Integrated analysis of patient networks and plasmid genomes reveals a regional, multi-species outbreak of carbapenemase-producing Enterobacterales carrying both blaIMP and mcr-9 genes.

BACKGROUND: Carbapenemase-producing Enterobacterales (CPE) are challenging in healthcare, with resistance to multiple classes of antibiotics. This study describes the emergence of IMP-encoding CPE amongst diverse Enterobacterales species between 2016 and 2019 across a London regional network. METHODS: We performed a network analysis of patient pathways, using electronic health records, to identify contacts between IMP-encoding CPE positive patients. Genomes of IMP-encoding CPE isolates were overlayed with patient contacts to imply potential transmission events. RESULTS: Genomic analysis of 84 Enterobacterales isolates revealed diverse species (predominantly Klebsiella spp, Enterobacter spp, E. coli); 86% (72/84) harboured an IncHI2 plasmid carrying blaIMP and colistin resistance gene mcr-9 (68/72). Phylogenetic analysis of IncHI2 plasmids identified three lineages showing significant association with patient contacts and movements between four hospital sites and across medical specialities, which was missed on initial investigations. CONCLUSIONS: Combined, our patient network and plasmid analyses demonstrate an interspecies, plasmid-mediated outbreak of blaIMPCPE, which remained unidentified during standard investigations. With DNA sequencing and multi-modal data incorporation, the outbreak investigation approach proposed here provides a framework for real-time identification of key factors causing pathogen spread. Plasmid-level outbreak analysis reveals that resistance spread may be wider than suspected, allowing more interventions to stop transmission within hospital networks.

Integrated Analysis of Patient Networks and Plasmid Genomes to Investigate a Regional, Multispecies Outbreak of Carbapenemase-Producing Enterobacterales Carrying Both blaIMP and mcr-9 Genes.

BACKGROUND: Carbapenemase-producing Enterobacterales (CPE) are challenging in healthcare, with resistance to multiple classes of antibiotics. This study describes the emergence of imipenemase (IMP)-encoding CPE among diverse Enterobacterales species between 2016 and 2019 across a London regional network. METHODS: We performed a network analysis of patient pathways, using electronic health records, to identify contacts between IMP-encoding CPE-positive patients. Genomes of IMP-encoding CPE isolates were overlaid with patient contacts to imply potential transmission events. RESULTS: Genomic analysis of 84 Enterobacterales isolates revealed diverse species (predominantly Klebsiella spp, Enterobacter spp, and Escherichia coli); 86% (72 of 84) harbored an IncHI2 plasmid carrying blaIMP and colistin resistance gene mcr-9 (68 of 72). Phylogenetic analysis of IncHI2 plasmids identified 3 lineages showing significant association with patient contacts and movements between 4 hospital sites and across medical specialties, which was missed in initial investigations. CONCLUSIONS: Combined, our patient network and plasmid analyses demonstrate an interspecies, plasmid-mediated outbreak of blaIMPCPE, which remained unidentified during standard investigations. With DNA sequencing and multimodal data incorporation, the outbreak investigation approach proposed here provides a framework for real-time identification of key factors causing pathogen spread. Plasmid-level outbreak analysis reveals that resistance spread may be wider than suspected, allowing more interventions to stop transmission within hospital networks.SummaryThis was an investigation, using integrated pathway networks and genomics methods, of the emergence of imipenemase-encoding carbapenemase-producing Enterobacterales among diverse Enterobacterales species between 2016 and 2019 in patients across a London regional hospital network, which was missed on routine investigations.

Changing Patterns of Bloodstream Infections in the Community and Acute Care Across 2 Coronavirus Disease 2019 Epidemic Waves: A Retrospective Analysis Using Data Linkage.

BACKGROUND: We examined community- and hospital-acquired bloodstream infections (BSIs) in coronavirus disease 2019 (COVID-19) and non-COVID-19 patients across 2 epidemic waves. METHODS: We analyzed blood cultures of patients presenting to a London hospital group between January 2020 and February 2021. We reported BSI incidence, changes in sampling, case mix, healthcare capacity, and COVID-19 variants. RESULTS: We identified 1047 BSIs from 34 044 blood cultures, including 653 (62.4%) community-acquired and 394 (37.6%) hospital-acquired. Important pattern changes were seen. Community-acquired Escherichia coli BSIs remained below prepandemic level during COVID-19 waves, but peaked following lockdown easing in May 2020, deviating from the historical trend of peaking in August. The hospital-acquired BSI rate was 100.4 per 100 000 patient-days across the pandemic, increasing to 132.3 during the first wave and 190.9 during the second, with significant increase in elective inpatients. Patients with a hospital-acquired BSI, including those without COVID-19, experienced 20.2 excess days of hospital stay and 26.7% higher mortality, higher than reported in prepandemic literature. In intensive care, the BSI rate was 421.0 per 100 000 intensive care unit patient-days during the second wave, compared to 101.3 pre-COVID-19. The BSI incidence in those infected with the severe acute respiratory syndrome coronavirus 2 Alpha variant was similar to that seen with earlier variants. CONCLUSIONS: The pandemic have impacted the patterns of community- and hospital-acquired BSIs, in COVID-19 and non-COVID-19 patients. Factors driving the patterns are complex. Infection surveillance needs to consider key aspects of pandemic response and changes in healthcare practice.

