Ceftolozane/tazobactam disrupts Pseudomonas aeruginosa biofilms under static and dynamic conditions.

Background: Pseudomonas aeruginosa biofilms limit the efficacy of currently available antibacterial therapies and pose significant clinical challenges. Pseudomonal biofilms are complicated further when other markers of persistence such as mucoid and hypermutable phenotypes are present. There is currently a paucity of data regarding the activity of the newer β-lactam/β-lactamase inhibitor combination ceftolozane/tazobactam against P.

What are ambulance personnel experiences of sexual harassment and sexual assault in the workplace? A rapid evidence review.

Introduction: Sexual assault and harassment of ambulance personnel in the workplace is widespread. Prevention via body worn cameras and legal efforts have been positive, however improvement is still needed to ensure the protection of staff from the negative impact of sexual violence at work.

Methods: A rapid evidence review was conducted following the Cochrane Rapid Review guidance.

Nocardia species distribution and antimicrobial susceptibility within Australia.

Background: Nocardia is a ubiquitous saprophyte capable of causing human disease. Disease is primarily respiratory or cutaneous, usually acquired via inhalation or inoculation. Under the influence of environmental and host factors, Nocardia incidence and species distribution demonstrate geographical variation.

The evolution of spinal cord surgery: history, people, instruments, and results.

Introduction: Spinal cord surgery has and always will be a challenging operation with satisfying results, but also with potentially devastating results. Over the last century, there has been an evolution in the way we perceive and conduct spinal cord surgery. The phenomenal evolution in technology from the very first x-ray pictures helps to localize the spinal pathology through the use of high-resolution MRI and ultrasonography that allows for high precision surgery with relatively minimal exposure.

Antimicrobial susceptibility of ceftolozane-tazobactam against multidrug-resistant Pseudomonas aeruginosa isolates from Melbourne, Australia.

We collected 163 clinical Pseudomonas aeruginosa isolates at a tertiary hospital specialising in adult cystic fibrosis (CF) and lung transplantation (LTx) in Melbourne, Australia, to explore the activity of ceftolozane-tazobactam (C/T) in populations at high-risk for antimicrobial resistance. Of these, 144 (88.3%) were collected from sputum, and 19 (11.

Therapeutics for Vancomycin-Resistant Enterococcal Bloodstream Infections.

Vancomycin-resistant enterococci (VRE) are common causes of bloodstream infections (BSIs) with high morbidity and mortality rates. They are pathogens of global concern with a limited treatment pipeline. Significant challenges exist in the management of VRE BSI, including drug dosing, the emergence of resistance, and the optimal treatment for persistent bacteremia and infective endocarditis.

The impact of daptomycin therapeutic drug monitoring on clinical outcomes: a systematic review.

Aim: Daptomycin therapeutic drug monitoring (TDM) is a potentially valuable intervention for a relatively new drug. The aim of this study was to determine whether daptomycin TDM, including dose adjustment where necessary, improves the clinical outcomes of adult patients with Gram-positive infections.

Methods: A systematic review of English-language studies in MEDLINE (Ovid MEDLINE and Epub Ahead of Print, In-process, In-Data-Review & Other Non-Indexed Citations, Daily and Versions), EMBASE via OVID, Cochrane Central Register of Controlled Trials via the OVID platform, Scopus and Web of Science online databases was performed and conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

Oral ciprofloxacin activity against ceftriaxone-resistant Escherichia coli in an in vitro bladder infection model.

Objectives: Pharmacodynamic profiling of oral ciprofloxacin dosing for urinary tract infections caused by ceftriaxone-resistant Escherichia coli isolates with ciprofloxacin MIC ≥ 0.25 mg/L.

Background: Urine-specific breakpoints for ciprofloxacin do not exist.

Successful Treatment of Pediatric Holo-Spinal Epidural Abscess With Percutaneous Drainage.

Spinal epidural abscess (SEA) is a rare and potentially devastating neurologic disease that is commonly treated with neurosurgical decompression and evacuation. We describe the case of an 11-month-old immunocompetent infant who presented with a large multiloculated methicillin-resistant abscess in the left lung apex with likely mediastinal involvement, extending into the epidural space from C7 down to L2 causing cord compression which was successfully treated with percutaneous placement of an epidural drainage catheter and antibiotic therapy. Although there are rare reports of percutaneous drainage of SEAs, to our knowledge, there are no reports of successful use of percutaneous indwelling catheters resulting in the complete resolution of an SEA.

Genomic dissection of Klebsiella pneumoniae infections in hospital patients reveals insights into an opportunistic pathogen.

Klebsiella pneumoniae is a major cause of opportunistic healthcare-associated infections, which are increasingly complicated by the presence of extended-spectrum beta-lactamases (ESBLs) and carbapenem resistance. We conducted a year-long prospective surveillance study of K. pneumoniae clinical isolates in hospital patients.

Antibiotic management of urinary tract infections in the post-antibiotic era: a narrative review highlighting diagnostic and antimicrobial stewardship.

Background: As one of the most common indications for antimicrobial prescription in the community, the management of urinary tract infections (UTIs) is both complicated by, and a driver of, antimicrobial resistance.

Objectives: To highlight the key clinical decisions involved in the diagnosis and treatment of UTIs in adult women, focusing on clinical effectiveness and both diagnostic and antimicrobial stewardship as we approach the post-antimicrobial era.

Sources: Literature reviewed via directed PubMed searches and manual searching of the reference list for included studies to identify key references to respond to the objectives.

Oral fosfomycin activity against Klebsiella pneumoniae in a dynamic bladder infection in vitro model.

Introduction: The use of oral fosfomycin for urinary tract infections (UTIs) caused by non-Escherichia coli uropathogens is uncertain, including Klebsiella pneumoniae, the second most common uropathogen.

