Rethinking Clostridioides difficile infection (CDI) surveillance definitions based on changing healthcare utilisation and a more realistic incubation period: reviewing data from a tertiary-referral hospital, Ireland, 2012 to 2021.

BackgroundCommunity-associated Clostridioides difficile infections (CA-CDI) have increased worldwide. Patients with CDI-related symptoms occurring < 48 hours after hospitalisation and no inpatient stay 12 weeks prior are classified as CA-CDI, regardless of hospital day attendances 3 months before CDI onset. Healthcare-associated (HA) CDIs include those with symptom onset ≥ 48 hours post hospitalisation.AimTo consider an incubation period more reflective of CDI, and changing healthcare utilisation, we measured how varying surveillance specifications to categorise patients according to their CDI origin resulted in changes in patients' distribution among CDI origin categories.MethodsNew CDI cases between 2012-2021 from our hospital were reviewed. For patients with CA-CDI, hospital day attendances in the 3 months prior were recorded. CA-CDI patients with hospital day attendances and recently discharged CDI patients (RD-CDI; CDI onset 4-12 weeks after discharge) were combined into a new 'healthcare-exposure' category (HE-CDI). Time from hospitalisation to disease onset was varied and the midpoint between optimal and balanced cut-offs was used instead of 48 hours to categorise HA-CDI.ResultsOf 1,047 patients, 801 (76%) were HA-CDI, 205 (20%) CA-CDI and 41 (4%) were RD-CDI. Of the CA-CDI cohort, 45 (22%) met recent HE-CDI criteria and, when reassigned, reduced CA-CDI to 15%. Sensitivity analysis indicated a day 4 cut-off for assigning HA-CDI. Applying this led to 46 HA-CDI reassigned as CA-CDI. Applying both HE and day 4 criteria led to 72% HA-CDI, 20% CA-CDI, and 8% HE-CDI (previously RD-CDI).ConclusionCDI surveillance specifications reflecting healthcare exposure and an incubation period more characteristic of C. difficile may improve targeted CDI prevention interventions.

Invasive pneumococcal surveillance to assess the potential benefits of extended spectrum conjugate vaccines (PCV15/PCV20) in older adults.

The introduction of pneumococcal conjugate vaccines (PCV) into the childhood vaccination programme has reduced invasive pneumococcal disease (IPD). Although anticipated from data elsewhere, surveillance in Ireland has confirmed reductions in IPD amongst those ⩾65 years of age due to a decline of PCV serotypes in this age group. Currently, direct protection against IPD in the elderly is focused on immunisation with the 23-valent pneumococcal polysaccharide vaccine (PPV23). However, immunity may not be as effective as with PCV and, furthermore, PPV23 uptake is poor in Ireland. Hence, consideration should be given to providing a PCV to this age group.

In situ generation of cold atmospheric plasma-activated mist and its biocidal activity against surrogate viruses for COVID-19.

AIMS: To provide an alternative to ultra violet light and vapourized hydrogen peroxide to enhance decontamination of surfaces as part of the response to the COVID-19 pandemic. METHODS AND RESULTS: We developed an indirect method for in situ delivery of cold plasma and evaluated the anti-viral activity of plasma-activated mist (PAM) using bacteriophages phi6, MS2, and phiX174, surrogates for SARS-CoV-2. Exposure to ambient air atmospheric pressure derived PAM caused a 1.71 log10 PFU ml-1 reduction in phi6 titer within 5 min and a 7.4 log10 PFU ml-1 reduction after 10 min when the the PAM source was at 5 and 10 cm. With MS2 and phiX174, a 3.1 and 1.26 log10 PFU ml-1 reduction was achieved, respectively, after 30 min. The rate of killing was increased with longer exposure times but decreased when the PAM source was further away. Trace amounts of reactive species, hydrogen peroxide and nitrite were produced in the PAM, and the anti-viral activity was probably attributable to these and their secondary reactive species. CONCLUSIONS: PAM exhibits virucidal activity against surrogate viruses for COVID-19, which is time and distance from the plasma source dependent.

Clostridioides difficile infection in neurosurgical patients in a national centre over 10 years: less common but associated with longer hospital stays.

