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Background: The use of assays detecting cytomegalovirus (CMV)-specific T cell-mediated immunity may individualize the duration of antiviral prophylaxis after transplantation., Methods: In this randomized trial, kidney and liver transplant recipients from 6 centers in Switzerland were enrolled if they were CMV-seronegative with seropositive donors or CMV-seropositive receiving antithymocyte globulins. Patients were randomized to a duration of antiviral prophylaxis based on immune monitoring (intervention) or a fixed duration (control). Patients in the control group were planned to receive 180 days (CMV-seronegative) or 90 days (CMV-seropositive) of valganciclovir. Patients were assessed monthly with a CMV ELISpot assay (T-Track CMV); prophylaxis in the intervention group was stopped if the assay was positive. The co-primary outcomes were the proportion of patients with clinically significant CMV infection and reduction in days of prophylaxis. Between-group differences were adjusted for CMV serostatus., Results: Overall, 193 patients were randomized (92 in the immune-monitoring group and 101 in the control group), of whom 185 had evaluation of the primary outcome (87 and 98 patients). CMV infection occurred in 26 of 87 (adjusted percentage, 30.9%) in the immune-monitoring group and in 32 of 98 (adjusted percentage, 31.1%) in the control group (adjusted risk difference, -0.1; 95% confidence interval [CI], -13.0% to 12.7%; P = .064). The duration of prophylaxis was shorter in the immune-monitoring group (adjusted difference, -26.0 days; 95%, CI, -41.1 to -10.8 days; P < .001)., Conclusions: Immune monitoring resulted in a significant reduction of antiviral prophylaxis, but we were unable to establish noninferiority of this approach on the co-primary outcome of CMV infection., Clinical Trials Registration: NCT02538172., Competing Interests: Potential conflicts of interest. O. M. reports research grants from Lophius Biosciences (acquired by Mikrogen), the Novartis Foundation, and the Swiss Transplant Cohort Study; participation on a data and safety monitoring board for Syneos and in advisory boards of MSD, Biotest, and Takeda; and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Takeda, paid to their institution. H. H. H. reports grants from Moderna paid to their institution; consulting fees from AiCuris, Allovir, Moderna, VeraTX, and Roche; and honoraria from VeraTX, Takeda, Biotest, and Gilead. P. J. reports serving as an unpaid member of the steering group of a trial funded by Terumo and research grants to their institution from Appili Therapeutics. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: The immunogenicity of the standard influenza vaccine is reduced in solid-organ transplant (SOT) recipients, so new vaccination strategies are needed in this population., Methods: Adult SOT recipients from 9 transplant clinics in Switzerland and Spain were enrolled if they were >3 months after transplantation. Patients were randomized (1:1:1) to a MF59-adjuvanted or a high-dose vaccine (intervention), or a standard vaccine (control), with stratification by organ and time from transplant. The primary outcome was vaccine response rate, defined as a ≥4-fold increase of hemagglutination-inhibition titers to at least 1 vaccine strain at 28 days postvaccination. Secondary outcomes included polymerase chain reaction-confirmed influenza and vaccine reactogenicity., Results: A total of 619 patients were randomized, 616 received the assigned vaccines, and 598 had serum available for analysis of the primary endpoint (standard, n = 198; MF59-adjuvanted, n = 205; high-dose, n = 195 patients). Vaccine response rates were 42% (84/198) in the standard vaccine group, 60% (122/205) in the MF59-adjuvanted vaccine group, and 66% (129/195) in the high-dose vaccine group (difference in intervention vaccines vs standard vaccine, 0.20; 97.5% confidence interval [CI], .12-1); P < .001; difference in high-dose vs standard vaccine, 0.24 [95% CI, .16-1]; P < .001; difference in