Summary: Vancomycin is an antibiotic used in the treatment of infections caused by multidrug‐resistant Gram‐positive bacteria, especially methicillin‐resistant Staphylococcus aureus. In the last decades, vancomycin has been widely used in hospital environments due to the increasing incidence of sepsis and septic shock. Sepsis may lead to multiple organ failure; it is considered a risk factor for the development of acute kidney injury (AKI), with an overall mortality rate of around 45%, which can reach the surprising rate of 70% with the combination of AKI and sepsis. Considering the high mortality rate of sepsis and its related costs of hospitalization and treatment, specific measures should be adopted, such as early‐goal treatment protocols: proper and early administration of antimicrobials, fluids, vasoactive drugs and transfusion support. Besides the careful selection of the antimicrobial, another concern related to critically ill patients is the proper dose of the antimicrobial, since pharmacokinetic changes are observed due to drug absorption, distribution, metabolism and elimination. Gram‐positive pathogens are very common in hospitalized patients with septic shock, so vancomycin has been the antimicrobial of choice for more than 60 years. However, discussions about its dosage, administration and monitoring are extremely important, considering the risk of nephrotoxicity and the emergence of resistant S. aureus. This narrative review aims to discuss controversial aspects related to the efficacy and safety of vancomycin, correlating them with data available in the literature and identifying knowledge gaps in guide future lines of research.

Renal involvement is frequent in COVID-19 (4–37%). This study evaluated the incidence and risk factors of acute kidney injury (AKI) in hospitalized patients with COVID-19.Methodology: This study represents a prospective cohort in a public and tertiary university hospital in São Paulo, Brazil, during the first 90 days of the COVID-19 pandemic, with patients followed up until the clinical outcome (discharge or death).Results: There were 101 patients hospitalized with COVID-19, of which 51.9% were admitted to the intensive care unit (ICU). The overall AKI incidence was 50%; 36.8% had hematuria or proteinuria (66.6% of those with AKI), 10.2% had rhabdomyolysis, and mortality was 36.6%. Of the ICU patients, AKI occurred in 77.3% and the mortality was 65.4%. The mean time for the AKI diagnosis was 6 ± 2 days, and Kidney Disease Improving Global Outcomes (KDIGO) stage 3 AKI was the most frequent (58.9%). Acute renal replacement therapy was indicated in 61.5% of patients. The factors associated with AKI were obesity [odds ratio (OR) 1.98, 95% confidence interval (CI) 1.04–2.76, p < 0.05] and the APACHE II score (OR 1.97, 95% CI 1.08–2.64, p < 0.05). Mortality was higher in the elderly (OR 1.03, 95% CI 1.01–1.66, p < 0.05), in those with the highest APACHE II score (OR 1.08, 95% CI 1.02–1.98, p < 0.05), and in the presence of KDIGO stage 3 AKI (OR 1.11, 95% CI 1.05–2.57, p < 0.05).Conclusion: AKI associated with severe COVID-19 in this Brazilian cohort was more frequent than Chinese, European, and North American data, and the risk factors associated with its development were obesity and higher APACHE II scores. Mortality was high, mainly in elderly patients, in those with a more severe disease manifestation, and in those who developed KDIGO stage 3 AKI.

Sepsis is the most common cause of death in critically ill patients and is associated with multiorgan failure, including acute kidney injury (AKI). This situation can require acute renal support and increase mortality. Therefore, it is essential to administer antimicrobials in doses that achieve adequate serum levels, avoiding both overdosing and drug toxicity as well as underdosing and the risk of antibiotic resistance and higher mortality. Currently, there are no validated guidelines on antibiotic dose adjustments in septic patients with AKI. The current recommendations were extrapolated from studies conducted in noncritical patients with end-stage chronic kidney disease receiving chronic renal replacement therapy. This study aimed to review and discuss the complexity of this issue, considering several factors related to drug metabolism, the characteristics of critically ill patients, the properties of antimicrobial drugs and dialysis methods.

