A practical approach to screening for carbapenemase-producing Enterobacterales- views of a group of multidisciplinary experts from English hospitals.

INTRODUCTION: Carbapenemase-producing Enterobacterales (CPE) are an important public health threat, with costly operational and economic consequences for NHS Integrated Care Systems and NHS Trusts. UK Health Security Agency guidelines recommend that Trusts use locally developed risk assessments to accurately identify high-risk individuals for screening, and implement the most appropriate method of testing, but this presents many challenges. METHODS: A convenience sample of cross-specialty experts from across England met to discuss the barriers and practical solutions to implementing UK Health Security Agency framework into operational and clinical workflows. The group derived responses to six key questions that are frequently asked about screening for CPE. KEY FINDINGS: Four patient groups were identified for CPE screening: high-risk unplanned admissions, high-risk elective admissions, patients in high-risk units, and known positive contacts. Rapid molecular testing is a preferred screening method for some of these settings, offering faster turnaround times and more accurate results than culture-based testing. It is important to stimulate action now, as several lessons can be learnt from screening during the COVID-19 pandemic, as well as from CPE outbreaks. CONCLUSION: Further decisive and instructive information is needed to establish CPE screening protocols based on local epidemiology and risk factors. Local management should continually evaluate local epidemiology, analysing data and undertaking frequent prevalence studies to understand risks, and prepare resources- such as upscaled screening- to prevent increasing prevalence, clusters or outbreaks. Rapid molecular-based methods will be a crucial part of these considerations, as they can reduce unnecessary isolation and opportunity costs.

Introduction of an antifungal stewardship programme targeting high-cost antifungals at a tertiary hospital in Cambridge, England.

BACKGROUND: Antifungal stewardship aims to promote the optimal use of antifungals through the careful selection of agents based on patient profile, target organism, toxicity, costs and the likelihood of emergence and spread of resistance. METHODS: We report on an observational prospective 12 month study conducted by an antifungal stewardship team targeting the use of echinocandins (caspofungin and micafungin), voriconazole and liposomal amphotericin B in a tertiary referral hospital in the UK. RESULTS: One-hundred-and-seventy-three patients were reviewed on 294 occasions. Clinical advice was given and implemented during review of 45 (88.2%) of micafungin prescriptions, 70 (78.7%) of those receiving voriconazole, 78 (62.4%) of those receiving liposomal amphotericin B and 3 (27.3%) of those receiving caspofungin. Except for voriconazole, nearly half of all treatments reviewed were stopped or changed. This study found that a crude cost saving of ∼£180 000 in antifungal drugs was generated compared with the previous year. CONCLUSIONS: Using a multidisciplinary team, antifungal stewardship can achieve significant improvements in patient management and it may reduce costs.

Antibiotic resistance: what, why, where, when and how?

BACKGROUND: Antibiotic resistance is a threat to the effective prevention and treatment of an ever-increasing range of infections caused by bacteria, parasites, viruses and fungi. SOURCES OF DATA: Peer-reviewed journal articles, governmental and professional society publications. AREAS OF AGREEMENT AND CONTROVERSY: There is consensus about the development and spread of antibiotic resistance, the reasons for the development of antibiotic resistance and the clinical impact. There is more debate about the most appropriate way of tackling this increasing problem. GROWING POINTS: This review discusses a number of initiatives (local and global) that are being undertaken to protect the antibiotics we currently have available for use and to encourage the development of newer agents.

Co-infection as a confounder for the role of Clostridium difficile infection in children with diarrhoea: a summary of the literature.

