Attributable nephrotoxicity of vancomycin in critically ill patients: a marginal structural model study

Abstract Background Although vancomycin nephrotoxicity is recognizable, critically ill patients have other potential reasons for acute kidney injury (AKI) and determining its attributable nephrotoxic risk in this population can be cumbersome. Objectives To determine the risk of AKI attributable to vancomycin, controlling for baseline and time-dependent confounders. Methods Time-fixed and daily time-varying variables were extracted from a large public database. The exposures analysed were: (i) IV vancomycin; (ii) serum trough level greater than 15 and 20 mg/L; and (iii) concomitant exposure to vancomycin and piperacillin/tazobactam or other antipseudomonal β-lactams. Censoring and exposure inverse probability of treatment weighting were calculated. Marginal structural models were plotted to evaluate AKI, severe AKI (stage 2/3) and need of renal replacement therapy (RRT). Results A total of 26 865 patients were included; 19.7% received vancomycin during ICU stay. After adjusting for fixed and time-variable confounders, vancomycin exposure was associated with AKI (HR = 1.24, 95% CI = 1.09–1.38), but not with severe AKI or need of RRT (HR = 1.05, 95% CI = 0.91–1.23 and HR = 0.97, 95% CI = 0.74–1.29, respectively). A serum trough level greater than 20 mg/L was associated with AKI (HR = 1.90, 95% CI = 1.52–2.30) and severe AKI (HR = 1.69, 95% CI = 1.31–2.19), but showed no statistically significant association with need of RRT (HR = 1.48, 95% CI = 0.92–2.56). The vancomycin + piperacillin/tazobactam combination was not associated with a greater risk than vancomycin alone. Conclusions The attributable nephrotoxicity of vancomycin in critically ill patients is significantly lower than previously suggested and severe AKI is related to vancomycin only when trough serum levels are greater than 20 mg/L.

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Association between serum levels of interleukin-6 on ICU admission and subsequent outcomes in critically ill patients with acute kidney injury

BMC Nephrology ◽

10.1186/s12882-019-1265-6 ◽

2019 ◽

Vol 20 (1) ◽

Cited By ~ 2

Author(s):

Takashi Shimazui ◽

Taka-aki Nakada ◽

Yoshihisa Tateishi ◽

Taku Oshima ◽

Tuerxun Aizimu ◽

...

Keyword(s):

Acute Kidney Injury ◽

Critically Ill ◽

Critically Ill Patients ◽

Interleukin 6 ◽

Kidney Injury ◽

Serum Levels ◽

Icu Admission

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Ribavirin and Interferon Therapy for Critically Ill Patients With Middle East Respiratory Syndrome: A Multicenter Observational Study

Clinical Infectious Diseases ◽

10.1093/cid/ciz544 ◽

2019 ◽

Vol 70 (9) ◽

pp. 1837-1844 ◽

Cited By ~ 99

Author(s):

Yaseen M Arabi ◽

Sarah Shalhoub ◽

Yasser Mandourah ◽

Fahad Al-Hameed ◽

Awad Al-Omari ◽

...

Keyword(s):

Middle East ◽

Observational Study ◽

Critically Ill ◽

Critically Ill Patients ◽

Structural Model ◽

Middle East Respiratory Syndrome ◽

Time Varying ◽

Marginal Structural Model ◽

Recombinant Interferon ◽

Multicenter Observational Study

Abstract Background The objective of this study was to evaluate the effect of ribavirin and recombinant interferon (RBV/rIFN) therapy on the outcomes of critically ill patients with Middle East respiratory syndrome (MERS), accounting for time-varying confounders. Methods This is a retrospective cohort study of critically ill patients with laboratory-confirmed MERS from 14 hospitals in Saudi Arabia diagnosed between September 2012 and January 2018. We evaluated the association of RBV/rIFN with 90-day mortality and MERS coronavirus (MERS-CoV) RNA clearance using marginal structural modeling to account for baseline and time-varying confounders. Results Of 349 MERS patients, 144 (41.3%) patients received RBV/rIFN (RBV and/or rIFN-α2a, rIFN-α2b, or rIFN-β1a; none received rIFN-β1b). RBV/rIFN was initiated at a median of 2 days (Q1, Q3: 1, 3 days) from intensive care unit admission. Crude 90-day mortality was higher in patients with RBV/rIFN compared to no RBV/rIFN (106/144 [73.6%] vs 126/205 [61.5%]; P = .02]. After adjusting for baseline and time-varying confounders using a marginal structural model, RBV/rIFN was not associated with changes in 90-day mortality (adjusted odds ratio, 1.03 [95% confidence interval {CI}, .73–1.44]; P = .87) or with more rapid MERS-CoV RNA clearance (adjusted hazard ratio, 0.65 [95% CI, .30–1.44]; P = .29). Conclusions In this observational study, RBV/rIFN (RBV and/or rIFN-α2a, rIFN-α2b, or rIFN-β1a) therapy was commonly used in critically ill MERS patients but was not associated with reduction in 90-day mortality or in faster MERS-CoV RNA clearance.

