Management of cytomegalovirus in adult solid organ transplant patients: GESITRA-IC-SEIMC, CIBERINFEC, and SET recommendations update.

Cytomegalovirus (CMV) infection remains a significant challenge in solid organ transplantation (SOT). The last international consensus guidelines on the management of CMV in SOT were published in 2018, highlighting the need for revision to incorporate recent advances, notably in cell-mediated immunity monitoring, which could alter the current standard of care. A working group including members from the Group for the Study of Infection in Transplantation and the Immunocompromised Host (GESITRA-IC) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) and the Spanish Society of Transplantation (SET), developed consensus-based recommendations for managing CMV infection in SOT recipients. Recommendations were classified based on evidence strength and quality using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The final recommendations were endorsed through a consensus meeting and approved by the expert panel.

Novel intervention based on an individualized bundle of care to decrease infection in kidney transplant recipients.

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.

Clinical Management and Outcomes of Nontuberculous Mycobacterial Infections in Solid Organ Transplant Recipients: A Multinational Case-control Study.

BACKGROUND: The management and outcomes of nontuberculous mycobacterial (NTM) infections in solid organ transplant (SOT) recipients are poorly characterized. We aimed to describe the management and 1-y mortality of these patients. METHODS: Retrospective, multinational, 1:2 matched case-control study included SOT recipients aged 12 y old or older diagnosed with NTM infection between January 1, 2008, and December 31, 2018. Controls were matched on transplanted organs, NTM treatment center, and posttransplant survival at least equal to the time to NTM diagnosis. The primary aim was 1-y mortality after NTM diagnosis. Differences between cases and controls were compared using the log-rank test, and Cox regression models were used to identify factors associated with mortality at 12 mo among cases. RESULTS: In 85 patients and 169 controls, the median age at the time of SOT was 54 y (interquartile range, 40-62 y), 59% were men, and the lungs were the most common site of infection after SOT (57.6%). One-year mortality was significantly higher in cases than in controls (20% versus 3%; P < 0.001), and higher mortality was associated with lung transplantation (hazard ratio 3.27; 95% confidence interval [1.1-9.77]; P = 0.034). Median time (interquartile range) from diagnosis to treatment initiation (20 [4-42] versus 11 [3-21] d) or the reduction of net immunosuppression (36% versus 45%, hazard ratio 1.35 [95% CI, 0.41-4.43], P = 0.618) did not differ between survivors and those who died. CONCLUSIONS: NTM disease in SOT recipients is associated with a higher mortality risk, especially among lung transplant recipients. Time to NTM treatment and reduction in net immunosuppression were not associated with mortality.

Severe Presentation of Mpox With Skin, Lung and Pleural Involvement in a Non-HIV-Infected Kidney Transplant Recipient.

Monkeypox (mpox) is an orthopoxviral zoonotic disease with a similar but less severe clinical presentation as smallpox. However, immunocompromised patients such as solid organ transplant recipients are at higher risk of developing severe forms of the disease. Herein, we describe the case of a 43-year-old female kidney transplant recipient that manifested severe skin ulcers alongside nodular lung opacities and pleural effusion attributed directly to the monkeypox virus. Notwithstanding the initiation of early treatment with tecovirimat, a satisfactory response was not achieved until a reduction in immunosuppression to everolimus monotherapy, coupled with the transition to cidofovir for antiviral treatment. In conclusion, mpox has the potential to produce a severe form of systemic infection in individuals who have undergone solid organ transplantation, demanding a meticulous approach involving sequential antiviral treatment and modifications to immunosuppressive regimens in order to achieve complete healing.

Dalbavancin as sequential therapy in infective endocarditis: Real-life experience in elder and comorbid patients.