Investigating Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Surface and Air Contamination in an Acute Healthcare Setting During the Peak of the Coronavirus Disease 2019 (COVID-19) Pandemic in London.

BACKGROUND: We evaluated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) surface and air contamination during the coronavirus disease 2019 (COVID-19) pandemic in London. METHODS: Prospective, cross-sectional, observational study in a multisite London hospital. Air and surface samples were collected from 7 clinical areas occupied by patients with COVID-19 and a public area of the hospital. Three or four 1.0-m3 air samples were collected in each area using an active air sampler. Surface samples were collected by swabbing items in the immediate vicinity of each air sample. SARS-CoV-2 was detected using reverse-transcription quantitative polymerase chain reaction (PCR) and viral culture; the limit of detection for culturing SARS-CoV-2 from surfaces was determined. RESULTS: Viral RNA was detected on 114 of 218 (52.3%) surfaces and in 14 of 31 (38.7%) air samples, but no virus was cultured. Viral RNA was more likely to be found in areas immediately occupied by COVID-19 patients than in other areas (67 of 105 [63.8%] vs 29 of 64 [45.3%]; odds ratio, 0.5; 95% confidence interval, 0.2-0.9; P = .025, χ2 test). The high PCR cycle threshold value for all samples (>30) indicated that the virus would not be culturable. CONCLUSIONS: Our findings of extensive viral RNA contamination of surfaces and air across a range of acute healthcare settings in the absence of cultured virus underlines the potential risk from environmental contamination in managing COVID-19 and the need for effective use of personal protective equipment, physical distancing, and hand/surface hygiene.

Development and Delivery of a Real-time Hospital-onset COVID-19 Surveillance System Using Network Analysis.

BACKGROUND: Understanding nosocomial acquisition, outbreaks, and transmission chains in real time will be fundamental to ensuring infection-prevention measures are effective in controlling coronavirus disease 2019 (COVID-19) in healthcare. We report the design and implementation of a hospital-onset COVID-19 infection (HOCI) surveillance system for an acute healthcare setting to target prevention interventions. METHODS: The study took place in a large teaching hospital group in London, United Kingdom. All patients tested for SARS-CoV-2 between 4 March and 14 April 2020 were included. Utilizing data routinely collected through electronic healthcare systems we developed a novel surveillance system for determining and reporting HOCI incidence and providing real-time network analysis. We provided daily reports on incidence and trends over time to support HOCI investigation and generated geotemporal reports using network analysis to interrogate admission pathways for common epidemiological links to infer transmission chains. By working with stakeholders the reports were co-designed for end users. RESULTS: Real-time surveillance reports revealed changing rates of HOCI throughout the course of the COVID-19 epidemic, key wards fueling probable transmission events, HOCIs overrepresented in particular specialties managing high-risk patients, the importance of integrating analysis of individual prior pathways, and the value of co-design in producing data visualization. Our surveillance system can effectively support national surveillance. CONCLUSIONS: Through early analysis of the novel surveillance system we have provided a description of HOCI rates and trends over time using real-time shifting denominator data. We demonstrate the importance of including the analysis of patient pathways and networks in characterizing risk of transmission and targeting infection-control interventions.

A Multispecies Cluster of GES-5 Carbapenemase-Producing Enterobacterales Linked by a Geographically Disseminated Plasmid.

