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Background: To evaluate the efficacy and safety of long-term use of tedizolid in osteoarticular infections. Methods: Multicentric retrospective study (January 2017&ndash, March 2019) of osteoarticular infection cases treated with tedizolid. Failure: clinical worsening despite antibiotic treatment or the need of suppressive treatment. Results: Cases (n = 51, 59% women, mean age of 65 years) included osteoarthritis (n = 27, 53%), prosthetic joint infection (n = 17, 33.3%), and diabetic foot infections (n = 9, 18%), where, 59% were orthopedic device-related. Most frequent isolates were Staphylococcus spp. (65%, n = 47, S. aureus, 48%). Reasons for choosing tedizolid were potential drug-drug interaction (63%) and cytopenia (55%), median treatment duration was 29 days (interquartile range -IQR- 15&ndash, 44), 24% received rifampicin (600 mg once daily) concomitantly, and adverse events were scarce (n = 3). Hemoglobin and platelet count stayed stable throughout treatment (from 108.6 g/L to 116.3 g/L, p = 0.079, and 240 &times, 109/L to 239 &times, 109/L, p = 0.942, respectively), also in the subgroup of cases with cytopenia. Among device-related infections, 33% were managed with implant retention. Median follow-up was 630 days and overall cure rate 83%, among failures (n = 8), 63% were device-related infections. Conclusions: Long-term use of tedizolid was effective, showing a better safety profile with less myelotoxicity and lower drug-drug interaction than linezolid. Confirmation of these advantages could make tedizolid the oxazolidinone of choice for most of osteoarticular infections.

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.

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Predominantly antibody deficiencies are the most prevalent primary immunodeficiency (PID) in adults. These are rare diseases difficult to diagnose. Therefore, they are diagnosed late. This study aims to evaluate whether an awareness campaign of PIDs among physicians is associated with an increase in number of diagnoses, a reduction in diagnostic delay and diagnosis at earlier stages.A single centre, interventional, quasi-experimental study was designed that included 2 periods, period 1 pre-intervention (1986-2008) and period 2 post-intervention (2009-2018). A descriptive comparative study of variables was carried out in both periods.116 patients were included [27 (23.3%) in period 1 and 89 (76.7%) in period 2]. The incidence rate increased significantly (0.204 and 1.236/100,000habs./year; P 0.05), the diagnosis delay tended to be lower (4 vs. 3.73 years). The reasons for diagnostic suspicion were diverse and the burden disease at diagnosis (expressed by bronchiectasis, altered spirometry, ability to generate antibodies by thymus-independent mechanism and need for substitute treatment) tended to decrease in period 2.Given the potentially serious complications of patients with late diagnosis of PIDs, it is necessary to create specialized multidisciplinary units, to unify assistance protocols and to design interventions to increase the knowledge of these entities.

Objective: To analyse all cases of Nocardia pneumonia occurring between 2010 and 2016 in five Spanish hospitals. Methods: This was a retrospective observational analysis of clinical and microbiological data collected from 55 cases of Nocardia pneumonia. Results: There were one to 20 cases per hospital and six to nine cases per year. Chronic obstructive pulmonary disease, bronchiectasis, and asthma were the main predisposing underlying respiratory conditions. Thirty-four patients were receiving systemic and/or inhaled corticosteroids prior to infection, eight had neoplasia, and six had haematological malignancies. Clinical and radiological findings were common to pneumonia of other infectious aetiologies, except for the frequent presence of nodules and cavitation. Overall, the 1-year mortality was high (38.2%), and mortality was directly related to the pulmonary disease in 15 patients (27.3%). The most frequently identified species were N. cyriacigeorgica (n = 21), N. abscessus (n = 8), and N. farcinica (n = 5). All Nocardia isolates were susceptible to linezolid and all but two were susceptible to amikacin and trimethoprim-sulfamethoxazole. Conclusions: Nocardia pneumonia-associated mortality remains high, probably because of the debilitated status of patients in whom this pathogen is able to cause pulmonary infection. (C) 2019 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.

