Spiral.imperial.ac.uk



Seasonal changes in the incidence of Escherichia coli bloodstream infection: variation with region and place of onsetSarah R. Deeny1,2*Esther van Kleef3Sabine Bou-Antoun4Russell J. Hope4Julie V. Robotham1,21 Modelling and Economics Unit, Centre for Infectious Disease Surveillance and Control, Public Health England and Health Protection Research Unit in Modelling Methodology2 National Institute for Health Research, Health Protection Research Unit in Healthcare Associated Infection and Antimicrobial Resistance at Imperial College London 3 Modelling and Economics Unit, Centre for Infectious Disease Surveillance and Control, Public Health England 4 Healthcare Associated Infection and Antimicrobial Resistance Department, Centre for Infectious Disease Surveillance and Control, Public Health England Corresponding author: Sarah R. DeenyEmail: sarah.deeny@.ukAddress: Public Health England, 61 Colindale Avenue, London, NW9 5EQPhone Number: 00442083276377Fax Number: NAAbstractPrevious research has shown that?Escherichia coli?infection rates peak in the summer, however to date there has been no investigation as to whether this is seen in both hospital and community-onset cases and how this differs across regions. We investigated and quantified E. coli?bloodstream infection (BSI) seasonality. A generalized additive Poisson model was fitted to mandatory?E. coli?BSI surveillance data reported in England. There was no impact of seasonality in hospital-onset cases, however for the community onset cases there was statistically significant seasonal variation over time nationally. When examined regionally, seasonality was significant in the North of England only. This variation resulted in an absolute increase of 0.06 (95% CI, 0.04-0.08) cases above the mean (3.2) in each hospital trust for each week of the peak summer season and a decrease of 0.08 (-0.1, -0.06) in the autumn. We estimate that less than one hospital bed day per week, per hospital, is lost due to seasonal increases during the summer. Our findings highlight the need to understand distinct community and hospital dynamics of E. coli BSI and explore the regional differences driving variation in incidence in order to design and implement effective control measures. IntroductionThere is increasing concern at the growing epidemic of Escherichia coli, particularly those strains resistant to multiple antibiotics ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/1469-0691.12757", "ISSN" : "1198743X", "author" : [ { "dropping-particle" : "", "family" : "Nabet", "given" : "C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raoult", "given" : "D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical Microbiology and Infection", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "792-793", "title" : "The hidden epidemic of Escherichia coli", "type" : "article-journal", "volume" : "20" }, "uris" : [ "", "" ] } ], "mendeley" : { "formattedCitation" : "[1]", "plainTextFormattedCitation" : "[1]", "previouslyFormattedCitation" : "[1]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[1]. Evidence from surveillance systems in England have shown that, in contrast to MRSA bloodstream infections (BSI) and Clostridium difficile, BSI due to E. coli have been increasing year on year with a 20% increase from 2009 to 2013, when a total of 31,023 cases were reported ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Gerver", "given" : "Sarah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sinnathamby", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bou-Antoun", "given" : "Sabine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kauser", "given" : "Sophina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Canvin", "given" : "Malcolm", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abernethy", "given" : "Julia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Davies", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hope", "given" : "Russell", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issue" : "July", "issued" : { "date-parts" : [ [ "2014" ] ] }, "publisher-place" : "London, England", "title" : "Annual Epidemiological Commentary : Mandatory MRSA , MSSA and E . coli bacteraemia and C . difficile infection About Public Health England", "type" : "report" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[2]", "plainTextFormattedCitation" : "[2]", "previouslyFormattedCitation" : "[2]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[2], with an estimated mortality rate of 18.2% (95% CI 17.8–18.7%) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "", "author" : [ { "dropping-particle" : "", "family" : "Abernethy", "given" : "J K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johnson", "given" : "A P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guy", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hinton", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sheridan", "given" : "E A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hope", "given" : "R J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clin Microbiol Infect", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "251.e1\u2013251.e8", "title" : "Thirty day all-cause mortality in patients with Escherichia coli bacteraemia in England", "type" : "article-journal", "volume" : "21" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[3]", "plainTextFormattedCitation" : "[3]", "previouslyFormattedCitation" : "[3]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[3]. The reason for this sustained increase is unclear ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Gerver", "given" : "Sarah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sinnathamby", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bou-Antoun", "given" : "Sabine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kauser", "given" : "Sophina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Canvin", "given" : "Malcolm", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abernethy", "given" : "Julia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Davies", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hope", "given" : "Russell", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issue" : "July", "issued" : { "date-parts" : [ [ "2014" ] ] }, "publisher-place" : "London, England", "title" : "Annual Epidemiological Commentary : Mandatory MRSA , MSSA and E . coli bacteraemia and C . difficile infection About Public Health England", "type" : "report" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[2]", "plainTextFormattedCitation" : "[2]", "previouslyFormattedCitation" : "[2]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[2], and a number of factors: poor treatment and prevention of urinary tract infections (UTI), antibiotic resistance and poor catheter care have been mooted as contributing ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/jac/dks082", "ISSN" : "1460-2091", "PMID" : "22438437", "abstract" : "OBJECTIVES: To investigate trends in Escherichia coli resistance, bacteraemia rates and post-bacteraemia outcomes over time.\n\nMETHODS: Trends in E. coli bacteraemia incidence were monitored from January 1999 to June 2011 using an infection surveillance database including microbiological, clinical risk factor, infection severity and outcome data in Oxfordshire, UK, with imported temperature/rainfall data.