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.

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.

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.

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.

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.

Enhancing engagement beyond the conference walls: analysis of Twitter use at #ICPIC2019 infection prevention and control conference.

BACKGROUND: Social media may provide a tool, when coupled with a patient-included™ conference, to enhance the engagement among the general public. We describe authors and potential readers of Twitter content surrounding a patient-included™ scientific congress, the International Consortium for Prevention and Infection Control (ICPIC) 2019. METHODS: Retrospective observational analysis of Twitter users posting with the #ICPIC2019 hashtag during the conference. Tweet authors, overall followers, and active followers were categorized according to their Twitter biographies using unsupervised learning. Diversity of professional backgrounds of Tweet authors and their followers was explored. Network analysis explored connectedness between the reach of authors. RESULTS: In total, 1264 participants attended ICPIC 2019, of which 28 were patients. From September 7 to 16, 2019, we were able to categorize 235'620 (41%) followers linked to 474 (76%) authors. Among authors and followers, respectively 34% and 14% were healthcare workers, 11% and 15% were from industry representatives, 8% and 7% were academic researchers. On average, 23% (range 9-39%) followers belonged to the same categories as authors. Among all followers categorized, only 582/235 620 (0.25%) interacted with original messages, including healthcare workers (37%), global and public health (12%), academic research (11%) and those from industry (11%). Though the similarity between Tweet authors and followers was supported by network analysis, we also observed that non-healthcare workers (including patients) appeared to have more diverse followers. CONCLUSIONS: We observed the participation of numerous Tweet authors and followers from diverse professional backgrounds potentially supporting the benefit of including patients in conferences to reach a more general, non-specialized public.

Rapid Detection of Mobilized Colistin Resistance using a Nucleic Acid Based Lab-on-a-Chip Diagnostic System.

The increasing prevalence of antimicrobial resistance is a serious threat to global public health. One of the most concerning trends is the rapid spread of Carbapenemase-Producing Organisms (CPO), where colistin has become the last-resort antibiotic treatment. The emergence of colistin resistance, including the spread of mobilized colistin resistance (mcr) genes, raises the possibility of untreatable bacterial infections and motivates the development of improved diagnostics for the detection of colistin-resistant organisms. This work demonstrates a rapid response for detecting the most recently reported mcr gene, mcr-9, using a portable and affordable lab-on-a-chip (LoC) platform, offering a promising alternative to conventional laboratory-based instruments such as real-time PCR (qPCR). The platform combines semiconductor technology, for non-optical real-time DNA sensing, with a smartphone application for data acquisition, visualization and cloud connectivity. This technology is enabled by using loop-mediated isothermal amplification (LAMP) as the chemistry for targeted DNA detection, by virtue of its high sensitivity, specificity, yield, and manageable temperature requirements. Here, we have developed the first LAMP assay for mcr-9 - showing high sensitivity (down to 100 genomic copies/reaction) and high specificity (no cross-reactivity with other mcr variants). This assay is demonstrated through supporting a hospital investigation where we analyzed nucleic acids extracted from 128 carbapenemase-producing bacteria isolated from clinical and screening samples and found that 41 carried mcr-9 (validated using whole genome sequencing). Average positive detection times were 6.58 ± 0.42 min when performing the experiments on a conventional qPCR instrument (n = 41). For validating the translation of the LAMP assay onto a LoC platform, a subset of the samples were tested (n = 20), showing average detection times of 6.83 ± 0.92 min for positive isolates (n = 14). All experiments detected mcr-9 in under 10 min, and both platforms showed no statistically significant difference (p-value > 0.05). When sample preparation and throughput capabilities are integrated within this LoC platform, the adoption of this technology for the rapid detection and surveillance of antimicrobial resistance genes will decrease the turnaround time for DNA detection and resistotyping, improving diagnostic capabilities, patient outcomes, and the management of infectious diseases.

Survival of nosocomial bacteria and spores on surfaces and inactivation by hydrogen peroxide vapor.

