Containment of carbapenem-resistant Enterobacterales colonisations and infections: Results from an integrated infection control intervention in a large hospital trust of northern Italy.

PURPOSE: We describe the results of an infection control intervention, implemented in 4 tertiary hospitals in Romagna, Italy, aiming at containing the spread of carbapenem-resistant Enterobacterales (CRE). METHODS: The intervention consisted of rectal screening in patients at risk for CRE; pre-emptive contact precaution waiting for screening results; timely notification of CRE identification and concomitant computerized alert; contact precaution for confirmed CRE-positive patients. We performed an interrupted time series analysis to compare the incidence of CRE bacteraemia, of other CRE infections, and CRE-positive rectal swabs in the pre and postintervention period (January 2015-July 2017 and August 2017-June 2020, respectively). RESULTS: 4,332 CRE isolates were collected. Klebsiella pneumoniae was the most represented pathogen (n = 3,716, 85%); KPC production was the most common resistance mechanism (n = 3,896, 90%). The incidence rate of CRE bacteraemia significantly decreased from 0.554 to 0.447 episodes per 10.000 patient days in the early postintervention period (P = .001). The incidence rate of other CRE infections significantly decreased from 2.09 to 1.49 isolations per 10.000 patient days in the early postintervention period (P = .021). The monthly number of rectal swabs doubled in the postintervention period and there was a significant reduction trend of CRE-positive swabs, sustained over time (P < .001). CONCLUSIONS: The infection control intervention was successful in containing the spread of CRE infections and colonisations.

Use of health databases to deal with underreporting of surgical site infections due to suboptimal post-discharge follow-up.

This study describes a combined surveillance of surgical site infection implemented in an Italian region, which relies on integration of the specific surveillance (SIChER) with other sources and the targeted review of a small proportion of cases. Additional information on post-surgical follow-up was obtained from hospital discharge, microbiology laboratory and emergency department databases. Based on these data, 76 patients were reclassified as possible cases and revised by the health trust representatives. Eventually 45 new cases were confirmed, leading to an increase in the infection ratio from 1.13% to 1.45%. The proposed method appears to be accurate and sustainable over time.

Colonization and infection due to carbapenemase-producing Enterobacteriaceae in liver and lung transplant recipients and donor-derived transmission: a prospective cohort study conducted in Italy.

OBJECTIVES: A prospective cohort study was conducted in Italy in order to describe the microbiologic aspects of colonization/infection by carbapenemase-producing Enterobacteriaceae (CPE) in donors and recipients of lung and liver transplants and the possible CPE transmission from donors to recipients. METHODS: Between 15 January 2014 and 14 January 2015, all recipients of solid organ transplants (SOT) at ten lung and eight liver transplantation centres and the corresponding donors were enrolled. Screening cultures to detect CPE were performed in donors, and screening and clinical cultures in recipients with a 28-day microbiologic follow-up after receipt of SOT. Detection of carbapenemase genes by PCR, genotyping by multilocus sequence typing, and pulsed-field gel electrophoresis and whole-genome sequencing were performed. RESULTS: Of 588 screened donors, 3.4% were colonized with CPE. Of the liver first transplant recipients (n = 521), 2.5% were colonized before receipt of SOT and 5% acquired CPE during follow-up. CPE colonization was higher in lung first transplant recipients (n = 111, 2.7% before SOT and 14.4% after SOT). CPE infections occurred in 1.9% and 5.3% of liver or lung recipients, respectively. CPE isolates were mostly Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae belonging to CG258. Three events of donor-recipient CPE transmission, confirmed by whole-genome sequencing and/or pulsed-field gel electrophoresis, occurred in lung recipients: two involving K. pneumoniae sequence type 512 and one Verona integron-encoded metallo-ß-lactamase (VIM)-producing Enterobacter aerogenes. CONCLUSIONS: This study showed a low risk of donor-recipient CPE transmission, indicating that donor CPE colonization does not necessarily represent a contraindication for donation unless colonization regards the organ to be transplanted. Donor and recipient screening remains essential to prevent CPE transmission and cross-infection in transplantation centres.

Strategies to control antibiotic resistance: results from a survey in Italian children's hospitals.

