Introduction: Microbiological surveillance of endoscopes is a safety measure for verifying the quality of reprocessing procedures and identifying contaminated devices, but duodenoscope-related outbreaks are still reported.Aim: To assess the effectiveness of duodenoscope reprocessing procedures in Italy.Methods: Between December 2019 and April 2020, data obtained from microbiological surveillance post-reprocessing in 15 Italian endoscopy units were collected. Sampling was carried out after reprocessing or during storage in a cabinet. In keeping with international guidelines and the Italian position paper, the micro-organisms were classified as highconcern organisms (HCOs) and low-concern organisms (LCOs).Findings: In total, 144 samples were collected from 51 duodenoscopes. Of these, 36.81% were contaminated: 22.92% were contaminated with HCOs and 13.89% were contaminated with LCOs [2.08% with an LCO load of 11-100 colony-forming units (CFU)/device and 0.69% with an LCO load of >100 CFU/device]. The contamination rate was 27.5% in samples collected after reprocessing, 40% in samples collected during storage in a cabinet that was compliant with EN 16442:2015 (C-I), and 100% in samples collected during storage in a cabinet that was not compliant with EN 16442:2015 (NC-I). The respective HCO rates were 15.00%, 27.27% and 66.67%. Correlation between LCO contamination and storage time was demonstrated (Spearman's rho=0.3701; P=0.0026). The Olympus duodenoscope TJFQ180V demonstrated the lowest rate of contamination (29.82%), although the contamination rate was 100% for duodenoscopes stored in an NC-I cabinet.

Abstract Background Randomized clinical trials in non-critically ill COVID-19 patients showed that therapeutic-dose heparin increased survival with reduced organ support as compared with usual-care thromboprophylaxis, albeit with increased bleeding risk. The purpose of the study is to assess the safety of intermediate dose enoxaparin in hospitalized patients with moderate to severe COVID-19. Methods A phase II single-arm interventional prospective study including patients receiving intermediate dose enoxaparin once daily according to body weight: 60 mg for 45–60 kg, 80 mg for 61–100 kg or 100 mg for > 100 kg for 14 days, with dose adjustment according to anti-factor Xa activity (target range: 0.4–0.6 UI/ml); an observational cohort (OC) included patients receiving enoxaparin 40 mg day for comparison. Follow-up was 90 days. Primary outcome was major bleeding within 30 and 90 days after treatment onset. Secondary outcome was the composite of all-cause 30 and 90-day mortality rates, disease severity at the end of treatment, intensive care unit (ICU) admission and length of ICU stay, length of hospitalization. All outcomes were adjudicated by an independent committee and analyzed before and after propensity score matching (PSm). Results Major bleeding was similar in IC (1/98 1.02%) and in the OC (none), with only one event observed in a patient receiving concomitantly anti-platelet therapy. The composite outcome was observed in 53/98 patients (54%) in the IC and 132/203 (65%) patients in the OC (p = 0.07) before PSm, while it was observed in 50/90 patients (55.6%) in the IC and in 56/90 patients (62.2%) in the OC after PSm (p = 0.45). Length of hospitalization was lower in the IC than in OC [median 13 (IQR 8–16) vs 14 (11–21) days, p = 0.001], however it lost statistical significance after PSm (p = 0.08). At 30 days, two patients had venous thrombosis and two pulmonary embolism in the OC. Time to first negative RT-PCR were similar in the two groups. Conclusions Weight adjusted intermediate dose heparin with anti-FXa monitoring is safe with potential positive impact on clinical course in COVID-19 non-critically ill patients. Trial registration The study INHIXACOVID19 was registred on ClinicalTrials.gov with the trial registration number (TRN) NCT04427098 on 11/06/2020.

BACKGROUND:Carbapenem resistance in Gram-negative bacteria is associated with severe infections in the hospital setting. No uniform screening policy or agreed set of criteria exists within the EU to inform treatment decisions for infections caused by carbapenem-resistant Gram-negative bacteria.AIM:To develop a range of consensus statements to survey experts in carbapenem resistance, to identify potential similarities and differences across the EU and across specialties.METHODS:The survey contained 43 statements, covering six key topics relating to carbapenem-resistant organisms: microbiological screening; diagnosis; infection control implementation; antibiotic stewardship; use of resources; and influencing policy.FINDINGS:In total, 136 survey responses were received (66% infectious disease specialists, 18% microbiologists, 11% intensive care specialists, 4% other/unknown) from France, Germany, Greece, Italy, Spain, and the UK. High, or very high, levels of agreement were seen for all 43 consensus statements, indicating good alignment concerning early identification and optimal management of infection due to carbapenem-resistant organisms.CONCLUSION:We offer the following recommendations: (1) screening is required when a patient may have been exposed to the healthcare system in countries/hospitals where carbapenem-resistant organisms are endemic; (2) rapid diagnostic tools should be available in every institution; (3) all institutions should have a specific policy for the control of carbapenem-resistant organisms, which is routinely audited; (4) clear strategies are required to define both appropriate and inappropriate use of carbapenems; (5) priority funding should be allocated to the management of infections due to carbapenem-resistant organisms; and (6) international co-operation is required to reduce country-to-country transmission of carbapenem-resistant organisms.

