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Background Antiviral prophylaxis is recommended in cytomegalovirus (CMV)-seropositive kidney transplant (KT) recipients receiving antithymocyte globulin (ATG) as induction. An alternative strategy of premature discontinuation of prophylaxis after CMV-specific cell-mediated immunity (CMV-CMI) recovery (immunoguided prevention) has not been studied. Our aim was to determine whether it is effective and safe to discontinue prophylaxis when CMV-CMI is detected and to continue with preemptive therapy. Methods In this open-label, noninferiority clinical trial, patients were randomized 1:1 to follow an immunoguided strategy, receiving prophylaxis until CMV-CMI recovery or to receive fixed-duration prophylaxis until day 90. After prophylaxis, preemptive therapy (valganciclovir 900 mg twice daily) was indicated in both arms until month 6. The primary and secondary outcomes were incidence of CMV disease and replication, respectively, within the first 12 months. Desirability of outcome ranking (DOOR) assessed 2 deleterious events (CMV disease/replication and neutropenia). Results A total of 150 CMV-seropositive KT recipients were randomly assigned. There was no difference in the incidence of CMV disease (0% vs 2.7%; P = .149) and replication (17.1% vs 13.5%; log-rank test, P = .422) between both arms. Incidence of neutropenia was lower in the immunoguided arm (9.2% vs 37.8%; odds ratio, 6.0; P < .001). A total of 66.1% of patients in the immunoguided arm showed a better DOOR, indicating a greater likelihood of a better outcome. Conclusions Prophylaxis can be prematurely discontinued in CMV-seropositive KT patients receiving ATG when CMV-CMI is recovered since no significant increase in the incidence of CMV replication or disease is observed. In cytomegalovirus (CMV)-seropositive kidney transplant recipients receiving ATG induction, immunoguided prevention is not inferior to prophylaxis to prevent CMV complications. Prophylaxis can be prematurely discontinued after CMV-cell-mediated immunity recovery with no significant increase in the incidence of CMV replication or disease.

New reliable biomarkers are needed to improve individual risk assessment for post-transplant infection, acute graft rejection and other immune-related complications after solid organ transplantation (SOT) and allogeneic hematopoietic stem cell transplantation (allo-HSCT). One promising strategy relies on the monitoring of replication kinetics of virome components as functional surrogate for the net state of immunosuppression. Torque Teno Virus (TTV) is a small, non-enveloped, circular, single-stranded DNA anellovirus with no attributable pathological effects. A major component of the human blood virome, TTV exhibits various features that facilitate its application as immune biomarker: high prevalence rates, nearly ubiquitous distribution, stable viral loads with little intra-individual variability, insensitivity to antiviral drugs, and availability of commercial PCR assays for DNA quantification. The present review summarizes the available studies supporting the use of post-transplant TTV viremia to predict patient and graft outcomes after SOT and allo-HSCT. Taken together, this evidence suggests that high or increasing TTV DNA levels precede the occurrence of infectious complications in the SOT setting, whereas low or decreasing viral loads are associated with the development of acute rejection. The interpretation in allo-HSCT recipients is further complicated by complex interplay with the underlying disease, conditioning regimen, and timing of recovery of lymphocyte counts, although TTV kinetics may act as a marker of immunological reconstitution at the early post-transplant period. The standardization of PCR methods and reporting units for TTV DNAemia and the results from ongoing interventional trials evaluating a TTV load-guided strategy to adjust immunosuppressive therapy are achievements expected in the coming years.

