A tolerability and patient acceptability pilot study of a novel antimicrobial urinary catheter for long-term use.

AIMS: We have developed a novel antimicrobial urinary catheter (AUC) impregnated with rifampicin, triclosan, and sparfloxacin and demonstrated that it has long-term (∼84 days) protection against bacterial colonization in vitro. This study aimed to assess the safety and patient acceptability of this device in long-term catheter users. METHODS: Adults who use long term (>28 days) indwelling urinary catheters with capacity to consent were invited to receive the AUC at their next catheter change. The primary outcome measure was adverse events (AE) attributable to antimicrobial impregnation of the catheter. Secondary outcome measures included severity of related AEs, patient acceptability, early removal of the trial catheter, and degree of microbial colonization of trial catheters. Except for the last, outcomes were assessed by telephone interviews. Original and trial catheters were collected, and the lumens and balloons were separated and analyzed for microbiological colonization. RESULTS: Thirty participants were recruited. Eighty four AEs were reported, and only one was rated as "probably" related to antimicrobial impregnation. The AE was mild and resolved within 48 h. A total of 82.14% of participants rated the catheter as no different or better than their usual catheter. Two participants chose to remove the AUC early due to it feeling shorter. There were significantly fewer bacterial isolates attached to the balloons of trial catheters compared to the matched original catheters. CONCLUSIONS: The AUC has an advantageous safety profile and was acceptable to the majority of participants. Information gained from this trial will support a larger randomized controlled study of efficacy.

Evaluation of combinations of putative anti-biofilm agents and antibiotics to eradicate biofilms of Staphylococcus aureus and Pseudomonas aeruginosa.

Objectives: To evaluate potential anti-biofilm agents for their ability to enhance the activity of antibiotics for local treatment of localized biofilm infections. Methods: Staphylococcus aureus and Pseudomonas aeruginosa in vitro biofilm models were developed. The putative antibiotic enhancers N-acetylcysteine, acetylsalicylic acid, sodium salicylate, recombinant human deoxyribonuclease I, dispersin B, hydrogen peroxide and Johnson's Baby Shampoo (JBS) were tested for their anti-biofilm activity alone and their ability to enhance the activity of antibiotics for 7 or 14 days, against 5 day old biofilms. The antibiotic enhancers were paired with rifampicin and clindamycin against S. aureus and gentamicin and ciprofloxacin against P. aeruginosa. Isolates from biofilms that were not eradicated were tested for antibiotic resistance. Results: Antibiotic levels 10× MIC and 100× MIC significantly reduced biofilm, but did not consistently eradicate it. Antibiotics at 100× MIC with 10% JBS for 14 days was the only treatment to eradicate both staphylococcal and pseudomonal biofilms. Recombinant human deoxyribonuclease I significantly reduced staphylococcal biofilm. Emergence of resistance of surviving isolates was minimal and was often associated with the small colony variant phenotype. Conclusions: JBS enhanced the activity of antibiotics and several other promising anti-biofilm agents were identified. Antibiotics with 10% JBS eradicated biofilms produced by both organisms. Such combinations might be useful in local treatment of localized biofilm infections.

EASL clinical practice guidelines: non-invasive liver tests for evaluation of liver disease severity and prognosis.

The European Association for the Study of the Liver has recently published updated guidelines on the use of non-invasive tests to identify and stratify chronic liver disease. Here, we provide a summary of the key recommendations from the guideline.

Acute otitis externa: Consensus definition, diagnostic criteria and core outcome set development.

