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The coronavirus disease 2019 (COVID-19) pandemic has posed significant global challenges for solid organ transplant (SOT) recipients. Mortality rates of COVID-19 in this patient population remain high, despite new available therapeutic options and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccination. Priority access to SARS-CoV-2 vaccination for waitlisted candidates and for SOT patients and their family members is recommended since the advantage from vaccination reduces the risk of COVID-19-related complications. However, immunogenicity and efficacy of COVID-19 vaccines are lower in waitlisted candidates and SOT recipients than in the general population. Routine systematic assessment of humoral and cellular immune responses after SARS-CoV-2 vaccination is controversial, although highly recommended for investigation and improvement of knowledge. SOT recipients should continue to adhere to preventive protective measures despite vaccination and may undergo passive antibody prophylaxis. This article seeks to provide an update on SARS-CoV-2 vaccination and preventive measures in SOT recipients based on existing literature and international guidelines.

The debate on the opportunity to use organs from donors testing positive for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in recipients with naïve resolved or active COVID-19 is ongoing. We aim to present the ethical analyses underlying the decision to perform liver transplantation (LT) in selected patients with resolved or active COVID-19 in Italy. We used Jonsen, Siegler, and Winslade's Four-Boxes casuistic method, addressing the four topics considered as constitutive of the essential structure of single clinical cases for their ethical analysis (medical indications, patient preferences, quality of life, and contextual features) to enable decision-making on a case-by-case basis. Based on these topics, we elucidate the meaning and balance among the principles of biomedical ethics. Clinical ethics judgment based on the relation between the risk of acquiring SARS-CoV-2 along with its potentially negative effects and the expected benefits of transplant lead to consider LT as clinically appropriate. Shared decision-making allows the integration of clinical options with the patient's subjective preferences and considerations, enabling a valid informed consent specifically tailored to the patients' individual circumstances. The inclusion of carefully selected SARS-CoV-2 positive donors represents an opportunity to offer lifesaving LT to patients who might otherwise have limited opportunities to receive one. COVID-19 positive donor livers are fairly allocated among equals, and respect for fundamental rights of the individual and the broader community in a context of healthcare rationing is guaranteed.The ethical analysis of the decision to perform LT in selected patients shows that the decision is ethically justifiable., (© 2022 Wiley Periodicals LLC.)

Infections are leading causes of morbidity/mortality following solid organ transplantation (SOT) and cytomegalovirus (CMV) is among the most frequent pathogens, causing a considerable threat to SOT recipients. A survey was conducted 19 July-31 October 2019 to capture clinical practices about CMV in SOT recipients (e.g., how practices aligned with guidelines, how adequately treatments met patients' needs, and respondents' expectations for future developments). Transplant professionals completed a ∼30-minute online questionnaire: 224 responses were included, representing 160 hospitals and 197 SOT programs (41 countries; 167[83%] European programs). Findings revealed a heterogenous approach to CMV diagnosis and management and, sometimes, significant divergence from international guidelines. Valganciclovir prophylaxis (of variable duration) was administered by 201/224 (90%) respondents in D+/R- SOT and by 40% in R+ cases, with pre-emptive strategies generally reserved for R+ cases: DNA thresholds to initiate treatment ranged across 10-10,000 copies/ml. Ganciclovir-resistant CMV strains were still perceived as major challenges, and tailored treatment was one of the most important unmet needs for CMV management. These findings may help to design studies to evaluate safety and efficacy of new strategies to prevent CMV disease in SOT recipients, and target specific educational activities to harmonize CMV management in this challenging population., Competing Interests: PG has been a consultant or member of an advisory committee for Angelini, Becton Dickinson, Biotest, Correvio, Gilead Sciences, Merck Sharpe & Dohme, Nordic Pharma, Paratek Pharmaceuticals, AlloVir, and Shire; and a speakers’ bureau member for Becton Dickinson, Biotest, Gilead Sciences, Merck Sharpe & Dohme, Pfizer, Atara, and Vertex. NK has been a speaker or an advisory board member for AbbVie, Amgen, Astellas, Biotest, Chiesi, CSL Behring, Gilead, Fresenius Medical Care, Merck Sharpe & Dohme, Neovii, Novartis Pharma, Sandoz, Sanofi, and Shire. FS has received speaker’s honoraria and/or research grants from Novartis, Astellas, Chiesi, Gilead, Merck Sharp & Dohme, Neovii, Sandoz, Pfizer, Biotest, Takeda, and Baxter. FB has received grants/research support from AB Analitica, DiaSorin, ELITechGroup, NTP, and Qiagen; he has also received honoraria or consultation fees from Biotest, DiaSorin, HUMABS, Merck Sharpe & Dohme, Qiagen, and Shire. JA has been a consultant and speakers’ bureau member for Astellas Pharma, Biotoscana, Gilead, Merck Sharpe & Dohme, Pfizer, Roche, and United Medical. LP has been a consultant for Novartis and Biotest and received speaker fees from AstraZeneca, Boehringer Ingelheim, Abbott, and Paragonix. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Grossi, Kamar, Saliba, Baldanti, Aguado, Gottlieb, Banas and Potena.)