BACKGROUND: Clostridioides difficile infection (CDI) is a leading cause of healthcare-associated (HA) diarrhoea, contributing to patient morbidity and prolonged length-of-stay (LOS). We retrospectively assessed CDI over a decade in a national neurosurgical centre, with a multi-disciplinary approach to CDI surveillance and antimicrobial stewardship, by comparing CDI patients with other patient groups. METHODS: Data on CDI in neurosurgical inpatients between January 2012 and December 2021 were collated. Disease-specific variables were compared to other inpatients with CDI. Rates per 10,000 bed days used were calculated. Patient-specific differences were compared with neurosurgical patients without CDI. CDI rates by patient group were explored using odds ratio (OR) and χ2 analyses. Negative binomial regression was used to investigate CDI rates over time. RESULTS: Of 50 neurosurgical patients with CDI, all were HA; the average age was 53 years (standard deviation (SD) 16.3 years), 49 were first-episode CDI, and three had severe CDI. The majority (76.7%) had received recent antimicrobials. Compared with non-neurosurgical CDI patients, neurosurgical CDI rates differed significantly (1.9 versus 3.6 per 10,000 bed days used, p < 0.05), neurosurgical patients were younger (p ≤ 0.01), C. difficile testing was more likely to be requested by neurosurgeons (OR 2.4; p ≤ 0.01), and the proportion of severe CDI was higher (6% versus 2%, OR 3.0, p = 0.07, confidence interval (CI) 0.54 to 11.3). Within the neurosurgical cohort, CDI patients had an average LOS four times that of other patients (CI 15.2 to 35.1; p < 0.01) and were older (53.5 versus 47.8 years, CI 0.1 to 11 years; p < 0.05). Only one CDI outbreak was linked to neurosurgical patients. CONCLUSION: CDI in neurosurgery patients differed from the wider hospital, with greater awareness of CDI testing. Longer LOS impacted bed utilisation with limited capacity. Robust surveillance supports proactive antimicrobial stewardship programmes in this vulnerable population.

Candida meningitis/ventriculitis over a decade. Increased morbidity and length of stay a concern.

AIM: The primary aim of this study was to review the diagnosis, management and outcome of Candida meningitis/ventriculitis in our hospital over a ten-year period. MATERIALS AND METHODS: We retrospectively reviewed all culture and 18s rRNA nucleic acid positive CSF specimens processed between 1st January 2010 and 31st December 2020. Patient records were subsequently reviewed to assess the significance of the isolate. RESULTS: Of 851 culture-positive cerebrospinal fluid (CSF) specimens, Candida spp. were isolated from 29 (3.4%), representing infection in 12 patients. One culture-negative specimen was positive for Candida on 18s rRNA testing. Of the 13 patients, eight were male; 61.5% and the median age was 47 years; range: 20-70. The median interval from admission to onset of infection and culture positivity was 24 days (range: 1-63 days). All patients had a central nervous system (CNS) device in situ (external ventricular drain: 11; ventriculoperitoneal shunt: 1; lumbar drain: 1). Four were colonised with Candida spp. before meningitis/ventriculitis diagnosis, from wounds (n = 3), respiratory (n = 3), and urine (n = 1) specimens. On culture, the most common species was Candida albicans (n = 8), followed by C. parapsilosis (n = 2), C. tropicalis (n = 1), and C. dubliniensis (n = 1). The median number of follow-up CSFs per patient was nine (range; 3-22), with a median of 6 days to CSF sterility (range 3-10 days). Treatment included; liposomal amphotericin B (n = 5), fluconazole (n = 2), liposomal amphotericin B, and flucytosine (n = 2), liposomal amphotericin B, fluconazole and flucytosine (n = 3), and intra-ventricular amphotericin B (n = 1). Median treatment duration was 25 days (range 11-76) and CNS device removal occurred in 12 patients. The median length-of-stay (LOS) was 58 days (range 24-406). On discharge, moderate to severe disability (Modified Rankin Scale [mRS] 3-5) was evident in eight patients. Two patients died and one was lost to follow-up. CONCLUSION: Meningitis/ventriculitis due to Candida spp. is an uncommon but challenging infection, usually associated with a device, increased morbidity, LOS, and necessitating prolonged treatment. Neurosurgeons need to be aware of these issues in managing and in communicating with such complex patients.

