Indwelling pleural catheter infection and colonisation: a clinical practice review.

Indwelling pleural catheters (IPCs) are used in the management of malignant pleural effusions, but they can become infected in 5.7% of cases. This review aims to provide a summary of the development of IPC infections and their microbiology, diagnosis and management. IPC infections can be deep, involving the pleural space, or superficial. The former are of greater clinical concern. Deep infection is associated with biofilm formation on the IPC surface and require longer courses of antibiotic treatment. Mortality from infections is low and it is common for patients to undergo pleurodesis following a deep infection. The diagnosis of pleural infections is based upon positive IPC pleural fluid cultures, changes in pleural fluid appearance and biochemistry, and signs or symptoms suggestive of infection. IPCs can also become colonised, where bacteria are grown from pleural fluid drained via an IPC but without evidence of infection. It is important to distinguish between infection and colonisation clinically, and though infections require antibiotic treatment, colonisation does not. It is unclear what proportion of IPCs become colonised. The most common causes of IPC infection and colonisation are Staphylococcus aureus and Coagulase-negative Staphylococci respectively. The management of deep IPC infections requires prolonged antibiotic therapy and the drainage of infected fluid, usually via the IPC. Intrapleural enzyme therapy (DNase and fibrinolytics) can be used to aid drainage. IPCs rarely need to be removed and patients can generally be managed as outpatients. Work is ongoing to study the incidence and significance of IPC colonisation. Other topics of interest include topical mupirocin to prevent IPC infections, and whether IPCs can be designed to limit infection risk.

Impact of daily octenidine skin washing versus nonwashing on antiseptic tolerance of coagulase-negative staphylococci in two neonatal intensive care units with different skin cleansing practices.

Background: There is wide variation in practices regarding routine bathing/washing of babies in neonatal intensive care units (NICUs). Evidence is lacking as to the benefit of routine antiseptic washes for reducing infection. We aimed to compare the antiseptic tolerance of Coagulase Negative Staphylococci (CoNS) within two UK NICUs with very different approaches to skin washing. Methods: We compared antiseptic susceptibility of CoNS isolated from skin swabs of neonates admitted to the Norfolk and Norwich University Hospital (NNUH) NICU in December 2017-March 2018 with those isolated in the Bradford Royal Infirmary (BRI) NICU in January-March 2020. The NNUH does not practise routine whole-body washing whereas BRI practises daily whole-body washing from post-menstrual age 27 weeks using Octenisan wash lotion (0.3% octenidine; 1 minute contact time before washing off with sterile water). A total of 78 CoNS isolates from BRI and 863 from the NNUH were tested for susceptibility against the antiseptics octenidine (OCT) and chlorhexidine (CHX). Results: Isolates from the BRI with practice of routine washing did not show increased antiseptic tolerance to OCT or CHX. Isolates from the NNUH which does not practise routine whole-body washing and rarely uses octenidine, were comparatively less susceptible to both CHX and OCT antiseptics. Conclusions: Daily whole-body skin washing with OCT does not appear to select for CoNS isolates that are antiseptic tolerant towards OCT and CHX. There remains considerable uncertainty about the impact of different antiseptic regimes on neonatal skin microbiota, the benefit of routine washing, and the development of antiseptic tolerance in the NICU.

Characterisation of neonatal Staphylococcus capitis NRCS-A isolates compared with non NRCS-A Staphylococcus capitis from neonates and adults.

Staphylococcus capitis is a frequent cause of late-onset sepsis in neonates admitted to Neonatal Intensive Care Units (NICU). One clone of S. capitis, NRCS-A has been isolated from NICUs globally although the reasons for the global success of this clone are not well understood.We analysed a collection of S. capitis colonising babies admitted to two NICUs, one in the UK and one in Germany as well as corresponding pathological clinical isolates. Genome analysis identified a population structure of three groups; non-NRCS-A isolates, NRCS-A isolates, and a group of 'proto NRCS-A' - isolates closely related to NRCS-A but not associated with neonatal infection. All bloodstream isolates belonged to the NRCS-A group and were indistinguishable from strains carried on the skin or in the gut. NRCS-A isolates showed increased tolerance to chlorhexidine and antibiotics relative to the other S. capitis as well as enhanced ability to grow at higher pH values. Analysis of the pangenome of 138 isolates identified characteristic nsr and tarJ genes in both the NRCS-A and proto groups. A CRISPR-cas system was only seen in NRCS-A isolates which also showed enrichment of genes for metal acquisition and transport.We found evidence for transmission of S. capitis NRCS-A within NICU, with related isolates shared between babies and multiple acquisitions by some babies. Our data show NRCS-A strains commonly colonise uninfected babies in NICU representing a potential reservoir for potential infection. This work provides more evidence that adaptation to survive in the gut and on skin facilitates spread of NRCS-A, and that metal acquisition and tolerance may be important to the biology of NRCS-A. Understanding how NRCS-A survives in NICUs can help develop infection control procedures against this clone.

Breathlessness Predicts Mortality in Adults: A Systematic Review and Meta-Analysis.

