External validation of WGS-based antimicrobial susceptibility prediction tools, KOVER-AMR and ResFinder 4.1, for Escherichia coli clinical isolates.

OBJECTIVE: To externally validate whole genome sequence-antimicrobial susceptibility testing phenotype prediction tools KOVER-AMR and ResFinder 4.1 for Escherichia coli clinical isolates from Dutch routine care. METHODS: A random sample of 234 E. coli and 283 third generation cephalosporin-resistant E. coli isolates from urine and blood were collected (2014-2017). Culture-antimicrobial susceptibility testing was performed using VITEK 2 and BD Phoenix. Sequences were used as input for KOVER-AMR-SCM, KOVER-AMR-CART, and ResFinder 4.1. The concordance, major error rate (MER), and very major error rate (VMER) were calculated, with subsequent comparison to U.S. Food and Drug Administration (FDA) criteria (MER ≤3% and VMER with a 95% confidence interval ≤1.5-≤7.5%). RESULTS: ResFinder 4.1 performed better than KOVER-AMR-models; however, neither tool achieved overall (V)MERs below FDA criteria. KOVER-AMR-SCM, KOVER-AMR-CART, and ResFinder 4.1, MER (cumulative all antimicrobials) were: 5.1% (4.4-5.9), 4.3% (3.6-5.0), and 5.1% (4.5-5.8), respectively. MERs ≤3% were achieved for 6 (SCM) and 5 (CART) of the 11 tested antimicrobials for KOVER-AMR-models and for 9/13 antimicrobials tested with ResFinder 4.1. KOVER-AMR-SCM, KOVER-AMR-CART, and ResFinder 4.1 cumulative VMERs were: 26% (24-28), 29% (27-31), and 11% (9.2-12). VMERs with a 95% CI ≤ 1.5-≤7.5 were only achieved for 4/13 tested antimicrobials with ResFinder 4.1. DISCUSSION: In this study, whole genome sequence-antimicrobial susceptibility testing phenotype prediction tools KOVER-AMR and ResFinder 4.1 did not meet the FDA criteria needed for clinical diagnostic use in 517 E. coli clinical isolates from Dutch routine care. The tested tools should be further improved before they can be used for clinical decision making.

Prevalence of methicillin-resistant Staphylococcus aureus (MRSA) carriage and pattern of antibiotic resistance among sheep farmers from Southern Italy.

PURPOSE: We conducted a cross-sectional study to measure the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) colonization, with a particular focus on livestock associated (LA)-MRSA in farmers working in contact with livestock (sheep) in one Italian region. Furthermore, we have assessed the antimicrobial resistance pattern of isolates and the association of carriage with specific characteristic of farms and working tasks. PATIENTS AND METHODS: Demographic data, occupational history, and contact with animals information was collected. Nasal and oropharyngeal swabs were collected and all samples were tested for the isolation and identification of S. aureus. Isolates were examined for antimicrobial susceptibility and all MRSA strains underwent molecular analyses through multiple-locus variable number of tandem repeat analysis (MLVA). RESULTS: A total of 115 sheep farms and 275 sheep farmers were enrolled. MRSA colonized workers were found in three farms; S. aureus was isolated in 97 workers (35.5%), whereas MRSA was isolated in 3 (1.1%) workers. All MRSA isolates were classified as multidrug resistant. Two of the MRSA isolates were resistant to quinupristin/dalfopristin (QDA), mupirocin, erythromycin, and tetracycline. Among methicillin-susceptible S. aureus (MSSA), 32 (34%) were resistant to tetracycline, 31 (33%) to erythromycin, 26 (27.6%) to QDA, and 22 (23.4%) to linezolid and clindamycin. One MRSA belonged to MLVA complex (MC) 001, found to colonize both humans and animals. CONCLUSION: The picture of MRSA transmission among sheep farmers does not seem to be critical, although there is the need to improve adequate control measures to prevent and minimize any biological risk in sheep farms for both animal and human health. Specific monitoring/surveillance programs would help in better understanding the epidemiology of resistant strains.

Prevalence of Staphylococcus aureus carriage and pattern of antibiotic resistance, including methicillin resistance, among contact sport athletes in Italy.