\n\nRESULTS: A total of 2240 E. coli (from 2080 patients) were studied, of which 1728 (77%) were susceptible to co-amoxiclav, cefotaxime, ciprofloxacin and gentamicin. E. coli bacteraemia incidence increased from 3.4/10,000 bedstays in 1999 to 5.7/10,000 bedstays in 2011. The increase was fastest around 2006, and was essentially confined to organisms resistant to ciprofloxacin, co-amoxiclav, cefotaxime and/or aminoglycosides. Resistant E. coli isolation rates increased similarly in those with and without recent hospital contact. The sharp increase also occurred in urinary isolates, with similar timing. In addition to these long-term trends, increases in ambient temperature, but not rainfall, were associated with increased E. coli bacteraemia rates. It is unclear whether resistant E. coli bacteraemia rates are currently still increasing [incidence rate ratio = 1.07 per annum (95% CI = 0.99-1.16), P = 0.07], whereas current susceptible E. coli bacteraemia rates are not changing significantly [incidence rate ratio = 1.01 (95% CI = 0.99-1.02)]. However, neither mortality nor biomarkers associated with mortality (blood creatinine, urea/albumin concentrations, neutrophil counts) changed during the study.\n\nCONCLUSIONS: E. coli bacteraemia rates have risen due to rising rates of resistant organisms; little change occurred in susceptible E. coli. Although the severity of resistant infections, and their outcome, appear similar to susceptible E. coli in the setting studied, the increasing burden of highly resistant organisms is alarming and merits on-going surveillance.", "author" : [ { "dropping-particle" : "", "family" : "Schlackow", "given" : "Iryna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stoesser", "given" : "Nicole", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walker", "given" : "a Sarah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Crook", "given" : "Derrick W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peto", "given" : "Tim E a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wyllie", "given" : "David H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of antimicrobial chemotherapy", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2012", "6" ] ] }, "page" : "1514-24", "title" : "Increasing incidence of Escherichia coli bacteraemia is driven by an increase in antibiotic-resistant isolates: electronic database study in Oxfordshire 1999-2011.", "type" : "article-journal", "volume" : "67" }, "uris" : [ "", "" ] } ], "mendeley" : { "formattedCitation" : "[4]", "plainTextFormattedCitation" : "[4]", "previouslyFormattedCitation" : "[4]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[4]. There therefore remains a clear need to understand the epidemiology and drivers of E. coli infections.There is an emerging consensus that Gram negative infection rates are seasonal, peaking in the summer months and correlating to increasing temperatures ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pone.0091105", "ISSN" : "1932-6203", "PMID" : "24599500", "abstract" : "BACKGROUND: We investigated the relationship between average monthly temperature and the most common clinical pathogens causing infections in intensive care patients.\n\nMETHODS: A prospective unit-based study in 73 German intensive care units located in 41 different hospitals and 31 different cities with total 188,949 pathogen isolates (102,377 Gram-positives and 86,572 Gram-negatives) from 2001 to 2012. We estimated the relationship between the number of clinical pathogens per month and the average temperature in the month of isolation and in the month prior to isolation while adjusting for confounders and long-term trends using time series analysis. Adjusted incidence rate ratios for temperature parameters were estimated based on generalized estimating equation models which account for clustering effects.\n\nRESULTS: The incidence density of Gram-negative pathogens was 15% (IRR 1.15, 95%CI 1.10-1.21) higher at temperatures \u2265 20\u00b0C than at temperatures below 5\u00b0C. E. cloacae occurred 43% (IRR=1.43; 95%CI 1.31-1.56) more frequently at high temperatures, A. baumannii 37% (IRR=1.37; 95%CI 1.11-1.69), S. maltophilia 32% (IRR=1.32; 95%CI 1.12-1.57), K. pneumoniae 26% (IRR=1.26; 95%CI 1.13-1.39), Citrobacter spp. 19% (IRR=1.19; 95%CI 0.99-1.44) and coagulase-negative staphylococci 13% (IRR=1.13; 95%CI 1.04-1.22). By contrast, S. pneumoniae 35% (IRR=0.65; 95%CI 0.50-0.84) less frequently isolated at high temperatures. For each 5\u00b0C increase, we observed a 3% (IRR=1.03; 95%CI 1.02-1.04) increase of Gram-negative pathogens. This increase was highest for A. baumannii with 8% (IRR=1.08; 95%CI 1.05-1.12) followed by K. pneumoniae, Citrobacter spp. and E. cloacae with 7%.\n\nCONCLUSION: Clinical pathogens vary by incidence density with temperature. Significant higher incidence densities of Gram-negative pathogens were observed during summer whereas S. pneumoniae peaked in winter. There is increasing evidence that different seasonality due to physiologic changes underlies host susceptibility to different bacterial pathogens. Even if the underlying mechanisms are not yet clear, the temperature-dependent seasonality of pathogens has implications for infection control and study design.", "author" : [ { "dropping-particle" : "", "family" : "Schwab", "given" : "Frank", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gastmeier", "given" : "Petra", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyer", "given" : "Elisabeth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PloS one", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2014", "1" ] ] }, "page" : "e91105", "title" : "The warmer the weather, the more gram-negative bacteria - impact of temperature on clinical isolates in intensive care units.", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1371/journal.pone.0025298", "ISSN" : "1932-6203", "PMID" : "21966489", "abstract" : "BACKGROUND: Knowledge of seasonal trends in hospital-associated infection incidence may improve surveillance and help guide the design and evaluation of infection prevention interventions. We estimated seasonal variation in the frequencies of inpatient bloodstream infections (BSIs) caused by common bacterial pathogens and examined associations of monthly BSI frequencies with ambient outdoor temperature, precipitation, and humidity levels.\n\nMETHODS: A database containing blood cultures from 132 U.S. hospitals collected between January 1999 and September 2006 was assembled. The database included monthly counts of inpatient blood cultures positive for several clinically important Gram-negative bacteria (Acinetobacter spp, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa) and Gram-positive bacteria (Enterococcus spp and Staphylococcus aureus). Monthly mean temperature, total precipitation, and mean relative humidity in the postal ZIP codes of participating hospitals were obtained from national meteorological databases.\n\nRESULTS: A total of 211,697 inpatient BSIs were reported during 9,423 hospital-months. Adjusting for long-term trends, BSIs caused by each gram-negative organism examined were more frequent in summer months compared with winter months, with increases ranging from 12.2% for E. coli (95% CI 9.2-15.4) to 51.8% for Acinetobacter (95% CI 41.1-63.2). Summer season was associated with 8.7% fewer Enterococcus BSIs (95% CI 11.0-5.8) and no significant change in S. aureus BSI frequency relative to winter. Independent of season, monthly humidity, monthly precipitation, and long-term trends, each 5.6\u00b0C (10\u00b0F) rise in mean monthly temperature corresponded to increases in gram-negative bacterial BSI frequencies ranging between 3.5% for E. coli (95% CI 2.1-4.9) to 10.8% for Acinetobacter (95% CI 6.9-14.7). The same rise in mean monthly temperature corresponded to an increase of 2.2% in S. aureus BSI frequency (95% CI 1.3-3.2) but no significant change in Enterococcus BSI frequency.