The COVID-19 pandemic is hitting hard even the most advanced healthcare systems [[1]Dong E. Du H. Gardner L. An interactive web-based dashboard to track COVID-19 in real time.Lancet Infect Dis. 2019; (published online Feb 19) (last visited on May, 19 2020, Available at:)https://doi.org/10.1016/S1473-3099(20)30120-1https://gisanddata.maps.arcgis.com/apps/opsdashboard/index.html#/bda7594740fd40299423467b48e9ecf6Abstract Full Text Full Text PDF Scopus (5770) Google Scholar]. We have had to care for large numbers of severely ill patients with limited resources (ventilators and specialists in respiratory failure management), often with a lack of healthcare workers (HCWs)—a terrible situation. The hospital of Cremona, Italy, is a 500-bed facility and was the second hospital in Europe to be hit, on February 21st, with this tsunami-like disease. Rapidly the number of patients with COVID-19-induced pneumonia reached 540. During the first 8 weeks of the pandemic the emergency room evaluated 1706 patients, with 1542 admissions; 242 patients were intubated, 419 underwent non-invasive ventilation (NIV), and 342 died. Home care was activated in 58 cases. At 2 months into the pandemic and in the phase of descent, we are offering advice—useful tips derived from real-life experience—to our colleagues facing this disease. Indications regarding preparedness are available, but a view from the 'battlefield' may help in everyday practice (Table 1) [[2]European Centre for Disease Prevention and ControlChecklist for hospitals preparing for the reception and care of coronavirus 2019 (COVID-19) patients. ECDC, Stockholm2020Google Scholar,[3]World Health Organization Critical preparedness, readiness and response actions for COVID-19.in: Interim guidance. Geneva. 22 March 2020Google Scholar].Table 1Our ten practical tips to help manage the COVID-19 pandemicProblem foundSolution1.EducationLimited knowledge of IPCNo information on COVID therapy'Fast and dirty' courses2.Home careGPs are not familiar with the diseaseWebinars on clinical picture, diagnosis, treatment, IPC3.Emergency roomHigh flow of patientsOrganize different priority linesOrganize patient reallocation to other hospitals4.Patients' wardsHigh number of admissionsProgramme when, where, and who will open a new COVID-19 ward5.Patients' ventilationExtremely high need for ventilatory support: ventilatory support (intubation/NIV)Identify all ventilators in the facilityOpen new ICU in sub-intensive units and in the operating theatre6.Laboratory and radiologyHigh request for PCR for SARS-CoV-2High need for pulmonary CTSelect a high-throughput instrument for SARS-CoV-2 PCROrganize a COVID-19 CT service7.COVID-19 therapyRight therapy at the right timeDrugs may go out of stockFind time to study or let somebody update youPharmacy has to check for critical drugs8.Sick HCWsHCWs may be infected when pandemic starts or may get infectedHave an emergency HCW shortage programme to reorganize ward staff9.Limited suppliesIncreased consumption of oxygen, blood gas syringes, surgical masks and FFP2/FFP3Check the oxygen system and supplyVerify supply of syringes, and PPE10.Check patients and HCW needsStress is common in patients and HCWsEvaluate psychological needs of the patientsOrganize a psychological service for HCWsNIV, non-invasive ventilation; FFP, filtering facepiece; GP, general practitioner; HCW, healthcare worker; HRCT, high-resolution computed tomography; ICU, Intensive Care Unit; IPC, infection prevention and control; PCR, polymerase chain reaction; PPE, personal protective equipment. Open table in a new tab NIV, non-invasive ventilation; FFP, filtering facepiece; GP, general practitioner; HCW, healthcare worker; HRCT, high-resolution computed tomography; ICU, Intensive Care Unit; IPC, infection prevention and control; PCR, polymerase chain reaction; PPE, personal protective equipment. The indications here described should be managed by a group of clinicians and management experts in charge of the organization of the hospital in this war-like setting, this being point zero. It is difficult to organize continuing HCW education in an emergency setting, but it is necessary to implement courses on infection control and prevention (ICP) and on COVID-19 management. Three main points need to addressed [4European Centre for Disease Prevention and ControlInfection prevention and control for COVID-19 in healthcare settings – Third update. 31 March 2020. ECDC, Stockholm2020Google Scholar, 5Marty F.M. Chen K. Verrill K.A. How to obtain a nasopharyngeal swab specimen.N Engl J Med. 2020; (published online ahead of print, 2020 Apr 17)https://doi.org/10.1056/NEJMvcm2010260Crossref Scopus (163) Google Scholar, 6Centers for Disease Control and PreventionInterim clinical guidance for management of patients with confirmed coronavirus disease (COVID-19).https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-guidance-management-patients.htmlGoogle Scholar, 7Bhimraj A. Morgan R.L. Shumaker A.H. Lavergne V. Baden L. Cheng V.C.-C. et al.Infectious diseases society of America guidelines on the treatment and management of patients with COVID-19.Clin Infect Dis. 2020; ([published online ahead of print, 2020 Apr 27]. ciaa478)https://doi.org/10.1093/cid/ciaa478Crossref Scopus (509) Google Scholar]. (a)Correct use of personal protective equipment (PPE). Many HCWs will be displaced from their routine work to a new task, the treatment of a transmissible infection. HCWs need to be rapidly updated on the necessary competencies required to manage highly infectious patients with respiratory failure. Rapid and thorough courses on the correct use of PPE is the first thing that should be done to protect both HCWs and patients. Doffing procedures are critical, due to a high risk of contamination [[4]European Centre for Disease Prevention and ControlInfection prevention and control for COVID-19 in healthcare settings – Third update. 31 March 2020. ECDC, Stockholm2020Google Scholar,[8]Verbeek J.H. Rajamaki B. Ijaz S. Sauni R. Toomey E. Blackwood B. et al.Personal protective equipment for preventing highly infectious diseases due to exposure to contaminated body fluids in healthcare staff.Cochrane Database Syst Rev. 2020; 4 (Published 2020 Apr 15): CD011621https://doi.org/10.1002/14651858.CD011621.pub4Crossref PubMed Scopus (30) Google Scholar]. While HCWs are often placing stress on the use of face masks, meticulous hand hygiene (HH) is probably the most important prevention strategy, and adherence to this is instrumental [[8]Verbeek J.H. Rajamaki B. Ijaz S. Sauni R. Toomey E. Blackwood B. et al.Personal protective equipment for preventing highly infectious diseases due to exposure to contaminated body fluids in healthcare staff.Cochrane Database Syst Rev. 2020; 4 (Published 2020 Apr 15): CD011621https://doi.org/10.1002/14651858.CD011621.pub4Crossref PubMed Scopus (30) Google Scholar,[9]Ong S.W.X. Tan Y.K. Chia P.Y. Lee T.H. Ng O.T. Wong M.S.Y. et al.Air, surface environmental, and personal protective equipment contamination by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from a symptomatic patient.JAMA. 2020; Crossref PubMed Scopus (1429) Google Scholar].(b)Proper nasopharyngeal swab-taking is fundamental to obtain the best sensitivity/specificity of testing.(c)COVID-19 management: 'fast and dirty' courses should be organized on the general principles of respiratory insufficiency, blood gas analysis, oxygen therapy, venous thromboembolism prevention, antivirals and anti-inflammatory drugs use [[7]Bhimraj A. Morgan R.L. Shumaker A.H. Lavergne V. Baden L. Cheng V.C.