OBJECTIVES: This study aimed to evaluate the effectiveness of dalbavancin as sequential therapy in patients with infective endocarditis (IE) due to gram positive bacteria (GPB) in a real-life heterogenous cohort with comorbid patients. METHODS: A single center retrospective cohort study including all patients with definite IE treated with dalbavancin between January 2017 and February 2022 was developed. A 6-month follow-up was performed. The main outcomes were clinical cure rate, clinical and microbiological relapse, 6-month mortality, and adverse effects (AEs) rate. RESULTS: The study included 61 IE episodes. The median age was 78.5 years (interquartile range [IQR] 63.2-85.2), 78.7% were male, with a median Charlson comorbidity index of 7 (IQR 4-9) points. Overall, 49.2% suffered native valve IE. The most common microorganism was Staphylococcus aureus (26.3%) followed by Enterococcus faecalis (21.3%). The median duration of initial antimicrobial therapy and dalbavancin therapy were 27 (IQR 20-34) and 14 days (IQR 14-28) respectively. The total reduction of hospitalization was 1090 days. The most frequent dosage was 1500mg of dalbavancin every 14 days (96.7%). An AE was detected in 8.2% of patients, only one (1.6%) was attributed to dalbavancin (infusion reaction). Clinical cure was achieved in 86.9% of patients. One patient (1.6%) with Enterococcus faecalis IE suffered relapse. The 6-month mortality was 11.5%, with only one IE-related death (1.6%). CONCLUSION: This study shows a high efficacy of dalbavancin in a heterogeneous real-world cohort of IE patients, with an excellent safety profile. Dalbavancin allowed a substantial reduction of in-hospital length of stay.

Infective endocarditis in pediatric patients: a decade of insights from a leading Spanish heart surgery reference center.

Infective endocarditis (IE) is a rare disease in children and is associated with significant morbidity and mortality. In recent years, significant changes have occurred in pediatric care that could have influenced the microbiology and presentation of IE. The aim of this work was to study epidemiological, microbiological, and clinical features of IE treated at a Pediatric Cardiac Surgery Reference Center located in Madrid (Spain) in a 10-years' period. A descriptive observational retrospective study was performed, including pediatric patients < 16 years old with definite or possible IE admitted to a reference center between January 2012 and December 2021. Thirty-two IE episodes were identified. Twenty-eight (87.5%) had congenital heart disease (CHD), 8 (25.0%) were preterm infants, 1 (3.1%) was immunocompromised and 6 (18.8%) had other chronic conditions; in 11 (34.4%) episodes more than one underlying condition was associated. In 20 (62.5%) episodes there was an indwelling central venous catheter (CVC); children with other comorbidities (preterm, immunocompromised, other chronic conditions) were more likely to have a CVC at diagnosis compared with patients with isolated CHD (p < 0.001). Thirty-six microbiological isolates were obtained in the 32 episodes; 4 (12.5%) episodes had 2 isolated microorganisms. Microbiological isolates were 20 (55.6%) Gram-positive bacteria (GPB), 10 (27.8%) non-HACEK Gram-negative bacteria (GNB), 1 (2.8%) HACEK-group bacterium, 4 (11.1%) fungi and 1 (2.8%) Coxiella burnetii. In 10 (31.3%) episodes, patients were colonized by multidrug-resistant bacteria (MDRB) and the etiology of IE in 3 (30.0%) of those episodes was the colonizing MDRB. MDRB colonization was associated with MDRB IE (p = 0.007). The most common complication was septic embolism: 11 (34.4%) episodes (9 pulmonary and 2 cerebral). In-hospital mortality was 6.3% (n = 2), all of them due to underlying conditions and not to IE or its complications. Clinical features and complications of IE episodes caused by non-HACEK GNB and those caused by GPB were compared, finding no statistically significant differences.    Conclusion: Risk factors for developing IE, the proportion of embolic complications, and mortality rate were consistent with previously published findings. Proportion of IE cases attributed to non-HACEK GNB was higher than previously reported, suggesting an evolving epidemiology of IE. One-third of children colonized with MDRB subsequently developed IE caused by the same MDRB strains, so empirical coverage of MDRB organisms must be considered when IE is suspected in MDRB colonized patients. No significant differences in clinical features and complications were observed when comparing IE episodes caused by non-HACEK GNB and those caused by GPB, however larger cohort studies are needed. What is Known: • Infective endocarditis (IE) is a rare disease in children, associated with significant morbidity and mortality. • The main risk factor for developing IE in children is an underlying congenital heart disease. What is New: • With current changing epidemiology in pediatric IE, a higher proportion of IE caused by non-HACEK Gram-negative bacteria should be expected. • A significant percentage of children colonized by multidrug-resistant bacteria can develop an IE due to those bacteria.

