Background: This is a prospective, multicenter, observational study in cytomegalovirus (CMV)-seropositive kidney transplant recipients with pretransplant CMV-specific cell-mediated immunity (CMV-CMI) receiving antithymocyte globulin (ATG). We aimed to investigate posttransplant CMV-CMI over time as well as the impact of the dose-dependent ATG. Methods: CMV-CMI was assessed at days +30, +45, +60 and +90 after transplantation with the QuantiFERON-CMV assay. A "Reactive" result (IFNG ¿0.2 UI/mL) indicated a positive CMV-CMI. Results: A total of 78 positive CMV-CMI patients were enrolled in the study, of which 59.5% had a positive CMV-CMI at day +30 and 82.7% at day +90. Multivariate logistic regression analysis showed that the ATG dose was not associated with positive CMV-CMI at any point. However, pretransplant IFNG level (>12 IU/mL vs. ¿12 IU/mL) was associated with having positive CMV-CMI at day +30 (OR 12.9; 95% CI 3.1-53.3; P < .001). In addition, all the patients who did not recover CMV-CMI at day +90 had a pretransplant IFNG level ¿12 IU/mL. Conclusion: More than half of CMV-seropositive kidney transplant recipients receiving ATG recover (or maintain) CMV-CMI by the first month after transplantation The pretransplant IFNG level, but not the ATG dose, shows a strong association with the kinetics of this recovery.

Background: Ivermectin inhibits the replication of SARS-CoV-2 in vitro at concentrations not readily achievable with currently approved doses. There is limited evidence to support its clinical use in COVID-19 patients. We conducted a Pilot, randomized, double-blind, placebo-controlled trial to evaluate the efficacy of a single dose of ivermectin reduce the transmission of SARS-CoV-2 when administered early after disease onset. Methods: Consecutive patients with non-severe COVID-19 and no risk factors for complicated disease attending the emergency room of the Clínica Universidad de Navarra between July 31, 2020 and September 11, 2020 were enrolled. All enrollments occurred within 72 h of onset of fever or cough. Patients were randomized 1:1 to receive ivermectin, 400 mcg/kg, single dose (n = 12) or placebo (n = 12). The primary outcome measure was the proportion of patients with detectable SARS-CoV-2 RNA by PCR from nasopharyngeal swab at day 7 post-treatment. The primary outcome was supported by determination of the viral load and infectivity of each sample. The differences between ivermectin and placebo were calculated using Fisher's exact test and presented as a relative risk ratio. This study is registered at ClinicalTrials.gov: NCT04390022. Findings: All patients recruited completed the trial (median age, 26 [IQR 19-36 in the ivermectin and 21-44 in the controls] years; 12 [50%] women; 100% had symptoms at recruitment, 70% reported headache, 62% reported fever, 50% reported general malaise and 25% reported cough). At day 7, there was no difference in the proportion of PCR positive patients (RR 0·92, 95% CI: 0·77-1·09, p = 1·0). The ivermectin group had non-statistically significant lower viral loads at day 4 (p = 0·24 for gene E; p = 0·18 for gene N) and day 7 (p = 0·16 for gene E; p = 0·18 for gene N) post treatment as well as lower IgG titers at day 21 post treatment (p = 0·24). Patients in the ivermectin group recovered earlier from hyposmia/anosmia (76 vs 158 patient-days; p < 0.001). Interpretation: Among patients with non-severe COVID-19 and no risk factors for severe disease receiving a single 400 mcg/kg dose of ivermectin within 72 h of fever or cough onset there was no difference in the proportion of PCR positives. There was however a marked reduction of self-reported anosmia/hyposmia, a reduction of cough and a tendency to lower viral loads and lower IgG titers which warrants assessment in larger trials. Funding: ISGlobal, Barcelona Institute for Global Health and Clínica Universidad de Navarra.

