Tobramycin Systemic Absorption in Lung Transplant Recipients Treated With Inhaled Tobramycin: A Cohort Study.

Inhaled tobramycin treatment has been associated with nephrotoxicity in some case reports, but limited data are available about serum levels and its possible systemic absorption in lung transplant recipients (LTR). We conducted a single-center, observational and retrospective study of all adult (>18 years old) LTR treated with inhaled tobramycin for at least 3 days between June 2019 and February 2022. Trough serum levels were collected and >2 µg/mL was considered a high drug level. The primary outcome assessed the presence of detectable trough levels, while the secondary outcome focused on the occurrence of acute kidney injury (AKI) in individuals with detectable trough levels. Thirty-four patients, with a median age of 60 years, were enrolled. The primary indications for treatment were donor bronchial aspirate bacterial isolation (18 patients) and tracheobronchitis (15 patients). In total, 28 patients (82%) exhibited detectable serum levels, with 9 (26%) presenting high levels (>2 µg/mL). Furthermore, 9 patients (26%) developed acute kidney injury during the treatment course. Median trough tobramycin levels were significantly elevated in invasively mechanically ventilated patients compared to non-ventilated individuals (2.5 µg/mL vs. 0.48 µg/mL) (p < 0.001). Inhaled tobramycin administration in LTRs, particularly in those requiring invasive mechanical ventilation, may result in substantial systemic absorption.

Impact of viral detection in patients with community-acquired pneumonia: An observational cohort study / Impacto de la detección viral en pacientes con neumonía comunitaria: estudio de cohortes observacional

Purpose The presence of a respiratory virus in patients with community-acquired pneumonia (CAP) may have an impact on the bacterial etiology and clinical presentation. In this study we aimed to assess the role of viral infection in the bacterial etiology and outcomes of patients with CAP. Methods We performed a retrospective study of all adults hospitalized with CAP between November 2017 and October 2018. Patients were classified according to the presence of viral infection. An unvaried and a multivaried analysis were performed to identify variables associated with viral infection and clinical outcomes. Results Overall 590 patients were included. A microorganism was documented in 375 cases (63.5%). A viral infection was demonstrated in 118 (20%). The main pathogens were Streptococcus pneumoniae (35.8%), Staphylococcus aureus (2.9%) and influenza virus (10.8%). A trend to a higher rate of S. aureus (p = 0.06) in patients with viral infection was observed. Patients with viral infection had more often bilateral consolidation patterns (17.8% vs 10.8%, p = 0.04), respiratory failure (59.3% vs 42.8%, p = 0.001), ICU admission (17.8% vs 7%, p = 0.001) and invasive mechanical ventilation (9.3% vs 2.8%, p = 0.003). Risk factors for respiratory failure were chronic lung disease, age >65 years, positive blood cultures and viral infection. Influenza, virus but no other respiratory viruses, was associated with respiratory failure (OR, 3.72; 95% CI, 2.06–6.73). Conclusions Our study reinforces the idea that co-viral infection has an impact in the clinical presentation of CAP causing a more severe clinical picture. This impact seems to be mainly due to influenza virus infection (AU)