MF59-adjuvanted vs standard vaccine, 0.17 [97.5% CI, .08-1]; P < .001). Influenza occurred in 6% of the standard, 5% in the MF59-adjuvanted, and 7% in the high-dose vaccine groups. Vaccine-related adverse events occurred more frequently in the intervention vaccine groups, but most of the events were mild., Conclusions: In SOT recipients, use of an MF59-adjuvanted or a high-dose influenza vaccine was safe and resulted in a higher vaccine response rate., Clinical Trials Registration: Clinicaltrials.gov NCT03699839., Competing Interests: Potential conflicts of interest. O. M. reports receiving grants from Lophius Bioscience and participated in advisory boards of Takeda and MSD. N. J. M. reports receiving grants from the Swiss Transplant Cohort Study, receiving support for attending a meeting by Biotest, and participating in the board of the Swiss Society for Infectious Diseases. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Importance: Vaccine responses are decreased in solid organ transplant (SOT) recipients, and given the complexity of implementation, vaccination programs may be suboptimal. The actual burden of vaccine-preventable infections (VPIs) among SOT recipients remains unclear., Objectives: To assess the incidence rate of VPIs among SOT recipients and to evaluate whether SOT recipients are at increased risk for specific VPIs compared with the general population., Design, Setting, and Participants: This nationwide cohort study used data from the Swiss Transplant Cohort Study on VPIs in individuals who underwent SOT from May 2008 to June 2019 (follow-up until December 2019) and data from the Swiss Federal Office of Public Health on notifiable VPIs in the general population in the same period. Data were analyzed from January 2021 to June 2022., Exposures: Solid organ transplant., Main Outcomes and Measures: The main outcomes were the incidence rate of the following VPIs in SOT recipients: hepatitis A and B, diphtheria, Haemophilus influenzae infection, influenza, measles, mumps, pertussis, pneumococcal disease, poliomyelitis, meningococcal disease, rubella, tetanus, tick-borne encephalitis, and varicella zoster virus infection. Age-adjusted standardized incidence ratios were used to assess whether VPIs occurred more frequently in SOT recipients compared with the general population. For SOT recipients, factors associated with occurrence of VPIs were explored and the associated morbidity and mortality assessed., Results: Of 4967 SOT recipients enrolled (median age, 54 years [IQR, 42-62 years]; 3191 [64.2%] male), 593 (11.9%) experienced at least 1 VPI. The overall VPI incidence rate was higher in the population that underwent SOT (30.57 per 1000 person-years [PY]; 95% CI, 28.24-33.10 per 1000 PY) compared with the general population (0.71 per 1000 PY). The standardized age-adjusted incidence ratio for notifiable VPIs in SOT recipients was higher compared with the general population (27.84; 95% CI, 25.00-31.00). In SOT recipients, influenza and varicella zoster virus infection accounted for most VPI episodes (16.55 per 1000 PY [95% CI, 14.85-18.46 per 1000 PY] and 12.83 per 1000 PY [95% CI, 11.40-14.44 per 1000 PY], respectively). A total of 198 of 575 VPI episodes in the population that underwent SOT (34.4%) led to hospital admission, and the occurrence of a VPI was associated with an increased risk for death and/or graft loss (hazard ratio, 2.44; 95% CI, 1.50-3.99; P = .002). In multivariable analysis, age 65 years or older at the time of transplant (incidence rate ratio [IRR], 1.29; 95% CI, 1.02-1.62) and receipt of a lung (IRR, 1.77; 95% CI, 1.38-2.26) or a heart (IRR, 1.40; 95% CI, 1.05-1.88) transplant were associated with an increased risk of VPI occurrence., Conclusions and Relevance: In this study, 11.9% of SOT recipients experienced VPIs, and the incidence rate was higher than in the general population. There was significant morbidity and mortality associated with these infections in the population that underwent SOT, which highlights the need for optimizing immunization strategies.

