- Email: [email protected]
Regional point prevalence study of healthcare-associated infections and antimicrobial use in acute care hospitals in Liguria, Italy
Accepted Manuscript Regional point prevalence study of healthcare-associated infections and antimicrobial use in acute care hospitals in Liguria, Italy Camilla Sticchi, Marisa Alberti, Stefania Artioli, Marina Assensi, Ivana Baldelli, Angela Battistini, Silvia Boni, Giovanni Cassola, Elio Castagnola, Mauro Cattaneo, Nadia Cenderello, Maria Luisa Cristina, Anna Maria De Mite, Paola Fabbri, Francesca Federa, Daniele Roberto Giacobbe, Daniela La Masa, Carolina Lorusso, Karine Marioni, VitaMaria Masi, Bruno Mentore, Silvana Montoro, Andrea Orsi, Doranna Raiteri, Rosamaria Riente, Ines Samengo, Claudio Viscoli, Roberto Carloni, Cristiano Alicino, Ilaria Barberis, Dorotea Bellina, Maria Paola Crisalli, Valerio Daturi, Anna Maria Di Bella, Valeria Faccio, Federico Grammatico, Barbara Guglielmi, Giancarlo Icardi, Laura Magnasco, Alessandra Morando, Chiara Paganino, Carolina Saffioti, Paola Sansone, Marco Santini, Giovanni Sarteschi, Antonella Talamini, Marco Tomei, Riccardo Ungaro PII:
S0195-6701(17)30679-5
DOI:
10.1016/j.jhin.2017.12.008
Reference:
YJHIN 5300
To appear in:
Journal of Hospital Infection
Received Date: 3 August 2017 Accepted Date: 8 December 2017
Please cite this article as: Sticchi C, Alberti M, Artioli S, Assensi M, Baldelli I, Battistini A, Boni S, Cassola G, Castagnola E, Cattaneo M, Cenderello N, Cristina ML, De Mite AM, Fabbri P, Federa F, Giacobbe DR, La Masa D, Lorusso C, Marioni K, Masi V, Mentore B, Montoro S, Orsi A, Raiteri D, Riente R, Samengo I, Viscoli C, Carloni R, The Collaborative Group for the Point Prevalence Survey of healthcare-associated infections in Liguria, Alicino C, Barberis I, Bellina D, Crisalli MP, Daturi V, Di Bella AM, Faccio V, Grammatico F, Guglielmi B, Icardi G, Magnasco L, Morando A, Paganino C, Saffioti C, Sansone P, Santini M, Sarteschi G, Talamini A, Tomei M, Ungaro R, Regional point prevalence study of healthcare-associated infections and antimicrobial use in acute care hospitals in Liguria, Italy, Journal of Hospital Infection (2018), doi: 10.1016/j.jhin.2017.12.008.
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ACCEPTED MANUSCRIPT Regional point prevalence study of healthcare-associated infections and antimicrobial use in acute care hospitals in Liguria, Italy Camilla Sticchi* - Infectious Diseases, Epidemiology and Prevention, Health Regional Agency,
Marisa Alberti - International Evangelical Hospital, Genoa, Italy Stefania Artioli - ASL 5 Spezzino, La Spezia, Italy Marina Assensi - ASL1 Imperiese, Imperia, Italy
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Ivana Baldelli - IRCCS Giannina Gaslini Institute, Genoa, Italy
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Liguria, Italy
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Angela Battistini - San Martino Polyclinic Hospital, Genoa, Italy Silvia Boni - ASL 5 Spezzino, La Spezia, Italy
Giovanni Cassola - Infectious Diseases Unit, Galliera Hospital, Genoa, Italy Elio Castagnola - Infectious Diseases Unit, Giannina Gaslini Institute, Genoa, Italy Mauro Cattaneo - ASL 3 Genovese, Genoa, Italy
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Nadia Cenderello - Galliera Hospital, Genoa, Italy Maria Luisa Cristina - Galliera Hospital, Genoa, Italy Anna Maria De Mite - ASL 3 Genovese, Genoa, Italy
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Paola Fabbri - Galliera Hospital, Genoa, Italy
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Francesca Federa - ASL 3 Genovese, Genoa, Italy Daniele Roberto Giacobbe - Infectious Diseases Unit, San Martino Polyclinic Hospital, University of Genoa, Italy
Daniela La Masa - IRCCS Giannina Gaslini Institute, Genoa, Italy Carolina Lorusso - ASL 4 Chiavarese, Genoa, Italy Karine Marioni - ASL 5 Spezzino, La Spezia, Italy VitaMaria Masi - International Evangelical Hospital, Genoa, Italy Bruno Mentore - ASL 4 Chiavarese, Genoa, Italy 1
ACCEPTED MANUSCRIPT Silvana Montoro - ASL1 Imperiese, Imperia, Italy Andrea Orsi - San Martino Polyclinic Hospital, University of Genoa, Italy Doranna Raiteri - Santa Corona Hospital, Pietra Ligure, Savona, Italy Rosamaria Riente - San Paolo Hospital, Savona, Italy
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Ines Samengo- ASL 4 Chiavarese, Genoa, Italy
Claudio Viscoli - Infectious Diseases Unit, San Martino Polyclinic Hospital, University of Genoa, Italy
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Roberto Carloni - Infectious Diseases, Epidemiology and Prevention, Health Regional Agency,
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Liguria, Italy
The Collaborative Group for the Point Prevalence Survey of healthcare-associated infections in Liguria:
Cristiano Alicino - University of Genoa, Italy
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Ilaria Barberis - University of Genoa, Italy
Dorotea Bellina - San Martino Polyclinic Hospital, Genoa, Italy Maria Paola Crisalli - Galliera Hospital, Genoa, Italy
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Valerio Daturi - San Martino Polyclinic Hospital, Genoa, Italy Anna Maria Di Bella - San Martino Polyclinic Hospital, Genoa, Italy
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Valeria Faccio - University of Genoa, Italy Federico Grammatico - University of Genoa, Italy Barbara Guglielmi - San Martino Polyclinic Hospital, Genoa, Italy Giancarlo Icardi - San Martino Polyclinic Hospital, University of Genoa, Italy Laura Magnasco - University of Genoa, Italy Alessandra Morando - San Martino Polyclinic Hospital, Genoa, Italy Chiara Paganino - University of Genoa, Italy
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ACCEPTED MANUSCRIPT Carolina Saffioti - University of Genoa, Italy Paola Sansone - Galliera Hospital, Genoa, Italy Marco Santini - Galliera Hospital, Genoa, Italy
Antonella Talamini - San Martino Polyclinic Hospital, Genoa, Italy Marco Tomei - San Martino Polyclinic Hospital, Genoa, Italy
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Riccardo Ungaro - University of Genoa, Italy
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Giovanni Sarteschi - University of Genoa, Italy
* Corresponding author. Address: Health Regional Agency, Liguria, Italy, Section of Epidemiology
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and Prevention, Piazza della Vittoria 15, 16121 Genoa, Italy. Tel: +39 010 5488212.
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E-mail address: [email protected]
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ACCEPTED MANUSCRIPT SUMMARY Background: In the light of the importance of monitoring healthcare-associated infections (HAI) and the consumption of antibiotics, a regional point prevalence survey was conducted in Liguria between March and April 2016.
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Aim: The aim of the study was to measure the overall prevalence of HAI and describe the use of antibiotics in all public hospitals.
Methods: Data on risk factors and use of antibiotics were collected for each hospitalised patient. To
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define the variables significantly associated with HAI, univariate and multivariate analyses were conducted. Standardized Infection Ratio (SIR) and Standardized Antimicrobial Use Ratio (SAUR)
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were measured for each participating hospital.
Findings: A total of 3,647 patients were enrolled. Four hundred twenty-nine HAIs were diagnosed in 376 patients, giving a prevalence of HAI of 10.3%. Respiratory tract (21.7%) and urinary tract (20%) were the most frequent sites of infection.
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High rates of meticillin-resistant Staphylococcus aureus (47.4%) and Enterobacteriaceae resistant to carbapenems (26.3%) were isolated.
Forty-six percent of patients received at least one antibiotic. Combinations of penicillins including
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beta-lactamase inhibitors (24.1%) were the most commonly used; the main indication (46.7%) was the treatment of a community-acquired infection.
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Conclusions: Our results showed an increase in HAI prevalence compared to a similar survey conducted in 2007; however, the performance of overlapping investigations will enable more reliable considerations. Nevertheless, data on antimicrobial resistance and use of antibiotics are consistent with the national trend. Despite methodological limitations, prevalence studies are useful to monitor HAI over time and encourage greater awareness of the problem in all stakeholders.
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ACCEPTED MANUSCRIPT Key words: healthcare-associated infections, point prevalence study, antibiotic resistance, antimicrobial use
INTRODUCTION
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The World Health Organization (WHO) and the European Centre for Disease Prevention and Control (ECDC) have repeatedly stressed the relevance and global spread of the phenomenon of healthcare-associated infections (HAIs) and antimicrobial resistance, recognized as significant
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danger to public health requiring specific interventions.1
In order to estimate the overall impact of HAI and to describe the consumption of antibiotics in
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Europe, ECDC has developed a protocol for the study of point prevalence (ECDC PPS) of HAIs and the use of antibiotics in acute care hospitals, providing a standardized methodology for Member States and hospitals that would allow a comparison of data collected in different countries.2 The first European survey, conducted in Europe in the years 2011-2012, showed a prevalence of
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infections in Italy of 6.3%, in line with the European average, although in our country multidrugresistant microorganisms cause many of these infections. 3 In Liguria, an administrative region in northwestern Italy, a prevalence study on a regional basis
of 9.8%.4
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was carried on for the first time between March and April 2007, showing a prevalence of infections
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The National Prevention Plan 2014-2018 emphasizes the importance of having information on HAIs in all health units and of monitoring the consumption of antibiotics. Liguria, in its Regional Prevention Plan, is committed to launch a systematic methodology through repeated regional prevalence studies every year, to get comparable information over time and with other European countries. In this context, a point prevalence survey was performed in 2016 in all adult and paediatric acutecare hospitals in our region, applying the protocol provided by the ECDC. The objectives of the
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ACCEPTED MANUSCRIPT study were to estimate the overall prevalence of HAIs and the use of antibiotics in acute care hospitals in Liguria, describe patients, invasive procedures, infections (sites, involved microorganisms, including antibiotic-resistance markers) and how antibiotics are used and the
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reasons why they are prescribed.
METHODS Study design and setting
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The study enrolled any public acute hospital, both small (<200 beds), medium (200-500 beds) and large size (>500 beds).
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According to ECDC PPS protocol version 4.3, all wards had to be involved with the exception of the long term care departments of acute care facilities. Nevertheless, similarly to some European countries (France, the Netherlands and Spain) using an adapted version of the ECDC PPS protocol, some rehabilitation wards of acute care hospitals were included in our surveillance.3
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Case definitions and data collection
The criteria for definition of HAIs and antibiotics use are those provided by the ECDC PPS protocol version 4.3.
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The survey was completed in one day in each ward and did not exceed three weeks for the whole hospital. The data were collected by infection control staff, consulting clinical documentation with
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the support of the ward's medical and nursing staff, and included patient’s personal data (sex and age), ward specialty, risk factors for all patients, infected or not, i.e. surgery since admission, both NHSN and not (the first corresponding to the surgical procedure monitored by the National Healthcare Safety Network), exposure to invasive devices and the McCabe severity of illness score.5 HAI data included HAI type, the origin of HAI, the date of onset for HAI if not present on admission, isolated microorganisms and selected antimicrobial resistance.