Objetivos La presencia de virus respiratorios en pacientes con neumonía adquirida en la comunidad (NAC) puede tener un impacto en la etiología bacteriana y en la presentación clínica. El objetivo de este estudio fue evaluar el papel de la infección viral en la etiología bacteriana y la evolución de los pacientes con NAC. Métodos Realizamos un estudio retrospectivo de todos los adultos hospitalizados con diagnóstico de NAC entre noviembre de 2017 y octubre de 2018. Los pacientes fueron clasificados según la presencia de infección viral. Se realizó un análisis univariado y multivariado para identificar variables asociadas con la infección viral y la evolución clínica. Resultados En total se incluyeron 590 pacientes. Se documentó el microorganismo en 375 casos (63,5%). Se demostró una infección viral en 118 (20%). Los principales patógenos fueron S. pneumoniae (35,8%), S. aureus (2,9%) y virus de la influenza (10,8%). Se observó una tendencia a una mayor tasa de S. aureus (p = 0,06) en pacientes con infección viral. Los pacientes con infección viral tenían con mayor frecuencia patrones de consolidación bilateral (17,8% vs 10,8%; p = 0,04), insuficiencia respiratoria (59,3% vs 42,8%; p = 0,001), ingreso en UCI (17,8% vs 7%; p = 0,001) y necesidad de ventilación mecánica invasiva (9,3% vs 2,8%; p = 0,003). Los factores de riesgo para insuficiencia respiratoria fueron enfermedad pulmonar crónica, edad >65 años, hemocultivos positivos e infección viral. El virus de la influenza, pero ningún otro virus respiratorio, se asoció con insuficiencia respiratoria (OR: 3,72; IC 95%: 2,06-6,73). Conclusiones Nuestro estudio refuerza la idea de que la infección viral tiene un impacto en la presentación clínica de la NAC provocando un cuadro clínico más grave. Este impacto parece deberse principalmente a la infección por el virus de la influenza (AU)

Isavuconazole use and TDM in real-world pediatric practice.

Isavuconazole (ISA) is approved for treating invasive aspergillosis and mucormycosis in adults, but its use in children remains off-label. We report on the use of ISA in real-world pediatric practice with 15 patients receiving ISA for treatment of invasive fungal infections. Therapeutic drug monitoring (TDM) was performed in all patients, with 52/111 (46.8%) Ctrough determinations out of range, thus supporting the need for TDM in children, especially those receiving extracorporeal membrane oxygenation (ECMO).

Impact of viral detection in patients with community-acquired pneumonia: An observational cohort study.

PURPOSE: The presence of a respiratory virus in patients with community-acquired pneumonia (CAP) may have an impact on the bacterial etiology and clinical presentation. In this study we aimed to assess the role of viral infection in the bacterial etiology and outcomes of patients with CAP. METHODS: We performed a retrospective study of all adults hospitalized with CAP between November 2017 and October 2018. Patients were classified according to the presence of viral infection. An unvaried and a multivaried analysis were performed to identify variables associated with viral infection and clinical outcomes. RESULTS: Overall 590 patients were included. A microorganism was documented in 375 cases (63.5%). A viral infection was demonstrated in 118 (20%). The main pathogens were Streptococcus pneumoniae (35.8%), Staphylococcus aureus (2.9%) and influenza virus (10.8%). A trend to a higher rate of S. aureus (p=0.06) in patients with viral infection was observed. Patients with viral infection had more often bilateral consolidation patterns (17.8% vs 10.8%, p=0.04), respiratory failure (59.3% vs 42.8%, p=0.001), ICU admission (17.8% vs 7%, p=0.001) and invasive mechanical ventilation (9.3% vs 2.8%, p=0.003). Risk factors for respiratory failure were chronic lung disease, age >65 years, positive blood cultures and viral infection. Influenza, virus but no other respiratory viruses, was associated with respiratory failure (OR, 3.72; 95% CI, 2.06-6.73). CONCLUSIONS: Our study reinforces the idea that co-viral infection has an impact in the clinical presentation of CAP causing a more severe clinical picture. This impact seems to be mainly due to influenza virus infection.

Dot Immunobinding Assay for the Rapid Serodetection of Scedosporium/Lomentospora in Cystic Fibrosis Patients.

