ABSTRACT
Pneumonia continues to be one of the most frequent infectious syndromes and a relevant cause of death and health resources utilization. The OPENIN ("Optimización de procesos clínicos para el diagnóstico y tratamiento de infecciones") Group is composed of Infectious Diseases specialists and Microbiologists and aims at generating recommendations that can contribute to improve the approach to processes with high impact on the health system. Such task relies on a critical review of the available scientific evidence. The first Group meeting (held in October 2023) aimed at answering the following questions: Can we optimize the syndromic and microbiological diagnosis of pneumonia? Is it feasible to safely shorten the length of antibiotic therapy? And, is there any role for the immunomodulatory strategies based on the adjuvant use of steroids, macrolides or immunoglobulins? The present review summarizes the literature reviewed for that meeting and offers a series of expert recommendations.
ABSTRACT
BACKGROUND: Infection remains a relevant complication after kidney transplantation (KT). A well-established strategy in modern medicine is the application of bundles of evidence-based practice in clinical settings. The objective of this study is to explore the application of a personalized bundle of measures aimed to reduce the incidence of infection in the first 12 months after KT. METHODS: A single-center prospective cohort of 148 patients undergoing KT between February 2018 and September 2019 that received an individualized infection prevention strategy was compared to a preintervention cohort (n = 159). The bundle comprised a review of the patient's immunization history, infection risk by country of origin, screening for latent tuberculosis infection (LTBI), antimicrobial prophylaxis, and immunological assessment. Individualized recommendations were accordingly provided at a scheduled visit at day +30 after transplantation. RESULTS: The intervention cohort showed a higher compliance rate with the recommended vaccine schedule, screening for geographically restricted infections and LTBI, and intravenous immunoglobulin and vitamin D supplementation (p values <.001). The 1-year incidence rate of infection was lower in the intervention cohort (42.6% vs. 57.9%; p value = .037), as was the rate of infection-related hospitalization (17.6% vs. 32.1%; p value = .003) and the incidence of severe bacterial infection. There were no differences in graft rejection or mortality rates between groups. CONCLUSIONS: A multifaceted intervention, including a bundle of evidence-based practices, enhanced compliance with recommended preventive measures and was correlated with a reduction in the 12-month incidence of infection after KT.
ABSTRACT
INTRODUCTION: Oxidative stress has been implicated in complications after kidney transplantation (KT), including delayed graft function (DGF) and rejection. However, its role in long-term posttransplant outcomes remains unclear. METHODS: We investigated oxidative damage and antioxidant defense dynamics, and their impact on the graft outcomes, in 41 KT recipients categorized by type of donation over 12 months. Oxidative status was determined using OxyScore and AntioxyScore indexes, which comprise several circulating biomarkers of oxidative damage and antioxidant defense. Donor types included donation after brain death (DBD [61.0%]), donation after circulatory death (DCD [26.8%]), and living donation (LD [12.1%]). RESULTS: There was an overall increase in oxidative damage early after transplantation, which was significantly higher in DCD as compared to DBD and LD recipients. The multivariate adjustment confirmed the independent association of OxyScore and type of deceased donation with DGF, donor kidney function, and induction therapy with antithymocyte globulin. There were no differences in terms of antioxidant defense. Lower oxidative damage at day 7 predicted better graft function at 1-year posttransplant only in DBD recipients. CONCLUSION: DCD induced greater short-term oxidative damage after KT, whereas the early levels of oxidative damage were predictive of the graft function 1 year after KT among DBD recipients.
ABSTRACT
Due to the severity of CMV infection in immunocompromised individuals the development of a vaccine has been declared a priority. However, despite the efforts made there is no yet a vaccine available for clinical use. We designed an approach to identify new CMV antigens able to inducing a broad immune response that could be used in future vaccine formulations. We have used serum samples from 28 kidney transplant recipients, with a previously acquired CMV-specific immune response to identify viral proteins that were recognized by the antibodies present in the patient serum samples by Western blot. A band of approximately 45 kDa, identified as UL44, was detected by most serum samples. UL44 immunogenicity was tested in BALB/c mice that received three doses of the UL44-pcDNA DNA vaccine. UL44 elicited both, a strong antibody response and CMV-specific cellular response. Using bioinformatic analysis we demonstrated that UL44 is a highly conserved protein and contains epitopes that are able to activate CD8 lymphocytes of the most common HLA alleles in the world population. We constructed a UL44 ORF deletion mutant virus that produced no viral progeny, suggesting that UL44 is an essential viral protein. In addition, other authors have demonstrated that UL44 is one of the most abundant viral proteins after infection and have suggested an essential role of UL44 in viral replication. Altogether, our data suggests that UL44 is a potent antigen, and favored by its abundance, it may be a good candidate to include in a vaccine formulation.