Tedizolid has demonstrated its efficacy and safety in clinical trials; however, data concerning its tolerability in long-term treatments are scarce. The aim of the study was to assess the indications and to describe the long-term safety profile of tedizolid. A multicentric retrospective study of patients who received tedizolid for more than 6 days was conducted. Adverse events (AEs) were identified from patients' medical records and laboratory data. The World Health Organization causality categories were used to discern AEs that were probably associated with tedizolid. Eighty-one patients, treated with tedizolid 200 mg once daily for a median (interquartile range [IQR]) duration of 28 (14 to 59) days, were included; 36 (44.4%) had previously received linezolid. The most common reasons for selecting tedizolid were to avoid linezolid potential toxicities or interactions (53.1%) or due to previous linezolid-related toxicities (27.2%). The most common indications were off-label, including prosthetic joint infections, osteomyelitis, and respiratory infections (77.8%). Overall, 9/81 patients (11.1%) experienced a probably associated AE. Two patients (2.5%) developed gastrointestinal disorders, 1 (1.2%) developed anemia, and 6 developed thrombocytopenia (7.4%) after a median (IQR) duration of treatment of 26.5 (17 to 58.5) days. Four (5%) patients discontinued tedizolid due to AEs. Among 23 patients with chronic renal failure (CRF), the rate of myelotoxicity was 17.4%, and only 8.7% had to stop tedizolid; 20 out of 22 with previous linezolid-associated toxicity had no AE. Long-term tedizolid treatments had good tolerance with rates of gastrointestinal AE and hematological toxicity lower than those reported with linezolid, particularly in patients with CRF and in those with a history of linezolid-associated toxicity.