\n\nCONCLUSIONS: Summer season and higher mean monthly outdoor temperature are associated with substantially increased frequency of BSIs, particularly among clinically important gram-negative bacteria.", "author" : [ { "dropping-particle" : "", "family" : "Eber", "given" : "Michael R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shardell", "given" : "Michelle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schweizer", "given" : "Marin L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Laxminarayan", "given" : "Ramanan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perencevich", "given" : "Eli N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PloS one", "id" : "ITEM-2", "issue" : "9", "issued" : { "date-parts" : [ [ "2011", "1" ] ] }, "page" : "e25298", "title" : "Seasonal and temperature-associated increases in gram-negative bacterial bloodstream infections among hospitalized patients.", "type" : "article-journal", "volume" : "6" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1086/592698", "ISSN" : "0899-823X", "author" : [ { "dropping-particle" : "", "family" : "Perencevich", "given" : "Eli N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McGregor", "given" : "Jessina C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shardell", "given" : "Michelle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Furuno", "given" : "Jon P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Harris", "given" : "Anthony D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris, Jr.", "given" : "J. Glenn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fisman", "given" : "David N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johnson", "given" : "Judith A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Infection Control and Hospital Epidemiology", "id" : "ITEM-3", "issue" : "12", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "1124-1131", "title" : "Summer Peaks in the Incidences of Gram Negative Bacterial Infection Among Hospitalized Patients", "type" : "article-journal", "volume" : "29" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Al-Hasan", "given" : "M.N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lahr", "given" : "B D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eckel-Passow", "given" : "J.E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baddour", "given" : "L M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical Microbiology and Infection", "id" : "ITEM-4", "issue" : "10", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "7-10", "title" : "Seasonal variation in Escherichia coli bloodstream infection : a population-based study", "type" : "article-journal", "volume" : "15" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[5\u20138]", "plainTextFormattedCitation" : "[5\u20138]", "previouslyFormattedCitation" : "[5\u20138]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[5–8]. However, previous evidence of seasonality in E. coli BSI did not distinguish between hospital onset and community onset cases ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/j.1469-0691.2010.03327.x", "ISSN" : "1198743X", "PMID" : "20673262", "author" : [ { "dropping-particle" : "", "family" : "Chazan", "given" : "B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Colodner", "given" : "R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Edelstein", "given" : "H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raz", "given" : "R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical Microbiology and Infection", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "851-854", "publisher" : "European Society of Clinical Infectious Diseases", "title" : "Seasonal variation in Escherichia coli bloodstream infections in northern Israel", "type" : "article-journal", "volume" : "17" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[9]", "plainTextFormattedCitation" : "[9]", "previouslyFormattedCitation" : "[9]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[9], which may have different underlying focus of infection and thus a different epidemiology and natural history ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "", "author" : [ { "dropping-particle" : "", "family" : "Abernethy", "given" : "J K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johnson", "given" : "A P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guy", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hinton", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sheridan", "given" : "E A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hope", "given" : "R J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clin Microbiol Infect", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "251.e1\u2013251.e8", "title" : "Thirty day all-cause mortality in patients with Escherichia coli bacteraemia in England", "type" : "article-journal", "volume" : "21" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[3]", "plainTextFormattedCitation" : "[3]", "previouslyFormattedCitation" : "[3]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[3]. There has also been a lack of examination of regional variability or a quantification of the clinical impact of any seasonality ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/j.1469-0691.2010.03262.x", "author" : [ { "dropping-particle" : "", "family" : "Wilson", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elgohari", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Livermore", "given" : "D M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cookson", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johnson", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lamagni", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chronias", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sheridan", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Street", "given" : "Pond", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical Microbiology and Infection", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "451-458", "title" : "Trends among pathogens reported as causing bacteraemia in England , 2004\u20132008", "type" : "article-journal", "volume" : "17" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[10]", "plainTextFormattedCitation" : "[10]", "previouslyFormattedCitation" : "[10]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[10]. This is particularly important in countries such as England where there is regional variation in the incidence of E. coli BSI, with higher rates of infection in the North of England ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Gerver", "given" : "Sarah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sinnathamby", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bou-Antoun", "given" : "Sabine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kauser", "given" : "Sophina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Canvin", "given" : "Malcolm", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abernethy", "given" : "Julia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Davies", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hope", "given" : "Russell", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issue" : "July", "issued" : { "date-parts" : [ [ "2014" ] ] }, "publisher-place" : "London, England", "title" : "Annual Epidemiological Commentary : Mandatory MRSA , MSSA and E . coli bacteraemia and C . difficile infection About Public Health England", "type" : "report" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[2]", "plainTextFormattedCitation" : "[2]", "previouslyFormattedCitation" : "[2]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[2].Understanding differences in the epidemiology, in this case seasonality, of community and hospital onset cases of E. coli BSI is important to allow inform the design of control strategies, controlling for factors that differ between hospital and community onset cases. It will also allow us to interpret surveillance data more accurately (allowing trends to be monitored) and to enable interventions to be evaluated in a robust way, controlling for seasonality, or not as appropriate. Likewise, in a country where there is evidence of regional heterogeneity, understanding geographical differences in the epidemiology of E. coli BSI is essential in order to design control measures that can be implemented and evaluated in a robust manner appropriate to each region.The aim of this study was to quantify patterns of seasonality regionally and nationally in E. coli BSI and separately examine the impact in hospital-onset cases.Methods The dataset consisted of mandatory