Subject(s)
Cytomegalovirus Infections , Cytomegalovirus , Mice, Inbred BALB C , Viral Proteins , Animals , Mice , Humans , Cytomegalovirus/immunology , Cytomegalovirus/genetics , Cytomegalovirus Infections/immunology , Cytomegalovirus Infections/virology , Viral Proteins/immunology , Viral Proteins/genetics , Antibodies, Viral/blood , Antibodies, Viral/immunology , Vaccines, DNA/immunology , Vaccines, DNA/administration & dosage , Female , Cytomegalovirus Vaccines/immunology , Cytomegalovirus Vaccines/administration & dosage , T-Lymphocytes/immunology , Antigens, Viral/immunology , Kidney Transplantation , CD8-Positive T-Lymphocytes/immunology , Immunity, CellularABSTRACT
BACKGROUND: Isavuconazole (ISA) and voriconazole (VORI) are recommended as the first-line treatment for invasive aspergillosis (IA). Despite theoretical advantages of ISA, both triazole agents have not been compared in solid organ transplant recipients. METHODS: We performed a post hoc analysis of 2 retrospective multicenter cohorts of solid organ transplant recipients with invasive fungal disease (the SOTIS [Solid Organ Transplantation and ISavuconazole] and DiasperSOT [DIagnosis of ASPERgillosis in Solid Organ Transplantation] studies). We selected adult patients with proven/probable IA that were treated for ≥48 h with ISA (nâ =â 57) or VORI (nâ =â 77) as first-line therapy, either in monotherapy or combination regimen. The primary outcome was the rate of clinical response at 12 wk from the initiation of therapy. Secondary outcomes comprised 12-wk all-cause and IA-attributable mortality and the rates of treatment-emergent adverse events and premature treatment discontinuation. RESULTS: Both groups were comparable in their demographics and major clinical and treatment-related variables. There were no differences in the rate of 12-wk clinical response between the ISA and VORI groups (59.6% versus 59.7%, respectively; odds ratio [OR], 0.99; 95% confidence interval [CI], 0.49-2.00). This result was confirmed after propensity score adjustment (OR, 0.81; 95% CI, 0.32-2.05) and matching (OR, 0.79; 95% CI, 0.31-2.04). All-cause and IA-attributable mortality were also similar. Patients in the ISA group were less likely to experience treatment-emergent adverse events (17.5% versus 37.7%; P = 0.011) and premature treatment discontinuation (8.8% versus 23.4%; P = 0.027). CONCLUSIONS: Front-line treatment with ISA for posttransplant IA led to similar clinical outcomes than VORI, with better tolerability and higher treatment completion.