Objectives: The primary objective is to determine the efficacy of a single dose of ivermectin, administered to low risk, non-severe COVID-19 patients in the first 48 hours after symptom onset to reduce the proportion of patients with detectable SARS-CoV-2 RNA by Polymerase Chain Reaction (PCR) test from nasopharyngeal swab at day 7 post-treatment. The secondary objectives are: 1.To assess the efficacy of ivermectin to reduce the SARS-CoV-2 viral load in the nasopharyngeal swab at day 7 post treatment.2.To assess the efficacy of ivermectin to improve symptom progression in treated patients.3.To assess the proportion of seroconversions in treated patients at day 21.4.To assess the safety of ivermectin at the proposed dose.5.To determine the magnitude of immune response against SARS-CoV-2.6.To assess the early kinetics of immunity against SARS-CoV-2. Trial design: SAINT is a single centre, double-blind, randomized, placebo-controlled, superiority trial with two parallel arms. Participants will be randomized to receive a single dose of 400 ¿g/kg ivermectin or placebo, and the number of patients in the treatment and placebo groups will be the same (1:1 ratio). Participants: The population for the study will be patients with a positive nasopharyngeal swab PCR test for SARS-CoV-2, with non-severe COVID-19 disease, and no risk factors for progression to severity. Vulnerable populations such as pregnant women, minors (i.e.; under 18 years old), and seniors (i.e.; over 60 years old) will be excluded. Inclusion criteria 1. Patients diagnosed with COVID-19 in the emergency room of the Clínica Universidad de Navarra (CUN) with a positive SARS-CoV-2 PCR. 2. Residents of the Pamplona basin ("Cuenca de Pamplona"). 3. The patient must be between the ages of 18 and 60 years of age. 4. Negative pregnancy test for women of child bearing age*. 5. The patient or his/her representative, has given informed consent to participate in the study. 6. The patient should, in the PI's opinion, be able to comply with all the requirements of the clinical trial (including home follow up during isolation). Exclusion criteria 1. Known history of ivermectin allergy. 2. Hypersensitivity to any component of ivermectin. 3. COVID-19 pneumonia. Diagnosed by the attending physician.Identified in a chest X-ray. 4. Fever or cough present for more than 48 hours. 5. Positive IgG against SARS-CoV-2 by rapid diagnostic test. 6. Age under 18 or over 60 years. 7. The following co-morbidities (or any other disease that might interfere with the study in the eyes of the PI): Immunosuppression.Chronic Obstructive Pulmonary Disease.Diabetes.Hypertension.Obesity.Acute or chronic renal failure.History of coronary disease.History of cerebrovascular disease.Current neoplasm. 8. Recent travel history to countries that are endemic for Loa loa (Angola, Cameroon, Central African Republic, Chad, Democratic Republic of Congo, Ethiopia, Equatorial, Guinea, Gabon, Republic of Congo, Nigeria and Sudan). 9. Current use of CYP 3A4 or P-gp inhibitor drugs such as quinidine, amiodarone, diltiazem, spironolactone, verapamil, clarithromycin, erythromycin, itraconazole, ketoconazole, cyclosporine, tacrolimus, indinavir, ritonavir or cobicistat. Use of critical CYP3A4 substrate drugs such as warfarin. *Women of child bearing age may participate if they use a safe contraceptive method for the entire period of the study and at least one month afterwards. A woman is considered to not have childbearing capacity if she is post-menopausal (minimum of 2 years without menstruation) or has undergone surgical sterilization (at least one month before the study). The trial is currently planned at a single center, Clínica Universidad de Navarra, in Navarra (Spain), and the immunology samples will be analyzed at the Barcelona Institute for Global Health (ISGlobal), in Barcelona (Spain). Participants will be recruited by the investigators at the emergency room and/or COVID-19 area of the CUN. They will remain in the trial for a period of 28 days at their homes since they will be patients with mild disease. In the interest of public health and to contain transmission of infection, follow-up visits will be conducted in the participant's home by a clinical trial team comprising nursing and medical members. Home visits will assess clinical and laboratory parameters of the patients. Intervention and comparator: Ivermectin will be administered to the treatment group at a 400¿g/Kg dose (included in the EU approved label of Stromectol and Scabioral). The control group will receive placebo. There is no current data on the efficacy of ivermectin against the virus in vivo, therefore the use of placebo in the control group is ethically justified. Main outcomes: Primary Proportion of patients with a positive SARS-CoV-2 PCR from a nasopharyngeal swab at day 7 post-treatment. Secondary 1.Mean viral load as determined by PCR cycle threshold (Ct) at baseline and on days 4, 7, 14, and 21.2.Proportion of patients with fever and cough at days 4, 7, 14, and 21 as well as proportion of patients progressing to severe disease or death during the trial.3.Proportion of patients with seroconversion at day 21.4.Proportion of drug-related adverse events during the trial.5.Median levels of IgG, IgM, IgA measured by Luminex, frequencies of innate and SARS-CoV-2-specific T cells assessed by flow cytometry, median levels of inflammatory and activation markers measured by Luminex and transcriptomics.6.Median kinetics of IgG, IgM, IgA levels during the trial, until day 28. Randomisation: Eligible patients will be allocated in a 1:1 ratio using a randomization list generated by the trial statistician using blocks of four to ensure balance between the groups. A study identification code with the format "SAINT-##" (##: from 01 to 24) will be generated using a sequence of random numbers so that the randomization number does not match the subject identifier. The sequence and code used will be kept in an encrypted file accessible only to the trial statistician. A physical copy will be kept in a locked cabinet at the CUN, accessible only to the person administering the drug who will not enrol or attend to patient care. A separate set of 24 envelopes for emergency unblinding will be kept in the study file. Blinding (masking): The clinical trial team and the patients will be blinded. The placebo will not be visibly identical, but it will be administered by staff not involved in the clinical care or participant follow up. Numbers to be randomised (sample size): The sample size is 24 patients: 12 participants will be randomised to the treatment group and 12 participants to the control group. Trial status: Current protocol version: 1.0 dated 16 of April 2020. Recruitment is envisioned to begin by May 14th and end by June 14th. Trial registration: EudraCT number: 2020-001474-29, registered April 1st. Clinicaltrials.gov: submitted, pending number FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Cytomegalovirus (CMV) infections can induce severe complications in immunosuppressed patients. Currently, ganciclovir represents the preferred treatment option; however, in patients with resistance or toxicity related to ganciclovir, the therapeutic options are limited. Cellular immunity plays an important role in the control of viral infections. Adoptive T-cell therapy can contribute to recovering immunological function in immunosuppressed patients. Selective T-cell depletion targeting CD45RA enhances early T-cell recovery and can represent a salvage therapy. In this study, an immunocompromised non-transplanted patient with CMV disease and toxicity to conventional therapy was successfully treated by adoptive transfer of CD45RA-depleted T-cells.

