Background: Meropenem is a carbapenem antibiotic widely employed for serious bacterial infections. Therapeutic drug monitoring (TDM) is a strategy to optimize dosing, especially in critically ill patients. This study aims to show how TDM influences the management of meropenem in a real-life setting, not limited to intensive care units. Methods: From December 2021 to February 2022, we retrospectively analyzed 195 meropenem serum concentrations (Css). We characterized patients according to meropenem exposure, focusing on the renal function impact. Results: A total of 36% (n = 51) of the overall observed patients (n = 144) were in the therapeutic range (8–16 mg/L), whereas 64% (n = 93) required a meropenem dose modification (37 patients (26%) underexposed; 53 (38%) overexposed). We found a strong relationship between renal function and meropenem concentrations (correlation coefficient = −0.7; p-value < 0.001). We observed different dose-normalized meropenem exposure (Css/D) among renal-impaired (severe and moderate), normal, and hyperfiltrating patients, with a median (interquartile range) of 13.1 (10.9–20.2), 7.9 (6.1–9.5), 3.8 (2.6–6.0), and 2.4 (1.6–2.7), respectively (p-value < 0.001). Conclusions: Meropenem TDM in clinical practice allows modification of dosing in patients inadequately exposed to meropenem to maximize antibiotic efficacy and minimize the risk of antibiotic resistance, especially in renal alterations despite standard dose adaptations.

Background: Enterococcus faecalis is responsible for a large variety of severe infections. This study is a case series reporting our experience in the treatment of E. faecalis invasive infections with ampicillin in combination with ceftobiprole (ABPR). Methods: We retrospectively analyzed all the medical records of patients admitted to the University Hospital of Udine from January to December 2020 with a diagnosis of infective endocarditis or primary or non-primary complicated or uncomplicated bacteremia caused by E. faecalis. Results: Twenty-one patients were included in the final analysis. The clinical success rate was very high, accounting for 81% of patients, and microbiological cure was obtained in 86% of patients. One relapse was recorded in one patient who did not adhere to the partial oral treatment prescribed. Therapeutic drug monitoring (TDM) was always performed for ampicillin and ceftobiprole, and serum concentrations of both drugs were compared to the MICs of the different enterococcal isolates. Conclusions: ABPR is a well-tolerated antimicrobial regimen with anti-E. faecalis activity. TDM can help clinicians optimize medical treatments to achieve the best possible efficacy with fewer side effects. ABPR might be a reasonable option for the treatment of severe invasive infections caused by E. faecalis due to the high level of enterococcal penicillin-binding protein (PBP) saturation.

Data on septic thrombosis caused by Gram-negative bacilli (GN-ST) in intensive care unit (ICU) patients are currently limited. The aim of this retrospective case-control study (matched 1:3) performed over a 15-month period on ICU patients with bacteraemia, associated (cases) or not (controls) with GN-ST, was to assess 30-day mortality and clinical/microbiological features of GN-ST. During the study period, 16 patients with GN-ST and 48 controls were analyzed. Polytrauma was the cause of ICU admission in 12 (75%) cases and 22 (46%) controls (p = 0.019). In no case of septic thrombosis was surgical debridement performed. The site of venous thrombosis was more frequently in the lower limbs, associated with bone fracture in nine out of 12 (75%) cases. The median duration of bacteraemia (22 days vs 1 day; p < 0.001) and time to clinical improvement (15 days vs 4 days; p < 0.001) were significantly longer in cases than in controls. On analysis of the receiver operating characteristics (ROC) curve, bacteraemia >72 h was significantly associated with GN-ST (area under the curve (AUC) 0.95, sensitivity 0.996 and specificity 0.810; p < 0.001). Finally, 30-day mortality was 20% in cases and 67% in controls (p < 0.001). Critically ill patients with GN-ST showed specific clinical features. Despite delayed bacteraemia clearance, targeted antibiotic therapy plus anticoagulation usually provided clinical improvement and a low 30-day mortality rate.

Giancarlo Ceccarelli, Simone Giuliano, Marco Falcone, Mario Venditti; Follow-Up Blood Cultures: A 2.0 Diagnostic Tool in Patients with Gram-Negative Bacteremia

Ceftobiprole is a fifth-generation cephalosporin used for different Gram-positive bacterial infections. A population pharmacokinetic analysis was conducted in real-life clinical patients to assess the adequacy of current dosages. Population pharmacokinetics was conducted using non-linear mixed effect modeling. Monte Carlo simulations were performed to determine the probability of target attainment (PTA) of free trough or steady-state concentration over MIC (fC_trough/MIC or fC_ss/MIC) ≥ 1 or ≥4 associated with both the standard and intensified dosing regimens adjusted for renal function. Cumulative fraction of response (CFR) against methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis (MRSE) were also calculated. A total of 132 patients with 503 concentrations were included. Most of them (107/132, 81.1%) had hospital- or community-acquired pneumonia, endocarditis, and bacteremia. A three-compartment model adequately fitted ceftobiprole concentration-time data. Estimated glomerular filtration rate significantly affected drug clearance. Monte Carlo simulations showed that the optimal target of fC_trough/MIC or fC_ss/MIC ≥ 4 is achieved only with the use of the standard dosages administered by continuous infusion (CI) against MRSA infections in patients with preserved renal function. Intensified dosages administered by CI are needed in patients with impaired renal function and/or augmented renal clearance against MRSA and in patients with preserved renal functions against MRSE.