International migration from Sub-Saharan African countries to the European Union and the United States has significantly increased over the past decades. Although the vast majority of these immigrants are young and healthy people, a minority can be affected by chronic conditions eventually leading to solid organ transplantation (SOT). Importantly, these candidates can bear geographically restricted fungal and parasitic latent infections that can reactivate after the procedure. An appropriate evaluation before transplantation followed by treatment, whenever necessary, is essential to minimize such risk, as covered in the present review. In short, infection due to helminths (Schistosoma spp. and Strongyloides stercoralis) and intestinal protozoa (Entamoeba histolytica, Giardia lamblia or Cyclospora cayetanensis) can be diagnosed by multiple direct stool examination, serological assays and stool antigen testing. Leishmaniasis can be assessed by means of serology, followed by nucleic acid amplification testing (NAAT) if the former test is positive. Submicroscopic malaria should be ruled out by NAAT. Screening for Histoplasma spp. or Cryptococcus spp. is not routinely indicated. Consultation with an Infectious Diseases specialist is recommended in order to adjust preemptive treatment among Sub-Saharan African SOT candidates and recipients., (Copyright © 2021 Elsevier Inc. All rights reserved.)

COVID-19 pandemic dramatically impacted transplantation landscape. Scientific societies recommend against the use of donors with active SARS-CoV-2 infection. Italian Transplant Authority recommended to test recipients/donors for SARS-CoV-2-RNA immediately before liver transplant (LT) and, starting from November 2020, grafts from deceased donors with active SARS-CoV-2 infection were allowed to be considered for urgent-need transplant candidates with active/resolved COVID-19. We present the results of the first 10 LTs with active COVID-19 donors within an Italian multicenter series. Only two recipients had a positive molecular test at LT and one of them remained positive up to 21 days post-LT. None of the other eight recipients was found to be SARS-CoV-2 positive during follow-up. IgG against SARS-CoV-2 at LT were positive in 80% (8/10) of recipients, and 71% (5/7) showed neutralizing antibodies, expression of protective immunity related to recent COVID-19. In addition, testing for SARS-CoV-2 RNA on donors' liver biopsy at transplantation was negative in 100% (9/9), suggesting a very low risk of transmission with LT. Immunosuppression regimen remained unchanged, according to standard protocol. Despite the small number of cases, these data suggest that transplanting livers from donors with active COVID-19 in informed candidates with SARS-CoV-2 immunity, might contribute to safely increase the donor pool., (© 2021 The Authors. American Journal of Transplantation published by Wiley Periodicals LLC on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: A growing body of observational evidence supports the value of ceftazidime-avibactam (CAZ-AVI) in managing infections caused by carbapenem-resistant Enterobacteriaceae., Methods: We retrospectively analyzed observational data on use and outcomes of CAZ-AVI therapy for infections caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp) strains. Multivariate regression analysis was used to identify variables independently associated with 30-day mortality. Results were adjusted for propensity score for receipt of CAZ-AVI combination regimens versus CAZ-AVI monotherapy., Results: The cohort comprised 577 adults with bloodstream infections (n = 391) or nonbacteremic infections involving mainly the urinary tract, lower respiratory tract, and intra-abdominal structures. All received treatment with CAZ-AVI alone (n = 165) or with ≥1 other active antimicrobials (n = 412). The all-cause mortality rate 30 days after infection onset was 25% (146/577). There was no significant difference in mortality between patients managed with CAZ-AVI alone and those treated with combination regimens (26.1% vs 25.0%, P = .79). In multivariate analysis, mortality was positively associated with presence at infection onset of septic shock (P = .002), neutropenia (P < .001), or an INCREMENT score ≥8 (P = .01); with lower respiratory tract infection (LRTI) (P = .04); and with CAZ-AVI dose adjustment for renal function (P = .01). Mortality was negatively associated with CAZ-AVI administration by prolonged infusion (P = .006). All associations remained significant after propensity score adjustment., Conclusions: CAZ-AVI is an important option for treating serious KPC-Kp infections, even when used alone. Further study is needed to explore the drug's seemingly more limited efficacy in LRTIs and potential survival benefits of prolonging CAZ-AVI infusions to ≥3 hours., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: The risk of disease transmission from nonstandard risk donors (NSRDs) is low, and outcomes are similar or better relative to transplants performed with standard criteria donors. However, NSRDs have posed new ethical challenges to the informed consent (IC) process. Based on the shared decision-making model, coinciding with the 3 main timings of the IC process ([1] pretransplant assessments and waiting list registration, [2] time on the waiting list, and [3] time of the organ offer), we put forward a model (3-T Model) to summarize the knowledge on IC for NSRDs and to deliver conceptual and practical support to transplant providers on this emergent issue., Methods: We searched PubMed and analyzed data from our area to provide evidence and ethical arguments to promote standardization of the timing of patient information, degree of patient participation, and disclosure of donor risk factors throughout the 3 stages of the time continuum leading to the potential acceptance of NSRDs., Results: Each of the 3 timings carries special ethical significance and entails well-defined duties for transplant providers relative to patient involvement and information of the benefits and risks associated with NSRDs. Based on our framework, experience, and interpretation of the literature, we put forward a list of recommendations to combine standardization (ie, timing, content, and degree of patient participation) and individualization of IC., Conclusions: The 3-T Model may enable the prevention of physicians' arbitrariness and the promotion of patient-centered care. Future studies will assess the effectiveness of the 3-T Model in transplant clinical practice., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

