Clinical experience in the treatment of COVID-19 with monoclonal antibodies in solid organ transplant recipients.

Solid organ transplant (SOT) recipients are at high risk for complications from coronavirus disease 2019 (COVID-19). SOT recipients mount lower immunological responses to vaccines than general population and are at high risk for breakthrough COVID-19 infections. Passive immunotherapy in the form of anti-Spike monoclonal antibodies (MoAbs) may be an alternative for the prophylaxis and treatment of COVID-19 in these patients. SARS-CoV-2 has evolved by accumulating resistance mutations that have escaped the neutralizing action of most MoAbs. However, MoAbs directed at more conserved epitopes and that maintain effector functions could maintain efficacy in the treatment of these patients. According to published data, SOT recipients with low anti-spike antibody responses to vaccination could benefit from the use of MoAbs in pre-exposure prophylaxis, in the treatment of COVID-19 mild to moderate and severe COVID-19 with less than 15 days of symptom duration and low oxygen requirements. Combination therapy could be more effective than monotherapy for the treatment of mild-to-moderate SARS-CoV-2 infection.

[Epidemiology and clinical of infections and colonizations caused by Enterobacterales producing carbapenemases in a tertiary hospital]. / Epidemiología y clínica de las infecciones y colonizaciones causadas por enterobacterias productoras de carbapenemasas en un hospital de tercer nivel.

OBJECTIVE: To describe the epidemiology of Enterobacterales producing carbapenemases (EPC) in a tertiary hospital. METHODS: A retrospective observational study, all patients with a positive sample for EPC treated in hospitalization or in the Emergency Department were included, between January 1, 2014 and December 31, 2016. RESULTS: A total of 272 patients (316 samples) were included: 155 (57%) male. Mean age of 70.4 years (95% CI 68.2 -72.7). Mean Charlson index was 3.6 (95% CI 3.4-3.8). In 63.2% the acquisition was nosocomial, in 35.3% it was health-care associated (HA). 55.1% presented infection, the most frequent infection was urinary tract infection (UTI) (58.7%). The most frequent species were Klebsiella pneumoniae (62.7%) and Enterobacter cloacae (10.1%). The most frequent types of carbapenemase were OXA-48 (53.8%) and VIM (43%). The nosocomial acquisition was associated with the male gender, transplantation, immunosuppression, admission to the Intensive Care Unit (ICU) or surgical service, prior antibiotic treatment, Enterobacter, VIM, respiratory and intra-abdominal infections. The HA acquisition was associated with age and comorbidity, nursery home origin, bladder catheterization, greater number of outpatient procedures, previous hospital admission, K. pneumoniae and E. coli, OXA-48, coproduction of extended spectrum betalactamases, UTI and sepsis. CONCLUSIONS: Patients who acquire EPC in nursery homes frequently have an infection. Patients with nosocomial acqui-sition are colonized by EPC in the ICU, in relation to invasive procedures and transplantation. This population has a higher mortality due to developing respiratory infections by EPC.

Fosfomycin in antimicrobial stewardship programs.

Due to the increase in antimicrobial resistance, strategies such as antimicrobial stewardship programs (ASP) have been developed to improve the clinical results, decrease the adverse effects and the development of resistances and ensure cost-effective therapies. Fosfomycin has a unique mechanism of action against Gram-positive and Gram-negative bacteria. Cross-resistance is uncommon; however, fosfomycin should be used in combination in severe infections to avoid selecting resistant mutations. Fosfomycin's oral formulation facilitates sequential treatment, has low toxicity and high tissue penetration, even in the central nervous system and bone. Fosfomycin is active against resistant Gram-positive bacteria such as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin- resistant enterococci and penicillin-resistant Streptococcus pneumoniae, as well as against resistant Gram-negative bacteria such as extended-spectrum beta-lactamase-producing and carbapenemase-producing enterobacteria. Fosfomycin is therefore useful for cases of persistent bacteremia, skin and soft tissue infections, as a glycopeptide-sparing and carbapenem-sparing drug for healthcare-associated infections and for polymicrobial infections. Published studies have demonstrated the synergy between fosfomycin and beta-lactams, daptomycin and glycopeptides against MSSA and MRSA; with linezolid in biofilm-associated infections and with aminoglycosides and colistin against Gram-negative bacteria, providing a nephroprotective effect.

