Case report: Chronic Candida albicans meningitis: a rare entity diagnosed by metagenomic next-generation sequencing.

The aetiology of chronic aseptic meningitis is difficult to establish. Candida meningitis in particular is often diagnosed late, as cerebrospinal fluid (CSF) work-up and imaging findings are nonspecific. A 35-year-old patient with chronic aseptic meningitis, for which repeated microbiological testing of CSF was unrevealing, was finally diagnosed with Candida albicans (C. albicans) meningitis with cauda equina involvement using metagenomic next-generation sequencing (mNGS). This report highlights the diagnostic challenges and the difficulties of treating shunt-associated fungal meningitis.

Frequency and impact on renal transplant outcomes of urinary tract infections due to extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella species.

Background: Enterobacterales are often responsible for urinary tract infection (UTI) in kidney transplant recipients. Among these, Escherichia coli or Klebsiella species producing extended-spectrum beta-lactamase (ESBL) are emerging. However, there are only scarce data on frequency and impact of ESBL-UTI on transplant outcomes. Methods: We investigated frequency and impact of first-year UTI events with ESBL Escherichia coli and/or Klebsiella species in a prospective multicenter cohort consisting of 1,482 kidney transplants performed between 2012 and 2017, focusing only on 389 kidney transplants having at least one UTI with Escherichia coli and/or Klebsiella species. The cohort had a median follow-up of four years. Results: In total, 139/825 (17%) first-year UTI events in 69/389 (18%) transplant recipients were caused by ESBL-producing strains. Both UTI phenotypes and proportion among all UTI events over time were not different compared with UTI caused by non-ESBL-producing strains. However, hospitalizations in UTI with ESBL-producing strains were more often observed (39% versus 26%, p = 0.04). Transplant recipients with first-year UTI events with an ESBL-producing strain had more frequently recurrent UTI (33% versus 18%, p = 0.02) but there was no significant difference in one-year kidney function as well as longer-term graft and patient survival between patients with and without ESBL-UTI. Conclusion: First-year UTI events with ESBL-producing Escherichia coli and/or Klebsiella species are associated with a higher need for hospitalization but do neither impact allograft function nor allograft and patient survival.

Risk factors for COVID-19-associated pulmonary aspergillosis: a systematic review and meta-analysis.

BACKGROUND: COVID-19-associated pulmonary aspergillosis (CAPA) has been reported to be an emerging and potentially fatal complication of severe COVID-19. However, risk factors for CAPA have not been systematically addressed to date. METHODS: In this systematic review and meta-analysis to identify factors associated with CAPA, we comprehensively searched five medical databases: Ovid MEDLINE; Ovid Embase; the Cochrane Database of Systematic Reviews; the Cochrane Central Register of Controlled Trials; and the WHO COVID-19 Database. All case-control and cohort studies in adults (aged >18 years) that described at least six cases of CAPA and evaluated any risk factors for CAPA, published from Dec 1, 2019, to July 27, 2023, were screened and assessed for inclusion. Only studies with a control population of COVID-19-positive individuals without aspergillosis were included. Two reviewers independently screened search results and extracted outcome data as summary estimates from eligible studies. The primary outcome was to identify the factors associated with CAPA. Meta-analysis was done with random-effects models, with use of the Mantel-Haenszel method to assess dichotomous outcomes as potential risk factors, or the inverse variance method to assess continuous variables for potential association with CAPA. Publication bias was assessed with funnel plots for factors associated with CAPA. The study is registered with PROSPERO, CRD42022334405. FINDINGS: Of 3561 records identified, 27 articles were included in the meta-analysis. 6848 patients with COVID-19 were included, of whom 1324 (19·3%) were diagnosed with CAPA. Diagnosis rates of CAPA ranged from 2·5% (14 of 566 patients) to 47·2% (58 of 123). We identified eight risk factors for CAPA. These factors included pre-existing comorbidities of chronic liver disease (odds ratio [OR] 2·70 [95% CI 1·21-6·04], p=0·02; I2=53%), haematological malignancies (OR 2·47 [1·27-4·83], p=0·008; I2=50%), chronic obstructive pulmonary disease (OR 2·00 [1·42-2·83], p<0·0001; I2=26%), and cerebrovascular disease (OR 1·31 [1·01-1·71], p=0·05; I2=46%). Use of invasive mechanical ventilation (OR 2·83; 95% CI 1·88-4·24; p<0·0001; I2=69%), use of renal replacement therapy (OR 2·26 [1·76-2·90], p<0·0001; I2=14%), treatment of COVID-19 with interleukin-6 inhibitors (OR 2·88 [1·52-5·43], p=0·001; I2=89%), and treatment of COVID-19 with corticosteroids (OR 1·88 [1·28-2·77], p=0·001; I2=66%) were also associated with CAPA. Patients with CAPA were typically older than those without CAPA (mean age 66·6 years [SD 3·6] vs 63·5 years [5·3]; mean difference 2·90 [1·48-4·33], p<0·0001; I2=86%). The duration of mechanical ventilation in patients with CAPA was longer than in those without CAPA (n=7 studies; mean duration 19·3 days [8·9] vs 13·5 days [6·8]; mean difference 5·53 days [1·30-9·77], p=0·01; I2=88%). In post-hoc analysis, patients with CAPA had higher all-cause mortality than those without CAPA (n=20 studies; OR 2·65 [2·04-3·45], p<0·0001; I2=51%). INTERPRETATION: The identified risk factors for CAPA could eventually be addressed with targeted antifungal prophylaxis in patients with severe COVID-19. FUNDING: None.