Although Clostridium difficile is a major cause of antibiotic-associated diarrhoea in adults, the incidence and severity of C. difficile infection (CDI) in children is unclear. One complicating factor in assessing the role of CDI in children is the possibility of co-infection with other gastrointestinal pathogens. In this review, we summarise the literature concerning C. difficile co-infections in young children, in an attempt to discuss the rate of co-infections and their potential role in the severity of CDI clinical presentation. We identified 31 studies where co-infections were analysed, comprising 1,718 patients with positive C. difficile tests. The pooled percentage of reported co-infections was 20.7% (range 0-100%). Viral co-infections were most commonly reported (46%), with bacteria and parasites accounting for 14.9% and 0.01% of cases, respectively. However, the panel of co-infections tested for varied considerably among studies and 38% of stated co-infections did not have a pathogen reported. Substantial variation in how and when tests for gastrointestinal co-infections are carried out, small sample sizes and a lack of clear CDI case definitions preclude meaningful conclusions on the true rate of co-infections in this patient population. This review suggests that co-infections may be common in children with diarrhoea who tested positive for C. difficile. Given a lack of CDI case definitions, especially in young children under the age of 5 years, a broad panel of pathogens should be tested for to exclude other microbiological causes. However, the summarised poor quality of the available literature on this subject highlights a need for further studies.

The role of hospital antimicrobial and infectious diseases pharmacists in the UK: a theoretically underpinned exploration.

Objectives: We sought to characterise the role of hospital infection pharmacists in the UK and to understand the core challenges being faced, future role development desires and the required support to address these. Methods: We developed a questionnaire underpinned by the theoretical domains framework exploring the barriers and enablers to pharmacists fulfilling their perceived roles and responsibilities. Any pharmacist whose role included 'specialist antimicrobial' or 'infectious diseases' was invited to complete a questionnaire sent via national infection and pharmacy groups/networks. Descriptive statistics were used to report responses to each item, and a content analysis was undertaken to summarize the key messages from an extended response option. Results: Of the 102 respondents, 91 (89.2%) were from English hospitals. Fifty-three (52%) were from district general hospitals and 45 (45.1%) from teaching hospitals. Most (97, 95%) respondents were of a senior grade. The need for a comprehensive educational programme, recognition of research as core to the role and integration with infection/microbiology departments were key requirements along with protected time to engage with the activities. Highlights of the role were opportunities to teach, making a significant contribution to patient care and scope to contribute to strategy and vision. The COVID-19 pandemic negatively impacted on respondents' capacity to undertake their perceived roles and responsibilities. Conclusions: Our study delineates the need for UK infection and pharmacy policy makers to review hospital infection pharmacist developmental pathways and roles. Joint learning, and closer working, with infection/microbiology departments may be an efficient strategy to address the issues raised.

Risk of complications and mortality following recurrent and non-recurrent Clostridioides difficile infection: a retrospective observational database study in England.

BACKGROUND: Clostridioides difficile infection (CDI) increases the risk of complications and mortality. We assessed the magnitude of these outcomes in a large cohort of English patients with initial and recurrent CDI. AIM: To compare the risk of complications and all-cause mortality, within 12 months, among hospitalized patients ≥18 years old with hospital-associated- (HA-) CDI and recurrent CDI. METHODS: Patients with HA-CDI during 2002-2013 were identified using inpatient hospital data linked to primary care and death data. Each HA-CDI case was frequency matched to two hospitalized patients without CDI on age group, sex, calendar year of admission, admission method and number of hospital care episodes. A second CDI episode starting on days 13-56 was defined as recurrence. Risks of mortality and complications at 12 months were analysed using Cox proportional hazard models. FINDINGS: We included 6862 patients with HA-CDI and 13,724 without CDI. Median age was 81.0 years (IQR 71.0-87.0). Patients with HA-CDI had more comorbidities than those without CDI, and significantly higher risks of mortality (adjusted hazard ratio (95% confidence interval) 1.77 (1.67-1.87)) and complications (1.66 (1.46-1.88)) within 12 months from hospital admission. Of those with HA-CDI, 1140 (16.6%) experienced CDI recurrence. Patients with recurrent versus non-recurrent CDI also had significantly increased risk of mortality (1.32 (1.20-1.45)) and complications (1.37 (1.01-1.84)) in the 12 months from the initial CDI. CONCLUSIONS: HA-CDI (versus no CDI) and recurrent CDI are both associated with significantly higher risks of complications or death within 12 months of the initial CDI episode.