Introduction: In recent years, an increase in the average annual incidence of Vibrio infections has been reported, probably related to global climate change. This includes cholera, a secretory diarrhoea caused by toxigenic strains of Vibrio cholerae serogroups O1 and O139. Pathogenic: Infections caused by the genus Vibrio produce diverse clinical manifestations, from gastrointestinal syndromes (of greater or lesser severity) to cutaneous infections and lethal septicaemia. Diagnosis: The epidemiological context as well as the use of appropriate culture media are keys, in conjunction with biochemical and agglutination tests. Treatment: It will vary depending on the clinical presentation, ranging from oral or intravenous fluid replacement, with administration of antibiotics in the most severe cases, until debridement of the necrotic tissues in cases of severe cutaneous involvement.

The human T-lymphotropic virus type 1 (HTLV-1) is a RNA retrovirus that infects a minimum of 5-10 million people worldwide. Transmission by cell-containing blood products and solid organ transplantation has been reported. Clinical disease occurs in about 5-10% of infected individuals and consists mainly in adult T cell leukemia and HTLV-1-associated myelopathy (HAM). We present a 54-year-old woman who underwent kidney transplant from cadaveric donor in March 2015. Donor also underwent cornea extraction for another recipient (corneal transplant protocol includes HTLV-1/2 serology). Twenty-four hours after completion of kidney transplant donor, HTLV-1 serology was revealed positive. Following experts' recommendations, once donor seropositivity was demonstrated, antiviral prophylaxis including zidovudine and raltegravir was initially given to our patient, in spite of which the patient developed HAM. Once the diagnosis of HAM was established, antiretroviral therapy was restarted, and intravenous pulses of methylprednisolone were periodically administered with transient initial improvement. Later on, the patient experienced neurological deterioration becoming wheelchair dependent. Since the occurrence of this case, HTLV-1 screening has become mandatory for solid organ transplantation in the Spanish province of Navarra, and the same should happen worldwide.

Most urinary tract infections (UTI) are uncomplicated infections occurring in young women. An extensive evaluation is not required in the majority of cases, and they can be safely managed as outpatients with oral antibiotics. Escherichia coli is by far the most common uropathogen, accounting for >80% of all cases. Other major clinical problems associated with UTI include asymptomatic bacteriuria, and patients with complicated UTI. Complicated UTIs are a heterogeneous group associated with conditions that increase the risk of acquiring infection or treatment failure. Distinguishing between complicated and uncomplicated UTI is important, as it influences the initial evaluation, choice, and duration of antimicrobial therapy. Diagnosis is especially challenging in the elderly and in patients with in-dwelling catheters. The increasing prevalence of resistant uropathogens, including extended-spectrum ß-lactamases and carbapenemase-producing Enterobacteriaceae, and other multidrug-resistant Gram-negative organisms further compromises treatment of both complicated and uncomplicated UTIs. The aim of these Clinical Guidelines is to provide a set of recommendations for improving the diagnosis and treatment of UT

