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Expected and unexpected donor-derived infections are a rare complication of solid organ transplantation, but can result in significant morbidity and mortality. Over the last years, the growing gap existing between patients on the waiting list and available organs has favored the use of organs from donors with suspected or confirmed infections, thanks to the improvement of risk mitigation strategies against transmission of well recognized and emerging infections. Given the recent developments, the particular interest of this review is to summarize data on how to maximize utilization of HIV+ donors in HIV+ recipients, the use of HCV-viremic donors and HBV positive donors. This article also covers the implications for recipient of organs from donors with bacteremia and the challenge of multidrug resistant (MDR) infections. Lastly this review describes emerging risks associated with recent Coronavirus Disease-2019 (COVID-19) pandemics.

Klebsiella pneumoniae carbapenemase–producing K. pneumoniae (KPC-Kp) has been endemic in Italy since 2013. In a multicenter cohort study, we investigated various aspects of KPC-Kp among patients, including 15-day mortality rates and delays in adequate therapy. Most (77%) KPC-Kp strains were sequence type (ST) ST512 or ST307. During 2017, KPC-Kp prevalence was 3.26 cases/1,000 hospitalized patients. Cumulative incidence of KPC-Kp acquired >48 hours after hospital admission was 0.68% but varied widely between centers. Among patients with mild infections and noninfected colonized patients, 15-day mortality rates were comparable, but rates were much higher among patients with severe infections. Delays of >4 days in receiving adequate therapy more frequently occurred among patients with mild infections than those with severe infections, and delays were less common for patients with known previous KPC-Kp colonization. Italy urgently needs a concerted surveillance system to control the spread of KPC-Kp.

A 39-year-old Ethiopian HIV-positive man with peripheral T-cell lymphoma developed Strongyloides stercoralis hyperinfection. The patient was initially treated with oral ivermectin for three weeks without response, most likely due to malabsorption because of concomitant paralytic ileus. Given the persistence of larvae in the body fluids, the worsening respiratory status and clinical malabsorption, veterinary parenteral formulation of ivermectin was administered. The very high plasma concentration of ivermectin achieved in the patient after parenteral administration led to a rapid improvement in his clinical condition and rapid disappearance of the parasite from biological samples, without any adverse reaction.

Bacterial infections remain a challenge to solid organ transplantation. Due to the alarming spread of carbapenem-resistant gram negative bacteria, these organisms have been frequently recognized as cause of severe infections in solid organ transplant recipients.Between 15 May and 30 September 2012 we enrolled 887 solid organ transplant recipients in Italy with the aim to describe the epidemiology of gram negative bacteria spreading, to explore potential risk factors and to assess the effect of early isolation of gram negative bacteria on recipients' mortality during the first 90 days after transplantation. During the study period 185 clinical isolates of gram negative bacteria were reported, for an incidence of 2.39 per 1000 recipient-days. Positive cultures for gram negative bacteria occurred early after transplantation (median time 26 days; incidence rate 4.33, 1.67 and 1.14 per 1,000 recipient-days in the first, second and third month after SOT, respectively). Forty-nine of these clinical isolates were due to carbapenem-resistant gram negative bacteria (26.5%; incidence 0.63 per 1000 recipient-days). Carbapenems resistance was particularly frequent among Klebsiella spp. isolates (49.1%). Recipients with longer hospital stay and those who received either heart or lung graft were at the highest risk of testing positive for any gram negative bacteria. Moreover recipients with longer hospital stay, lung recipients and those admitted to hospital for more than 48h before transplantation had the highest probability to have culture(s) positive for carbapenem-resistant gram negative bacteria. Forty-four organ recipients died (0.57 per 1000 recipient-days) during the study period. Recipients with at least one positive culture for carbapenem-resistant gram negative bacteria had a 10.23-fold higher mortality rate than those who did not.The isolation of gram-negative bacteria is most frequent among recipient with hospital stays >48 hours prior to transplant and in those receiving either heart or lung transplants. Carbapenem-resistant gram negative isolates are associated with significant mortality.

