UK clinicians' attitudes towards the application of molecular diagnostics to guide antibiotic use in ICU patients with pneumonias: a quantitative study.

Background: Molecular diagnostic tests may improve antibiotic prescribing by enabling earlier tailoring of antimicrobial therapy. However, clinicians' trust and acceptance of these tests will determine their application in practice.

Objectives: To examine ICU prescribers' views on the application of molecular diagnostics in patients with suspected hospital-acquired and ventilator-associated pneumonia (HAP/VAP).

Antimicrobial Resistance Genes, Virulence Genes, and Associated Mobile Genetic Elements of Eight Multidrug-Resistant Isolated from Hospital-Acquired Urinary Tract Infections in Sri Lanka.

The study describes the first isolation of multidrug-resistant (MDR) ST16, ST131 (Esc), and subsp. steigerwaltii ST93 ( complex [ECC]) in Sri Lanka. Eight MDR strains of uropathogenic Enterobacterales isolated from hospital acquired urinary tract infections (UTIs) were analyzed using genomic sequencing and comparative genomics.

Multicentre evaluation of two multiplex PCR platforms for the rapid microbiological investigation of nosocomial pneumonia in UK ICUs: the INHALE WP1 study.

Background: Culture-based microbiological investigation of hospital-acquired or ventilator-associated pneumonia (HAP or VAP) is insensitive, with aetiological agents often unidentified. This can lead to excess antimicrobial treatment of patients with susceptible pathogens, while those with resistant bacteria are treated inadequately for prolonged periods. Using PCR to seek pathogens and their resistance genes directly from clinical samples may improve therapy and stewardship.

INHALE: the impact of using FilmArray Pneumonia Panel molecular diagnostics for hospital-acquired and ventilator-associated pneumonia on antimicrobial stewardship and patient outcomes in UK Critical Care-study protocol for a multicentre randomised controlled trial.

Background: Hospital-acquired and ventilator-associated pneumonias (HAP and VAP) are common in critical care and can be life-threatening. Rapid microbiological diagnostics, linked to an algorithm to translate their results into antibiotic choices, could simultaneously improve patient outcomes and antimicrobial stewardship.

Methods: The INHALE Randomised Controlled Trial is a multi-centre, parallel study exploring the potential of the BioFire FilmArray molecular diagnostic to guide antibiotic treatment of HAP/VAP in intensive care units (ICU); it identifies pathogens and key antibiotic resistance in around 90 min.

Intensivists' beliefs about rapid multiplex molecular diagnostic testing and its potential role in improving prescribing decisions and antimicrobial stewardship: a qualitative study.

Background: Rapid molecular diagnostic tests to investigate the microbial aetiology of pneumonias may improve treatment and antimicrobial stewardship in intensive care units (ICUs). Clinicians' endorsement and uptake of these tests is crucial to maximise engagement; however, adoption may be impeded if users harbour unaddressed concerns or if device usage is incompatible with local practice. Accordingly, we strove to identify ICU clinicians' beliefs about molecular diagnostic tests for pneumonias before implementation at the point-of-care.

Understanding decisions about antibiotic prescribing in ICU: an application of the Necessity Concerns Framework.

Background: Antibiotics are extensively prescribed in intensive care units (ICUs), yet little is known about how antibiotic-related decisions are made in this setting. We explored how beliefs, perceptions and contextual factors influenced ICU clinicians' antibiotic prescribing.

Methods: We conducted 4 focus groups and 34 semistructured interviews with clinicians involved in antibiotic prescribing in four English ICUs.

Rapid and Point-of-Care Testing in Respiratory Tract Infections: An Antibiotic Guardian?

This is a narrative review on the potential of rapid and point-of-care microbiological testing in pneumonia patients, focusing particularly on hospital-acquired and ventilator-associated pneumonia, which have substantial mortality and diverse microbiology. This work is written from a United Kingdom perspective, but much of it is generalizable internationally. In a world where antimicrobial resistance is a major international threat, the use of rapid molecular diagnostics has great potential to improve both the management of pneumonia patients and the stewardship of antibiotics.

Presence of Type I-F CRISPR/Cas systems is associated with antimicrobial susceptibility in Escherichia coli.

Background: Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and their associated cas genes are sequence-specific DNA nuclease systems found in bacteria and archaea. CRISPR/Cas systems use RNA transcripts of previously acquired DNA (spacers) to target invading genetic elements with the same sequence, including plasmids. In this research we studied the relationship between CRISPR/Cas systems and multidrug resistance in Escherichia coli .

40 years of veterinary papers in JAC - what have we learnt?

This review, for the occasion of the 40th anniversary of the Journal of Antimicrobial Chemotherapy (JAC), gives an overview of the manuscripts related to veterinary bacteriology published in the journal in the past 40 years with a focus on 'One Health' aspects. From 1975 to 2000 the number of manuscripts related to veterinary medicine was limited, but thereafter, the number steadily increased. Most manuscripts published were related to food-producing animals, but companion animals and minor species were also covered.