Immunogenicity of High-Dose Versus MF59-Adjuvanted Versus Standard Influenza Vaccine in Solid Organ Transplant Recipients: The Swiss/Spanish Trial in Solid Organ Transplantation on Prevention of Influenza (STOP-FLU Trial).

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.

Immune Monitoring-Guided Versus Fixed Duration of Antiviral Prophylaxis Against Cytomegalovirus in Solid-Organ Transplant Recipients: A Multicenter, Randomized Clinical Trial.

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.

Vaccine-Preventable Infections Among Solid Organ Transplant Recipients in Switzerland.

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.

Ten-year retrospective cohort analysis of ventricular assist device infections.

BACKGROUND: The number of patients treated by ventricular assist devices (VAD) and the duration of VAD treatment is increasing. One of the main complications in terms of morbidity and mortality for VAD patients are microbial infections. With this study, we aimed to investigate the epidemiology and microbiological characteristics of infections occurring in a VAD population to identify modifiable factors. METHODS: We retrospectively analyzed patient characteristics, treatments and outcomes of VAD-specific/related infections. All patients implanted in our institution with a continuous flow VAD between January 2009 and January 2019 were included. Risk factors for VAD infection were assessed using simple and multiple linear regressions. RESULTS: Of the 104 patients screened, 99 were included in the analysis, the majority of which were men (78%). At implantation, the mean age was 56 years and the median time on VAD support was 541 days. The overall infection rate per year per patient was 1.4. Forty-seven patients (60%) suffered from VAD-specific/related infection. Half of all infection episodes occurred in the first 4 months but the proportion of VAD-specific/related infection was higher after the first 4 months (74% of all infection). Using regression models, no patient specific risk factors were associated with VAD-specific/related infections. CONCLUSION: No predictive factors for infection during VAD support were identified in this study. By extension, diabetes, renal insufficiency, age or high BMI are not sufficient to deny a patient access to ventricular support.

Higher risk for influenza-associated pulmonary aspergillosis (IAPA) in asthmatic patients: A Swiss multicenter cohort study on IAPA in critically ill influenza patients.

BACKGROUND: Influenza-associated pulmonary aspergillosis (IAPA) is an important complication of severe influenza with high morbidity and mortality. METHODS: We conducted a retrospective multicenter study in tertiary hospitals in Switzerland during 2017/2018 and 2019/2020 influenza seasons. All adults with PCR-confirmed influenza infection and treatment on intensive-care unit (ICU) for >24 h were included. IAPA was diagnosed according to previously published clinical, radiological, and microbiological criteria. We assessed risk factors for IAPA and predictors for poor outcome, which was a composite of in-hospital mortality, ICU length of stay ≥7 days, mechanical ventilation ≥7 days, or extracorporeal membrane oxygenation. RESULTS: One hundred fifty-eight patients (median age 64 years, 45% females) with influenza were included, of which 17 (10.8%) had IAPA. Asthma was more common in IAPA patients (17% vs. 4% in non-IAPA, P = 0.05). Asthma (OR 12.0 [95% CI 2.1-67.2]) and days of mechanical ventilation (OR 1.1 [1.1-1.2]) were associated with IAPA. IAPA patients frequently required organ supportive therapies including mechanical ventilation (88% in IAPA vs. 53% in non-IAPA, P = 0.001) and vasoactive support (75% vs. 45%, P = 0.03) and had more complications including ARDS (53% vs. 26%, P = 0.04), respiratory bacterial infections (65% vs. 37%, P = 0.04), and higher ICU-mortality (35% vs. 16.4%, P = 0.05). IAPA (OR 28.8 [3.3-253.4]), influenza A (OR 3.3 [1.4-7.8]), and higher SAPS II score (OR 1.07 [1.05-1.10]) were independent predictors of poor outcome. INTERPRETATION: High clinical suspicion, early diagnostics, and therapy are indicated in IAPA because of high morbidity and mortality. Asthma is likely an underappreciated risk factor for IAPA.