Evolution of the impact of the COVID-19 pandemic on heart transplant recipients: Decreasing risk, improving perspective.

BACKGROUND AND METHODS: Heart transplant recipients (HTr) have a higher probability of suffer from severe coronavirus disease-2019 (COVID-19) in comparison to general population, but their risk has changed over the course of the pandemic in relation to various factors. We conducted a prospective study including all HTr at risk of COVID-19 in a tertiary center between February 2020 and October 2022. The aim was to analyze how the prognosis (incidence of pneumonia and mortality) of COVID-19 in HTr has evolved over time, contextualizing variants, vaccination, and other treatments. RESULTS: Of 308 HTr included, 124 got the infection (39.2%). COVID and non-COVID HTr had similar baseline characteristics. COVID-19 patients with pneumonia had a poorer prognosis than those with less severe presentations, with a higher rate of hospitalization (93.3 vs. 14.1%, p < .001) and death (41.0 vs. 1.2%, p < .001). Multivariate analysis identified age ≥60 years (odds ratio [OR] 3.65, 95% confidence interval [CI] 1.16-11.49, p = .027), and chronic kidney disease ≥3a (OR 4.95, 95% CI 1.39-17.54, p = .014) as predictors of pneumonia. Two-dose vaccination (OR 0.20, CI 95% 0.05-0.72, p = .02) and early remdesivir administration (OR 0.17, CI 0.03-0.90, p = .037) were protective factors. Over the course of the pandemic considering three periods in the follow-up (prevaccination February-December 2020, postvaccination January-December 2021, and post early remdesivir indication January-October 2022), we observed a reduction in pneumonia incidence from 62% to 19% (p < .001); and mortality (from 23% to 4%, p < .001). CONCLUSIONS: The prognosis of COVID-19 in HTr has improved over time, likely due to vaccination and early administration of remdesivir.

Human microRNA sequencing and cytomegalovirus infection risk after kidney transplantation.

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.

Predictive value of fecal calprotectin and lactoferrin levels for negative outcomes in Clostridioides difficile infection.

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.

Production of OXA-48 carbapenemase acts as an independent risk factor for poor outcome in Klebsiella pneumoniae infection.

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.

Cell-mediated and Neutralizing Antibody Responses to the SARS-CoV-2 Omicron BA.4/BA.5-adapted Bivalent Vaccine Booster in Kidney and Liver Transplant Recipients.

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.

Post-transplant dynamics and clinical significance of CMV-specific neutralizing antibodies in kidney transplant recipients treated with T-cell-depleting agents.

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.

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.

Enhancing screening adherence for strongyloides infection in latinx inpatients with COVID-19: a local protocol implementation study.

Strongyloides stercoralis hyperinfection syndrome has been observed in immunosuppressed coronavirus disease 2019 (COVID-19) patients. Detecting and treating asymptomatic Strongyloides infection in individuals from endemic areas can effectively prevent hyperinfection. Unfortunately, many clinicians are unaware of this neglected infection. Therefore, we aimed to evaluate whether including Strongyloides screening in COVID-19 management protocols would encourage this practice. To accomplish this, we conducted a retrospective single-center study at 'Hospital Universitario 12 de Octubre' in Madrid, Spain, comparing two consecutive cohorts. The first cohort comprised all Latinx patients over 18 years old who were admitted for COVID-19 between March 1st and April 30th, 2020. The second cohort consisted of Latinx patients admitted between July 1st and December 31st, 2020, following an amendment to the COVID-19 management protocol that recommended screening for strongyloidiasis in at-risk patients. We identified 559 and 795 patients in the first and second periods, respectively. The percentage of individuals screened increased significantly from 8.8% to 51.6% after the screening recommendation was included in the protocol (odds ratio [OR] 11.08, 95% confidence interval [CI] 8.01-15.33). In both periods, the screening rate was significantly higher among those receiving immunosuppression than those who did not receive steroids and/or tocilizumab. No other factors influenced the screening rate. In conclusion, including strongyloidiasis screening recommendations in COVID-19 management protocols led to its increased implementation. However, the overall screening rate remained low, emphasizing the need for further efforts to enhance screening practices.

