Background: The optimal ampicillin-sulbactam dosing regimen for carbapenem-susceptible Acinetobacter baumannii isolates in critically ill trauma patients has not been clearly defined. One strategy to provide the adequate sulbactam dose includes high-dose continuous infusion. Case(s) Description: We present three cases of critically ill trauma patients with augmented renal clearance treated with high-dose ampicillin-sulbactam through an intravenous continuous infusion for ventilator-associated pneumonia. All A. baumannii isolates were susceptible to sulbactam with low minimum inhibitory concentrations. All achieved clinical cure at the end of therapy and no recurrent pneumonia was noted. No clinically substantial adverse effect attributable to ampicillin-sulbactam therapy occurred. Discussion: There is limited evidence to endorse high-dose, continuous infusion ampicillin-sulbactam for treatment of infections caused by carbapenem-susceptible A. baumannii. This report presents three critically ill trauma patients with augmented renal clearance that achieved positive clinical outcomes with higher doses of ampicillin-sulbactam administered through a continuous infusion.

To describe the pharmacokinetics/pharmacodynamics (PK/PD) of a 2 h infusion of ceftazidime-avibactam (CAZ-AVI) in critically ill patients with augmented renal clearance (ARC). A retrospective review of all critically ill patients with ARC who were treated with CAZ-AVI between August 2020 and May 2023 was conducted. Patients whose 12-h creatinine clearance prior to CAZ-AVI treatment and steady-state concentration (Css) of CAZ-AVI were both monitored were enrolled. The free fraction (fCss) of CAZ-AVI was calculated from Css. The joint PK/PD targets of CAZ-AVI were considered optimal when a Css/minimum inhibitory concentration (MIC) ratio for CAZ ≥4 (equivalent to 100% fT > 4 MIC) and a Css/CT ratio of AVI >1 (equivalent to 100% fT > CT 4.0 mg/L) were reached simultaneously, quasioptimal when only one of the two targets was reached, and suboptimal when neither target was reached. The relationship between PK/PD goal achievement, microbial eradication and the clinical efficacy of CAZ-AVI was evaluated. Four patients were included. Only one patient achieved optimal joint PK/PD targets, while the other three reached suboptimal targets. The patient with optimal PK/PD targets achieved microbiological eradication, while the other three patients did not, but all four patients achieved good clinical efficacy. Standard dosages may not enable most critically ill patients with ARC to reach the optimal joint PK/PD targets of CAZ-AVI. Optimal drug dose adjustment of CAZ-AVI in ARC patients requires dynamic drug concentration monitoring.

Augmented renal clearance (ARC) is commonly described in critically ill patients, making drug pharmacokinetics even harder to predict in this population. This case report displays the value of therapeutic drug monitoring (TDM) of piperacillin/tazobactam (PTZ) in this population. We identified two patients with ARC and intermittent administration of PTZ who took part in a prospective, descriptive study conducted at Hôpital du Sacré-Cœur de Montréal. Both had plasma samples drawn at peak, middle, and end of their dosing intervals of PTZ. Minimal inhibitory concentrations (MICs) of 4 and 8 mg/L were chosen to evaluate therapeutic target attainment at middle and end of dosing interval. The first patient was a 52-year-old male with a renal clearance rate estimated at 147 mL/min who received 3.375 g PTZ every 6 h. The second patient, a 49-year-old male, had an estimated renal clearance rate of 163 mL/min and received the same regimen. Both patients had piperacillin concentrations above the target MICs at middle of the dosing interval, but they failed to reach a trough concentration above 8 mg/L. The present case report showcases two patients with subtherapeutic PTZ concentrations despite strict following of local administration protocols. This suboptimal administration could not only lead to treatment failure, but also to the selection and growth of resistant pathogens. Implementing TDM would offer the possibility to adjust drug regimens in real-time and prevent situations like these from occurring.

Augmented renal clearance (ARC) is a pathophysiological phenomenon that can occur in critically ill patients, leading to enhanced renal function. It is defined as a creatinine clearance of >130 mL/min/1.73 m2 . ARC can lead to subtherapeutic levels of renally cleared drugs and subsequent treatment failure. In COVID-19, it has only been described in the literature in a few cases. We present the case of a 38-year-old critically ill patient with COVID-19 who developed ARC with an initial clearance of 226 mL/min/1.73 m2 , persisting for 30 days. He required high doses of sedatives and neuromuscular blocking agents, as well as increased doses of vancomycin and dalteparin, to reach adequate serum levels. This case emphasizes the importance for clinicians to consider ARC in the dosing of all renally cleared drugs, including antibiotics, low molecular weight heparins, and sedatives, to prevent subtherapeutic drug levels and treatment failure.