An outbreak of meticillin-resistant Staphylococcus aureus colonization in a neonatal intensive care unit: use of a case-control study to investigate and control it and lessons learnt.

AIM: To describe the investigation and management of a meticillin-resistant Staphylococcus aureus (MRSA) outbreak on a neonatal intensive care unit (NICU) and the lessons learnt. METHODS: This was an outbreak report and case-control study conducted in a 40-cot NICU in a tertiary referral hospital and included all infants colonized/infected with gentamicin-resistant MRSA. INTERVENTION: Standard infection-control measures including segregation of infants, barrier precautions, enhanced cleaning, assessment of staff practice including hand hygiene, and increased MRSA screening of infants were implemented. Continued MRSA acquisitions led to screening of all NICU staff. A case-control study was performed to assess staff contact with colonized babies and inform the management of the outbreak. FINDINGS: Eight infants were colonized with MRSA (spa type t2068), one of whom subsequently developed an MRSA bacteraemia. MRSA colonization was significantly associated with lower gestational age; lower birthweight and with being a twin. Three nurses were MRSA colonized but only one nurse (45) was colonized with MRSA spa type t2068. Multivariable logistic regression analysis identified being cared for by nurse 45 as an independent risk factor for MRSA colonization. CONCLUSIONS: Lack of accurate recording of which nurses looked after which infants (and when) made identification of the risk posed by being cared for by particular nurses difficult. If this had been clearer, it may have enabled earlier identification of the colonized nurse, avoiding subsequent cases. This study highlights the benefit of using a case-control study, which showed that most nurses had no association with colonized infants.

Doxycycline or moxifloxacin for the management of community-acquired pneumonia in the UK?

Macrolide monotherapy is currently recommended as first-line treatment of mild-to-moderate community-acquired pneumonia (CAP) in penicillin-intolerant/allergic individuals in the UK. However, resistance rates among the commonest cause, Streptococcus pneumoniae, now exceed 10% in the UK and a review of alternative agents is therefore timely. This review considers the relative merits of two agents, doxycycline and moxifloxacin, which are candidates to replace macrolides for second-line therapy of non-severe CAP.

Investigation and management of an outbreak of multidrug-carbapenem-resistant Acinetobacter baumannii in Cambridge, UK.

Multidrug-resistant Acinetobacter baumannii resistant to carbapenems (MRAB-C) has become endemic in many hospitals in the UK. We describe an outbreak of MRAB-C that occurred on two intensive care units using ORION criteria (Outbreak Reports and Intervention studies Of Nosocomial infection). All patients colonised or infected with MRAB-C were included. Enhanced infection control precautions were introduced in Phase 1 of the outbreak. The adult neurosciences critical care unit (NCCU) was partially closed in Phase 2 and strict patient segregation, barrier nursing and screening thrice weekly was introduced. When control was achieved, NCCU was reopened (Phase 3) with post-discharge steam cleaning and monthly cleaning of extract and supply vents. There were 19 cases, 16 on NCCU and three on the general intensive care unit (ICU). Mean age was 52 years, with six cases being female. All patients were mechanically ventilated and ten had either an extraventricular drain or intracranial pressure monitoring device in place. Four patients developed a bacteraemia, with one further case of ventriculitis. Nine patients had no clinical evidence of infection and four were identified initially on screening. Ten patients were treated; there were eight deaths. Environmental samples showed heavy contamination throughout NCCU. MRAB-C affects critically ill patients and is associated with high mortality. This outbreak was controlled by early involvement of management, patient segregation, screening of patients and the environment, and increased hand hygiene environmental cleaning and clinical vigilance. A multidisciplinary approach to outbreak control is mandatory.

Bone and joint mycobacterial infection: a retrospective review of cases presenting to a UK district hospital.