ABSTRACT
Background: Uncontrolled donation after circulatory death (uDCD) increases organ availability for kidney transplantation (KT) at the expense of a higher risk of primary graft nonfunction (PNF). At least half of the cases of PNF are secondary to graft venous thrombosis. The potential benefit from prophylactic anticoagulation in this scenario remains unclear. Methods: In this single-center retrospective study we compared 2 consecutive cohorts of KT from uDCD with increased (≥0.8) renal resistive index (RRI) in the Doppler ultrasound examination performed within the first 24-72 h after transplantation: 36 patients did not receive anticoagulation ("nonanticoagulation group") and 71 patients underwent prophylactic anticoagulation until normalization of RRI in follow-up Doppler examinations ("anticoagulation group"). Results: Anticoagulation was initiated at a median of 2 d (interquartile range, 2-3) after transplantation and maintained for a median of 12 d (interquartile range, 7-18). In 4 patients (5.6%), anticoagulation had to be prematurely stopped because of the development of a hemorrhagic complication. In comparison with the nonanticoagulation group, recipients in the anticoagulation group had a lower 2-wk cumulative incidence of graft venous thrombosis (19.4% versus 0.0%; Pâ <â 0.001) and PNF (19.4% versus 2.8%; Pâ =â 0.006). The competing risk analysis with nonthrombotic causes of PNF as the competitive event confirmed the higher risk of graft thrombosis in the nonanticoagulation group (Pâ =â 0.0001). The anticoagulation group had a higher incidence of macroscopic hematuria (21.1% versus 5.6%; Pâ =â 0.049) and blood transfusion requirements (39.4% versus 19.4%; Pâ =â 0.050) compared with the nonanticoagulation group. No graft losses or deaths were attributable to complications potentially associated with anticoagulation. Conclusions: Early initiation of prophylactic anticoagulation in selected KT recipients from uDCD with an early Doppler ultrasound RRI of ≥0.8 within the first 24-72 h may reduce the incidence of graft venous thrombosis as a cause of PNF.
ABSTRACT
Introduction: Leuconostoc spp. are facultatively anaerobic Gram-positive cocci involved in cases of hospital-acquired bacteremia, mainly in immunocompromised hosts. The available data is scarce due to its uncommon presentation. Methods: We describe all the episodes of Leuconostoc spp. bacteremia in a third level hospital in a 13-year period (20082021). Results: Four cases of clinically relevant bacteremia were detected. All cases were categorized as catheter-related. The following risk factors were found: previous glycopeptide therapy (75%), use of parenteral nutrition (100%) and cancer (75%). All isolates showed susceptibility to beta-lactams. Catheter removal was performed and wide spectrum antimicrobials were administered, with clinical response in all cases except one. Discussion: Apart from cancer and glycopeptide exposure, disruption of skin barrier and gastrointestinal conditions were identified as risk factors, as it was concordantly underlined in other case series. Susceptibility to beta-lactams is usually maintained. Catheter removal and administration of an active antibacterial therapy seem to be the best approach for Leuconostoc spp. catheter-related bacteremia.(AU)
Introducción: Los microorganismos del género Leuconostoc son cocos grampositivos anaerobios facultativos, involucrados en casos de bacteriemia en pacientes hospitalizados, especialmente con factores de inmunosupresión. La literatura disponible es escasa por su baja frecuencia. Métodos: Describimos todos los episodios de bacteriemia por Leuconostoc spp. en un hospital de tercer nivel en un periodo de 13 años (2008-2021). Resultados: Se detectaron 4 aislamientos clínicamente significativos. Todos ellos fueron categorizados como bacteriemia relacionada con catéter. Se identificaron como factores de riesgo: la exposición previa a glucopéptidos (75%), nutrición parenteral (100%) y cáncer (75%). Todos los aislamientos presentaron sensibilidad a betalactámicos. Se procedió a retirada del catéter y se administraron antimicrobianos de amplio espectro con buena respuesta clínica, salvo en un caso. Discusión: Además del cáncer y la exposición a glucopéptidos, la disrupción de la barrera cutánea y las enfermedades gastrointestinales se identificaron como factores de riesgo, al igual que en otras series. La sensibilidad a betalactámicos suele mantenerse. La retirada del catéter y el uso de terapia antibiótica activa parece ser la mejor alternativa terapéutica para la bacteriemia relacionada con catéter por Leuconostoc spp.(AU)
Subject(s)
Humans , Male , Female , Bacteremia , Leuconostoc , beta-Lactams , Risk FactorsABSTRACT
INTRODUCTION: Solid organ transplant (SOT) recipients face an increased susceptibility to invasive fungal infection (IFI) due to filamentous fungi. Post-transplant invasive aspergillosis (IA) and mucormycosis are related to exceedingly high mortality rates and graft loss risk, and its management involve a unique range of clinical challenges. AREAS COVERED: First, the current treatment recommendations for IA and mucormycosis among SOT recipients are critically reviewed, including the supporting evidence. Next, we discussed particular concerns in this patient population, such as drug-drug interactions (DDIs) between triazoles and post-transplant immunosuppression or treatment-related toxicity. The role for immunomodulatory and host-targeted therapies is also considered, as well as the theoretical impact of the intrinsic antifungal activity of calcineurin inhibitors. Finally, a personal opinion is made on future directions in the pharmacological approach to post-transplant IFI. EXPERT OPINION: Despite relevant advances in the treatment of mold IFIs in the SOT setting, such as the incorporation of isavuconazole (with lower incidence of DDIs and better tolerability than voriconazole), there remains a large room for improvement in areas such as the position of combination therapy or the optimal strategy for the reduction of baseline immunosuppression. Importantly, future studies should define the specific contribution of newer antifungal agents and classes.