BACKGROUND: Torque teno virus, the major member of the genus Alphatorquevirus, is an emerging biomarker of the net state of immunosuppression after kidney transplantation. Genetic diversity constitutes a main feature of the Anelloviridae family, although its posttransplant dynamics and clinical correlates are largely unknown.; METHODS: The relative abundance of Alphatorquevirus, Betatorquevirus, and Gammatorquevirus genera was investigated by high-throughput sequencing in plasma specimens obtained at various points during the first posttransplant year (n = 91 recipients). Total loads of all members of the Anelloviridae family were also quantified by an "in-house" polymerase chain reaction assay targeting conserved DNA sequences (n = 195 recipients). In addition to viral kinetics, clinical study outcomes included serious infection, immunosuppression-related adverse event (opportunistic infection and cancer)' and acute rejection.; RESULTS: Alphatorquevirus DNA was detected in all patients at every point, with an increase from pretransplantation to month 1. A variable proportion of recipients had detectable Betatorquevirus and Gammatorquevirus at lower frequencies. At least 1 change in the predominant genus (mainly as early transition to Alphatorquevirus predominance) was shown in 35.6% of evaluable patients. Total anelloviruses DNA levels increased from baseline to month 1, to peak by month 3 and decrease thereafter, and were higher in patients treated with T-cell depleting agents. There was a significant albeit weak-to-moderate correlation between total anelloviruses and TTV DNA levels. No associations were found between the predominant Anelloviridae genus or total anelloviruses DNA levels and clinical outcomes.; CONCLUSIONS: Our study provides novel insight into the evolution of the anellome after kidney transplantation. Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

Background Increasing evidence suggests that infection with the nonpathogenic human pegivirus type 1 (HPgV-1) exerts a clinical benefit in human immunodeficiency virus (HIV) patients, which could be attributable to immunomodulatory effects. Whether this impact can be extrapolated to kidney transplantation (KT) remains largely unknown. Methods We measured plasma HPgV-1 RNA by real-time polymerase chain reaction targeting the 5 ' untranslated region at various points (pretransplantation, day 7, months 1, 3, 6, and 12) in 199 KT recipients. Study outcomes included posttransplant serious infection, immunosuppression-related adverse event (opportunistic infection and/or de novo cancer), and acute graft rejection. Results HPgV-1 infection was demonstrated in 52 (26.1%) patients, with rates increasing from 14.7% at baseline to 19.1% by month 12 (p-value = .071). De novo infection occurred in 13.8% of patients with no detectable HPgV-1 RNA before transplantation. Double-organ (liver-kidney or kidney-pancreas) transplantation (odds ratio [OR]: 5.62; 95% confidence interval [CI]: 1.52-20.82) and donation after brain death (OR: 2.21; 95% CI: 1.00-4.88) were associated with posttransplant HPgV-1 infection, whereas pretransplant hypertension was protective (OR: 0.23; 95% CI: 0.09-0.55). There were no significant differences in the incidence of study outcomes according to HPgV-1 status. Plasma HPgV-1 RNA levels at different points did not significantly differ between patients that subsequently developed outcomes and those remaining free from these events. No correlation between HPgV-1 RNA and immune parameters or torque teno virus DNA load was observed either. Conclusion Unlike patients living with HIV, HPgV-1 infection does not seem to influence patient or graft outcomes after KT.

The immune system plays a key role in the host defense against viral pathogens. A signaling cascade is activated upon infection involving a variety of molecules such as pattern-recognition receptors (PRRs), interleukins or antiviral interferons. Long-term immunosuppression after solid organ transplantation (SOT) mainly abrogates adaptive T-cell-mediated responses, thus highlighting the relative contribution of innate immunity. Single-nucleotide polymorphisms (SNPs) within genes coding for PRRs or soluble mediators have been associated with differential susceptibility to viral infections among SOT recipients. A protective effect against cytomega-lovirus (CMV) infection or disease has been attributed to certain SNPs in TLR9 or IFNL3 genes, whereas the opposite effect has been attributed to genetic polymorphisms in TLR2, MBL2, DC-SIGN, IL10 or IFNG. The presence of SNPs in other molecules not directly involved in innate or adaptive immune responses such as aquaporins or pregnane X appear to modulate the risk of CMV or BK polyomavirus infection, respectively. Little information is available on the genetic determinants of the post-transplant susceptibility to herpesviruses causing clinical infection (herpes simplex virus or varicella zoster virus) or the replication kinetics of components of the human blood virome used as immune surrogates (Torque teno virus). The present review critically summarizes the current knowledge on how SNP genotyping would be useful to stratify SOT recipients according to the in-dividual risk of viral infection and proposes next research steps. Genetic susceptibility testing may improve personalized medicine and contribute to minimize the risk of viral infection after SOT.

[This corrects the article DOI: 10.1093/ofid/ofab250.].