[CD64 index as a marker of infection in patients with postoperative fever]. / El índice CD64 como marcador de infección en pacientes con fiebre postoperatoria.

OBJECTIVE: To evaluate the utility of the granulocyte CD64 index as a marker of infection in patients with postoperative fever. METHODS: Prospective observational study of a cohort of patients with postoperative fever (2nd-21st day after the intervention) collected during 14 months. Obtaining blood samples during the first 24 hours after the febrile peak to determine the CD64 index (ratio of fluorescence intensity, measured, in the granulocytes of the patient with respect to healthy controls), procalcitonin and C-reactive protein (CRP). RESULTS: During the study period, 50 patients were included, 28 patients (56%) with infection and 22 patients (44%) without evidence of infection. The PCR, procalcitonin and the CD64 index showed significantly higher values in the group of patients who suffered infection. The CD64 index showed a sensitivity of 88.9%, with a specificity of 65.2%. The positive predictive value (PPV) was 75% and the negative predictive value (NPV) was 83.3%, with an area under the curve (AUC) of 0.805 (95% CI 0.68-0.93). Procalcitonin presented a sensitivity of 53.9% and specificity of 86.4%, with NPV and PPV of 82.4% and 61.3% respectively, with AUC of 0.752 (95% CI 0.61-0.89). Regarding the PCR, it showed a sensitivity of 100%, with specificity of 4.4% with an area under the curve of 0.676 (95% CI 0.52-0.83). CONCLUSIONS: The quantification of the CD64 index in patients who develop fever in the early postoperative period is useful to distinguish post-surgical inflammatory phenomena from episodes of established infection.

[Infections in immunocompromised patients (II). The transplanted patient]. / Infecciones en el paciente inmunocomprometido (II). Paciente trasplantado.

Recipients of the different types of transplantation are at high risk of infection. Nosocomial infections predominate in patients who have undergone haematopoietic stem cell transplantation during the early post-engraftment period (30-100 days after the infusion); the incidence of infection is higher in graft-versus-host disease. Nodular lesions can appear in the lungs due to invasive fungal infection. A diffuse pattern is usually secondary to viral infection or P. jirovecii pneumonia. After the first 100 days a moderate risk of infection by conventional and opportunistic infections persists, such as late CMV infection. Advances in surgical techniques and the use of calcineurinics have reduced mortality from infections in recipients of solid organ transplantations. Nosocomial infections are common during the first month; opportunistic infections that are dependent on cellular immunity are more common between the first and the sixth month, from the sixth month the risk lowers and community-based infections similar to those of immunocompetent patients predominate.

[Flu virus and respiratory virus infections]. / Infecciones por virus de la gripe y virus respiratorios.

In general, respiratory infections are benign and self-limiting, but occasionally they can cause severe symptoms and become a major cause of mortality and morbidity, especially in the more vulnerable population groups. Flu epidemics occur annually, and there can be pandemics every few years, such as those caused by types H1N1 or H3N2. The main clinical manifestations are respiratory symptoms associated with fever, and complications such as pneumonia can arise. Nasopharyngeal swab and RT-PCR should be performed to confirm the diagnosis, which can yield results for other viruses as well. Treatment is generally symptomatic, reserving neuraminidase inhibitors for the more serious cases. The best preventive measure is annual vaccination of the population at risk. The coronavirus is also particularly relevant, due to its potential prognostic implications, and the respiratory syncytial virus and parainfluenza virus should be borne in mind in children.

The efficacy of fidaxomicin in the treatment of Clostridium difficile infection in a real-world clinical setting: a Spanish multi-centre retrospective cohort.