BACKGROUND: Early and accurate treatment of infections due to carbapenem-resistant organisms is facilitated by rapid diagnostics, but rare resistance mechanisms can compromise detection. One year after a Guiana Extended-Spectrum (GES)-5 carbapenemase-positive Klebsiella oxytoca infection was identified by whole-genome sequencing (WGS; later found to be part of a cluster of 3 cases), a cluster of 11 patients with GES-5-positive K. oxytoca was identified over 18 weeks in the same hospital. METHODS: Bacteria were identified by matrix-assisted laser desorption/ionization-time of flight mass spectrometry, antimicrobial susceptibility testing followed European Committee on Antimicrobial Susceptibility Testing guidelines. Ertapenem-resistant isolates were referred to Public Health England for characterization using polymerase chain reaction (PCR) detection of GES, pulsed-field gel electrophoresis (PFGE), and WGS for the second cluster. RESULTS: The identification of the first GES-5 K. oxytoca isolate was delayed, being identified by WGS. Implementation of a GES-gene PCR informed the occurrence of the second cluster in real time. In contrast to PFGE, WGS phylogenetic analysis refuted an epidemiological link between the 2 clusters; it also suggested a cascade of patient-to-patient transmission in the later cluster. A novel GES-5-encoding plasmid was present in K. oxytoca, Escherichia coli, and Enterobacter cloacae isolates from unlinked patients within the same hospital group and in human and wastewater isolates from 3 hospitals elsewhere in the United Kingdom. CONCLUSIONS: Genomic sequencing revolutionized the epidemiological understanding of the clusters; it also underlined the risk of covert plasmid propagation in healthcare settings and revealed the national distribution of the resistance-encoding plasmid. Sequencing results also informed and led to the ongoing use of enhanced diagnostic tests for detecting carbapenemases locally and nationally.

Detecting carbapenemase-producing Enterobacterales (CPE): an evaluation of an enhanced CPE infection control and screening programme in acute care.

OBJECTIVES: The transmission of carbapenemase-producing Enterobacterales (CPE) poses an increasing healthcare challenge. A range of infection prevention activities, including screening and contact precautions, are recommended by international and national guidelines. We evaluated the introduction of an enhanced screening programme in a multisite London hospital group. METHODS: In June 2015, an enhanced CPE policy was launched in response to a local rise in CPE detection. This increased infection prevention measures beyond the national recommendations, with enhanced admission screening, contact tracing and environmental disinfection, improved laboratory protocols and staff/patient education. We report the CPE incidence and trends of CPE in screening and clinical cultures and the adoption of enhanced CPE screening. All non-duplicate CPE isolates identified between April 2014 and March 2018 were included. RESULTS: The number of CPE screens increased progressively, from 4530 in July 2015 to 10 589 in March 2018. CPE detection increased from 18 patients in July 2015 (1.0 per 1000 admissions) to 50 patients in March 2018 (2.7 per 1000 admissions). The proportion of CPE-positive screening cultures remained at approximately 0.4% throughout, suggesting that whilst the CPE carriage rate was unchanged, carrier identification increased. Also, 123 patients were identified through positive CPE clinical cultures over the study period; there was no significant change in the rate of CPE from clinical cultures per 1000 admissions (P = 0.07). CONCLUSIONS: Our findings suggest that whilst the enhanced screening programme identified a previously undetected reservoir of CPE colonization in our patient population, the rate of detection of CPE in clinical cultures did not increase.

Frequent Undetected Ward-Based Methicillin-Resistant Staphylococcus aureus Transmission Linked to Patient Sharing Between Hospitals.

Background: Recent evidence suggests that hospital transmission of methicillin-resistant Staphylococcus aureus (MRSA) is uncommon in UK centers that have implemented sustained infection control programs. We investigated whether a healthcare-network analysis could shed light on transmission paths currently sustaining MRSA levels in UK hospitals. Methods: A cross-sectional observational study was performed in 2 National Health Service hospital groups and a general district hospital in Southeast London. All MRSA patients identified at inpatient, outpatient, and community settings between 1 November 2011 and 29 February 2012 were included. We identified genetically defined MRSA transmission clusters in individual hospitals and across the healthcare network, and examined genetic differentiation of sequence type (ST) 22 MRSA isolates within and between hospitals and inpatient or outpatient and community settings, as informed by average and median pairwise single-nucleotide polymorphisms (SNPs) and SNP-based proportions of nearly identical isolates. Results: Two hundred forty-eight of 610 (40.7%) MRSA patients were linked in 90 transmission clusters, of which 27 spanned multiple hospitals. Analysis of a large 32 patient ST22-MRSA cluster showed that 26 of 32 patients (81.3%) had multiple contacts with one another during ward stays at any hospital. No residential, outpatient, or significant community healthcare contacts were identified. Genetic differentiation between ST22 MRSA inpatient isolates from different hospitals was less than between inpatient isolates from the same hospitals (P ≤ .01). Conclusions: There is evidence of frequent ward-based transmission of MRSA brought about by frequent patient admissions to multiple hospitals. Limiting in-ward transmission requires sharing of MRSA status data between hospitals.