BACKGROUND: Antimicrobial stewardship programs and comprehensive infection control programs represent the main strategies to limit the emergence and transmission of multi-drug resistant bacteria in hospital settings. The purpose of this study was to describe strategies implemented in Italian children's hospitals for controlling antibiotic resistance. STUDY DESIGN: Cross sectional multicenter study. METHODS: Four tertiary care Italian children's hospitals were invited to participate in a survey aimed at collecting information on activities implemented as of December 2015 using a self-administered online questionnaire. The questionnaire was divided in three sections focalizing on: i) policies for prevention and control of hospital-acquired infection, ii) prevention and control of multi-drug resistant bacteria, and iii) antibiotic prescribing policies and Antimicrobial stewardship programs. Questionnaires were compiled between May and July 2016. RESULTS: All hospitals had multidisciplinary infection control committee, procedures on hand hygiene, isolation measures, disinfection/sterilization, waste disposal and prevention on infections associated to invasive procedures. All sites screened patients for multi-drug resistant bacteria colonization in selected units, and adopted contact precautions for colonized patients. Screening during hospitalization, or in case of infections in the same ward were not universally implemented. All hospitals had policies on surgical prophylaxis, while policies on medical prophylaxis and treatment of bacterial infections varied among sites. Two sites recommended to review the appropriateness of antibiotic prescribing after 48-72 hours and one recommended de-escalation therapy. CONCLUSIONS: This study highlighted several areas of improvement, such as actions for screening patients in case of occurrence of multi-drug resistant bacteria, antimicrobial stewardship programs and implementation of policies targeting antibiotic prescriptions for therapeutic purposes and medical prophylaxis.

Control of carbapenemase-producing Klebsiella pneumoniae: a region-wide intervention.

Starting in 2010, there was a sharp increase in infections caused by Klebsiella pneumoniae resistant to carbapenems in the Emilia-Romagna region in Italy. A region-wide intervention to control the spread of carbapenemase-producing K. pneumoniae (CPKP) in Emilia-Romagna was carried out, based on a regional guideline issued in July 2011. The infection control measures recommended to the Health Trusts (HTs) were: phenotypic confirmation of carbapenemase production, active surveillance of asymptomatic carriers and contact isolation precautions for carriers. A specific surveillance system was activated and the implementation of control measures in HTs was followed up. A significant linear increase of incident CPKP cases over time (p<0.001) was observed at regional level in Emilia-Romagna in the pre-intervention period, while the number of cases remained stable after the launch of the intervention (p=0.48). Considering the patients hospitalised in five HTs that provided detailed data on incident cases, a downward trend was observed in incidence after the release of the regional guidelines (from 32 to 15 cases per 100,000 hospital patient days). The spread of CPKP in Emilia-Romagna was contained by a centrally-coordinated intervention. A further reduction in CPKP rates might be achieved by increased compliance with guidelines and specific activities of antibiotic stewardship.

Hospital statistics for antibiotics: defined versus prescribed daily dose.

PURPOSE: Defined daily doses (DDD) are widely used as a unit to measure drug use in hospital and community settings. However, discrepancies exist between DDD and actual prescribed daily dose (PDD). The present study aims at estimating an alternative PDD (PDD-proxy) to calculate rates of systemic antibiotic consumption and to compare these results with those obtained using DDD. METHODS: The study considered a 9-year period (2004-2012) and included the 17 Health Trusts (HTs) in the Emilia-Romagna Region, Italy. Drugs under study were antibacterials for systemic use (group J01). Data were obtained from the database for hospital drug prescription of Emilia-Romagna Region. The PDD-proxy was estimated by averaging the doses of antibiotic prescriptions from a point prevalence survey for healthcare-associated infections and antimicrobial use, conducted in Emilia-Romagna hospitals in 2012. RESULTS: Significant discrepancies between DDD and PDD were observed, especially for some antibiotics, resulting in DDD rates that were systematically higher than PDD-proxy rates. In 2012, HT median rates of antibiotic consumption were 90 DDD/100 bed days and 70 PDD-proxy/100 bed-days. However, PDD-proxy and DDD rates showed comparable trends within HTs, although some HTs ranked differently when one or the other measure was used. Interquartile ranges of DDD rates were systematically wider than those of PDD-proxy rates in most years in the period of interest. CONCLUSIONS: Comparison of HT antibiotic consumption using DDDs may artificially increase observed differences and affect the true HT ranking. Therefore, an additional unit of measurement is useful for in-depth analysis at the local level.

The Italian national surgical site infection surveillance programme and its positive impact, 2009 to 2011.

