Natural history and prognostic factors of candidemia in kidney transplant recipients: A retrospective, multinational study.

BACKGROUND: The natural history of candidemia in kidney transplant recipients (KTR) remains poorly understood. This study aimed to evaluate mortality, prognostic factors and overall graft loss after candidemia in KTRs. METHODS: This is a retrospective multicentre study enrolling all KTRs ≥15 years old with candidemia diagnosed at hospitals in Brazil, Spain and Italy from 2010 to 2020. Primary endpoints were mortality rates at 14 and 30 days. Secondary endpoints were prognostic factors of 14-day mortality and overall graft loss. RESULTS: We enrolled 93 KTRs of which 75 were from Brazil. The mean time interval from transplantation to the onset of candidemia was 45.2 ± 61.5 months. 42% of all patients were on haemodialysis, 31.3% had an episode of sepsis and 39% underwent surgery within 30 days before fungemia. European patients were more likely to receive echinocandin (32 vs. 72%, p < .001). 22.7% of Brazilian patients did not receive any antifungal before death. All-cause mortality at 14 days was higher in Brazil (41.3 vs. 11.1%, p = .016). Candida colonisation (OR 6.91 [95% CI: 1.08-44.3], p = .042) and hypotension (OR 4.87 [95% CI: 1.62-14.66], p = .005) were associated with 14-day mortality. Echinocandin treatment had a protective effect (OR 0.19 [95% CI: 0.05-0.73], p = .015). Graft loss at 90 days occurred in 48% of patients (70.7 in Brazil vs. 22.2% in Europe, p < .01). CONCLUSIONS: Candidemia in KTR is usually documented late after engraftment in patients requiring HD, surgical procedures and dysbiosis secondary to antibiotic use. Mortality was higher in Brazil. Echinocandin therapy was associated with improved survival.

Nirmatrelvir/ritonavir for the treatment of immunocompromised adult patients with early-stage symptomatic COVID-19: A real-life experience.

Regardless of vaccination status, progression to severe coronavirus disease 2019 (COVID-19) is still a relevant cause of morbidity among immunocompromised patients. Despite the proven efficacy of nirmatrelvir/ritonavir (NMV/r), concerns remain regarding the potential for drug-to-drug interactions (DDIs) and the safety in this at-risk population. We aimed to evaluate the clinical outcomes of immunocompromised patients treated with NMV/r, as well as the occurrence of DDIs and treatment-emergent adverse events (TEAEs). This retrospective observational study included all the patients with some form of immunosuppression and laboratory-confirmed COVID-19 that received NMV/r at our center from April to August 2022. The main outcome was worsening of the clinical status (increase of ≥1 point from baseline in a validated clinical progression scale) by Days +7 and +28 after the initiation of therapy. Safety outcomes included the rates of any TEAE and potentially severe DDIs. We included 110 patients. Main causes of immunosuppression were hematological malignancy (58.2%) (mainly multiple myeloma [22.7%] and non-Hodgkin lymphoma [13.6%]), active chemotherapy (30.0%) and hematopoietic stem cell transplantation (14.5%). Clinical worsening by Days +7 and +28 was observed in four (3.6%) and five patients (4.5%), respectively. Only one patient had a positive SARS-CoV-2 polymerase chain reaction test at Day +28. At least one potentially severe DDI was observed in 56.4% of the patients. The rate of attributable TEAEs was 10.9%, although only two patients (1.8%) required premature discontinuation of NMV/r. Early initiation of NMV/r therapy should be considered in immunocompromised patients with COVID-19, with particular attention to interacting medications.

Dynamics of Human Anelloviruses in Plasma and Clinical Outcomes Following Kidney Transplantation.

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.

Genetic polymorphisms in TLR3, IL10 and CD209 influence the risk of BK polyomavirus infection after kidney transplantation.

Genetic determinants of BK polyomavirus infection after kidney transplantation remain poorly investigated. We assessed the potential impact of 13 different single nucleotide polymorphisms within genes mainly involved in innate immune responses on the risk of BKPyV viremia in 204 KT recipients. After a median follow-up of 1121.5 days, the cumulative incidence of any-level BKPyV viremia was 24.5% (50/204). There was a significant association between the minor T allele of TLR3 (rs3775291) SNP and the development of BKPyV viremia (adjusted hazard ratio [aHR]: 2.16; 95% confidence interval [CI]: 1.08-4.30; P value = 0.029), whereas the minor G allele of CD209 (rs4804803) SNP exerted a protective role (aHR: 0.54; 95% CI: 0.29-1.00; P value = 0.050). A higher incidence of BKPyV viremia was also observed for the minor G allele of IL10 (rs1800872) SNP, although the absence of BKPyV events among homozygotes for the reference allele prevented multivariable analysis. The BKPyV viremia-free survival rate decreased with the increasing number of unfavorable genotypes (100% [no unfavorable genotypes], 85.4% [1 genotype], 70.9% [2 genotypes], 52.5% [3 genotypes]; P value = 0.008). In conclusion, SNPs in TLR3, CD209 and IL10 genes play a role in modulating the susceptibility to any-level BKPyV viremia among KT recipients.

