Comparative simulation of intraperitoneal aminoglycoside regimens for patients with peritonitis on automated peritoneal dialysis.

Background: Intraperitoneal (IP) aminoglycosides (AGs) continue to be the cornerstone of empiric management of peritonitis. AG dosing during automated peritoneal dialysis (APD), however, has not been well studied in patients with peritonitis. We sought to identify differences in AG exposure in the peritoneum and plasma for two different dosing regimens with little supporting evidence in patients on APD with peritonitis.

Effective Antimicrobial Prophylaxis in Surgery: The Relevance and Role of Pharmacokinetics-Pharmacodynamics.

Appropriate surgical antimicrobial prophylaxis (SAP) is an important measure in preventing surgical site infections (SSIs). Although antimicrobial pharmacokinetics-pharmacodynamics (PKPD) is integral to optimizing antibiotic dosing for the treatment of infections, there is less research on preventing infections postsurgery. Whereas clinical studies of SAP dose, preincision timing, and redosing are informative, it is difficult to isolate their effect on SSI outcomes.

An updated vancomycin dosing protocol for initiating therapy in patients undergoing intermittent high-flux hemodialysis.

Purpose: To design an updated vancomycin dosing protocol for initiating therapy in patients undergoing chronic intermittent high-flux hemodialysis (iHFHD) that is congruent with the revised 2020 consensus guidelines for therapeutic drug monitoring (TDM).

Methods: Monte Carlo simulation methods were used to study vancomycin dosing for patients on iHFHD. Vancomycin regimens were constructed as intravenous infusions (for intradialytic administration) of a loading dose and maintenance doses 3 times weekly during subsequent dialysis sessions.

Clinical Blood Isolates from Hemodialysis Patients: Distribution of Organisms and Antimicrobial Resistance, 2007-2014.

Background: Given the morbidity and mortality associated with bloodstream infections in hemodialysis patients, understanding the microbiology is essential to optimizing treatment in this high-risk population.

Objectives: To conduct a retrospective surveillance study of clinical blood isolates from adult hemodialysis patients, and to predict the microbiological coverage of empiric therapies for bloodstream infections in this population.

Methods: Clinical blood isolate data were collected from the 4 main outpatient hemodialysis units in Winnipeg, Manitoba, from 2007 to 2014.

Antimicrobial Prophylaxis for Patients Undergoing Cardiac Surgery: Intraoperative Cefazolin Concentrations and Sternal Wound Infections.

This study characterizes the pharmacodynamics of antimicrobial prophylaxis and sternal wound infections following cardiac surgery. Duration of surgery and cefazolin plasma concentration during wound closure were independently associated with surgical site infection at 30 days. Furthermore, a duration of surgery of >346 min and a total cefazolin closure concentration of <104 mg/liter were significant thresholds for an increased risk of infection.

Limitations of ceftriaxone compared with cefazolin against MSSA: an integrated pharmacodynamic analysis.

Objectives: Despite the convenience of once-daily dosing, the use of ceftriaxone for Staphylococcus aureus infections has significant limitations, including scarce clinical evidence and increasingly questionable pharmacodynamic activity. Our goal was to conduct an integrated pharmacokinetic-pharmacodynamic analysis of the appropriateness of ceftriaxone compared with cefazolin for treating serious MSSA infections.

Methods: Ceftriaxone and cefazolin activity against five clinical MSSA isolates was characterized in an in vitro pharmacodynamic model.

Evaluation of cefazolin antimicrobial prophylaxis during cardiac surgery with cardiopulmonary bypass.

Objectives: Although clinical practice guidelines recommend standard cefazolin antimicrobial prophylaxis (AP) dosing for cardiac surgery, limited data exist as to whether adequate concentrations are achieved in this patient population. The goal of our study was to characterize intraoperative cefazolin concentrations particularly at wound closure with regards to maintaining target cefazolin closure concentrations ≥40 mg/L.

Methods: Adults undergoing cardiac surgery with cardiopulmonary bypass (CPB) and receiving cefazolin AP according to protocol were studied.

No role for patient body weight on renal function assessment for drug dosing.

Objectives: To evaluate the ability of body-weight-driven renal function assessment (RFA) formulae to predict on-target elimination rate ranges for gentamicin in patients with varying degrees of renal function.

Methods: A 6 year retrospective pharmacokinetic study was conducted at a university teaching hospital.