OBJECTIVE: Evidence for the management of acute otitis externa (AOE) is limited, with unclear diagnostic criteria and variably reported outcome measures that may not reflect key stakeholder priorities. We aimed to develop 1) a definition, 2) diagnostic criteria and 3) a core outcome set (COS) for AOE. STUDY DESIGN: COS development according to Core Outcome Measures in Effectiveness Trials (COMET) methodology and parallel consensus selection of diagnostic criteria/definition. SETTING: Stakeholders from the United Kingdom. SUBJECTS AND METHODS: Comprehensive literature review identified candidate items for the COS, definition and diagnostic criteria. Nine individuals with past AOE generated further patient-centred candidate items. Candidate items were rated for importance by patient and professional (ENT doctors, general practitioners, microbiologists, nurses, audiologists) stakeholders in a three-round online Delphi exercise. Consensus items were grouped to form the COS, diagnostic criteria, and definition. RESULTS: Candidate COS items from patients (n = 28) and literature (n = 25) were deduplicated and amalgamated to a final candidate list (n = 46). Patients emphasised quality-of-life and the impact on daily activities/work. Via the Delphi process, stakeholders agreed on 31 candidate items. The final COS covered six outcomes: pain; disease severity; impact on quality-of-life and daily activities; patient satisfaction; treatment-related outcome; and microbiology. 14 candidate diagnostic criteria were identified, 8 reaching inclusion consensus. The final definition for AOE was 'diffuse inflammation of the ear canal skin of less than 6 weeks duration'. CONCLUSION: The development and adoption of a consensus definition, diagnostic criteria and a COS will help to standardise future research in AOE, facilitating meta-analysis. Consulting former patients throughout development highlighted deficiencies in the outcomes adopted previously, in particular concerning the impact of AOE on daily life.

Micro-organisms attached to the lumens and balloons of indwelling urinary catheters and correlation with symptoms, antibiotic use and catheter specimen of urine results.

To determine micro-organisms attached to removed urethral catheters and relate this to patient-specific information. Indwelling urethral catheters were collected from patients at a UK teaching hospital. The balloon and lumen were sonicated, and micro-organisms were enumerated. Catheter specimen urine results were retrospectively reviewed. Escherichia coli and Enterococcus faecalis were the most common isolates from 61 catheters. 19.7% of patients received antibiotics and 25 % of those had a multi-drug-resistant (MDR) organism in the lumen. Only 2.04% of catheters from patients not receiving antibiotics had a MDR organism. All lumens were colonized irrespective of antibiotic use. Symptom presentation did not correlate with numbers of colonizing organisms or species. Despite heavy colonization, only 8/61 patients were symptomatic. Indwelling urinary catheters in place for ≥10 days were universally colonized and there was no correlation with symptom presentation. Symptom presentation remains the most important factor for defining catheter-associated urinary tract infection.

An antimicrobial impregnated urinary catheter that reduces mineral encrustation and prevents colonisation by multi-drug resistant organisms for up to 12 weeks.

Two major complications of indwelling urinary catheterisation include infection and mineral encrustation of the catheter. Our antimicrobial urinary catheter (AUC) impregnated with rifampicin, triclosan, and sparfloxacin has demonstrated long-term protective activity against major uropathogens. This study aimed to firstly assess the ability of the AUC to resist mineral encrustation in the presence and absence of bacteria. Secondly, it aimed to investigate the AUC's anti-biofilm activity against multi-drug resistant organisms. There was no difference in surface roughness between AUC and control segments. In a static and a perfusion model, phosphate deposition was significantly reduced on AUCs challenged with P. mirabilis. Furthermore, none of the AUCs blocked during the 28 day test period, unlike controls. The AUC prevented colonisation by methicillin-resistant Staphylococcus aureus, methicillin-resistant Staphylococcus epidermidis, extended-spectrum beta-lactamase producing E. coli, and carbapenemase-producing E. coli for 12 consecutive weekly challenges. All three drugs impregnated into the catheter continued to exert protective activity throughout 12 weeks of constant perfusion. The drugs appear to migrate into the crystalline biofilm to continually protect against bacteria not it direct contact with the catheter surface. In conclusion, the AUC reduces mineral encrustation and may increase time to blockage in the presence of P. mirabilis, and does not predispose to mineral deposition under other conditions. It also offers 12 weeks of protection against multi-drug resistant bacteria. STATEMENT OF SIGNIFICANCE: Infection and associated mineral encrustation of urinary catheters are two serious complications of indwelling urinary catheters. Others have attempted to address this through various technologies such as coatings, dips, and surface modifications to prevent infection and/or encrustation. However, all current 'anti-infective' urinary catheter technologies are limited to short-term use. Some patients with spinal injuries, multiple sclerosis, stroke survivors and others use long-term catheters for 4-12 weeks at a time with multiple catheterisation possibly throughout the rest of their life. We present a urinary catheter for long-term use that is impregnated with three antimicrobials by a patient-protected process to prevent infection and encrustation for up to 12 weeks, the maximum lifetime of a long-term catheter before it is changed.