Background and purpose: Athletes participating in contact or collision sports have a great chance of acquiring Staphylococcus aureus infections. The risk factors for colonization and infections include frequent antibiotic use, close contact situations, skin trauma, sharing of sports equipment, and poor hygiene. Therefore, our specific goals were to determine (1) prevalence of S. aureus among different types of contact sport athletes which were barely studied in the European region, (2) antimicrobial resistance of S. aureus isolates, and (3) association of carriage with particular risk factors of spor t practices. Patients and methods: A cross-sectional study was conducted among contact or collision sport athletes in Italy. A questionnaire was used to gather information about sociodemographic characteristics, specific sport activities, and participants' health conditions. Swabs were collected from the nares, oropharynx, and fingers and tested for S. aureus isolation and antimicrobial susceptibility. Results: S. aureus was carried by 42% of 238 enrolled athletes. Colonization was associated with number of weekly training days, sharing of sports equipment, not taking a shower immediately after training, and a previous history of pharyngitis or sinusitis and skin manifestations. Isolates were resistant to clindamycin (24.8%) and erythromycin (15.8%). Of all athletes, 1.3% carried methicillin-resistant S. aureus (MRSA); MRSA were 3% of all S. aureus isolates. No strains were resistant to sulfamethoxazole/trimethoprim. Conclusion: Our results have shown a high prevalence of S. aureus carriage and a relevant resistance to antimicrobials used for the treatment of S. aureus infections. Prevention efforts aimed at reducing S. aureus colonization, and thus potentially reducing infections, should be improved.

HPV vaccination coverage and willingness to be vaccinated among 18-30 year-old students in Italy.

OBJECTIVES: In Italy, free HPV vaccination has been offered to 12 years-old girls since 2007, while for males only since 2015. THE AIMS OF OUR STUDY WERE: to measure HPV vaccination coverage among young women; to assess willingness to receive HPV vaccination among unvaccinated males and females; to evaluate the association of coverage and attitudes with knowledge regarding HPV and with sexual behavior. METHODS: A cross-sectional survey was conducted in an Italian region among 18-30 year-old students attending medical and healthcare professions schools. Participants completed a self-administered questionnaire exploring knowledge, attitudes and behaviors related to HPV infections, sexually transmitted diseases and their prevention. Information on vaccination status was also verified for each student through the immunization records provided by the participants during the occupational medical visit. RESULTS: 517 students were enrolled, with a 97% response rate. Of female participants, 40.5% had received at least one dose of HPV vaccine, while among unvaccinated participants, 60.5% stated their willingness to be vaccinated. A negative attitude towards HPV vaccination was associated with an older age, whereas a correct knowledge that both sexes are at risk of HPV infection, and the knowledge that vaccine protects against cervical cancer were confirmed to be associated to a willingness to receive HPV vaccination. CONCLUSIONS: Our results showed low HPV vaccination coverage among young women and high reported willingness to receive vaccination among both sexes. More active education on the link between HPV and all related cancers could be beneficial to help prevent significant burden of the HPV-related diseases.

Parent perspectives on childhood vaccination: How to deal with vaccine hesitancy and refusal?

BACKGROUND: The aims of the study are to evaluate attitudes about childhood vaccines and vaccine refusal or delay among parents and to assess the role played by the variables mapped as potential determinants to suggest strategies that could improve childhood vaccination rates. METHODS: The cross-sectional study was intended for parents of kindergarteners. Parental attitudes were measured using the Parent Attitudes about Childhood Vaccines (PACV) survey, to screen for Vaccine Hesitancy (VH). In addition, selected factors have been grouped in three categories (contextual, individual and group and vaccine/vaccination-specific influences), and were explored as potential determinant of VH and vaccination refusal or delay. RESULTS: 7.7% of subjects were defined as VH parents (VHPs) through PACV score, while 24.6% reported having refused or delayed at least one dose of vaccine for their child. VH was more common in those parents that decided not to vaccinate their child after having received information from mass-media, in those who did not agree with mandatory vaccinations, and in those who agreed with political leaders who oppose to vaccination. Vaccine refusing/delaying parents were more frequently those who agreed that infant vaccinations are primarily an economic business of pharmaceutical companies, and who disagreed that access to the kindergarten should only be allowed to children who had been vaccinated. CONCLUSION: The findings of the present study emphasize the importance of PACV as a tool to screen VHPs. Furthermore, results highlight important potential determinants of VH, such as communication and media environment, and attitudes about prevention. Health care providers could act as key components to improve the public trust to scientific and epidemiological evidence.

Antibiotic prescriptions to adults with acute respiratory tract infections by Italian general practitioners.