REIPI/ESGICH/ESGBIS/INCREMENT-SOT Group., There are scarce data on the efficacy of ertapenem in the treatment of bacteremia due to extended-spectrum-beta-lactamase (ESBL)-producing Enterobacterales (ESBL-E) in kidney transplant (KT) recipients. We evaluated the association between treatment with ertapenem or meropenem and clinical cure in KT recipients with nonsevere bacteremic urinary tract infections (B-UTI) caused by ESBL-E. We performed a registered, retrospective, international (29 centers in 14 countries) cohort study (INCREMENT-SOT, NCT02852902). The association between targeted therapy with ertapenem versus meropenem and clinical cure at day 14 (the principal outcome) was studied by logistic regression. Propensity score matching and desirability of outcome ranking (DOOR) analyses were also performed. A total of 201 patients were included; only 1 patient (treated with meropenem) in the cohort died. Clinical cure at day 14 was reached in 45/100 (45%) and 51/101 (50.5%) of patients treated with ertapenem and meropenem, respectively (adjusted OR 1.29; 95% CI 0.51 to 3.22; P = 0.76); the propensity score-matched cohort included 55 pairs (adjusted OR for clinical cure at day 14, 1.18; 95% CI 0.43 to 3.29; P = 0.74). In this cohort, the proportion of cases treated with ertapenem with better DOOR than with meropenem was 49.7% (95% CI, 40.4 to 59.1%) when hospital stay was considered. It ranged from 59 to 67% in different scenarios of a modified (weights-based) DOOR sensitivity analysis when potential ecological advantage or cost was considered in addition to outcome. In conclusion, targeted therapy with ertapenem appears as effective as meropenem to treat nonsevere B-UTI due to ESBL-E in KT recipients and may have some advantages., This work was supported by Plan Nacional de I+D+i 2013‐2016 and Instituto de Salud Carlos III (ISCIII), Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0001, RD16/0016/0002, RD16/0016/0008; RD16/0016/00010) and was cofinanced by the European Development Regional Fund “A way to achieve Europe,” Operative program Intelligent Growth 2014‐2020; ESCMID Study Group for Infections in Compromised Hosts (ESGICH grant to J.M.A.); Sociedad Andaluza de Trasplante de Órgano Sólido (SATOT grant to L.M.-M.); ESCMID Study Group for Bloodstream Infections and Sepsis (ESGBIS); and ESCMID Study Group for Antimicrobial Resistance Surveillance (ESGARS). B.G.-G. (PI 18/01849) and E.P.-N. (PI 16/01631) have received research funds from the Spanish Ministry of Science and Innovation, ISCIII; M.F.-R. holds a research contract “Miguel Servet” (CP 18/00073) from the Spanish Ministry of Science and Innovation, ISCIII.

Invasive fusariosis has a global increasing incidence and has emerged as a severe infection in nonneutropenic patients., Invasive fusariosis (IF) is associated with severe neutropenia in patients with concurrent hematologic conditions. We conducted a retrospective observational study to characterize the epidemiology of IF in 18 Spanish hospitals during 2000–2015. In that time, the frequency of IF in nonneutropenic patients increased from 0.08 cases per 100,000 admissions in 2000–2009 to 0.22 cases per 100,000 admissions in 2010–2015. Nonneutropenic IF patients often had nonhematologic conditions, such as chronic cardiac or lung disease, rheumatoid arthritis, history of solid organ transplantation, or localized fusariosis. The 90-day death rate among nonneutropenic patients (28.6%) and patients with resolved neutropenia (38.1%) was similar. However, the death rate among patients with persistent neutropenia (91.3%) was significantly higher. We used a multivariate Cox regression analysis to characterize risk factors for death: persistent neutropenia was the only risk factor for death, regardless of antifungal therapy.