Etiology, Antibiotic Resistance and Risk Factors for Neonatal Sepsis in a Large Referral Center in Zambia.

Background: In sub-Saharan Africa, there is scanty data on the causes of neonatal sepsis and antimicrobial resistance among common invasive pathogens that might guide policy and practice.

Methods: A cross-sectional observational prevalence and etiology study of neonates with suspected sepsis admitted to the neonatal intensive care unit, University Teaching Hospital, Lusaka, Zambia, between October 2013 and May 2014. Data from blood cultures and phenotypic antibiotic susceptibility testing were compared with multivariate analysis of risk factors for neonatal sepsis.

Comparison of Established Diagnostic Methodologies and a Novel Bacterial smpB Real-Time PCR Assay for Specific Detection of Haemophilus influenzae Isolates Associated with Respiratory Tract Infections.

Haemophilus influenzae is a significant causative agent of respiratory tract infections (RTI) worldwide. The development of a rapid H. influenzae diagnostic assay that would allow for the implementation of infection control measures and also improve antimicrobial stewardship for patients is required.

Rapid point of care diagnostic tests for viral and bacterial respiratory tract infections--needs, advances, and future prospects.

Respiratory tract infections rank second as causes of adult and paediatric morbidity and mortality worldwide. Respiratory tract infections are caused by many different bacteria (including mycobacteria) and viruses, and rapid detection of pathogens in individual cases is crucial in achieving the best clinical management, public health surveillance, and control outcomes. Further challenges in improving management outcomes for respiratory tract infections exist: rapid identification of drug resistant pathogens; more widespread surveillance of infections, locally and internationally; and global responses to infections with pandemic potential.

Rapid nucleic acid diagnostics for the detection of antimicrobial resistance in Gram-negative bacteria: is it time for a paradigm shift?

A key component for tackling the ever more serious antimicrobial resistance problem in Gram-negative bacteria is the introduction of rapid nucleic acid diagnostics. Successful incorporation of new diagnostic technologies has the potential benefit of improving not only patient treatment but also infection control and antimicrobial stewardship. However, there are still many hurdles to overcome, such as the complexity of resistance mechanisms in Gram-negative bacteria, the discrepancy between phenotype and genotype and the difficulty in distinguishing pathogens from background commensals.

Aetiology of hospital-acquired pneumonia and trends in antimicrobial resistance.

Purpose Of Review: Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) continue to present very significant diagnostic and management challenges. The development, introduction and use of a wider range of immunosuppressive therapies are leading to a broader spectrum of microorganisms causing HAP and VAP. The persistent clinical dilemma regarding their cause is that detection of a microorganism from a respiratory tract sample does not necessarily signify it is the causative agent of the pneumonia.

Fitness of Escherichia coli strains carrying expressed and partially silent IncN and IncP1 plasmids.

Background: Understanding the survival of resistance plasmids in the absence of selective pressure for the antibiotic resistance genes they carry is important for assessing the value of interventions to combat resistant bacteria. Here, several poorly explored questions regarding the fitness impact of IncP1 and IncN broad host range plasmids on their bacterial hosts are examined; namely, whether related plasmids have similar fitness impacts, whether this varies according to host genetic background, and what effect antimicrobial resistance gene silencing has on fitness.

Results: For the IncP1 group pairwise in vitro growth competition demonstrated that the fitness cost of plasmid RP1 depends on the host strain.

Persistence of a wild type Escherichia coli and its multiple antibiotic-resistant (MAR) derivatives in the abattoir and on chilled pig carcasses.

The aim of this study was to evaluate the ability of an Escherichia coli with the multiple antibiotic resistance (MAR) phenotype to withstand the stresses of slaughter compared to an isogenic progenitor strain. A wild type E. coli isolate (345-2RifC) of porcine origin was used to derive 3 isogenic MAR mutants.

Methods to determine antibiotic resistance gene silencing.

The occurrence of antibiotic-resistant bacteria is an increasingly serious problem world-wide. In addition, to phenotypically resistant bacteria, a threat may also be posed by isolates with silent, but intact, antibiotic resistance genes. Such isolates, which have recently been described, possess wild-type genes that are not expressed, but may convert to resistance by activating expression of the silent genes.

Reducing antimicrobial resistance in the community by restricting prescribing: can it be done?

The strategy of decreasing antimicrobial prescribing to reduce existing antimicrobial resistance appears attractive, but its effectiveness, particularly in the community setting, remains unclear. Contrasting results obtained from the relatively few studies in this area confuse matters further. Prescribing reductions have successfully reduced the prevalence of resistance among respiratory pathogens, but in these cases single bacterial clones dominated the resistant population.

Mechanochemical synthesis and in vitro anti-Helicobacter pylori and uresase inhibitory activities of novel zinc(II)-famotidine complex.

The mechanochemical synthesis and characterization of a zinc complex with famotidine is described. The complex was characterized by microanalysis and a number of spectroscopic techniques. The complex was of M:L dihydrate type.