Background: ABO-incompatible (ABOi) kidney transplantation (KT) expands the kidney donor pool and may help to overcome organ shortage. Nonetheless, concerns about infectious complications associated with ABOi-KT have been raised., Methods: In a nationwide cohort (Swiss Transplant Cohort Study), we compared the risk for infectious complications among ABOi and ABO-compatible (ABOc) renal transplant recipients. Infections needed to fulfill rigorous, prespecified criteria to be classified as clinically relevant. Unadjusted and adjusted competing risk regression models were used to compare the time to the first clinically relevant infection among ABOi-KT and ABOc-KT recipients. Inverse probability weighted generalized mixed-effects Poisson regression was used to estimate incidence rate ratios for infection., Results: We included 757 living-donor KT recipients (639 ABOc; 118 ABOi) and identified 717 infection episodes. The spectrum of causative pathogens and the anatomical sites affected by infections were similar between ABOi-KT and ABOc-KT recipients. There was no significant difference in time to first posttransplant infection between ABOi-KT and ABOc-KT recipients (subhazard ratio, 1.24; 95% confidence interval [CI], 0.93-1.66; P = 0.142). At 1 y, the crude infection rate was 1.11 (95% CI, 0.93-1.33) episodes per patient-year for ABOi patients and 0.94 (95% CI, 0.86-1.01) for ABOc-KT recipients. Inverse probability weighted infection rates were similar between groups (adjusted incidence rate ratio, 1.12; 95% CI, 0.83-1.52; P = 0.461)., Conclusions: The burden of infections during the first year posttransplant was high but not relevantly different in ABOi-KT and ABOc-KT recipients. Our results highlight that concerns regarding infectious complications should not affect the implementation of ABOi-KT programs., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: To describe the epidemiology and clinical presentation of central nervous system (CNS) infections in solid organ transplant (SOT) recipients in the current era of transplantation., Methods: Patients from the Swiss Transplant Cohort Study (STCS) transplanted between 2008 and 2018 were included with a median follow-up of 3.8 years. Epidemiological, microbiological, and clinical data were extracted from the STCS database and patients' medical records. We calculated incidence rates and 90-day survival of transplant recipients with CNS infection., Results: Among 4762 patients, 42 episodes of CNS infection in 41 (0.8%) SOT recipients were identified, with an overall incidence rate of 2.06 per 1000 patient-years. Incidence of CNS infections was similar across all types of transplantations. Time to CNS infection onset ranged from 0.6 to 97 months after transplant. There were 22/42 (52.4%) cases of viral infections, 11/42 (26.2%) of fungal infections, 5/42 (11.9%) of bacterial infections and 4/42 (9.5%) of probable viral/bacterial etiology. Clinical presentation was meningitis/encephalitis in 25 cases (59.5%) and brain-space occupying lesions in 17 cases (40.5%). Twenty-three cases (60.5%) were considered opportunistic infections. Diagnosis were achieved mainly by brain biopsy/necropsy (15/42, 36%) or by cerebrospinal fluid analysis (20/42, 48%). Up to 40% of cases (17/42) had concurrent extra-neurological disease localizations. Overall, 90-day mortality rate was 29.0% (73.0% for fungal, 14.0% for viral and 11.0% for bacterial and probable infections, p<0.0001)., Conclusions: CNS infections were rare in the STCS, with viral meningoencephalitis being the most common disease. Fungal infections were associated with a high mortality., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Ltd.)

Aspergillus endocarditis is a rare infection that may affect immunocompetent patients following heart valve replacement or heart surgery. We report the case of a 39 year old woman with a history of intravenous drug use who developed endocarditis with direct examination of the resected valve and vegetation showing the presence of mycelia. Cultures were positive for an Aspergillus of section Nigri, which was subsequently identified as Aspergillus tubingensis by sequencing. The clinical course was favorable following surgery and prolonged antifungal therapy (8 months in total). Antifungal susceptibility testing showed good in vitro activity of amphotericin B, voriconazole and echinocandins against planktonic cells of this A. tubingensis isolate. However, only amphotericin B displayed significant activity against biofilms. In vitro combinations of voriconazole or amphotericin B with echinocandins did not meet the criteria of synergism. Our review of the literature identified 17 other cases of endocarditis attributed to Aspergillus of section Nigri with an overall mortality rate of 57% (100% in the absence of surgery). Endocarditis caused by Aspergillus niger and related cryptic species are rare events, for which surgical management appears to be crucial for outcome. While amphotericin B was the only antifungal drug displaying significant anti-biofilm activity, the type and duration of antifungal therapy remain to be determined., (© 2022. The Author(s).)

Introduction: In solid organ transplant (SOT) recipients, viral infections are associated with direct morbidity and mortality and may influence long-term allograft outcomes. Prevention of viral infections by vaccination, antiviral prophylaxis, and behavioral measures is therefore of paramount importance., Areas Covered: We searched Pubmed to select publications to review current preventive strategies against the most important viral infections in SOT recipients, including SARS-CoV-2, influenza, CMV, and other herpesvirus, viral hepatitis, measles, mumps, rubella, and BK virus., Expert Opinion: The clinical significance of the reduced humoral response following mRNA SARS-CoV-2 vaccines in SOT recipients still needs to be better clarified, in particular with regard to the vaccines' efficacy in preventing severe disease. Although a third dose improves immunogenicity and is already integrated into routine practice in several countries, further research is still needed to explore additional interventions. In the upcoming years, further data are expected to better delineate the role of virus-specific cell mediated immune monitoring for the prevention of CMV and potentially other viral diseases, and the role of the letermovir in the prevention of CMV in SOT recipients. Future studies including clinical endpoints will hopefully facilitate the integration of successful new influenza vaccination strategies into clinical practice.