Subject(s)
Antifungal Agents , Drug Interactions , Invasive Fungal Infections , Organ Transplantation , Humans , Antifungal Agents/therapeutic use , Antifungal Agents/adverse effects , Invasive Fungal Infections/drug therapy , Organ Transplantation/adverse effects , Mucormycosis/drug therapy , Aspergillosis/drug therapy , Transplant Recipients , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use , AnimalsABSTRACT
Cytomegalovirus (CMV)-seropositive kidney transplant recipients (KTRs) with detectable CMV-specific cell-mediated immunity according to the QuantiFERON-CMV assay (QTF-CMV) are expected to have adequate immune protection. Nevertheless, a proportion of patients still develop CMV infection. Human microRNAs (hsa-miRNAs) are promising biomarkers owing to their high stability and easy detection. We performed whole blood miRNA sequencing in samples coincident with the first reactive QTF-CMV after transplantation or cessation of antiviral prophylaxis to investigate hsa-miRNAs differentially expressed according to the occurrence of CMV infection. One-year incidence of CMV viremia was 55.0% (median interval from miRNA sequencing sampling of 29 days). After qPCR validation, we found that hsa-miR-125a-5p was downregulated in KTRs developing CMV viremia within the next 90 days (ΔCt: 7.9 ± 0.9 versus 7.3 ± 1.0; P = .011). This difference was more evident among KTRs preemptively managed (8.2 ± 0.9 versus 6.9 ± 0.8; P < .001), with an area under the receiver operating characteristic curve of 0.865. Functional enrichment analysis identified hsa-miR-125a-5p targets involved in cell cycle regulation and apoptosis, including the BAK1 gene, which was significantly downregulated in KTRs developing CMV viremia. In conclusion, hsa-miR-125a-5p may serve as biomarker to identify CMV-seropositive KTRs at risk of CMV reactivation despite detectable CMV-CMI.
Subject(s)
Cytomegalovirus Infections , Cytomegalovirus , Kidney Transplantation , MicroRNAs , Humans , Kidney Transplantation/adverse effects , MicroRNAs/genetics , MicroRNAs/blood , Cytomegalovirus Infections/virology , Cytomegalovirus Infections/diagnosis , Cytomegalovirus Infections/etiology , Male , Cytomegalovirus/genetics , Middle Aged , Female , Follow-Up Studies , Risk Factors , Biomarkers/blood , Prognosis , Graft Rejection/etiology , Graft Rejection/virology , Kidney Failure, Chronic/surgery , Postoperative Complications/diagnosis , Viremia/virology , Viremia/diagnosis , Viremia/epidemiology , Adult , Graft Survival , Kidney Function TestsABSTRACT
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.
Subject(s)
Candidemia , Kidney Transplantation , Adolescent , Humans , Antifungal Agents/therapeutic use , Candidemia/drug therapy , Candidemia/epidemiology , Candidemia/microbiology , Echinocandins/therapeutic use , Kidney Transplantation/adverse effects , Prognosis , Retrospective Studies , Risk Factors , AdultABSTRACT
INTRODUCTION: Leuconostoc spp. are facultatively anaerobic Gram-positive cocci involved in cases of hospital-acquired bacteremia, mainly in immunocompromised hosts. The available data is scarce due to its uncommon presentation. METHODS: We describe all the episodes of Leuconostoc spp. bacteremia in a third level hospital in a 13-year period (2008-2021). RESULTS: Four cases of clinically relevant bacteremia were detected. All cases were categorized as catheter-related. The following risk factors were found: previous glycopeptide therapy (75%), use of parenteral nutrition (100%) and cancer (75%). All isolates showed susceptibility to beta-lactams. Catheter removal was performed and wide spectrum antimicrobials were administered, with clinical response in all cases except one. DISCUSSION: Apart from cancer and glycopeptide exposure, disruption of skin barrier and gastrointestinal conditions were identified as risk factors, as it was concordantly underlined in other case series. Susceptibility to beta-lactams is usually maintained. Catheter removal and administration of an active antibacterial therapy seem to be the best approach for Leuconostoc spp. catheter-related bacteremia.