Upside-down positioning of a peri-interventional cava filter during endovascular thrombectomy of a septic superior vena cava thrombosis.

A 43-year-old male patient with advanced colon carcinoma presented with disseminated staphylococcus aureus bacteremia and central venous catheter associated septic thrombosis of the superior vena cava. Despite appropriate antimicrobial therapy and surgical debridement of distant foci, bacteremia persisted, so an endovascular thrombectomy was performed. Contrary to the usual application, the Capturex® peri-interventional cava filter was positioned upside down, in the direction of the blood flow, in the superior vena cava to prevent septic embolism during mechanical thrombectomy. The wall-adherent septic thrombus was mechanically detached using a RAT fragmentation basket® followed by Aspirex® rotational thrombectomy. Final phlebography showed complete thrombus removal. Small thrombus fragments could be demonstrated in the filter after retrieval. The adapted technique of a reverse positioning of the Capturex® filter in the superior vena cava seems feasible and effective.

Challenges of Antimicrobial Resistance and Stewardship in Solid Organ Transplant Patients.

Purpose of Review: Without effective antimicrobials, patients cannot undergo transplant surgery safely or sustain immunosuppressive therapy. This review examines the burden of antimicrobial resistance in solid organ transplant recipients and identifies opportunities for antimicrobial stewardship. Recent Findings: Antimicrobial resistance has been identified to be the leading cause of death globally. Multidrug-resistant pathogens are associated with significant morbidity and mortality in transplant recipients. Methicillin-resistant S. aureus affects liver and lung recipients, causing bacteremia, pneumonia, and surgical site infections. Vancomycin-resistant enterococci is a nosocomial pathogen primarily causing bacteremia in liver recipients. Multidrug-resistant Gram-negative pathogens present urgent and serious threats to transplant recipients. Extended-spectrum beta-lactamase-producing E. coli and K. pneumoniae commonly cause bacteremia and intra-abdominal infections in liver and kidney recipients. Carbapenemase-producing Enterobacterales, mainly K. pneumoniae, are responsible for infections early-post transplant in liver, lung, kidney, and heart recipients. P. aeruginosa and A. baumannii continue to be critical threats. While there are new antimicrobial agents targeting resistant pathogens, judicious prescribing is crucial to minimize emerging resistance. The full implications of the COVID-19 global pandemic on antimicrobial resistance in transplant recipients remain to be understood. Currently, there are no established standards on the implementation of antimicrobial stewardship interventions, but strategies that leverage existing antimicrobial stewardship program structure while tailoring to the needs of transplant recipients may help to optimize antimicrobial use. Summary: Clinicians caring for transplant recipients face unique challenges tackling emerging antimcirobial resistance. Coordinated antimicrobial stewardship interventions in collaboration with appropriate expertise in transplant and infectious diseases may mitigate against such threats.

Central nervous system infections in solid organ transplant recipients: Results from the Swiss Transplant Cohort Study.

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.

Infection Risk in the First Year After ABO-incompatible Kidney Transplantation: A Nationwide Prospective Cohort Study.

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.

Impact of different urinary tract infection phenotypes within the first year post-transplant on renal allograft outcomes.