Food-safety measures are recommended to solid organ transplant (SOT) recipients. However, the burden of foodborne infections in SOT recipients has not been established. We describe the epidemiology and outcomes of bacterial foodborne infections in a nationwide cohort including 4405 SOT recipients in Switzerland between 2008 and 2018. Participants were prospectively followed for a median of 4.2 years with systematic collection of data on infections, and patient and graft-related outcomes. We identified 151 episodes of microbiologically confirmed bacterial foodborne infections occurring in median 1.6 years (IQR 0.58-3.40) after transplantation (131 [88%] Campylobacter spp. and 15 [10%] non-typhoidal Salmonella). The cumulative incidence of bacterial foodborne infections was 4% (95% CI 3.4-4.8). Standardized incidence rates were 7.4 (95% CI 6.2-8.7) and 4.6 (95% CI 2.6-7.5) for Campylobacter and Salmonella infections, respectively. Invasive infection was more common with Salmonella (33.3% [5/15]) compared to Campylobacter (3.2% [4/125]; p = .001). Hospital and ICU admission rates were 47.7% (69/145) and 4.1% (6/145), respectively. A composite endpoint of acute rejection, graft loss, or death occurred within 30 days in 3.3% (5/151) of cases. In conclusion, in our cohort bacterial foodborne infections were late post-transplant infections and were associated with significant morbidity, supporting the need for implementation of food-safety recommendations., (© 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: The effect of the Toll-like receptor 7 agonist imiquimod before intradermal (ID) or intramuscular (IM) influenza vaccine in immunocompromised hosts is unknown., Methods: In this open-label randomized controlled trial, kidney transplant recipients (KT) and people living with HIV (PLWH) were randomized to receive IM trivalent inactivated influenza vaccine alone (IM), IM vaccine after topical imiquimod (imi+IM) or ID vaccine after topical imiquimod (imi+ID). Immunogenicity was assessed by hemagglutination inhibition assay. The primary outcome was vaccine response, defined as seroconversion to at least one viral strain at day 21., Results: Seventy patients (35 KT and 35 PLWH) received IM (24), imi+IM (22), or imi+ID (24) vaccine. Vaccine response was 61% (14/23) with IM, 59% (13/22) with imi+IM, and 65% (15/23) with imi+ID vaccine (P = 0.909). Vaccine response was associated with HIV infection compared to kidney transplantation (adjusted-OR 3.74, 95% CI 1.25 - 11.23, P = 0.019), but not with imiquimod application nor ID injection. After vaccination, seroprotection to all viral strains was 79% (19/24) with IM, 68% (15/22) with imi+IM, and 70% (16/23) with imi+ID (P = 0.657). We did not observe any vaccine-related severe adverse event., Conclusions: In our study, topical imiquimod did not improve the immunogenicity of influenza vaccine in KT and in PLWH., Competing Interests: Declaration of Competing Interest OM reports grants from Lophius Biosciences, personal fees from MSD, personal fees from Gilead, outside the submitted work. MC reports grants from Gilead, MSD and Viiv, outside the submitted work paid to his institution. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (Copyright © 2021. Published by Elsevier Ltd.)

Posttransplant lymphoproliferative disorder (PTLD) is a serious complication of solid organ transplantation (SOT). Most PTLD cases are associated with Epstein-Barr virus (EBV) infection. The role of antiviral prophylaxis or rituximab therapy for prevention of PTLD in SOT recipients is controversial. In a nationwide cohort, we assessed the incidence, presentation, and outcome of histologically proven PTLD. We included 4765 patients with a follow-up duration of 23 807 person-years (py). Fifty-seven PTLD cases were identified; 39 (68%) were EBV positive (EBV+ PTLD). Incidence rates for EBV+ PTLD at 1, 2, and 3 years posttransplant were 3.51, 2.24, and 1.75/1000 py and 0.44, 0.25, and 0.29/1000 py for EBV- PTLD. We did not find an effect of antiviral prophylaxis on early and late EBV+ PTLD occurrence (early EBV+ PTLD: SHR 0.535 [95% CI 0.199-1.436], p = .264; late EBV+ PTLD: SHR 2.213, [95% CI 0.751-6.521], p = .150). However, none of the patients (0/191) who received a rituximab-containing induction treatment experienced PTLD, but 57 of 4574 patients without rituximab induction developed PTLD. In an adjusted restricted mean survival time model, PTLD-free survival was significantly longer (0.104 years [95% CI 0.077-0.131]) in patients receiving rituximab as induction treatment. This study provides novel data on the association of rituximab induction and reduced risk for PTLD., (© 2020 The Authors. American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.)