-C. et al.Infectious diseases society of America guidelines on the treatment and management of patients with COVID-19.Clin Infect Dis. 2020; ([published online ahead of print, 2020 Apr 27]. ciaa478)https://doi.org/10.1093/cid/ciaa478Crossref Scopus (509) Google Scholar]. Intensive care patient management retraining for HCWs should be performed. Since indications evolve rapidly, courses should be repeated regularly. Collaborating with GPs to correctly manage patients at home—limiting access to the hospital only for patients with possible pneumonia—is of paramount importance. Webinars on COVID-19 ICP strategies and management should be implemented: 1-hour courses on one-two items are much appreciated. We saw up to 70 COVID-19 patients per day. A reorganization of the ER will be necessary. Consider: how and where to perform triage, and to receive patients into the ER; clean and COVID-19 triage areas may be necessary. You may rapidly be struggling for beds and even for oxygen therapy points, since most COVID-19 patients have respiratory failure. We had to admit over 60 patients with COVID-19 every day, forcing us to quickly reorganize the hospital. Anticipatory planning on when and where to open new COVID-19 units is of paramount importance. Activation should be triggered by objective indicators (i.e. number of patients in the ER awaiting hospitalization); staff dedicated to opening new care units should be pre-alerted, to ensure work/rest shifts and to avoid HCW burnout. We had to increase our intubation capacity from ten to 52 beds in 3 weeks. Early intubation is recommended to manage COVID-19 patients [[7]Bhimraj A. Morgan R.L. Shumaker A.H. Lavergne V. Baden L. Cheng V.C.-C. et al.Infectious diseases society of America guidelines on the treatment and management of patients with COVID-19.Clin Infect Dis. 2020; ([published online ahead of print, 2020 Apr 27]. ciaa478)https://doi.org/10.1093/cid/ciaa478Crossref Scopus (509) Google Scholar] and you may very rapidly run out of ventilators. Since ventilation weaning often takes over 2 weeks, a rapid saturation of the ICU is easily foreseeable, and early intubation may become a difficult problem to solve. You should programme in advance when to convert areas with ventilators (i.e. operating theatres) to COVID-19 intensive and semi-intensive care units. Consider to prone patients to improve respiratory function. A reorganization of the staff is also fundamental since high-level skills are needed to manage these patients. Organize high-throughput nasopharyngeal SARS-CoV-2 swabs and define which exams have to be performed to manage these patients, including D-dimer, ferritin, and IL-6 determination. The need for high-resolution computed tomography (HRTC), the best diagnostic exam for interstitial pneumonia, will grow rapidly [[10]Li M. Lei P. Zeng B. Li Z. Yu P. Fan B. et al.Coronavirus disease (COVID-19): spectrum of CT findings and temporal progression of the disease.Acad Radiol. 2020 Mar 20; ([Epub ahead of print]. pii: S1076-6332(20)30144-30146)https://doi.org/10.1016/j.acra.2020.03.003Abstract Full Text Full Text PDF Scopus (171) Google Scholar,[11]Dai H. Zhang X. Xia J. Zhang T. Shang Y. Huang R. et al.High-resolution chest CT features and clinical characteristics of patients infected with COVID-19 in Jiangsu, China.Int J Infect Dis. 2020; 95: 106-112https://doi.org/10.1016/j.ijid.2020.04.003Abstract Full Text Full Text PDF PubMed Scopus (94) Google Scholar]. We performed over 2400 pulmonary HRTC in March, as compared to a standard of 200. A dedicated CT service has to be organized. Antithrombotic prophylaxis due to an increased risk of venous thromboembolism should not be overlooked. To improve knowledge, all efforts should be made to treat all patients within randomized controlled trials. Patients are so numerous that almost any drug utilized will rapidly go out of stock. It is likely that a certain number of HCWs will already be infected at the beginning of the epidemic, thus others will become infected. An emergency plan on how to reorganize services and how to reallocate HCWs to continue to offer a high level of services is of primary importance. Infected HCWs should be visited through dedicated internal services and treated following standard procedures. Ensure that all you need for patients with respiratory failure is in place. Oxygen consumption will rapidly increase and oxygen may become insufficient: in our hospital oxygen use skyrocketed from 3 m3/day to >80 m3/day. Drug use will increase similarly: norepinephrine and midazolam passed from 2500 and 800 vials/month to 21 000 and 7000, respectively. Blood gas analysis syringe use will increase: in our hospital consumption passed from 1900 in January 2020 to 12 900 in March. PPE use will be critical: mask use—i.e. surgical masks and FFP2/FFP3 respirators—increased from 5000 to 41 000/week, impermeable gowns from 1300 to 11 700/week, goggles/face shields from 30 to 1200/week. Adequate supplies have to be organized. Patients are scared of the disease, and visits, at least in our country, are forbidden. Time individually spent with patients is not enough, and the whole team—doctors, nurses, nurses' aids—should try to stay as close to them as possible. In our experience this is exactly what every HCW is willing to do, limiting the sense of anxiety and fear that is common during COVID-19. On the side of the HCWs, working with COVID-19 patients is an incredibly stressful duty since it is a highly transmittable disease. Furthermore, the level of uncertainty in management is high, the mortality is dreadful, and patients' social lives within the hospital are extremely difficult. Additionally, bringing home the stresses from work and worrying about the risk of transmitting SARS-CoV-2 infection to family members is a source of anxiety to the extent that normal marital relationship may be altered. Psychological support from the very beginning of the outbreak would be very useful for both patients and HCWs. The latin motto estote parati—be prepared—is what we learnt from this terrible pandemic; while waiting for possible new waves, we are working on education on PPE, HH, and ventilation, and programming how to dedicate general wards and ICUs to manage new COVID-19 patients. Finally, once the tsunami has passed, you will need to have rehabilitation services to manage patients discharged after long ICU stays: be prepared [[12]Grabowski D.C. Joynt Maddox K.E. Postacute care preparedness for COVID-19. Thinking ahead.JAMA. 2020 March 25; https://doi.org/10.1001/jama.2020.4686Crossref Scopus (108) Google Scholar]. To conclude, we have proposed what we think could be of help to our colleagues facing the COVID-19 pandemic (see Table 1). This experience has so far taught us that even in these extremely difficult situations you have to struggle for collaboration and discussion. We think that aid to coordinate such a strenuous situation could be sourced from experts in catastrophe medicine or war medicine; the needs of the hospital, its patients and HCWs undergo a rapid and dramatical change over only a few days, similar to what is observed during war. All authors made substantial contributions to the conception of the work, literature search and analysis, and discussion and interpretation of data. AP, AZ and ST drafted the work. All authors revised it critically for important intellectual content. All authors gave final approval of the version to be published. All authors agreed to be accountable for all aspects of the work. All authors ensured that all questions related to the accuracy or integrity of any part of the work have been appropriately investigated and resolved. The authors declare that they have no conflicts of interest. The study did not receive any external funding. We want to thank Pantelis Tsoulfas for his thoughtful review and Allegra Della Ragione for the language review.