The detection of Scedosporium/Lomentospora is still based on non-standardized low-sensitivity culture procedures. This fact is particularly worrying in patients with cystic fibrosis (CF), where these fungi are the second most common filamentous fungi isolated, because a poor and delayed diagnosis can worsen the prognosis of the disease. To contribute to the discovery of new diagnostic strategies, a rapid serological dot immunobinding assay (DIA) that allows the detection of serum IgG against Scedosporium/Lomentospora in less than 15 min was developed. A crude protein extract from the conidia and hyphae of Scedosporium boydii was employed as a fungal antigen. The DIA was evaluated using 303 CF serum samples (162 patients) grouped according to the detection of Scedosporium/Lomentospora in the respiratory sample by culture, obtaining a sensitivity and specificity of 90.48% and 79.30%, respectively; positive and negative predictive values of 54.81% and 96.77%, and an efficiency of 81.72%. The clinical factors associated with the results were also studied using a univariate and a multivariate analysis, which showed that Scedosporium/Lomentospora positive sputum, elevated anti-Aspergillus serum IgG and chronic Pseudomonas aeruginosa infection were significantly associated with a positive result in DIA, while Staphylococcus aureus positive sputum showed a negative association. In conclusion, the test developed can offer a complementary, rapid, simple and sensitive method to contribute to the diagnosis of Scedosporium/Lomentospora in patients with CF.

A survey to describe common practices on antifungal monitoring among Spanish clinicians.

INTRODUCTION: We developed a survey to obtain information on the monitoring practices of major systemic antifungals for treatment and prevention of serious fungal infection. METHODS: The survey included questions relating to methodology and practice and was distributed among 137 colleagues of the Study Group of Medical Mycology (GEMICOMED) from July to December 2019. RESULTS: Monitoring was routinely carried out by most respondents, mainly for voriconazole, and was more likely used to determine the efficacy of the dose administered and less for minimizing drug toxicity. Most responders did not follow the strategies of voriconazole dosage based on CYP2C19 genotyping. Monitoring of posaconazole, itraconazole, or other azole metabolites was not carried out or scarcely demanded. Most responders rarely used flucytosine in their clinical practice nor did they monitor it. According to the answers given by some responders, monitoring isavuconazole, amphotericin B, caspofungin and fluconazole exposure would be also interesting in daily clinical practice in selected patient populations. CONCLUSIONS: The survey reveals common practices and attitudes towards antifungal monitoring, sometimes not performed as per best recommendations, offering an opportunity for education and research. Appropriate use of therapeutic drug monitoring may be an objective of antifungal stewardship programmes.

A survey to describe common practices on antifungal monitoring among Spanish clinicians / Monitorización de antifúngicos sistémicos: resultados de una encuesta distribuida en España

Introduction: We developed a survey to obtain information on the monitoring practices of major systemic antifungals for treatment and prevention of serious fungal infection. Methods: The survey included questions relating to methodology and practice and was distributed among 137 colleagues of the Study Group of Medical Mycology (GEMICOMED) from July to December 2019. Results: Monitoring was routinely carried out by most respondents, mainly for voriconazole, and was more likely used to determine the efficacy of the dose administered and less for minimizing drug toxicity. Most responders did not follow the strategies of voriconazole dosage based on CYP2C19 genotyping. Monitoring of posaconazole, itraconazole, or other azole metabolites was not carried out or scarcely demanded. Most responders rarely used flucytosine in their clinical practice nor did they monitor it. According to the answers given by some responders, monitoring isavuconazole, amphotericin B, caspofungin and fluconazole exposure would be also interesting in daily clinical practice in selected patient populations. Conclusions: The survey reveals common practices and attitudes towards antifungal monitoring, sometimes not performed as per best recommendations, offering an opportunity for education and research. Appropriate use of therapeutic drug monitoring may be an objective of antifungal stewardship programmes.(AU)