Fast and expensive (PCR) or cheap and slow (culture)? A mathematical modelling study to explore screening for carbapenem resistance in UK hospitals.

BACKGROUND: Enterobacteriaceae are a common cause of hospital infections. Carbapenems are a clinically effective treatment of such infections. However, resistance is on the rise. In particular, carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CP-CRE) are increasingly common. In order to limit spread in clinical settings, screening and isolation is being recommended, but many different screening methods are available. We aimed to compare the impact and costs of three algorithms for detecting CP-CRE carriage. METHODS: We developed an individual-based simulation model to compare three screening algorithms using data from a UK National Health Service (NHS) trust. The first algorithm, "Direct PCR", was highly sensitive/specific and quick (half a day), but expensive. The second, "Culture + PCR", was relatively sensitive/specific but slower, requiring 2.5 days. A third algorithm, "PHE", repeated the "Culture + PCR" three times with an additional PCR. Scenario analysis was used to compare several levels of CP-CRE prevalence and coverage of screening, different specialities as well as isolation strategies. Our outcomes were (1) days that a patient with CP-CRE was not detected and hence not isolated ("days at risk"), (2) isolation bed days, (3) total costs and (4) mean cost per CP-CRE risk day averted per year. We also explored limited isolation bed day capacity. RESULTS: We found that although a Direct PCR algorithm would reduce the number of CP-CRE days at risk, the mean cost per CP-CRE risk day averted per year was substantially higher than for a Culture + PCR algorithm. For example, in our model of an intensive care unit, during a year with a 1.6% CP-CRE prevalence and 63% screening coverage, there were 508 (standard deviation 15), 642 (14) and 655 (14) days at risk under screening algorithms Direct PCR, Culture + PCR and PHE respectively, with mean costs per risk day averted of £192, £61 and £79. These results were robust to sensitivity analyses. CONCLUSIONS: Our results indicate that a Culture + PCR algorithm provides the optimal balance of cost and risk days averted, at varying isolation, prevalence and screening coverage scenarios. Findings from this study will help clinical organisations determine the optimal screening approach for CP-CRE, balancing risk and resources.

Treatment of infections caused by multidrug-resistant Gram-negative bacteria: report of the British Society for Antimicrobial Chemotherapy/Healthcare Infection Society/British Infection Association Joint Working Party.

The Working Party makes more than 100 tabulated recommendations in antimicrobial prescribing for the treatment of infections caused by multidrug-resistant (MDR) Gram-negative bacteria (GNB) and suggest further research, and algorithms for hospital and community antimicrobial usage in urinary infection. The international definition of MDR is complex, unsatisfactory and hinders the setting and monitoring of improvement programmes. We give a new definition of multiresistance. The background information on the mechanisms, global spread and UK prevalence of antibiotic prescribing and resistance has been systematically reviewed. The treatment options available in hospitals using intravenous antibiotics and in primary care using oral agents have been reviewed, ending with a consideration of antibiotic stewardship and recommendations. The guidance has been derived from current peer-reviewed publications and expert opinion with open consultation. Methods for systematic review were NICE compliant and in accordance with the SIGN 50 Handbook; critical appraisal was applied using AGREE II. Published guidelines were used as part of the evidence base and to support expert consensus. The guidance includes recommendations for stakeholders (including prescribers) and antibiotic-specific recommendations. The clinical efficacy of different agents is critically reviewed. We found there are very few good-quality comparative randomized clinical trials to support treatment regimens, particularly for licensed older agents. Susceptibility testing of MDR GNB causing infection to guide treatment needs critical enhancements. Meropenem- or imipenem-resistant Enterobacteriaceae should have their carbapenem MICs tested urgently, and any carbapenemase class should be identified: mandatory reporting of these isolates from all anatomical sites and specimens would improve risk assessments. Broth microdilution methods should be adopted for colistin susceptibility testing. Antimicrobial stewardship programmes should be instituted in all care settings, based on resistance rates and audit of compliance with guidelines, but should be augmented by improved surveillance of outcome in Gram-negative bacteraemia, and feedback to prescribers. Local and national surveillance of antibiotic use, resistance and outcomes should be supported and antibiotic prescribing guidelines should be informed by these data. The diagnosis and treatment of both presumptive and confirmed cases of infection by GNB should be improved. This guidance, with infection control to arrest increases in MDR, should be used to improve the outcome of infections with such strains. Anticipated users include medical, scientific, nursing, antimicrobial pharmacy and paramedical staff where they can be adapted for local use.