Do orally administered antibiotics reach concentrations in the middle ear sufficient to eradicate planktonic and biofilm bacteria? A review.

INTRODUCTION: Infectious conditions of the middle ear are a common and significant cause of morbidity and mortality worldwide. Systemic antibiotics are frequently used, but their effectiveness will depend on whether an adequate antibiotic concentration is achieved in the middle ear; this is especially important in biofilm infections such as otitis media with effusion (OME), where high antibiotic concentrations are typically required for effective treatment. OBJECTIVE: This review examines what antibiotic levels can be reached in the middle ear with oral administration, as a means of guiding rational antibiotic choice in the clinic and future research, and to determine whether levels high enough for biofilm eradication are reached. METHODS: A literature search of studies measuring levels of antibiotics in the plasma and in the middle ear after oral administration was conducted. These levels were compared to the minimum inhibitory concentrations (MIC) provided by the European Committee for Antimicrobial Susceptibility Testing (EUCAST) to determine if antibiotic doses were reaching sufficient levels to inhibit planktonic bacteria. The middle ear concentrations were then calculated as a multiple of the MIC to determine if the concentrations were reaching biofilm eradication concentrations (typically up to 1000×MIC). RESULTS: The highest antibiotic levels against Staphylococcus aureus reach 8.3×MIC, against Moraxella catarrhalis 33.2×MIC, against Haemophilus influenzae 31.2×MIC, and against Streptococcus pneumoniae 46.2×MIC. The macrolide antibiotics reach higher levels in the middle ear than in plasma. CONCLUSIONS: Orally administered antibiotics reach levels above the MIC in the middle ear. However, they do not reach levels that would be likely to eradicate biofilms.

Update on otitis media - prevention and treatment.

Acute otitis media and otitis media with effusion are common childhood disorders, a source of significant morbidity, and a leading cause of antibiotic prescription in primary health care. Although effective treatments are available, some shortcomings remain, and thus better treatments would be welcome. Recent discoveries within the field of otitis media research relating to its etiology and pathogenesis have led to further investigation aimed at developing novel treatments. This article provides a review of the latest evidence relating to the understanding of acute otitis media and otitis media with effusion, current treatment strategies, their limitations, new areas of research, and novel strategies for treatment.

Acute airway obstruction by Ascaris lumbricoides in a 14-month-old boy.

We describe the case of a 14-month-old child with airway obstruction caused by a mature Ascaris lumbricoides worm. The child had been admitted to the paediatric intensive care unit due to overwhelming sepsis, and during the course of his illness developed acute airway obstruction that resolved once the worm was removed from the airway. The Ascaris life-cycle is detailed, and a literature review of patients with airway obstruction due to Ascaris worms is presented.

Expanding the diversity of mycobacteriophages: insights into genome architecture and evolution.

Mycobacteriophages are viruses that infect mycobacterial hosts such as Mycobacterium smegmatis and Mycobacterium tuberculosis. All mycobacteriophages characterized to date are dsDNA tailed phages, and have either siphoviral or myoviral morphotypes. However, their genetic diversity is considerable, and although sixty-two genomes have been sequenced and comparatively analyzed, these likely represent only a small portion of the diversity of the mycobacteriophage population at large. Here we report the isolation, sequencing and comparative genomic analysis of 18 new mycobacteriophages isolated from geographically distinct locations within the United States. Although no clear correlation between location and genome type can be discerned, these genomes expand our knowledge of mycobacteriophage diversity and enhance our understanding of the roles of mobile elements in viral evolution. Expansion of the number of mycobacteriophages grouped within Cluster A provides insights into the basis of immune specificity in these temperate phages, and we also describe a novel example of apparent immunity theft. The isolation and genomic analysis of bacteriophages by freshman college students provides an example of an authentic research experience for novice scientists.