Results: A total of 85 patients met the inclusion criteria and 127 pharmacokinetic files were analysed from patients on medical-surgical wards (53%) and medical-surgical ICUs (13%) receiving intravenous gentamicin for treatment, as well as those for patients receiving it for surgical prophylaxis (34%).

Microbiological Trends and Antimicrobial Resistance in Peritoneal Dialysis-Related Peritonitis, 2005 to 2014.

♦ BACKGROUND: Information related to the microbiology of peritonitis is critical to the optimal management of patients receiving peritoneal dialysis (PD). The goal was to characterize the microbiological etiology and antimicrobial susceptibilities of PD-related peritonitis (PDRP) from 2005 to 2014, inclusive. ♦ METHODS: The distribution of organisms in culture-positive PDRP was described for new episodes and relapse infections, and further detailed for monomicrobial and polymicrobial peritonitis.

Successful treatment of pulmonary blastomycosis with continuously infused amphotericin B deoxycholate after failure with liposomal amphotericin B.

Objective: To describe a case of successful treatment of severe pulmonary blastomycosis with amphotericin B deoxycholate after failure of liposomal amphotericin B.

Case Summary: A 35-year-old male was exposed to damp decomposing wood while cleaning his basement. He subsequently developed a cough, malaise, fever, nausea, vomiting, and diarrhea.

Integrating pharmacokinetics, pharmacodynamics and MIC distributions to assess changing antimicrobial activity against clinical isolates of Pseudomonas aeruginosa causing infections in Canadian hospitals (CANWARD).

Objectives: To study antimicrobial pharmacodynamic (PD) activity over time against clinical isolates of Pseudomonas aeruginosa in Canadian hospitals.

Methods: Integrated pharmacokinetic (PK)/PD analyses with Monte Carlo simulations were used to study cefepime, meropenem, piperacillin/tazobactam, ciprofloxacin, amikacin, gentamicin and colistin. Profiles of P.

Initial vancomycin dosing protocol to achieve therapeutic serum concentrations in patients undergoing hemodialysis.

Background: Although recent consensus guidelines proposed more aggressive vancomycin troughs of >10 or 15-20 mg/L for complicated Staphylococcus aureus infections, dosing information to achieve these targets in patients undergoing hemodialysis (HD) is scarce.

Methods: We used Monte Carlo simulation (MCS) methods with a previously published population-pharmacokinetic model and relevant patient demographics to evaluate and revise our existing vancomycin dosing protocol (1000-mg load followed by 500-mg maintenance dose, with doses infused during the last hour of dialysis). A new protocol (1000-mg load followed by 500-mg maintenance dose for patients <70 kg, 1250-mg followed by 750-mg for those 70-100 kg, and 1500-mg followed by 1000-mg for those >100 kg) was developed and prospectively validated to achieve therapeutic serum troughs in patients undergoing high-flux HD.

Optimization of meropenem dosage in the critically ill population based on renal function.

Purpose: To develop a meropenem population pharmacokinetic model in critically ill patients with particular focus on optimizing dosing regimens based on renal function.

Methods: Population pharmacokinetic analysis was performed with creatinine clearance (CrCl) and adjusted body weight to predict parameter estimates. Initial modeling was performed on 21 patients (55 samples).

Pharmacodynamics of empirical antibiotic monotherapies for an intensive care unit (ICU) population based on Canadian surveillance data.

Objectives: To evaluate, using Monte Carlo simulation, the pharmacodynamics (PD) of empirical antibiotic monotherapies for serious infections consistent with Canadian intensive care unit (ICU) surveillance data.

Methods: Meropenem, piperacillin/tazobactam and cefepime, along with ceftobiprole, a broad-spectrum cephalosporin active against methicillin-resistant Staphylococcus aureus (MRSA), were tested at standard and highest recommended doses with and without prolonged infusion times (t'). Population pharmacokinetic models were used to simulate antibiotic serum concentrations (n = 5000).

Support for higher ciprofloxacin AUC 24/MIC targets in treating Enterobacteriaceae bloodstream infection.

Objectives: Given concerns regarding optimal therapy for serious Gram-negative infections, the goal was to characterize the pharmacodynamics of ciprofloxacin in the context of treating bloodstream infection.

Patients And Methods: Data were collected from the medical records of 178 clinical cases. Blood isolates were retrieved and ciprofloxacin MICs were measured.

Enteric absorption and pharmacokinetics of oseltamivir in critically ill patients with pandemic (H1N1) influenza.