PURPOSE: The overuse, misuse, and underuse of antimicrobial agents often lead to the spread of antibiotic-resistant microorganisms. The aim of our study was to describe the pattern of antibiotic prescriptions for acute respiratory tract infections (RTIs) among the adult population and the factors associated with antibiotic prescribing. PATIENTS AND METHODS: The study involved patients who visited a general practitioner with suspected acute RTI. Patients with diagnosis of acute sinusitis, acute pharyngitis, acute bronchitis, and influenza were included in the study. We evaluated the presence of an indication for antibiotic therapy for selected diseases according to international guidelines. The appropriateness of any prescribed molecule was also evaluated. RESULTS: A total of 1,979 cases of acute RTIs were included: 1,196 (60.4%) pharyngitis, 359 (18.2%) bronchitis, 234 (11.8%) influenza, and 190 (9.6%) sinusitis. An antibiotic prescription was given in 67.3% of the consultations and was not indicated by the guidelines in 66.5% of the total RTIs. Macrolides were the most frequently prescribed antibiotics accounting for 32.5% of all those prescribed, followed by amoxicillin with clavulanic acid (31.1%) and fluoroquinolones (14.2%). The highest overprescription was associated with pharyngitis (65.9%) and the lowest with influenza (4.9%). A throat swab was performed only in 11 of all the patients with a diagnosis of acute pharyngitis. CONCLUSION: The present study showed a very high frequency of nonevidence-based prescription of antibiotics at the primary care level. Future improvement programs should focus on development of evidence-based guidelines, access to postgraduate training, and better availability of diagnostic tools.

Prevalence of Livestock-Associated Methicillin-Resistant Staphylococcus Aureus (LA-MRSA) Among Farm and Slaughterhouse Workers in Italy.

OBJECTIVE: We measured the prevalence of livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) in swine livestock workers, examined LA-MRSA resistance profile, and associated carriage with the working activities. METHODS: Information was collected on demographics and occupational history. Swabs were collected and tested for the isolation of S. aureus, examined for antimicrobial susceptibility, and all MRSA underwent ST398qPCR assay. RESULTS: LA-MRSA was isolated in 7.3% of the 396 enrolled workers. LA-MRSA colonization was more likely in farmers than in slaughterhouse workers (Fisher exact P = 0.001). Carriage was associated with herd size, being less frequent in small/medium farms (odds ratio = 0.20; 95% confidence interval = 0.07 to 0.53), and with the number of working days per week (OR = 2.11; 95% confidence interval = 1.07 to 4.19). CONCLUSIONS: LA-MRSA carriage is strongly animal-exposure related, and educational intervention informing about the risks related to the activity with livestock is needed.

Ventilator Bundle and Its Effects on Mortality Among ICU Patients: A Meta-Analysis.

OBJECTIVES: To assess the effectiveness of the ventilator bundle in the reduction of mortality in ICU patients. DATA SOURCES: PubMed, Scopus, Web of Science, Cochrane Library for studies published until June 2017. STUDY SELECTION: Included studies: randomized controlled trials or any kind of nonrandomized intervention studies, made reference to a ventilator bundle approach, assessed mortality in ICU-ventilated adult patients. DATA EXTRACTION: Items extracted: study characteristics, description of the bundle approach, number of patients in the comparison groups, hospital/ICU mortality, ventilator-associated pneumonia-related mortality, assessment of compliance to ventilator bundle and its score. DATA SYNTHESIS: Thirteen articles were included. The implementation of a ventilator bundle significantly reduced mortality (odds ratio, 0.90; 95% CI, 0.84-0.97), with a stronger effect with a restriction to studies that reported mortality in ventilator-associated pneumonia patients (odds ratio, 0.71; 95% CI, 0.52-0.97), to studies that provided active educational activities was analyzed (odds ratio, 0.88; 95% CI, 0.78-0.99), and when the role of care procedures within the bundle (odds ratio, 0.87; 95% CI, 0.77-0.99). No survival benefit was associated with compliance to ventilator bundles. However, these results may have been confounded by the differential implementation of evidence-based procedures at baseline, which showed improved survival in the study subgroup that did not report implementation of these procedures at baseline (odds ratio, 0.82; 95% CI, 0.70-0.96). CONCLUSIONS: Simple interventions in common clinical practice applied in a coordinated way as a part of a bundle care are effective in reducing mortality in ventilated ICU patients. More prospective controlled studies are needed to define the effect of ventilator bundles on survival outcomes.

Prospective surveillance of healthcare-associated infections and patterns of antimicrobial resistance of pathogens in an Italian intensive care unit.