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ACCEPTED MANUSCRIPT Data on antimicrobial use included the antimicrobial agent, the route of administration, the indication for prescription and the site of infection if the indication was the treatment of an established infection. Antimicrobial agents for systemic use as well as non-absorbable anti-infectives, dermatological
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antifungals, antibacterials, antimycotics, antimycobacterials for treatment of mycobacteria other than tuberculosis and nitroimidazole-derived antiprotozoals were included, while antiviral agents and antimicrobials for the treatment of tuberculosis were not included.
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Data entry and statistical analysis
To facilitate data entry at hospital level, the ECDC freeware software HelicsWin.Net V3.0 was
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used.
The prevalence of HAIs and of antimicrobial use was reported as the percentage of patients with at least one HAI or receiving at least one antimicrobial agent, respectively. Univariate and multivariate analyses were carried out in order to assess the risk of developing HAIs.
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The association between HAIs and each risk factor was evaluated by calculating the odds ratio (OR) and 95% confidence intervals (95% CI). To assess the independent role of risk factors, variables with a P value < 0.05 in univariate comparisons were included in a multivariate logistic regression
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model.
Statistical analyses were performed with Epi-Info v. 3.5 (CDC, USA) and JMP v. 10.0 (SAS
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Institute, USA).
To compare hospitals with different patient characteristics (age, pre-study length of stay, surgery, McCabe score and invasive devices), a risk model based on the total population enrolled in Liguria was applied. Standardized Infection Ratios (SIRs) and Standardized Antimicrobial Use Ratios (SAURs) were calculated as observed over expected rate of patients with at least one infection or at least one antimicrobial, respectively.
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ACCEPTED MANUSCRIPT RESULTS Description of the enrolled population The study was conducted between 22th March and 22th April 2016. A total of 3,647 patients were enrolled in 18 participating hospitals. The median number of patients per hospital was 145 (SD:
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201.5; IQR: 187.5). As shown in Table I, most patients (48.0%) were enrolled in medical wards followed by 17.8% in surgical wards and 4.9% in intensive care units; mean age of the population investigated was 64.2 years (SD: 25.1; range: 0-101).
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At least one invasive device was placed in 2,591 patients enrolled (71%), 57.4% of patients had a
catheter (CVC) and 2.7% were intubated.
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peripheral vascular catheter (PVC), 28.4% a urinary catheter (UC), 12.6% a central vascular
The median length of hospital stay was 7 days (SD: 20.2; range: 0-289; IQR: 13.0), ranging from three days in gynaecology-obstetrics wards (SD: 10.3; range: 0-95 IQR: 4.5) to 26 days in rehabilitation (SD: 51.5; range: 0-289 IQR: 47.0).
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According to the McCabe score, 60.8% of the studied patients presented with a basic non-fatal disease, 20% had a fatal disease (expected survival between one year and five years) and 14.3% a rapidly fatal disease (expected death within the year); in 4.9% of cases the data were missing.
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Since hospital admission, 30.6% of patients had been exposed to surgery, and
20.3% had
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undergone a major surgical procedure.
Healthcare associated infections According to ECDC definitions, 429 infections were diagnosed in 376 patients, corresponding to a HAI prevalence of 10.3% (95% CI: 9.4-11.3); the majority of patients (n=326, 86.7%) had only one HAI, 47 (12.5%) had two HAIs and three patients (0.8%) had three HAIs. Prevalence of HAI varied considerably among hospitals enrolled, ranging from 1.7% (95% CI: 0.09.2) to 30.6% (95% CI: 19.6-43.7).
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ACCEPTED MANUSCRIPT Seventy-two percent of HAIs (308 infections) were not present at admission, while 28% (121 infections) were associated with a previous hospitalization, the latter mainly pneumonia (n=24), bone and joint (n=19), surgical site (n=15) and gastro-intestinal infections (n=14). Detected HAIs were mostly associated with the hospital where the prevalence study was conducted (327 infections,
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76.6%), while 23 infections (5.4%) were acquired in another acute care hospital and 77 (18%) had other origins.
The distribution of HAIs by location and ward specialties is shown in Table II.
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During the study, 248 microorganisms from 215 HAIs were isolated. Table III shows the
microorganisms are reported in Table IV.
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distribution of pathogens by infection site, while antibiotic susceptibility profiles of detected
In the univariate analysis all patient characteristics with the exception of gender and exposure to peripheral vascular line were associated with a higher risk of developing a HAI; when included in the multivariate logistic regression model, age > 54 years, length of pre-survey hospitalization,
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McCabe score, surgery, exposure to more devices and exposure to CVC were confirmed to be factors independently associated with HAIs. Interestingly, no association between specialty of ward and size of hospital with occurrence of HAI was revealed by multivariate analysis (Table I).
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Figure 1 shows that in 13 of the 18 participating hospitals the prevalence of infections observed is less than expected, whereas in four of these the SIR is greater than one; in particular, one hospital
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reached a value of 4.90, which means an excess of 390% of infections than expected.
Antimicrobial use
On the day of the study a total of 1,663 patients received at least one antimicrobial agent (prevalence: 45.6%; 95% CI: 44.0-47.2), for a total of 2,289 antibiotic prescriptions and an average of 1.4 antibiotics per patient (Table V).
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ACCEPTED MANUSCRIPT The prevalence of patients receiving an antibiotic ranged from 7.4% (95% CI: 3.3-14.1) in psychiatry to 57.2% (95% CI: 49.9-64.2) in intensive care unit; among them, 1,162 patients (69.9%) received one antimicrobial agent, 401 (24.1%) received two antimicrobial agents and 100 (6.0%) received three or more antimicrobial agents. Overall, the most commonly used classes of antibiotic
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were beta-lactam antibacterials (27.3%), followed by fluoroquinolones (16.2%), third-generation cephalosporins (15.2%), first-generation cephalosporins (4.9%) and carbapenems (4.6%).
The most prescribed antibiotics for the treatment of an infection were combinations of penicillins,
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including beta-lactamase inhibitors (26.6%), fluoroquinolones (17.4%) and third-generation cephalosporins (15.2%), while the most used agents in surgical prophylaxis were first-generation
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cephalosporins (37.2%) and amoxicillin and enzyme inhibitor (17%).
Similarly to the differences in the frequency of infections, the use of antibiotics also showed some variability, as illustrated in Figure 1, which compares the SAURs measured for each hospital.
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DISCUSSION
Despite several interventions carried out in Liguria in the last decade in terms of prevention and control, this recent prevalence study, performed nine years after the first survey in the same
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hospitals, shows an increase in HAI prevalence (10.3% vs 8.9%). 4 The number of patients enrolled in our survey is comparable with those studied in 2007 (3,176
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hospitalized subjects). The two populations are also similar for their features in terms of mean age (64.2 years in 2016 vs 64.8 years in 2007) and exposure to invasive medical devices (the percentage of patients with at least one device is 71% in our study compared to 69% measured in the 2007 survey). 4
The different frequency of HAI measured in the two studies could be explained by the changed criteria in the ECDC PPS protocol as an inclusion of infections acquired in other hospitals and, at the same time, the clinical definition of certain infections without microbiological confirmation could justify the increased number of infections, but it is also true that our study included the 10
ACCEPTED MANUSCRIPT psychiatric wards, with lower HAIs frequency usually, excluded instead in the 2007 survey. So all these differences suggest the results of the two studies should be compared with some caution. Nevertheless, in our study, the prevalence of patients with at least one infection is higher than the national average recorded during the European survey of 20113 and compared to other surveys 6, 7
, as well as greater than several studies
conducted in Europe in previous years. 8-15
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conducted in Italy in similar epidemiological settings
However, in large-scale investigations at European level, spontaneously participating hospitals are
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usually the most virtuous, already sensitive to the problem of HAIs, excluding on the contrary other more backward realities; this may have led to underestimate the national prevalence rate, measured
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only on 49 Italian hospitals. 3
On the other hand, the wide inclusion of hospitals enrolled in Liguria, also including those with more complex case mix, could partly explain the high prevalence rate measured in 2016, for example, 35% of the population studied in Liguria had at least one fatal or rapidly fatal disease
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against 22% of the national population involved in the 2011 European survey. 3 As expected, and similar to studies conducted in other Italian regions
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or in other European
countries8, the highest prevalence rates of infections were in intensive care units, but reaching
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greater values in Liguria, both in the 2007 and 2016 studies (44.4% and 23.9%, respectively) when compared to the national value registered in 2011 (14.8%). 3
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Of interest is the high occurrence in sites of infection generally less frequent such as bone and joints and in general the HAIs prevalence (13.5%) measured in orthopaedic and trauma wards, which is much higher than the one measured during the previous survey conducted in Liguria in 2007 (5.3%). 4 This may be justified by the presence in our region of a structure highly specialized in the treatment of bone and joint infectious diseases, a specialist center with a regional value since 2011, attracting
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ACCEPTED MANUSCRIPT patients from throughout northern Italy and corresponding to the highest measured SIR in one of the participating hospitals (Figure 1). The distribution of isolated pathogens in different infection sites is comparable to what was observed in a similar study conducted in Piedmont in 2010, with the exception of respiratory tract
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infections (RTIs); in the Piedmont study the prevailing microorganisms cultured from RTIs were Staphylococcus aureus (23.4%) and Pseudomonas aeruginosa (20.8%), while in our study the most common pathogens were, in order of frequency, Klebsiella pneumoniae (27.3%) followed by
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Enterobacter spp (13.6%) and only 9% of RTIs were caused by Staphylococcus aureus.6 This may
microorganisms. As is clear from the ECDC reports
3, 16
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suggest a growing trend of Enterobacteriaceae which tends to replace gram-positive
, Italy is among the European countries with the highest
levels of antibiotic resistance in Staphylococcus aureus and Enterobacteriaceae. Our data partially confirm the national trend, with 50% of Staphylococcus aureus resistant to meticillin (although
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lower than the national average of 62.1%), over 80% of Klebsiella pneumoniae resistant to thirdgeneration cephalosporin and over 60% to carbapenems, and proportions of Enterobacteriaceae
respectively.