A Randomized Clinical Trial Evaluating the Efficacy and Quality of Life of Antibiotic-only Treatment of Acute Uncomplicated Appendicitis: Results of the COMMA Trial.

OBJECTIVE: Evaluate the efficacy and quality of life associated with conservative treatment of acute uncomplicated appendicitis. SUMMARY BACKGROUND DATA: Conservative management with antibiotics only has emerged as a potential treatment option for acute uncomplicated appendicitis. However the reported failure rates are highly variable and there is a paucity of data in relation to quality of life. METHODS: Symptomatic patients with radiological evidence of acute, uncomplicated appendicitis were randomized to either intravenous antibiotics only or undergo appendectomy. RESULTS: One hundred eighty-six patients underwent randomization. In the antibiotic-only group, 23 patients (25.3%) experienced a recurrence within 1 year following randomization. There was a significantly better EQ-VAS quality of life score in the surgery group compared with the antibiotic-only group at 3 months (94.3 vs 91.0, P < 0.001) and 12 months postintervention (94.5 vs 90.4, P < 0.001). The EQ-5D-3L quality-of-life score was significantly higher in the surgery group indicating a better quality of life (0.976 vs 0.888, P < 0.001). The accumulated 12-month sickness days was 3.6 days shorter for the antibiotics only group (5.3 vs 8.9 days; P < 0.01). The mean length of stay in both groups was not significantly different (2.3 vs 2.8 days, P = 0.13). The mean total cost in the surgery group was significantly higher than antibiotics only group (€4,816 vs €3,077, P < 0.001). CONCLUSIONS: Patients with acute, uncomplicated appendicitis treated with antibiotics only experience high recurrence rates and an inferior quality of life. Surgery should remain the mainstay of treatment for this commonly encountered acute surgical condition.

Out-of-hours calls in clinical microbiology: the when, the why and from whom.

Microbiology services provided to hospitals must be delivered 24 h a day. In addition to during routine so-called 'office hours', clinical microbiologists have to provide an on-call service 7 days a week. However, there are few data on what that involves and how the service is delivered. I reviewed the source, reason for, grade of staff from whom the call came and the need for any follow-up, over an 11-year period using a pro-forma, that had been used to review data before this time period. Details were available for 90% of calls received, and data from 809 calls were analysed. The sources of calls were most commonly from medicine specialties [163/809 (20.1%)], neurosurgery (which is a national referral centre) [148/809 (18.3%)] and the intensive care unit [143/809 (17.7%)]. The number of calls received between 23.00 hours and 07.00 hours was 107 (13.2%). Just over half of calls, i.e. 440/809 (54.6%), were related to treatment; 247/809 (30.5%) were for advice on diagnosis; and 79/809 (9.8%) were related to infection prevention and control (IPC) issues. Registrars (a senior training grade) accounted for 492/809 (60.8%) of calls, and 64/809 (7.9%) came from nurses mainly related to IPC matters. Overall, 25.4% (206/809) of calls required follow-up the next day but this increased from 4.5% in 2013 to 67.6% in 2018. The nature of calls received by a clinical microbiologist out-of-hours is varied and may be increasing due to the complexity of case mix and changes in medical staffing. Professional and other organisations would do well to review such workload when deciding on staffing levels and service planning, given increasing public and patient expectations, and the trend towards the centralisation/consolidation of laboratory diagnostic services.

Surveillance of common infections in the early period after renal transplantation in a national center: 2014-2017.