Current guidelines recommend against systematic screening for or treating asymptomatic bacteriuria (AB) among kidney transplant (KT) recipients, although the evidence regarding episodes occurring early after transplantation or in the presence of anatomical abnormalities is inconclusive. Oral fosfomycin may constitute a good option for the treatment of posttransplant AB, particularly due to the emergence of multidrug-resistant (MDR) uropathogens. Available clinical evidence supporting its use in this specific setting, however, remains scarce. We performed a retrospective study in 14 Spanish institutions from January 2005 to December 2017. Overall, 137 episodes of AB diagnosed in 133 KT recipients treated with oral fosfomycin (calcium and trometamol salts) with a test-of-cure urine culture within the first 30 days were included. Median time from transplantation to diagnosis was 3.1 months (interquartile range [IQR], 1.1 to 10.5). Most episodes (96.4% [132/137]) were caused by Gram-negative bacteria (GNB), and 56.9% (78/137) were categorized as MDR (extended-spectrum beta-lactamase-producing Enterobacterales [20.4%] and carbapenem-resistant GNB [2.9%]). Rate of microbiological failure at month 1 was 40.1% (95% confidence interval [CI], 31.9% to 48.9%) for the whole cohort and 42.3% (95% CI, 31.2% to 54.0%) for episodes due to MDR pathogens. Previous urinary tract infection (odds ratio [OR], 2.42; 95% CI, 1.11 to 5.29; P value = 0.027) and use of fosfomycin as salvage therapy (OR, 8.31; 95% CI, 1.67 to 41.35; P value = 0.010) were predictors of microbiological failure. No severe treatment-related adverse events were detected. Oral fosfomycin appears to be a suitable and safe alternative for the treatment (if indicated) of AB after KT, including those episodes due to MDR uropathogens.

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

Background: The purpose of this study was to compare the clinical outcomes after first metatarsophalangeal (MTP) joint arthrodesis for hallux rigidus between patients who underwent primary arthrodesis and those who had had a prior surgery for hallux valgus. Methods: Our design was a retrospective cohort study comparing 29 patients who underwent primary arthrodesis (primary group) and 34 patients with hallux rigidus after hallux valgus surgery (secondary group). The clinical assessment included the American Orthopaedic Foot & Ankle Society (AOFAS) score and a visual analog scale (VAS) for pain. Radiological evaluation was also performed. Overall, the mean postoperative follow-up was 3.4 (range, 2-5) years. Results: At final follow-up, AOFAS and VAS pain scores significantly improved in both groups (P = .001). However, the mean AOFAS (P = .001) and VAS pain (P = .008) scores were significantly better in the primary group than in the secondary group. Radiologically, there were no significant differences between the groups in any angle after arthrodesis. Revision surgeries were not required in the primary group. In the secondary group, there was 1 revision due to deep infection, and 3 other patients required dorsal plate removal. Excluding plate removal, the Kaplan-Meier survival at 3 years was not significantly different between groups (P = .775). Conclusion: Although arthrodesis of the first MTP joint was an effective procedure for hallux rigidus, the clinical outcomes in patients who had prior hallux valgus surgery were worse than those for patients who underwent primary surgery for hallux rigidus.

Whether immunosuppression impairs severe acute respiratory syndrome coronavirus 2-specific T cell-mediated immunity (SARS-CoV-2-CMI) after liver transplantation (LT) remains unknown. We included 31 LT recipients in whom SARS-CoV-2-CMI was assessed by intracellular cytokine staining (ICS) and interferon (IFN)-gamma FluoroSpot assay after a median of 103days from COVID-19 diagnosis. Serum SARS-CoV-2 IgG antibodies were measured by ELISA. A control group of nontransplant immunocompetent patients were matched (1:1 ratio) by age and time from diagnosis. Post-transplant SARS-CoV-2-CMI was detected by ICS in 90.3% (28/31) of recipients, with higher proportions for IFN-gamma-producing CD4+ than CD8+ responses (93.5% versus 83.9%). Positive spike-specific and nucleoprotein-specific responses were found by FluoroSpot in 86.7% (26/30) of recipients each, whereas membrane protein-specific response was present in 83.3% (25/30). An inverse correlation was observed between the number of spike-specific IFN-gamma-producing SFUs and time from diagnosis (Spearman's rho: -0.418; p value=.024). Two recipients (6.5%) failed to mount either T cell-mediated or IgG responses. There were no significant differences between LT recipients and nontransplant patients in the magnitude of responses by FluoroSpot to any of the antigens. Most LT recipients mount detectable-but declining over time-SARS-CoV-2-CMI after a median of 3months from COVID-19, with no meaningful differences with immunocompetent patients.