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non susceptible to third-generation cephalosporins and carbapenems of 52.2% and 26.7%,
With regard to the antimicrobial use, despite the higher HAI prevalence, the use of antibiotics is
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lower than in the previous study conducted in Liguria (45.6% of subjects exposed to antibiotics versus 58.4%, respectively). 4
This difference may be due to the inclusion in our study of psychiatric wards with low antibiotic use, although only 108 patients were enrolled in psychiatry, too few to influence the overall prevalence of antimicrobial use. Moreover, the difference could be explained by an increased attention to the use of antibiotics for indications other than healthcare-associated infections, also because of some control measures introduced meantime in our region with the aim of improving the
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ACCEPTED MANUSCRIPT use of antibiotics; for example, in recent years in Liguria a semi-restrictive mode has been introduced for the authorization to use certain classes of antibiotics in public health facilities, which requires the approval of a specialist physician in infectious diseases However, the antimicrobial use measured in our study is slightly higher than the national average
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(44.0%) and even greater than the European data on antibiotic consumption, reaching overall 32.7%.3, 17This data is even more worrying considering that Italy is among the European countries with the widest spread of antibiotic-resistant strains. 3, 16
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Similar to the Italian trend, the data collected in Liguria show that carbapenems are ranked fifth among the most widely used antibiotic classes. 3 This could be explained by the higher frequency of 3, 16
In addition, some data show an
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gram-negatives resistant to third-generation cephalosporins.
improper use of antibiotics, as in the case of surgical prophylaxis, where the use of antimicrobials exceeded one day in 50.5% of cases. 3 Conclusions
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Although significant progress has been made in recent years to implement prevention strategies in Ligurian hospitals, HAIs remain a serious public health problem. The high prevalence of HAIs, especially in ICUs, requires both HAI surveillance and effective policies to contain outbreaks,
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through a full understanding of the types of HAIs and the affected patient populations. The high rates of carbapenem resistance and the high levels of antimicrobial use often unjustified,
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as evidenced, for example, in the use of antibiotics in prophylaxis extended over one day, illustrate the urgent need for the capacity of strengthening in both rational antimicrobial use and infection control efforts at national, regional and local levels. Recently, the Italian Ministry of Health has presented to the State-Regions Conference the National Plan for the Antimicrobial Resistance 2017-2020, which involves all Italian regions in countering the phenomenon, through the prevention and control of infections by resistant microorganisms, the training of healthcare professionals, population education and research aimed at appropriate use of
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ACCEPTED MANUSCRIPT antibiotics and the surveillance of their consumption with the purpose of achieving a significant reduction of antibiotic employment, both in the health and veterinary sectors. Despite the intrinsic limitations of prevalence investigations, for the first time, an international protocol was used in Liguria for a regional survey, allowing us to compare our results with those of
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similar studies conducted at national and European levels. Moreover, point prevalence studies, when periodically repeated, provide a large amount of information on the size of the phenomenon and its trend over time, highlighting the potential effects of strategies adopted. Furthermore, data
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sharing should promote greater attention to the problem, at the local and regional level, and strengthen infrastructure and expertise to implement the surveillance. Additionally, the
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identification of common problems allows the establishment of shared priorities, and evaluation of the impact of the strategies.
Although a previous investigation was carried out in Liguria with the same purpose, the results are not directly comparable due to the different study protocol used in the 2007 survey; therefore our
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most recent experience must be considered a starting point and further assessments will be possible when future surveillance data are available, according to the regional prevention plan 2014-2018,
REFERENCES
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which requires a prevalence survey every year.
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1. K Weist and L Diaz Högberg. ECDC publishes 2015 surveillance data on antimicrobial resistance and antimicrobial consumption in Europe. Euro Surveill 2016 Nov 17; 21(46): 30401. doi: 10.2807/1560-7917.ES.2016.21.46.30399 2. Zarb P, Coignard B, Griskeviciene J et al. The European Centre for Disease Prevention and Control (ECDC) pilot point prevalence survey of healthcare-associated infections and antimicrobial
use.
Euro
Surveill
2012;17(46):pii=20316.
http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20316
14
Available
online:
ACCEPTED MANUSCRIPT 3. European Centre for Disease Prevention and Control. Point prevalence survey of healthcare associated
infections
and
antimicrobial
use
in
European
acute
care
hospitals. ECDC, Stockholm, Sweden; 2013 4. Durando P, Icardi G, Ansaldi F et al. Surveillance of hospital-acquired infections in Liguria,
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Italy: results from a regional prevalence study in adult and paediatric acute-care hospitals. J Hosp Infect 2009 Jan;71(1):81-87
5. McCabe WR, Jackson GG. Gram-negative bacteraemia: I. Etiology and ecology. Arch
SC
Intern Med 1962; 110:847-53
6. Charrier et al. Surveillance of healthcare-associated infections in Piemonte, Italy: results
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from a second regional prevalence study. BMC Public Health 2014; 14:558 7. Pellizzer G, Mantoan P, Timillero L et al. Prevalence and risk factors for nosocomial infections in hospitals of the Veneto region, north-eastern Italy. Infection 2008; 36:112–119 8. The French Prevalence Survey Study Group: Prevalence of nosocomial infections in France:
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results of the nationwide survey in 1996. J Hosp Infect 2000; 46:186–193 9. Plowman R, Graves N, Griffin MA et al. The rate and cost of hospital-acquired infections occurring in patients admitted to selected specialties of a district general hospital in England
EP
and the national burden impose. J Hosp Infect 2001; 47:198–209 10. Hopmans TE, Blok HE, Troelstra A, Bonten MJ. Prevalence of hospital-acquired infections
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during successive surveillance surveys conducted at a University Hospital in the Netherlands. Infect Control Hosp Epidemiol 2007; 28:459–465 11. Gordts B, Vrijens F, Hulstaert F, Devriese S, Van de Sande S. The 2007 Belgian national prevalence survey for hospital-acquired infections. J Hosp Infect 2010; 75:163–167 12. Moro ML, Stazi MA, Marasca G, Greco D, Zampieri A. National prevalence survey of hospital-acquired infections in Italy, 1983. J Hosp Infect 1986; 8:72–85
15
ACCEPTED MANUSCRIPT 13. EPINE Working Group. Prevalence of hospital-acquired infections in Spain. J Hosp Infect 1992; 20:1–13 14. Vaqué J, Rosselló J, Trilla A et al. Nosocomial infections in Spain: results of five nationwide serial prevalence surveys (EPINE Project, 1990 to 1994). Nosocomial Infections
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Prevalence Study in Spain. Infect Control Hosp Epidemiol 1996; 17:293–297
15. Emmerson AM, Enstone JE, Griffin M, Kelsey MC, Smyth ET. The Second National Prevalence Survey of infection in hospitals – overview of the results. J Hosp Infect 1996;
SC
32:175–19
16. European Centre for Disease Prevention and Control. Antimicrobial resistance surveillance
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in Europe 2014. Annual Report of the European Antimicrobial Resistance Surveillance Network (EARS-Net). Stockholm: ECDC; 2015
17. European Centre for Disease Prevention and Control. Surveillance of antimicrobial
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consumption in Europe 2012. Stockholm: ECDC; 2014.
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Table I. Risk factor assessment: results of univariate and multivariable analysis Patients with HAI (N = 376) (n, %)
Patients without HAI (N = 3271) (n, %)
Crude OR (95% CI)
1916 (52.54) 1730 (47.44) 1 (0.03)
195 (51.86) 181 (48.14) 0 (0)
1721 (52.61) 1549 (47.36) 1 (0.03)
Reference 1.03 (0.83 – 1.28) -
934 (25.61) 2713 (74.39)
48 (12.77) 328 (87.23)
886 (27.09) 2385 (72.91)
936 (26.81) 842 (24.12) 751 (21.51) 962 (27.56)
21 (5.68) 27 (7.30) 81 (21.89) 241 (65.14)
915 (29.32) 815 (26.11) 670 (21.47) 721 (23.10)
108 (2.96) 1749 (47.96) 649 (17.80) 304 (8.34) 230 (6.31) 189 (5.18) 180 (4.94) 162 (4.44) 76 (2.08)
2 (0.53) 180 (47.87) 58 (15.43) 41 (10.90) 7 (1.86) 29 (7.71) 43 (11.44) 4 (1.06) 12 (3.19)
106 (3.24) 1569 (47.97) 591 (18.07) 263 (8.04) 223 (6.82) 160 (4.89) 137 (4.19) 158 (4.83) 64 (1.96)
Reference 6.08 (1.91 – 37.04) 5.20 (1.59 – 32.02) 8.26 (2.48 – 51.25) 1.66 (0.39 – 11.29) 9.61 (2.81 – 60.20) 16.64 (4.97 – 103.40) 1.34 (0.26 – 9.80) 9.94 (2.60 – 65.18)
2217 (60.79) 730 (20.02) 521 (14.29) 179 (4.91)
147 (39.10) 115 (30.59) 93 (24.73) 21 (5.59)
2070 (63.28) 615 (18.80) 428 (13.08) 158 (4.83)
Reference 2.63 (2.03 – 3.41) 3.06 (2.31 – 4.04) 1.88 (1.12 – 2.98)
190 (50.53) 59 (15.69) 127 (33.78) 0 (0)
2337 (71.45) 317 (9.69) 614 (18.77) 3 (0.09)
Reference 2.29 (1.66 – 3.12) 2.54 (1.99 – 3.23) -
34 (9.04) 171 (45.48) 136 (36.17) 35 (9.31)
1022 (31.24) 1446 (44.21) 730 (22.32) 73 (2.23)
Reference 3.55 (2.47 – 5.26) 5.60 (3.85 – 8.37) 14.41 (8.50 – 24.53)
1035 (28.38) 2093 (57.39) 466 (12.78) 107 (2.93)
179 (47.61) 210 (55.85) 138 (36.70) 33 (8.78)
856 (26.17) 1883 (57.57) 328 (10.03) 74 (2.26)
2.56 (2.06 – 3.18) 0.94 (0.76 – 1.16) 5.20 (4.09 – 6.59) 4.16 (2.69 – 6.32)
716 (19.63) 2032 (55.72) 899 (24.65)
64 (17.02) 193 (51.33) 119 (31.65)
652 (19.93) 1839 (56.22) 780 (23.85)
Reference 1.07 (0.8 – 1.45) 1.55 (1.13 – 2.15)
p-value
Adjusted OR (95%CI)
p-value
1056 (28.96) 1617 (44.34) 866 (23.75) 108 (2.96)
LOS, length of stay (days); NHSN, National Healthcare Safety Network
SC
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2527 (69.29) 376 (10.31) 741 (20.32) 3 (0.08)
RI PT
0.86