Solid organ transplant (SOT) recipients are exposed to respiratory viral infection (RVI) during seasonal epidemics; however, the associated burden of disease has not been fully characterized. We describe the epidemiology and outcomes of RVI in a cohort enrolling 3294 consecutive patients undergoing SOT from May 2008 to December 2015 in Switzerland. Patient and allograft outcomes, and RVI diagnosed during routine clinical practice were prospectively collected. Median follow-up was 3.4 years (interquartile range 1.61-5.56). Six hundred ninety-six RVIs were diagnosed in 151/334 (45%) lung and 265/2960 (9%) non-lung transplant recipients. Cumulative incidence was 60% (95% confidence interval [CI] 53%-69%) in lung and 12% (95% CI 11%-14%) in non-lung transplant recipients. RVI led to 17.9 (95% CI 15.7-20.5) hospital admissions per 1000 patient-years. Intensive care unit admission was required in 4% (27/691) of cases. Thirty-day all-cause case fatality rate was 0.9% (6/696). Using proportional hazard models we found that RVI (adjusted hazard ratio [aHR] 2.45; 95% CI 1.62-3.73), lower respiratory tract RVI (aHR 3.45; 95% CI 2.15-5.52), and influenza (aHR 3.57; 95% CI 1.75-7.26) were associated with graft failure or death. In this cohort of SOT recipients, RVI caused important morbidity and may affect long-term outcomes, underlying the need for improved preventive strategies., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Immunocompromised patients may be at increased risk for complications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, comprehensive data of SARS-CoV-2 infection in solid organ transplant (SOT) recipients are still lacking. We performed a multicenter nationwide observational study within the Swiss Transplant Cohort Study (STCS) to describe the epidemiology, clinical presentation, treatment and outcomes of the first microbiologically documented SARS-CoV-2 infection among SOT recipients. Overall, 21 patients were included with a median age of 56 years (10 kidney, 5 liver, 1 pancreas, 1 lung, 1 heart and 3 combined transplantations). The most common presenting symptoms were fever (76%), dry cough (57%), nausea (33%), and diarrhea (33%). Ninety-five percent and 24% of patients required hospital and ICU admission, respectively, and 19% were intubated. After a median of 33 days of follow-up, 16 patients were discharged, 3 were still hospitalized and 2 patients died. These data suggest that clinical manifestations of SARS-CoV-2 infection in middle-aged SOT recipients appear to be similar to the general population without an apparent higher rate of complications. These results need to be confirmed in larger cohorts., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Food-safety measures are recommended in solid organ transplant (SOT) recipients. However, the actual adherence of patients in a real-life setting and the impact on the incidence of foodborne infections remain largely unexplored. We performed a survey among SOT recipients followed at our institution, aiming to evaluate their food-safety behavior. We assessed the incidence of microbiologically proven foodborne infections by chart review. One hundred ninety-seven SOT recipients (kidney = 117, lung = 35, liver = 29, and heart = 16) participated in the survey. Overall, 17.7% of the participants observed all food-safety recommendations (22.0% avoided food at risk of contamination while 67.9% applied hygiene recommendations). Patients within the first year after transplantation (odds ratio [OR] 5.42; P = .001) and females (OR 4.67; P = .001) followed food-safety recommendations more closely. Although the majority of SOT recipients felt concerned and actively sought information on food safety (68%-70%), only 27% were able to recognize all risks of foodborne infection in hypothetical scenarios. Incidence of proven foodborne infections was 17.9% (95% confidence interval 9.9%-30.9%) 5 years after transplantation. Importantly, foodborne infections occurred exclusively among patients not following food-safety recommendations. In summary, most SOT recipients eat foods that make them at risk of foodborne infections. Our results indicate that there is room for improvement in patient education, particularly later after transplantation, and reinforce current food-safety recommendations., (© 2019 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Skin infections are a frequent cause of consultation, yet the diagnosis can be challenging for physicians. Microbiological documentation is rare, and empiric antibiotic regimens should cover the most commonly identified bacteria, i.e. streptococci Staphylococcus aureus. Other pathogens should be