Objectives: To evaluate the incidence and risk factors for liver enzyme elevations (LEE) in patients initiating first-line ART in the ICONA prospective observational cohort, between June 2009 and December 2017. Patients and methods: In total, 6575 ART-naive patients were selected, initiating two NRTIs with the third drug being a boosted PI (n=2436; 37.0%), an NNRTI (n=2384; 36.3%) or an integrase strand transfer inhibitor (INSTI) (n=1755; 26.7%). HBV surface antigen and HCV RNA were detected in 3.9% and 5.8% of the study population. Inverse probability weighted Cox regression analysis was used to calculate the HRs, according to first-line regimen, for LEE, defined as ALT or AST increases of >= 2.5x upper limit of normal (ULN) for patients with normal baseline values or >= 2.5x baseline for patients with higher baseline values. Results: One hundred and eighty-three LEE occurred over 20722 patient-years of follow-up. After adjusting for the main confounders, the risk of LEE halved with INSTIs compared with NNRTIs (HR 0.46, 95% CI 0.25-0.86), with a significant reduction in the raltegravir group (HR 0.11, 95% CI 0.02-0.84 using the NNRTI class as reference). HRs for LEE were significantly higher in subjects with HBV or HCV coinfection, in patients with poorly controlled HIV infection and in those who acquired HIV through homosexual transmission. Conclusions: In our study, INSTI use almost halved the risk of LEE compared with other regimens. This finding could be particularly important for choosing ART in patients with risk factors for liver toxicity such as HCV and HBV coinfections.