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Gender Female Male Other Age (years) 0 – 54 > 54 LOS before inclusion in the survey (days) (n=3491) 0–3 4–7 8 – 14 > 14 Specialty of ward Psychiatry Medicine Surgery Orthopaedy and traumatology Paediatrics and neonatology Rehabilitation Intensive care Gynaecology and obstetrics Geriatrics McCabe Score Nonfatal Ultimately fatal Rapidly fatal Unknown Surgery None Non-NHSN NHSN Unknown Number of devices 0 1 2 >2 Type of device Urinary catheter Peripheral vascular line Central vascular line Tracheal intubation or tracheostomy Size of hospital < 200 beds 200 – 500 beds > 500 beds
Overall (N = 3,647) (n, %)
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Characteristics
< 0.001
Reference 2.54 (1.88 – 3.51)
0.03 Reference 1.53 (1.05 – 2.28)
< 0.001
Reference 1.44 (0.81 – 2.60) 5.27 (3.29 – 8.81) 14.56 (9.45 – 23.67)
< 0.001 Reference 1.32 (0.73 – 2.42) 4.09 (2.50 – 7) 10.84 (6.75 – 18.24)
< 0.001
0.22 Reference 1.08 (0.31 – 6.91) 0.85 (0.23 – 5.55) 1.63 (0.43 – 10.75) 0.64 (0.14 – 4.56) 1.42 (0.38 – 9.28) 1.20 (0.30 – 8.09) 1.52 (0.35 – 10.71) 0.95 (0.14 – 7.76)
< 0.001
0.049 Reference 1.50 (1.10 – 2.05) 1.38 (0.98 – 1.95) 1.55 (0.81 – 2.82)
< 0.001
0.007 Reference 1.52 (1.04 – 2.20) 1.67 (1.18 – 2.37) -
< 0.001
< 0.001 Reference 3.47 (2.26 – 5.48) 3.26 (1.67 – 6.46) 3.66 (1.17 – 11.25)
< 0.001 0.56 < 0.001 < 0.001 0.005
1.09 (0.67 – 1.76)
0.71
2.23 (1.62 – 3.07) 1.35 (0.60 – 3)
< 0.001 0.47 0.10
Reference 0.94 (0.67 – 1.33) 0.71 (0.48 – 1.05)
ACCEPTED MANUSCRIPT
Table II. Prevalence of healthcare-associated infections (HAIs) according to site and ward specialties SUR (N = 649)
ORT (N = 304)
PED (N = 230)
RHB (N = 189)
ICU (N = 180)
GYN (N = 162)
PSI (N = 108)
GER (N = 76)
N (%)
P (%) (95%CI)
N (%)
P (%) (95%CI)
N (%)
P (%) (95%CI)
N (%)
P (95%CI)
N (%)
P (%) (95%CI)
N (%)
P (%) (95%CI)
N (%)
P (%) (95%CI)
N (%)
P (%) (95%CI)
N (%)
P (%) (95%CI)
N (%)
P (%) (95%CI)
N. of pts with HAI
376
10.3 (9.4-11.3)
180
10.3 (8.9-11.8)
58
8.9 (7-11.4)
41
13.5 (10.1-17.8)
7
3 (1.2-6.2)
29
15.3 (10.5-21.3)
43
23.9 (17.9-30.8)
4
2.5 (0.7 – 6.2)
2
1.9 (0.2-6.5)
12
15.8 (8.4-26)
N. of HAIs
429
11.8 (10.7-12.9)
201
11.5 65 (10.1-13.1)
15.8 (12-20.5)
7
3 (1.2-6.2)
34
18 (12.9-24.4)
51
28.3 (22-35.6)
4
2.5 (0.7 – 6.2)
2
1.9 (0.2-6.5)
17
22.4 (13.9-33.7)
RTI
93 (21.7)
2.6 (2.1-3.1)
51 2.9 (25.4) (2.2-3.9)
10 (15.4)
1.5 (0.8-2.9)
8 2.6 (16.6) (1.2-5.3)
-
-
2 (5.9)
17 9.4 (33.3) (5.8-14.9)
1 (25)
0.6 (0.03-3.9)
2 1.9 (100) (0.2-6.5)
2 2.6 (11.8) (0.5-10.1)
UTI
86 (20.1)
2.4 (1.9-2.9)
38 2.2 (18.9) (1.6-3)
6 (9.2)
0.9 (0.4-2.1)
13 4.3 (27.1) (2.4-7.4)
3 1.3 (42.8) (0.3-4.1)
15 7.9 (44.1) (4.7-13)
6 3.3 (11.8) (1.4-7.4)
-
-
-
-
5 6.6 (29.4) (2.5-15.3)
BSI
72 (16.8)
2 (1.6-2.5)
36 2.1 (17.9) (1.5-2.9)
10 (15.4)
1.5 (0.8-2.9)
1 (2.1)
2 0.9 (28.6) (0.2-3.4)
5 2.6 (14.7) (1-6.4)
13 7.2 (25.5) (4.1-12.3)
-
-
-
-
5 6.6 (29.4) (2.5-15.3)
SSI
43 (10)
1.2 (0.9-1.6)
10 (5)
0.6 (0.3-1.1)
18 (27.7)
2.8 (1.7-4.4)
6 2 (12.5) (0.8-4.5)
-
-
2 (5.9)
1.1 (0.2-4.2)
5 (9.8)
2.8 (1-6.7)
1 (25)
0.6 (0.03-3.9)
-
-
1 (5.9)
1.3 (0.1-8.1)
GGI
43 (10)
1.2 (0.9-1.6)
19 (9.4)
1.1 (0.7-1.7)
12 (18.5)
1.9 (1-3.3)
1 (2.1)
2 0.9 (28.6) (0.2-3.4)
3 (8.8)
1.6 (0.4-5)
5 (9.8)
2.8 (1-6.7)
-
-
-
-
1 (5.9)
1.3 (0.1-8.1)
CSEP
28 (6.5)
0.8 (0.5-1.1)
18 (9)
1 (0.6-1.7)
3 (4.6)
0.5 (0.1-1.5)
-
-
-
-
1 (2.9)
0.5 (0.03-3.4)
5 (9.8)
2.8 (1-6.7)
1 (25)
0.6 (0.03-3.9)
-
-
-
-
Other
64 (14.9)
1.7 (1.4-2.2)
29 1.6 (14.5) (1.1-2.4)
6 (9.2)
0.9 (0.4-2.1)
19 6.3 (39.6) (3.9-9.8)
-
-
6 3.2 (17.7) (1.3-7.1)
-
-
1 (25)
0.6 (0.03-3.9)
-
-
3 4 (17.6) (1-11.9)
10 48 (7.9-12.6)
0.3 (0.02-2.1)
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0.3 (0.02-2.1)
1.1 (0.2-4.2)
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N. of sites with HAI
RI PT
MED (N = 1749)
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Total (N = 3647)
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MED, Medicine; SUR, Surgery; ORT, Orthopaedy and traumatology; PED, Paediatrics and neonatology; RHB, Rehabilitation; ICU, Intensive care; GYN, Gynaecology and obstetrics; PSI, Psychiatry; GER, Geriatrics.
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P, Prevalence of infected sites in all patients; 95%CI, 95% confidence interval
RTI, respiratory tract infection; UTI, urinary tract infection; BSI, laboratory-confirmed bloodstream infection; SSI, surgical site infection; GII, gastro-intestinal infection; SST, soft skin tissue infection; OTH, other infection
ACCEPTED MANUSCRIPT
Table III. Distribution of pathogens causing HAIs, overall and stratified for site infection
72 (100)
21 (48.8)
75
81
24
61 (81.3) 30 (40.1) 10 (13.3) 2 (2.7) 4 (5.3) 8 (10.7) 2 (2.7) 1 (1.3) 0 (0) 3 (4.9) 1 (1.3) 11 (14.7) 2 (2.7) 0 (0) 8 (10.7) 0 (0) 0 (0) 1 (1.3) 3 (4) 2 (2.7) 1 (1.3) 0 (0) 0 (0)
24 (29.6) 8 (9.9) 10 (12.4) 1 (1.2) 3 (3.7) 0 (0) 1 (1.2) 0 (0) 0 (0) 1 (1.2) 0 (0) 46 (56.8) 9 (11.1) 26 (32.1) 8 (9.9) 3 (3.7) 0 (0) 0 (0) 11 (13.6) 4 (4.9) 7 (8.7) 0 (0) 0 (0)
17 (70.8) 6 (25) 3 (12.5) 0 (0) 2 (8.3) 1 (4.2) 2 (8.3) 0 (0) 2 (8.3) 1 (4.2) 0 (0) 6 (25) 2 (8.3) 1 (4.2) 3 (12.5) 0 (0) 0 (0) 0 (0) 1 (4.2) 1 (4.2) 0 (0) 0 (0) 0 (0)
OTH (N = 77)
29 (67.4)
4 (26.7)
11 (14.3)
31
4
11
4 (12.9) 1 (3.2) 3 (9.7) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 26 (83.9) 0 (0) 3 (9.7) 1 (3.2) 0 (0) 22 (71) 0 (0) 1 (3.2) 1 (3.2) 0 (0) 0 (0) 0 (0)
2 (50) 0 (0) 1 (25) 0 (0) 1 (25) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 2 (50) 1 (25) 0 (0) 0 (0) 0 (0) 0 (0) 1 (25) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0)
3 (27.3) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 2 (18.2) 0 (0) 1 (9.1) 0 (0) 6 (54.5) 3 (27.3) 1 (9.1) 1 (9.1) 1 (9.1) 0 (0) 0 (0) 1 (9.1) 1 (9.1) 0 (0) 0 (0) 1 (9.1)
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SST (N = 30)
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16 (72.8) 0 (0) 6 (27.3) 1 (4.6) 2 (9.1) 1 (4.6) 3 (13.6) 0 (0) 0 (0) 0 (0) 3 (13.6) 3 (13.6) 2 (9.1) 0 (0) 1 (4.6) 0 (0) 0 (0) 0 (0) 3 (13.6) 1 (4.6) 0 (0) 2 (9.1) 0 (0)
61 (70.9)
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Gram-negative bacteria Escherichia coli Klebsiella pneumoniae Other Klebsiella spp Pseudomonas aeruginosa Proteus spp. Enterobacter spp. Acinetobacter baumannii Citrobacter spp. Other enterobacteriacee Other Gram-negative bacteria Gram-positive bacteria Staphylococcus aureus Coagulase-negative Staphylococci Enterococcus spp. Streptococcus spp. Clostridium difficile Other Gram-positive bacteria Fungi Candida albicans Other candida Aspergillus spp. Virus
BSI (N = 72)
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N. of infections with isolation of 17 (18.2) at least one pathogens (N, %) Total isolated pathogens 22
UTI (N = 86)
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RTI (N = 93)
HAI-type, N (%) SSI (N = 43) GII (N = 43)
All (N= 429) 215 (50.1) 248 127 (51.2) 45 (18.2) 33 (13.4) 4 (1.6) 12 (4.8) 10 (4) 8 (3.2) 3 (1.2) 2 (0.8) 6 (2.4) 4 (1.6) 100 (40.3) 19 (7.7) 31 (12.5) 22 (8.9) 4 (1.6) 22 (8.9) 2 (0.8) 20 (8.1) 10 (4) 8 (3.2) 2 (0.8) 1 (0.4)
RTI, respiratory tract infection; UTI, urinary tract infection; BSI, laboratory-confirmed bloodstream infection; SSI, surgical site infection; GII, gastro-intestinal infection; SST, soft skin tissue infection; OTH, other infection
ACCEPTED MANUSCRIPT
Table IV. Antimicrobial resistance of the main isolated microorganisms Tested sensitivity N
Oxacillin
Third generation cephalosporins
Carbapenems
Resistant N (%)
Resistant N (%)
Resistant N (%)
-
47 (52.2)
24 (26.7)
-
13 (35.1)
1 (2.7)
-
28 (82.4)
22 (64.7)
108
90
-
Escherichia coli
45
37
-
Klebsiella spp
37
34
-
Proteus spp
10
7
-
-
2 (28.6)
1 (14.3)
Other Enterobacteriaceae
16
12
-
-
4 (33.3)
0 (0)
Enterococcus spp
22
15
-
1 (6.7)
-
-
Staphylococcus aureus
19
18
9 (50)
-
-
-
Acinetobacter baumannii
3
1
-
-
-
1 (100.0)
Pseudomonas spp
13
8
-
-
-
3 (37.5)
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EP
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Total Enterobacteriaceae
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Resistant N (%)
Glycopeptides (vancomycin, teicoplanin)
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Total isolated N
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Table V. Prescribed antibiotic molecules and indications for their use Percentage indication for treatment
Percentage of Total prescriptions
Therapy 30.0
20.8
1 064
67.0
46.5
47
3.0
2.1
Total therapy
1 588
100.0
69.4
396
58.9
Prophylaxis Medical prophylaxis
140
20.8
Surgical prophylaxis, single dose
112
16.6
Surgical prophylaxis, one day
25
3.7
Total prophylaxis
673
100.0
Other indication Truly unknown, information not verified during the survey
12
Unknown indication (confirmed)
12
Total other indications/unknown
28
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4
17.3 6.1
4.9
1.1
29.4
42.9
0.5
14.2
0.2
42.9
0.5
EP
Other indications/unknown
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Surgical prophylaxis, > 1 day
SC
477
Community-acquired infection Infection acquired in long-term care facility (e.g. nursing home) or chronic care hospital
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Acute hospital-acquired infection
100.0
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Total prescribed antibiotic molecules
Number of antibiotics 2 289
1.2
ACCEPTED MANUSCRIPT
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EP
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SC
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Figure 1. Standardized ratios observed/expected and 95% confidence intervals of infections and antimicrobial use measured for each of the eighteen hospitals enrolled in Liguria
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ACCEPTED MANUSCRIPT LEGENDS
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EP
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SC
RI PT
Figure 1 SIR, Standardized Infection Ratio; SAUR, Standardized Antimicrobial Use Ratio; The vertical lines are placed at the value 1, no difference between observed and expected cases; SIR<1, fewer infections observed than expected; SIR>1, number of infections observed higher than expected; SAUR<1, fewer antibiotic treatments observed than expected; SAUR>1, number of antibiotic treatments observed higher than expected
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S0195-6701(17)30679-5
DOI:
10.1016/j.jhin.2017.12.008
Reference:
YJHIN 5300
To appear in:
Journal of Hospital Infection
Received Date: 3 August 2017 Accepted Date: 8 December 2017
Please cite this article as: Sticchi C, Alberti M, Artioli S, Assensi M, Baldelli I, Battistini A, Boni S, Cassola G, Castagnola E, Cattaneo M, Cenderello N, Cristina ML, De Mite AM, Fabbri P, Federa F, Giacobbe DR, La Masa D, Lorusso C, Marioni K, Masi V, Mentore B, Montoro S, Orsi A, Raiteri D, Riente R, Samengo I, Viscoli C, Carloni R, The Collaborative Group for the Point Prevalence Survey of healthcare-associated infections in Liguria, Alicino C, Barberis I, Bellina D, Crisalli MP, Daturi V, Di Bella AM, Faccio V, Grammatico F, Guglielmi B, Icardi G, Magnasco L, Morando A, Paganino C, Saffioti C, Sansone P, Santini M, Sarteschi G, Talamini A, Tomei M, Ungaro R, Regional point prevalence study of healthcare-associated infections and antimicrobial use in acute care hospitals in Liguria, Italy, Journal of Hospital Infection (2018), doi: 10.1016/j.jhin.2017.12.008.
