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.

Specific surface area of overlapping spheres in the presence of obstructions.

This study considers the random placement of uniform sized spheres, which may overlap, in the presence of another set of randomly placed (hard) spheres, which do not overlap. The overlapping spheres do not intersect the hard spheres. It is shown that the specific surface area of the collection of overlapping spheres is affected by the hard spheres, such that there is a minimum in the specific surface area as a function of the relative size of the two sets of spheres. The occurrence of the minimum is explained in terms of the break-up of pore connectivity. The configuration can be considered to be a simple model of the structure of a porous composite material. In particular, the overlapping particles represent voids while the hard particles represent fillers. Example materials are pervious concrete, metallurgical coke, ice cream, and polymer composites. We also show how the material properties of such composites are affected by the void structure.

Pulling the plug on a pseudomonas outbreak: ancillary equipment as vectors of infection.

OBJECTIVES: Outbreaks of infection related to flexible endoscopes are well described. However, flexible endoscopy also requires the use of ancillary equipment such as irrigation plugs. These are potential vectors of infection but are infrequently highlighted in the literature. This paper reports a cystoscopy-associated outbreak of Pseudomonas aeruginosa from contaminated irrigation plugs in a UK tertiary care centre. METHODS: Laboratory, clinical and decontamination unit records were reviewed, and audits of the decontamination unit were performed. Flexible cystoscopes and irrigation plugs were assessed for contamination. Retrospective and prospective case finding was performed utilizing the microbiology laboratory information management system. Available P. aeruginosa isolates underwent variable nucleotide tandem repeat (VNTR) typing. Confirmed cases were defined as P. aeruginosa infection with an identical VNTR profile to an outbreak strain. RESULTS: Three strains of P. aeruginosa were isolated from five irrigation plugs but none of the flexible cystoscopes. No acquired resistance mechanisms were detected. Fifteen confirmed infections occurred, including bacteraemia, septic arthritis and urinary tract infection. While failure of decontamination likely occurred because the plugs were not dismantled prior to reprocessing, the manufacturer's reprocessing instructions were also incompatible with standard UK practice. The Medicines and Healthcare Products Regulatory Agency was informed. A field safety notice was issued, and the manufacturer issued updated reprocessing instructions. CONCLUSIONS: Ancillary equipment can represent an important vector for infection, and should be considered during outbreak investigations. Users should review the manufacturer's instructions for reprocessing ancillary equipment to ensure that they are compatible with available procedures.

An outbreak of two strains of OXA-48 producing Klebsiella pneumoniae in a teaching hospital.

OXA-48 producers can be difficult to detect in clinical specimens due to phenotypic low-level resistance to carbapenems. Additionally, low infection rates make clinical specimens poor sentinels for the presence of OXA-48 producers within a healthcare institution. We report an outbreak of OXA-48-producing Klebsiella pneumoniae (OXAKp) that was discovered following culture of OXAKp in a urine specimen from a patient with no known risk factors for acquisition. Widespread screening across medical wards in the trust revealed evidence of transmission across several wards. Samples from 60 patients were positive for OXAKp. Five patients had OXAKp clinical infection, four of whom were treated with ceftazidime/avibactam. Variable number tandem repeat analysis of the OXAKp isolates revealed two predominant strain types clustered around two groups of wards. Infection prevention measures included isolation and cohort nursing of infected and colonized patients, restriction of affected ward areas to new admissions, stringent hand hygiene and use of personal protective equipment. Environmental cleaning of patient areas was carried out using chlorine-releasing disinfectants and hydrogen peroxide vapour. Entire wards were decanted to enable effective cleaning of empty ward areas. The outbreak lasted almost five months and is estimated to have cost around £400 000. During the course of the outbreak, there were five reported prescription and administration incidents related to confusion between ceftazidime and ceftazidime/avibactam. No patient harm resulted from these incidents and the implementation of brand name prescribing for ceftazidime/avibactam prevented further incidents.

Optimizing antibiotic prescribing: collective approaches to managing a common-pool resource.

BACKGROUND: Antimicrobial resistance (AMR) is one of the greatest threats in 21st century medicine. AMR has been characterized as a social dilemma. A familiar version describes the situation in which a collective resource (in this case, antibiotic efficacy) is exhausted due to over-exploitation. The dilemma arises because individuals are motivated to maximize individual payoffs, although the collective outcome is worse if all act in this way. OBJECTIVES: We aim to outline the implications for antimicrobial stewardship of characterizing antibiotic overuse as a social dilemma. SOURCES: We conducted a narrative review of the literature on interventions to promote the conservation of resources in social dilemmas. CONTENT: The social dilemma of antibiotic over-use is complicated by the lack of visibility and imminence of AMR, a loose coupling between individual actions and the outcome of AMR, and the agency relationships inherent in the prescriber role. We identify seven strategies for shifting prescriber behaviour and promoting a focus on the collectively desirable outcome of conservation of antibiotic efficacy: (1) establish clearly defined boundaries and access rights; (2) raise the visibility and imminence of the problem; (3) enable collective choice arrangements; (4) conduct behaviour-based monitoring; (5) use social and reputational incentives and sanctions; (6) address misalignment of goals and incentives; and (7) provide conflict resolution mechanisms. IMPLICATIONS: We conclude that this theoretic analysis of antibiotic stewardship could make the problem of optimizing antibiotic prescribing more tractable, providing a theory base for intervention development.