Reduction of Instrumentation-Related Spine Surgical Site Infections After Optimization of Surgical Techniques. A Single Center Retrospective Analysis.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: Although surgical risk factors for developing spine surgical site infections (S-SSI) have been identified, the impact of such knowledge in its prevention has not been demonstrated. METHODS: We evaluated in 500 patients undergoing spine surgery between 2011 and 2019 at Hospital 12 de Octubre the changes in S-SSI rates over time. Surgical variables independently related to S-SSI were analyzed by univariate and multivariate analysis using binary logistic regression models. A case-control sub-analysis (1:4), matched by the surgical variables identified in the overall cohort was also performed. RESULTS: Twenty cases of S-SSI were identified (4%), with a significant decrease in the incidence rate across consecutive time periods (6.6% [2011-2014] vs .86% [2015-2019]; P-value <.0001)). Multivariate analysis identified arthrodesis involving sacral levels (odds ratio [OR]: 2.57; 95% confidence interval [95%CI]: 1.02-6.47; P-value = .044) and instrumentation over 4-8 vertebrae (OR: 2.82; 95%CI: 1.1-7.1; P-value = .027) as independent risk factors for S-SSI. The reduction in the incidence of S-SSI concurred temporally with a reduction in instrumentations involving 4-8 vertebrae (55% vs 21.8%; P-value <.0001) and sacral vertebrae (46.9% vs 24.6%; P-value <.0001) across both periods. The case-control analysis matched by these surgical variables failed to identify other factors independently related to the occurrence of S-SSI. CONCLUSIONS: Spinal fusion of more than 4 levels and the inclusion of sacral levels were independently related to the risk of S-SSI. Optimization of surgical techniques by reducing these two types of instrumentation could significantly reduce S-SSI rates.

Derivation of a score to predict infection due to multidrug-resistant Pseudomonas aeruginosa: a tool for guiding empirical antibiotic treatment.

OBJECTIVES: Multidrug-resistant Pseudomonas aeruginosa (MDR-PSA) constitutes an emerging health problem. A predictive score of MDR-PSA infection would allow an early adaptation of empirical antibiotic therapy. METHODS: We performed a single-centre case-control (1:2) retrospective study including 100 patients with MDR-PSA and 200 with a non-MDR-PSA infection. Cases and controls were matched by site of infection, clinical characteristics and immunosuppression. A point risk score for prediction of MDR-PSA infection was derived from a logistic regression model. Secondary outcomes (clinical improvement, complications and discharge) were also compared. RESULTS: Cases with MDR-PSA infection were younger than controls (67.5 vs. 73.0 y; P = 0.031) and have more frequent cirrhosis (9% vs. 2%; P = 0.005). Independent risk factors for MDR-PSA infection were prior antibiotic treatment (80% vs. 50.5%; P < 0.001), prior colonisation with MDR bacteria (41% vs. 13.5%; P < 0.001), hospital-acquired infection (63% vs. 47%; P = 0.009) and septic shock at diagnosis (33% vs. 14%; P < 0.001). Adequate therapy was less frequent in MDR-PSA infections (31% vs. 66.5% for empirical therapy; P < 0.001). The risk score included: previous MDR-PSA isolation (11 points), prior antibiotic use (3 points), hospital-acquired infection (2 points) and septic shock at diagnosis (2 points). It showed an area under the curve of 0.755 (95% CI: 0.70-0.81) and allowed to classify individual risk into various categories: 0-2 points (<20%), 3-5 points (25%-45%), 7-11 points (55%-60%), 13-16 points (75%-87%) and a maximum of 18 points (93%). CONCLUSION: Infections due to MDR-PSA have a poorer prognosis than those produced by non-MDR-PSA. Our score could guide empirical therapy for MDR-PSA when P. aeruginosa is isolated.

CMV infection, valganciclovir exposure, and the risk of BK viremia and associated nephropathy after kidney transplantation: Is there a link?

BACKGROUND: Immunomodulatory effects attributable to cytomegalovirus (CMV) would predispose to BK polyomavirus (BKPyV) infection after kidney transplantation (KT), although available evidence is conflicting. It has been suggested that (val)ganciclovir therapy may increase the risk of BKPyV viremia and BKPyV-associated nephropathy (BKPyVAN) as a result of drug-induced T-cell impairment. METHODS: We investigated whether CMV replication and/or (val)ganciclovir exposure (either as prophylaxis or treatment) were associated with the development of BKPyV viremia or BKPyVAN in a prospective cohort of 399 KT recipients. CMV infection (any level or high-level viremia and area under the curve of DNAemia) and (val)ganciclovir exposure (any duration of therapy and cumulative days of treatment) during the first post-transplant year were explored through separate landmark survival analyses. RESULTS: Cumulative incidence of BKPyV viremia and BKPyVAN after a median follow-up of 551 days was 23.1% and 2.5%, respectively. One-year rates of CMV infection and (val)ganciclovir therapy were 47.4% and 54.1%, respectively. No differences were observed in BKPyV viremia- or BKPyVAN-free survival according to previous CMV infection or (val)ganciclovir exposure in any of the landmark analyses. Adjusted Cox models confirmed this lack of association. CONCLUSION: Our findings do not confirm the existence of a relevant impact of CMV infection or (val)ganciclovir therapy on the risk of post-transplant BKPyV events.

A case of pulmonary cryptococcoma due to Cryptococcus gattii in the United Kingdom.

We report a case of Cryptococcus gattii infection in the UK in a 76-year-old woman on biologic therapy for intra-abdominal non-Hodgkin lymphoma. An incidental nodular lung lesion was found on a chest imaging and histology, culture and molecular mycology studies of the lobectomy specimen revealed the presence of C. gattii.