BACKGROUND: Infection prevention and timely and effective treatment are among the major aims of care in kidney transplant recipients. Pre-transplant vaccination and pre-transplant viral screening have been extensively studied and are now considered standard practice. Early post-operative infection surveillance is mandatory in other vulnerable cohorts, but has not been extensively studied in this population. We hypothesized that surveillance of the most common bacterial infection types in the post-transplant setting would be beneficial and identify key areas for improvement. METHODS: All adult kidney transplant recipients whose surgeries were performed in the Irish national kidney transplant unit over a 1-year period had prospective early post-transplant (first 30 days) infection surveillance in 2014 for surgical site infection, urinary tract infection, and secondary bloodstream infections (Group T0). Several key changes were implemented following scrutiny of infection patterns and clinical practice. Subsequently, infection surveillance was undertaken for 2016 and 2017 (Group T1) to assess the impact of these changes. RESULTS: Between 2014 and 2017, the number of kidney transplants increased by 32%. The following aspects of clinical practice were the focus of change following analysis of Group T0 data: timing of surgical antimicrobial prophylaxis (SAP) administration, choice of SAP antimicrobial agent, and routine microbiological testing in the peri-operative period. Following implementation of these changes, the timing of SAP administration was greatly improved (45%-100% of cases appropriately timed). The infection rate decreased from 8.9% to 7.4% in 2016, with a further decrease to 4% in 2017 (OR 0.42 (95% CI: 0.16-1.10); P = .08). Compliance with pre-operative microbiological screening improved in Group T1. CONCLUSIONS: Simple clinical practice changes, implemented upon analysis of common bacterial infection surveillance data in the first 30 days after kidney transplantation resulted in more effective SAP administration and improved compliance with routine microbiological testing in the peri-operative period. These interventions have potentially contributed to reduced early post-operative infection rates, despite increased transplant activity in the unit. Infection surveillance is an important and under-utilized way of reducing infections in this vulnerable patient cohort.

Alpha-1 Antitrypsin-A Target for MicroRNA-Based Therapeutic Development for Cystic Fibrosis.

Cystic fibrosis (CF) is an autosomal recessive genetic disorder arising from mutations to the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Disruption to normal ion homeostasis in the airway results in impaired mucociliary clearance, leaving the lung more vulnerable to recurrent and chronic bacterial infections. The CF lung endures an excess of neutrophilic inflammation, and whilst neutrophil serine proteases are a crucial part of the innate host defence to infection, a surplus of neutrophil elastase (NE) is understood to create a net destructive effect. Alpha-1 antitrypsin (A1AT) is a key antiprotease in the control of NE protease activity but is ineffective in the CF lung due to the huge imbalance of NE levels. Therapeutic strategies to boost levels of protective antiproteases such as A1AT in the lung remain an attractive research strategy to limit the damage from excess protease activity. microRNAs are small non-coding RNA molecules that bind specific cognate sequences to inhibit expression of target mRNAs. The inhibition of miRNAs which target the SERPINA1 (A1AT-encoding gene) mRNA represents a novel therapeutic approach for CF inflammation. This could involve the delivery of antagomirs that bind and sequester the target miRNA, or target site blockers that bind miRNA recognition elements within the target mRNA to prevent miRNA interaction. Therefore, miRNA targeted therapies offer an alternative strategy to drive endogenous A1AT production and thus supplement the antiprotease shield of the CF lung.

Would hemodialysis patients benefit from a Staphylococcus aureus vaccine?

Staphylococcus aureus bloodstream infection can have potentially catastrophic consequences for patients on hemodialysis. Consequently, an effective vaccine to prevent S aureus infection would have a significant influence on morbidity and mortality in this group. To date, however, efforts to develop a vaccine have been unsuccessful. Previous antibody-inducing vaccine candidates did not prevent or attenuate S aureus infection in clinical trials. Recent advances have helped to elucidate the role of specific T-cell subsets, notably T-helper cell 1 and T-helper cell 17, in the immune response to S aureus. These cells are essential for coordinating an effective phagocytic response via cytokine production, indirectly leading to destruction of the organism. It is now widely accepted that next-generation S aureus vaccines must also induce effective T-cell-mediated immunity. However, there remains a gap in our knowledge: how will an S aureus vaccine drive these responses in those patients most at risk? Given that patients on hemodialysis are an immunocompromised population, in particular with specific T-cell defects, including defects in T-helper cell subsets, this is likely to affect their ability to respond to an S aureus vaccine. We urgently need a better understanding of T-cell-mediated immunity in this cohort if an efficacious vaccine is ever to be realized for these patients.

Can e-learning improve the performance of undergraduate medical students in Clinical Microbiology examinations?