Background: The study aimed to evaluate the distribution of healthcare-associated infections (HAIs), the incidence rates and device utilization ratio (DUR) of device-associated infections (DAIs), as well as the distribution and patterns of antimicrobial resistance of the responsible pathogens. Methods: Eligible patients who were admitted to an adult Intensive Care Unit (ICU) from May 1, 2013 to December 31, 2016 were included in the surveillance. Demographics, intrinsic and extrinsic risk factors, information regarding infection and isolated pathogens with antibiogram results were collected. Results: One thousand two hundred eighty-three patients were included in the surveillance. One hundred forty-seven HAIs were detected with a cumulative incidence of 9.2 per 100 patients 4-year period and an incidence rate of 17.4 per 1000 patient days. Fifty-six out of 1283 patients were affected by at least one episode of ICU-acquired pneumonia, and 72.7% of these were associated with intubation. ICU-acquired bloodstream infections (BSIs) occurred in 4.4% of patients and 89.5% were catheter-related. ICU-acquired urinary tract infections (UTIs) occurred in 1% of patients, with 84.6% of the episodes being associated with the use of an urinary catheter. The pattern of antimicrobial-resistance in the isolates showed, among the Gram-positive bacteria, that 66.6% and 16.6% of Staphylococcus epidermidis were oxacillin and teicoplanin resistant, respectively. Among the Gram-negative bacteria, carbapenem resistance was found in 91.6% of Acinetobacter baumannii and 28.5% of Klebsiella pneumoniae isolates. Conclusions: The majority of HAIs in the ICU studied were associated with the use of invasive devices. Since a significant proportion of these HAIs are considered preventable, reinforcement of the evidence-based preventive procedures are needed.

Non-typhoidal Salmonella in Calabria, Italy: a laboratory and patient-based survey.

INTRODUCTION: Although there has been a decrease in the number of cases of salmonellosis in the European Union, it still represents the primary cause of foodborne outbreaks. In Calabria region, data are lacking for the incidence of human non-typhoid salmonellosis as active surveillance has never been carried out. OBJECTIVE: To report the results of a laboratory and patient-based morbidity survey in Calabria to describe the incidence and distribution of Salmonella serovars isolated from humans, with a focus on antimicrobial resistance patterns. METHODS: Positive cultures from human samples were collected from every laboratory participating in the surveillance, with a minimum set of information about each isolate. A questionnaire was then administered to the patients by telephone interview to assess the potential risk exposures.Salmonella isolates underwent biochemical identification, molecular analysis by PCR and antimicrobial susceptibility testing by the disk-diffusion method. RESULTS: During a 2-year period, 105 strains of Salmonella spp were isolated from samples of patients with diarrhoea, with the highest isolation rate for children aged 1-5 years. The standardised rate was 2.7 cases per 1 00 000 population. The most common Salmonella isolates belonged to monophasic variant of S. Typhimurium (S. 4,[5],12:i:-) (33.3%), followed by S. Typhimurium (21.9%). 30.5% of the isolates were susceptible to all microbial agents tested and the most common pan-susceptible serotype was S. Napoli (100%). S. 4,[5],12:i:- was resistant to ampicillin, streptomycin, sulfonamides and tetracyclines in 42.9% cases, while resistance to quinolones was seen in 14.3% of the isolates. CONCLUSIONS: The results provide evidence that an active surveillance system effectively enhances Salmonella notifications. The high prevalence of antimicrobial resistance, including resistance to quinolones and multiresistance, enforces the need to strengthen strategies of surveillance and monitoring of antimicrobial use.

Role of serum ferritin level on overall survival in patients with myelodysplastic syndromes: Results of a meta-analysis of observational studies.

BACKGROUND: The role of serum ferritin (SF) as a prognostic factor has been analyzed in patients with myelodysplastic syndromes (MDS) who have undergone hematopoietic stem cell transplantation (HSCT), but the prognostic role of elevated SF levels is still controversial in lower risk MDS patients. Therefore, we performed a meta-analysis of all available published literature to evaluate whether elevated SF levels are associated with a worse overall survival (OS) among patients with low risk MDS. MATERIAL AND METHODS: A systematic bibliographic search of relevant studies was undertaken in accordance with guidelines for meta-analysis of observational studies in epidemiology. Electronic databases were searched through July 2016 for studies examining the level of SF as a prognostic factor in the adults affected by MDS. RESULTS: Six articles were included in the meta-analysis. A significant association between OS and SF was achieved for the threshold of SF≥1000 ng/mL, when the only study that used SF cut-off ≥2000 ng/mL was not included in the meta-analysis (RR = 1.33; 95% CI = 1.06-1.67). The estimated risk was 2.58 (95% CI = 1.41-4.74) when a SF cut-off≥500 ng/mL was considered. CONCLUSIONS: Our findings underlined a worse survival in patients with MDS who had higher SF levels. The association was stronger and achieved statistical significance after stratification of analyses in which we excluded cut-offs of SF level considered as outliers. These results suggest that negative impact on OS already exist at SF level ≥500 ng/mL. Prospective studies, are needed to better understand this relationship and, above all, to clarify whether earlier iron chelation therapy could improve patients' OS.