In the period 1 January to 31 December 2017 as members of the Italian Measles and Rubella Surveillance Network (MoRoNet) for the Lombardy Region (Northern Italy 10 million inhabitants), we evaluated 429 suspected measles cases during the large measles epidemic in Italy. In the period 7 January to 13 February 2017 an outbreak of measles genotype H1 was identified in the southern part of Lombardy Region. The index case was an Italian traveller returning to Italy after a vacation in Southeast Asia. The chain of infection was investigated in detail detecting 16 cases (Fig. 1): 13 were laboratory confirmed and three were probable. Genotyping was obtained in 12 of the 13 laboratory-confirmed measles cases. Phylogenetic analysis showed that measles H1 sequences were 100% identical to each other. All sequences are available in the World Health Organization's measles nucleotide surveillance (MeaNS) database (ID numbers: 106831-106832, 106834-106835, 106837-106838, 125251-125252, 125258-125261). The median age of subjects was 34 years (range 7 months to 56 years). The majority of cases (13/16, 81.0%) were not vaccinated, two out of 16 (12.5%) were vaccinated, and in one out of 16 (6.5%) the vaccination status was unknown. In this outbreak seven subjects who were involved attended the same high school in Cremona, four subjects worked at or had visited the Cremona Hospital, four subjects were relatives or community contacts of the first measles cases, and one subject had no evident relationship with other measles cases (Fig. 1). The index case was a 56-year-old male teacher in the Cremona High School. He presented with fever and diarrhoea on 7 January. Despite the presence of symptoms he worked at the school on 9 January to 11 January. On 11 January he was seen at the Emergency Department of the Cremona Hospital with persistent high fever, maculo-papular rash, and conjunctivitis and he was admitted to the Infectious Diseases Department. The patient tested positive for measles virus IgM, while he was negative for IgG. In addition, measles virus RNA was detected in his urine and saliva. RT-PCR amplicon sequencing on urine documented the presence of a measles genotype H1 strain. To limit the outbreak, all confirmed measles cases were isolated and isolation of suspected cases or unvaccinated contacts was strongly recommended. In addition, post-exposure prophylaxis with measles vaccination was offered to all seronegative contacts. In the Lombardy Hospitals, a systematic review of the healthcare workers measles immunization status was started and vaccination was offered to all who were seronegative. Despite great efforts, the goal of measles elimination in Europe, as advanced by the World Health Organization (WHO), has not been reached. One of the key strategies to eradicate measles in WHO European Regions is to achieve and sustain high vaccination coverage (≥95%), with two doses of measles vaccine [[1]World Health Organization (WHO) Surveillance guideline for measles, rubella and congenital rubella syndrome in the WHO European Region update December.2012https://www.euro.who.int/data/assets/pdf_file/0018/79020/e93035-2013. .pdf?ua=1Google Scholar]. Unfortunately, in Italy the vaccine coverage for the first dose of the combined measles–mumps–rubella (MMR) vaccine in children aged 2 years decreased from 90.4% in 2013 to 85.3% in 2015 [[2]Magurano F. Baggieri M. Filia A. Del Manso M. Lazzarotto T. Amendola A. et al.Towards measles elimination in Italy: virological surveillance and genotypes trend (2013-2015).Virus Res. 2017; 236: 24-29https://doi.org/10.1016/j.viruses.2017.05.009Crossref Google Scholar]. Thus, it is highly possible that the large measles epidemic involving Italy in 2017 is a consequence of this decreased herd immunity. Phylogenetic analysis in our Regional Reference laboratory showed that D8 was the most common genotype detected in Lombardy Region in 2017 and co-circulated with B3, in accordance with published data [[3]Amendola A. Bianchi S. Frati E.R. Ciceri G. Faccini M. Senatore S. et al.Ongoing large measles outbreak with nosocomial transmission in Milan, northern Italy, March-August 2017.Euro Surveill. 2017; 22 (pii=30596.)https://doi.org/10.2807/1560-7917.ES.2017.22.33.30596Crossref Scopus (32) Google Scholar]. The co-circulation of genotype H1 in the Lombardy Region in 2017 was unexpected. Before this event, genotype H1 was identified only in four cases in 2014 in Central Italy (Marche Region) [[2]Magurano F. Baggieri M. Filia A. Del Manso M. Lazzarotto T. Amendola A. et al.Towards measles elimination in Italy: virological surveillance and genotypes trend (2013-2015).Virus Res. 2017; 236: 24-29https://doi.org/10.1016/j.viruses.2017.05.009Crossref Google Scholar]. The outbreak of measles genotype H1 described in this paper was unanticipated, since this genotype, endemic in Asia, was not previously associated with local outbreaks. The index case was a traveller returning to Italy after a vacation in Eastern Asia and in 12 of the 13 laboratory confirmed cases the virus common origin was demonstrated by the strains' genetic identity. This outbreak involved distinct social settings including school, family and hospital environments. This finding underscores a relevant point concerning measles in aggregative contexts such as schools and hospitals [3Amendola A. Bianchi S. Frati E.R. Ciceri G. Faccini M. Senatore S. et al.Ongoing large measles outbreak with nosocomial transmission in Milan, northern Italy, March-August 2017.Euro Surveill. 2017; 22 (pii=30596.)https://doi.org/10.2807/1560-7917.ES.2017.22.33.30596Crossref Scopus (32) Google Scholar, 4Porretta A. Quattrone F. Aquino F. Pieve G. Bruni B. Gemignani G. et al.A nosocomial measles outbreak in Italy, February-April 2017.Euro Surveill. 2017; 22 (pii=30597)https://doi.org/10.2807/1560-7917.ES.2017.22.33.30597Crossref Scopus (52) Google Scholar, 5Maltezou H.C. Wicker S. Measles in healthcare settings.Am J Infect Contr. 2013; 41: 661-663https://doi.org/10.1016/j.ajic.2012.09.017Abstract Full Text Full Text PDF PubMed Scopus (77) Google Scholar] that may act as crucial nodal points for infection spread. Significant resources were spent to contain this outbreak including real-time case detection and isolation, tracking information and vaccination of contacts, genotyping, and outcome surveillance. To prevent and avoid this occurrence is fundamental to improve measles vaccine coverage in students, school, and healthcare workers. In conclusion, measles surveillance and virus genetic analysis are fundamental for virus control, to define the measles genotypes circulation, and to support cases and outbreak confirmation. Besides the primary requirement to improve population immunity and to increase routine vaccination coverage to eradicate measles, the surveillance activities proved to be of great relevance to detect and monitor the introduction of imported measles genotype. There were no conflicts of interest. This study was supported by funds from Lombardy Region and grants from the Ministero della Salute, Ricerca Corrente, Fondazione IRCCS Policlinico San Matteo, grant no. 80622 to Dr Antonella Sarasini. The local Ethics Committee consent was not required as the investigation was conducted according to the National Integrated Surveillance Plan to eliminate measles, rubella and congenital rubella syndrome (Italian Ministry of Health, DGPRE 0004460-P-20/02/2013) and to the Regional Surveillance and Control Plan for measles and rubella (decree n. 2131, 1 March 2017). Informed consent was not necessary as patients with suspected measles or rubella infections were included in a National and Regional diagnostic and surveillance protocol. The samples (blood, saliva and urine) were collected by clinicians and handled by Molecular Virology Unit personnel and data were analysed anonymously. We thank all the technical staff for handling the specimens and performing the assays and Dr Bianca Mariani for medical support. We thank Mrs Daniela Sartori for manuscript editing and Lauren Kelly for English revision. The results of this research were previously presented at the 28th ECCMID, the European Congress of Clinical Microbiology and Infectious Diseases, in the oral session 'respiratory viruses-keeping one step behind', in Madrid, Spain, 21–24 April 2018.