Breathlessness is a commonly encountered symptom, and although its relationship with mortality is well established for many conditions, less clear is this relationship in healthy adults. This systematic review and meta-analysis examines whether breathlessness is associated with mortality in a general population. This is important in understanding the impact of this common symptom on a patient's prognosis. This review was registered with PROSPERO (CRD42023394104). Medline, EMBASE, CINAHL and EMCARE were searched for the terms 'breathlessness' and 'survival' or 'mortality' on January 24, 2023. Longitudinal studies of >1,000 healthy adults comparing mortality between breathless and non-breathless controls were eligible for inclusion. If an estimate of effect size was provided, studies were included in the meta-analysis. Eligible studies underwent critical appraisal, data extraction and risk of bias assessment. A pooled effect size was estimated for the relationship between the presence of breathlessness and mortality and levels of severity of breathlessness and mortality. Of 1,993 studies identified, 21 were eligible for inclusion in the systematic review and 19 for the meta-analysis. Studies were of good quality with a low risk of bias, and the majority controlled for important confounders. Most studies identified a significant relationship between the presence of breathlessness and increased mortality. A pooled effect size was estimated, with the presence of breathlessness increasing the risk of mortality by 43% (risk ratio (RR): 1.43, 95% confidence interval (CI): 1.28-1.61). As breathlessness severity increased from mild to severe, mortality increased by 30% (RR: 1.30, 95% CI: 1.21-1.38) and 103%, respectively (RR: 2.03, 95% CI: 1.75-2.35). The same trend was seen when breathlessness was measured using the modified Medical Research Council (mMRC) Dyspnoea Scale: mMRC grade 1 conferred a 26% increased mortality risk (RR: 1.26, 95% CI: 1.16-1.37) compared with 155% for grade 4 (RR: 2.55, 95% CI: 1.86-3.50). We conclude that mortality is associated with the presence of breathlessness and its severity. The mechanism underlying this is unclear and may reflect the ubiquity of breathlessness as a symptom of many diseases.

Chlorhexidine gluconate usage is associated with antiseptic tolerance in staphylococci from the neonatal intensive care unit.

BACKGROUND: Intravascular catheters are essential for care in Neonatal Intensive Care Units (NICUs) but predispose infants to catheter-associated infections including late-onset sepsis, commonly caused by CoNS. Antiseptics are applied to prevent infection with chlorhexidine (CHG) and octenidine (OCT) the most common agents used. OBJECTIVES: To investigate the association between antiseptic use and bacterial susceptibility. METHODS: CoNS isolates were collected from two NICUs with differing antiseptic regimens: Norwich, UK (using CHG) and Lubeck, Germany (using OCT). CoNS were isolated from different body sites of babies upon admission, and weekly thereafter. Antiseptic susceptibility testing was performed, and a selection underwent genome sequencing. RESULTS: A total of 1274 isolates were collected. UK isolates (n = 863) were significantly less susceptible than German isolates (n = 411) to both CHG (mean MIC: 20.1 mg/L versus 8.9 mg/L) and OCT (mean MIC: 2.3 mg/L versus 1.6 mg/L). UK isolates taken on admission were more susceptible to CHG than subsequent isolates. No cross-resistance between the agents was seen. Genome sequencing of 122 CoNS showed the most common species to be Staphylococcus epidermidis and Staphylococcus haemolyticus and phylogenetic analysis suggested antiseptic tolerance evolved multiple times in independent lineages. There was no evidence of dominant antiseptic tolerant clones and carriage of genes previously implicated in antimicrobial susceptibility (qac, smr, norA/B), did not correlate with CHG or OCT susceptibility. CONCLUSIONS: Long-term CHG use may select for CHG and OCT tolerance in CoNS. This highlights the different potential for separate antiseptic regimens to select for resistance development. This could be an important factor in developing future infection control policies.

Large-scale sequencing of SARS-CoV-2 genomes from one region allows detailed epidemiology and enables local outbreak management.

The COVID-19 pandemic has spread rapidly throughout the world. In the UK, the initial peak was in April 2020; in the county of Norfolk (UK) and surrounding areas, which has a stable, low-density population, over 3200 cases were reported between March and August 2020. As part of the activities of the national COVID-19 Genomics Consortium (COG-UK) we undertook whole genome sequencing of the SARS-CoV-2 genomes present in positive clinical samples from the Norfolk region. These samples were collected by four major hospitals, multiple minor hospitals, care facilities and community organizations within Norfolk and surrounding areas. We combined clinical metadata with the sequencing data from regional SARS-CoV-2 genomes to understand the origins, genetic variation, transmission and expansion (spread) of the virus within the region and provide context nationally. Data were fed back into the national effort for pandemic management, whilst simultaneously being used to assist local outbreak analyses. Overall, 1565 positive samples (172 per 100 000 population) from 1376 cases were evaluated; for 140 cases between two and six samples were available providing longitudinal data. This represented 42.6 % of all positive samples identified by hospital testing in the region and encompassed those with clinical need, and health and care workers and their families. In total, 1035 cases had genome sequences of sufficient quality to provide phylogenetic lineages. These genomes belonged to 26 distinct global lineages, indicating that there were multiple separate introductions into the region. Furthermore, 100 genetically distinct UK lineages were detected demonstrating local evolution, at a rate of ~2 SNPs per month, and multiple co-occurring lineages as the pandemic progressed. Our analysis: identified a discrete sublineage associated with six care facilities; found no evidence of reinfection in longitudinal samples; ruled out a nosocomial outbreak; identified 16 lineages in key workers which were not in patients, indicating infection control measures were effective; and found the D614G spike protein mutation which is linked to increased transmissibility dominates the samples and rapidly confirmed relatedness of cases in an outbreak at a food processing facility. The large-scale genome sequencing of SARS-CoV-2-positive samples has provided valuable additional data for public health epidemiology in the Norfolk region, and will continue to help identify and untangle hidden transmission chains as the pandemic evolves.