The objective of this study was to evaluate the efficacy and safety of fidaxomicin in the real-life clinical setting. This was a retrospective cohort of patients with Clostridium difficile infection (CDI) treated with fidaxomicin in 20 Spanish hospitals between July 2013 and July 2014. Clinical cure, 30-day recurrence, 30-day mortality, sustained cure, and factors associated with the failure to achieve sustained cure were analyzed. Of the 72 patients in the cohort 41 (56.9 %) had a fatal underlying disease. There were 44 (61.1 %) recurrent episodes and 26 cases (36.1 %) with a history of multiple recurrences. Most episodes were severe (26, 36 %) or severe-complicated (14, 19.4 %). Clinical cure rate was 90.3 %, recurrence rate was 16.7 % and three patients (4.2 %) died during the follow-up period. Sustained cure was achieved in 52 cases (72.2 %). Adverse events were reported in five cases (6.9 %). Factors associated with the lack of sustained cure were cardiovascular comorbidity (OR 11.4; 95 %CI 1.9-67.8), acute kidney failure (OR 7.4; 95 %CI 1.3-43.1), concomitant systemic antibiotic treatment (OR 6.2; 95 %CI 1.1-36.8), and C-reactive protein value at diagnosis (OR 1.2 for each 1 mg/dl increase; 95 %CI 1.03-1.3). Fidaxomicin is an effective and well tolerable treatment for severe CDI and for cases with elevated recurrence risk.

Changes in epidemiology, clinical features and severity of influenza A (H1N1) 2009 pneumonia in the first post-pandemic influenza season.

Although the influenza A (H1N1) 2009 virus is expected to circulate as a seasonal virus for some years after the pandemic period, its behaviour cannot be predicted. We analysed a prospective cohort study of hospitalized adults with influenza A (H1N1) 2009 pneumonia at 14 teaching hospitals in Spain to compare the epidemiology, clinical features and outcomes of influenza A (H1N1) 2009 pneumonia between the pandemic period and the first post-pandemic influenza season. A total of 348 patients were included: 234 during the pandemic period and 114 during the first post-pandemic influenza season. Patients during the post-pandemic period were older and more likely to have chronic obstructive pulmonary disease, chronic kidney disease and cancer than the others. Septic shock, altered mental status and respiratory failure on arrival at hospital were significantly more common during the post-pandemic period. Time from illness onset to receipt of antiviral therapy was also longer during this period. Early antiviral therapy was less frequently administered to patients during the post-pandemic period (22.9% versus 10.9%; p 0.009). In addition, length of stay was longer, and need for mechanical ventilation and intensive-care unit admission were significantly higher during the post-pandemic period. In-hospital mortality (5.1% versus 21.2%; p <0.001) was also greater during this period. In conclusion, significant epidemiological changes and an increased severity of influenza A (H1N1) 2009 pneumonia were found in the first post-pandemic influenza season. Physicians should consider influenza A (H1N1) 2009 when selecting microbiological testing and treatment in patients with pneumonia in the upcoming influenza season.

[Antibiotic treatment optimization by means of antibiotic treatment experts participation]. / Optimización del tratamiento antibiótico mediante la participación de expertos en antibióticos.

BACKGROUND: Antibiotics account for a high percentage of hospital pharmacy expenses. An elevated proportion of the prescriptions are considered inappropriate. Infectious diseases specialist could help other physicians in improving antibiotics prescriptions. METHODS: Treatments in all patients hospitalized in four surgical wards were checked daily and recommendations were made in cases with signs of inadequate antibiotics prescriptions. The program was carried out during for 4 months and the results were compared with a similar period of the previous year. RESULTS: 562 treatments of 393 patients were reviewed . Five hundred twenty four recommendations were made (90% of them were accepted). There was a significant reduction in the number of inadequate prescriptions. Antibiotic expenditure decreased by 29,262 euros (7,240 euros/month), implying a reduction of 2.35 euros/hospitalization-bed/day. There were no statistically significant differences in the amount of hospital resistant bacteria nor in mortality between the two periods. CONCLUSIONS: Following application of a non-compulsory control program, antibiotic prescription improved and expenditure decreased, with no change in mortality. Acceptation of the program by the physicians of the departments implicated was favourable.