reported details of every BSI with a blood specimen that tested positive for E. coli collected between July 2011 and December 2013 from all National Health Service (NHS) Trusts, of which there were 167 (Trusts are groups of hospitals under the same management), via a web-enabled surveillance system held by Public Health England (PHE) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Gerver", "given" : "Sarah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sinnathamby", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bou-Antoun", "given" : "Sabine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kauser", "given" : "Sophina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Canvin", "given" : "Malcolm", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abernethy", "given" : "Julia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Davies", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hope", "given" : "Russell", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issue" : "July", "issued" : { "date-parts" : [ [ "2014" ] ] }, "publisher-place" : "London, England", "title" : "Annual Epidemiological Commentary : Mandatory MRSA , MSSA and E . coli bacteraemia and C . difficile infection About Public Health England", "type" : "report" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[2]", "plainTextFormattedCitation" : "[2]", "previouslyFormattedCitation" : "[2]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[2]. Details included in our dataset were the dates of admission, date of blood specimen and the hospital code. A case was defined as hospital-onset if the BSI specimen date was on or after the third day, where day one was the date of admission and community-onset if it occurred before, or within two days of admission. We removed from the dataset episodes without admission date, specimen date and hospital site code. We also removed episodes reported from hospitals in one NHS trust with incomplete reporting standards over the period of the dataset. We aggregated the reported data per NHS hospital site by week, using the date of blood specimen as the time of onset of E. coli BSI. We analysed all BSI cases at a national level, as well as community-onset and hospital-onset cases separately, to determine seasonality. We then stratified the dataset and our analyses according to English regions (North of England, Midlands and East of England, London, and South of England). Regional geographical boundaries ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "URL" : "", "accessed" : { "date-parts" : [ [ "2015", "6", "22" ] ] }, "author" : [ { "dropping-particle" : "", "family" : "PHE", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "title" : "Contacts: PHE regions and local centres", "type" : "webpage" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[11]", "plainTextFormattedCitation" : "[11]", "previouslyFormattedCitation" : "[11]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[11], mid year population numbers ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "URL" : "", "accessed" : { "date-parts" : [ [ "2015", "6", "1" ] ] }, "author" : [ { "dropping-particle" : "", "family" : "Office of National Statistics", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2014" ] ] }, "title" : "Office for National Statistics mid-year population estimates", "type" : "webpage" }, "uris" : [ "", "" ] } ], "mendeley" : { "formattedCitation" : "[12]", "plainTextFormattedCitation" : "[12]", "previouslyFormattedCitation" : "[12]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[12] and over night bed availability ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "URL" : "", "accessed" : { "date-parts" : [ [ "2015", "6", "22" ] ] }, "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "0" ] ] }, "title" : "Bed Availability and Occupancy Data \u2013 Overnight", "type" : "webpage" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[13]", "plainTextFormattedCitation" : "[13]", "previouslyFormattedCitation" : "[13]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[13], were used as described previously ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Gerver", "given" : "Sarah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sinnathamby", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bou-Antoun", "given" : "Sabine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kauser", "given" : "Sophina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Canvin", "given" : "Malcolm", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abernethy", "given" : "Julia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Davies", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hope", "given" : "Russell", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issue" : "July", "issued" : { "date-parts" : [ [ "2014" ] ] }, "publisher-place" : "London, England", "title" : "Annual Epidemiological Commentary : Mandatory MRSA , MSSA and E . coli bacteraemia and C . difficile infection About Public Health England", "type" : "report" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[2]", "plainTextFormattedCitation" : "[2]", "previouslyFormattedCitation" : "[2]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[2].We analysed weekly observations of E. coli counts using a generalized additive Poisson model, with a log link using a method that has been described in detail previously ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pone.0099860", "ISSN" : "1932-6203", "PMID" : "24932484", "abstract" : "BACKGROUND: Recent evidence suggests that less than one-quarter of patients with symptomatic nosocomial Clostridium difficile infections (CDI) are linked to other in-patients. However, this evidence was limited to one geographic area. We aimed to investigate the level of symptomatic CDI transmission in hospitals located across England from 2008 to 2012.\n\nMETHODS: A generalized additive mixed-effects Poisson model was fitted to English hospital-surveillance data. After adjusting for seasonal fluctuations and between-hospital variation in reported CDI over time, possible clustering (transmission between symptomatic in-patients) of CDI cases was identified. We hypothesised that a temporal proximity would be reflected in the degree of correlation between in-hospital CDI cases per week. This correlation was modelled through a latent autoregressive structure of order 1 (AR(1)).\n\nFINDINGS: Forty-six hospitals (33 general, seven specialist, and six teaching hospitals) located in all English regions met our criteria. In total, 12,717 CDI cases were identified; seventy-five per cent of these occurred >48 hours after admission. There were slight increases in reports during winter months. We found a low, but statistically significant, correlation between successive weekly CDI case incidences (phi = 0.029, 95%CI: 0.009-0.049). This correlation was five times stronger in a subgroup analysis restricted to teaching hospitals (phi = 0.104, 95%CI: 0.048-0.159).