Dynamic PK/PD Infection Models for the Development and Optimisation of Antimicrobial Regimens: A Narrative Review.

The antimicrobial concentration-time profile in humans affects antimicrobial activity, and as such, it is critical for preclinical infection models to simulate human-like dynamic concentration-time profiles for maximal translatability. This review discusses the setup, principle, and application of various dynamic PK/PD infection models commonly used in the development and optimisation of antimicrobial treatment regimens. It covers the commonly used dynamic infection models, including the one-compartment model, hollow fibre infection model, biofilm model, bladder infection model, and aspergillus infection model.

Positive effect of erythromycin on ineffective oesophageal motility in laryngopharyngeal reflux patients: Room for a novel treatment?

Introduction: Laryngopharyngeal reflux (LPR) management guidelines are currently derived from the management of gastroesophageal reflux disease (GORD) which has been shown to be poorly effective in controlling symptoms for these patients. Erythromycin is a macrolide antibiotic that has been used extensively as a prokinetic agent for the gastrointestinal tract. The management of LPR with prokinetics is a novel therapy being investigated with regard to its effectiveness.

A Pooled Pharmacokinetic Analysis for Piperacillin/Tazobactam Across Different Patient Populations: From Premature Infants to the Elderly.

Background And Objectives: The pharmacokinetics (PK) of piperacillin/tazobactam (PIP/TAZ) is highly variable across different patient populations and there are controversies regarding non-linear elimination as well as the fraction unbound of PIP (f). This has led to a plethora of subgroup-specific models, increasing the risk of misusing published models when optimising dosing regimens. In this study, we aimed to develop a single model to simultaneously describe the PK of PIP/TAZ in diverse patient populations and evaluate the current dosing recommendations by predicting the PK/pharmacodynamics (PD) target attainment throughout life.

A systematic review and individual bacterial species level meta-analysis of in vitro studies on the efficacy of ceftazidime/avibactam combined with other antimicrobials against carbapenem-resistant Gram-negative bacteria.

Background: Carbapenem-resistant Gram-negative bacteria (CR-GNB) develop resistance to many antimicrobials. To effectively manage infections caused by these organisms, novel agents and/or combinations of antimicrobials are required.

Objectives: Evaluated the in vitro efficacy of ceftazidime/avibactam in combination with other antimicrobials against CR-GNB.

A review of antimicrobial stability testing guidance for outpatient parenteral antimicrobial therapy programmes: is it time for global harmonization of testing frameworks?

Antimicrobial stability is an important consideration for treatment planning and service delivery in outpatient parenteral antimicrobial therapy (OPAT) programmes. Regulation of stability assessment varies by region, and conflicting guidance and standards exist. This leads to disparity of equity in access and limits availability of certain antimicrobials for managing infections in the outpatient setting.

Outpatient parenteral antimicrobial therapy with carbapenems: A systematic review.

Objective: To review the literature on parenteral carbapenems in OPAT and present comprehensive evidence on their safety, efficacy, and stability.

Methods: A systematic review following PRISMA guidelines was conducted through 17 January 2024, using PubMed, Embase, Web of Science, Scopus, and the Cochrane Library to find relevant articles.

Results: Ertapenem (1 g QD) in OPAT showed high clinical (81-97%) and microbiological (67-90.

Is there evidence on the optimal duration of aminoglycoside therapy in β-lactam/aminoglycoside combination regimens used for the treatment of gram-negative bacterial infections? A systematic review.

Background: The optimal duration of therapy of aminoglycosides in combination regimens is expected to be different from that of monotherapy regimens, and shorter durations could help minimize toxicity without compromising efficacy. The aim of this review was to assess the evidence for the optimal duration of aminoglycosides in β-lactam/aminoglycoside combinations used for the treatment of Gram-negative bacterial infections.

Materials And Methods: PubMed, Cochrane, Embase, Scopus, Web of Science, and CINHAL databases were searched.

Safety and efficacy of outpatient parenteral antimicrobial therapy: A systematic review and meta-analysis of randomized clinical trials.

