This paper presents a robust and efficient method for validating the accuracy of orientation sensors commonly used in practical applications, leveraging measurements from a commercial robotic manipulator as a high-precision reference. The key concept lies in determining the rotational transformations between the robot's base frame and the sensor's reference, as well as between the TCP (Tool Center Point) frame and the sensor frame, without requiring precise alignment. Key advantages of the proposed method include its independence from the exact measurement of rotations between the reference instrumentation and the sensor, systematic testing capabilities, and the ability to produce repeatable excitation patterns under controlled conditions.
View Article and Find Full Text PDFBackground: Sulbactam is an effective therapy for infections. Previous sulbactam pharmacokinetics/pharmacodynamics (PK/PD) analyses established exposure efficacy targets in plasma against pneumonia. Herein, we established sulbactam efficacy targets in epithelial lining fluid (ELF).
View Article and Find Full Text PDFPersons with CF (pwCF) present altered pharmacokinetics (PK) and are often infected with multidrug-resistant (MDR) bacteria. Herein, we describe the PK of cefiderocol, a siderophore cephalosporin with potent activity against MDR Gram-negative rods, in hospitalized adult pwCF with acute pulmonary exacerbation (APE). PwCF received ≥3 doses of 2 g cefiderocol (3 h infusion) with frequency determined according to their estimated glomerular filtration rate (eGFR).
View Article and Find Full Text PDFSulbactam-durlobactam is approved for the treatment of hospital-acquired and ventilator-associated bacterial pneumonia caused by susceptible isolates of complex. Patients with serious infections may require support with continuous renal replacement therapy (CRRT), which presents challenges for optimal dosing of antibiotics. Sulbactam-durlobactam dosing regimens were derived for this population using an CRRT model and Monte Carlo simulation (MCS).
View Article and Find Full Text PDFExpert Rev Anti Infect Ther
January 2025
Introduction: Carbapenem-resistant (CRAB) is a critical priority pathogen posing a substantial threat to our public health due to its virulence and resistance to broad-spectrum antimicrobials. Sulbactam-durlobactam (Xacduro) is a newly approved β-lactam-β-lactamase inhibitor combination agent with potent and activity against CRAB. The phase III randomized trial (ATTACK) demonstrated the safety and efficacy of sulbactam-durlobactam in combination with imipenem-cilastatin as background therapy in treating adult patients with hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia caused by CRAB.
View Article and Find Full Text PDFBackground: Sulbactam dosing for Acinetobacter baumannii infections has not been standardized due to limited available pharmacokinetics/pharmacodynamics (PK/PD) data. Herein, we report a comprehensive PK/PD analysis of ampicillin-sulbactam against A. baumannii pneumonia.
View Article and Find Full Text PDFSurg Infect (Larchmt)
August 2024
Antibiotics are frequently administered prophylactically to trauma patients with various injury patterns to prevent infectious complications. Trauma patients may also require large volume resuscitation with blood products. Limited data are available to support antibiotic dosing recommendations in this population.
View Article and Find Full Text PDFAntibiotic resistance has become a global threat as it is continuously growing due to the evolution of β-lactamases diminishing the activity of classic β-lactam (BL) antibiotics. Recent antibiotic discovery and development efforts have led to the availability of β-lactamase inhibitors (BLIs) with activity against extended-spectrum β-lactamases as well as Klebsiella pneumoniae carbapenemase (KPC)-producing carbapenem-resistant organisms (CRO). Nevertheless, there is still a lack of drugs that target metallo-β-lactamases (MBL), which hydrolyze carbapenems efficiently, and oxacillinases (OXA) often present in carbapenem-resistant Acinetobacter baumannii.
View Article and Find Full Text PDFObjectives: In 2020, cefiderocol became the first Food and Drug Administration-approved medication with continuous renal replacement therapy (CRRT) dosing recommendations based on effluent flow rates (). We aimed to evaluate the magnitude and frequency of factors that may influence these recommendations, that is, intrapatient variability and residual renal function.
Design: Retrospective observational cohort study.
Background: Extracorporeal membrane oxygenation (ECMO) is a life-saving modality but has the potential to alter the pharmacokinetics (PK) of antimicrobials. Imipenem/cilastatin/relebactam is an antibiotic with utility in treating certain multi-drug resistant Gram-negative infections. Herein, we describe the population pharmacokinetics of imipenem and relebactam in critically ill patients supported on ECMO.
View Article and Find Full Text PDFGram-negative antibiotic resistance continues to grow as a global problem due to the evolution and spread of β-lactamases. The early β-lactamase inhibitors (BLIs) are characterized by spectra limited to class A β-lactamases and ineffective against carbapenemases and most extended spectrum β-lactamases. In order to address this therapeutic need, newer BLIs were developed with the goal of treating carbapenemase producing, carbapenem resistant organisms (CRO), specifically targeting the Klebsiella pneumoniae carbapenemase (KPC).
