsevere hypoalbuminemia (34.52 [25.93] vs 15.37 [10.48], P = .04). Conclusion: In critically ill septic patients with severe hypoalbuminemia, there is a high probability that the loading dose of vancomycin is not necessary since it is associated with potentially toxic vancomycin C min, while in the patients with nonsevere hypoalbuminemia the loading dose may be necessary to achieving therapeutic C min.

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Pharmacokinetics of Meropenem in Critically Ill Patients with Acute Renal Failure Treated by Continuous Hemodiafiltration

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.42.9.2421 ◽

1998 ◽

Vol 42 (9) ◽

pp. 2421-2424 ◽

Cited By ~ 60

Author(s):

W. A. Krueger ◽

T. H. Schroeder ◽

M. Hutchison ◽

E. Hoffmann ◽

H.-J. Dieterich ◽

...

Keyword(s):

Renal Failure ◽

Acute Renal Failure ◽

Critically Ill ◽

Critically Ill Patients ◽

Plasma Drug ◽

Continuous Hemodiafiltration ◽

Drug Levels ◽

Continuous Venovenous Hemodiafiltration ◽

Renal Replacement Therapies ◽

Trough Levels

ABSTRACT The pharmacokinetics of meropenem were studied in nine anuric critically ill patients treated by continuous venovenous hemodiafiltration. Peak levels after infusion of 1,000 mg over 30 min amounted to 103.2 ± 45.9 μg/ml, and trough levels at 12 h were 9.6 ± 3.8 μg/ml. A dosage of 1,000 mg of meropenem twice a day provides plasma drug levels covering intermediately susceptible microorganisms. Further reductions of the dosage might be appropriate for highly susceptible bacteria or when renal replacement therapies with lower clearances are applied.

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The Risk of Acute Kidney Injury in Critically Ill Patients Receiving Concomitant Vancomycin With Piperacillin–Tazobactam or Cefepime

Journal of Intensive Care Medicine ◽

10.1177/0885066619828290 ◽

2019 ◽

Vol 35 (12) ◽

pp. 1434-1438 ◽

Cited By ~ 5

Author(s):

Kyle C. Molina ◽

Jeffrey F. Barletta ◽

Scott T. Hall ◽

Cyrus Yazdani ◽

Vanthida Huang

Keyword(s):

Risk Factors ◽

Acute Kidney Injury ◽

Multivariate Analysis ◽

Combination Therapy ◽

Critically Ill ◽

Critically Ill Patients ◽

Kidney Injury ◽

Severity Of Illness ◽

Baseline Serum ◽

Vancomycin Trough

Purpose: The objective of this study was to compare the incidence of acute kidney injury (AKI) among critically ill patients receiving combination therapy with vancomycin plus piperacillin–tazobactam (VPT) against patients receiving vancomycin plus cefepime (VC). Methods: A retrospective cohort study of adult patients admitted to an intensive care unit between September 2012 and December 2016 was conducted. Patients were included if they received combination therapy with VPT or VC for ≥48 hours. Patients were excluded if creatinine clearance was <60 mL/min or received renal replacement therapy prior to the initiation of therapy. The primary end point was AKI, as defined by the Acute Kidney Injury Network classification, during or within 48 hours of completion of therapy. The incidence of AKI was compared between groups and multivariate analysis was performed to control for relevant confounders. Results: A total of 394 patients received either VPT (n = 258) or VC (n = 136). There were no differences in baseline serum creatinine (0.8 [0.3]mg/dL vs 0.7 [0.3] mg/dL, P = 0.207), use of vasopressors (44% vs 38%, P = 0.255), mechanical ventilation (45% vs 40%, P = 0.350), or initial vancomycin trough (11.2 [5] mg/L vs 11 [4.8] mg/L, P = 0.668) between VPT and VC groups, respectively. The incidence of AKI was 28.7% for VPT patients versus 21.3% for VC patients ( P = 0.114). Multivariate analysis revealed vancomycin trough >20 mg/L (odds ratio, OR [95% confidence interval, CI] = 2.69 [1.62-4.47]), baseline SCr (OR [95% CI] = 3.34 [1.43-7.80]), vasopressors (OR [95% CI] = 1.77 [1.04-3.04]), and duration of combination therapy (OR [95% CI] = 1.009 [1.003-1.015]) as independent risk factors for AKI. Conclusion: The risk of AKI was similar between VPT and VC groups in critically ill patients. Risk factors for AKI were related to baseline renal function, duration of combination therapy, supratherapeutic vancomycin troughs, and severity of illness.

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The Impact of Early Achievement of Therapeutic Levels of Vancomycin in Critically ill Patients with Confirmed Gram-positive Infection: A Retrospective Cohort Study

10.21203/rs.3.rs-384175/v2 ◽

2021 ◽

Author(s):

Khalid Al Sulaiman ◽

Abdulrahman Alshaya ◽

Amjad Alsaeed ◽

Nadiyah Alshehri ◽

Ramesh Vishwakarma ◽

...

Keyword(s):

Cohort Study ◽

Critically Ill ◽

Retrospective Cohort Study ◽

Critically Ill Patients ◽

Retrospective Cohort ◽

Kidney Injury ◽

Gram Positive ◽

Tertiary Teaching ◽

The Impact ◽

Trough Levels

Abstract Background: Vancomycin is a commonly used antibiotic in critically ill patients for various indications. Critical illness imposes pharmacokinetic-pharmacodynamics challenges which makes optimizing vancomycin in this population cumbersome. Data are scarce on the clinical impact of time to therapeutic trough levels of vancomycin in critically ill patients. The aim of this study to evaluate the timing to achieve therapeutic trough level vancomycin on 30-day mortality in critically ill patients.Method: A retrospective cohort study for all adult critically ill patients aged 18 years or older with confirmed Gram-positive infection and received vancomycin between January 1st, 2017 and December 31st, 2018 at a tertiary teaching hospital. We compared early (<48 hours) versus late (≥ 48 hours) attainment of vancomycin therapeutic trough levels. Primary outcome was the 30-day mortality in critically ill patients. Secondary outcomes were development of resistant organisms, eradicating microorganisms within 4-5 days of vancomycin initiation, vancomycin-induced acute kidney injury (AKI), and ICU length of stay (LOS). Results: Two hundred and nine patients were included. No significant differences between comparative groups in baseline characteristics. Achieving therapeutic levels were associated with better survival at 30 days (OR: 0.48; 95% CI [0.26-0.87]; p<0.01). Additionally, patients who achieved therapeutic levels of vancomycin early were less likely to develop resistant organisms (OR=0.08; 95% CI [0.01-0.59]; p=0.01). The AKI and ICU LOS were not significant between the two groups.Conclusion: Early attainment of vancomycin therapeutic levels was associated with possible survival benefit.

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