Methods: A multicompartment bladder infection in vitro model was used with standard media and synthetic human urine (SHU) to simulate urinary fosfomycin exposure after a single 3 g oral dose (fAUC0-72 16884 mg·h/L, t½ 5.5 h) against 15 K.

Pharmacokinetic/pharmacodynamic analysis of oral fosfomycin against Enterobacterales, Pseudomonas aeruginosa and Enterococcus spp. in an in vitro bladder infection model: impact on clinical breakpoints.

Objectives: Fosfomycin is an established treatment for uncomplicated urinary tract infections (UTIs), yet evidence supporting susceptibility breakpoints is limited. We examine the UTI susceptibility criteria.

Methods: Fosfomycin susceptibility, heteroresistance and in vitro growth in a bladder infection model, after a single 3 g dose of oral fosfomycin, were bridged to human pharmacokinetics with pharmacokinetic/pharmacodynamic and Monte Carlo analyses.

Genomic surveillance of antimicrobial resistant bacterial colonisation and infection in intensive care patients.

Background: Third-generation cephalosporin-resistant Gram-negatives (3GCR-GN) and vancomycin-resistant enterococci (VRE) are common causes of multi-drug resistant healthcare-associated infections, for which gut colonisation is considered a prerequisite. However, there remains a key knowledge gap about colonisation and infection dynamics in high-risk settings such as the intensive care unit (ICU), thus hampering infection prevention efforts.

Methods: We performed a three-month prospective genomic survey of infecting and gut-colonising 3GCR-GN and VRE among patients admitted to an Australian ICU.

Treatment of invasive IMP-4 Enterobacter cloacae infection in transplant recipients using ceftazidime/avibactam with aztreonam: A case series and literature review.

Infections caused by carbapenemase-producing Enterobacteriaceae (CPE) are an emerging threat in both solid organ and stem cell transplant recipients. Invasive CPE infections in transplant recipients are associated with a high mortality, often due to limited therapeutic options and antibacterial toxicities. One of the most therapeutically challenging group of CPE are the metallo-β-lactamase (MBL)-producing Gram-negative bacteria, which are now found worldwide, and often need treatment with older, highly toxic antimicrobial regimens.

Antimicrobial pharmacokinetics and preclinical models to support optimized treatment approaches for uncomplicated lower urinary tract infections.

Introduction: Urinary tract infections (UTIs) are extremely common. Millions of people, particularly healthy women, are affected worldwide every year. One-in-two women will have a recurrence within 12-months of an initial UTI.

Efficacy of single and multiple oral doses of fosfomycin against Pseudomonas aeruginosa urinary tract infections in a dynamic in vitro bladder infection model.

Objectives: We used a dynamic bladder infection in vitro model with synthetic human urine (SHU) to examine fosfomycin exposures to effectively kill, or prevent emergence of resistance, among Pseudomonas aeruginosa isolates.

Methods: Dynamic urinary fosfomycin concentrations after 3 g oral fosfomycin were simulated, comparing single and multiple (daily for 7 days) doses. Pharmacodynamic response of 16 P.

Oral Fosfomycin Treatment for Enterococcal Urinary Tract Infections in a Dynamic Model.

There are limited treatment options for enterococcal urinary tract infections, especially vancomycin-resistant (VRE). Oral fosfomycin is a potential option, although limited data are available guiding dosing and susceptibility. We undertook pharmacodynamic profiling of fosfomycin against and isolates using a dynamic bladder infection model.

Evaluation of pooled human urine and synthetic alternatives in a dynamic bladder infection in vitro model simulating oral fosfomycin therapy.

The impact of the bladder environment on fosfomycin activity and treatment response is uncertain. Standard laboratory media does not reflect the biomatrix of urine, where limited nutritional factors are important for growth and antimicrobial kill rates. We compared fosfomycin activity against Enterobacteriaceae in laboratory media, human urine and synthetic alternatives.

Oral Fosfomycin Efficacy with Variable Urinary Exposures following Single and Multiple Doses against : the Importance of Heteroresistance for Growth Outcome.

Oral fosfomycin trometamol is licensed as a single oral dose for the treatment of uncomplicated urinary tract infections, with activity against multidrug-resistant uropathogens. The impact of interindividual variability in urinary concentrations on antimicrobial efficacy, and any benefit of giving multiple doses, is uncertain. We therefore performed pharmacodynamic profiling of oral fosfomycin, using a dynamic bladder infection model, to assess high and low urinary exposures following a single oral dose and three repeat doses given every 72 h, 48 h, and 24 h against 16 clinical isolates with various MICs of fosfomycin (8 , 4 , and 4 isolates).

Impact of bacterial species and baseline resistance on fosfomycin efficacy in urinary tract infections.

Objectives: To assess the antibacterial effects of a single 3 g oral fosfomycin dose on Escherichia coli and Klebsiella pneumoniae clinical isolates within a dynamic bladder infection model.

Methods: An in vitro model simulating dynamic urinary fosfomycin concentrations was used. Target fosfomycin exposure (Cmax = 1984 mg/L and Tmax = 7.

Urinary antibacterial activity of fosfomycin and nitrofurantoin at registered dosages in healthy volunteers.

Given emerging uropathogen resistance to more recent antibiotics, old antibiotics used for uncomplicated urinary tract infection (UTI) warrant re-examination. In this study, the urinary antibacterial activities of fosfomycin and nitrofurantoin were investigated by determining the urinary inhibitory titre and urinary bactericidal titre against uropathogens in urine samples from female volunteers following administration of single-dose fosfomycin (3 g) or nitrofurantoin (50 mg q6h or 100 mg q8h). Urine samples were collected over 48 h (fosfomycin) or 6 or 8 h (nitrofurantoin), with drug levels quantified with every void.