Previous use of statins does not improve the outcome of bloodstream infection after kidney transplantation.

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.

A joint program of antimicrobial stewardship and hospital-acquired infection control to reduce healthcare-associated infections after kidney transplantation: The Hipomenes study.

Infection is a common complication in kidney transplant recipients (KTRs). The usefulness of antimicrobial stewardship programs (ASP) and hospital-acquired infection control (HAIC) initiatives in the general inpatient population is well established. We performed a quasi-experimental study to evaluate a joint ASP/HAIC initiative focused on KTRs. A dedicated ASP team optimized antimicrobial prescriptions in consecutive KTRs during the intervention period (June 2015-March 2016). A multifaceted, evidence-based HAIC program was concurrently implemented. Results were compared with the preceding period (June 2014-March 2015). We included 96 and 100 KTRs in the intervention and preintervention periods, respectively. There was a reduction in the consumption of meropenem (rate ratio [RR]: 0.63; 95% confidence interval [CI]: 0.53-0.75; P <.0001), ceftazidime (RR: 0.31; 95% CI: 0.21-0.45; P <.0001), vancomycin (RR: 0.65; 95% CI: 0.53-0.8; P <.0001), and ciprofloxacin (RR: 0.66; 95% CI: 0.55-0.81; P <.0001) and an increase of fosfomycin (RR: 1.80; 95% CI: 1.17-2.76; P =.008) during the intervention period. The incidence of cystitis (RR: 0.30; 95% CI: 0.28-0.33; P <.001) and upper urinary tract infection (RR: 0.56; 95% CI: 0.33-0.95; P =.04) decreased. A specific ASP/HAIC initiative was effective in optimizing antimicrobial use and reducing the incidence of common bacterial infections among KTRs.

Comprehensive analysis of current epidemiology, clinical features and prognostic factors of puerperal endometritis: A retrospective cohort analysis.

Background: Puerperal endometritis has not been recently investigated. We aimed to describe the current dimension of the endometritis in the context of other causes of puerperal fever and investigate the microbiology and need for curettage in these patients. Methods: A retrospective cohort study was conducted based on a prospectively maintained database of patients with puerperal fever, (2014-2020) in which cases fulfilling criteria for endometritis were selected for further analysis. Description of clinical and microbiological features was performed and determination of the factors related with puerperal curettage requirement were studied using univariate and multivariate analysis through binary logistic regression. Results: From 428 patients with puerperal fever, endometritis was the main cause of puerperal fever (233 patients, 52.7 %). Curettage was required in 96 of them (41.2 %). Culture of endometrial samples were performed in 62 (64.5 %), of which 32 (51.6 %) yielded bacterial growth. Escherichia coli was the most common microorganism in curettage cultures (46.9 %). Multivariate analysis identified the following predictive factors for curettage: the presence of pattern compatible with retained products of conception (RPOC) in transvaginal ultrasonography (odds ratio [OR]: 17.6 [95 % confidence interval [CI]: 8.4-36.6]; P-value < 0.0001), fever during the first 14 days after delivery (OR:5.1; [95 % CI: 1.57-16.5]; P-value 0.007), abdominal pain (OR: 2.9; [95 % CI: 1.36-6.1]; P-value 0.012) and malodorous lochia (OR:3.5; [95 % CI: 1.25-9.9]; P-value 0.017). Scheduled cesarean delivery was protective (OR: 0.11 [95 % CI 0.01-1.2]; P-value 0.08). Conclusions: Endometritis is still the main cause of puerperal fever. Women requiring curettage typically presented with abdominal pain and foul-smelling lochia, an ultrasound image compatible with RPOC and fever in the first 14 days postpartum. Curettage culture is useful for the microbiological affiliation mostly yielding gram-negative enteric flora.

Comparison of intracellular cytokine staining versus an ELISA-based assay to assess CMV-specific cell-mediated immunity in high-risk kidney transplant recipients.