considered in case of immunosuppression or certain exposures. Necrotizing fasciitis (NF) is a severe but rare infection. Early surgical management in parallel with antibiotics is the cornerstone of treatment. Despite the high incidence of these infections, little progress has been made in their management and some areas of uncertainty exist, especially regarding the optimal duration of treatment, the prevention of recurrences and the use of polyclonal immunoglobulins for NF. This article reviews the main aspects of diagnosis and treatment of these infections., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Introduction : In solid organ transplant (SOT) recipients, influenza is associated with significant morbidity, including high hospital admission and mortality rates. Influenza may also impair allograft outcomes, in particular in lung transplant recipients. Early treatment with antivirals and seasonal vaccination contribute to reduce influenza-associated morbidity in this population. Areas covered : We selected a number of publications by searching into Pubmed to review the epidemiology, clinical presentation, outcomes, and management of influenza in SOT recipients. We discuss current treatment options and recent advances in the development of new vaccination strategies. Expert opinion : Our review showed that despite recent studies addressing the current epidemiology of influenza in SOT recipients, data in this population remain sparse. Large international multi-season cohort studies should better describe the actual burden of influenza. Although oseltamivir is an effective drug and should be given to all SOT recipients, the use of novel antivirals and combination therapies need to be tested prospectively in this population. Finally, recent studies aiming to improve the immunogenicity of influenza vaccine in SOT recipients showed promising results, in particular with the use of high-dose vaccines and booster-dose. Clinical trials using clinical endpoints would be important to foster the introduction of these vaccines in the routine clinical practice.

Objectives: To investigate differences in chest computed tomography (CT) and chest radiographs (CXRs) of Pneumocystis jirovecii pneumonia (PJP) between renal transplant recipients (RTRs) and human immunodeficiency virus (HIV)-positive patients., Methods: From 2005 to 2012, 84 patients with PJP (RTR n = 24; HIV n = 60) were included in this retrospective multicentre study. Written informed consent was obtained. CT scans and CXRs were recorded within 2 weeks after the onset of symptoms. PJP diagnosis was confirmed either by cytology/histology or successful empirical treatment. Two blinded radiologists analysed the conventional chest films and CT images, and recorded the radiological lung parenchyma patterns, lymph node enlargement and pleural pathologies (pneumothorax, effusion). The radiological features of the two subgroups were compared., Results: Consolidations and solid nodules prevailed on CT in RTRs (91.7 &plusmn; 5.6% vs 58.3 &plusmn; 6.4% with HIV, p = 0.019 and 91.7 &plusmn; 5.6% vs 51.6 &plusmn; 6.5% with HIV, p = 0.005). HIV-positive patients with PJP showed more atelectasis (41.7 &plusmn; 6.4% vs 4.2 &plusmn; 4.1% in RTRs, p = 0.017) and hilar lymph node enlargement (23.3 &plusmn; 5.5% vs 0.0 &plusmn; 0.0% in RTRs, p = 0.088). Ground glass opacification was found in all cases. Pneumothorax was a rare complication, occurring in 3% of the HIV-positive patients; no pneumothorax was found in the RTRs. On CXR, the basal lungs were more affected in HIV-positive patients as compared with RTRs (p = 0.024)., Conclusions: PJP on CT differs substantially between RTRs and HIV-positive patients. Physicians should be aware of such differences in order not to delay treatment, particularly in renal transplant recipients.

The Roche Cobas 6800 CT/NG assay was compared to the Abbott m2000 Real Time CT/NG assay for detecting Chlamydia trachomatis and Neisseria gonorrhoeae in 714 specimens referred to the bacteriology laboratory at Geneva University Hospitals, between November 2017 and March 2018, and in nine external quality controls for molecular diagnostics (seven from QCMD Glasgow and two from UK NEQAS). For C. trachomatis, the sensitivity of C6800 compared to m2000 was 100 % (95 % confidence interval [CI], 97.5 to 100 %), the specificity was 99.1 % (95 % CI, 98.0 to 99.7 %). For N. gonorrhoeae, the sensitivity of the C6800 compared to m2000 was 100 % (95 % CI, 90.5 to 100 %), whereas the specificity was 99.7 % (95 % CI, 98.9 to 99.9 %). The C6800 CT/NG assay appears to perform with great accuracy the detection of C. trachomatis and N. gonorrhoeae.