BACKGROUND: The magnitude and kinetics of severe acute respiratory syndrome coronavirus 2-specific cell-mediated immunity (SARS-CoV-2-CMI) in kidney transplant (KT) recipients remain largely unknown. METHODS: We enumerated SARS-CoV-2-specific interferon-gamma-producing CD69+ CD4+ and CD8+ T cells at months 4 and 6 from the diagnosis of coronavirus disease 2019 (COVID-19) in 21 KT recipients by intracellular cytokine staining. Overlapping peptides encompassing the SARS-CoV-2 spike (S) glycoprotein N-terminal 1- to 643-amino acid sequence and the membrane protein were used as stimulus. SARS-CoV-2 IgG antibodies targeting the S1 protein were assessed by ELISA at month 6. RESULTS: Detectable (=0.1%) SARS-CoV-2-specific CD4+ T-cell response was found in 57.1% and 47.4% of patients at months 4 and 6. Corresponding rates for CD8+ T cells were 19.0% and 42.1%, respectively. Absolute SARS-CoV-2-specific T-cell counts increased from month 4 to month 6 in CD8+ (P=0.086) but not CD4+ subsets (P=0.349). Four of 10 patients with any detectable response at month 4 had lost SARS-CoV-2-CMI by month 6, whereas 5 of 9 patients mounted SARS-CoV-2-CMI within this period. All but 2 patients (89.5%) tested positive for SARS-CoV-2 IgG. Patients lacking detectable SARS-CoV-2-specific CD4+ response by month 6 were more likely to be under tacrolimus (100.0% versus 66.7%; P=0.087) and to have received tocilizumab for the previous COVID-19 episode (40.0% versus 0.0%; P=0.087). CONCLUSIONS: Although still exploratory and limited by small sample size, the present study suggests that a substantial proportion of KT recipients exhibited detectable SARS-CoV-2-CMI after 6 months from COVID-19 diagnosis.

Treatment of carbapenemase-producing Enterobacterales bloodstream infections in solid organ transplant recipients is challenging. The objective of this study was to develop a specific score to predict mortality in solid organ transplant recipients with carbapenemase-producing Enterobacterales bloodstream infections. A multinational, retrospective (2004-2016) cohort study (INCREMENT-SOT, ClinicalTrials.gov NCT02852902) was performed. The main outcome variable was 30-day all-cause mortality. The INCREMENT-SOT-CPE score was developed using logistic regression. The global cohort included 216 patients. The final logistic regression model included the following variables: INCREMENT-CPE mortality score >= 8 (8 points), no source control (3 points), inappropriate empirical therapy (2 points), cytomegalovirus disease (7 points), lymphopenia (4 points), and the interaction between INCREMENT-CPE score >= 8 and CMV disease (minus 7 points). This score showed an area under the receiver operating characteristic curve of 0.82 (95% confidence interval [CI] 0.76-0.88) and classified patients into 3 strata: 0-7 (low mortality), 8-11 (high mortality), and 12-17 (very-high mortality). We performed a stratified analysis of the effect of monotherapy vs combination therapy among 165 patients who received appropriate therapy. Monotherapy was associated with higher mortality only in the very-high (adjusted hazard ratio [HR] 2.82, 95% CI 1.13-7.06, P = .03) and high (HR 9.93, 95% CI 2.08-47.40, P = .004) mortality risk strata. A score-based algorithm is provided for therapy guidance.