Background: Outpatient parenteral antimicrobial therapy (OPAT) offers an alternative to inpatient (hospital bed-based) treatment of infections that require intravenous administration of antimicrobials. This meta-analysis aimed to summarise the evidence available from randomised controlled trials (RCTs) regarding the efficacy and safety of OPAT compared to inpatient parenteral antimicrobial therapy.

Methods: We searched the Cochrane Library, MEDLINE, Embase, PubMed, and Web of Sciences databases for RCTs comparing outpatient versus inpatient parenteral antimicrobial therapy.

Evaluation of the stability of ceftazidime/avibactam in elastomeric infusion devices used for outpatient parenteral antimicrobial therapy utilizing a national stability protocol framework.

Objectives: To evaluate the stability of ceftazidime/avibactam in elastomeric infusers, utilizing the UK's Yellow Cover Document (YCD) stability testing framework, in conditions representative of OPAT practice.

Methods: Ceftazidime/avibactam was reconstituted with sodium chloride 0.9% (w/v) in two elastomeric infusers at concentrations (dose) levels of 1500/375, 3000/750 and 6000 mg/1500 mg in 240 mL.

What are the optimal pharmacokinetic/pharmacodynamic targets for β-lactamase inhibitors? A systematic review.

Background: Pharmacokinetic/pharmacodynamic (PK/PD) indices are widely used for the selection of optimum antibiotic doses. For β-lactam antibiotics, fT>MIC, best relates antibiotic exposure to efficacy and is widely used to guide the dosing of β-lactam/β-lactamase inhibitor (BLI) combinations, often without considering any PK/PD exposure requirements for BLIs.

Objectives: This systematic review aimed to describe the PK/PD exposure requirements of BLIs for optimal microbiological efficacy when used in combination with β-lactam antibiotics.

Barriers and facilitators for the implementation and expansion of outpatient parenteral antimicrobial therapy: a systematic review.

Outpatient parenteral antimicrobial therapy (OPAT) has been expanding in recent years and serves as a viable solution in reducing the shortage of hospital beds. However, the wider implementation of OPAT faces numerous challenges. This review aimed to assess implementation barriers and facilitators of OPAT services.

The global epidemiology of ventilator-associated pneumonia caused by multi-drug resistant Pseudomonas aeruginosa: A systematic review and meta-analysis.

Objectives: The objective of this systematic review and meta-analysis was to estimate the global prevalence of multi-drug resistant (MDR) Pseudomonas aeruginosa causing ventilator-associated pneumonia (VAP).

Methods: The systematic search was conducted in four databases. Original studies describing MDR P.

A protocol for an international, multicentre pharmacokinetic study for Screening Antifungal Exposure in Intensive Care Units: The SAFE-ICU study.

Objective: To describe whether contemporary dosing of antifungal drugs achieves therapeutic exposures in critically ill patients that are associated with optimal outcomes. Adequate antifungal therapy is a key determinant of survival of critically ill patients with fungal infections. Critical illness can alter an antifungal agents' pharmacokinetics, increasing the risk of inappropriate antifungal exposure that may lead to treatment failure and/or toxicity.

An in vitro dynamic bioreactor model for evaluating antimicrobial effectiveness on periodontal polymicrobial biofilms: a proof-of-concept study.

Background: The aim of this study was to investigate an in vitro dynamic bioreactor model by evaluating the antimicrobial effect of clinically relevant amoxicillin doses on polymicrobial microcosm biofilms derived from subgingival plaque.

Methods: Biofilms from pooled subgingival plaque were grown for 108  hours in control and experimental dynamic biofilm reactors. Amoxicillin was subsequently infused into the experimental reactor to simulate the pharmacokinetic profile of a standard 500 mg thrice-daily dosing regimen over 5 days and biofilms were assessed by live/dead staining, scanning electron microscopy, and quantitative polymerase chain reaction.