SARS-CoV-2 infection represents a new challenge for solid organ transplantation (SOT) with evolving recommendations. A cross-sectional survey was performed (February–June 2024) to describe practices among Member States of the Council of Europe (COE) on the use of organs from deceased donors with resolved or active SARS-CoV-2 infection. Overall, 32 out of 47 Member States with a transplant program participated in the study. Four (12.5%) countries did not use organs from deceased donors either with resolved or with active SARS-CoV-2 infection and 8 (25%) countries accepted organs only from deceased donors with resolved SARS-CoV-2 infection. Donor evaluation for SARS-CoV-2 included universal screening with standard PCR testing on respiratory specimens generally (61.4%) performed within 24 h prior to organ recovery. Further microbiological, immunological and radiological investigations varied. Most waitlisted patients receiving organs from a deceased donor with active (94.5%) or resolved (61.5%) SARS-CoV-2 infection were preferred to have natural, vaccine-induced or hybrid SARS-CoV-2 immunity. Most countries did not require recipients to undergo specific anti-SARS-CoV-2 treatment as pre-exposure (0%), post-exposure prophylaxis (15.4%) or modification of immunosuppression regimen (24%). This study highlights similarities and heterogeneities in the management of SARS-CoV-2 positive donors between COE countries, and a potential to safely expand donors’ pool.

Objectives: To retrospectively describe the patterns of use of dalbavancin for treating infections in diabetic patients in Italian and Spanish standard clinical practice. Methods: DALBADIA [NCT04959799] was a multicentre, observational, retrospective cohort study, conducted in Italy and Spain. The study enrolled 97 adults with type 1 or 2 diabetes mellitus, treated with dalbavancin as per standard clinical practice for a Gram-positive bacterial infection or the Gram-positive component of a mixed infection. Results: Dalbavancin was used to treat cellulitis (18/92 patients, 19.6%), followed by prosthetic joint infection (14 patients, 15.2%), endocarditis (13 patients, 14.1%), and primary bacteraemia (10 patients, 10.9%); 78/92 (84.8%) patients had Gram-positive infections only, and 14 (15.2%) had mixed infections. The most frequently isolated microorganisms were Staphylococcus aureus in 43 (55.8% of the patients with microbial isolation), 25.6% of which methicillin-resistant; Staphylococcus epidermidis in 13 (16.9%), 53.8% of which methicillin-resistant; Enterococcus faecalis in 11 (14.3%). The main reason for the dalbavancin choice was the intent to simplify the antibiotic regimen (81.5% of cases). A multidisciplinary team participated in the treatment choice process for 53 (57.6%) patients. Dalbavancin was given as first-line antibiotic in 34 (37.0%) patients and administered as one infusion in 32 (34.8%), and as two infusions in 39 (42.4%). In total, 57/62 (91.9%) eligible patients with available assessment were judged clinically cured or improved at the end of observation. Conclusion: In clinical practice, dalbavancin was used in diabetic patients to treat ABSSSIs and other difficult-to-treat infections with a favourable safety profile and a high rate of positive clinical responses.