In this study, we investigated the clinical impact of different urinary tract infection (UTI) phenotypes occurring within the first year after renal transplantation. The population included 2368 transplantations having 2363 UTI events. Patients were categorized into four groups based on their compiled UTI events observed within the first year after transplantation: (i) no colonization or UTI (n = 1404; 59%), (ii) colonization only (n = 353; 15%), (iii) occasional UTI with 1-2 episodes (n = 456; 19%), and (iv) recurrent UTI with ≥3 episodes (n = 155; 7%). One-year mortality and graft loss rate were not different among the four groups, but patients with recurrent UTI had a 7-10 ml/min lower eGFR at year one (44 ml/min vs. 54, 53, and 51 ml/min; p < .001). UTI phenotypes had no impact on long-term patient survival (p = .33). However, patients with recurrent UTI demonstrated a 10% lower long-term death-censored allograft survival (p < .001). Furthermore, recurrent UTI was a strong and independent risk factor for reduced death-censored allograft survival in a multivariable analysis (HR 4.41, 95% CI 2.53-7.68, p < .001). We conclude that colonization and occasional UTI have no impact on pertinent outcomes, but recurrent UTI are associated with lower one-year eGFR and lower long-term death-censored allograft survival. Better strategies to prevent and treat recurrent UTI are needed.

Neuro-axonal injury in COVID-19: the role of systemic inflammation and SARS-CoV-2 specific immune response.

Background: In coronavirus disease-2019 (COVID-19) patients, there is increasing evidence of neuronal injury by the means of elevated serum neurofilament light chain (sNfL) levels. However, the role of systemic inflammation and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immune response with regard to neuronal injury has not yet been investigated. Methods: In a prospective cohort study, we recruited patients with mild-moderate (n = 39) and severe (n = 14) COVID-19 and measured sNfL levels, cytokine concentrations, SARS-CoV-2-specific antibodies including neutralizing antibody titers, and cell-mediated immune responses at enrollment and at 28(±7) days. We explored the association of neuro-axonal injury as by the means of sNfL measurements with disease severity, cytokine levels, and virus-specific immune responses. Results: sNfL levels, as an indicator for neuronal injury, were higher at enrollment and increased during follow-up in severely ill patients, whereas during mild-moderate COVID-19, sNfL levels remained unchanged. Severe COVID-19 was associated with increased concentrations of cytokines assessed [interleukin (IL)-6, IL-8, interleukin-1 beta (IL-1ß), and tumor necrosis factor-alpha (TNF-α)], higher anti-spike IgG and anti-nucleocapsid IgG concentrations, and increased neutralizing antibody titers compared with mild-moderate disease. Patients with more severe disease had higher counts of defined SARS-CoV-2-specific T cells. Increases in sNfL concentrations from baseline to day 28(±7) positively correlated with anti-spike protein IgG antibody levels and with titers of neutralizing antibodies. Conclusion: Severe COVID-19 is associated with increased serum concentration of cytokines and subsequent neuronal injury as reflected by increased levels of sNfL. Patients with more severe disease developed higher neutralizing antibody titers and higher counts of SARS-CoV-2-specific T cells during the course of COVID-19 disease. Mounting a pronounced virus-specific humoral and cell-mediated immune response upon SARS-CoV-2 infection did not protect from neuro-axonal damage as by the means of sNfL levels.

Epidemiology and outcomes of medically attended and microbiologically confirmed bacterial foodborne infections in solid organ transplant recipients.

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.

Distinct Clinical and Laboratory Patterns of Pneumocystis jirovecii Pneumonia in Renal Transplant Recipients.

Late post-transplant Pneumocystis jirovecii pneumonia (PcP) has been reported in many renal transplant recipients (RTRs) centers using universal prophylaxis. Specific features of PcP compared to other respiratory infections in the same population are not well reported. We analyzed clinical, laboratory, administrative and radiological data of all confirmed PcP cases between January 2009 and December 2014. To identify factors specifically associated with PcP, we compared clinical and laboratory data of RTRs with non-PcP. Over the study period, 36 cases of PcP were identified. Respiratory distress was more frequent in PcP compared to non-PcP (tachypnea: 59%, 20/34 vs. 25%, 13/53, p = 0.0014; dyspnea: 70%, 23/33 vs. 44%, 24/55, p = 0.0181). In contrast, fever was less frequent in PcP compared to non-PcP pneumonia (35%, 11/31 vs. 76%, 42/55, p = 0.0002). In both cohorts, total lymphocyte count and serum sodium decreased, whereas lactate dehydrogenase (LDH) increased at diagnosis. Serum calcium increased in PcP and decreased in non-PcP. In most PcP cases (58%, 21/36), no formal indication for restart of PcP prophylaxis could be identified. Potential transmission encounters, suggestive of interhuman transmission, were found in 14/36, 39% of patients. Interhuman transmission seems to contribute importantly to PcP among RTRs. Hypercalcemia, but not elevated LDH, was associated with PcP when compared to non-PcP.