There are scarce data on the efficacy of ertapenem in the treatment of bacteremia due to extended-spectrum-beta-lactamase (ESBL)-producing Enterobacterales (ESBL-E) in kidney transplant (KT) recipients. We evaluated the association between treatment with ertapenem or meropenem and clinical cure in KT recipients with nonsevere bacteremic urinary tract infections (B-UTI) caused by ESBL-E. We performed a registered, retrospective, international (29 centers in 14 countries) cohort study (INCREMENT-SOT, NCT02852902). The association between targeted therapy with ertapenem versus meropenem and clinical cure at day 14 (the principal outcome) was studied by logistic regression. Propensity score matching and desirability of outcome ranking (DOOR) analyses were also performed. A total of 201 patients were included; only 1 patient (treated with meropenem) in the cohort died. Clinical cure at day 14 was reached in 45/100 (45%) and 51/101 (50.5%) of patients treated with ertapenem and meropenem, respectively (adjusted OR 1.29; 95% CI 0.51 to 3.22; P  = 0.76); the propensity score-matched cohort included 55 pairs (adjusted OR for clinical cure at day 14, 1.18; 95% CI 0.43 to 3.29; P  = 0.74). In this cohort, the proportion of cases treated with ertapenem with better DOOR than with meropenem was 49.7% (95% CI, 40.4 to 59.1%) when hospital stay was considered. It ranged from 59 to 67% in different scenarios of a modified (weights-based) DOOR sensitivity analysis when potential ecological advantage or cost was considered in addition to outcome. In conclusion, targeted therapy with ertapenem appears as effective as meropenem to treat nonsevere B-UTI due to ESBL-E in KT recipients and may have some advantages.

Background: HHV-8/Kaposi Sarcoma herpesvirus has been associated with a broad spectrum of diseases in solid organ transplant (SOT) recipients. Primary donor-derived infection can be associated with severe and rapidly fatal non-neoplastic disease, and diagnosis is made with high HHV-8 DNAemia., Methods: We carried out an international survey to investigate the current approach to HHV-8 screening, and management in SOT since a protocol has not been established by international guidelines., Results: A total of 51 transplant centers from 15 countries filled out the survey. HHV-8-associated diseases in SOT have been diagnosed during the previous 5 years in 67% of centers. Pretransplant serological screening is performed in 17 centers (33%), and posttransplant HHV-8 nucleic acid testing (NAT) monitoring is performed in 21 centers (41%). Performing HHV-8 NAT monitoring and serological screening were found associated with having diagnosed in the previous 5 years a non-malignant HHV-8-associated disease., Conclusions: Serological pretransplant screening of donors and recipients and post-transplant HHV-8 NAT monitoring recommendations should be standardized. Even though serological assays are not optimal, they could contribute to increasing knowledge on epidemiology and management of HHV-8-associated diseases after SOT., (© 2021 Wiley Periodicals LLC.)

According to a recent World Health Organization estimate, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, which originated in China in 2019, has spread globally, infecting nearly 100 million people worldwide by January 2021. Patients with chronic liver diseases (CLD), particularly cirrhosis, hepatobiliary malignancies, candidates for liver transplantation, and immunosuppressed individuals after liver transplantation appear to be at increased risk of infections in general, which in turn translates into increased mortality. This is also the case for SARS-CoV-2 infection, where patients with cirrhosis, in particular, are at high risk of a severe COVID-19 course. Therefore, vaccination against various pathogens including SARS-CoV-2, administered as early as possible in patients with CLD, is an important protective measure. However, due to impaired immune responses in these patients, the immediate and long-term protective response through immunisation may be incomplete. The current SARS-CoV-2 pandemic has led to the exceptionally fast development of several vaccine candidates. A small number of these SARS-CoV-2 vaccine candidates have already undergone phase III, placebo-controlled, clinical trials in healthy individuals with proof of short-term safety, immunogenicity and efficacy. However, although regulatory agencies in the US and Europe have already approved some of these vaccines for clinical use, information on immunogenicity, duration of protection and long-term safety in patients with CLD, cirrhosis, hepatobiliary cancer and liver transplant recipients has yet to be generated. This review summarises the data on vaccine safety, immunogenicity, and efficacy in this patient population in general and discusses the implications of this knowledge on the introduction of the new SARS-CoV-2 vaccines., Competing Interests: Conflict of interest MC reports personal fees from Abbvie, personal fees from Gilead Sciences, personal fees from Merck Sharp & Dohme (MSD), personal fees from GlaxoSmithKline (GSK), personal fees from Janssen-Cilag, personal fees from Spring Bank Pharmaceuticals, personal fees from Novartis, from Swedish Orphan Biovitrum (SOBI), personal fees from Falk Foundation, grants and personal fees from Roche, outside the submitted work. PAG reports personal fees from Merck, Sharp & Dohme, personal fees from Biotest, personal fees from Angelini, personal fees from Nordic Pharma, personal fees from Vertex, personal fees from Gilead, personal fees from Astellas, outside the submitted work. MB, CSE and DS have nothing to disclose., (Copyright © 2021 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

We report an imported case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant P.1 detected in an asymptomatic traveler who arrived in Italy on an indirect flight from Brazil. This case shows the risk for introduction of SARS-CoV-2 variants from indirect flights and the need for continued SARS-CoV-2 surveillance.