Balancing the risks to individual and society: a systematic review and synthesis of qualitative research on antibiotic prescribing behaviour in hospitals.

BACKGROUND: Antimicrobial resistance is a global health threat, partly driven by inappropriate antibiotic prescriptions for acute medical patients in hospitals. AIM: To provide a systematic review of qualitative research on antibiotic prescribing decisions in hospitals worldwide, including broad-spectrum antibiotic use. METHODS: A systematic search of qualitative research on antibiotic prescribing for adult hospital patients published between 2007 and 2017 was conducted. Drawing on the Health Belief Model, a framework synthesis was conducted to assess threat perceptions associated with antimicrobial resistance, and perceived benefits and barriers associated with antibiotic stewardship. FINDINGS: The risk of antimicrobial resistance was generally perceived to be serious, but the abstract and long-term nature of its consequences led physicians to doubt personal susceptibility. While prescribers believed in the benefits of optimizing prescribing, the direct link between over-prescribing and antimicrobial resistance was questioned, and prescribers' behaviour change was frequently considered futile when fighting the complex problem of antimicrobial resistance. The salience of individual patient risks was a key barrier to more conservative prescribing. Physicians perceived broad-spectrum antibiotics to be effective and low risk; prescribing broad-spectrum antibiotics involved low cognitive demand and enabled physicians to manage patient expectations. Antibiotic prescribing decisions in low-income countries were shaped by a context of heightened uncertainty and risk due to poor microbiology and infection control services. CONCLUSIONS: When tackling antimicrobial resistance, the tensions between immediate individual risks and long-term collective risks need to be taken into account. Efforts to reduce diagnostic uncertainty and to change risk perceptions will be critical in shifting practice.

Meticillin-resistant Staphylococcus aureus (MRSA) in hospitals and the community: model predictions based on the UK situation.

Theoretical modelling has shown that patient movements in and out of hospitals are likely to affect nosocomial transmission dynamics considerably. The community acts as a "reservoir" and readmission of individuals colonised during previous admissions can result in sporadic transmission episodes within hospitals. We investigated patient movement patterns and frequency of readmissions using seven years of complete data from the University Hospitals of Leicester NHS Trust. Sufficient information is held on individual patients to study the heterogeneity in readmission. Overall, we found that an infected person has a 44.2% chance of being readmitted to the Trust while still infected. This value is far higher than previous estimates (3.7% [Cooper et al., Health Technol Assess 2003;7(39)]), highlighting the potential importance of transmission driven by hospital admissions. For this reason we believe consideration of readmissions from the community population to be critical to the success of hospital acquired infection control.

The pharmacokinetics of linezolid in the non-inflamed human eye.

AIM: This study describes the ocular pharmacokinetics of linezolid, an antibiotic with broad spectrum activity against those Gram positive bacteria that are the most frequent cause of postoperative endophthalmitis. METHOD: Patients undergoing routine cataract surgery were given a single oral 600 mg dose of linezolid at a variable time before surgery. Aqueous and serum levels of linezolid were assayed by high performance liquid chromatography, and a pharmacokinetic curve constructed from the pooled results. RESULTS: Orally administered linezolid rapidly achieves levels in the aqueous of non-inflamed eyes that exceed the concentration required to kill Gram positive bacteria (maximum mean concentration 6.8 (SD 1.2) microg/ml at 2-4 hours post-dose). An effective concentration is maintained for at least 12 hours, the standard interdose interval for this antimicrobial. CONCLUSION: Linezolid offers the possibility of a rapid, oral approach to effective treatment of most cases of postoperative endophthalmitis, with the potential of improving visual outcome.

Optimal spacing and penetration of cracks in a shrinking slab.