OBJECTIVE: Torque teno virus (TTV) is a highly prevalent non-pathogenic anellovirus whose plasma levels may be a biomarker of immunosuppression. The aim of this study was to assess whether specific immune-targeting with different biologic drugs may differentially modulate TTV viremia in arthritis patients.; METHODS: TTV DNA load was quantified by PCR in a cross-sectional sample of 79 patients with chronic arthritis on biologic therapy (abatacept, infliximab, rituximab or tocilizumab), 31 patients treated with conventional DMARDs (methotrexate and/or leflunomide), and 54 healthy individuals.Longitudinal changes in TTV load were analysed in a second group of 59 patients at baseline and 4-months after biologic therapy. Correlations between clinical or biological characteristics of recruited patients and TTV viremia were also analysed.; RESULTS: In the cross-sectional study, TTV load was significantly higher in patients who received abatacept, infliximab or tocilizumab compared to healthy individuals. Patients treated with rituximab or conventional DMARDs showed TTV loads similar to healthy controls. In the longitudinal study, an increase in the TTV load was observed after anti-TNF, tocilizumab, abatacept and rituximab, but not after secukinumab therapy. Correlations between TTV load and clinical variables such as disease duration, concomitant glucocorticoid or DMARDs therapy, lymphocytes or previous infections were not found. A non-significant trend towards higher TTV load was observed in therapy responders.; CONCLUSION: Patients with chronic arthritis on biologic but not on conventional DMARD or anti-IL17 therapy have increased TTV viremia. This observation provides a basis to prospectively explore the potential value of TTV load as a potential pharmacodynamic biomarker. Copyright © 2019 Elsevier Inc. All rights reserved.

BACKGROUND: We aimed at constructing a composite score based on EBVd and simple clinical and immunological parameters to predict late severe infection (LI) beyond month 6 in SOT recipients.; METHODS: Kidney and liver transplant recipients between May 2014-August 2016 at four participating centers were included. Serum immunoglobulins and complement factors, peripheral blood lymphocyte subpopulations, and whole-blood EBVd were determined at months 1, 3 and 6. Cox regression analyses were performed to generate a weighted score for the prediction of LI.; RESULTS: Overall, 309 SOT recipients were followed-up for a median of 1,000 days from transplant (IQR: 822-1124). LI occurred in 104 patients (33.6%). The CLIV score consisted of the following variables at month 6: high-level EBVd (>1,500 IU/ml) and recurrent infection during the previous months (6 points); recipient age =70 years and chronic graft dysfunction (5 points); CMV mismatch (4 points); and CD8+ T-cell count

External validation of the INCREMENT-CPE risk score (ICS) for 30-day all-cause mortality is needed. There is also scarce information about whether colistin resistance influences the prognosis of carbapenem-resistant Klebsiella pneumoniae (CRKp) bacteraemia. In this study, the ability of ICS to predict all-cause mortality in the KAPECOR cohort was calculated using the area under the receiver operating characteristic (AUROC) curve. The association of colistin resistance with mortality was studied. The ICS showed an AUROC curve of 0.77 (95% CI 0.68-0.86). A cut-off of 8 points showed 96.8% sensitivity and 50.7% specificity. Mortality of low-risk patients was not different in those treated with monotherapy versus combination therapy. However, mortality of high-risk patients treated with combination therapy (37.8%) was significantly lower than in those treated with monotherapy (68.4%) (P = 0.008). To study the prognostic significance of colistin resistance, 83 selected cases of bacteraemia due to colistin-susceptible CRKp were obtained from the INCREMENT cohort for comparison. Colistin resistance could not be shown to be associated with higher mortality in either the high-risk ICS group [adjusted odds ratio (aOR) = 1.56, 95% CI 0.69-3.33; P = 0.29] or in 37 ICS-matched pairs (aOR = 1.38, 95% CI 0.55-3.42; P = 0.49), or in a sensitivity analysis including only KPC isolates (aOR = 1.81, 95% CI 0.73-4.57; P = 0.20), but the precision of estimates was low. These results validate ICS for all-cause mortality and to optimise targeted therapy for CRKp bacteraemia. Colistin resistance was not clearly associated with increased mortality. (C) 2019 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Background Despite being considered a high-risk population for invasive fungal disease, specific features of candidemia among solid organ transplant (SOT) recipients remain poorly characterized. Methods We compiled prospective data from two multicenter studies on candidemia performed over two consecutive periods in Spain: the CANDIPOP Study (2010-2011) and the CANDI-Bundle Study (2016-2018). Episodes diagnosed in adult SOT recipients in 10 participating centers were included. Risk factors for clinical failure (all-cause 7-day mortality and/or persistent candidemia for >= 72 hours) and 30-day mortality were investigated by univariate analysis. Results We included 55 episodes of post-transplant candidemia (32 and 23 of which occurred during the first and second periods). Kidney (38.2%) and liver recipients (30.9%) were the most common populations. Candida albicans accounted for 27.3% of episodes. The proportion of C glabrata increased over time (18.8% vs 30.4% for the first and second periods). There were no differences in the rate of fluconazole non-susceptible isolates (50.0% vs 60.0%, respectively). Clinical failure and 30-day mortality occurred in 25.5% and 27.3% of episodes and were associated with the severity of candidemia (Pitt score and severe sepsis/septic shock). Kidney transplantation (unadjusted odds ratio [uOR]: 0.17; 95% confidence interval [CI]: 0.03-0.85; P-value = .020), early catheter removal (uOR: 0.15; 95% CI: 0.03-0.76; P-value = .013), and appropriate early antifungal therapy (uOR: 0.14; 95% CI: 0.02-0.89; P-value = .041) were protective for 30-day mortality. Conclusions High rates of non-albicans species and fluconazole non-susceptibility must be taken into account to optimize therapeutic management and outcomes in SOT recipients with candidemia.