Background: Despite the high rate of virological success of combined antiretroviral therapy (cART), HIV infected individuals continue to fail. In this contest, it is unclear whether having previously experienced virological failure (VF) of cART remains an important predictor of future risk of VF in people receiving cART in modern times. We investigated the rate of VF and factors potentially associated with this event in 9220 HIV-1 infected patients enrolled in the Icona Cohort who showed a stable viral suppression on modern cART regimens after January 1, 2006. Methods: We investigated two main exposure factors: current calendar period (2006-2009; 2010-2013; 2014-2017) and number of VFs (0; 1-3;> 3) prior to baseline. Relative rates of VF were estimated from fitting a Poisson regression model. Results: Seven-hundred-seventy-nine patients experienced VF over follow-up for an overall rate of 2.08 per 100 person years of follow-up (PYFU, 95% CI: 1.93-2.22). The rate of VF increased with higher numbers of previous VFs: patients with> 3 previous VFs had a rate of 4.87 (4.10-5.78), 2.75-fold higher than that observed in patients without any previous VF (p < 0.001). The rate of VF was lower in recent years: 3.81 (3.36, 4.32) in 2006-2009; 1.36 (1.20-1.53) in 2014-2017 (p < 0.001). Other factors independently associated with lower risk of VF were Italian origin, longer history of virological suppression, and university education level. Conclusions: In HIV-infected patients virologically suppressed after January 2006, the rate of VF continues to show a decline even in the most recent years. Previous VFs should be carefully considered.