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Pharmacokinetic Assessment of Vancomycin Loading Dose in Critically Ill Patients

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00280-17 ◽

2017 ◽

Vol 61 (8) ◽

Cited By ~ 14

Author(s):

Osvaldo Álvarez ◽

Jose Cristian Plaza-Plaza ◽

Manuel Ramirez ◽

Alexis Peralta ◽

Cristián A. Amador ◽

...

Keyword(s):

Critically Ill ◽

Critically Ill Patients ◽

Serum Levels ◽

The Body ◽

Critically Ill Patient ◽

Pharmacokinetic Parameters ◽

Population Pharmacokinetic ◽

Loading Dose ◽

Trough Serum ◽

Number Of Patients

ABSTRACT The vancomycin loading dose (LD) of 25 to 30 mg/kg is a frequently practiced strategy to achieve effective concentrations from the first-treatment dose. However, considering only the body weight for dosing might be inadequate in critically ill patients due to pharmacokinetics changes. We sought to assess achieving optimal trough serum levels of vancomycin and AUC0–24/MIC in the first 24 h of treatment by using an LD based on population pharmacokinetic parameters of critically ill patients. We performed a concurrent cohort study over 22 months of patients with severe sepsis who received intravenous vancomycin. The patients were treated with three different strategies to initiate vancomycin: without an LD (group A), with an LD of 25 to 30 mg/kg (group B), and with an LD based on population pharmacokinetic parameters of the critically ill patient (group C). An optimal trough serum concentration was achieved in 5, 9, and 83% of patients in groups A, B, and C, respectively. The number of patients that reached optimal AUC0–24 was 2 of 18 (11%), 5 of 11 (46%), and 11 of 12 (92%) in groups A, B, and C, respectively. The statistical analysis for both parameters revealed significant differences in group C with respect to other groups. The administration of the LD calculated from population pharmacokinetic parameters from the beginning of therapy is a more efficient strategy to obtain adequate trough serum concentrations and AUC0–24/MIC in critical patients.

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Vancomycin-Associated Acute Kidney Injury in a Large Veteran Population

American Journal of Nephrology ◽

10.1159/000496484 ◽

2019 ◽

Vol 49 (2) ◽

pp. 133-142 ◽

Cited By ~ 3

Author(s):

Geeta Gyamlani ◽

Praveen K. Potukuchi ◽

Fridtjof Thomas ◽

Oguz Akbilgic ◽

Melissa Soohoo ◽

...

Keyword(s):

Acute Kidney Injury ◽

Estimated Glomerular Filtration Rate ◽

Trough Level ◽

Kidney Injury ◽

Serum Levels ◽

Glycopeptide Antibiotics ◽

Serum Trough ◽

Antibiotics Use ◽

Vancomycin Trough ◽

Serum Vancomycin

Background: To determine the association of vancomycin with acute kidney injury (AKI) in relation to its serum concentration value and to examine the risk of AKI in patients treated with vancomycin when compared with a matched cohort of patients receiving non-glycopeptide antibiotics (linezolid/daptomycin). Methods: From a cohort of > 3 million US veterans with baseline estimated glomerular filtration rate ≥60 mL/min/1.73 m2, we identified 33,527 patients who received either intravenous vancomycin (n = 22,057) or non-glycopeptide antibiotics (linezolid/daptomycin, n = 11,470). We examined the association of the serum trough vancomycin level recorded within the first 48 h of administration with subsequent AKI in all patients treated with vancomycin and association of vancomycin vs. non-glycopeptide antibiotics use with the risk of incident AKI. Results: The overall multivariable adjusted ORs of AKI stages 1, 2, and 3 in patients on vancomycin vs. non-glycopeptides were 1.1 (1.1–1.2), 1.2 (1–1.4), and 1.4 (1.1–1.7), respectively. When examined in strata divided by vancomycin trough level, the odds of AKI were similar or lower in patients receiving vancomycin compared to non-glycopeptide antibiotics as long as serum vancomycin levels were ≤20 mg/L. However, in patients with serum vancomycin levels > 20 mg/L, the ORs of AKI stages 1, 2, and 3 in patients on vancomycin vs. non-glycopeptide antibiotics were 1.5 (1.4–1.7), 1.9 (1.5–2.3), and 2.7 (2–3.5), respectively. Conclusions: Vancomycin use is associated with a higher risk of AKI when serum levels exceed > 20 mg/L.