Antibacterial treatment with cotrimoxazol (TxS), a combination of trimethoprim and sulfamethoxazole, generates resistance by, among others, acquisition of thymidine auxotrophy associated with mutations in the thymidylate synthase gene thyA, which can modify the biology of infection. The opportunistic pathogen non-typeable Haemophilus influenzae (NTHi) is frequently encountered in the lower airways of chronic obstructive pulmonary disease (COPD) patients, and associated with acute exacerbation of COPD symptoms. Increasing resistance of NTHi to TxS limits its suitability as initial antibacterial against COPD exacerbation, although its relationship with thymidine auxotrophy is unknown. In this study, the analysis of 2,542 NTHi isolates recovered at Bellvitge University Hospital (Spain) in the period 2010-2014 revealed 119 strains forming slow-growing colonies on the thymidine low concentration medium Mueller Hinton Fastidious, including one strain isolated from a COPD patient undergoing TxS therapy that was a reversible thymidine auxotroph. To assess the impact of thymidine auxotrophy in the NTHi-host interplay during respiratory infection, thyA mutants were generated in both the clinical isolate NTHi375 and the reference strain RdKW20. Inactivation of the thyA gene increased TxS resistance, but also promoted morphological changes consistent with elongation and impaired bacterial division, which altered H. influenzae self-aggregation, phosphorylcholine level, C3b deposition, and airway epithelial infection patterns. Availability of external thymidine contributed to overcome such auxotrophy and TxS effect, potentially facilitated by the nucleoside transporter nupC. Although, thyA inactivation resulted in bacterial attenuation in a lung infection mouse model, it also rendered a lower clearance upon a TxS challenge in vivo. Thus, our results show that thymidine auxotrophy modulates both the NTHi host airway interplay and antibiotic resistance, which should be considered at the clinical setting for the consequences of TxS administration.

Treatment of an infected postpneumonectomy cavity is very difficult. We present a patient with an infection of a postpneumonectomy cavity by Staphylococcus epidermidis treated with local daptomycin for different dwell times, maintaining high antibiotic levels above the MIC. Clinical and microbiological cure were achieved successfully.

La PT en la consulta de Medicina del Trabajo está justificada al tratarse de una prueba diagnóstica con alta sensibilidad, pero al generar un gran número de falsos positivos, precisa posteriormente de una prueba con una alta especificidad como el QTF-GIT para evitar la quimioprofilaxis innecesaria.

Enterococci are implicated in less than 2.3% of prosthetic joint infections. These infections can be difficult to treat and therapeutic failures are not uncommon. In these situations, daptomycin is a safe and effective alternative. We present a clinical case with a successful response to the prolonged use of high-dose daptomycin.

Mitochondrial toxicity has been recently suggested to be the underlying mechanism of long-term linezolid-associated toxicity in patients with 16S rRNA genetic polymorphisms. Here, we report for the first time two cases of lactic acidosis due to long-term linezolid exposure in liver transplant recipients who presented an A2706G mitochondrial DNA polymorphism.

We describe a Schistosoma haematobium infection with asymptomatic eosinophilia, persistently negative urine microscopy, and late seroconversion (7.5months) in a traveler returning from Mali. After initial negative parasitological tests, travel history led to diagnostic cystoscopy, allowing final diagnosis with urine microscopy after the bladder biopsy. The patient was successfully treated with praziquantel. Difficulties in making the diagnosis of schistosomiasis in asymptomatic returning travelers are discussed; we propose a trial treatment in these cases.

The purpose of this investigation was to compare the genotypic profiles of Staphylococcus aureus isolated from atopic dermatitis (AD) patients and from control subjects, and to study the relationship between clinical severity, immune response, and genomic pattern of S. aureus isolated from AD patients. We selected 32 patients with AD and S. aureus skin colonization and 31 atopic controls with no history of AD who where asymptomatic carriers of S. aureus. Microarray-based genotyping was performed on S. aureus isolates. In AD patients, clinical severity was assessed using the Scoring Atopic Dermatitis index and total IgE levels and staphylococcal superantigen-specific IgE levels (SEA, SEB, SEC, TSST1) were determined. The genes lukE, lukD, splA, splB, ssl8, and sasG were more frequent in isolates from AD patients. CC30 was more common in isolates from atopic controls than in AD patients. There was a correlation between total IgE and clinical severity, but an association between clinical severity, immune response, and the presence of S. aureus superantigen genes, including enterotoxin genes, could not be demonstrated. Finally, a correlation was found between AD severity and other S. aureus genes, such as sasG and scn. S. aureus factors besides superantigens could be related to the worsening and onset of AD.