Subject(s)
Bacteremia , Gram-Positive Bacterial Infections , Neoplasms , Humans , Bacteremia/microbiology , beta-Lactams/pharmacology , Catheters, Indwelling/microbiology , Glycopeptides/adverse effects , Gram-Positive Bacterial Infections/diagnosis , Gram-Positive Bacterial Infections/drug therapy , Gram-Positive Bacterial Infections/etiology , Leuconostoc , Neoplasms/complicationsABSTRACT
PURPOSE: We investigated the role of fecal calprotectin (FC) and lactoferrin (FL) as predictive biomarkers in Clostridioides difficile infection (CDI). METHODS: We assembled a prospective cohort including all patients with a laboratory-confirmed CDI diagnosis between January and December 2017. FL and FC levels were measured at diagnosis by commercial ELISA and EIA kits. We investigated the diagnostic accuracy of FC and FL to predict CDI recurrence and severity (study outcomes) and explored optimal cut-off values in addition to those proposed by the manufacturers (200 µg/g and 7.2 µg/mL, respectively). RESULTS: We included 170 CDI cases (152 first episodes and 18 recurrences). The rates of recurrence (first episodes only) and severity (entire cohort) were 9.2% (14/152) and 46.5% (79/170). Both FL and FC levels were significantly higher in patients who developed study outcomes. Optimal cut-off values for FC and FL to predict CDI recurrence were 1052 µg/g and 6.0 µg/mL. The optimal cut-off value for FC yielded higher specificity (60.9%) and positive predictive value (PPV) (16.9%) than that proposed by the manufacturer. Regarding CDI severity, the optimal cut-off value for FC (439 µg/g) also provided higher specificity (43.9%) and PPV (54.1%) than that of the manufacturer, whereas the optimal cut-off value for FL (4.6 µg/mL) resulted in an improvement of PPV (57.5%). CONCLUSION: By modifying the thresholds for assay positivity, the measurement of FC and FL at diagnosis is useful to predict recurrence and severity in CDI. Adding these biomarkers to current clinical scores may help to individualize CDI management.
Subject(s)
Clostridium Infections , Lactoferrin , Humans , Lactoferrin/metabolism , Leukocyte L1 Antigen Complex/analysis , Prospective Studies , Feces/chemistry , Biomarkers/analysis , Clostridium Infections/diagnosis , Clostridium Infections/microbiologyABSTRACT
Utilizing assays that assess specific T-cell-mediated immunity against cytomegalovirus (CMV) holds the potential to enhance personalized strategies aimed at preventing and treating CMV in organ transplantation. This includes improved risk stratification during transplantation compared to relying solely on CMV serostatus, as well as determining the optimal duration of antiviral prophylaxis, deciding on antiviral therapy when asymptomatic replication occurs, and estimating the risk of recurrence. In this review, we initially provide an overlook of the current concepts into the immune control of CMV after transplantation. We then summarize the existent literature on the clinical experience of the use of immune monitoring in organ transplantation, with a particular interest on the outcomes of interventional trials. Current evidence indicates that cell-mediated immune assays are helpful in identifying patients at low risk for replication for whom preventive measures against CMV can be safely withheld. As more data accumulates from these and other clinical scenarios, it is foreseeable that these assays will likely become part of the routine clinical practice in organ transplantation.