Background: Whether the enteric absorption of the neuraminidase inhibitor oseltamivir is impaired in critically ill patients is unknown. We documented the pharmacokinetic profile of oseltamivir in patients admitted to intensive care units (ICUs) with suspected or confirmed pandemic (H1N1) influenza.

Methods: We included 41 patients 18 years of age and older with suspected or confirmed pandemic (H1N1) influenza who were admitted for ventilatory support to nine ICUs in three cities in Canada and Spain.

Population pharmacokinetics of high-dose, prolonged-infusion cefepime in adult critically ill patients with ventilator-associated pneumonia.

A population pharmacokinetic model of cefepime was constructed from data from adult critical care patients with ventilator-associated pneumonia (VAP). A total of 32 patients treated with high-dose cefepime, 2 g every 8 h (3-h infusion) or a renal function-adjusted equivalent dose, were randomized into two groups--26 for the initial model and 6 for model validation. Serum samples of cefepime were collected at steady state.

Aminoglycoside-induced vestibular injury: maintaining a sense of balance.

Objective: To describe the mechanism and risk factors for the development of aminoglycoside-induced vestibular injury and discuss their implications for therapeutic monitoring of aminoglycoside antibiotics.

Data Sources: A MEDLINE search (1975-January 2008) was performed to identify literature on aminoglycoside-induced vestibular injury and risk factors associated with this outcome and their impact on therapeutic drug monitoring. Additional references were identified through review of bibliographies of identified articles.

Effectiveness of a 30% ethanol/4% trisodium citrate locking solution in preventing biofilm formation by organisms causing haemodialysis catheter-related infections.

Objectives: Antibiotic locks may be used to prevent haemodialysis catheter-related infections (CRIs). This in vitro study tested the effectiveness of a novel 30% ethanol/4% trisodium citrate lock solution in preventing biofilm formation by the most common pathogens causing haemodialysis CRIs.

Methods: Ten clinical isolates of Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa and Escherichia coli were tested.

Effect of an ethanol/trisodium citrate hemodialysis catheter locking solution on isolates of Candida albicans.

We conducted an in vitro study to assess the effect of a 30% ethanol/4% trisodium citrate (TSC) catheter locking solution on isolates of Candida albicans. Twelve isolates obtained from human blood cultures were tested in control solutions composed of broth and normal saline, and a test solution of 30% ethanol, 4% TSC, and broth. Colony counts were determined for control and test solutions at baseline and after 1, 24, and 48 hours of exposure.

Adequacy of a vancomycin dosing regimen in patients receiving high-flux hemodialysis.

Background: Some investigators have recommended the convenient practice of administering vancomycin doses during the last hour of the hemodialysis treatment. Accepting that a greater amount of vancomycin is lost to dialysis with this recent approach, the objective of this study is to determine the pharmacokinetics of vancomycin and assess the adequacy of this dosing regimen in maintaining therapeutic predialysis concentrations.

Methods: A sampling of 22 consecutive patients administered intradialytic vancomycin, 1 g, intravenously (IV) and maintenance doses of 500 mg during the last hour of high-flux dialysis sessions was studied.

An evaluation of an optimal sampling strategy for meropenem in febrile neutropenics.

Optimal sampling design with nonparametric population modeling offers the opportunity to determine pharmacokinetic parameters for patients in whom blood sampling is restricted. This approach was compared to a standard individualized modeling method for meropenem pharmacokinetics in febrile neutropenic patients. The population modeling program, nonparametric approach of expectation maximization (NPEM), with a full data set was compared to a sparse data set selected by D-optimal sampling design.

Antibiotic combinations significantly more active than monotherapy in an in vitro infection model of Stenotrophomonas maltophilia.

The goal of this study was to investigate clinical doses of trimethoprim-sulfamethoxazole (TMP-SMX) alone and in combination against Stenotrophomonas maltophilia in an in vitro pharmacodynamic infection model. A 1-compartment model was established using 4 clinical isolates of S. maltophilia susceptible to TMP-SMX and susceptible or intermediately susceptible to at least one other agent (ie, ceftazidime, ciprofloxacin, gentamicin, tobramycin).

Pharmacokinetics and pharmacodynamics of meropenem in febrile neutropenic patients with bacteremia.

Background: Pharmacodynamic investigations with antimicrobials define the relationship between the infecting organism and achievable drug concentrations with clinical outcome.

Objective: To examine this relationship for meropenem in a population of patients who are at high risk of infection-related morbidity and mortality.

Methods: The study was a retrospective analysis of a multicenter, randomized, blinded clinical trial.