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ACCEPTED MANUSCRIPT Regional point prevalence study of healthcare-associated infections and antimicrobial use in acute care hospitals in Liguria, Italy Camilla Sticchi* - Infectious Diseases, Epidemiology and Prevention, Health Regional Agency,
Marisa Alberti - International Evangelical Hospital, Genoa, Italy Stefania Artioli - ASL 5 Spezzino, La Spezia, Italy Marina Assensi - ASL1 Imperiese, Imperia, Italy
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Ivana Baldelli - IRCCS Giannina Gaslini Institute, Genoa, Italy
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Liguria, Italy
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Angela Battistini - San Martino Polyclinic Hospital, Genoa, Italy Silvia Boni - ASL 5 Spezzino, La Spezia, Italy
Giovanni Cassola - Infectious Diseases Unit, Galliera Hospital, Genoa, Italy Elio Castagnola - Infectious Diseases Unit, Giannina Gaslini Institute, Genoa, Italy Mauro Cattaneo - ASL 3 Genovese, Genoa, Italy
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Nadia Cenderello - Galliera Hospital, Genoa, Italy Maria Luisa Cristina - Galliera Hospital, Genoa, Italy Anna Maria De Mite - ASL 3 Genovese, Genoa, Italy
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Paola Fabbri - Galliera Hospital, Genoa, Italy
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Francesca Federa - ASL 3 Genovese, Genoa, Italy Daniele Roberto Giacobbe - Infectious Diseases Unit, San Martino Polyclinic Hospital, University of Genoa, Italy
Daniela La Masa - IRCCS Giannina Gaslini Institute, Genoa, Italy Carolina Lorusso - ASL 4 Chiavarese, Genoa, Italy Karine Marioni - ASL 5 Spezzino, La Spezia, Italy VitaMaria Masi - International Evangelical Hospital, Genoa, Italy Bruno Mentore - ASL 4 Chiavarese, Genoa, Italy 1
ACCEPTED MANUSCRIPT Silvana Montoro - ASL1 Imperiese, Imperia, Italy Andrea Orsi - San Martino Polyclinic Hospital, University of Genoa, Italy Doranna Raiteri - Santa Corona Hospital, Pietra Ligure, Savona, Italy Rosamaria Riente - San Paolo Hospital, Savona, Italy
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Ines Samengo- ASL 4 Chiavarese, Genoa, Italy
Claudio Viscoli - Infectious Diseases Unit, San Martino Polyclinic Hospital, University of Genoa, Italy
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Roberto Carloni - Infectious Diseases, Epidemiology and Prevention, Health Regional Agency,
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Liguria, Italy
The Collaborative Group for the Point Prevalence Survey of healthcare-associated infections in Liguria:
Cristiano Alicino - University of Genoa, Italy
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Ilaria Barberis - University of Genoa, Italy
Dorotea Bellina - San Martino Polyclinic Hospital, Genoa, Italy Maria Paola Crisalli - Galliera Hospital, Genoa, Italy
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Valerio Daturi - San Martino Polyclinic Hospital, Genoa, Italy Anna Maria Di Bella - San Martino Polyclinic Hospital, Genoa, Italy
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Valeria Faccio - University of Genoa, Italy Federico Grammatico - University of Genoa, Italy Barbara Guglielmi - San Martino Polyclinic Hospital, Genoa, Italy Giancarlo Icardi - San Martino Polyclinic Hospital, University of Genoa, Italy Laura Magnasco - University of Genoa, Italy Alessandra Morando - San Martino Polyclinic Hospital, Genoa, Italy Chiara Paganino - University of Genoa, Italy
2
ACCEPTED MANUSCRIPT Carolina Saffioti - University of Genoa, Italy Paola Sansone - Galliera Hospital, Genoa, Italy Marco Santini - Galliera Hospital, Genoa, Italy
Antonella Talamini - San Martino Polyclinic Hospital, Genoa, Italy Marco Tomei - San Martino Polyclinic Hospital, Genoa, Italy
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Riccardo Ungaro - University of Genoa, Italy
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Giovanni Sarteschi - University of Genoa, Italy
* Corresponding author. Address: Health Regional Agency, Liguria, Italy, Section of Epidemiology
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and Prevention, Piazza della Vittoria 15, 16121 Genoa, Italy. Tel: +39 010 5488212.
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E-mail address: [email protected]
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ACCEPTED MANUSCRIPT SUMMARY Background: In the light of the importance of monitoring healthcare-associated infections (HAI) and the consumption of antibiotics, a regional point prevalence survey was conducted in Liguria between March and April 2016.
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Aim: The aim of the study was to measure the overall prevalence of HAI and describe the use of antibiotics in all public hospitals.
Methods: Data on risk factors and use of antibiotics were collected for each hospitalised patient. To
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define the variables significantly associated with HAI, univariate and multivariate analyses were conducted. Standardized Infection Ratio (SIR) and Standardized Antimicrobial Use Ratio (SAUR)
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were measured for each participating hospital.
Findings: A total of 3,647 patients were enrolled. Four hundred twenty-nine HAIs were diagnosed in 376 patients, giving a prevalence of HAI of 10.3%. Respiratory tract (21.7%) and urinary tract (20%) were the most frequent sites of infection.
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High rates of meticillin-resistant Staphylococcus aureus (47.4%) and Enterobacteriaceae resistant to carbapenems (26.3%) were isolated.
Forty-six percent of patients received at least one antibiotic. Combinations of penicillins including
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beta-lactamase inhibitors (24.1%) were the most commonly used; the main indication (46.7%) was the treatment of a community-acquired infection.
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Conclusions: Our results showed an increase in HAI prevalence compared to a similar survey conducted in 2007; however, the performance of overlapping investigations will enable more reliable considerations. Nevertheless, data on antimicrobial resistance and use of antibiotics are consistent with the national trend. Despite methodological limitations, prevalence studies are useful to monitor HAI over time and encourage greater awareness of the problem in all stakeholders.
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ACCEPTED MANUSCRIPT Key words: healthcare-associated infections, point prevalence study, antibiotic resistance, antimicrobial use
INTRODUCTION
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The World Health Organization (WHO) and the European Centre for Disease Prevention and Control (ECDC) have repeatedly stressed the relevance and global spread of the phenomenon of healthcare-associated infections (HAIs) and antimicrobial resistance, recognized as significant
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danger to public health requiring specific interventions.1
In order to estimate the overall impact of HAI and to describe the consumption of antibiotics in
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Europe, ECDC has developed a protocol for the study of point prevalence (ECDC PPS) of HAIs and the use of antibiotics in acute care hospitals, providing a standardized methodology for Member States and hospitals that would allow a comparison of data collected in different countries.2 The first European survey, conducted in Europe in the years 2011-2012, showed a prevalence of
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infections in Italy of 6.3%, in line with the European average, although in our country multidrugresistant microorganisms cause many of these infections. 3 In Liguria, an administrative region in northwestern Italy, a prevalence study on a regional basis
of 9.8%.4
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was carried on for the first time between March and April 2007, showing a prevalence of infections
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The National Prevention Plan 2014-2018 emphasizes the importance of having information on HAIs in all health units and of monitoring the consumption of antibiotics. Liguria, in its Regional Prevention Plan, is committed to launch a systematic methodology through repeated regional prevalence studies every year, to get comparable information over time and with other European countries. In this context, a point prevalence survey was performed in 2016 in all adult and paediatric acutecare hospitals in our region, applying the protocol provided by the ECDC. The objectives of the
5
ACCEPTED MANUSCRIPT study were to estimate the overall prevalence of HAIs and the use of antibiotics in acute care hospitals in Liguria, describe patients, invasive procedures, infections (sites, involved microorganisms, including antibiotic-resistance markers) and how antibiotics are used and the
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reasons why they are prescribed.
METHODS Study design and setting
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The study enrolled any public acute hospital, both small (<200 beds), medium (200-500 beds) and large size (>500 beds).
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According to ECDC PPS protocol version 4.3, all wards had to be involved with the exception of the long term care departments of acute care facilities. Nevertheless, similarly to some European countries (France, the Netherlands and Spain) using an adapted version of the ECDC PPS protocol, some rehabilitation wards of acute care hospitals were included in our surveillance.3
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Case definitions and data collection
The criteria for definition of HAIs and antibiotics use are those provided by the ECDC PPS protocol version 4.3.
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The survey was completed in one day in each ward and did not exceed three weeks for the whole hospital. The data were collected by infection control staff, consulting clinical documentation with
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the support of the ward's medical and nursing staff, and included patient’s personal data (sex and age), ward specialty, risk factors for all patients, infected or not, i.e. surgery since admission, both NHSN and not (the first corresponding to the surgical procedure monitored by the National Healthcare Safety Network), exposure to invasive devices and the McCabe severity of illness score.5 HAI data included HAI type, the origin of HAI, the date of onset for HAI if not present on admission, isolated microorganisms and selected antimicrobial resistance.
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ACCEPTED MANUSCRIPT Data on antimicrobial use included the antimicrobial agent, the route of administration, the indication for prescription and the site of infection if the indication was the treatment of an established infection. Antimicrobial agents for systemic use as well as non-absorbable anti-infectives, dermatological
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antifungals, antibacterials, antimycotics, antimycobacterials for treatment of mycobacteria other than tuberculosis and nitroimidazole-derived antiprotozoals were included, while antiviral agents and antimicrobials for the treatment of tuberculosis were not included.
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Data entry and statistical analysis
To facilitate data entry at hospital level, the ECDC freeware software HelicsWin.Net V3.0 was
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used.