Optimización del tratamiento antibiótico mediante la participación de expertos en antibióticos / Antibiotic treatment optimization by means of antibiotic experts participation

Antecedentes: Los antibióticos representan un porcentaje elevado del gasto de farmacia de un hospital. Una elevada proporción de las prescripciones se consideran inapropiadas. La ayuda prestada por infectólogos con una formación extensa en el manejo de los antibióticos podría mejorar la prescripción de este tipo de medicamentos. Métodos: Revisión diaria de las prescripciones antibióticas realizadas en cuatro salas de hospitalización de varias especialidades quirúrgicas. Examen diario de los casos que cumplían algunos de los signos de sospecha de prescripción inadecuada. Si existían casos sugestivos de este tipo de prescripción se efectuaba una recomendación a los médicos prescriptores. La intervención se realizó durante 4 meses. Se compararon los resultados con un periodo similar del año anterior. Resultados: Se revisaron 562 tratamientos en 393 pacientes. Se realizaron 524 recomendaciones (el 90% fueron aceptadas). Se logró una reducción importante de prescripciones consideradas inadecuadas. Se consiguió una disminución del gasto en antibióticos de 29.363 € (7.240 €/mes), lo que supone un ahorro de 2,35 €/cama de hospitalización/día. No hubo diferencias estadísticamente significativas ni en la en mortalidad ni en el aislamiento de bacterias nosocomiales resistentes Conclusiones: Empleando un programa de asesoramiento sobre el tratamiento antibiótico se consiguió una mejor utilización y una disminución del gasto en antibióticos, sin variaciones en la mortalidad. El programa fue muy bien aceptado por los médicos de los servicios implicados

Background: Antibiotics account for a high percentage of hospital pharmacy expenses. An elevated proportion of the prescriptions are considered inappropriate. Infectious diseases specialist could help other physicians in improving antibiotics prescriptions Methods: Treatments in all patients hospitalized in four surgical wards were checked daily and recommendations were made in cases with signs of inadequate antibiotics prescriptions. The program was carried out during for 4 months and the results were compared with a similar period of the previous year. Results: 562 treatments of 393 patients were reviewed . Five hundred twenty four recommendations were made (90% of them were accepted). There was a significant reduction in the number of inadequate prescriptions. Antibiotic expenditure decreased by 29,262 euros (7,240 euros/month), implying a reduction of 2.35 euros/hospitalizationbed/ day. There were no statistically significant differences in the amount of hospital resistant bacteria nor in mortality between the two periods. Conclusions: Following application of a non-compulsory control program, antibiotic prescription improved and expenditure decreased, with no change in mortality. Acceptation of the program by the physicians of the departments implicated was favourable

Osteomielitis por Escherichia coli sobre fractura cerrada de húmero / Osteomyelitis due to eschirichia coli complicating a closed humeral fracture

Los pacientes sometidos a sondaje vesical permanente presentan riesgo de padecer episodios de bacteriemias por Escherichia coli. Se presenta el caso de un varón de 88 años portador de sonda vesical permanente que ingresó por fractura cerrada subcapital del húmero izquierdo y hematuria debida a un carcinoma de vejiga. Durante el ingreso fue sometido a lavados vesicales y a una cistoscopia. Al octavo día de ingreso presentó un incremento de la tumefacción en el hombro izquierdo. Tanto la radiografía simple como la TAC demostraron aire en la proximidad de la fractura. Se intervino al paciente comprobando la existencia de un absceso maloliente sobre la fractura. Se aisló E. coli. La osteomielitis hematógena sobre un fractura cerrada es una complicación infrecuente que puede pasar desapercibida y se acompaña de un mal pronóstico. El uso racional y selectivo del sondaje vesical podría evitar algunos casos semejantes al presentado

Patients with indwelling urethral catheters have an important risk of developing Escherichia coli bacteremia. Several cases of hematogenous vertebral osteomyelitis due to E. coli after diagnostic or therapeutic urinary tract procedures have been reported. An 88-years-old male patient with indwelling urethral catheter was admitted because of a closed subcapital humeral fracture and macroscopic hematuria due to bladder carcinoma. During his hospital admission he was treated with bladder irrigations with glycine solution. Also a cystoscopy was done. On 8th day after admission the size of his left shoulder increased. Free air in the proximity of the humeral fracture was observed at X-ray radiography and at CT scan.The patient was operated and an abscess close to the fracture with malodorous pus was drained. A culture of pus yielded E. coli. In order to prevent infections similar cases, use of indwelling urethral catheters should be strictly limited to patients that do not have any other option

[Osteomyelitis due to Escherichia coli complicating a closed humeral fracture]. / Osteomielitis por Escherichia coli sobre fractura cerrada de húmero.