A method based on energy minimization is used to determine the spacing and penetration of a regular array of cracks in a slab that is shrinking due to a changing temperature field. The results show a range of different crack propagation behavior dependent on a single dimensionless parameter, being the ratio of the slab thickness and a characteristic length for the material. At low parameter values the minimum energy state can be achieved by continually adding more cracks until a steady state is achieved. At higher values, a minimum crack spacing is reached at finite time, beyond which the cracks are constrained to propagate with the minimum spacing. In the latter case, the uniform propagation is potentially unstable to a spatial period doubling, leading to increasingly complex crack penetration patterns. The energy minimization combined with the period doubling instability provides a means of determining the minimum energy state of cracks for all time. The problem considered here can be seen as a paradigm for cracking phenomena that occur on a large range of scales, from planetary to microscopic.

Immunologic and structural relatedness of the integrin beta 7 complex and the human intraepithelial lymphocyte antigen HML-1.

We recently cloned the newest human integrin beta subunit, termed beta 7, from a cDNA library constructed from SEA-activated T lymphocytes. In this communication, we report on the structure of the human integrin beta 7 protein complex determined using a rabbit anti-beta 7 peptide antibody raised to an N-terminal 22 amino acid residue sequence deduced from the human beta 7 subunit cDNA. The beta 7 subunit (Mr 116,000) expressed on PHA lymphoblasts associates with a single major alpha subunit (alpha H) that is distinct from the prominent T cell marker, integrin alpha 4. The alpha H subunit (Mr 180,000 nonreduced) displays a distinctive shift in size on reduction to an apparent Mr of 150,000. We show that these structural properties of the integrin beta 7 complex are shared with the cell surface antigen HML-1 found highly expressed on T cells which populate the intestinal epithelium and are proposed to be involved in mucosal immunity. Sequential immunoprecipitation and Western blotting demonstrate identity or close homology between the alpha H beta 7 and HML-1 proteins.

Comparative efficacy of transthoracic and transesophageal echocardiography in detection of an intracardiac bullet fragment.

A 19-year-old man received a gunshot wound to the heart. Transthoracic echocardiography was unable to localize the bullet fragment, whereas transesophageal echocardiography localized the bullet fragment in the posteroseptal wall at the base of the posteromedial papillary muscle.

Kytococcus schroeteri endocarditis successfully managed with daptomycin: a case report and review of the literature.

Kytococcus shroeteri is a rare cause of prosthetic valve endocarditis. Here, we report what is believed to be the first case of K. schroeteri endocarditis to be treated successfully by daptomycin and review the published literature of K. schroeteri endocarditis. There are no published daptomycin susceptibility data for Kytococcus and additional work was carried out on six other isolates stored at the Laboratory of HealthCare Associated Infections (LHCAI), Health Protection Agency (HPA) Centre for Infections, Colindale, London.

Screening strategies in surveillance and control of methicillin-resistant Staphylococcus aureus (MRSA).

With reports of hospital-acquired methicillin-resistant Staphylococcus aureus (MRSA) continuing to increase and therapeutic options decrease, infection control methods are of increasing importance. Here we investigate the relationship between surveillance and infection control. Surveillance plays two roles with respect to control: it allows detection of infected/colonized individuals necessary for their removal from the general population, and it allows quantification of control success. We develop a stochastic model of MRSA transmission dynamics exploring the effects of two screening strategies in an epidemic setting: random and on admission. We consider both hospital and community populations and include control and surveillance in a single framework. Random screening was more efficient at hospital surveillance and allowed nosocomial control, which also prevented epidemic behaviour in the community. Therefore, random screening was the more effective control strategy for both the hospital and community populations in this setting. Surveillance strategies have significant impact on both ascertainment of infection prevalence and its control.

Disseminated Sporothix schenckii in a patient with AIDS.

Sporothrix schenckii is a widespread dimorphic fungus which can cause cutaneous infection following local implantation. Disseminated sporotrichosis may occur in immunodeficient individuals but meningitis remains a rare complication. Diagnosis is usually difficult, requiring isolation of the organism from the CSF or skin so appropriate treatment can be promptly initiated. We present the first case of S. schenckii meningitis reported in the UK in a patient with AIDS. He presented with insidious features of meningoencephalitis, hydrocephalus and multiple cutaneous lesions and failed to respond to therapy.

Covalent binding of [35S]cysteine to the labile binding site of the third component of complement: a physiological approach.

The alternative pathway of complement was activated physiologically by agarose beads to which [35S]cysteine had been bound by a disulfide link. The activated form of the third component of complement, C3b, which had bound to the radioactive cysteine was then released from the agarose bead with dithiothreitol. The [35S]cysteine was shown to be covalently bound to the alpha' chain of C3b, and to its known major breakdown product, the 66,000-Da polypeptide. This is highly suggestive that complement activation has led to formation of a peptide bond between the radioactive cysteine and the labile binding site on the alpha' chain of C3b. This radioactive marker will enable the amino acid sequence of the labile binding site to be determined, with the knowledge that the labeling of the amino acid(s) has occurred during physiological activation.