\n\nCONCLUSIONS: The results suggest that symptomatic patient-to-patient transmission has been a source of CDI-acquisition in English hospitals in recent years, and that this might be a more important transmission route in teaching hospitals. Nonetheless, the weak correlation indicates that, in line with recent evidence, symptomatic cases might not be the primary source of nosocomial CDI in England.", "author" : [ { "dropping-particle" : "", "family" : "Kleef", "given" : "Esther", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gasparrini", "given" : "Antonio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guy", "given" : "Rebecca", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cookson", "given" : "Barry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hope", "given" : "Russell", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jit", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Robotham", "given" : "Julie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deeny", "given" : "Sarah R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Edmunds", "given" : "W John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PloS one", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2014", "1" ] ] }, "page" : "e99860", "title" : "Nosocomial transmission of C. difficile in English hospitals from patients with symptomatic infection.", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Goldstein", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "edition" : "4th", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2010" ] ] }, "publisher" : "Wiley-Blackwell", "publisher-place" : "Chichester", "title" : "Multilevel Statistical Models.", "type" : "book" }, "uris" : [ "", "" ] }, { "id" : "ITEM-3", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Wood", "given" : "Simon N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "edition" : "1st", "id" : "ITEM-3", "issued" : { "date-parts" : [ [ "2006" ] ] }, "publisher" : "Chapman and Hall/CRC", "publisher-place" : "London", "title" : "Generalized Additive Models: an introduction with R", "type" : "book" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[14\u201316]", "plainTextFormattedCitation" : "[14\u201316]", "previouslyFormattedCitation" : "[14\u201316]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[14–16]. Two effects were controlled for in the basic model; firstly, hospital was introduced as a categorical variable to allow for differences in weekly counts between hospitals due to differences in size and case-mix. Secondly, a fixed linear polynomial by-hospital interaction term was included to accommodate varying rates of change (primarily increase) over the 131-week period in observed E. coli BSI per site. A seasonal effect was added to the model, using a cyclic periodic penalised cubic regression spline fitted to the week of the year variable. Equations describing the model structure, are provided in the supplementary material. To determine the presence or absence of seasonal variation, the model fit, was compared with and without this seasonal term. The distributional assumption under the null-hypothesis (chi-square) does not have a firm theoretical basis and is conditional on the smoothing parameter (i.e. the degrees of freedom estimated for the smooth term). Therefore the p-value provided by the generalized additive model for the seasonal trend is an approximation ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Wood", "given" : "Simon N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "edition" : "1st", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2006" ] ] }, "publisher" : "Chapman and Hall/CRC", "publisher-place" : "London", "title" : "Generalized Additive Models: an introduction with R", "type" : "book" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[16]", "plainTextFormattedCitation" : "[16]", "previouslyFormattedCitation" : "[16]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[16] and is not the most appropriate method in this context for model fitting. Therefore, to compare model fit, we quantified the reduction in Akaike information criterion (AIC) to determine whether seasonality should be included in the final model. The per hospital, per week impact of seasonality in an average hospital, was quantified by calculating the increase/decrease in number of E. coli BSI relative to the weekly mean for each week of the year, as predicted by the seasonal model. We defined the seasons bounded by the solar solstice and equinox for each year i.e. winter (mid December to mid March), spring (mid March to mid June), summer (mid June to mid September) and autumn (mid September to mid December).We carried out the statistical analysis on all data, and then restricted the dataset to hospital-onset E. coli BSI and repeated for community-onset cases. In each case we examined the full national dataset and then carried out the same analysis for each region. All analyses were performed with R 3.0.1 (Team R Development Core, website: ) using the R package mgcv ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "URL" : "", "author" : [ { "dropping-particle" : "", "family" : "Wood", "given" : "Author Simon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wood", "given" : "Maintainer Simon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "edition" : "1.8-6", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2015" ] ] }, "publisher" : "CRAN", "publisher-place" : "Bath", "title" : "Mixed GAM Computation Vehicle with GCV/AIC/REML Smoothness Estimation", "type" : "webpage" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[17]", "plainTextFormattedCitation" : "[17]", "previouslyFormattedCitation" : "[17]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[17] and splines ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "URL" : "", "author" : [ { "dropping-particle" : "", "family" : "Bates", "given" : "Douglas M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Venables", "given" : "William N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "1999" ] ] }, "number" : "2.07", "title" : "splines: Regression Spline Functions and Classes", "type" : "webpage" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[18]", "plainTextFormattedCitation" : "[18]", "previouslyFormattedCitation" : "[18]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[18].ResultsBetween 1st July 2011 and 31st December 2013, 82,136 cases of E. coli BSI were reported to the E. coli mandatory surveillance database by 11th November 2013. When the dataset was restricted to those with complete information and NHS trusts with full reporting there were 79,155 cases of E. coli BSI remaining. In the restricted dataset, 25% (19,374/79,155) of cases occurred two or more days after admission and were defined as hospital-onset cases. Between 1st July 2011 and 31st June 2013 there was a 5% increase in total annual E. coli BSI reported. The average number of cases reported per week increased from 606 in 2011/2012, to 629 in 2012/2013. When adjusted for the mid-year resident population size ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "URL" : "", "accessed" : { "date-parts" : [ [ "2015", "6", "22" ] ] }, "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "0" ] ] }, "title" : "Bed Availability and Occupancy Data \u2013 Overnight", "type" : "webpage" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Gerver", "given" : "Sarah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sinnathamby", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bou-Antoun", "given" : "Sabine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kauser", "given" : "Sophina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Canvin", "given" : "Malcolm", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abernethy", "given" : "Julia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Davies", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hope", "given" : "Russell", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-2", "issue" : "July", "issued" : { "date-parts" : [ [ "2014" ] ] }, "publisher-place" : "London, England", "title" : "Annual Epidemiological Commentary : Mandatory MRSA , MSSA and E . coli bacteraemia and C . difficile infection About Public Health England", "type" : "report" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "URL" : "", "accessed" : { "date-parts" : [ [ "2015", "6", "1" ] ] }, "author" : [ { "dropping-particle" : "", "family" : "Office of National Statistics", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-3", "issued" : { "date-parts" : [ [ "2014" ] ] }, "title" : "Office for National Statistics mid-year population estimates", "type" : "webpage" }, "uris" : [ "", "" ] } ], "mendeley" : { "formattedCitation" : "[2,12,13]", "plainTextFormattedCitation" : "[2,12,13]", "previouslyFormattedCitation" : "[2,12,13]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[2,12,13], the North had the greatest number of reported cases over the timescale of the study (199 per 100,000 