This article presents a case of rapidly progressive glomerulonephritis following the Oxford-AstraZeneca COVID-19 vaccine in a female patient 58 years old. After 5 days, she presented fatigue, paleness, arthralgia on hands, knees, ankles, foamy urine, and elevated blood pressure. Exams showed serum creatinine of 2.2 mg/dL (baseline creatinine of 1.0 mg/dL). Urinalysis revealed hematuria, and her 24-h urinary protein excretion was 4.4 g. Additional exams showed hypercholesterolemia, severe anemia, and normal serum albumin. Testing of antineutrophil cytoplasmic antibodies anti-myeloperoxidase was positive at a titer of 1/80. Serum and urine protein electrophoresis and other exams showed no alterations. She was started on steroid pulse therapy after worsening kidney function, reaching serum creatinine of 3.3 mg/dL. A kidney biopsy revealed crescentic glomerulonephritis with glomerular sclerosis, fibrous crescents, interstitial fibrosis, and tubular atrophy. Induction therapy was given with intravenous cyclophosphamide 0.5 g/m² for 6-monthly pulses, followed by maintenance therapy with oral azathioprine at 2 mg/kg and prednisone tapering. The patient did not develop any complications during the induction therapy, and is currently on maintenance therapy with a serum creatinine of 1.87 mg/dL.

Introduction and Aim: There have been few studies to evaluate the monitoring of plasmatic concentrations of vancomycin in septic patients and their association with acute kidney injury (AKI) and death. This study aimed to evaluate the prevalence of adequate, subtherapeutic, and toxic serum concentrations of vancomycin in hospitalized septic patients and to associate the adequacy of therapeutic monitoring with clinical outcomes. Methodology: This was a cohort-unicentric study that evaluated septic patients aged >18 years using vancomycin admitted to clinical and surgical wards of a Brazilian university center from August 2016 to July 2017 in a daily and uninterrupted way. We excluded patients with AKI prior to the introduction of vancomycin or with AKI development <48 hours after use, patients with AKI of other etiologies, stage V chronic kidney disease, and pregnant women. Results: We evaluated 225 patients, and 135 were included. Evaluation of serum concentration of vancomycin was realized in 94.1%, and of those, 59.3% presented toxic concentrations. The prevalence of AKI was 27.4% and happened on average on the ninth day of vancomycin usage. Between the fourth and sixth days, vancomycin serum concentration of >21.5 mg/L was a predictor of AKI, with area under the curve of 0.803 (95% CI 0.62-0.98, p=0.005), preceding the diagnosis of AKI by at least 3 days. Of these patients, 20.7% died, and serum concentrations of vancomycin between the fourth and sixth days were identified as risk factors associated with negative outcomes. Conclusion: Serum concentration of vancomycin is an excellent predictor of AKI in patients admitted to wards, preceding the diagnosis of AKI by at least 72 hours. Toxic concentrations of vancomycin are associated with AKI, and AKI was a risk factor for death. Also, serum concentration of vancomycin >21.5 mg/L was the only variable associated with death in the Cox model.

The impact of serum concentrations of vancomycin is a controversial topic. Results: 182 critically ill patients were evaluated using vancomycin and 63 patients were included in the study. AKI occurred in 44.4% of patients on the sixth day of vancomycin use. Vancomycin higher than 17.53 mg/L between the second and the fourth days of use was a predictor of AKI, preceding AKI diagnosis for at least two days, with an area under the curve of 0.806 (IC 95% 0.624–0.987, p = 0.011). Altogether, 46.03% of patients died, and in the Cox analysis, the associated factors were age, estimated GFR, CPR, and vancomycin between the second and the fourth days. Discussion: The current 2020 guidelines recommend using Bayesian-derived AUC monitoring rather than trough concentrations. However, due to the higher number of laboratory analyses and the need for an application to calculate the AUC, many centers still use therapeutic trough levels between 15 and 20 mg/L. Conclusion: The results of this study suggest that a narrower range of serum concentration of vancomycin was a predictor of AKI in critically ill septic patients, preceding the diagnosis of AKI by at least 48 h, and it can be a useful monitoring tool when AUC cannot be used.