The prevalence of HAIs and of antimicrobial use was reported as the percentage of patients with at least one HAI or receiving at least one antimicrobial agent, respectively. Univariate and multivariate analyses were carried out in order to assess the risk of developing HAIs.
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The association between HAIs and each risk factor was evaluated by calculating the odds ratio (OR) and 95% confidence intervals (95% CI). To assess the independent role of risk factors, variables with a P value < 0.05 in univariate comparisons were included in a multivariate logistic regression
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model.
Statistical analyses were performed with Epi-Info v. 3.5 (CDC, USA) and JMP v. 10.0 (SAS
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Institute, USA).
To compare hospitals with different patient characteristics (age, pre-study length of stay, surgery, McCabe score and invasive devices), a risk model based on the total population enrolled in Liguria was applied. Standardized Infection Ratios (SIRs) and Standardized Antimicrobial Use Ratios (SAURs) were calculated as observed over expected rate of patients with at least one infection or at least one antimicrobial, respectively.
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ACCEPTED MANUSCRIPT RESULTS Description of the enrolled population The study was conducted between 22th March and 22th April 2016. A total of 3,647 patients were enrolled in 18 participating hospitals. The median number of patients per hospital was 145 (SD:
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201.5; IQR: 187.5). As shown in Table I, most patients (48.0%) were enrolled in medical wards followed by 17.8% in surgical wards and 4.9% in intensive care units; mean age of the population investigated was 64.2 years (SD: 25.1; range: 0-101).
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At least one invasive device was placed in 2,591 patients enrolled (71%), 57.4% of patients had a
catheter (CVC) and 2.7% were intubated.
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peripheral vascular catheter (PVC), 28.4% a urinary catheter (UC), 12.6% a central vascular
The median length of hospital stay was 7 days (SD: 20.2; range: 0-289; IQR: 13.0), ranging from three days in gynaecology-obstetrics wards (SD: 10.3; range: 0-95 IQR: 4.5) to 26 days in rehabilitation (SD: 51.5; range: 0-289 IQR: 47.0).
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According to the McCabe score, 60.8% of the studied patients presented with a basic non-fatal disease, 20% had a fatal disease (expected survival between one year and five years) and 14.3% a rapidly fatal disease (expected death within the year); in 4.9% of cases the data were missing.
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Since hospital admission, 30.6% of patients had been exposed to surgery, and
20.3% had
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undergone a major surgical procedure.
Healthcare associated infections According to ECDC definitions, 429 infections were diagnosed in 376 patients, corresponding to a HAI prevalence of 10.3% (95% CI: 9.4-11.3); the majority of patients (n=326, 86.7%) had only one HAI, 47 (12.5%) had two HAIs and three patients (0.8%) had three HAIs. Prevalence of HAI varied considerably among hospitals enrolled, ranging from 1.7% (95% CI: 0.09.2) to 30.6% (95% CI: 19.6-43.7).
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ACCEPTED MANUSCRIPT Seventy-two percent of HAIs (308 infections) were not present at admission, while 28% (121 infections) were associated with a previous hospitalization, the latter mainly pneumonia (n=24), bone and joint (n=19), surgical site (n=15) and gastro-intestinal infections (n=14). Detected HAIs were mostly associated with the hospital where the prevalence study was conducted (327 infections,
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76.6%), while 23 infections (5.4%) were acquired in another acute care hospital and 77 (18%) had other origins.
The distribution of HAIs by location and ward specialties is shown in Table II.
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During the study, 248 microorganisms from 215 HAIs were isolated. Table III shows the
microorganisms are reported in Table IV.
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distribution of pathogens by infection site, while antibiotic susceptibility profiles of detected
In the univariate analysis all patient characteristics with the exception of gender and exposure to peripheral vascular line were associated with a higher risk of developing a HAI; when included in the multivariate logistic regression model, age > 54 years, length of pre-survey hospitalization,
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McCabe score, surgery, exposure to more devices and exposure to CVC were confirmed to be factors independently associated with HAIs. Interestingly, no association between specialty of ward and size of hospital with occurrence of HAI was revealed by multivariate analysis (Table I).
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Figure 1 shows that in 13 of the 18 participating hospitals the prevalence of infections observed is less than expected, whereas in four of these the SIR is greater than one; in particular, one hospital
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reached a value of 4.90, which means an excess of 390% of infections than expected.
Antimicrobial use
On the day of the study a total of 1,663 patients received at least one antimicrobial agent (prevalence: 45.6%; 95% CI: 44.0-47.2), for a total of 2,289 antibiotic prescriptions and an average of 1.4 antibiotics per patient (Table V).
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ACCEPTED MANUSCRIPT The prevalence of patients receiving an antibiotic ranged from 7.4% (95% CI: 3.3-14.1) in psychiatry to 57.2% (95% CI: 49.9-64.2) in intensive care unit; among them, 1,162 patients (69.9%) received one antimicrobial agent, 401 (24.1%) received two antimicrobial agents and 100 (6.0%) received three or more antimicrobial agents. Overall, the most commonly used classes of antibiotic
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were beta-lactam antibacterials (27.3%), followed by fluoroquinolones (16.2%), third-generation cephalosporins (15.2%), first-generation cephalosporins (4.9%) and carbapenems (4.6%).
The most prescribed antibiotics for the treatment of an infection were combinations of penicillins,
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including beta-lactamase inhibitors (26.6%), fluoroquinolones (17.4%) and third-generation cephalosporins (15.2%), while the most used agents in surgical prophylaxis were first-generation
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cephalosporins (37.2%) and amoxicillin and enzyme inhibitor (17%).
Similarly to the differences in the frequency of infections, the use of antibiotics also showed some variability, as illustrated in Figure 1, which compares the SAURs measured for each hospital.
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DISCUSSION
Despite several interventions carried out in Liguria in the last decade in terms of prevention and control, this recent prevalence study, performed nine years after the first survey in the same
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hospitals, shows an increase in HAI prevalence (10.3% vs 8.9%). 4 The number of patients enrolled in our survey is comparable with those studied in 2007 (3,176
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hospitalized subjects). The two populations are also similar for their features in terms of mean age (64.2 years in 2016 vs 64.8 years in 2007) and exposure to invasive medical devices (the percentage of patients with at least one device is 71% in our study compared to 69% measured in the 2007 survey). 4
The different frequency of HAI measured in the two studies could be explained by the changed criteria in the ECDC PPS protocol as an inclusion of infections acquired in other hospitals and, at the same time, the clinical definition of certain infections without microbiological confirmation could justify the increased number of infections, but it is also true that our study included the 10
ACCEPTED MANUSCRIPT psychiatric wards, with lower HAIs frequency usually, excluded instead in the 2007 survey. So all these differences suggest the results of the two studies should be compared with some caution. Nevertheless, in our study, the prevalence of patients with at least one infection is higher than the national average recorded during the European survey of 20113 and compared to other surveys 6, 7
, as well as greater than several studies
conducted in Europe in previous years. 8-15
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conducted in Italy in similar epidemiological settings
However, in large-scale investigations at European level, spontaneously participating hospitals are
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usually the most virtuous, already sensitive to the problem of HAIs, excluding on the contrary other more backward realities; this may have led to underestimate the national prevalence rate, measured
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only on 49 Italian hospitals. 3
On the other hand, the wide inclusion of hospitals enrolled in Liguria, also including those with more complex case mix, could partly explain the high prevalence rate measured in 2016, for example, 35% of the population studied in Liguria had at least one fatal or rapidly fatal disease
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against 22% of the national population involved in the 2011 European survey. 3 As expected, and similar to studies conducted in other Italian regions
6
or in other European
countries8, the highest prevalence rates of infections were in intensive care units, but reaching
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greater values in Liguria, both in the 2007 and 2016 studies (44.4% and 23.9%, respectively) when compared to the national value registered in 2011 (14.8%). 3
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Of interest is the high occurrence in sites of infection generally less frequent such as bone and joints and in general the HAIs prevalence (13.5%) measured in orthopaedic and trauma wards, which is much higher than the one measured during the previous survey conducted in Liguria in 2007 (5.3%). 4 This may be justified by the presence in our region of a structure highly specialized in the treatment of bone and joint infectious diseases, a specialist center with a regional value since 2011, attracting
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ACCEPTED MANUSCRIPT patients from throughout northern Italy and corresponding to the highest measured SIR in one of the participating hospitals (Figure 1). The distribution of isolated pathogens in different infection sites is comparable to what was observed in a similar study conducted in Piedmont in 2010, with the exception of respiratory tract
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infections (RTIs); in the Piedmont study the prevailing microorganisms cultured from RTIs were Staphylococcus aureus (23.4%) and Pseudomonas aeruginosa (20.8%), while in our study the most common pathogens were, in order of frequency, Klebsiella pneumoniae (27.3%) followed by
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Enterobacter spp (13.6%) and only 9% of RTIs were caused by Staphylococcus aureus.6 This may
microorganisms. As is clear from the ECDC reports
3, 16
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suggest a growing trend of Enterobacteriaceae which tends to replace gram-positive
, Italy is among the European countries with the highest
levels of antibiotic resistance in Staphylococcus aureus and Enterobacteriaceae. Our data partially confirm the national trend, with 50% of Staphylococcus aureus resistant to meticillin (although
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lower than the national average of 62.1%), over 80% of Klebsiella pneumoniae resistant to thirdgeneration cephalosporin and over 60% to carbapenems, and proportions of Enterobacteriaceae
respectively.
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non susceptible to third-generation cephalosporins and carbapenems of 52.2% and 26.7%,
With regard to the antimicrobial use, despite the higher HAI prevalence, the use of antibiotics is
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lower than in the previous study conducted in Liguria (45.6% of subjects exposed to antibiotics versus 58.4%, respectively). 4
This difference may be due to the inclusion in our study of psychiatric wards with low antibiotic use, although only 108 patients were enrolled in psychiatry, too few to influence the overall prevalence of antimicrobial use. Moreover, the difference could be explained by an increased attention to the use of antibiotics for indications other than healthcare-associated infections, also because of some control measures introduced meantime in our region with the aim of improving the
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ACCEPTED MANUSCRIPT use of antibiotics; for example, in recent years in Liguria a semi-restrictive mode has been introduced for the authorization to use certain classes of antibiotics in public health facilities, which requires the approval of a specialist physician in infectious diseases However, the antimicrobial use measured in our study is slightly higher than the national average
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(44.0%) and even greater than the European data on antibiotic consumption, reaching overall 32.7%.3, 17This data is even more worrying considering that Italy is among the European countries with the widest spread of antibiotic-resistant strains. 3, 16
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Similar to the Italian trend, the data collected in Liguria show that carbapenems are ranked fifth among the most widely used antibiotic classes. 3 This could be explained by the higher frequency of 3, 16
In addition, some data show an
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gram-negatives resistant to third-generation cephalosporins.
improper use of antibiotics, as in the case of surgical prophylaxis, where the use of antimicrobials exceeded one day in 50.5% of cases. 3 Conclusions
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Although significant progress has been made in recent years to implement prevention strategies in Ligurian hospitals, HAIs remain a serious public health problem. The high prevalence of HAIs, especially in ICUs, requires both HAI surveillance and effective policies to contain outbreaks,
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through a full understanding of the types of HAIs and the affected patient populations. The high rates of carbapenem resistance and the high levels of antimicrobial use often unjustified,
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as evidenced, for example, in the use of antibiotics in prophylaxis extended over one day, illustrate the urgent need for the capacity of strengthening in both rational antimicrobial use and infection control efforts at national, regional and local levels. Recently, the Italian Ministry of Health has presented to the State-Regions Conference the National Plan for the Antimicrobial Resistance 2017-2020, which involves all Italian regions in countering the phenomenon, through the prevention and control of infections by resistant microorganisms, the training of healthcare professionals, population education and research aimed at appropriate use of
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ACCEPTED MANUSCRIPT antibiotics and the surveillance of their consumption with the purpose of achieving a significant reduction of antibiotic employment, both in the health and veterinary sectors. Despite the intrinsic limitations of prevalence investigations, for the first time, an international protocol was used in Liguria for a regional survey, allowing us to compare our results with those of
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similar studies conducted at national and European levels. Moreover, point prevalence studies, when periodically repeated, provide a large amount of information on the size of the phenomenon and its trend over time, highlighting the potential effects of strategies adopted. Furthermore, data
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sharing should promote greater attention to the problem, at the local and regional level, and strengthen infrastructure and expertise to implement the surveillance. Additionally, the
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identification of common problems allows the establishment of shared priorities, and evaluation of the impact of the strategies.