Background: SARS-CoV-2 infection is heterogeneous in clinical presentation and disease evolution. To investigate whether immune response to the virus can be influenced by genetic factors, we compared HLA and AB0 frequencies in organ transplant recipients and waitlisted patients according to presence or absence of SARS-CoV-2 infection., Methods: A retrospective analysis was performed on an Italian cohort composed by transplanted and waitlisted patients in a January 2002 to March 2020 time frame. Data from this cohort were merged with the Italian registry of COVID+ subjects, evaluating infection status of transplanted and waitlisted patients. A total of 56 304 cases were studied with the aim of comparing HLA and AB0 frequencies according to the presence (n = 265, COVID+) or absence (n = 56 039, COVID-) of SARS-CoV-2 infection., Results: The cumulative incidence rate of COVID-19 was 0.112% in the Italian population and 0.462% in waitlisted/transplanted patients (OR = 4.2; 95% CI, 3.7-4.7; P < 0.0001). HLA-DRB1*08 was more frequent in COVID+ (9.7% and 5.2%: OR = 1.9, 95% CI, 1.2-3.1; P = 0.003; Pc = 0.036). In COVID+ patients, HLA-DRB1*08 was correlated to mortality (6.9% in living versus 17.5% in deceased: OR = 2.9, 95% CI, 1.15-7.21; P = 0.023). Peptide binding prediction analyses showed that these DRB1*08 alleles were unable to bind any of the viral peptides with high affinity. Finally, blood group A was more frequent in COVID+ (45.5%) than COVID- patients (39.0%; OR = 1.3; 95% CI, 1.02-1.66; P = 0.03)., Conclusions: Although preliminary, these results suggest that HLA antigens may influence SARS-CoV-2 infection and clinical evolution of COVID-19 and confirm that blood group A individuals are at greater risk of infection, providing clues on the spread of the disease and indications about infection prognosis and vaccination strategies., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

The impact of immigration background on kidney graft function (eGFR) is unknown. Italy has a publicly funded health system with universal coverage. Since immigration from non-European Union (EU) countries beyond Eastern Europe is a recent and extensive phenomenon, Italy is a rather unique setting for studying the effect of immigration status as a socioeconomic and cultural condition. We retrospectively identified all adult deceased donor kidney transplant recipients (KTRs) in Italy (2010-2015) and followed them until death, dialysis or 5-years post-transplantation; 6346 were EU-born, 161 Eastern European-born, and 490 non-European-born. We examined changes in eGFR after 1-year post-transplant using multivariable-adjusted joint longitudinal survival random-intercept Cox regression. Compared to EU-born KTRs, in non-European-born KTRs the adjusted average yearly eGFR decline was -0.96 ml/min/year (95% confidence interval: -1.48 to -0.45; P < 0.001), whereas it was similar in Eastern European-born KTRs [+0.02 ml/min/year (-0.77 to +0.81; P = 0.96)]. Adjusted 5-year transplant survival did not statistically differ between non-European-born, Eastern European-born, and EU-born. In those surviving beyond 1-year, it was 91.8% in EU-born (87.1-96.8), 92.5% in Eastern European-born (86.1-99.4), and 89.3% in non-European-born KTRs (83.0-96.0). This study provides evidence that among EU KTRs, non-European immigration background is associated with eGFR decline., (© 2020 Steunstichting ESOT. Published by John Wiley & Sons Ltd.)