Background: The use of vaccines with higher doses of antigen is an attractive strategy to improve the immunogenicity of influenza vaccination in transplant recipients. However, the effect of vaccination with a double-dose (DD) containing 30 µg of antigen in this population remains unknown., Methods: We performed a randomized controlled trial to compare the immunogenicity and safety of DD (30 µg) vs. standard dose (SD, 15 µg) of a trivalent inactivated influenza vaccine in kidney and liver transplant recipients. Immunogenicity was assessed by hemagglutination-inhibition assay. Vaccine response was defined as seroconversion to at least one viral strain 2 weeks after vaccination and seroprotection as a titer ≥40., Results: Sixty-three kidney and 16 liver transplant recipients were enrolled. Forty patients received the DD and 39 the SD vaccine. Overall, 40% of patients in the DD compared to 26% in the SD group (P = 0.174) responded to vaccine. In the DD arm, more patients were seroprotected to all viral strains after vaccination (88% vs 69%, P = 0.048). Post vaccination geometric mean titers of antibodies were 131.9 vs. 89.7 (P = 0.187) for H1N1, 185.4 vs. 138.7 (P = 0.182) for H3N2, and 96.6 vs. 68.8 (P = 0.081) for influenza B with the DD vs. SD. In both groups, most of the adverse events were mild and no vaccine-related severe adverse events were observed., Conclusion: Double-dose influenza vaccine is safe and may increase antibody response in transplant recipients. In this population, DD vaccination could be an alternative when high-dose vaccine is not available. NCT02746783., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Cytomegalovirus (CMV) disease has been associated with the development of chronic lung allograft dysfunction (CLAD) after transplantation. However, the relevance of CMV replication occurring after the discontinuation of antiviral prophylaxis on the development of CLAD has not been fully established. Patients who underwent lung transplantation during 2004-2014 were included. All patients received antiviral prophylaxis for 3-6 months, followed by monitoring of CMV replication during the first year post-transplantation (preemptive therapy). Risk factors for the development of CLAD were assessed by Cox models. A linear regression model with an interaction coefficient between time and CMV infection was used to evaluate the influence of CMV infection on the evolution of FEV 1 . Overall, 69 patients were included, 30/69 (43%) patients developed at least 1 episode of significant CMV infection, and 8/69 (11.5%) patients developed CMV disease. After a median follow-up of 3.67 years, 25/69 (36%) patients developed CLAD and 14/69 (20%) patients died. In the univariate Cox analysis, significant CMV infection (HR 1.177, P = .698), CMV disease (HR 1.001, P = .998), and duration of CMV replication (HR 1.004, P = .758) were not associated with CLAD. Only bacterial pneumonia tended to be associated with CLAD in the multivariate model (HR 2.579, P = .062). We did not observe a significant interaction between CMV replication and evolution FEV 1 (interaction coefficient 0.006, CI 95% [-0.084 to 0.096], P = .890). In this cohort of lung transplant recipients receiving antiviral prophylaxis and monitored by preemptive therapy post-prophylaxis, CMV infection did not have impact on long-term allograft lung function., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Sirtuin 2 (SIRT2) is one of the seven members of the family of NAD + -dependent histone deacetylases. Sirtuins target histones and non-histone proteins according to their subcellular localization, influencing various biological processes. SIRT2 resides mainly in the cytoplasm and regulates cytoskeleton dynamics, cell cycle, and metabolic pathways. As such, SIRT2 has been implicated in the pathogenesis of neurodegenerative, metabolic, oncologic, and chronic inflammatory disorders. This motivated the development of SIRT2-directed therapies for clinical purposes. However, the impact of SIRT2 on antimicrobial host defense is largely unknown. Here, we address this question using SIRT2 knockout mice. We show that SIRT2 is the most highly expressed sirtuin in myeloid cells, especially macrophages. SIRT2 deficiency does not affect immune cell development and marginally impacts on intracellular signaling and cytokine production by splenocytes and macrophages. However, SIRT2 deficiency enhances bacterial phagocytosis by macrophages. In line with these observations, in preclinical models, SIRT2 deficiency increases survival of mice with chronic staphylococcal infection, while having no effect on the course of toxic shock syndrome toxin-1, LPS or TNF-induced shock, fulminant Escherichia coli peritonitis, sub-lethal Klebsiella pneumoniae pneumonia, and chronic candidiasis. Altogether, these data support the safety profile of SIRT2 inhibitors under clinical development in terms of susceptibility to infections.