Introduction Methicillin-susceptibleStaphylococcus aureus(MSSA) bacteraemia is a frequent condition, with high mortality rates. There is a growing interest in identifying new therapeutic regimens able to reduce therapeutic failure and mortality observed with the standard of care of beta-lactam monotherapy. In vitro and small-scale studies have found synergy between cloxacillin and fosfomycin againstS. aureus. Our aim is to test the hypothesis that cloxacillin plus fosfomycin achieves higher treatment success than cloxacillin alone in patients with MSSA bacteraemia. Methods We will perform a superiority, randomised, open-label, phase IV–III, two-armed parallel group (1:1) clinical trial at 20 Spanish tertiary hospitals. Adults (≥18 years) with isolation of MSSA from at least one blood culture ≤72 hours before inclusion with evidence of infection, will be randomly allocated to receive either cloxacillin 2 g/4-hour intravenous plus fosfomycin 3 g/6-hour intravenous or cloxacillin 2 g/4-hour intravenous alone for 7 days. After the first week, sequential treatment and total duration of antibiotic therapy will be determined according to clinical criteria by the attending physician. Primary endpoints: (1) Treatment success at day 7, a composite endpoint comprising all the following criteria: patient alive, stable or with improved quick-Sequential Organ Failure Assessment score, afebrile and with negative blood cultures for MSSA at day 7. (2) Treatment success at test of cure (TOC) visit: patient alive and no isolation of MSSA in blood culture or at another sterile site from day 8 until TOC (12 weeks after randomisation). We assume a rate of treatment success of 74% in the cloxacillin group. Accepting alpha risk of 0.05 and beta risk of 0.2 in a two-sided test, 183 subjects will be required in each of the control and experimental groups to obtain statistically significant difference of 12% (considered clinically significant). Ethics and dissemination Ethical approval has been obtained from the Ethics Committee of Bellvitge University Hospital (AC069/18) and from the Spanish Medicines and Healthcare Product Regulatory Agency (AEMPS, AC069/18), and is valid for all participating centres under existing Spanish legislation. The results will be presented at international meetings and will be made available to patients and funders. Trial registration number The protocol has been approved by AEMPS with the Trial Registration Number EudraCT 2018-001207-37. ClinicalTrials.gov Identifier:NCT03959345; Pre-results.

Background Data on the incidence, etiology, and prognosis of non–ventilator-associated pneumonia in hospitalized patients with solid tumors are scarce. We aimed to study the characteristics of non–ventilator-associated pneumonia in hospitalized patients with solid tumors. Materials and Methods This was a prospective noninterventional cohort study of pneumonia in patients hospitalized in an oncology ward in a tertiary teaching hospital. Pneumonia was defined according to the American Thoracic Society criteria. Patients were followed for 1 month after diagnosis or until discharge. Survivors were compared with nonsurvivors. Results A total of 132 episodes of pneumonia were diagnosed over 1 year (9.8% of admissions to the oncology ward). They were health care–related (67.4%) or hospital-acquired pneumonia (31.8%). Lung cancer was the most common malignancy. An etiology was established in 48/132 episodes (36.4%). Knowing the etiology led to changes in antimicrobial therapy in 58.3%. Subsequent intensive care unit admission was required in 10.6% and was linked to inappropriate empirical therapy. Ten-day mortality was 24.2% and was significantly associated with hypoxia (odds ratio [OR], 2.1). Thirty-day mortality was 46.2%. The independent risk factors for 30-day mortality were hypoxia (OR, 3.3), hospital acquisition (OR, 3.1), and a performance status >1 (OR, 2.6). Only 40% of patients who died within 30 days were terminally ill. Conclusion Pneumonia is a highly prevalent condition in hospitalized patients with solid tumors, even with nonterminal disease. Etiology is diverse, and poor outcome is linked to inappropriate empirical therapy. Efforts to get the empirical therapy right and reach an etiological diagnosis to subsequently de-escalate are warranted. Implications for Practice The present study shows that pneumonia is a prevalent infectious complication in patients admitted to oncology wards, with a very high mortality, even in non–terminally ill patients. Etiology is diverse, and etiological diagnosis is reached in fewer than 40% of cases in nonintubated patients. Intensive care unit admission, a marker of poor outcome, is associated with inappropriate empirical therapy. These results suggest that, to improve prognosis, a more precise and appropriate antimicrobial empirical therapy for pneumonia in patients with solid tumors is necessary, together with an effort to reach an etiological diagnosis to facilitate subsequent de-escalation.