Background: Several small studies on patients with COVID-19 and haematological malignancies are available showing a high mortality in this population. The Italian Hematology Alliance on COVID-19 aimed to collect data from adult patients with haematological malignancies who required hospitalisation for COVID-19., Methods: This multicentre, retrospective, cohort study included adult patients (aged ≥18 years) with diagnosis of a WHO-defined haematological malignancy admitted to 66 Italian hospitals between Feb 25 and May 18, 2020, with laboratory-confirmed and symptomatic COVID-19. Data cutoff for this analysis was June 22, 2020. The primary outcome was mortality and evaluation of potential predictive parameters of mortality. We calculated standardised mortality ratios between observed death in the study cohort and expected death by applying stratum-specific mortality rates of the Italian population with COVID-19 and an Italian cohort of 31 993 patients with haematological malignancies without COVID-19 (data up to March 1, 2019). Multivariable Cox proportional hazards model was used to identify factors associated with overall survival. This study is registered with ClinicalTrials.gov, NCT04352556, and the prospective part of the study is ongoing., Findings: We enrolled 536 patients with a median follow-up of 20 days (IQR 10-34) at data cutoff, 85 (16%) of whom were managed as outpatients. 440 (98%) of 451 hospitalised patients completed their hospital course (were either discharged alive or died). 198 (37%) of 536 patients died. When compared with the general Italian population with COVID-19, the standardised mortality ratio was 2·04 (95% CI 1·77-2·34) in our whole study cohort and 3·72 (2·86-4·64) in individuals younger than 70 years. When compared with the non-COVID-19 cohort with haematological malignancies, the standardised mortality ratio was 41·3 (38·1-44·9). Older age (hazard ratio 1·03, 95% CI 1·01-1·05); progressive disease status (2·10, 1·41-3·12); diagnosis of acute myeloid leukaemia (3·49, 1·56-7·81), indolent non-Hodgin lymphoma (2·19, 1·07-4·48), aggressive non-Hodgkin lymphoma (2·56, 1·34-4·89), or plasma cell neoplasms (2·48, 1·31-4·69), and severe or critical COVID-19 (4·08, 2·73-6·09) were associated with worse overall survival., Interpretation: This study adds to the evidence that patients with haematological malignancies have worse outcomes than both the general population with COVID-19 and patients with haematological malignancies without COVID-19. The high mortality among patients with haematological malignancies hospitalised with COVID-19 highlights the need for aggressive infection prevention strategies, at least until effective vaccination or treatment strategies are available., Funding: Associazione italiana contro le leucemie, linfomi e mieloma-Varese Onlus., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Purpose: We aimed to implement and to assess the impact of the antifungal stewardship programme (AFSp) on prescription appropriateness of antifungals, management and outcomes of candidaemia patients, and antifungal consumption and costs at our solid organ transplant (SOT) institute., Methods: Local epidemiology of invasive fungal infections (IFIs) from 2009 to 2017 was analysed in order to prepare an effective AFSp, implemented in January 2018. It included suspension of empirical antifungal prescriptions after 72 hours (antifungal time-out), automated alert and infectious disease (ID) consult for empirical prescriptions and for every patient with IFI, and indication for step-down to oral fluconazole when possible. We used process measures and results measures to assess the effects of the implemented programme., Results: The ASFp led to significant improvements in selection of the appropriate antifungal (40.5% in pre-AFS vs 78.6% in post-AFS), correct dosing (51.2% vs 79.8%), correct length of treatment (55.9% vs 75%) and better management of patients with candidaemia. Analysis of prescribed empirical antifungal revealed that defined daily doses (DDDs) per 100 patient days decreased by 36.7% in 2018 compared to the average of pre-AFSp period, with important savings in costs., Conclusion: This AFSp led to a better use of antifungal drugs in terms of appropriateness and consumption, with stable clinical and microbiological outcomes in patients with IFI., (© 2020 Blackwell Verlag GmbH.)

Objectives: The aim of this study was to assess colistin use in a country endemic for multidrug-resistant Gram-negative bacteria (MDR-GNB)., Methods: Colistin prescription patterns were evaluated in 22 Italian centres. Factors associated with use of colistin in combination with other anti-MDR-GNB agents were also assessed., Results: A total of 221 adults receiving colistin were included in the study. Their median age was 64 years (interquartile range 52-73 years) and 134 (61%) were male. Colistin was mostly administered intravenously (203/221; 92%) and mainly for targeted therapy (168/221; 76%). The most frequent indications for colistin therapy were bloodstream infection and lower respiratory tract infection. Intravenous colistin was administered in combination with at least another anti-MDR-GNB agent in 80% of cases (163/203). A loading dose of 9 MU of colistimethate was administered in 79% of patients receiving i.v. colistin and adequate maintenance doses in 85%. In multivariable analysis, empirical therapy [odds ratio (OR) = 3.25, 95% confidence interval (CI) 1.24-8.53;P = 0.017] and targeted therapy for carbapenem-resistant Enterobacterales infection (OR = 4.76, 95% CI 1.69-13.43; P = 0.003) were associated with use of colistin in combination with other agents, whilst chronic renal failure (OR = 0.39, 95% CI 0.17-0.88; P =  0.024) was associated with use of colistin monotherapy., Conclusion: Colistin remains an important option for severe MDR-GNB infections when other treatments are not available. Despite inherent difficulties in optimising its use owing to peculiar pharmacokinetic/pharmacodynamic characteristics, colistin was mostly used appropriately in a country endemic for MDR-GNB., (Copyright © 2019 International Society for Antimicrobial Chemotherapy. Published by Elsevier Ltd. All rights reserved.)