persons), further details provided in Table 1. Table SEQ Table \* ARABIC 1: Description of E. coli BSI data from eligible NHS Trusts. NTotal cases per 100,000 populationaCases per 100,000 bed daysaMedian/Mean All cases p.h. p.w.bInter-quartile range(Q1-Q3)Number of weeks131----All Cases79,155147.979.23/3.22-4National Hospital Onset Cases (HOC)19,37436.222.251/1.51-2PHE Region and Centre(All/HOC)(All/HOC)(All/HOC)AllAllLondonc11,910/ 3,162143.35/38.088.87/2.353/2.881-4Midlands and East of England22,461/5,004533/11637/83/3.432-5North of England26,715/7,135880/23246/123/3.332-4South of England18,069/4,072646/14845/103/2.982-5a Denominator data taken from ONS mid year population size [9] and NHS available bed days [10] as described in [6].b p.h. per hospital, p.w. per week, c London is an integrated PHE region and Centre A model which included seasonal variation and a linear increase in E. coli BSI over time provided the best description of the weekly data nationally as measured by AIC. We estimated statistically significant weekly increase during the summer season of 0.06 (0.02, 0.10) cases of E. coli BSI per week using this model. We estimated that with a mean of 3.25 E. coli BSI per hospital per week, this would increase to a mean of 3.31 E. coli BSI cases per week in summer, leading to, when summed over the season, an extra 0.5 cases per hospital for the total summer period and 0.5 fewer cases per hospital each winter.The results for each region are provided in Figure 1. and Table 2. Seasonality improved the fit of model, when measured by AIC (from AIC value of 29,816 to 29,778), in the North (Table 2). There was a much smaller improvement in AIC for the Midlands (from AIC value of 24,755 to 24,737), South (from AIC value of 21,904 to 21,883) and London (from AIC value of 14,581 to 14,577). When we quantified the weekly impact of seasonality, this was statistically significant in the North of England only, as shown in Figure 1. and Table 2. We then examined the hospital-onset cases only, adding a seasonal component to this statistical model did not improve the fit as measured by AIC, (Figure 1. and Table 2) indicating that seasonality did not effect the variation in this group. Given that there was no evidence for seasonality in the hospital-onset E. coli and they constituted only 25% of the full dataset, it is reasonable to assume that any seasonal effects in the dataset arise from community cases of E. coli. This was confirmed by results from analysis of community-onset cases only which did not differ from that of the whole dataset (data not shown).Figure 1. Seasonal variation of E. coli BSI. Fitted cyclic penalised cubic regression spline (representing seasonal variations) for the linear model fitted to weekly reported counts of national E. coli BSI all cases (National) and hospital onset cases (National-Hospital onset). All E. coli BSI in each region (North, Midlands and East, South, London), with 95% CI plotted as dashed lines and mean expected value, plotted as a solid horizontal line with y intercept of 1. All plotted on the normal scale.Table 2. Modela results: predicted impact of seasonal trends.Additional E. coli BSI p.w. p.h. at maximum week of yearbReduction in numbers of E. coli BSI p.w. p.h. at minimum week of year Peak/Trough Season mean (95% CI)mean (95% CI)National (All)0.06 (0.02, 0.10)-0.07 (-0.11, -0.03)Summer/AutumnNational Hospital Onset Cases (HOC)0 (-0.03, 0.03)0 (-0.03, 0.03)NonecNational Late Onset Cases (LOC)0 (-0.03, 0.04)0 (-0.03, 0.04)NonecRegion (LOC and HOC cases)Londond0.03 (-0.03, 0.09)-0.03 (-0.09, 0.04)Summer/Autumn Midlands and East of England0.05 (-0.01, 0.11)-0.05 (-0.1, 0.01)Summer/WinterNorth of England 0.07 (0.01, 0.14)-0.09 (-0.16, -0.02)Summer/AutumnSouth of England0.03 (-0.03, 0.1)-0.04 (-0.1, 0.03)Summer/WinteraModel: hospital (categorical variable), linear polynomial cyclic and periodic penalised cubic regression spline bp.h. per hospital, p.w. per week, c No seasonality, determined by: no change in AIC of model with inclusion of seasonal spline d London is an integrated PHE region and CentreDiscussionWe show for the first time that seasonality is not observed in hospital-onset cases of E. coli BSI. We have also shown the regional variation in the impact of seasonality on E. coli BSI rates and that the clinical impact of seasonal variation was modest. From our findings, any national indication of seasonality in the overall data in England is due to seasonal increases predominantly in the North of England and in community-onset cases. Our findings contrast with international studies ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pone.0091105", "ISSN" : "1932-6203", "PMID" : "24599500", "abstract" : "BACKGROUND: We investigated the relationship between average monthly temperature and the most common clinical pathogens causing infections in intensive care patients.\n\nMETHODS: A prospective unit-based study in 73 German intensive care units located in 41 different hospitals and 31 different cities with total 188,949 pathogen isolates (102,377 Gram-positives and 86,572 Gram-negatives) from 2001 to 2012. We estimated the relationship between the number of clinical pathogens per month and the average temperature in the month of isolation and in the month prior to isolation while adjusting for confounders and long-term trends using time series analysis. Adjusted incidence rate ratios for temperature parameters were estimated based on generalized estimating equation models which account for clustering effects.\n\nRESULTS: The incidence density of Gram-negative pathogens was 15% (IRR 1.15, 95%CI 1.10-1.21) higher at temperatures \u2265 20\u00b0C than at temperatures below 5\u00b0C. E. cloacae occurred 43% (IRR=1.43; 95%CI 1.31-1.56) more frequently at high temperatures, A. baumannii 37% (IRR=1.37; 95%CI 1.11-1.69), S. maltophilia 32% (IRR=1.32; 95%CI 1.12-1.57), K. pneumoniae 26% (IRR=1.26; 95%CI 1.13-1.39), Citrobacter spp. 19% (IRR=1.19; 95%CI 0.99-1.44) and coagulase-negative staphylococci 13% (IRR=1.13; 95%CI 1.04-1.22). By contrast, S. pneumoniae 35% (IRR=0.65; 95%CI 0.50-0.84) less frequently isolated at high temperatures. For each 5\u00b0C increase, we observed a 3% (IRR=1.03; 95%CI 1.02-1.04) increase of Gram-negative pathogens. This increase was highest for A. baumannii with 8% (IRR=1.08; 95%CI 1.05-1.12) followed by K. pneumoniae, Citrobacter spp. and E. cloacae with 7%.\n\nCONCLUSION: Clinical pathogens vary by incidence density with temperature. Significant higher incidence densities of Gram-negative pathogens were observed during summer whereas S. pneumoniae peaked in winter. There is increasing evidence that different seasonality due to physiologic changes underlies host susceptibility to different bacterial pathogens. Even if the underlying mechanisms are not yet clear, the temperature-dependent seasonality of pathogens has implications for infection control and study design.", "author" : [ { "dropping-particle" : "", "family" : "Schwab", "given" : "Frank", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gastmeier", "given" : "Petra", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyer", "given" : "Elisabeth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PloS one", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2014", "1" ] ] }, "page" : "e91105", "title" : "The warmer the weather, the more gram-negative bacteria - impact of temperature on clinical isolates in intensive care units.", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1371/journal.pone.0025298", "ISSN" : "1932-6203", "PMID" : "21966489", "abstract" : "BACKGROUND: Knowledge of seasonal trends in hospital-associated infection incidence may improve surveillance and help guide the design and evaluation of infection prevention interventions. We estimated seasonal variation in the frequencies of inpatient bloodstream infections (BSIs) caused by common bacterial pathogens and examined associations of monthly BSI frequencies with ambient outdoor temperature, precipitation, and humidity levels.