Abstract Introduction Polymorphonuclear cell influx into the interstitial and bronchoalveolar spaces is a cardinal feature of severe coronavirus disease 2019 (COVID-19), principally mediated by interleukin-8 (IL-8). We sought to determine whether reparixin, a novel IL-8 pathway inhibitor, could reduce disease progression in patients hospitalized with severe COVID-19 pneumonia. Methods In this Phase 3, randomized, double-blind, placebo-controlled, multicenter study, hospitalized adult patients with severe COVID-19 pneumonia were randomized 2:1 to receive oral reparixin 1200 mg three times daily or placebo for up to 21 days or until hospital discharge. The primary endpoint was the proportion of patients alive and free of respiratory failure at Day 28, with key secondary endpoints being the proportion of patients free of respiratory failure at Day 60, incidence of intensive care unit (ICU) admission by Day 28 and time to recovery by Day 28. Results Of 279 patients randomized, 182 received at least one dose of reparixin and 88 received placebo. The proportion of patients alive and free of respiratory failure at Day 28 was similar in the two groups {83.5% versus 80.7%; odds ratio 1.63 [95% confidence interval (CI) 0.75, 3.51]; p = 0.216}. There were no statistically significant differences in the key secondary endpoints, but a numerically higher proportion of patients in the reparixin group were alive and free of respiratory failure at Day 60 (88.7% versus 84.6%; p = 0.195), fewer required ICU admissions by Day 28 (15.8% versus 21.7%; p = 0.168), and a higher proportion recovered by Day 28 compared with placebo (81.6% versus 74.9%; p = 0.167). Fewer patients experienced adverse events with reparixin than placebo (45.6% versus 54.5%), most mild or moderate intensity and not related to study treatment. Conclusions This trial did not meet the primary efficacy endpoints, yet reparixin showed a trend toward limiting disease progression as an add-on therapy in COVID-19 severe pneumonia and was well tolerated. Trial Registration ClinicalTrials.gov: NCT04878055, EudraCT: 2020-005919-51. Graphical Abstract

Lung transplant recipients (LTRs) respond poorly to vaccination. SARS-CoV-2 pre-exposure prophylaxis (PrEP) with tixagevimab/cilgavimab (TIX/CIL) reduces the incidence of infection and the evolution to severe COVID-19. In vitro data show decreased activity against Omicron variants. We evaluated the clinical efficacy and safety of TIX/CIL in LTRs during the Omicron wave. A prospective observational cohort study was conducted at ISMETT in Palermo (Italy). In June 2022, SARS-CoV-2 PrEP with TIX/CIL 150/150 mg was offered to LTRs. LTRs who received TIX/CIL were compared to LTRs who did not. Logistic regression analysis (adjusted for prior COVID-19, SARS-CoV-2 vaccination, age, years from transplant, and rejection) was performed. The objective of this study was to compare the following among the two populations: prevalence of SARS-CoV-2, length of SARS-CoV-2 positivity, and COVID-19 disease severity. Among 110 eligible LTRs, 79 (72%) received TIX/CIL and 31 (28%) did not. SARS-CoV-2 infections occurred in 6% (n = 5) of patients who received TIX/CIL and 29% (n = 9) of patients who did not (p < 0.001). In both groups, infections were mild/asymptomatic, and no one was hospitalized or died. At multivariate analysis, TIX/CIL was associated with a lower risk of infection (aOR 0.22; 95%CI 0.06–0.78; p = 0.02). TIX/CIL was safe and effective in reducing the risk of SARS-CoV-2 in LTRs during the Omicron wave.

Background: Cytomegalovirus (CMV) infection usually occurs asymptomatically but can represent an important cause of morbidity and mortality in patients with compromised immune system such as transplant patients. Infection may not respond to standard therapies leading to refractoriness (with or without resistance) which jeopardizes transplant successful outcome. Objective: Since refractoriness represents a critical point, a project has been conducted to verify the epidemiology in the Italian context and to convey the current patients’ unmet medical needs. Methods: The project included: literature analysis, expert interviews and results’ validation through expert opinion. Based on literature data, a questionnaire was built and submitted to 8 experts with proven experience in the management of post-transplant CMV infection. Topics included epidemiology, patient management, unmet needs and future perspective. Outcomes were validated by 3 additional national experts in solid organ transplantation, hematopoietic stem cell transplantation and infectious diseases. Results: Epidemiological rates from literature applied to current transplantation numbers in Italy estimate approximately 109 adults and 8 children with refractory post-transplant CMV infection in 2021. If valganciclovir/ganciclovir are ineffective, foscarnet is predominantly used. When foscarnet fails, patients have no therapeutic alternatives. Despite being a minority, this represents a high medical need. Therefore, the introduction of new therapeutic options with a better efficacy/safety profile would lead to a significant improvement in refractory CMV infection management. Conclusion: Although refractory infections represent a minority, they are the most critical issue that can occur in post-transplant patients resulting in a high unmet need due to the lack of specific treatment options and the toxicity of current treatments used.

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.

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. 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.