Subject(s)
Cytomegalovirus Infections , Organ Transplantation , Humans , Cytomegalovirus , Cytomegalovirus Infections/drug therapy , Antiviral Agents/therapeutic use , Immunity, CellularABSTRACT
PURPOSE: To know whether the production of OXA-48 carbapenemase exerts an independent impact on the outcome of Klebsiella pneumoniae infection, once adjusted by clinical syndrome and baseline risk factors. METHODS: We performed a case-cohort study including 117 infectious episodes due to OXA-48-producing K. pneumoniae (OXA-48-Kp) and 117 episodes due to non-OXA-48-producing strains (non-OXA-48-Kp). Both groups were matched (1:1 ratio) by clinical syndrome (source of infection, preceding invasive procedures and indwelling devices, and associated bacteremia) and hospitalization ward at infection onset. Multivariate Cox regression was used to investigate the association between OXA-48-Kp infection and clinical cure by day 14 (primary outcome) and 30-day all-cause mortality (secondary outcome). RESULTS: Both study groups were well balanced regarding underlying conditions and comorbidity burden. Sepsis or septic shock were more frequent in OXA-48-Kp cases than non-OXA-48-Kp controls (41 [35.0%] vs. 17 [14.5%]; P-value < 0.0001). Clinical cure by day 14 was less commonly achieved in OXA-48-Kp cases (49 [41.9%] vs. 95 [81.2%]; P-value < 0.001), whereas 30-day all-cause mortality was higher (33 [28.2%] vs. 18 [15.4%]; P-value = 0.018). Multivariate analysis confirmed that OXA-48-Kp infection was independently associated with the lack of 14-day clinical cure (adjusted hazard ratio [aHR]: 0.45; 95% confidential interval [95%CI]: 0.29-0.70; P-value < 0.0001). A non-significant association was observed for 30-day all-cause mortality (aHR: 1.65; 95%CI: 0.92-2.94; P-value = 0.093). CONCLUSION: Our matched analysis suggests that the production of OXA-48 carbapenemase acts as an independent risk factor for poor outcome in K. pneumoniae infection as compared to episodes due to non-carbapenemase-producing strains.
Subject(s)
Klebsiella Infections , Klebsiella pneumoniae , Humans , Anti-Bacterial Agents/therapeutic use , Cohort Studies , Klebsiella Infections/microbiology , Retrospective Studies , beta-Lactamases , Bacterial Proteins , Risk FactorsABSTRACT
Background: The immunogenicity elicited by the Omicron BA.4/BA.5-adapted bivalent booster vaccine after solid organ transplantation (SOT) has not been characterized. Methods: We assessed cell-mediated and neutralizing IgG antibody responses against the BA.4/BA.5 spike receptor-binding domain at baseline and 2 wk after the administration of an mRNA-based bivalent (ancestral strain and BA.4/BA.5 subvariants) vaccine among 30 SOT recipients who had received ≥3 monovalent vaccine doses. Previous coronavirus disease 2019 history was present in 46.7% of them. We also recruited a control group of 19 nontransplant healthy individuals. Cell-mediated immunity was measured by fluorescent ELISpot assay for interferon (IFN)-γ secretion, whereas the neutralizing IgG antibody response against the BA.4/BA.5 spike receptor-binding domain was quantified with a competitive ELISA. Results: The median number of BA.4/BA.5 spike-specific IFN-γ-producing spot-forming units (SFUs) increased from baseline to 2 wk postbooster (83.8 versus 133.0 SFUs/106 peripheral blood mononuclear cells; P = 0.0017). Seropositivity rate also increased (46.7%-83.3%; P = 0.001), as well as serum neutralizing activity (4.2%-78.3%; P < 0.0001). Patients with no prior coronavirus disease 2019 history experienced higher improvements in cell-mediated and neutralizing responses after booster vaccination. There was no correlation between BA.4/BA.5 spike-specific IFN-γ-producing SFUs and neutralizing activity. Nontransplant controls showed more robust postbooster cell-mediated immunity than SOT recipients (591.1 versus 133.0 IFN-γ-producing SFUs/106 peripheral blood mononuclear cells; P < 0.0001), although no differences were observed for antibody responses in terms of postbooster seropositivity rates or neutralizing activity. Conclusions: Booster with the BA.4/BA.5-adapted bivalent vaccine generated strong subvariant-specific responses among SOT recipients. Booster-induced cell-mediated immunity, however, remained lower than in immunocompetent individuals.