Evidence for Community Transmission of Community-Associated but Not Health-Care-Associated Methicillin-Resistant Staphylococcus Aureus Strains Linked to Social and Material Deprivation: Spatial Analysis of Cross-sectional Data.

BACKGROUND: Identifying and tackling the social determinants of infectious diseases has become a public health priority following the recognition that individuals with lower socioeconomic status are disproportionately affected by infectious diseases. In many parts of the world, epidemiologically and genotypically defined community-associated (CA) methicillin-resistant Staphylococcus aureus (MRSA) strains have emerged to become frequent causes of hospital infection. The aim of this study was to use spatial models with adjustment for area-level hospital attendance to determine the transmission niche of genotypically defined CA- and health-care-associated (HA)-MRSA strains across a diverse region of South East London and to explore a potential link between MRSA carriage and markers of social and material deprivation. METHODS AND FINDINGS: This study involved spatial analysis of cross-sectional data linked with all MRSA isolates identified by three National Health Service (NHS) microbiology laboratories between 1 November 2011 and 29 February 2012. The cohort of hospital-based NHS microbiology diagnostic services serves 867,254 usual residents in the Lambeth, Southwark, and Lewisham boroughs in South East London, United Kingdom (UK). Isolates were classified as HA- or CA-MRSA based on whole genome sequencing. All MRSA cases identified over 4 mo within the three-borough catchment area (n = 471) were mapped to small geographies and linked to area-level aggregated socioeconomic and demographic data. Disease mapping and ecological regression models were used to infer the most likely transmission niches for each MRSA genetic classification and to describe the spatial epidemiology of MRSA in relation to social determinants. Specifically, we aimed to identify demographic and socioeconomic population traits that explain cross-area extra variation in HA- and CA-MRSA relative risks following adjustment for hospital attendance data. We explored the potential for associations with the English Indices of Deprivation 2010 (including the Index of Multiple Deprivation and several deprivation domains and subdomains) and the 2011 England and Wales census demographic and socioeconomic indicators (including numbers of households by deprivation dimension) and indicators of population health. Both CA-and HA-MRSA were associated with household deprivation (CA-MRSA relative risk [RR]: 1.72 [1.03-2.94]; HA-MRSA RR: 1.57 [1.06-2.33]), which was correlated with hospital attendance (Pearson correlation coefficient [PCC] = 0.76). HA-MRSA was also associated with poor health (RR: 1.10 [1.01-1.19]) and residence in communal care homes (RR: 1.24 [1.12-1.37]), whereas CA-MRSA was linked with household overcrowding (RR: 1.58 [1.04-2.41]) and wider barriers, which represent a combined score for household overcrowding, low income, and homelessness (RR: 1.76 [1.16-2.70]). CA-MRSA was also associated with recent immigration to the UK (RR: 1.77 [1.19-2.66]). For the area-level variation in RR for CA-MRSA, 28.67% was attributable to the spatial arrangement of target geographies, compared with only 0.09% for HA-MRSA. An advantage to our study is that it provided a representative sample of usual residents receiving care in the catchment areas. A limitation is that relationships apparent in aggregated data analyses cannot be assumed to operate at the individual level. CONCLUSIONS: There was no evidence of community transmission of HA-MRSA strains, implying that HA-MRSA cases identified in the community originate from the hospital reservoir and are maintained by frequent attendance at health care facilities. In contrast, there was a high risk of CA-MRSA in deprived areas linked with overcrowding, homelessness, low income, and recent immigration to the UK, which was not explainable by health care exposure. Furthermore, areas adjacent to these deprived areas were themselves at greater risk of CA-MRSA, indicating community transmission of CA-MRSA. This ongoing community transmission could lead to CA-MRSA becoming the dominant strain types carried by patients admitted to hospital, particularly if successful hospital-based MRSA infection control programmes are maintained. These results suggest that community infection control programmes targeting transmission of CA-MRSA will be required to control MRSA in both the community and hospital. These epidemiological changes will also have implications for effectiveness of risk-factor-based hospital admission MRSA screening programmes.

Universal hospital admission screening for carbapenemase-producing organisms in a low-prevalence setting.