Although a previous investigation was carried out in Liguria with the same purpose, the results are not directly comparable due to the different study protocol used in the 2007 survey; therefore our
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most recent experience must be considered a starting point and further assessments will be possible when future surveillance data are available, according to the regional prevention plan 2014-2018,
REFERENCES
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which requires a prevalence survey every year.
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1. K Weist and L Diaz Högberg. ECDC publishes 2015 surveillance data on antimicrobial resistance and antimicrobial consumption in Europe. Euro Surveill 2016 Nov 17; 21(46): 30401. doi: 10.2807/1560-7917.ES.2016.21.46.30399 2. Zarb P, Coignard B, Griskeviciene J et al. The European Centre for Disease Prevention and Control (ECDC) pilot point prevalence survey of healthcare-associated infections and antimicrobial
use.
Euro
Surveill
2012;17(46):pii=20316.
http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20316
14
Available
online:
ACCEPTED MANUSCRIPT 3. European Centre for Disease Prevention and Control. Point prevalence survey of healthcare associated
infections
and
antimicrobial
use
in
European
acute
care
hospitals. ECDC, Stockholm, Sweden; 2013 4. Durando P, Icardi G, Ansaldi F et al. Surveillance of hospital-acquired infections in Liguria,
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Italy: results from a regional prevalence study in adult and paediatric acute-care hospitals. J Hosp Infect 2009 Jan;71(1):81-87
5. McCabe WR, Jackson GG. Gram-negative bacteraemia: I. Etiology and ecology. Arch
SC
Intern Med 1962; 110:847-53
6. Charrier et al. Surveillance of healthcare-associated infections in Piemonte, Italy: results
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from a second regional prevalence study. BMC Public Health 2014; 14:558 7. Pellizzer G, Mantoan P, Timillero L et al. Prevalence and risk factors for nosocomial infections in hospitals of the Veneto region, north-eastern Italy. Infection 2008; 36:112–119 8. The French Prevalence Survey Study Group: Prevalence of nosocomial infections in France:
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results of the nationwide survey in 1996. J Hosp Infect 2000; 46:186–193 9. Plowman R, Graves N, Griffin MA et al. The rate and cost of hospital-acquired infections occurring in patients admitted to selected specialties of a district general hospital in England
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and the national burden impose. J Hosp Infect 2001; 47:198–209 10. Hopmans TE, Blok HE, Troelstra A, Bonten MJ. Prevalence of hospital-acquired infections
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during successive surveillance surveys conducted at a University Hospital in the Netherlands. Infect Control Hosp Epidemiol 2007; 28:459–465 11. Gordts B, Vrijens F, Hulstaert F, Devriese S, Van de Sande S. The 2007 Belgian national prevalence survey for hospital-acquired infections. J Hosp Infect 2010; 75:163–167 12. Moro ML, Stazi MA, Marasca G, Greco D, Zampieri A. National prevalence survey of hospital-acquired infections in Italy, 1983. J Hosp Infect 1986; 8:72–85
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ACCEPTED MANUSCRIPT 13. EPINE Working Group. Prevalence of hospital-acquired infections in Spain. J Hosp Infect 1992; 20:1–13 14. Vaqué J, Rosselló J, Trilla A et al. Nosocomial infections in Spain: results of five nationwide serial prevalence surveys (EPINE Project, 1990 to 1994). Nosocomial Infections
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Prevalence Study in Spain. Infect Control Hosp Epidemiol 1996; 17:293–297
15. Emmerson AM, Enstone JE, Griffin M, Kelsey MC, Smyth ET. The Second National Prevalence Survey of infection in hospitals – overview of the results. J Hosp Infect 1996;
SC
32:175–19
16. European Centre for Disease Prevention and Control. Antimicrobial resistance surveillance
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in Europe 2014. Annual Report of the European Antimicrobial Resistance Surveillance Network (EARS-Net). Stockholm: ECDC; 2015
17. European Centre for Disease Prevention and Control. Surveillance of antimicrobial
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consumption in Europe 2012. Stockholm: ECDC; 2014.
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ACCEPTED MANUSCRIPT
Table I. Risk factor assessment: results of univariate and multivariable analysis Patients with HAI (N = 376) (n, %)
Patients without HAI (N = 3271) (n, %)
Crude OR (95% CI)
1916 (52.54) 1730 (47.44) 1 (0.03)
195 (51.86) 181 (48.14) 0 (0)
1721 (52.61) 1549 (47.36) 1 (0.03)
Reference 1.03 (0.83 – 1.28) -
934 (25.61) 2713 (74.39)
48 (12.77) 328 (87.23)
886 (27.09) 2385 (72.91)
936 (26.81) 842 (24.12) 751 (21.51) 962 (27.56)
21 (5.68) 27 (7.30) 81 (21.89) 241 (65.14)
915 (29.32) 815 (26.11) 670 (21.47) 721 (23.10)
108 (2.96) 1749 (47.96) 649 (17.80) 304 (8.34) 230 (6.31) 189 (5.18) 180 (4.94) 162 (4.44) 76 (2.08)
2 (0.53) 180 (47.87) 58 (15.43) 41 (10.90) 7 (1.86) 29 (7.71) 43 (11.44) 4 (1.06) 12 (3.19)
106 (3.24) 1569 (47.97) 591 (18.07) 263 (8.04) 223 (6.82) 160 (4.89) 137 (4.19) 158 (4.83) 64 (1.96)
Reference 6.08 (1.91 – 37.04) 5.20 (1.59 – 32.02) 8.26 (2.48 – 51.25) 1.66 (0.39 – 11.29) 9.61 (2.81 – 60.20) 16.64 (4.97 – 103.40) 1.34 (0.26 – 9.80) 9.94 (2.60 – 65.18)
2217 (60.79) 730 (20.02) 521 (14.29) 179 (4.91)
147 (39.10) 115 (30.59) 93 (24.73) 21 (5.59)
2070 (63.28) 615 (18.80) 428 (13.08) 158 (4.83)
Reference 2.63 (2.03 – 3.41) 3.06 (2.31 – 4.04) 1.88 (1.12 – 2.98)
190 (50.53) 59 (15.69) 127 (33.78) 0 (0)
2337 (71.45) 317 (9.69) 614 (18.77) 3 (0.09)
Reference 2.29 (1.66 – 3.12) 2.54 (1.99 – 3.23) -
34 (9.04) 171 (45.48) 136 (36.17) 35 (9.31)
1022 (31.24) 1446 (44.21) 730 (22.32) 73 (2.23)
Reference 3.55 (2.47 – 5.26) 5.60 (3.85 – 8.37) 14.41 (8.50 – 24.53)
1035 (28.38) 2093 (57.39) 466 (12.78) 107 (2.93)
179 (47.61) 210 (55.85) 138 (36.70) 33 (8.78)
856 (26.17) 1883 (57.57) 328 (10.03) 74 (2.26)
2.56 (2.06 – 3.18) 0.94 (0.76 – 1.16) 5.20 (4.09 – 6.59) 4.16 (2.69 – 6.32)
716 (19.63) 2032 (55.72) 899 (24.65)
64 (17.02) 193 (51.33) 119 (31.65)
652 (19.93) 1839 (56.22) 780 (23.85)
Reference 1.07 (0.8 – 1.45) 1.55 (1.13 – 2.15)
p-value
Adjusted OR (95%CI)
p-value
1056 (28.96) 1617 (44.34) 866 (23.75) 108 (2.96)
LOS, length of stay (days); NHSN, National Healthcare Safety Network
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2527 (69.29) 376 (10.31) 741 (20.32) 3 (0.08)
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0.86
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Gender Female Male Other Age (years) 0 – 54 > 54 LOS before inclusion in the survey (days) (n=3491) 0–3 4–7 8 – 14 > 14 Specialty of ward Psychiatry Medicine Surgery Orthopaedy and traumatology Paediatrics and neonatology Rehabilitation Intensive care Gynaecology and obstetrics Geriatrics McCabe Score Nonfatal Ultimately fatal Rapidly fatal Unknown Surgery None Non-NHSN NHSN Unknown Number of devices 0 1 2 >2 Type of device Urinary catheter Peripheral vascular line Central vascular line Tracheal intubation or tracheostomy Size of hospital < 200 beds 200 – 500 beds > 500 beds
Overall (N = 3,647) (n, %)
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Characteristics
< 0.001
Reference 2.54 (1.88 – 3.51)
0.03 Reference 1.53 (1.05 – 2.28)
< 0.001
Reference 1.44 (0.81 – 2.60) 5.27 (3.29 – 8.81) 14.56 (9.45 – 23.67)
< 0.001 Reference 1.32 (0.73 – 2.42) 4.09 (2.50 – 7) 10.84 (6.75 – 18.24)
< 0.001
0.22 Reference 1.08 (0.31 – 6.91) 0.85 (0.23 – 5.55) 1.63 (0.43 – 10.75) 0.64 (0.14 – 4.56) 1.42 (0.38 – 9.28) 1.20 (0.30 – 8.09) 1.52 (0.35 – 10.71) 0.95 (0.14 – 7.76)
< 0.001
0.049 Reference 1.50 (1.10 – 2.05) 1.38 (0.98 – 1.95) 1.55 (0.81 – 2.82)
< 0.001
0.007 Reference 1.52 (1.04 – 2.20) 1.67 (1.18 – 2.37) -