Introducción: Describimos los resultados de una encuesta diseñada para obtener información sobre prácticas de monitorización de los principales antifúngicos sistémicos utilizados en el tratamiento y la prevención de la infección fúngica grave en España. Métodos: La encuesta, que incluye preguntas relacionadas tanto con metodología como con su uso práctico, se distribuyó entre 137 compañeros del Grupo de Estudio de Micología Médica (GEMICOMED), de la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. Resultados: La mayoría de los encuestados respondieron utilizar la monitorización de antifúngicos de forma rutinaria, principalmente para voriconazol, y en especial para evaluar la eficacia de la dosis administrada y menos para minimizar su toxicidad. La mayoría de ellos no siguieron las estrategias de dosificación de voriconazol basadas en el conocimiento previo del genotipo CYP2C19, relacionado con su metabolización. Por el contrario, la monitorización de posaconazol, itraconazol o de algunos de sus metabolitos no se realizó o apenas se solicitó. La mayoría de los encuestados rara vez usan 5-fluocitosina en su práctica clínica y por tanto tampoco monitorizan su exposición. Un alto porcentaje consideraría de utilidad poder evaluar la exposición a isavuconazol, anfotericina B, caspofungina y fluconazol en determinadas situaciones en la práctica clínica. Conclusiones: La encuesta revela prácticas y actitudes hacia la monitorización de antifúngicos que en ocasiones no se realizan según las principales recomendaciones, lo que ofrece una oportunidad para la educación y la investigación. Abordar esta formación podría convertirse en objetivo de los programas racionales del uso de antimicrobianos a nivel nacional.(AU)

Aplicación de un balón de contrapulsación intraaórtico en procedimientos obstétricos. Reporte de caso / Use of an intra-aortic balloon pump in Obstetrics. Case report

Resumen ANTECEDENTES: Las anomalías en la inserción placentaria son cada vez más frecuentes en nuestro medio. En la atención de la paciente embarazada es importante la prevención de la pérdida hemática con balones de contrapulsación intraaórticos, como una opción útil. CASO CLÍNICO: Paciente de 38 años, embarazada, con antecedente de parto eutócico y sin enfermedades de interés, ni intervenciones quirúrgicas previas. El seguimiento prenatal se inició a las 17 semanas, con retraso diagnóstico debido a que continuaba en tratamiento anticonceptivo. La invasión trofoblástica estaba limitada al miometrio, sin evidencia de invasión a los órganos vecinos. Se le expusieron a la paciente las posibles complicaciones a fin de minimizar los riesgos de hemorragia masiva, potencialmente mortal en el momento del parto. Puesto que la paciente expresó no desear volver a embarazarse, se le recomendó la histerectomía poscesárea, dejando la placenta in situ. CONCLUSIONES: La oclusión endovascular con balón de contrapulsación intraaórtico es una opción segura y eficaz para minimizar la pérdida de sangre en casos de anomalías en la inserción placentaria. Además del clásico acceso por vía femoral es posible colocarlo por vía axilar, con igual efectividad. La baja tasa de complicaciones maternas y la seguridad, en términos de irradiación fetal, la convierten en una opción razonable en la atención de pacientes embarazadas en quienes se espera una alta pérdida sanguínea.

Abstract BACKGROUND: Anomalies of placental insertion are becoming increasingly common. Prevention of blood loss with intra-aortic counterpulsation balloons is a useful option in the care of pregnant patients. CLINICAL CASE: 38-year-old pregnant woman with a history of euthyroid delivery and no medical or surgical history. Prenatal follow-up was initiated at 17 weeks, with a delay in diagnosis due to the fact that she was still on contraceptive treatment. Trophoblastic invasion was limited to the myometrium with no evidence of invasion into adjacent organs. The patient was counseled on the potential complications to minimize the risk of massive, potentially fatal hemorrhage at delivery. As the patient did not wish to become pregnant again, a post-cesarean hysterectomy was recommended, leaving the placenta in situ. CONCLUSIONS: Endovascular occlusion with intra-aortic balloon counterpulsation is a safe and effective option to minimize blood loss in cases of placental insertion anomalies. In addition to the classical femoral approach, the axillary route can be used with equal efficacy. The low rate of maternal complications and the safety with respect to fetal irradiation make it a reasonable option in the management of pregnant patients in whom high blood loss is expected.