BACKGROUND: Clinical Microbiology is a core subject in medical undergraduate curricula. However, students struggle to cover the content and clinically contextualise basic microbiology. Our aim was to evaluate student engagement with new e-learning material and to investigate the impact it had on examination performance in a Clinical Microbiology module. METHODS: An online resource was designed to support didactic teaching in a Fundamentals of Clinical Microbiology module. One cohort of students had access to the online material (2017/2018 class) and the other did not (2016/2017 class). Each cohort sat the same multiple-choice question (MCQ) and short-note question (SNQ) examination papers and the impact of engagement with the online resource and examination performance was analysed. RESULTS: Both groups were of the same academic standard prior to beginning the module. In the 2017/2018 cohort, 227/309 (73.5%) students had ≥80% engagement with the content. Students engaged most with the index of pathogens and pathogen focused clinical cases related to diverse genera and families of clinically important microorganisms. A statistically higher difference in the mean percentage grade in both the MCQ and SNQ examinations was seen for 2017/2018 compared to 2016/2017 cohort. For the MCQ examination, the 2017/2018 cohort were on average 5.57% (95% confidence interval (CI): 3.92 to 7.24%; P < 0.001) higher, and for the SNQ examination the 2017/2018 cohort were on average 2.08% (95% CI: 0.74 to 3.41%; P = 0.02) higher. When the results were adjusted for previous examination performance, for every percentage increase in online engagement the grade in the SNQ examination only increased by 0.05% (95% CI: 0.02 to 0.08) on average. CONCLUSIONS: These findings suggest students engage with e-learning when studying and that such activities may help students perform better in assessments.

Molecular Characterization of Nasal Methicillin-Resistant Staphylococcus aureus Isolates Showing Increasing Prevalence of Mupirocin Resistance and Associated Multidrug Resistance following Attempted Decolonization.

Sequential methicillin-resistant Staphylococcus aureus (MRSA) isolates from patients following attempted mupirocin nasal decolonization showed an increase in mupirocin resistance (MR) from 6.6% to 20%. MR isolates from patients who failed decolonization yielded indistinguishable spa types and carried multiple antimicrobial and antiseptic resistance genes, which may guide infection control and prevention.

A survey of practice and opinions on the use of topical antibiotics to prevent surgical site infection: more confusion than consensus.

Background: Surgical site infection (SSI) is one of the most common causes of healthcare-associated infection. Although the use of topical antibiotics to prevent SSI is not recommended by current guidelines, published studies document conflicting results and conclusions. Objectives: The objectives of this survey were to: (i) determine the extent of the use of topical antibiotics to prevent SSI in clinical practice; and (ii) gather the opinions of healthcare professionals most likely to be involved in their use. Methods: A questionnaire was circulated to members of BSAC and the European Wound Management Association (EWMA). Results: The questionnaire received 160 responses from a variety of healthcare professionals around the world. Most respondents (70%) did not have guidelines for the use of topical antibiotics for the prevention of SSI in their institution; if present, local guidance was based on national guidelines (20/31, 65%). Most respondents did not use or recommend topical antibiotics to prevent SSI; of those that did, gentamicin collagen sponges were most commonly used (24/96 responses, 25%). Over half of the surgeons (18/33, 55%) who responded to the survey did not use topical antibiotics for the prevention of SSI but, when used, contaminated surgery (8/33, 24%) was the most commonly stated indication. Conclusions: There are diverse opinions and practices among healthcare professionals about the use of topical antibiotics for the prevention of SSI. This considerable, and possibly inappropriate, variation in clinical practice needs to be addressed as part of antibiotic stewardship.

Eradication of Staphylococcus aureus Biofilm Infections Using Synthetic Antimicrobial Peptides.