Background/aim: Direct-acting antivirals (DAAs) have revolutionized treatment of hepatitis C virus (HCV). We investigated DAA effectiveness and evolution of treatment schedules in a large real-life Italian setting.

IntroductionConcerns about dolutegravir (DTG) tolerability in the real-life setting have recently arisen. We aimed to estimate the risk of treatment discontinuation and virological failure of DTG-based regimens from a large cohort of HIV-infected individuals. MethodsWe performed a multicentre, observational study including all antiretroviral therapy (ART)-naive and virologically suppressed treatment-experienced (TE) patients from the Icona (Italian Cohort Naive Antiretrovirals) cohort who started, for the first time, a DTG-based regimen from January 2015 to December 2017. We estimated the cumulative risk of DTG discontinuation regardless of the reason and for toxicity, and of virological failure using Kaplan-Meier curves. We used Cox regression model to investigate predictors of DTG discontinuation. ResultsAbout 1679 individuals (932 ART-naive, 747 TE) were included. The one- and two-year probabilities (95% CI) of DTG discontinuation were 6.7% (4.9 to 8.4) and 11.5% (8.7 to 14.3) for ART-naive and 6.6% (4.6 to 8.6) and 7.6% (5.4 to 9.8) for TE subjects. In both ART-naive and TE patients, discontinuations of DTG were mainly driven by toxicity with an estimated risk (95% CI) of 4.0% (2.6 to 5.4) and 2.5% (1.3 to 3.6) by one year and 5.6% (3.8 to 7.5) and 4.0% (2.4 to 5.6) by two years respectively. Neuropsychiatric events were the main reason for stopping DTG in both ART-naive (2.1%) and TE (1.7%) patients. In ART-naive, a concomitant AIDS diagnosis predicted the risk of discontinuing DTG for any reason (adjusted relative hazard (aRH)=3.38, p=0.001), whereas starting DTG in combination with abacavir (ABC) was associated with a higher risk of discontinuing because of toxicity (aRH=3.30, p=0.009). TE patients starting a DTG-based dual therapy compared to a triple therapy had a lower risk of discontinuation for any reason (adjusted hazard ratio (aHR)=2.50, p=0.037 for ABC-based triple-therapies, aHR=3.56, p=0.012 for tenofovir-based) and for toxicity (aHR=5.26, p=0.030 for ABC-based, aHR=6.60, p=0.024 for tenofovir-based). The one- and two-year probabilities (95% CI) of virological failure were 1.2% (0.3 to 2.0) and 4.6% (2.7 to 6.5) in the ART naive group and 2.2% (1.0 to 3.3) and 2.9% (1.5 to 4.3) in the TE group. ConclusionsIn this large cohort, DTG showed excellent efficacy and optimal tolerability both as first-line and switching ART. The low risk of treatment-limiting toxicities in ART-naive as well as in treated individuals reassures on the use of DTG in everyday clinical practice.