CANDIPOP Project, the CANDI‐Bundle Group GEIRAS‐GEMICOMED (SEIMC) REIPI., [Background] Despite being considered a high‐risk population for invasive fungal disease, specific features of candidemia among solid organ transplant (SOT) recipients remain poorly characterized., [Methods] We compiled prospective data from two multicenter studies on candidemia performed over two consecutive periods in Spain: the CANDIPOP Study (2010‐2011) and the CANDI‐Bundle Study (2016‐2018). Episodes diagnosed in adult SOT recipients in 10 participating centers were included. Risk factors for clinical failure (all‐cause 7‐day mortality and/or persistent candidemia for ≥72 hours) and 30‐day mortality were investigated by univariate analysis., [Results] We included 55 episodes of post‐transplant candidemia (32 and 23 of which occurred during the first and second periods). Kidney (38.2%) and liver recipients (30.9%) were the most common populations. Candida albicans accounted for 27.3% of episodes. The proportion of C glabrata increased over time (18.8% vs 30.4% for the first and second periods). There were no differences in the rate of fluconazole non‐susceptible isolates (50.0% vs 60.0%, respectively). Clinical failure and 30‐day mortality occurred in 25.5% and 27.3% of episodes and were associated with the severity of candidemia (Pitt score and severe sepsis/septic shock). Kidney transplantation (unadjusted odds ratio [uOR]: 0.17; 95% confidence interval [CI]: 0.03‐0.85; P ‐value = .020), early catheter removal (uOR: 0.15; 95% CI: 0.03‐0.76; P ‐value = .013), and appropriate early antifungal therapy (uOR: 0.14; 95% CI: 0.02‐0.89; P ‐value = .041) were protective for 30‐day mortality., [Conclusions] High rates of non‐albicans species and fluconazole non‐susceptibility must be taken into account to optimize therapeutic management and outcomes in SOT recipients with candidemia., The CANDIPOP Project was supported by non‐restrictive research grants from Gilead Sciences, MSD, Astellas Pharma, and Pfizer. This study was cofounded by Fundación SEIMC‐GESIDA, by the Spanish Ministry of Science, Innovation and Universities, Instituto de Salud Carlos III (co‐financed by the European Development Regional Fund [ERDF] >A way to achieve Europe>), and by the Spanish Network for Research in Infectious Diseases (REIPI RD12/0015). The CANDI‐Bundle Study was supported by “Plan Nacional de I + D+I” and Instituto de Salud Carlos III (Fondo de Investigaciones Sanitarias [FIS] PI15/00744), Subdirección General de Redes y Centros de Investigación Cooperativa, Spanish Ministry of Science, Innovation and Universities, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016). MFR holds a research contract “Miguel Servet” (CP 18/00073) from the Spanish Ministry of Science, Innovation and Universities, Instituto de Salud Carlos III.