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Serum Neutrophil Gelatinase-Associated Lipocalin (NGAL) Could Provide Better Accuracy Than Creatinine in Predicting Acute Kidney Injury Development in Critically Ill Patients

Journal of Clinical Medicine ◽

10.3390/jcm10225379 ◽

2021 ◽

Vol 10 (22) ◽

pp. 5379

Author(s):

Edison Jahaj ◽

Alice G. Vassiliou ◽

Maria Pratikaki ◽

Parisis Gallos ◽

Zafeiria Mastora ◽

...

Keyword(s):

Acute Kidney Injury ◽

Critically Ill ◽

Critically Ill Patients ◽

Kidney Injury ◽

Roc Curves ◽

Serum Levels ◽

Icu Admission ◽

Neutrophil Gelatinase Associated Lipocalin ◽

Increased Risk ◽

Neutrophil Gelatinase

Acute kidney injury (AKI) is one of the most common complications in critically ill patients. In recent years, studies have focused on exploring new biomarkers for the early diagnosis and prognosis of AKI. The aim of this study was to investigate serum prognostic biomarkers (neutrophil gelatinase-associated lipocalin, NGAL, and creatinine) of AKI in critically ill patients. The study included 266 critically ill, initially nonseptic, patients admitted to a multidisciplinary ICU. Serum levels of NGAL and creatinine were measured at ICU admission. ROC curves were generated to estimate the prognostic value of the biomarkers, while a logistic regression analysis was performed to assess their association with an increased AKI risk. Patients were divided in two groups based on the development (n = 98) or not (n = 168) of AKI during their ICU stay. Serum NGAL levels at ICU admission were significantly higher in those who subsequently developed AKI compared to those who did not (p < 0.0001). NGAL was shown to be more accurate in predicting AKI development than creatinine; furthermore, NGAL levels were associated with an increased risk of AKI development (1.005 (1.002–1.008), p < 0.0001). In the present study, we were able to demonstrate that increased serum NGAL levels at ICU admission might be predictive of AKI development during ICU hospitalization. Further studies are needed to support NGAL as a prognostic marker of acute kidney injury.

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Elimination of fosfomycin during dialysis with the Genius system in septic patients

Scientific Reports ◽

10.1038/s41598-021-91423-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

T. Dimski ◽

T. Brandenburger ◽

M. Janczyk ◽

T. Slowinski ◽

C. MacKenzie ◽

...

Keyword(s):

Critically Ill ◽

Critically Ill Patients ◽

Prospective Observational Study ◽

Kidney Injury ◽

Serum Levels ◽

Therapeutic Drug ◽

Loading Dose ◽

Dialysis Therapy ◽

Daily Dialysis ◽

Wide Variability

AbstractTo assess fosfomycin (FOS) elimination in patients with sepsis and acute kidney injury (AKI) undergoing slow-extended daily dialysis (SLEDD) with the Genius system in a prospective observational study. After ethics committee approval ten patients with sepsis and AKI stage 3 underwent daily SLEDD sessions of eight hours. FOS was applied i.v. at doses of 3 × 5 g per day. FOS serum levels were measured pre- and post hemofilter before, during, and after SLEDD sessions, and instantaneous clearance was calculated. In five of the patients, we analyzed FOS levels after the first dose, in the other five patients serum levels were measured during ongoing therapy. FOS was eliminated rapidly via the hemofilter. FOS clearance decreased from 152 ± 10 mL/min (start of SLEED session) to 43 ± 38 mL/min (end of SLEDD session). In 3/5 first-dose patients after 4–6 h of SLEDD the FOS serum level fell below the EUCAST breakpoint of 32 mg/L for Enterobacterales and Staphylococcus species. In all patients with ongoing fosfomycin therapy serum levels were high and above the breakpoint at all times. FOS toxicity or adverse effects were not observed. FOS serum concentrations exhibit wide variability in critically ill patients with sepsis and AKI. FOS is eliminated rapidly during SLEDD. A loading dose of 5 g is not sufficient to achieve serum levels above the EUCAST breakpoint for common bacteria in all patients, considering that T > MIC > 70% of the dosing interval indicates sufficient plasma levels. We thus recommend a loading dose of 8 g followed by a maintenance dose of 5 g after a SLEDD session in anuric patients. We strongly recommend therapeutic drug monitoring of FOS levels in critically ill patients with AKI and dialysis therapy.

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