The impact of extracorporeal support on antimicrobial pharmacokinetics in critically ill neonatal and paediatric patients: A systematic review.

Objectives: Infections represent a major risk for critically ill neonatal and paediatric patients requiring extracorporeal life-saving support such as extracorporeal membrane oxygenation (ECMO) and/or continuous renal replacement therapies (CRRT). Patient outcomes rely on achieving target antimicrobial concentrations. In critically ill adults on extracorporeal support, suboptimal antimicrobial concentrations have been shown to be common.

Dalbavancin as suppressive antibiotic therapy in patients with prosthetic infections: efficacy and safety.

Suppressive antibiotic therapy (SAT) is a strategy to alleviate symptoms and/or to reduce the progression of an infection when other treatment options cannot be used. Dalbavancin, due to its prolonged half-life, enables (bi) weekly dosing. Here, we report our multicenter real-life clinical experience with dalbavancin used as SAT in patients with prosthetic joint or vascular infections.

Antifungal Dosing in Critically Ill Patients on Extracorporeal Membrane Oxygenation.

Extracorporeal membrane oxygenation (ECMO) is an established advanced life support system, providing temporary cardiac and/or respiratory support in critically ill patients. Fungal infections are associated with increased mortality in patients on ECMO. Antifungal drug dosing for critically ill patients is highly challenging because of altered pharmacokinetics (PK).

A Systematic Review on Antimicrobial Pharmacokinetic Differences between Asian and Non-Asian Adult Populations.

While the relevance of inter-ethnic differences to the pharmacokinetic variabilities of antimicrobials has been reported in studies recruiting healthy subjects, differences in antimicrobial pharmacokinetics between Asian and non-Asian patients with severe pathologic conditions require further investigation. For the purpose of describing the potential differences in antimicrobial pharmacokinetics between Asian and non-Asian populations, a systematic review was performed using six journal databases and six theses/dissertation databases (PROSPERO record CRD42018090054). The pharmacokinetic data of healthy volunteers and non-critically ill and critically ill patients were reviewed.

Population Pharmacokinetics and Dosing Simulations of Ampicillin and Sulbactam in Hospitalised Adult Patients.

Background: The pharmacokinetic variability of ampicillin-sulbactam in adults has not been extensively described, particularly in patients with a reduced renal function (i.e., < 60 mL/min).

Population pharmacokinetics and dose optimization of intravenous levofloxacin in hospitalized adult patients.

Although levofloxacin has been used for the last 25 years, there are limited pharmacokinetic data to guide levofloxacin dosing in adult patients. This study aimed to develop a population pharmacokinetic model of levofloxacin for adult hospitalized patients and define dosing regimens that attain pharmacokinetic/pharmacodynamic target associated with maximum effectiveness. Blood samples were drawn from 26 patients during one dosing interval.

Hospital-Based Antimicrobial Stewardship Programs Used in Low- and Middle-Income Countries: A Scoping Review.

The burden of antimicrobial resistance (AMR) is considerable in many low- and middle-income countries (LMICs), and it is important to describe the antimicrobial stewardship program (ASP) activities found in these countries and report their impact. Importantly, as these programs target prescribing behavior, the factors influencing prescription of antimicrobials must also be taken into account. This scoping review aimed to (1) describe hospital-based ASP activities, (2) report methods used to measure the impact of ASPs, and (3) explore factors influencing antimicrobial prescribing behavior in LMICs.

Indonesian healthcare providers' perceptions and attitude on antimicrobial resistance, prescription and stewardship programs.

A successful antimicrobial stewardship program (ASP) is sustained through improving antimicrobial prescribing by changing prescribing behavior. This requires a better understanding of hospital stakeholders' views regarding antimicrobial resistance (AMR), antimicrobial use and participation in ASP activities. Identify perceptions and attitudes among physicians and pharmacists in a public hospital toward AMR, prescription and ASP.

Knowledge, Perception, and Antibiotic Prescribing Practice in the Intensive Care Unit: Findings from the Malaysian Public Setting.

Introduction: Approach to managing infection in the intensive care unit (ICU) often varies between institutions and not many readily adapt to available local guidelines despite it was constructed to suite local clinical scenario. Malaysia already has two published guidelines on managing infection in the ICU but data on its compliance are largely unknown.

Objectives: A cross-sectional survey was carried out and sent to a total of 868 specialists working primarily in the ICU.

Provider perspectives on beta-lactam therapeutic drug monitoring programs in the critically ill: a protocol for a multicenter mixed-methods study.

Background: Beta-lactams (i.e., penicillins, cephalosporins, carbapenems, monobactams) are the most widely used class of antibiotics in critically ill patients.

A case report: Community-acquired necrotizing fasciitis in a morbidly obese diabetic young man can be fatal.