PURPOSE: Peterborough has one of the highest rates of tuberculosis (TB) in the east of England. We reviewed the epidemiology, management and outcome of all cases of bone and joint TB (BJTB) diagnosed since 2000. METHODOLOGY: Retrospective review of all adult cases of BJTB between 1 January 2000 and 31 December 2015. Patients' notes were reviewed with regard to their presentation, investigation, management and outcomes. RESULTS: In total, 21 patients diagnosed with BJTB were reviewed. Thoracic and lumbar spine were the most common sites affected (62 %). The most common clinical manifestations included localized pain (76 %), fever (53 %) and weight loss (48 %). Fourteen (67 %) patients had a bone biopsy or aspirate sent for microbiological investigation; none were smear-positive, but 11 were culture-positive. Eleven patients (77 %) were fully susceptible to anti-tuberculous drugs, one was isoniazid-resistant and one was pyrazinamide-resistant. Anti-tuberculous therapy was given for 6-16 months. Nineteen (90 %) patients completed therapy. CONCLUSIONS: BJTB requires a high index of clinical suspicion. BJTB should be considered in any patient with unexplained pain, fever and weight loss. The diagnosis is proven by aspiration and biopsy and should be undertaken as soon as possible for culture purposes, as microscopy alone can be negative.

Point-prevalence survey of carbapenemase-producing Enterobacteriaceae and vancomycin-resistant enterococci in adult inpatients in a university teaching hospital in the UK.

Infections with carbapenemase-producing Enterobacteriaceae (CPE) and vancomycin-resistant enterococci (VRE) are associated with increased morbidity and mortality, but the carriage rates of CRE and VRE among hospital inpatients are unknown. A point-prevalence survey was conducted to determine CPE and VRE carriage rates in hospitalized adults. Eight hundred and eighteen of 960 (85.2%) adult inpatients were invited to participate in the study. Of these, 595 patients (72.7%) consented and provided specimens. Of 540 samples tested, none were positive for CPE. One hundred and thirty of 540 (24.1%) samples were VRE positive, and 34 of 40 (85%) of wards had cases. Universal screening for CPE may not be cost-effective in low-prevalence settings, but targeted screening of high-risk patients should continue. The optimal screening strategy for VRE remains to be determined, as universal screening and isolation is not feasible in the study setting.

Real-world use of fidaxomicin in a large UK tertiary hospital: how effective is it for treating recurrent disease?

All courses of fidaxomicin use in the study hospital were reviewed. It was used for first recurrence (six times), second recurrence (eight times) and one case of third recurrence. One patients received fidaxomicin as first-line treatment. Eight patients initially responded to therapy; of these, three patients were asymptomatic at 90 days, three patients remained asymptomatic at 30 days, and two patients had recurrences five and nine days after stopping therapy. Four patients failed to respond; of these, two patients required faecal transplantation and one patient required a colectomy. Two patients deteriorated and two patients died. Fidaxomicin was well tolerated. These findings suggest that the utility of fidaxomicin at this stage of infection is unclear.

Non-fermentative Gram-negative bacteria.

Over the past decade, non-fermenting Gram-negative bacteria have emerged as important opportunistic pathogens in the increasing population of patients who are immunocompromised by their disease or medical treatment. These bacteria are assisted by their ubiquitous distribution in the environment and have a propensity for multiple, intrinsic or acquired drug resistance. The infections that they cause now pose significant problems in terms of treatment and infection control, whilst the commonly observed rapid emergence of bacterial resistance to new antimicrobial compounds raises concerns regarding the clinical lifespan of these agents. Studies are urgently required to assess whether combination therapy can improve the long-term utility of new drugs in the treatment of patients infected with non-fermenters.

Candidaemia in a large teaching hospital: a clinical audit.