Patients with indwelling urethral catheters have an important risk of developing Escherichia coli bacteremia. Several cases of hematogenous vertebral osteomyelitis due to E. coli after diagnostic or therapeutic urinary tract procedures have been reported. An 88-years-old male patient with indwelling urethral catheter was admitted because of a closed subcapital humeral fracture and macroscopic hematuria due to bladder carcinoma. During his hospital admission he was treated with bladder irrigations with glycine solution. Also a cystoscopy was done. On 8th day after admission the size of his left shoulder increased. Free air in the proximity of the humeral fracture was observed at X-ray radiography and at CT scan. The patient was operated and an abscess close to the fracture with malodorous pus was drained. A culture of pus yielded E. coli. In order to prevent infections similar cases, use of indwelling urethral catheters should be strictly limited to patients that do not have any other option.

Epidemiología de la exacerbación de la EPOC y de la infección respiratoria en urgencias / Epidemiology of COPD exacerbation and respiratory tract infection at the emergency room

La falta de una definición uniforme de exacerbación de la EPOC hace que haya diferencias entre diversas series al valorar la prevalencia. En España la prevalencia de EPOC es del 2,5 al 3,5% de la población, aumentando al 19% en mayores de 65 años. La exacerbación de la EPOC constituye el 1-2% de las urgencias hospitalarias. Estos enfermos tienen una media de 3 visitas al año, el 4,8% vuelven antes de una semana y la mitad ingresan en el hospital. La mortalidad hospitalaria es del 2,5%. Existe un claro paralelismo entre la prevalencia de exacerbación de la EPOC e infecciones respiratorias. Las infecciones respiratorias constituyen la causa más frecuente de consulta médica. En atención primaria las infecciones respiratorias representan el 14,25% de las consultas y el 63,82% de las infecciones atendidas. La más frecuente es la faringitis (33,7%), seguida de catarro común (31,7%) y bronquitis (18,7%). La prevalencia de infección respiratoria de origen comunitario en enfermos ingresados en hospitales españoles pasó de 28,65% en 1990 a 36,41% en 1999. En los centros de salud la urgencia más frecuente es la faringoamigdalitis. En urgencias de hospitales comarcales las infecciones constituyen el 15%, y de ellas el 31% son de vías bajas. En hospitales de 2º y 3er nivel la infección constituye el 10,4% de las urgencias. Las infecciones respiratorias son las más frecuentes (3,2% de las urgencias) y las que mayor número de ingresos ocasionan. La más frecuente es la bronquitis aguda (28,4%), seguida de neumonía (22,1%), reagudización de EPOC (20,4%), infección ORL (19,8%) y gripe (8,7%) (AU)

The lack of a consistent definition of chronic obstructive pulmonary disease (COPD) exacerbation in diverse series has led to differences in relation to the prevalence of the disease. The prevalence of COPD in the overall population in Spain is 2,5-3,5%, increasing to 19% in older people (> 65 years). Up to 1-2% of the patients assessed at the emergency room have a COPD exacerbation. All the patients with COPD go to the emergency room 3 times/year, 4,8% will return within a week and a half of them will be admitted to the hospital. The inpatient mortality is 2,5%. A clear association was found between the prevalence of COPD exacerbation and respiratory tract infections. The most common cause of looking for attention in primary care practices is respiratory tract infections. The respiratory tract infections and all cause-infectious diseases account for 14,25% and 63,82% of the global amount of consultations at primary care practices, respectively. Among these diseases, the most frequent is pharyngitis (33,7%), followed by common cold (31,7%) and bronchitis (18,7%). The prevalence of community-acquired respiratory tract infections in Spanish hospitals varied from 28,65% in 1990 to 36,41% in 1999. Pharyngotonsillitis is the emergency illness most frequently treated in health care practices. The rate of infectious diseases is 15% at emergency rooms in rural areas, and 31% of these are IVRB. The rate of consultations to the emergency room for infectious diseases in reference secondary and tertiary care hospitals is 10,4% (AU)