The clinical value of information provided by the Microbiology Laboratory may be reduced by the time it takes to generate results for healthcare providers. The aim of this study was to measure the clinical and economic impact associated with rapid reporting of microbiological results. Methods: 574 hospitalized patients with a bacterial clinical infection confirmed by culture were evaluated. 284 hospitalized patients were included in the historical control group (results available the day following the analysis) and 290 in the intervention group (results available the same day of the analysis). The Vitek (R) 2 system (bioMerieux) was used for identification and antimicrobial susceptibility testing in both groups. Results: Faster reporting of microbiological results enabled the clinician to optimize the antibiotic treatment sooner (P < 0.001). This reduction in turnaround time (17.6 h) was associated with improved clinical outcome, a significant reduction in the length of hospitalization and the number of microbiological and biochemical tests performed. Intubation requirements were significantly lower in the intervention group. Mortality rates did not differ significantly between the two groups. Costs incurred for patients in the intervention group were significantly lower than those in the control group, including costs for Microbiology Laboratory testing, antibiotic costs, length of hospitalization and other patient care costs. Conclusions: Rapid microbiological information was associated with quality improvement seen in earlier changes in antibiotic use, an improved clinical outcome and financial benefits. (C) 2012 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Inappropriate antibiotic prescriptions are associated with an increase in healthcare costs and a decrease in the quality of care. The aim of this study was to measure the clinical and economic impact of rapid microbiological reporting on the specimens most frequently processed by the Microbiology Laboratory. The Vitek® 2 system (bioMérieux) was used for identification and susceptibility testing. Only hospitalized patients with bacterial infections were included. Two groups were established, a historical control group (results available the day following the analysis) and an intervention group (results available the same day of the analysis). Specimens studied and the median length of time from the introduction of the microorganism in the Vitek® 2 until microbiological report were as follows: wound and abscess (control¿=¿23.5 h, intervention¿=¿9.5 h, p¿<¿0.001), blood (control¿=¿23.5 h, intervention¿=¿9.2 h, p¿<¿0.001), and urine (control¿=¿23.4 h, intervention¿=¿9.3 h, p¿<¿0.001). Outcome parameters were hospital stay and mortality rates. Hospital costs were calculated. The mortality rates did not differ significantly between the two groups. Faster reporting of identification and antimicrobial susceptibility results was associated with a significant reduction in hospital stay and in overall costs for those patients from whom wound, abscess, and urine specimens were analyzed. However, the antimicrobial results of blood culture isolates did not lead to significant clinical or f

DPT lock therapy demonstrated good in vivo efficacy in LT-CRBI caused by coagulase negative staphylococci and Enterococcus species.

Listeriosis can be a cause of arthritis. Here, we present a case of Listeria monocytogenes septic arthritis of the right hip in a 66-year-old male treated with mycophenolate mofetil for polyarteritis nodosa. So far, septic arthritis due to this microorganism has not been reported in patients treated with mycophenolate mofetil. We review the literature of L. monocytogenes septic arthritis and discuss the role of mycophenolate mofetil treatment in precipitating listeriosis.

Here, we report a case of multidrug-resistant tuberculosis (TB) presenting as a solitary splenic mass in a 60-year-old immunocompetent patient. Splenic TB is unusual and, when present, is usually associated with disseminated disease in immunocompromised patients. A high level of suspicion is required for diagnosis, and, as occurred in our case, it may be an unexpected finding following surgery. Diagnosis was made by polymerase chain reaction, which showed the presence of Mycobacterium tuberculosis DNA. Interestingly, rifampicin- and isoniazid-resistant genes were detected in our analysis. Splenic TB diagnosis and treatment are reviewed.