Programmes surveying surgical site infection (SSI) have been implemented throughout the world and are associated with a reduction in SSI rates. We report data on non-prosthetic surgery from the Italian SSI surveillance programme for the period 2009 to 2011. Participation in the programme was voluntary. We evaluated the occurrence of SSI, based on protocols from the European Centre for Disease Prevention and Control, within 30 days of surgery. Demographic data, risk factors, type of surgery and presence of SSI were recorded. The National Coordinating Centre analysed the pooled data. On 355 surgical wards 60,460 operations were recorded, with the number of surveyed intervention doubling over the study period. SSI was observed in 1,628 cases (2,6%) and 60% of SSI were diagnosed through 30-days post discharge surveillance. Operations performed in hospitals with at least two years of surveillance showed a 29% lower risk of SSI. Longer intervention duration, American Society of Anesthesiologists' (ASA) score of at least three, and pre-surgery hospital stay of at least two days were associated with increased risk of SSI, while videoscopic procedures had reduced SSI rates. Implementation of a national surveillance programme was helpful in reducing SSI rates and should be prioritised in all healthcare systems.

Active surveillance for asymptomatic carriers of carbapenemase-producing Klebsiella pneumoniae in a hospital setting.

The spread of carbapenemase-producing Klebsiella pneumoniae (CPKP) is a challenging public health threat. Early identification and isolation of infected patients and carriers are key measures of control. This study describes a CPKP screening strategy in a tertiary Italian hospital. During the five-month study period, 1687 patients were screened by rectal swabs. Of these, 65 (3.9%) tested positive for CPKP; 5.1% of case contacts tested positive. Screening case contacts appears to be the essential surveillance component for detecting asymptomatic carriers of CPKP. The added value of selective CPKP screening on hospital admission depends on the frequency of carriers among incoming patients.

Long-term chikungunya infection clinical manifestations after an outbreak in Italy: a prognostic cohort study.

OBJECTIVES: Following a Chikungunya (CHIKV) outbreak in Italy, a cohort study was conducted to describe the infection long-term clinical course and outcome. METHODS: Persons identified through active and passive surveillance as confirmed or possible CHIKV cases during the outbreak were enrolled and interviewed by trained public health nurses, between 4-5 and 12-13 months following the acute stage. Patients reporting persistent clinical symptoms were evaluated by rheumatologists. Serum samples were obtained and anti-CHIKV specific IgG and IgM immune responses detected. Only confirmed cases who completed the follow-up were analysed. RESULTS: Out of 250 patients, 66.5% still reported myalgia, asthenia or arthralgia (most frequent sign) after 12 months. Functional ability, measured by the ROAD index, was more impaired for lower extremities (3.75; Inter Quartile Range - IQR 4.4), and the activities of daily living (average 4.2; IQR 5). Variables independently associated with the presence of joint pain at 12-13 months were increasing age, and history of rheumatologic diseases). Elderly, females, and persons with history of rheumatologic diseases had higher anti-CHIKV IgG titres at 12-13 months. CONCLUSIONS: This study confirms, in an unselected population, that the long-lasting burden of CHIKV infection is significant.

Secular trends in antibiotic consumption in the adult population in Emilia-Romagna, Italy, 2003-2009.

Antibiotic resistance is closely related to antibiotic use and Italy is a country with high levels of both antibiotic use and antimicrobial resistance. We analysed the trend in antibiotic use in the community among adults (≥15 years) and elderly, in the period 2003-2009, in Emilia-Romagna, Italy, a region with over 4 000 000 inhabitants. Data regarding antibiotic use were obtained from the regional public health system databases. Between 2003 and 2009 the antibiotic consumption increased from 15.4 to 18.7 defined daily doses/1000 inhabitants per day (DID) (+21.4%, p <0.0001). The prescription rate in 2009 was 2.19 prescriptions/1000 inhabitants per day, an increase of 13.8% compared with 2003. The highest increase in antibiotic use was observed among persons aged 20-59 years (+24.7%). The proportion of inhabitants receiving at least one antibiotic treatment was 36.4% in 2003 and 39.7% in 2009, and the proportions receiving at least three antibiotic treatments were 3.5% and 4.2%, respectively. The H1N1 pandemic was associated, in October and November 2009, with a 37-90% increase in antibiotic use among the 15-19-year and 20-59-year age groups compared with 2007 and 2008. No other difference was observed in any other age group. The analysis per antibiotic class showed increases for penicillin + beta-lactamase inhibitor (from 3.6 to 6.3 DID), quinolones (from 2.6 to 3.0 DID) and macrolides (from 3.1 to 3.7 DID), whereas cephalosporin use was stable (1.4 DID). A steady increase in antibiotic use in the adult population has been observed in the Emilia-Romagna: public health interventions are mandatory to counteract this trend.