Short chain fatty acids (SCFAs) produced by intestinal microbes mediate anti-inflammatory effects, but whether they impact on antimicrobial host defenses remains largely unknown. This is of particular concern in light of the attractiveness of developing SCFA-mediated therapies and considering that SCFAs work as inhibitors of histone deacetylases which are known to interfere with host defenses. Here we show that propionate, one of the main SCFAs, dampens the response of innate immune cells to microbial stimulation, inhibiting cytokine and NO production by mouse or human monocytes/macrophages, splenocytes, whole blood and, less efficiently, dendritic cells. In proof of concept studies, propionate neither improved nor worsened morbidity and mortality parameters in models of endotoxemia and infections induced by gram-negative bacteria (Escherichia coli, Klebsiella pneumoniae), gram-positive bacteria (Staphylococcus aureus, Streptococcus pneumoniae) and Candida albicans. Moreover, propionate did not impair the efficacy of passive immunization and natural immunization. Therefore, propionate has no significant impact on host susceptibility to infections and the establishment of protective anti-bacterial responses. These data support the safety of propionate-based therapies, either via direct supplementation or via the diet/microbiota, to treat non-infectious inflammation-related disorders, without increasing the risk of infection.

Antibiotic overuse in primary care setting is a major contributor to the development of resistant bacteria. Antibiotic consumption is low in Switzerland compared to neighbour countries, but improvement is possible and has to be pursued. Antibiotic stewardship helps physician to better recognize patients who need antibiotic (guidelines implementation, electronic decision support and laboratory testing) and educate patients about the uselessness of antibiotics in a given situation (delayed prescription and shared decision making). Clinical studies demonstrated the efficacy of these interventions in reducing antibiotic consumption, mainly in acute respiratory infections, without affecting patients' clinical outcome.

Histone deacetylases (HDACs) control gene expression by deacetylating histones and nonhistone proteins. HDAC inhibitors (HDACi) are powerful anticancer drugs that exert anti-inflammatory and immunomodulatory activities. We recently reported a proof-of-concept study demonstrating that HDACi increase susceptibility to bacterial infections in vivo. Yet, still little is known about the effects of HDACi on antimicrobial innate immune defenses. Here we show that HDACi belonging to different chemical classes inhibit at multiple levels the response of macrophages to bacterial infection. HDACi reduce the phagocytosis and the killing of Escherichia coli and Staphylococcus aureus by macrophages. In line with these findings, HDACi decrease the expression of phagocytic receptors and inhibit bacteria-induced production of reactive oxygen and nitrogen species by macrophages. Consistently, HDACi impair the expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits and inducible nitric oxide synthase. These data indicate that HDACi have a strong impact on critical antimicrobial defense mechanisms in macrophages.

Regulated by histone acetyltransferases and deacetylases (HDACs), histone acetylation is a key epigenetic mechanism controlling chromatin structure, DNA accessibility, and gene expression. HDAC inhibitors induce growth arrest, differentiation, and apoptosis of tumor cells and are used as anticancer agents. Here we describe the effects of HDAC inhibitors on microbial sensing by macrophages and dendritic cells in vitro and host defenses against infection in vivo. HDAC inhibitors down-regulated the expression of numerous host defense genes, including pattern recognition receptors, kinases, transcription regulators, cytokines, chemokines, growth factors, and costimulatory molecules as assessed by genome-wide microarray analyses or innate immune responses of macrophages and dendritic cells stimulated with Toll-like receptor agonists. HDAC inhibitors induced the expression of Mi-2β and enhanced the DNA-binding activity of the Mi-2/NuRD complex that acts as a transcriptional repressor of macrophage cytokine production. In vivo, HDAC inhibitors increased the susceptibility to bacterial and fungal infections but conferred protection against toxic and septic shock. Thus, these data identify an essential role for HDAC inhibitors in the regulation of the expression of innate immune genes and host defenses against microbial pathogens.