The best method for monitoring cytomegalovirus (CMV)-specific cell-mediated immunity (CMV-CMI) among high-risk kidney transplant (KT) recipients remains uncertain. We assessed CMV-CMI by intracellular cytokine staining (ICS) by flow cytometry and a commercial interferon (IFN)-γ release assay (QuantiFERON®-CMV [QTF-CMV]) at posttransplant months 3, 4, and 5 in 53 CMV-seropositive KT recipients that had received induction therapy with antithymocyte globulin (ATG) and a 3-month course of valganciclovir prophylaxis. The discriminative capacity (areas under receiver operating characteristics curve [auROCs]) and diagnostic accuracy to predict immune protection against CMV infection from the discontinuation of prophylaxis to month 12 were compared between both methods. There was significant although moderate correlations between CMV-specific IFN-γ-producing CD8+ T-cell counts enumerated by ICS and IFN-γ levels by QTF-CMV at months 3 (rho: 0.493; p = 0.005) and 4 (rho: 0.440; p = 0.077). The auROCs for CMV-specific CD4+ and CD8+ T-cells by ICS were nonsignificantly higher than that of QTF-CMV (0.696 and 0.733 vs. 0.678; p = 0.900 and 0.692, respectively). The optimal cut-off of ≥0.395 CMV-specific CD8+ T-cells yielded a sensitivity of 86.4%, specificity of 54.6%, positive predictive value of 79.2% and negative predictive value of 66.7% to predict protection. The corresponding estimates for QTF-CMV (IFN-γ levels ≥0.2 IU/mL) were 78.9%, 37.5%, 75.0%, and 42.9%, respectively. The enumeration of CMV-specific IFN-γ-producing CD8+ T-cells at the time of cessation of prophylaxis performed slightly better than the QTF-CMV assay to predict immune protection in seropositive KT recipients previously treated with ATG.

Proof of concept of a new device for the insertion of peripheral venous catheters in aseptic conditions.

According to the recommendations by the World Health Organization, the insertion of a peripheral venous catheter (PVC) must be an aseptic procedure while using non-sterile gloves. To overcome this apparent contradiction we have invented and patented (WO/2021/123482) a new device to be used during PVC insertion. The device permits the PVC placement in the vein while avoiding to directly touch the catheter with the fingertips. A total of 16 PVCs were inserted in the veins of a venipuncture anatomic training model while the operator was wearing non-sterile gloves. The gloves had been previously contaminated by embedding the fingertips in an agar plate inoculated with Staphylococcus epidermidis. Following insertion, the PVCs were sterilely removed and deposited on a bacterial culture plate. The tip cultures of PVCs that had been inserted with or without the use of the device were compared. Eight out of eight cultures (100.0%) were positive for S. epidermidis when the PVC had been inserted without using the device, whereas only one out of eight (12.5%) was positive when the device had been used. The single positive tip culture in the latter group corresponded to an insertion in which the operator had inadvertently touched the sterile part of the device while manipulating it. In conclusion, an auxiliary novel device allows the aseptic insertion of PVCs while the operator is wearing non-sterile gloves. Regulatory institutions should consider to recommend the insertion of PVCs by means of devices aimed at avoiding the contamination of the catheter.

Executive summary - Diagnosis, treatment and prophylaxis of influenza virus infection - Consensus statement of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), the Spanish Society of Pediatric Infectious Diseases (SEIP), the Spanish Association of Vaccinology (AEV), the Spanish Society of Family and Community Medicine (SEMFYC) and the Spanish Society of Preventive Medicine, Public Health and Health Management (SEMPSPGS).

The influenza virus has accompanied humans since time immemorial, in the form of annual epidemics and occasional pandemics. It is a respiratory infection with multiple repercussions on people's lives at an individual and social level, as well as representing a significant burden on the health system. This Consensus Document arises from the collaboration of various Spanish scientific societies involved in influenza virus infection. The conclusions drawn are based on the highest quality evidence available in the scientific literature and, failing that, on the opinion of the experts convened. The Consensus Document addresses the clinical, microbiological, therapeutic, and preventive aspects (with respect to the prevention of transmission and in relation to vaccination) of influenza, for both adult and pediatric populations. This Consensus Document aims to help facilitate the clinical, microbiological, and preventive approach to influenza virus infection and, consequently, to reduce its important consequences on the morbidity and mortality of the population.