< 0.001
< 0.001 Reference 3.47 (2.26 – 5.48) 3.26 (1.67 – 6.46) 3.66 (1.17 – 11.25)
< 0.001 0.56 < 0.001 < 0.001 0.005
1.09 (0.67 – 1.76)
0.71
2.23 (1.62 – 3.07) 1.35 (0.60 – 3)
< 0.001 0.47 0.10
Reference 0.94 (0.67 – 1.33) 0.71 (0.48 – 1.05)
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Table II. Prevalence of healthcare-associated infections (HAIs) according to site and ward specialties SUR (N = 649)
ORT (N = 304)
PED (N = 230)
RHB (N = 189)
ICU (N = 180)
GYN (N = 162)
PSI (N = 108)
GER (N = 76)
N (%)
P (%) (95%CI)
N (%)
P (%) (95%CI)
N (%)
P (%) (95%CI)
N (%)
P (95%CI)
N (%)
P (%) (95%CI)
N (%)
P (%) (95%CI)
N (%)
P (%) (95%CI)
N (%)
P (%) (95%CI)
N (%)
P (%) (95%CI)
N (%)
P (%) (95%CI)
N. of pts with HAI
376
10.3 (9.4-11.3)
180
10.3 (8.9-11.8)
58
8.9 (7-11.4)
41
13.5 (10.1-17.8)
7
3 (1.2-6.2)
29
15.3 (10.5-21.3)
43
23.9 (17.9-30.8)
4
2.5 (0.7 – 6.2)
2
1.9 (0.2-6.5)
12
15.8 (8.4-26)
N. of HAIs
429
11.8 (10.7-12.9)
201
11.5 65 (10.1-13.1)
15.8 (12-20.5)
7
3 (1.2-6.2)
34
18 (12.9-24.4)
51
28.3 (22-35.6)
4
2.5 (0.7 – 6.2)
2
1.9 (0.2-6.5)
17
22.4 (13.9-33.7)
RTI
93 (21.7)
2.6 (2.1-3.1)
51 2.9 (25.4) (2.2-3.9)
10 (15.4)
1.5 (0.8-2.9)
8 2.6 (16.6) (1.2-5.3)
-
-
2 (5.9)
17 9.4 (33.3) (5.8-14.9)
1 (25)
0.6 (0.03-3.9)
2 1.9 (100) (0.2-6.5)
2 2.6 (11.8) (0.5-10.1)
UTI
86 (20.1)
2.4 (1.9-2.9)
38 2.2 (18.9) (1.6-3)
6 (9.2)
0.9 (0.4-2.1)
13 4.3 (27.1) (2.4-7.4)
3 1.3 (42.8) (0.3-4.1)
15 7.9 (44.1) (4.7-13)
6 3.3 (11.8) (1.4-7.4)
-
-
-
-
5 6.6 (29.4) (2.5-15.3)
BSI
72 (16.8)
2 (1.6-2.5)
36 2.1 (17.9) (1.5-2.9)
10 (15.4)
1.5 (0.8-2.9)
1 (2.1)
2 0.9 (28.6) (0.2-3.4)
5 2.6 (14.7) (1-6.4)
13 7.2 (25.5) (4.1-12.3)
-
-
-
-
5 6.6 (29.4) (2.5-15.3)
SSI
43 (10)
1.2 (0.9-1.6)
10 (5)
0.6 (0.3-1.1)
18 (27.7)
2.8 (1.7-4.4)
6 2 (12.5) (0.8-4.5)
-
-
2 (5.9)
1.1 (0.2-4.2)
5 (9.8)
2.8 (1-6.7)
1 (25)
0.6 (0.03-3.9)
-
-
1 (5.9)
1.3 (0.1-8.1)
GGI
43 (10)
1.2 (0.9-1.6)
19 (9.4)
1.1 (0.7-1.7)
12 (18.5)
1.9 (1-3.3)
1 (2.1)
2 0.9 (28.6) (0.2-3.4)
3 (8.8)
1.6 (0.4-5)
5 (9.8)
2.8 (1-6.7)
-
-
-
-
1 (5.9)
1.3 (0.1-8.1)
CSEP
28 (6.5)
0.8 (0.5-1.1)
18 (9)
1 (0.6-1.7)
3 (4.6)
0.5 (0.1-1.5)
-
-
-
-
1 (2.9)
0.5 (0.03-3.4)
5 (9.8)
2.8 (1-6.7)
1 (25)
0.6 (0.03-3.9)
-
-
-
-
Other
64 (14.9)
1.7 (1.4-2.2)
29 1.6 (14.5) (1.1-2.4)
6 (9.2)
0.9 (0.4-2.1)
19 6.3 (39.6) (3.9-9.8)
-
-
6 3.2 (17.7) (1.3-7.1)
-
-
1 (25)
0.6 (0.03-3.9)
-
-
3 4 (17.6) (1-11.9)
10 48 (7.9-12.6)
0.3 (0.02-2.1)
TE D
0.3 (0.02-2.1)
1.1 (0.2-4.2)
M AN U
N. of sites with HAI
RI PT
MED (N = 1749)
SC
Total (N = 3647)
EP
MED, Medicine; SUR, Surgery; ORT, Orthopaedy and traumatology; PED, Paediatrics and neonatology; RHB, Rehabilitation; ICU, Intensive care; GYN, Gynaecology and obstetrics; PSI, Psychiatry; GER, Geriatrics.
AC C
P, Prevalence of infected sites in all patients; 95%CI, 95% confidence interval
RTI, respiratory tract infection; UTI, urinary tract infection; BSI, laboratory-confirmed bloodstream infection; SSI, surgical site infection; GII, gastro-intestinal infection; SST, soft skin tissue infection; OTH, other infection
ACCEPTED MANUSCRIPT
Table III. Distribution of pathogens causing HAIs, overall and stratified for site infection
72 (100)
21 (48.8)
75
81
24
61 (81.3) 30 (40.1) 10 (13.3) 2 (2.7) 4 (5.3) 8 (10.7) 2 (2.7) 1 (1.3) 0 (0) 3 (4.9) 1 (1.3) 11 (14.7) 2 (2.7) 0 (0) 8 (10.7) 0 (0) 0 (0) 1 (1.3) 3 (4) 2 (2.7) 1 (1.3) 0 (0) 0 (0)
24 (29.6) 8 (9.9) 10 (12.4) 1 (1.2) 3 (3.7) 0 (0) 1 (1.2) 0 (0) 0 (0) 1 (1.2) 0 (0) 46 (56.8) 9 (11.1) 26 (32.1) 8 (9.9) 3 (3.7) 0 (0) 0 (0) 11 (13.6) 4 (4.9) 7 (8.7) 0 (0) 0 (0)
17 (70.8) 6 (25) 3 (12.5) 0 (0) 2 (8.3) 1 (4.2) 2 (8.3) 0 (0) 2 (8.3) 1 (4.2) 0 (0) 6 (25) 2 (8.3) 1 (4.2) 3 (12.5) 0 (0) 0 (0) 0 (0) 1 (4.2) 1 (4.2) 0 (0) 0 (0) 0 (0)
OTH (N = 77)
29 (67.4)
4 (26.7)
11 (14.3)
31
4
11
4 (12.9) 1 (3.2) 3 (9.7) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 26 (83.9) 0 (0) 3 (9.7) 1 (3.2) 0 (0) 22 (71) 0 (0) 1 (3.2) 1 (3.2) 0 (0) 0 (0) 0 (0)
2 (50) 0 (0) 1 (25) 0 (0) 1 (25) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 2 (50) 1 (25) 0 (0) 0 (0) 0 (0) 0 (0) 1 (25) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0)
3 (27.3) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 2 (18.2) 0 (0) 1 (9.1) 0 (0) 6 (54.5) 3 (27.3) 1 (9.1) 1 (9.1) 1 (9.1) 0 (0) 0 (0) 1 (9.1) 1 (9.1) 0 (0) 0 (0) 1 (9.1)
SC
RI PT
SST (N = 30)
M AN U
16 (72.8) 0 (0) 6 (27.3) 1 (4.6) 2 (9.1) 1 (4.6) 3 (13.6) 0 (0) 0 (0) 0 (0) 3 (13.6) 3 (13.6) 2 (9.1) 0 (0) 1 (4.6) 0 (0) 0 (0) 0 (0) 3 (13.6) 1 (4.6) 0 (0) 2 (9.1) 0 (0)
61 (70.9)
TE D
Gram-negative bacteria Escherichia coli Klebsiella pneumoniae Other Klebsiella spp Pseudomonas aeruginosa Proteus spp. Enterobacter spp. Acinetobacter baumannii Citrobacter spp. Other enterobacteriacee Other Gram-negative bacteria Gram-positive bacteria Staphylococcus aureus Coagulase-negative Staphylococci Enterococcus spp. Streptococcus spp. Clostridium difficile Other Gram-positive bacteria Fungi Candida albicans Other candida Aspergillus spp. Virus
BSI (N = 72)
EP
N. of infections with isolation of 17 (18.2) at least one pathogens (N, %) Total isolated pathogens 22
UTI (N = 86)
AC C
RTI (N = 93)
HAI-type, N (%) SSI (N = 43) GII (N = 43)
All (N= 429) 215 (50.1) 248 127 (51.2) 45 (18.2) 33 (13.4) 4 (1.6) 12 (4.8) 10 (4) 8 (3.2) 3 (1.2) 2 (0.8) 6 (2.4) 4 (1.6) 100 (40.3) 19 (7.7) 31 (12.5) 22 (8.9) 4 (1.6) 22 (8.9) 2 (0.8) 20 (8.1) 10 (4) 8 (3.2) 2 (0.8) 1 (0.4)
RTI, respiratory tract infection; UTI, urinary tract infection; BSI, laboratory-confirmed bloodstream infection; SSI, surgical site infection; GII, gastro-intestinal infection; SST, soft skin tissue infection; OTH, other infection
ACCEPTED MANUSCRIPT
Table IV. Antimicrobial resistance of the main isolated microorganisms Tested sensitivity N
Oxacillin
Third generation cephalosporins
Carbapenems
Resistant N (%)
Resistant N (%)
Resistant N (%)
-
47 (52.2)
24 (26.7)
-
13 (35.1)
1 (2.7)
-
28 (82.4)
22 (64.7)
108
90
-
Escherichia coli
45
37
-
Klebsiella spp
37
34
-
Proteus spp
10
7
-
-
2 (28.6)
1 (14.3)
Other Enterobacteriaceae
16
12
-
-
4 (33.3)
0 (0)
Enterococcus spp
22
15
-
1 (6.7)
-
-
Staphylococcus aureus
19
18
9 (50)
-
-
-
Acinetobacter baumannii
3
1
-
-
-
1 (100.0)
Pseudomonas spp
13
8
-
-
-
3 (37.5)
AC C
EP
TE D
M AN U
Total Enterobacteriaceae
SC
Resistant N (%)
Glycopeptides (vancomycin, teicoplanin)
RI PT
Total isolated N
ACCEPTED MANUSCRIPT
Table V. Prescribed antibiotic molecules and indications for their use Percentage indication for treatment
Percentage of Total prescriptions
Therapy 30.0
20.8
1 064
67.0
46.5
47
3.0
2.1
Total therapy
1 588
100.0
69.4
396
58.9
Prophylaxis Medical prophylaxis
140
20.8
Surgical prophylaxis, single dose
112
16.6
Surgical prophylaxis, one day
25
3.7
Total prophylaxis
673
100.0
Other indication Truly unknown, information not verified during the survey
12
Unknown indication (confirmed)
12
Total other indications/unknown
28
AC C
4
17.3 6.1
4.9
1.1
29.4
42.9
0.5
14.2
0.2
42.9
0.5
EP
Other indications/unknown
TE D
Surgical prophylaxis, > 1 day
SC
477
Community-acquired infection Infection acquired in long-term care facility (e.g. nursing home) or chronic care hospital
M AN U
Acute hospital-acquired infection
100.0
RI PT
Total prescribed antibiotic molecules
Number of antibiotics 2 289
1.2
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
Figure 1. Standardized ratios observed/expected and 95% confidence intervals of infections and antimicrobial use measured for each of the eighteen hospitals enrolled in Liguria
1
ACCEPTED MANUSCRIPT LEGENDS
AC C
EP
TE D
M AN U
SC
RI PT
Figure 1 SIR, Standardized Infection Ratio; SAUR, Standardized Antimicrobial Use Ratio; The vertical lines are placed at the value 1, no difference between observed and expected cases; SIR<1, fewer infections observed than expected; SIR>1, number of infections observed higher than expected; SAUR<1, fewer antibiotic treatments observed than expected; SAUR>1, number of antibiotic treatments observed higher than expected
2