ABSTRACT
We measured cytomegalovirus (CMV)-specific antibodies that neutralize epithelial cell infection (CMV-AbNEIs) in 101 CMV-seropositive kidney transplant recipients (KTRs) at baseline and post-transplant months 3 and 6. All the patients received antithymocyte globulin and 3-month valganciclovir prophylaxis. There were no significant differences in pre-transplant AbNEIs titers between KTRs that developed or did not develop any-level CMV infection or the composite of high-level infection and/or disease. One-year CMV infection-free survival was comparable between KTRs with or without pre-transplant CMV-AbNEIs. No differences were observed by months 3 and 6 either. We observed no protective role for CMV-AbNEIs among CMV-seropositive KTRs undergoing T-cell-depleting induction.
ABSTRACT
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.
Subject(s)
COVID-19 , Ritonavir , Humans , Adult , SARS-CoV-2 , COVID-19 Drug Treatment , Immunocompromised HostABSTRACT
INTRODUCTION: Clostridioides difficile infection (CDI) is the most prevalent cause of nosocomial bacterial diarrhoea and it is strongly associated with antibiotic use. The recurrence of CDI is a growing medical problem. Data from real-life studies and one open label randomised clinical trial (RCT) suggest that secondary prophylaxis with oral vancomycin (SPV) during subsequent courses of systemic antibiotics is a promising approach for reducing the risk of CDI recurrence. Our aim is to confirm the role of SPV through a double-blind RCT. METHODS AND ANALYSIS: We will perform a phase III, multicentre, placebo-controlled RCT (PREVAN trial) in a 2:1 ratio in favour of SPV (experimental treatment), in four tertiary care hospitals in Spain. Adult patients (≥18 years) with a previous history of CDI in the previous 180 days and with requirement for hospitalisation and systemic antibiotic therapy will be randomly allocated to receive either 125 mg of oral vancomycin or placebo every 6 hours for 10 days. Patients will be followed for 60 days after the end of treatment to verify a reduction in the rate of CDI recurrence in the experimental group. We assume a recurrence rate of 5% in the experimental group versus 25% in the placebo group. Accepting an alpha risk of 0.05 and a beta risk of 0.2 in a two-sided test, 104 subjects will be required in total (68 assigned to the SPV group and 34 to the placebo group). ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Ethic Committee for Research with medicinal products of the University Hospital '12 de Octubre' (AC069/18) and from the Spanish Medicines and Healthcare Product Regulatory Agency (AEMPS, AC069/18), which is valid for all participating centres under existing Spanish legislation. The results will be presented at international meetings and will be made available to patients and funders. TRIAL REGISTRATION NUMBER: NCT05320068.
Subject(s)
Clostridium Infections , Vancomycin , Adult , Humans , Vancomycin/therapeutic use , Anti-Bacterial Agents/therapeutic use , Clostridium Infections/prevention & control , Secondary Prevention , Hospitals, UniversityABSTRACT
Previous studies have suggested that exposure to statins confers a protective effect in bloodstream infection (BSI) due to the anti-inflammatory and immunomodulatory properties attributed to these lipid-lowering drugs. Scarce evidence is available for the solid organ transplant population. Therefore, we compared the time to clinical cure (primary outcome) and the time to fever resolution, new requirement of intensive care unit admission or renal replacement therapy, and 30-day all-cause mortality (secondary outcomes) between kidney transplant (KT) recipients with post-transplant BSI that were receiving or not statin therapy for at least the previous 30 days. We included 80 KT recipients that developed 109 BSI episodes (43 [39.4%] and 66 [60.6%] episodes within the statin and non-statin groups, respectively). The median interval since the initial prescription to BSI was 512 days (interquartile range [IQR]: 172-1388). Most episodes were of urinary source and due to Enterobacterales. There were no differences in the median time to clinical cure in the statin and non-statin groups (3.4 [IQR: 3-6.8] versus 4 [IQR: 2-6] days; p-value = .112). The lack of effect was confirmed by multiple linear regression analysis adjusted for confounding factors (standardized ß coefficient = 0.040; p-value = .709). No significant differences were observed for any of the secondary outcomes either. Vital signs and laboratory values at BSI onset and after 72-96 h were similar in both groups. In conclusion, previous statin therapy had no apparent protective effect on the outcome of post-transplant BSI among KT recipients.