Current and Emerging Treatment Options for Multidrug Resistant Urosepsis: A Review.

is a versatile commensal and pathogenic member of the human microflora. As the primary causative pathogen in urosepsis, places an immense burden on healthcare systems worldwide. To further exacerbate the issue, multi drug resistance (MDR) has spread rapidly through populations, making infections more troublesome and costlier to treat.

Evaluation of Fosfomycin-Sulbactam Combination Therapy against Carbapenem-Resistant Isolates in a Hollow-Fibre Infection Model.

Static concentration in vitro studies have demonstrated that fosfomycin- or sulbactam-based combinations may be efficacious against carbapenem-resistant (CRAB). In the present study, we aimed to evaluate the bacterial killing and resistance suppression potential of fosfomycin-sulbactam combination therapies against CRAB isolates in a dynamic infection model. We simulated clinically relevant dosing regimens of fosfomycin (8 g every 8 h, 1 h infusion) and sulbactam (12 g continuous infusion or 4 g every 8 h, 4 h infusion) alone and in combination for 7 days in a hollow-fibre infection model (HFIM) against three clinical isolates of CRAB.

Pharmacodynamic evaluation of intermittent versus extended and continuous infusions of piperacillin/tazobactam in a hollow-fibre infection model against Escherichia coli clinical isolates.

Objectives: To compare the bacterial killing and emergence of resistance of intermittent versus prolonged (extended and continuous infusions) infusion dosing regimens of piperacillin/tazobactam against two Escherichia coli clinical isolates in a dynamic hollow-fibre infection model (HFIM).

Methods: Three piperacillin/tazobactam dosing regimens (4/0.5 g 8 hourly as 0.

Pharmacodynamics of Piperacillin-Tazobactam/Amikacin Combination versus Meropenem against Extended-Spectrum β-Lactamase-Producing Escherichia coli in a Hollow Fiber Infection Model.

Carbapenems are recommended for the treatment of urosepsis caused by extended-spectrum β-lactamase (ESBL)-producing, multidrug-resistant Escherichia coli however, due to selection of carbapenem resistance, there is an increasing interest in alternative treatment regimens including the use of β-lactam-aminoglycoside combinations. We compared the pharmacodynamic activity of piperacillin-tazobactam and amikacin as mono and combination therapy versus meropenem monotherapy against extended-spectrum β-lactamase (ESBL)-producing, piperacillin-tazobactam resistant E. coli using a dynamic hollow fiber infection model (HFIM) over 7 days.

Pharmacodynamic evaluation of piperacillin/tazobactam against extended-spectrum β-lactamase (ESBL)-producing versus non-ESBL-producing Escherichia coli in a hollow-fibre infection model.

Extended-spectrum β-lactamase (ESBL)-producing Escherichia coli are a global public-health concern. We evaluated the pharmacodynamic activity of piperacillin/tazobactam (TZP) dosing regimens against ESBL-producing versus non-ESBL-producing E. coli.

Pharmacodynamic evaluation of piperacillin/tazobactam versus meropenem against extended-spectrum β-lactamase-producing and non-producing Escherichia coli clinical isolates in a hollow-fibre infection model.

Background: Urosepsis caused by extended-spectrum β-lactamase (ESBL)-producing Escherichia coli is increasing worldwide. Carbapenems are commonly recommended for the treatment of ESBL infections; however, to minimize the emergence of carbapenem resistance, interest in alternative treatments has heightened.

Objectives: This study compared pharmacodynamics of piperacillin/tazobactam versus meropenem against ESBL-producing and non-producing E.

Evaluation of the stability of temocillin in elastomeric infusion devices used for outpatient parenteral antimicrobial therapy in accordance with the requirements of the UK NHS Yellow Cover Document.

Objective: To evaluate the stability of temocillin solution in two elastomeric infusion devices - Easypump II LT 270-27- S and Dosi-Fusor L25915-250D1 for OPAT administration during 14 days of 5°C±3°C fridge storage followed by 24 hour exposure at an in-use temperature of 32°C, when reconstituted with 0.3% citrate buffer at pH7.

Methods: Stability testing was conducted in accordance with standard protocols in the UK National Health Service Yellow Cover Document (YCD).