Escherichia coli and Staphylococcus aureus: bad news and good news from the European Antimicrobial Resistance Surveillance Network (EARS-Net, formerly EARSS), 2002 to 2009.

Based on data collected by the European Antimicrobial Resistance Surveillance Network (EARS-Net) and the former EARSS, the present study describes the trends in antimicrobial susceptibility patterns and occurrence of invasive infections caused by Escherichia coli and Staphylococcus aureus in the period from 2002 to 2009. Antimicrobial susceptibility results from 198 laboratories in 22 European countries reporting continuously on these two microorganisms during the entire study period were included in the analysis. The number of bloodstream infections caused by E. coli increased remarkably by 71% during the study period, while bloodstream infections caused by S. aureus increased by 34%. At the same time, an alarming increase of antimicrobial resistance in E. coli was observed, whereas for S. aureus the proportion of meticillin resistant isolates decreased. The observed trend suggests an increasing burden of disease caused by E. coli. The reduction in the proportion of meticillin-resistant S. aureus and the lesser increase in S. aureus infections, compared with E. coli, may reflect the success of infection control measures at hospital level in several European countries.

Knowledge, attitudes and practices survey after an outbreak of chikungunya infections.

In 2007, the first chikungunya outbreak ever occurring in a temperate area of the Northern Hemisphere was reported in Emilia-Romagna, Italy. The present study aims to evaluate knowledge, attitudes and practices regarding chikungunya infection. Information was collected by standardised telephone questionnaire, administered to 325 people during a seroprevalence survey performed in the outbreak area. Most people (61%) knew that Chikungunya virus is transmitted through mosquito bites. A significant proportion of respondents perceived chikungunya infection as a high-risk disease (49.8%) and declared their intention to use mosquito repellents in the future (47.4%). Willingness to use skin repellents was more often declared by women, residents in households with children and people who knew infection transmission routes, while perception of high risk related to Chikungunya did not influence claimed future behaviour. Knowledge of the mechanisms of infection transmission was inversely related to risk perception: elderly people were less likely to know the disease than young people, but ranked the risk highest compared to younger age groups. Less educated residents were much more likely to perceive a high risk. After a chikungunya infection outbreak in a temperate area, where mosquito-borne infections have not been previously reported, only half of the study participants declared their intention to use individual protection in the future. Anticipated behaviour was not explained by the level of risk perception, but was associated with knowledge of the disease and demographic characteristics.

Emergence of ciprofloxacin resistance in Escherichia coli isolates from outpatient urine samples.

This study investigated the association between prescription of fluoroquinolones and emergence of ciprofloxacin resistance among Escherichia coli isolates in the urine of outpatients from whom a ciprofloxacin-sensitive E. coli strain had been isolated previously. Patients were identified and followed using the healthcare databases of Emilia-Romagna Region, Italy. The outcome of interest was the first isolation from urine of an E. coli strain resistant to ciprofloxacin. Prescription of fluoroquinolones during the previous 6 months was associated independently with the emergence of ciprofloxacin resistance; the strength of the association varied according to individual fluoroquinolone agents.

Antibiotic treatments for children ages 0-23 months in a northern Italy region: a cohort study.

BACKGROUND: This study aims to describe the pattern of antibiotic treatments in the community for children ages 0-23 months in Emilia-Romagna (a northern Italy region) pointing out possible changes of prescribed agents when first treatments in the life of each children are compared to successive ones. MATERIALS AND METHODS: The Regional Drug Prescription and the Resident Population databases were used as data sources to study the cohort of children born between January 1 and December 31, 2000 and resident in Emilia-Romagna. RESULTS: The cumulative incidences of children with at least one treatment were 22%, 55% and 82% at 6, 12 and 24 months of age, respectively. Broad spectrum penicillins were the most prescribed antibiotic class for children at their first treatment while cephalosporins were the most prescribed class for successive treatments and when pooling all treatments. CONCLUSION: Cephalosporins and other second line antibiotics are frequently prescribed to 0 to 23-month-old residents in Emilia-Romagna even when only first treatments are considered; further research is needed to quantify inappropriateness of antibiotic prescription.