Transplant represents an effective strategy in the management of chronic organ dysfunction. Nonetheless, life threatening risks remain, especially in the post-transplant; among them, human cytomegalovirus (CMV) is a major concern, currently causing active infections in at least one-third of transplant recipients. Microbiologist and transplant scientific societies redefined guidance on CMV disease prevention and the best use for universal prophylaxis and pre-emptive virological monitoring. Developments in molecular diagnostic supported the spread of the pre-emptive strategy, and quantitative Real Time-PCR assays has unravelled the potential of viral load measurement as a predictor of the infection development in CMV post-transplant management. However, despite the WHO 1st CMV International Standard, the standardization of diagnostic and clinical practice has been limited by the absence of algorithms for calculating conversion factor to International Units and the lack of shared monitoring procedure, both at national and international level. At a regional level, the Italian scientific societies, AMCLI (Italian Clinical Microbiologist Association), SITO (Organ Transplant Italian Society), GITMO (Italian Group for Bone Marrow Transplant), recently tried to define a consensus for post-transplant monitoring. The concerted practice encompasses molecular quantitative PCR assays technical aspects and endorses the relevance of immunologic monitoring for improvement in patient risk stratification and prognosis. Here, we provide an overview of the state of the art of CMV management strategies, with a specific focus on the clinical practices and on the scientific societies' initiatives that aim to implement international standardization guidelines at a national level., (Copyright © 2019. Published by Elsevier B.V.)

Yellow fever has never previously been reported in transplant recipients. The first reported case of yellow fever in a kidney transplant recipient in Brazil and the re-emergence of arboviruses in many areas of the world dictate the need of studies aimed to answer multiple unanswered questions., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Introduction : Ceftobiprole is a fifth-generation cephalosporin with a broad spectrum of antimicrobial activity, including also methicillin-resistant Staphylococcus aureus (MRSA). Ceftobiprole is approved for the treatment of community-acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP), excluding ventilator-associated pneumonia, in several European and non-European countries. Areas covered : In this narrative review, we discuss the current place in therapy of ceftobiprole, both within and outside approved indications. An inductive MEDLINE/PubMed search of the available literature was conducted. Expert opinion : There are three main reasons which render ceftobiprole an attractive option for the empirical and targeted treatment of CAP and HAP: ( i ) its broad spectrum of activity; ( ii ) its activity against MRSA; ( iii ) its good safety profile. For these indications, ceftobiprole should be employed thoughtfully, in those scenarios in which its intrinsic advantages could be maximized. The use of ceftobiprole outside approved indications could be justified in specific scenarios, such as when other approved alternatives are ineffective, when the risk of toxicity due to other agents is unacceptable, and for salvage therapy. In the near future, ongoing phase 3 studies and further observational experiences could both enlarge the current panel of approved indications and enrich our knowledge on the use of ceftobiprole for off-label indications.

To explore the attitudes of European physicians on adherence and how treatment modalities impact adherence in complicated forms of soft skin and skin structure infections, now referred as acute bacterial skin and skin structures infections (ABSSSI). After literature review, a questionnaire was prepared. Topics focused on (1) the importance of adherence, (2) the importance of administration regimen on adherence, (3) the importance of drug selection on adherence, (4) the importance of complexity on choice of drug for treatment, (5) the role of adherence in drug resistance, and (6) the role of adherence in administration of long-acting antibiotics (ABs). The questionnaire was administered to 323 European infectious diseases specialists, of whom 74% responded. A modified Delphi method was used to obtain the highest consensus. Results varied by countries. We found a high degree of agreement of the importance of adherence in ABSSSI treatment. Experts agreed that complexity of patient's conditions, drug selection, drug resistance, the type of regimen, and the number of infusions impact adherence. Two items linking oral switching and adherence did not reach consensus. Adherence for ABSSSI therapies appears a crucial factor for therapeutic management and reduces the risk of AB resistance. Among new treatment opportunities, long-acting agents, with their characteristics, may represent an interesting options.

Purpose of Review: Donor-derived transmission of infectious diseases is a well-recognized complication of solid organ transplantation (SOT). Most donor-derived disease transmissions are expected. Although uncommon, unexpected donor-derived infections can be associated with significant morbidity and mortality, and as the volume of patients undergoing SOT increases, the number of infections transmitted through organ donation can also be expected to rise. The growing gap between the number of patients waiting for transplantation and available organs continue in fact to be the number one issue facing the transplant community. As a consequence the major focus in organ transplantation has been developing strategies to increase the available organs, including the use of organs from donors with infections or risky behaviors that have disqualified them from the donation in the past., Recent Findings: In addition to the commonly reported donor-derived transmissions, an increasing number of studies have reported unusual infections transmitted by SOT., Summary: Transplant surgeons and physicians should increase their awareness toward uncommon donor-derived infections including them in the differential diagnosis of unusual clinical pictures in their recipients.

Introduction: Ceftolozane/tazobactam (C/T) is a new antibiotic resulting from the combination of a novel cephalosporin, structurally similar to ceftazidime, with tazobactam, a well-known beta-lactamase inhibitor. C/T remains active against extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae and multi-drug resistant (MDR) P. aeruginosa, and has been recently approved for the treatment of complicated intra-abdominal infections (cIAI) and complicated urinary tract infections (cUTI). A trial on hospital-acquired pneumonia is ongoing. Areas covered: The place in therapy of C/T is delineated by addressing the following main topics: (i) antimicrobial properties; (ii) pharmacological properties; (iii) results of clinical studies. Expert commentary: C/T is approved for cIAI and cUTI. However, the drug has a special value for clinicians in any kind of infectious localization for two main reasons. The first is that C/T is especially valuable in suspected or documented severe infections due to MDR P. aeruginosa, which is not a rare occurrence in many countries. The second is that C/T may provide an alternative to carbapenems for the treatment of infections caused by ESBL-producers, thus allowing a carbapenem-sparing strategy. Reporting of off-label use is mandatory to increase the body of evidence and the clinicians' confidence in using it for indications other than cIAI and cUTI.