Risk factors for invasive pulmonary aspergillosis (IPA) after kidney transplantation have been poorly explored. We performed a multinational case-control study that included 51 kidney transplant (KT) recipients diagnosed with early (first 180 posttransplant days) IPA at 19 institutions between 2000 and 2013. Control recipients were matched (1:1 ratio) by center and date of transplantation. Overall mortality among cases was 60.8%, and 25.0% of living recipients experienced graft loss. Pretransplant diagnosis of chronic pulmonary obstructive disease (COPD; odds ratio [OR]: 9.96; 95% confidence interval [CI]: 1.09-90.58; p = 0.041) and delayed graft function (OR: 3.40; 95% CI: 1.08-10.73; p = 0.037) were identified as independent risk factors for IPA among those variables already available in the immediate peritransplant period. The development of bloodstream infection (OR: 18.76; 95% CI: 1.04-339.37; p = 0.047) and acute graft rejection (OR: 40.73, 95% CI: 3.63-456.98; p = 0.003) within the 3 mo prior to the diagnosis of IPA acted as risk factors during the subsequent period. In conclusion, pretransplant COPD, impaired graft function and the occurrence of serious posttransplant infections may be useful to identify KT recipients at the highest risk of early IPA. Future studies should explore the potential benefit of antimold prophylaxis in this group. A multinational case-control study in kidney transplant recipients finds that pretransplant diagnosis of chronic obstructive pulmonary disease, delayed graft function, bloodstream infection and acute graft rejection identify patients at the highest risk for early invasive pulmonary aspergillosis.

Background Aspergillus spp. of section Usti (A. ustus) represent a rare cause of invasive aspergillosis (IA). This multicenter study describes the epidemiology and outcome of A. ustus infections. Methods Patients with A. ustus isolated from any clinical specimen were retrospectively identified in 22 hospitals from 8 countries. When available, isolates were sent for species identification (BenA/CaM sequencing) and antifungal susceptibility testing. Additional cases were identified by review of the literature. Cases were classified as proven/probable IA or no infection, according to standard international criteria. Results Clinical report forms were obtained for 90 patients, of whom 27 had proven/probable IA. An additional 45 cases were identified from literature review for a total of 72 cases of proven/probable IA. Hematopoietic cell and solid-organ transplant recipients accounted for 47% and 33% cases, respectively. Only 8% patients were neutropenic at time of diagnosis. Ongoing antimold prophylaxis was present in 47% of cases. Pulmonary IA represented 67% of cases. Primary or secondary extrapulmonary sites of infection were observed in 46% of cases, with skin being affected in 28% of cases. Multiple antifungal drugs were used (consecutively or in combination) in 67% of cases. The 24-week mortality rate was 58%. A. calidoustus was the most frequent causal agent. Minimal inhibitory concentrations encompassing 90% isolates (MIC90) were 1, 8, >16, and 4 µg/mL for amphotericin B, voriconazole, posaconazole, and isavuconazole, respectively. Conclusions Aspergillus ustus IA mainly occurred in nonneutropenic transplant patients and was frequently associated with extrapulmonary sites of infection. Mortality rate was high and optimal antifungal therapy remains to be defined.

Solid organ transplant (SOT) recipients are especially at risk of developing infections by multidrug resistant (MDR) Gram-negative bacilli (GNB), as they are frequently exposed to antibiotics and the healthcare setting, and are regulary subject to invasive procedures. Nevertheless, no recommendations concerning prevention and treatment are available. A panel of experts revised the available evidence; this document summarizes their recommendations: (1) it is important to characterize the isolate´s phenotypic and genotypic resistance profile; (2) overall, donor colonization should not constitute a contraindication to transplantation, although active infected kidney and lung grafts should be avoided; (3) recipient colonization is associated with an increased risk of infection, but is not a contraindication to transplantation; (4) different surgical prophylaxis regimens are not recommended for patients colonized with carbapenem-resistant GNB; (5) timely detection of carriers, contact isolation precautions, hand hygiene compliance and antibiotic control policies are important preventive measures; (6) there is not sufficient data to recommend intestinal decolonization; (7) colonized lung transplant recipients could benefit from prophylactic inhaled antibiotics, specially for Pseudomonas aeruginosa; (8) colonized SOT recipients should receive an empirical treatment which includes active antibiotics, and directed therapy should be adjusted according to susceptibility study results and the severity of the infection. J.T.S. holds a research contract from the Fundación para la Formación e Investigación de los Profesionales de la Salud de Extremadura (FundeSalud), Instituto de Salud Carlos III. M.F.R. holds a clinical research contract “Juan Rodés” (JR14/00036) from the Spanish Ministry of Economy and Competitiveness, Instituto de Salud Carlos III.