Global Emergence of Resistance to Fluconazole and Voriconazole in Candida parapsilosis in Tertiary Hospitals in Spain During the COVID-19 Pandemic.

Background: Candida parapsilosis is a frequent cause of candidemia worldwide. Its incidence is associated with the use of medical implants, such as central venous catheters or parenteral nutrition. This species has reduced susceptibility to echinocandins, and it is susceptible to polyenes and azoles. Multiple outbreaks caused by fluconazole-nonsusceptible strains have been reported recently. A similar trend has been observed among the C. parapsilosis isolates received in the last 2 years at the Spanish Mycology Reference Laboratory. Methods: Yeast were identified by molecular biology, and antifungal susceptibility testing was performed using the European Committee on Antimicrobial Susceptibility Testing protocol. The ERG11 gene was sequenced to identify resistance mechanisms, and strain typing was carried out by microsatellite analysis. Results: We examined the susceptibility profile of 1315 C. parapsilosis isolates available at our reference laboratory between 2000 and 2021, noticing an increase in the number of isolates with acquired resistance to fluconazole, and voriconazole has increased in at least 8 different Spanish hospitals in 2020-2021. From 121 recorded clones, 3 were identified as the most prevalent in Spain (clone 10 in Catalonia and clone 96 in Castilla-Leon and Madrid, whereas clone 67 was found in 2 geographically unrelated regions, Cantabria and the Balearic Islands). Conclusions: Our data suggest that concurrently with the coronavirus disease 2019 pandemic, a selection of fluconazole-resistant C. parapsilosis isolates has occurred in Spain, and the expansion of specific clones has been noted across centers. Further research is needed to determine the factors that underlie the successful expansion of these clones and their potential genetic relatedness.

Community-acquired pneumonia in hospitalised patients: changes in aetiology, clinical presentation, and severity outcomes in a 10-year period.

BACKGROUND AND OBJECTIVE: Community-acquired pneumonia (CAP) is a frequent cause of hospitalisation. Several factors, such as pandemics, vaccines and globalisation may lead to changes in epidemiology, clinical presentation, and outcomes of CAP, which oblige to a constant actualisation. We performed this study to analyse how these factors have evolved over a 10-year period. MATERIALS AND METHODS: Patients diagnosed with CAP for two 1-year periods that were 10 years apart (2007-2008 and 2017-2018) were included. We compared microbiological information, clinical data and evolutive outcomes in the two periods. A mortality analysis was performed. RESULTS: 1043 patients were included: 452 during the first period (2007- 2008), and 591 during the second period (2017-2018). Bacterial aetiology did not change during the 10-year period, besides a slight increase in Staphylococcus aureus (0.9% vs 2.9%, p = 0.026). There was a decline in the proportion of bacteraemia in the second period (14.8% vs 9.6%, p = 0.012). The incidence of complicated pleural effusion and septic shock declined too (6.4% vs 3.6%, p = 0.04 and 15.5% vs 6.3%, p < 0.001). Respiratory failure and Intensive care unit (ICU) admission were similar in both periods. Variables independently associated with mortality were age and septic shock. Influenza vaccine was a protective factor against mortality in the second period. CONCLUSIONS: We have not found relevant differences in the bacterial aetiology of CAP over this 10-year period. There has been a decline in septic complications of CAP such as septic shock, bacteraemia, and complicated pleural effusion. Influenza vaccination is an important tool to reduce mortality.KEY MESSAGESThere were no differences in the bacterial pathogens causing CAP among the 10-year study period. There has been a decline in septic complications of CAP such as septic shock, bacteraemia, and complicated pleural effusion.

Real clinical experience after one year of treatment with tolvaptan in patients with autosomal dominant polycystic kidney disease.