Patients with burn injuries are at high risk for infection as well as altered antimicrobial pharmacokinetics. Patients suffering from a burn injury, generally encompassing a total body surface area (TBSA) ≥ 20%, have been cited as at risk for augmented renal clearance (ARC). Our case report describes an obese patient with 3.2% TBSA partial thickness burns who suffered from burn wound cellulitis with Pseudomonas aeruginosa. Measured CLcr documented the presence of ARC, and 22.5 grams daily continuous infusion of piperacillin-tazobactam was initiated. Therapeutic monitoring of piperacillin at steady state was 78 mcg/mL, achieving the prespecified goal piperacillin concentration of 100% 4-times the minimum inhibitory concentration assuming MIC for susceptible P. aeruginosa at 16/4 mcg/mL per Clinical Laboratory Standards Institute. Available literature suggests younger critically ill patients with lower organ failure scores, and for a burn injury, a higher percentage of TBSA, are most likely to exhibit ARC which does not entirely align with the characteristics of our patient. In addition, piperacillin-tazobactam has been associated with altered pharmacokinetics in ARC, burn, and obese populations, demonstrating failure to meet target attainment with standard doses. We suggest a continuous infusion of piperacillin-tazobactam be used when ARC is identified. This case report describes the unique findings of ARC in a non-critically ill burn patient and rationalizes the need for further prospective research to classify incidence, risk factors, and appropriate antimicrobial regimens for burn patients with ARC.

Streptococcus intermedius occasionally causes brain abscesses that can be life-threatening, requiring prompt antibiotic and neurosurgical treatment. The source is often dental, and it may spread to the eye or the brain parenchyma. We report the case of a 34-year-old man with signs of apical periodontitis, endophthalmitis, and multiple brain abscesses caused by Streptococcus intermedius. Initial treatment with meropenem and vancomycin was unsuccessful due to subtherapeutic concentrations, despite recommended dosages. Adequate concentrations could be reached only after increasing the dose of meropenem to 16 g/day and vancomycin to 1.5 g × 4. The patient exhibited high creatinine clearance consistent with augmented renal clearance, although iohexol and cystatin C clearances were normal. Plasma free vancomycin clearance followed that of creatinine. A one-day dose of trimethoprim-sulfamethoxazole led to an increase in serum creatinine and a decrease in both creatinine and urea clearances. These results indicate that increased tubular secretion of the drugs was the cause of suboptimal antibiotic treatment. The patient eventually recovered, but his left eye needed enucleation. Our case illustrates that augmented renal clearance can jeopardize the treatment of serious bacterial infections and that high doses of antibiotics are needed to achieve therapeutic concentrations in such cases. The mechanisms for regulation of kidney tubular transporters of creatinine, urea, vancomycin, and meropenem in critically ill patients are discussed.

Augmented renal clearance (ARC) is a unique clinical scenario observed in critically ill patients. We present a case of a 30-year-old male with sepsis secondary to methicillin-resistant Staphylococcus aureus (MRSA) bacteremia treated with vancomycin. ARC was observed in the patient with a maximum estimated glomerular filtration rate (eGFR) of 161.9 ml/min/1.73 m2, and therapeutic drug monitoring was used to adjust the vancomycin dosage. Despite the maximal recommended dose of vancomycin, the therapeutic vancomycin level was not achieved, leading to treatment failure and subsequent mortality. Our case report suggests the necessity of other strategies, such as early dose adjustment of vancomycin based on vancomycin clearance and continuous vancomycin infusion, not merely conventional adjustment based on eGFR and vancomycin levels.

UNASSIGNED: Infections with multidrug resistant Acinetobacter baumannii in immunocompromised patients are life-threatening. Therapeutic options are rare in this context, but patients are dependent on an effective antibiotic therapy. Thus, new antibiotic strategies are deemed necessary.
UNASSIGNED: This case report recounts the therapeutic drug monitoring-guided meropenem therapy of a 32 years old patient admitted with acute exacerbation of cystic fibrosis. Veno-venous extracorporeal membrane oxygenation was initiated on the first day of admission to the intensive care unit. The patient showed insufficient serum trough levels of meropenem despite the maximum approved dose (2g every 8h) was administered which was due to augmented renal clearance. Through continuous infusion of the same cumulative dose, target levels were reached. On day 17 of admission, the patient underwent successful double-lung-transplant surgery and extracorporeal membrane oxygenation was ended. Unfortunately, the donor\'s lung was colonized with a multidrug resistant Acinetobacter baumannii that was positive for OXA-23 carbapenemase. Hence a combination therapy of intravenous sulbactam, tigecycline, meropenem and inhalative colistin was established, with a known minimal inhibitory concentration for meropenem of 32 mg/l. Under continuous infusion of 8 g meropenem/day, serum levels exceeded 32 mg/l over 12 days. The patient was transferred from the intensive care unit to a general ward without any signs of infection.
UNASSIGNED: Therapeutic drug monitoring-guided meropenem may be a sound new therapeutic option in eradicating multidrug resistant Acinetobacter and offer a novel therapeutic option in the field of personalized medicine.