View Article and Find Full Text PDFBackground: Novel treatments are needed for Staphylococcus aureus bacteremia, particularly for methicillin-resistant S. aureus (MRSA). Exebacase is a first-in-class antistaphylococcal lysin that is rapidly bactericidal and synergizes with antibiotics.
View Article and Find Full Text PDFEmpiric antibiotics may affect bacterial pathogen recovery using conventional culture methods (CCMs), while PCR-based diagnostics are likely less affected. Herein, we conducted an study of bronchoalveolar lavage fluid (BAL) inoculated with bacteria and clinically relevant antibiotic concentrations to compare the recovery between the BioFire FILMARRAY Pneumonia Panel (Pn Panel) and CCMs. Remnant clinical BAL specimens were inoculated to ~10 cfu/mL using 12 clinical isolates.
View Article and Find Full Text PDFAntimicrob Agents Chemother
November 2023
is a common multidrug-resistant pathogen in patients with cystic fibrosis (CF). The activity of imipenem/relebactam and imipenem was compared with other antipseudomonal antibiotics against 105 isolates from patients with CF from three US hospitals. Imipenem/relebactam, imipenem, meropenem, ceftazidime/avibactam, and ceftolozane/tazobactam susceptibilities were 77%, 55%, 58%, 90%, and 92%, respectively.
View Article and Find Full Text PDFIntravenous β-lactam antibiotics remain a cornerstone in the management of bacterial infections due to their broad spectrum of activity and excellent tolerability. β-lactams are well established to display time-dependent bactericidal activity, where reductions in bacterial burden are directly associated with the time that free drug concentrations remain above the minimum inhibitory concentration (MIC) of the pathogen during the dosing interval. In an effort to take advantage of these bactericidal characteristics, prolonged (extended and continuous) infusions (PIs) can be applied during the administration of intravenous β-lactams to increase time above the MIC.
View Article and Find Full Text PDFIntravenous β-lactam antibiotics remain a cornerstone in the management of bacterial infections due to their broad spectrum of activity and excellent tolerability. β-lactams are well established to display time-dependent bactericidal activity, where reductions in bacterial burden are directly associated with the time that free drug concentrations remain above the minimum inhibitory concentration (MIC) of the pathogen during the dosing interval. In an effort to take advantage of these bactericidal characteristics, prolonged (extended and continuous) infusions (PI) can be applied during the administration of intravenous β-lactams to increase time above the MIC.
View Article and Find Full Text PDFEur J Drug Metab Pharmacokinet
July 2023
Background And Objective: Extracorporeal membrane oxygenation (ECMO) is used in critically ill patients that require respiratory and/or cardiac support. Cefiderocol is a novel siderophore antibiotic that may require use in infected critically ill patients supported by ECMO. The objective of this study was to determine the loss of cefiderocol through an ex vivo adult ECMO circuit using a Quadrox-iD oxygenator.
View Article and Find Full Text PDFExpert Opin Drug Metab Toxicol
January 2023
Introduction: Determining antibiotic exposure in the lung and the threshold(s) needed for effective antibacterial killing is paramount during development of new antibiotics for the treatment of nosocomial pneumonia, as these exposures directly affect clinical outcomes and resistance development. The use of pharmacokinetic and pharmacodynamic modeling is recommended by regulatory agencies to evaluate antibiotic pulmonary exposure and optimize dosage regimen selection. This process has been implemented in newer antibiotic development.
View Article and Find Full Text PDFIntroduction: Taniborbactam (formerly VNRX-5133) is an investigational β-lactamase inhibitor in clinical development in combination with cefepime for the treatment of MDR Gram-negative pathogens.
Objectives: To assess the safety profile and pulmonary disposition of 2-0.5 g cefepime/taniborbactam administered as a 2 h IV infusion every 8 h following three doses in healthy adult subjects.
Patients hospitalized with coronavirus disease 2019 (COVID-19) often receive empiric antibiotic coverage. Procalcitonin (PCT) is a biomarker with Food and Drug Administration-approved guidance cutoffs for antibiotic use in lower respiratory tract infections. Herein we describe the implementation and impact of a pharmacist-managed PCT monitoring program in hospitalized patients with COVID-19.
View Article and Find Full Text PDFBackground: Trimethoprim/sulfamethoxazole has historically been the treatment of choice for infection caused by Stenotrophomonas maltophilia. This study sought to define the pharmacodynamic indices and magnitude of exposure required for stasis and 1 log10 cfu reductions.
Methods: Pharmacodynamic studies were conducted using the in vitro chemostat model over 24 h against three trimethoprim/sulfamethoxazole-susceptible S.