BACKGROUND: Carbapenemase-producing Enterobacteriaceae (CPE) are an emerging threat for healthcare providers worldwide. OBJECTIVES: To determine CPE carriage rates and risk factors in an unselected hospital cohort at the time of admission. METHODS: We approached 4567 patients within 72 h of admission to provide a rectal swab and answer a questionnaire on risk factors for carriage. Rectal swabs were cultured for carbapenem-resistant organisms on chromogenic and non-chromogenic agar, and tested for carbapenemase production by PCR (Check-Direct CPE). The study was approved by the NHS Research Ethics Committee. RESULTS: Only 6 CPE were cultured from 5 (0.1%) of 4006 patients who provided a rectal swab; only 1 was cultured using non-chromogenic media. An additional 76 culture-negative rectal swabs were initially PCR positive, but none grew a carbapenem-resistant organism despite enrichment culture and only two were positive when retested several months later by Check-Direct and a second PCR assay (Cepheid GeneXpert® Carba-R). A modified Ct cut-off of <35 would have resolved these apparent false-positives. 40% of patients had a risk factor that should prompt screening and pre-emptive isolation as defined by UK CPE guidelines but only 8.1% and 20.2% of these patients had been screened and pre-emptively isolated by clinical teams, respectively. Overseas hospitalization was the only significant risk factor for CPE carriage (P < 0.001, OR 64.3, 95% CI 7.3-488.5). CONCLUSIONS: This study highlights a very low carriage rate of CPE. Hospitalization abroad is the most important risk factor to guide admission screening in this low-prevalence setting.

Clonal variation in high- and low-level phenotypic and genotypic mupirocin resistance of MRSA isolates in south-east London.

OBJECTIVES: Both low-level mupirocin resistance (LMR) and high-level mupirocin resistance (HMR) have been identified. The aim of this study was to determine the epidemiology of LMR and HMR in MRSA isolates at five hospitals that have used mupirocin for targeted decolonization as part of successful institutional control programmes. METHODS: All MRSA identified in three microbiology laboratories serving five central and south-east London hospitals and surrounding communities between November 2011 and February 2012 were included. HMR and LMR were determined by disc diffusion testing. WGS was used to derive multilocus sequence types (MLSTs) and the presence of HMR and LMR resistance determinants. RESULTS: Prevalence of either HMR or LMR amongst first healthcare episode isolates from 795 identified patients was 9.69% (95% CI 7.72-11.96); LMR was 6.29% (95% CI 4.70-8.21) and HMR was 3.40% (95% CI 2.25-4.90). Mupirocin resistance was not significantly different in isolates identified from inpatients at each microbiology laboratory, but was more common in genotypically defined 'hospital' rather than 'community' isolates (OR 3.17, 95% CI 1.36-9.30, P = 0.002). LMR was associated with inpatient stay, previous history of MRSA and age ≥65 years; HMR was associated with age ≥65 years and residential postcode outside London. LMR and HMR varied by clone, with both being low in the dominant UK MRSA clone ST22 compared with ST8, ST36 and ST239/241 for LMR and with ST8 and ST36 for HMR. V588F mutation and mupA carriage had high specificity (>97%) and area under the curve (>83%) to discriminate phenotypic mupirocin resistance, but uncertainty around the sensitivity point estimate was large (95% CI 52.50%-94.44%). Mutations in or near the mupA gene were found in eight isolates that carried mupA but were not HMR. CONCLUSIONS: Mupirocin resistance was identified in <10% of patients and varied significantly by clone, implying that changes in clonal epidemiology may have an important role in determining the prevalence of resistance in conjunction with selection due to mupirocin use.

Evaluating the dynamics of hospital COVID-19 contacts and subsequent conversion to SARS-CoV-2 infection: a multi-centre retrospective cohort study.

We investigated the dynamics of COVID-19 contacts subsequent conversion to SARS-CoV-2 infection in an inpatient setting across three National Health Service (NHS) Trusts. 9.2% (476/5,156) COVID-19 contacts met inclusion criteria, were typable and tested positive for COVID-19. There was no significant difference between Omicron and non-Omicron contacts overall conversion proportions. Omicron contacts converted faster than non-Omicron contacts (median 3 days vs 4 days, P=0.03), and had significantly greater proportions of early conversions at day 3, 5, and 7 timepoints.

Use of a peracetic acid (PAA) disinfectant to reduce total viable bacteria count in hospital wastewater drains.

