This study aimed to determine cefazolin target attainment in patients with invasive Staphylococcus aureus (S. aureus) infections and to develop a population pharmacokinetic (PK) model. Adult patients with invasive S. aureus infections treated with cefazolin bolus infusions were included. Unbound and total trough and mid-dose cefazolin concentrations were measured, and strain-specific MICs were determined. The primary outcome was the proportion of patients attaining 100% fT_>MIC at all time points evaluated. A population PK model was developed, using non-linear mixed-effects modelling. Overall, 51 patients were included, with a total of 226 unbound and total cefazolin concentrations measured (mean: 4.4 per patient). The median daily dosage in patients with an estimated glomerular filtration rate of >60 mL/min/m² was 8 g. The median age was 74 years (interquartile range (IQR) 57–82) and 26% were female. A history of chronic kidney disease and acute kidney injury were present in 10/51 (19.6%) and 6/51 (11.7%), respectively. Achievement of 100% fT_>MIC occurred in 86% of the patients and decreased to 45% when a target of 100% fT_>4xMIC was evaluated. The mean unbound cefazolin fraction was 27.0% (standard deviation (SD) 13.4). Measured and estimated mean cefazolin trough concentrations differed significantly [13.1 mg/L (SD 23.5) vs. 7.4 mg/L (SD 7.9), p < 0.001]. In the population PK model, elevated estimated creatinine clearance and bolus instead of continuous application were covariates for target non-attainment. In conclusion, cefazolin target achievement was high, and the measurement of the unbound cefazolin concentration may be favored. The Monte Carlo simulations indicated that target attainment was significantly improved with continuous infusion.

Neurotoxicity is a well-described adverse effect of cefepime. Clinical presentation includes mild neurological deficits, aphasia, impairment of consciousness, and even nonconvulsive status epilepticus. Impaired kidney function is considered the most important risk factor for cefepime-induced neurotoxicity (CIN) and frequently occurs during the course of critical diseases with concomitant acute kidney injury (AKI). Physicians should be aware of situations with increased risk of AKI and the preventive actions required to reduce the risk of CIN. We present three patients with AKI who were treated with cefepime for healthcare-associated infections. Subsequently, two patients developed CIN demonstrating very high cefepime levels in plasma. In the third patient, CIN was likely prevented as the increased risk of neurotoxicity was noted and cefepime treatment was ceased immediately. Diagnosis of CIN might be challenging due to various causes of encephalopathy, in particular in the setting of severely ill patients. Electroencephalogram may assist in establishing the diagnosis, in particular when cefepime therapeutic drug monitoring is not available. As CIN is potentially reversible, it is an important differential diagnosis to consider especially in patients with impaired renal function or being susceptible to AKI. Preventive measures of CIN include therapeutic drug monitoring, consideration of a therapeutic alternative, awareness regarding a potential overestimation of the glomerular filtration rate, and electronic health record alerts about risk constellations for potential overdosing.

Background: The benefit of adjunctive aminoglycosides in the treatment of patients with febrile neutropenia (FN) is controversial. We investigated the incidence of acute kidney injury (AKI) in patients with FN or suspected infection according to empirical amikacin treatment. Methods: This two-centre, retrospective cohort study was conducted at the University Hospitals of Basel (amikacin group) and Bern (non-amikacin group), Switzerland, between 2016 and 2022. Adult patients requiring antibiotic treatment after autologous hematopoietic stem cell transplantation (HSCT) were included. All patients received empiric beta-lactam treatment combined with amikacin in the amikacin group (only University Hospital Basel). The primary endpoint was the incidence of AKI within seven days after the initiation of antibiotic treatment. Results: Overall, 250 patients were included. The majority was male (n = 163, 65.2%) and had a median age of 61 years (interquartile range (IQR) 55 to 67). The median baseline eGFR was similar in both groups (>90 mL/min/1.7 m²). There was no statistically significant difference in the incidence of AKI (4/125 vs. 5/125, p = 1.0). The maximum decline in eGFR from baseline within 7 days was significantly higher in the amikacin group (−4 mL/min/1.7 m² (IQR 8 to −12) vs. −2 mL/min/1.7 m² (IQR −7 to −1), p = 0.001). Two patients suffered from an infection with an extended spectrum beta-lactamase producing (ESBL) pathogen. Conclusions: Amikacin treatment did not significantly impact the incidence of AKI in patients undergoing autologous HSCT. The short-term administration of amikacin in patients with normal to high baseline eGFR is safe regarding renal function. However, in a low-resistance setting, the omission of empirical amikacin treatment should be considered.