Delay in the treatment of pulmonary TB in a changing demographic scenario.

OBJECTIVE: To quantify patient and health care delays in the treatment of pulmonary tuberculosis (PTB) in Emilia-Romagna region, Italy, and to study the association between migration status and delay. DESIGN: All patients with symptomatic PTB, aged >15 years, who were notified in Emilia-Romagna during 2003 and were alive at time of data collection, were included. An individual form was completed for each notified patient by the local health authority officer in charge of surveillance data. RESULTS: Median patient delay, health care delay and total delay were 7, 36 and 65 days, respectively. Recent migrants (stay in Italy < or = 3 years) had the longest patient delay (16 days), while Italian patients had the longest health care delay (60 days). Migration status was independently associated with both patient and health care delay, although the direction of association changed according to which delay was considered. CONCLUSION: Public health interventions aiming to reduce delay in treatment of PTB should improve the access of recent migrants to health care and increase suspicion of TB among Italian patients. Studies on delays in treatment of TB should investigate patient delay and health care delay as distinct outcomes.

Barriers to effective tuberculosis control: a qualitative study.

SETTING: Emilia Romagna region, Italy. OBJECTIVE: To explore chest and infectious disease physicians' views of barriers to effective tuberculosis (TB) control and possible solutions. DESIGN: A series of nine focus groups including a total of 49 physicians. RESULTS: Three categories of barriers to effective TB control were identified: 1) uncertainty about appropriate clinical practice in the treatment of specific sub-groups of patients, such as the elderly or immigrants; 2) organisational factors, such as the availability of diagnostic services and of sufficient resources; and 3) multiple barriers to a viable and effective TB control programme in a country with a low prevalence of TB. CONCLUSIONS: The lack of integration and coordination of health services, as well as the scarcity of dedicated TB nurses, were perceived by the participants as crucial barriers to effective TB control. As a result of this study, a regional programme was started with the goals of quantifying the need for TB nurses and developing a better network for required health services. Qualitative studies such as this can be useful in improving TB control in a low-prevalence TB country, to identify problems and increase the participation of key professionals.

Quality of local guidelines for surgical antimicrobial prophylaxis.

Surgical antimicrobial prophylaxis (AMP) is an effective measure to prevent surgical site infections. To determine the quality and availability of local guidelines for AMP, a survey was conducted in the public hospitals of a Northern Italian region. The guidelines for "Antimicrobial Prophylaxis in Surgery" by the Scottish Intercollegiate Guidelines Network (SIGN) were used as a standard by which the quality of the local guidelines was compared. The coverage of surgical specialities by local AMP guidelines was 93.1% for hospitals where guidelines had been developed at hospital level and 47% for hospitals where guidelines had been developed by individual surgical departments. Local guidelines recommended AMP for most surgical procedures (96%), including procedures with evidence against the use of antimicrobial prophylaxis (87% of these procedures). Only 8% of all procedure-specific guidelines (PSG) recommended an incorrect timing of AMP (not administering AMP at the induction of anaesthesia), while 41% recommended an incorrect duration (additional antimicrobial doses after completion of the surgical operation). This survey showed that having written protocols at local level does not necessarily mean they comply with available scientific evidence. Thus, the quality of local guidelines needs to be improved.

[Cholestatic liver disease and thrombocytopenia associated with long exposure to ticlopidine]. / Colestasi epatica e trombocitopenia associate a trattamento protratto con ticlopidina.

A 45-year-old woman was admitted to the hospital because of cholestatic liver disease and severe thrombocytopenia following a 4-day history of fever and malaise. In her childhood the patient suffered from acute rheumatic fever with secondary mitral stenosis. Three years before admission, an atrial fibrillation had been diagnosed for which the patient was put on ticlopidine, 250 mg daily, that was taken regularly, without any adverse event. The patient had no history of cholestatic hepatitis or biliary colic. The abdominal ultrasonography was negative for biliary tract diseases and histological features were compatible with drug induced hepatotoxicity. Laboratory tests for viral and bacterial infection were negative. No other medications, apart from 2 doses of nimesulide, had been taken by the patient in the previous days. Ticlopidine was discontinued on admission and both bilirubin and platelet count rapidly normalized. We think that, in our patient, ticlopidine may be responsible of concomitant hematologic and hepatic toxicity and the trigger event might have been the reduced renal excretion of the drug following acute renal failure.