The periphery of the hospital water system interfaces at multiple points with patients and staff in clinical areas. This comprises mostly of sinks and showers and presents a significant infection control risk. Wastewater drains in particular act as a reservoir of pathogens that can be transmitted to patients. Numerous strategies have been investigated as potential methods to reduce biofilm and bacterial load including regular application of biocidal chemicals. Traditional methods of assessing the efficacy of such products relies on culture based microbiological techniques, usually targeting a limited range of key pathogens. We assessed the efficacy of a peracetic acid containing drain disinfectant product on seven clinical handwash basin drains, taking daily samples over six weeks (before, during and after use of the drain disinfectant product). We used a rapid, culture independent estimation of total bacterial viable count (TVC) to assess efficacy. We applied long read metagenomic sequencing to study the entire drain microbiome, which allowed taxonomic changes to be documented following use of the drain disinfectant product. All samples were found to be heavily contaminated, however the drain disinfectant product reduced the TVC from an estimated mean of 4228 cfu/mL to 2874 cfu/mL. This reduction was sustained in the two weeks following cessation of the product. Long-read metagenomic sequencing showed a microbiome dominated with Gram negative organisms, with some taxonomic shifts in samples before and after application of the drain disinfectant. The impact on hospital-acquired infections from reducing bioburden in hospital drains by approximately a third, along with any associated changes in bacterial composition, needs evaluation in future studies.

The drainome: longitudinal metagenomic characterisation of wastewater from hospital ward sinks to characterize the microbiome and resistome and assess the effects of decontamination interventions.

BACKGROUND: Hospital drains and water interfaces are implicated in nosocomial transmission of pathogens. Metagenomics can assess the microbial composition and presence of antimicrobial resistance genes in drains ('the drainome') but studies applying these methods longitudinally and to assess infection control interventions are lacking. AIM: Apply long-read metagenomics coupled with microbiological measurements to investigate the drainome and assess the effects of a peracetic acid-containing decontamination product. METHODS: 12-week study in three phases: a baseline phase, an intervention phase of enhanced decontamination with peracetic acid, and a post-intervention phase. Five hospital sink drains on an intensive care unit were sampled twice weekly. Each sample had 1) measurement of total viable count (TVC), 2) metagenomic analyses including i) taxonomic classification of bacteria and fungi ii) antibiotic resistance gene detection iii) plasmid identification, and 3) immunochromatographic detection of antimicrobial residues. FINDINGS: Overall TVCs remain unchanged in the intervention phase (+386 CFU/mL, SE 705, p=0.59). There was a small but significant increase in the microbial diversity in the intervention phase (-0.07 in Simpson's index, SE 0.03, p=0.007), which was not sustained post-intervention (-0.05, SE 0.03, p=0.08). The intervention was associated with increased relative abundance of the Pseudomonas genus (18.3% to 40.5% [+22.2%], SE 5.7%, p<0.001). Extended spectrum beta-lactamases were found in all samples, with NDM-carbapenemase found in 3 drains in 6 samples. Antimicrobial residues were detected in a large proportion of samples (31/115, 27%), suggesting use of sinks for non-handwashing activities. CONCLUSIONS: Metagenomics and other measurements can measure the composition of the drainome and assess the effectiveness of decontamination interventions.

An evaluation of environmental decontamination with hydrogen peroxide vapor for reducing the risk of patient acquisition of multidrug-resistant organisms.

BACKGROUND: Admission to a room previously occupied by a patient with certain multidrug-resistant organisms (MDROs) increases the risk of acquisition. Traditional cleaning strategies do not remove all environmental MDROs. We evaluated the environmental and clinical impact of hydrogen peroxide vapor (HPV) room disinfection. METHODS: We performed a 30-month prospective cohort intervention study on 6 high-risk units in a 994-bed tertiary care hospital. Following a 12-month preintervention phase, HPV was implemented on 3 units to decontaminate the rooms of patients known to be infected or colonized with epidemiologically important MDROs, following their discharge. Monthly environmental samples for MDROs were collected on all study units for 3 preintervention and 6 intervention months. The risk of MDRO acquisition in patients admitted to rooms decontaminated using HPV was compared with rooms disinfected using standard methods. RESULTS: The prior room occupant was known to be infected or colonized with an MDRO in 22% of 6350 admissions. Patients admitted to rooms decontaminated using HPV were 64% less likely to acquire any MDRO (incidence rate ratio [IRR], 0.36; 95% confidence interval [CI], .19-.70; P < .001) and 80% less likely to acquire VRE (IRR, 0.20; 95% CI, .08-.52; P < .001) after adjusting for other factors. The risk of acquiring Clostridium difficile, methicillin-resistant Staphylococcus aureus, and multidrug-resistant gram-negative rods individually was reduced, but not significantly. The proportion of rooms environmentally contaminated with MDROs was reduced significantly on the HPV units (relative risk, 0.65, P = .03), but not on non-HPV units. CONCLUSIONS: HPV decontamination reduced environmental contamination and the risk of acquiring MDROs compared with standard cleaning protocols.