Trimethoprim/sulfamethoxazole for nocardiosis in solid organ transplant recipients: Real-life data from a multicentre retrospective study.

BACKGROUND: Little is known regarding the optimal management of nocardiosis among solid organ transplant (SOT) recipients. It is often suggested to avoid trimethoprim/sulfamethoxazole (TMP-SMX) monotherapy in heavily immunocompromised patients (such as SOT recipients) and/or in case of severe or disseminated nocardiosis. Our aim was to report our experience with TMP-SMX monotherapy in SOT recipients with nocardiosis. METHODS: Using data from a previously published European study, we assessed the incidence of adverse events in SOT recipients receiving TMP-SMX monotherapy and assessed its effectiveness. RESULTS: Thirty-one SOT recipients with nocardiosis were included, mostly kidney transplant recipients (20/31, 65%). Eleven (36%) had disseminated infection, and four (13%) had brain nocardiosis. Most patients had lung and/or pleural involvement (26/31, 84%). Daily dose of trimethoprim at initiation was 10 [6.4-14.8] mg/kg. The median estimated glomerular filtration rate at time of diagnosis of nocardiosis was 44 [30-62] ml/min/1.73 m². TMP-SMX was discontinued prematurely in one third of the patients (10/31, 32%, mostly for hematological toxicity [n = 3] or increased serum creatinine [n = 3]). Focusing on the 24 (77%) patients who completed at least 30 days of TMP-SMX monotherapy, 4 had late (>30 days) drug discontinuation, 1 experienced treatment failure, and 19 completed planned TMP-SMX monotherapy. Clinical outcome was favorable in these 19 patients, despite the fact that 8 (42%) had disseminated infection and 2 (11%) brain nocardiosis. Overall, all-cause 1-year mortality was 10% (3/31). CONCLUSIONS: TMP-SMX monotherapy appears to be effective for the treatment of most nocardiosis among SOT recipients. Interventional studies are needed to compare its safety and effectiveness with those of other regimens used to treat posttransplant nocardiosis.

Temporal trends, risk factors and outcomes of infections due to extended-spectrum ß-lactamase producing Enterobacterales in Swiss solid organ transplant recipients between 2012 and 2018.

BACKGROUND: The burden of antimicrobial resistance is high in solid organ transplant (SOT) recipients. Among Swiss SOT recipients, we assessed temporal trends of ESBL-producing Enterobacterales (ESBL-E), identified risk factors for ESBL-E, and assessed the impact of resistance on patient outcome. METHODS: Data from the Swiss Transplant Cohort Study (STCS), a nationwide prospective cohort of SOT-recipients, were analysed. Temporal trends were described for ESBL-detection among Escherichia coli and non-Escherichia coli. In a nested case-control study, cases with ESBL-E infection were 1:1 matched (by time since transplantation, organ transplant, pathogen) to controls infected with non-ESBL-E. Factors associated with resistance and with unfavourable 30-day outcome (death, infection relapse, graft loss) were assessed. RESULTS: From 2012 to 2018, we identified 1'212 infection episodes caused by Enterobacterales in 1'074 patients, thereof 11.4% (138/1'212) caused by ESBL-E. The proportion of ESBL-production among Escherichia coli remained stable over time (p = 0.93) but increased for non-E. coli (p = 0.02) Enterobacterales. In the case-control study (n = 102), antibiotic pre-treatment was independently associated with ESBL-production (aOR = 2.6, 95%-CI: 1.0-6.8, p = 0.046). Unfavourable outcome occurred in 24/51 (47%) cases and 9/51 (18%) controls (p = 0.003). Appropriate empiric antibiotic therapy was the only modifiable factor associated with unfavourable outcome. CONCLUSIONS: In Swiss SOT-recipients, proportion of infections with ESBL-producing non-E. coli Enterobacterales increased in recent years. Antibiotic pre-treatment represents a risk factor for ESBL-E. Improving appropriateness of empiric antibiotic treatment might be an important measure to reduce unfavourable outcome, which was observed in almost half of SOT-recipients with ESBL-E infections.