Background and aims: Elderly hepatitis C virus (HCV) patients may benefit from direct-acting antivirals (DAA)-based regimens. Since these patients may be at risk of impaired renal function, we assessed DAA impact on kidney function in elderly HCV patients.

Background/aim: Hepatitis C virus (HCV) recurrence after liver transplantation (LT) is universal and introduction of direct-acting antiviral agents (DAAs) has dramatically increased possibility of curative treatment. This study was aimed to report the rate of virological response to DAA treated recipients with recurrent HCV after LT.

Background: Directly acting antivirals have allowed safe and effective treatment in patients with chronic hepatitis C infection. Real life data in Italian patients with advanced fibrosis and older age are still few.

Background: In DAA era, genotype 3 has emerged as a difficult-to-treat viral strain, achieving response rates lower than other genotypes. We aimed to explore the real life outcome of genotype 3-infected patients treated with DAAs.

The arrival of potent directly acting antivirals (DAAs) for the treatment of chronic Hepatitis C virus (HCV) infection was a challenge for the regional health system of the Lombardia Region. Lombardia represents roughly 8% of the Italian territory but includes nearly 16% of the Italian population. In 2014, nearly 37,600 HCV patients were routinely followed-up in liver centers across the region; nearly 16,000 were classified as having advanced fibrosis or cirrhosis (Metavir F3-F4). The creation of a regional network was necessary to ensure uniformity in treatment access and treatment management. The first database analysis of the Lombardia Hepatitis Network was conducted in January 2016, and included data on 2432 patients who had received treatment from December 2014 to December 2015. The most prevalent HCV genotypes were HCV-1 found in 63% and HCV-3 found in 17%. Overall 90.4% patients achieved an SVR, SVR rates were 92.9% in HCV-1, 89.3% in HCV-2, 81.1% in HCV-3 and 88.9% in HCV-4.

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.

Healthcare-associated infections due to multidrug-resistant Gram-negative bacteria (MDR-GNB) are a leading cause of morbidity and mortality worldwide. These evidence-based guidelines have been produced after a systematic review of published studies on infection prevention and control interventions aimed at reducing the transmission of MDR-GNB. The recommendations are stratified by type of infection prevention and control intervention and species of MDR-GNB and are presented in the form of 'basic' practices, recommended for all acute care facilities, and 'additional special approaches' to be considered when there is still clinical and/or epidemiological and/or molecular evidence of ongoing transmission, despite the application of the basic measures. The level of evidence for and strength of each recommendation, were defined according to the GRADE approach.