Selection for qacA carriage in CC22, but not CC30, methicillin-resistant Staphylococcus aureus bloodstream infection isolates during a successful institutional infection control programme.

OBJECTIVES: The increasing use of chlorhexidine for methicillin-resistant Staphylococcus aureus (MRSA) decolonization raises concerns about reduced susceptibility. We evaluated the carriage of chlorhexidine resistance genes and chlorhexidine susceptibility in MRSA before and after introduction of an institutional MRSA control programme incorporating chlorhexidine-based decolonization in 2004. METHODS: MRSA bloodstream infection (BSI) isolates identified between 2001 and 2009 were tested for spa and staphylococcal cassette chromosome mec type and carriage of qacA, qacB and smr. Selected isolates were tested for chlorhexidine susceptibility. Logistic regression was used to evaluate associations between clone type, carriage of resistance genes and chlorhexidine susceptibility. Temporal trends in qacA or smr carriage were analysed using separate binomial generalized linear models. RESULTS: Typing identified two dominant clones: CC22 (n = 224) and CC30 (n = 197). Annual MRSA BSI rates declined from 2004, although the rate of decline for CC22 was slower than for CC30. Carriage of qacA and smr and having a chlorhexidine MIC ≥2 mg/L did not increase overall amongst MRSA BSI isolates; however, qacA carriage increased in CC22 compared with in CC30 (OR, 7.21; 95% CI, 1.32-39.17). Furthermore, qacA+ CC22 isolates were more likely to have a chlorhexidine MIC ≥2 mg/L than qacA+ CC30 isolates (OR, 21.67; CI, 2.54-185.20). CONCLUSIONS: A successful infection control programme was associated with the selection of qacA linked with a higher chlorhexidine MIC in one dominant endemic MRSA clone (CC22), but not another (CC30). The slower reduction in the CC22 MRSA BSI rate suggests that carriage of qacA confers a selective advantage, with implications for the sustainability of decolonization practice.

Can precision antibiotic prescribing help prevent the spread of carbapenem-resistant organisms in the hospital setting?

The emergence of carbapenem-resistant organisms (CROs) is a significant global threat. Reduction of carbapenem consumption can decrease CROs. In the global endemic era of ESBL-producing bacteria, carbapenems are considered the treatment of choice, leading to challenge in limiting carbapenem use. This review describes the role of precision prescribing for prevention of CROs. This involves improving antibiotic selection, dosing and shortening duration. The effect of different antibiotics, dosing and duration on CRO development are explored. Available options for precision prescribing, gaps in the scientific evidence, and areas for future research are also presented.

An association between bacterial genotype combined with a high-vancomycin minimum inhibitory concentration and risk of endocarditis in methicillin-resistant Staphylococcus aureus bloodstream infection.

INTRODUCTION: Antimicrobial resistance and bacterial virulence factors may increase the risk of hematogenous complications during methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI). This study reports on the impact of increasing vancomycin minimum inhibitory concentrations (V-MICs) and MRSA clone type on risk of hematogenous complications from MRSA BSI during implementation of an effective MRSA control program. METHODS: In sum, spa typing, staphylococcal cassette chromosome mec allotyping, and vancomycin and teicoplanin MICs were performed on 821 consecutive MRSA bloodstream isolates from 1999 to 2009. Prospectively collected data, including focus of infection, were available for 695 clinically significant cases. Logistic and multinomial logistic regression was used to determine the association between clone type, vancomycin MIC (V-MIC), and focus of infection. RESULTS: MRSA BSIs decreased by ∼90% during the 11 years. Typing placed isolates into 3 clonal complex (CC) groups that had different population median V-MICs (CC30, 0.5 µg/mL [n = 349]; CC22, 0.75 µg/mL [n = 272]; non-CC22/30, 1.5 µg/mL [n = 199]). There was a progressive increase in the proportion of isolates with a V-MIC above baseline median in each clonal group and a disproportionate fall in the clone group with lowest median V-MIC (CC30). In contrast, there were no increases in teicoplanin MICs. High V-MIC CC22 isolates (1.5-2 µg/mL) were strongly associated with endocarditis (odds ratio, 12; 95% confidence interval, 3.72-38.9) and with a septic metastasis after catheter-related BSI (odds ratio, 106; 95% confidence interval, 12.6-883) compared with other clone type/V-MIC combinations. CONCLUSIONS: An interaction between clone type and V-MIC can influence the risk of endocarditis associated with MRSA BSI, implying involvement of both therapeutic and host-pathogen factors.