\n\nMETHODS: A database containing blood cultures from 132 U.S. hospitals collected between January 1999 and September 2006 was assembled. The database included monthly counts of inpatient blood cultures positive for several clinically important Gram-negative bacteria (Acinetobacter spp, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa) and Gram-positive bacteria (Enterococcus spp and Staphylococcus aureus). Monthly mean temperature, total precipitation, and mean relative humidity in the postal ZIP codes of participating hospitals were obtained from national meteorological databases.\n\nRESULTS: A total of 211,697 inpatient BSIs were reported during 9,423 hospital-months. Adjusting for long-term trends, BSIs caused by each gram-negative organism examined were more frequent in summer months compared with winter months, with increases ranging from 12.2% for E. coli (95% CI 9.2-15.4) to 51.8% for Acinetobacter (95% CI 41.1-63.2). Summer season was associated with 8.7% fewer Enterococcus BSIs (95% CI 11.0-5.8) and no significant change in S. aureus BSI frequency relative to winter. Independent of season, monthly humidity, monthly precipitation, and long-term trends, each 5.6\u00b0C (10\u00b0F) rise in mean monthly temperature corresponded to increases in gram-negative bacterial BSI frequencies ranging between 3.5% for E. coli (95% CI 2.1-4.9) to 10.8% for Acinetobacter (95% CI 6.9-14.7). The same rise in mean monthly temperature corresponded to an increase of 2.2% in S. aureus BSI frequency (95% CI 1.3-3.2) but no significant change in Enterococcus BSI frequency.\n\nCONCLUSIONS: Summer season and higher mean monthly outdoor temperature are associated with substantially increased frequency of BSIs, particularly among clinically important gram-negative bacteria.", "author" : [ { "dropping-particle" : "", "family" : "Eber", "given" : "Michael R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shardell", "given" : "Michelle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schweizer", "given" : "Marin L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Laxminarayan", "given" : "Ramanan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perencevich", "given" : "Eli N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PloS one", "id" : "ITEM-2", "issue" : "9", "issued" : { "date-parts" : [ [ "2011", "1" ] ] }, "page" : "e25298", "title" : "Seasonal and temperature-associated increases in gram-negative bacterial bloodstream infections among hospitalized patients.", "type" : "article-journal", "volume" : "6" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1086/592698", "ISSN" : "0899-823X", "author" : [ { "dropping-particle" : "", "family" : "Perencevich", "given" : "Eli N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McGregor", "given" : "Jessina C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shardell", "given" : "Michelle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Furuno", "given" : "Jon P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Harris", "given" : "Anthony D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris, Jr.", "given" : "J. Glenn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fisman", "given" : "David N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johnson", "given" : "Judith A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Infection Control and Hospital Epidemiology", "id" : "ITEM-3", "issue" : "12", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "1124-1131", "title" : "Summer Peaks in the Incidences of Gram Negative Bacterial Infection Among Hospitalized Patients", "type" : "article-journal", "volume" : "29" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Al-Hasan", "given" : "M.N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lahr", "given" : "B D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eckel-Passow", "given" : "J.E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baddour", "given" : "L M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical Microbiology and Infection", "id" : "ITEM-4", "issue" : "10", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "7-10", "title" : "Seasonal variation in Escherichia coli bloodstream infection : a population-based study", "type" : "article-journal", "volume" : "15" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[5\u20138]", "plainTextFormattedCitation" : "[5\u20138]", "previouslyFormattedCitation" : "[5\u20138]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[5–8], which have emphasised the importance of seasonality in the occurrence of Gram negative infections. In explaining the findings from previous research, the authors suggested that warmer temperatures encourage E. coli bacterial growth, persistence or virulence, or an increase in dehydration related E. coli UTI ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pone.0025298", "ISSN" : "1932-6203", "PMID" : "21966489", "abstract" : "BACKGROUND: Knowledge of seasonal trends in hospital-associated infection incidence may improve surveillance and help guide the design and evaluation of infection prevention interventions. We estimated seasonal variation in the frequencies of inpatient bloodstream infections (BSIs) caused by common bacterial pathogens and examined associations of monthly BSI frequencies with ambient outdoor temperature, precipitation, and humidity levels.\n\nMETHODS: A database containing blood cultures from 132 U.S. hospitals collected between January 1999 and September 2006 was assembled. The database included monthly counts of inpatient blood cultures positive for several clinically important Gram-negative bacteria (Acinetobacter spp, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa) and Gram-positive bacteria (Enterococcus spp and Staphylococcus aureus). Monthly mean temperature, total precipitation, and mean relative humidity in the postal ZIP codes of participating hospitals were obtained from national meteorological databases.\n\nRESULTS: A total of 211,697 inpatient BSIs were reported during 9,423 hospital-months. Adjusting for long-term trends, BSIs caused by each gram-negative organism examined were more frequent in summer months compared with winter months, with increases ranging from 12.2% for E. coli (95% CI 9.2-15.4) to 51.8% for Acinetobacter (95% CI 41.1-63.2). Summer season was associated with 8.7% fewer Enterococcus BSIs (95% CI 11.0-5.8) and no significant change in S. aureus BSI frequency relative to winter. Independent of season, monthly humidity, monthly precipitation, and long-term trends, each 5.6\u00b0C (10\u00b0F) rise in mean monthly temperature corresponded to increases in gram-negative bacterial BSI frequencies ranging between 3.5% for E. coli (95% CI 2.1-4.9) to 10.8% for Acinetobacter (95% CI 6.9-14.7). The same rise in mean monthly temperature corresponded to an increase of 2.2% in S. aureus BSI frequency (95% CI 1.3-3.2) but no significant change in Enterococcus BSI frequency.