The purpose of this study was to assess the safety and the clinical outcome associated with organ transplantation from increased infectious risk donors (IRD). We retrospectively identified all adult deceased IRD referred to the Nord Italia Transplant program coordinating center from November 2006 to November 2011. All potential donors were screened for social risk factors that may increase the risk of donor-derived infection with human immunodeficiency (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV). All recipients were followed monthly for the first 6 months post-transplant. A total of 86 potential IRD were identified during the study period. Three hundred and seventy-nine organs from IRD were offered to the transplant centers, but only 185 (48.8%) were used for transplantation. Organs from IRD were transplanted into 174 recipients. The complete follow-up data were available for 152 of 174 (87.3%) recipients. During a mean follow-up of 11.7 months (median 12; range 2.4-12), no transmission of HIV, HBV, or syphilis was documented by serology and nucleic acid testing (NAT) testing. Two patients transplanted with organs from HCV-RNA-positive donors, as expected, developed post-transplant HCV infection. In conclusion, the use of organs from IRD was associated with a safe increase in the transplant procedures in our country., (© 2017 Steunstichting ESOT.)

We describe two cases of Zika virus infection involving an Italian patient returning from the Dominican Republic and his wife, who remained in Italy and had not travelled to Zika virus endemic areas in the previous months. The infection was transmitted through unprotected sexual intercourse after the man's return to Italy.

Background: Scant information is available about how transplant centers are managing their use of quantitative molecular testing (QNAT) assays for active cytomegalovirus (CMV) infection monitoring in solid organ transplant (SOT) recipients. The current study was aimed at gathering information on current practices in the management of CMV infection across European centers in the era of molecular testing assays., Methods: A questionnaire-based cross-sectional survey study was conducted by the European Study Group of Infections in Immunocompromised Hosts (ESGICH) of the Society of Clinical Microbiology and Infectious Diseases (ESCMID). The invitation and a weekly reminder with a personal link to an Internet service provider (https://es.surveymonkey.com/) was sent to transplant physicians, transplant infectious diseases specialists, and clinical virologists working at 340 European transplant centers., Results: Of the 1181 specialists surveyed, a total of 173 responded (14.8%): 73 transplant physicians, 57 transplant infectious diseases specialists, and 43 virologists from 173 institutions located at 23 different countries. The majority of centers used QNAT assays for active CMV infection monitoring. Most centers preferred commercially available real-time polymerase chain reaction (RT-PCR) assays over laboratory-developed procedures for quantifying CMV DNA load in whole blood or plasma. Use of a wide variety of DNA extraction platforms and RT-PCR assays was reported. All programs used antiviral prophylaxis, preemptive therapy, or both, according to current guidelines. However, the centers used different criteria for starting preemptive antiviral treatment, for monitoring systemic CMV DNA load, and for requesting genotypic assays to detect emerging CMV-resistant variants., Conclusions: Significant variation in CMV infection management in SOT recipients still remains across European centers in the era of molecular testing. International multicenter studies are required to achieve commutability of CMV testing and antiviral management procedures., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: This paper describes our experience in the management of acute and chronic invasive fungal rhinosinusitis (IFRS) in adults., Methods: Medical files of all patients aged >18 years treated in our institutions for IFRS from 2002 to 2013 were retrospectively reviewed., Results: A total of 18 cases (10 acute and 8 chronic) were recorded. In acute form, haematological malignancies represented the principal comorbidity (100%), while in chronic form this was diabetes mellitus (87.5%). All patients received systemic antifungal agents. Endoscopic sinus surgery was performed in 16/18 patients (88.9%). Among patients with an acute IFRS, 4/10 died of fungal infection (40%), on the other side 2/8 patients with chronic IFRS died of the evolution of the mycosis (25%)., Conclusions: Acute and chronic IFRS are different entities: in acute form, prognosis is poor, so therapy should be promptly performed, although host immune status and evolution of the haematological disease are key factors for the outcome. In chronic form, a wide surgical excision of the disease is recommended in order to obtain a complete removal of fungal infection. In both forms, early clinical findings are non-specific and ambiguous, so diagnosis depends on a high index of suspicion, taking into account predisposing factors., (Copyright © 2016 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Background: Sex medicine studies have shown that there are sex differences with regard to disease characteristics in immune-mediated inflammatory diseases, including psoriasis, in immune response and susceptibility to viral infections. We performed a post hoc analysis of the Observational Study of infectious events in psoriasis complicated by active psoriatic arthritis (SYNERGY) study in patients with psoriatic arthritis (PsA) treated with immunosuppressive regimens including cyclosporine, in order to evaluate potential between-sex differences in severity of disease and prevalence of viral infections., Methods: SYNERGY was an observational study conducted in 24 Italian dermatology clinics, which included 238 consecutively enrolled patients with PsA, under treatment with immunosuppressant regimens including cyclosporin A. In this post hoc analysis, patients' demographical data and clinical characteristics of psoriasis, severity and activity of PsA, prevalence of seropositivity for at least one viral infection, and treatments administered for PsA and infections were compared between sexes., Results: A total of 225 patients were evaluated in this post hoc analysis, and 121 (54%) were males. Demographic characteristics and concomitant diseases were comparable between sexes. Statistically significant sex differences were observed at baseline in Psoriasis Area and Severity Index score (higher in males), mean number of painful joints, Bath Ankylosing Spondylitis Disease Activity Index, and the global activity of disease assessed by patients (all higher in females). The percentage of patients with at least one seropositivity detected at baseline, indicative of concomitant or former viral infection, was significantly higher among women than among men. No between-sex differences were detected in other measures, at other time points, and in treatments. Patients developed no hepatitis B virus or hepatitis C virus reactivation during cyclosporine treatment., Conclusion: Our post hoc sex analysis suggests that women with PsA have a greater articular involvement and a higher activity of disease compared to males. Immunosuppressive treatment with cyclosporine seems not to increase susceptibility to new infections or infectious reactivations, with no sex differences.