Extended anticoagulation and mortality in venous thromboembolism. A meta-analysis of six randomized trials.

Data on all-cause mortality in patients with venous thromboembolism (VTE) and prolonged anticoagulation are inconclusive. The aim of this study was to compare the incidence of all-cause mortality in patients with VTE at intermediate risk of recurrence, i.e. without transient risk factors or cancer, exposed to shorter (at least three months) or longer anticoagulation. We did a systematic revue and meta-analysis of randomized clinical trials searching MEDLINE and COCHRANE bibliographic databases. A random-effects model was used to pool study results. I2 testing was used to test for heterogeneity. Six studies (5920 patients) entered in the final analysis. Mean course of anticoagulation was 7.5months in the shorter and 18.6months in the longer treatment arm. Prolonged anticoagulation was associated with a statistically significant reduction in all-cause mortality (RR 0.47, 95% CI 0.29 to 0.75; 0.8% vs 1.8%). Pulmonary embolism-related death was also lowered in the longer anticoagulation arm (RR 0.32, 95% CI 0.12 to 0.83; 0.2% vs 0.6%). Longer compared with shorter anticoagulation significantly reduced all-cause mortality in patients with VTE at intermediate risk of recurrence.

Immunogenicity and Safety of Intradermal Influenza Vaccine in the Elderly: A Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: Immunosenescence makes the elderly more susceptible to influenza complications and less responsive to vaccination. An intradermal formulation (IDflu) is one of several strategies being investigated to increase the immunogenicity of influenza vaccines. OBJECTIVE: The overall goal of the study was to assess the safety and immunogenicity of IDflu compared with the intramuscular route (IMflu) in the elderly. METHODS: A meta-analysis of randomized controlled trials (RCTs) was performed. Included articles met the following criteria: RCTs; primary studies, not re-analyses or reviews; enrolment of elderly people; comparing the immunogenicity and/or safety of IDflu with IMflu; measuring seroprotection and/or seroconversion rate to assess immunogenicity; measuring local reactions and/or general symptoms and/or other mild local reactions that could affect acceptability of vaccine as safety indicators, according to the European Medicines Agency (EMA) criteria; published through January 2015. RESULTS: The results of our meta-analysis on seroprotection showed that IDflu is comparable to IMflu for each strain (A/H1N1: risk ratio [RR] 1.02, 95% confidence interval [CI] 0.98-1.07; A/H3N2: RR 1.01, 95% CI 0.99-1.04; B 1.02, 95% CI 0.98-1.08). The seroconversion rate achieved with IDflu was comparable to that of the control group (A/H1N1: RR 1.08, 95% CI 0.97-1.2; A/H3N2: RR 1.08, 95% CI 0.96-1.21; B: RR 1.21, 95% CI 1-1.45). Systemic reactogenicity appeared similar in the two groups, while local reactions were significantly more frequent in the IDflu group. CONCLUSIONS: The novel IDflu appears to have the adequate balance between immunogenicity and safety in the elderly compared with IMflu, and its utilization may be considered among the possible strategies to enhance the control of seasonal influenza outbreaks according to the existing policy recommendations in the elderly.

Over-the-Counter Drugs and Complementary Medications Use among Children in Southern Italy.

The use of nonprescription medicines (NPDs) for children illnesses without a doctor's suggestion can lead to unnecessary medication use and is not free of risks. The aim of our study was to examine attitudes and practice of parents towards NPDs use for their children. We also investigated the conditions that may predict NPDs use. A cross-sectional survey was conducted on parents of children attending Community Based Pediatrician (CBP) consultation and data were collected through structured interviews. Positive attitude on NPDs use was reported by 71.4% of parents, and 61.5% of them had administered NPDs in the previous 6 months. Antipyretic drugs were the most frequently used medication class without the supervision of the CBP. A positive attitude towards NPDs was significantly more frequent in parents who did not use the CBP as the sole source of information about drugs. The study demonstrated a widespread use of NPDs in children in our context, supported by a substantial positive attitude towards their safety. However, considering potential harms related to some NPDs and the finding that most parents rely on CBP advice, role of CBP on appropriate use of NPDs by parents should be emphasized.