We present a case study of a 26-year-old morbidly obese man with a three-day history of right leg pain and swelling. The swelling was associated with low grade fever. He was alert and conscious upon presentation to the hospital.

The role of antibiotic pharmacokinetic studies performed post-licensing.

Post-licensing pharmacometric studies can provide a better understanding of the pharmacokinetic (PK) alterations in special patient populations and may lead to better clinical outcomes. Some patient populations exhibit markedly different pathophysiology to general ward patients or healthy individuals. This may be developmental (paediatric patients), a manifestation of an underlying disease pathology (patients with obesity or haematological malignancies) or due to medical interventions (critically ill patients receiving extracorporeal therapies).

Prolonged Versus Intermittent Infusion of β-Lactam Antibiotics: A Systematic Review and Meta-Regression of Bacterial Killing in Preclinical Infection Models.

Background: Administering β-lactam antibiotics via prolonged infusions for critically ill patients is mainly based on preclinical evidence. Preclinical data on this topic have not been systematically reviewed before.

Objectives: The aim of this study was to describe the pharmacokinetic/pharmacodynamic (PK/PD) indices and targets reported in preclinical models and to compare the bactericidal efficacy of intermittent and prolonged infusions of β-lactam antibiotics.

Infections by multidrug-resistant Gram-negative Bacteria: What's new in our arsenal and what's in the pipeline?

The spread of multidrug-resistant bacteria is an ever-growing concern, particularly among Gram-negative bacteria because of their intrinsic resistance and how quickly they acquire and spread new resistance mechanisms. Treating infections caused by Gram-negative bacteria is a challenge for medical practitioners and increases patient mortality and cost of care globally. This vulnerability, along with strategies to tackle antimicrobial resistance development, prompts the development of new antibiotic agents and exploration of alternative treatment options.

Optimising drug dosing in patients receiving extracorporeal membrane oxygenation.

Optimal pharmacological management during extracorporeal membrane oxygenation (ECMO) involves more than administering drugs to reverse underlying disease. ECMO is a complex therapy that should be administered in a goal-directed manner to achieve therapeutic endpoints that allow reversal of disease and ECMO wean, minimisation of complications (treatment of complications when they do occur), early interruption of sedation and rehabilitation, maximising patient comfort and minimising risks of delirium. ECMO can alter both the pharmacokinetics (PK) and pharmacodynamics (PD) of administered drugs and our understanding of these alterations is still evolving.

Prolonged administration of β-lactam antibiotics - a comprehensive review and critical appraisal.

Prolonged infusion of β-lactam antibiotics as either extended (over at least 2 hours) or continuous infusion is increasingly applied in intensive care units around the world in an attempt to optimise treatment with this most commonly used class of antibiotics, whose effectiveness is challenged by increasing resistance rates. The pharmacokinetics of β-lactam antibiotics in critically ill patients is profoundly altered secondary to an increased volume of distribution and the presence of altered renal function, including augmented renal clearance. This may lead to a significant decrease in plasma concentrations of β-lactam antibiotics.

Continuous versus Intermittent β-Lactam Infusion in Severe Sepsis. A Meta-analysis of Individual Patient Data from Randomized Trials.

Rationale: Optimization of β-lactam antibiotic dosing for critically ill patients is an intervention that may improve outcomes in severe sepsis.

Objectives: In this individual patient data meta-analysis of critically ill patients with severe sepsis, we aimed to compare clinical outcomes of those treated with continuous versus intermittent infusion of β-lactam antibiotics.

Methods: We identified relevant randomized controlled trials comparing continuous versus intermittent infusion of β-lactam antibiotics in critically ill patients with severe sepsis.

What is the effect of obesity on piperacillin and meropenem trough concentrations in critically ill patients?

Objectives: The objectives of this study were to determine the effects of obesity on unbound trough concentrations and on the achievement of pharmacokinetic (PK)/pharmacodynamic (PD) targets of piperacillin and meropenem in critically ill patients.

Methods: This study retrospectively analysed therapeutic-drug-monitoring data from ICU databases in Australia, Germany and Spain, as well as from a large PK study. The presence of obesity was defined as a BMI ≥30 kg/m(2), and patients were also categorized based on level of renal function.

Continuous infusion vs. bolus dosing: implications for beta-lactam antibiotics.

Beta-lactam antibiotics display time-dependant pharmacodynamics whereby constant antibiotic concentrations rather than high peak concentrations are most likely to result in effective treatment of infections caused by susceptible bacteria. Continuous administration has been suggested as an alternative strategy, to conventional intermittent dosing, to optimise beta-lactam pharmacokinetic/pharmacodynamic (PK/PD) properties. With the availability of emerging data, we elected to systematically investigate the published literature describing the comparative PK/PD and clinical outcomes of beta-lactam antibiotics administered by continuous or intermittent infusion.