With inocula of 6 to 7 log(10) CFU, most vegetative bacteria and spores tested survived on surfaces for more than 5 weeks, but all were inactivated within 90 min of exposure to hydrogen peroxide vapor in a 100-m(3) test room even in the presence of 0.3% bovine serum albumin to simulate biological soiling.

Hydrogen peroxide vapor: a novel method for the environmental control of lactococcal bacteriophages.

Bacteriophage contamination can be problematic, especially in industrial settings. We examined the in vitro efficacy of hydrogen peroxide vapor (HPV) for the inactivation of two lactococcal bacteriophages dried onto stainless steel discs. A more than 6-log reduction was achieved on both bacteriophages compared with unexposed controls by 50 min of HPV exposure in an isolator. HPV might be useful for the environmental control of bacteriophages.

Effectiveness of daily chlorhexidine bathing for reducing gram-negative infections: A meta-analysis.

OBJECTIVE: Multiple studies have demonstrated that daily chlorhexidine gluconate (CHG) bathing is associated with a significant reduction in infections caused by gram-positive pathogens. However, there are limited data on the effectiveness of daily CHG bathing on gram-negative infections. The aim of this study was to determine whether daily CHG bathing is effective in reducing the rate of gram-negative infections in adult intensive care unit (ICU) patients. DESIGN: We searched MEDLINE and 3 other databases for original studies comparing daily bathing with and without CHG. Two investigators extracted data independently on baseline characteristics, study design, form and concentration of CHG, incidence, and outcomes related to gram-negative infections. Data were combined using a random-effects model and pooled relative risk ratios (RRs), and 95% confidence intervals (CIs) were derived. RESULTS: In total, 15 studies (n = 34,895 patients) met inclusion criteria. Daily CHG bathing was not significantly associated with a lower risk of gram-negative infections compared with controls (RR, 0.89; 95% CI, 0.73-1.08; P = .24). Subgroup analysis demonstrated that daily CHG bathing was not effective for reducing the risk of gram-negative infections caused by Acinetobacter, Escherichia coli, Klebsiella, Enterobacter, or Pseudomonas spp. CONCLUSIONS: The use of daily CHG bathing was not associated with a lower risk of gram-negative infections. Further, better designed trials with adequate power and with gram-negative infections as the primary end point are needed.

Tolerance of MRSA ST239-TW to chlorhexidine-based decolonization: Evidence for keratinocyte invasion as a mechanism of biocide evasion.

OBJECTIVES: Information on genetic determinants of chlorhexidine tolerance (qacA carriage and MIC) in vitro is available, although evidence of the clinical impact and mechanisms remain poorly understood. We investigated why, following chlorhexidine intervention, prevalent epidemic MRSA ST22 and ST36 clones declined at an ICU, whilst an ST239-TW clone did not. The chlorhexidine tolerant ST239-TW phenotypes were assessed for their protein binding, cell adhesion and intracellular uptake potential. METHODS: Six ST22, ST36 and ST239-TW bloodstream infection isolates with comparable chlorhexidine MICs were selected from a 2-year outbreak in an ICU at Guy's and St. Thomas' Hospital. Isolates were tested for fibrinogen and fibronectin binding, and adhesion/internalization into human keratinocytes with and without biocide. RESULTS: Binding to fibrinogen and fibronectin, adhesion and intracellular uptake within keratinocytes (P < 0.001) and intracellular survival in keratinocytes under chlorhexidine pressure (ST22 3.18%, ST36 4.57% vs ST239-TW 12.79%; P < 0.0001) was consistently higher for ST239-TW. CONCLUSIONS: We present evidence that MRSA clones with similarly low in vitro tolerance to chlorhexidine exhibit different in vivo susceptibilities. The phenomenon of S. aureus adhesion and intracellular uptake into keratinocytes could therefore be regarded as an additional mechanism of chlorhexidine tolerance, enabling MRSA to evade infection control measures.