\n\nCONCLUSIONS: Summer season and higher mean monthly outdoor temperature are associated with substantially increased frequency of BSIs, particularly among clinically important gram-negative bacteria.", "author" : [ { "dropping-particle" : "", "family" : "Eber", "given" : "Michael R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shardell", "given" : "Michelle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schweizer", "given" : "Marin L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Laxminarayan", "given" : "Ramanan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perencevich", "given" : "Eli N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PloS one", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2011", "1" ] ] }, "page" : "e25298", "title" : "Seasonal and temperature-associated increases in gram-negative bacterial bloodstream infections among hospitalized patients.", "type" : "article-journal", "volume" : "6" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[6]", "plainTextFormattedCitation" : "[6]", "previouslyFormattedCitation" : "[6]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[6]. We would suggest that any interventions focusing solely on preventing seasonal drivers of E. coli infections (i.e. prevention of dehydration and UTI in the summer months only) are unlikely to have a significant clinical impact on the occurrence of BSI in most regions of England and limited impact on hospital-onset cases. Our analysis had several limitations; first, we did not analyse temperature and humidity in our study. Given that seasonality was most pronounced in the North of England, we would suggest that a simple association between higher temperatures and increased infection rates does not seem to hold in England. Additionally, we suggest that purely meteorological factors could not explain the lack of seasonality seen in hospital-onset cases. Secondly, we did not include information as to patient co-morbidities and age in our analysis. However, controlling for between hospitals variation will control for patient related case-mix and the average age of patients with E. coli BSI does not vary significantly with season. Thirdly, we had no information as to the antibiotic resistance profile of the E. coli isolates, this may play an important role in regional variation seen in the analysis and will be an important subject for future research, though any potential impact on variation in seasonality is unclear. Finally, and most importantly, as reporting of E. coli infection cases is only mandatory for BSI, we are certainly underestimating the total burden of E. coli infection and reservoirs of transmission from UTI ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/1469-0691.12757", "ISSN" : "1198743X", "author" : [ { "dropping-particle" : "", "family" : "Nabet", "given" : "C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raoult", "given" : "D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical Microbiology and Infection", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "792-793", "title" : "The hidden epidemic of Escherichia coli", "type" : "article-journal", "volume" : "20" }, "uris" : [ "", "" ] } ], "mendeley" : { "formattedCitation" : "[1]", "plainTextFormattedCitation" : "[1]", "previouslyFormattedCitation" : "[1]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[1]. ConclusionIn conclusion, we believe our findings highlight the need to understand distinct community and hospital dynamics of E. coli, including UTI and other infectionsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/1469-0691.12757", "ISSN" : "1198743X", "author" : [ { "dropping-particle" : "", "family" : "Nabet", "given" : "C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raoult", "given" : "D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical Microbiology and Infection", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "792-793", "title" : "The hidden epidemic of Escherichia coli", "type" : "article-journal", "volume" : "20" }, "uris" : [ "", "" ] } ], "mendeley" : { "formattedCitation" : "[1]", "plainTextFormattedCitation" : "[1]", "previouslyFormattedCitation" : "[1]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[1]. Furthermore, as seasonal variation does not explain regional differences in hospital and community onset E. coli, more research is required. Firstly on the demographic, socio-economic and microbiological variation which may drive regional differences, and secondly to explore local variation in clinical and antibiotic prescribing practice in the community and the hospital, to ultimately understand and stem the increasing burden of E.coli infection.AcknowledgementsWe wish to thank all NHS hospitals and laboratories who have contributed data to the mandatory surveillance scheme for E. coli bacteraemia. This research has received funding (SRD, JVR and EvK) from the European Community’s Seventh Framework Programme FP7/2007-2013 under agreement no. 282512. The research was partially funded by the National Institute for Health Research (NIHR) Health Protection Research Unit (HPRU) in Healthcare Associated Infection and Antimicrobial Resistance at Imperial College London in partnership with Public Health England (PHE), and the UK National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Modelling Methodology at Imperial College London in partnership with Public Health England (PHE) [grant number HPRU-2012-10080]. Transparency DeclarationsNone of the authors has any financial conflicts of interest to declare. The funding bodies had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, the Department of Health or Public Health England.ReferencesADDIN Mendeley Bibliography CSL_BIBLIOGRAPHY [1]Nabet C, Raoult D. The hidden epidemic of Escherichia coli. Clin Microbiol Infect 2014;20:792–3. doi:10.1111/1469-0691.12757.[2]Gerver S, Sinnathamby M, Bou-Antoun S, Kauser S, Canvin M, Abernethy J, et al. Annual Epidemiological Commentary?: Mandatory MRSA , MSSA and E . coli bacteraemia and C . difficile infection About Public Health England. London, England: 2014.[3]Abernethy JK, Johnson AP, Guy R, Hinton N, Sheridan EA, Hope RJ. Thirty day all-cause mortality in patients with Escherichia coli bacteraemia in England. Clin Microbiol Infect 2015;21:251.e1–251.e8. doi:.[4]Schlackow I, Stoesser N, Walker a S, Crook DW, Peto TE a, Wyllie DH. Increasing incidence of Escherichia coli bacteraemia is driven by an increase in antibiotic-resistant isolates: electronic database study in Oxfordshire 1999-2011. J Antimicrob Chemother 2012;67:1514–24. doi:10.1093/jac/dks082.[5]Schwab F, Gastmeier P, Meyer E. The warmer the weather, the more gram-negative bacteria - impact of temperature on clinical isolates in intensive care units. PLoS One 2014;9:e91105. doi:10.1371/journal.pone.0091105.[6]Eber MR, Shardell M, Schweizer ML, Laxminarayan R, Perencevich EN. Seasonal and temperature-associated increases in gram-negative bacterial bloodstream infections among hospitalized patients. PLoS One 2011;6:e25298. doi:10.1371/journal.pone.0025298.[7]Perencevich EN, McGregor JC, Shardell M, Furuno JP, Harris AD, Morris, Jr. JG, et al. Summer Peaks in the Incidences of Gram Negative Bacterial Infection Among Hospitalized Patients. Infect Control Hosp Epidemiol 2008;29:1124–31. doi:10.1086/592698.[8]Al-Hasan MN, Lahr BD, Eckel-Passow JE, Baddour LM. Seasonal variation in Escherichia coli bloodstream infection?: a population-based study. Clin Microbiol Infect 2009;15:7–10.[9]Chazan B, Colodner R, Edelstein H, Raz R. Seasonal variation in Escherichia coli bloodstream infections in northern Israel. Clin Microbiol Infect 2011;17:851–4. doi:10.1111/j.1469-0691.2010.03327.x.[10]Wilson J, Elgohari S, Livermore DM, Cookson B, Johnson A, Lamagni T, et al. Trends among pathogens reported as causing bacteraemia in England , 2004–2008. Clin Microbiol Infect 2011;17:451–8. doi:10.1111/j.1469-0691.2010.03262.x.[11]PHE. Contacts: PHE regions and local centres 2013. (accessed June 22, 2015).[12]Office of National Statistics. Office for National Statistics mid-year population estimates 2014. (accessed June 1, 2015).[13]Bed Availability and Occupancy Data – Overnight n.d. (accessed June 22, 2015).[14]Van Kleef E, Gasparrini A, Guy R, Cookson B, Hope R, Jit M, et al. Nosocomial transmission of C. difficile in English hospitals from patients with symptomatic infection. PLoS One 2014;9:e99860. doi:10.1371/journal.pone.0099860.[15]Goldstein H. Multilevel Statistical Models. 4th ed. Chichester: Wiley-Blackwell; 2010.[16]Wood SN. Generalized Additive Models: an introduction with R. 1st ed. London: Chapman and Hall/CRC; 2006.[17]Wood AS, Wood MS. Mixed GAM Computation Vehicle with GCV/AIC/REML Smoothness Estimation 2015. .[18]Bates DM, Venables WN. splines: Regression Spline Functions and Classes 1999. . ................
................

In order to avoid copyright disputes, this page is only a partial summary.

Google Online Preview   Download