BACKGROUND: Candidaemias are associated with significant morbidity and mortality. The British Society of Medical Mycology and Infectious Diseases Society of America recently published audit standards, to address the changing epidemiology of candidaemia and to improve outcomes. AIM: To investigate the local epidemiology of candidaemia and the standard of care in a large teaching hospital. DESIGN: Retrospective audit. METHODS: Data were obtained for all candidaemia episodes over the 4-year period ending July 2004, from the medical and nursing notes, laboratory computer and patient administration system. RESULTS: We identified 92 episodes in 90 patients. The main predisposing factors were being on an intensive care unit, having a central venous catheter, and (for neonates) prematurity. Central venous catheters were removed at a mean 1.8 days following candidaemia; 79% (37/47) were removed within 48 h (the audit standard). Identification and susceptibility tests were performed for 94.7% of isolates. All were susceptible to amphotericin B; 87% were susceptible to fluconazole. Antifungal treatment was started within 24 h of a positive blood culture in 84% of episodes. Initial antifungal therapy was appropriate in 95% (61/64) of treated cases. Most patients (81%) who survived or completed their intended course of treatment before death received at least 2 weeks treatment. However, only 45% of those transferred to other hospitals had accompanying guidance on the intended further duration of therapy. Thirty-day mortality was 41%. After adjustment for age, the presence of Candida-related complications was associated with an odds ratio for mortality of 6.5 (95% CI 1.2-36.5, p = 0.03). DISCUSSION: Overall the audit standards set by the BSMM and IDSA were met, and discrepancies did not lead to a change in outcome. Improved intravenous catheter care, a more pro-active approach to searching for complications, and improvement in the inter-hospital transfer process, will assist in reducing morbidity and mortality.

Invasive fungal infections: a review of epidemiology and management options.

Fungi are increasingly recognised as major pathogens in critically ill patients. Candida spp. and Cryptococcus spp. are the yeasts most frequently isolated in clinical practice. The most frequent filamentous fungi (moulds) isolated are Aspergillus spp., but Fusarium spp., Scedosporium spp., Penicillium spp., and Zygomycetes are increasingly seen. Several reasons have been proposed for the increase in invasive fungal infections, including the use of antineoplastic and immunosuppressive agents, broad-spectrum antibiotics, and prosthetic devices and grafts, and more aggressive surgery. Patients with burns, neutropenia, HIV infection and pancreatitis are also predisposed to fungal infection. The epidemiology and clinical features of fungal infections are reviewed, together with antifungal agents currently or soon to be available.

Two cases of parotid gland infection with bacteraemia due to meticillin-resistant Staphylococcus aureus.

Parotid gland infection as a source of meticillin-resistant Staphylococcus aureus bacteraemia has been rarely reported. It is predominantly a disease of the elderly and is associated with significant mortality. Two cases are described here that presented over a 6 month history at a district general hospital. Many cases may be preventable with adequate hydration and good oral hygiene, combined with effective infection control.

Aeromonas veronii biovar sobria bacteraemia with septic arthritis confirmed by 16S rDNA PCR in an immunocompetent adult.

An 81-year-old man developed septic arthritis and bacteraemia with Aeromonas veronii biovar sobria. Cultures of the joint wash-out fluid were negative; however, DNA matching that of Aeromonas veronii was identified by 16S rDNA PCR. The patient was successfully treated with a 4 week course of ciprofloxacin. No recognized risk factors were found.

Community-onset healthcare-associated MRSA bacteraemia in a district general hospital.

Methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia is associated with significant mortality and morbidity. This retrospective study involved 76 episodes over four years in a district general hospital in the UK. Twenty-eight of these episodes (36.8%) occurred within 72 h of admission. All of these, however, had risk factors for MRSA acquisition and were classified as healthcare-associated bacteraemias. The mortality rates (all causes) at seven days and three months were 31.5% and 53.4%, respectively. Ten patients died before targeted therapy could be commenced. All patients in the study had multiple comorbidities, and pneumonia was a common diagnosis. Previous antibiotics, increased age, admission on surgical wards/intensive care units, and the presence of central venous cannulae and urinary catheters were risk factors for infection. In 48.7% of episodes, patients were not known to be colonized with MRSA prior to their bacteraemia. Empirical targeted therapy should be given to patients with risk factors for MRSA and staphylococci in blood cultures pending susceptibility results. Increased use of screening may also be required to reduce transmission and increase the likelihood of appropriate empirical antimicrobial therapy. Eradication of MRSA from carriers in the community should be considered to reduce the number of community-onset healthcare-associated bacteraemias.