Background: Tolvaptan (TV) is the first vasopressin-receptor antagonist approved for the treatment of autosomal dominant polycystic kidney disease (ADPKD). No publications report TV experience in real clinical practice during the first year of treatment. Methods: A prospective study of an initial cohort of 220 rapidly progressing patients treated with TV for 12 months. The tolerability of TV, the evolution of the estimated glomerular filtration rate (eGFR), analytical parameters, and blood pressure were analyzed. Results: A total of 163 patients (78.2%) received TV for 1 year. The main causes of treatment withdrawal were the aquaretic effects (11%), eGFR deterioration (5%), and hepatic toxicity (2.3%). eGFR decreased significantly after 1 month of treatment without further changes. The decrease in eGFR in the first month was higher in patients with an initially higher eGFR. The eGFR drop during the first year of treatment with TV was lower than that reported by patients in the 2 years prior to TV treatment (-1.7 ± 7.6 vs. -4.4 ± 4.8 mL/min, p = 0.003). Serum sodium and uric acid concentrations increased, and morning urinary osmolality decreased in the first month, with no further changes. Blood pressure decreased significantly without changes in antihypertensive medication. Conclusion: TV treatment is well tolerated by most patients. Liver toxicity is very rare and self-limited. TV reduces eGFR in the first month without showing further changes during the first year of treatment. Patients with a higher starting eGFR will suffer a greater initial drop, with a longer recovery. We suggest using the eGFR observed after a month of treatment as the reference for future comparisons and calculating the rate of eGFR decline in patients undergoing TV treatment.

Vehicle Windshield Wiper Fluid as Potential Source of Sporadic Legionnaires' Disease in Commercial Truck Drivers.

Sporadic Legionnaires' disease is frequently detected in commercial truck drivers. We report 2 sporadic cases of this disease in Barcelona, Spain, that occurred during December 2019 and September 2020. Laboratory findings were consistent with windshield wiper fluid without added screen wash as a possible source of infection for both cases.

Safety and Effectiveness of Isavuconazole Treatment for Fungal Infections in Solid Organ Transplant Recipients (ISASOT Study).

Isavuconazole (ISA) is an alternative treatment for Aspergillus spp. and other fungal infections, but evidence regarding its use in solid organ transplant recipients (SOTR) is scarce. All SOTR who received ISA for treatment of a fungal infection (FI) at our center from December 2017 to January 2021 were included. The duration of the treatment depended on the type of infection. All patients were followed up to 3 months after treatment. Fifty-three SOTR were included, and the majority (44, 83%) were lung transplant recipients. The most frequently treated FI was tracheobronchitis (25, 46.3%). Aspergillus spp. (43, 81.1%); specially A. flavus (16, 37.2%) and A. fumigatus (12, 27.9%), was the most frequent etiology. Other filamentous fungi including one mucormycosis, and four yeast infections were treated. The median duration of treatment was 81 days (IQR 15-197). Mild gamma-glutamyltransferase elevation was the most frequent adverse event (34%). ISA was prematurely discontinued in six patients (11.3%) due to mild hepatotoxicity (2), fatigue (2), gastrointestinal intolerance (1) and myopathy (1). The mean tacrolimus dose decrease was 30% after starting ISA. Seven patients received ISA with mTOR inhibitors with good tolerability. Two patients developed breakthrough FI (3.8%). Among patients who completed the treatment, 27 (50.9%) showed clinical cure and 15 (34.1%) presented fungal persistence. Three patients (6%) died while on ISA due to FI. ISA was well tolerated and appeared to be an effective treatment for FI in SOTR. IMPORTANCE We describe 53 solid organ transplant recipients treated with isavuconazole for fungal infections. Because its use in clinical practice, there is scarce data of its use in solid organ transplant recipients, where interactions with calcineurin inhibitors and mTOR and adverse drug events have limited the use of other triazoles. To the best of our knowledge, this is the first article describing the safety regarding adverse events and drug interactions of isavuconazole for the treatment of fungal infections in a cohort of solid organ transplant recipients. Also, although this is a noncomparative study, we report some real world effectivity data of these patients, including treatment of non-Aspergillus fungal infections.