Here, we demonstrate that antimicrobial peptides (AMPs) are an effective antibiofilm treatment when applied as catheter lock solutions (CLSs) against S. aureus biofilm infections. The activity of synthetic AMPs (Bac8c, HB43, P18, Omiganan, WMR, Ranalexin, and Polyphemusin) was measured against early and mature biofilms produced by methicillin-resistant S. aureus and methicillin-susceptible S. aureus isolates from patients with device-related infections grown under in vivo-relevant biofilm conditions. The cytotoxic and hemolytic activities of the AMPs against human cells and their immunomodulatory potential in human blood were also characterized. The D-Bac8c2,5Leu variant emerged as the most effective AMP during in vitro studies and was also highly effective in eradicating S. aureus biofilm infection when used in a CLS rat central venous catheter infection model. These data support the potential use of D-Bac8c2,5Leu, alone or in combination with other AMPs, in the treatment of S. aureus intravenous catheter infections.

Memory Th1 Cells Are Protective in Invasive Staphylococcus aureus Infection.

Mechanisms of protective immunity to Staphylococcus aureus infection in humans remain elusive. While the importance of cellular immunity has been shown in mice, T cell responses in humans have not been characterised. Using a murine model of recurrent S. aureus peritonitis, we demonstrated that prior exposure to S. aureus enhanced IFNγ responses upon subsequent infection, while adoptive transfer of S. aureus antigen-specific Th1 cells was protective in naïve mice. Translating these findings, we found that S. aureus antigen-specific Th1 cells were also significantly expanded during human S. aureus bloodstream infection (BSI). These Th1 cells were CD45RO+, indicative of a memory phenotype. Thus, exposure to S. aureus induces memory Th1 cells in mice and humans, identifying Th1 cells as potential S. aureus vaccine targets. Consequently, we developed a model vaccine comprising staphylococcal clumping factor A, which we demonstrate to be an effective human T cell antigen, combined with the Th1-driving adjuvant CpG. This novel Th1-inducing vaccine conferred significant protection during S. aureus infection in mice. This study notably advances our understanding of S. aureus cellular immunity, and demonstrates for the first time that a correlate of S. aureus protective immunity identified in mice may be relevant in humans.

Ralstonia species - do these bacteria matter in cystic fibrosis?

Ralstonia species, often regarded as an environmental organism of low pathogenicity, can cause significant disease in certain at-risk patient groups, including those with cystic fibrosis. Difficulties with its identification in the clinical laboratory mean that it may be misidentified and therefore under recognised as a cause of disease. A number of outbreaks have been associated with the use of devices for inhaled respiratory therapy, putting those with chronic respiratory conditions at risk. Antimicrobial treatment of infection is challenging and limited due to frequent antimicrobial resistance. This review highlights issues regarding the identification, treatment and prevention of infection due to Ralstonia spp. in children with cystic fibrosis.

A comparative study: do "clickers" increase student engagement in multidisciplinary clinical microbiology teaching?

BACKGROUND: Audience response devices, or "clickers", have been used in the education of future healthcare professionals for several years with varying success. They have been reported to improve the learning experience by promoting engagement and knowledge retention. In 2014, our department evaluated the use of "clickers" in a newly introduced multidisciplinary approach to teaching large groups of third year medical students clinical cases developed around a microbiology theme. METHODS: Six multidisciplinary teaching sessions covering community-acquired pneumonia, tuberculosis, infective endocarditis, peritonitis, bloodstream infection with pyelonephritis and bacterial meningitis were included in the study. Three involved the use of the "clickers" and three did not. Consenting undergraduate students attended the designated classes and afterwards answered a short online quiz relating to the session. Students also answered a short questionnaire about the "clickers" to gauge their attitudes on the use of these devices. RESULTS: Of 310 students, 294 (94.8%) agreed to participate in the study. Interestingly, the grades of online quizzes after a session where a "clicker" was used were slightly lower. Looking only at the grades of students who engaged completely with the process (n = 19), there was no statistical difference to suggest that the devices had a positive or negative impact on knowledge retention. However, student attitudes to using the devices were positive overall. Fifty-five percent strongly agreed and 27% agreed that teaching sessions where the "clickers" were used were more engaging. Thirty-four percent strongly agreed and 36% agreed that the "clickers" made important concepts more memorable and 54% felt the device enhanced their understanding of the topic being covered. CONCLUSIONS: Overall, it appears that "clickers" help in improving student engagement in large classroom environments, enhance the learning experience, and are received positively by medical students but their impact on knowledge retention is variable.