In the summer of 2013, an outbreak of West Nile virus (WNV) infection occurred in the Lombardy, a region of northern Italy to the west of districts affected by WNV in previous years. Eighteen cases of human WNV infection were diagnosed--10 cases of acute WNV neuroinvasive disease and eight of WNV fever. In the same period, WNV was detected in birds (one crow) in horses (11 cases) and from mosquitoes (six pools).

Increasingly potent immunosuppressive agents have dramatically reduced the incidence of rejection of transplanted organs while increasing patients' susceptibility to opportunistic infections. Invasive fungal infections (IFIs) following solid organ transplantation, despite having a lower incidence than bacterial and viral infections, remain a major cause of morbidity and mortality. Fungal infections in patients with different types of solid organ transplant have different incidences, underlying pathogenetic mechanisms and modes of clinical presentation. Two genera, Aspergillus and Candida, are responsible for the vast majority of fungal infections in solid organ transplant recipients accounting for more than 80% of IFIs. Candidaemia is the most frequent clinical manifestation of Candida spp. infection, regardless of the transplanted organ and typically occurs within 1 month of transplantation. Management of fungal infections varies widely among different transplant centres. Large multicentre, randomized controlled trials evaluating risk factors, diagnosis, prophylaxis and treatment strategies for fungal infection in organ transplant recipients are lacking. Consequently, a uniform consensus on each of these does not exist, and clinical practice has evolved mainly from case series, anecdotal experiences and single-centre trials. Targeted prophylaxis is recommended for high-risk liver, pancreas and small bowel patients. Management of established infection is based on guidelines in the general population and should take into consideration prior prophylaxis, severity of infection and the possibility of drug-drug interactions in these immunosuppressed patients.

Background: The roles of hepatitis C virus (HCV) viremia and HCV genotype in the immune response to highly active antiretroviral therapy (HAART) are poorly understood. Our aim was to assess the CD4+ cell count recovery after HAART in human immunodeficiency virus (HIV)-infected patients with HCV viremia and HIV-infected patients who tested negative for HCV antibody (HCV-Ab). We also aimed to assess whether the response to HAART in these patients varied according to HCV genotype., Methods: The analysis focused on 1219 HCV-Ab-negative patients and 284 HCV-viremic patients from a cohort of HIV-infected subjects that includes persons who were antiretroviral naive before initiating HAART after cohort enrollment. HCV RNA load and HCV genotype were determined in plasma specimens obtained and stored during the 6-month period preceding the initiation of HAART., Results: The chance of achieving a CD4+ cell count increase of > or = 100 cells/microL from the pre-HAART level tended to be poorer in HCV-viremic patients than in patients who tested negative for HCV-Ab (adjusted relative hazard [RH], 0.82; 95% confidence interval [CI], 0.66-1.01; P = .06). In contrast, a comparison of patients who had a HCV RNA load >1 x 10(6) IU/mL with patients who had a HCV RNA load of 5-1 x 10(6) IU/mL revealed no significant association between HCV RNA load and achievement of an increased CD4+ cell count (adjusted RH, 0.97; 95% CI, 0.75-1.27; P = .83). There was no clear association between HCV genotype and the probability of achieving a CD4+ cell count increase., Conclusions: An association between the presence of HCV-Ab and immune reconstitution after HAART has been shown elsewhere. Results of our large, prospective study support a direct role of HCV viremia in the CD4+ cell count response to HAART. Moreover, our results underline the fact that, in individuals coinfected with HIV and HCV, the goal of treating HCV infection is to eradicate HCV, to both slow the rate of HCV progression and limit potential interference with the response to HAART.