Resumen Fundamento y objetivo La reparacion valvular mitral es el tratamiento de eleccion de la insuficiencia mitral degenerativa. Sin embargo, no esta tan clara su indicacion en el caso de insuficiencias mitrales (IM) secundarias a endocarditis infecciosas (EI), particularmente cuando se intervienen durante su fase activa. Si bien varios estudios observacionales han mostrado la superioridad de la reparacion con respecto a la sustitucion mitral en pacientes sometidos a cirugia de EI, en la mayoria de los centros se sigue optando por la sustitucion valvular por su facilidad y reproducibilidad tecnica. Exponemos a continuacion la experiencia de nuestro centro. Pacientes y metodo Se trata de 4 pacientes intervenidos recientemente durante la fase activa de una endocarditis infecciosa. Se discuten las caracteristicas epidemiologicas y clinicas de cada paciente. Resultados Los 4 pacientes fueron sometidos a distintas tecnicas de reparacion valvular mitral. No se han descrito recaidas ni reinfecciones, y todos los pacientes presentan IM de grado 0 o i / iv en el seguimiento. Conclusiones La reparacion valvular mitral durante la fase activa de la EI es una tecnica factible y que permite obtener buenos resultados postoperatorios.

Legionnaire's disease (LD) is the pneumonic form of legionellosis caused by aerobic gram-negative bacilli of the genus Legionella. Individuals become infected when they inhale aerosolized water droplets contaminated with Legionella species. Forty years after the identification of Legionella pneumophila as the cause of the 1976 pneumonia outbreak in a hotel in Philadelphia, we have non-culture-based diagnostic tests, effective antibiotics, and preventive measures to handle LD. With a mortality rate still around 10%, underreporting, and sporadic outbreaks, there is still much work to be done. In this article, the authors review the microbiology, laboratory diagnosis, and epidemiology of LD.

Following the explosion of the influenza A pandemic (H1N1) during the first semester of 2009, oseltamivir and zanamivir were used as the treatment of choice in the absence of rigorous clinical studies demonstrating their efficacy in the treatment and prophylaxis of this disease. Knowledge of seasonal influenza, flu pandemics and particularly the H1N1, which produces more severe infection and a higher mortality rate during pregnancy, led to the use of antiviral treatment despite the scarcity of clinical studies on their efficacy and effectiveness, mainly due to the influence of the media. This study reviewed the experimental and clinical studies performed on the safety of oseltamivir and zanamivir in pregnancy. Likewise, the recommendations made by the different health care and governmental authorities as well as other institutions and scientific and health care organizations on the therapeutic management and prophylaxis of influenza A 2009 in pregnant women were reviewed.

Background Erythromycin has been the treatment of choice for Legionnaires disease (LD). However, treatment failure and experimental evidence of its bacteriostatic effect have led to evaluation of new drugs such as fluoroquinolones. This study compared the evolution of patients with LD treated with macrolides and fluoroquinolones. Methods A prospective observational study was performed, and 130 patients from three centers were included. Diagnoses were made using Legionella urinary antigen assay in all patients. Patients receiving any antibiotic > 36 h before starting the study therapy were excluded. Group 1 included 76 patients who received macrolides (33 patients with erythromycin and 43 patients with clarithromycin), and group 2 included 54 patients treated with fluoroquinolones (50 patients with levofloxacin and 4 patients with ofloxacin). Results No significant differences were seen between the two groups regarding age, sex, smoking, alcohol intake, underlying diseases, or community/hospital acquisition. The time from onset of LD symptoms until the initiation of antibiotic treatment was 78.5 h and 92.7 h in groups 1 and 2, respectively (p = 0.1). Time to apyrexia was significantly longer in the macrolide group (77.1 h vs 48 h for groups 1 and 2, respectively; p=0.000). There were no differences according to radiology, clinical complications, or mortality. Nevertheless, a trend to a longer hospital stay was observed in the macrolide group (9.9 days vs 7.6 days in groups 1 and 2, respectively; p=0.09). Conclusions Fluoroquinolones were as effective as erythromycin in the treatment of LD. It is of note that time to apyrexia was significantly shorter and hospital stay tended to be shorter in patients receiving fluoroquinolones.

Study objectives To compare the outcome of Legionnaires disease (LD) in patients with and without HIV infection. Design Retrospective review of clinical charts. Setting Six hundred-bed university hospital. Patients We studied the clinical findings of 64 patients without HIV and 15 patients with HIV. Patients with a serologic diagnosis only were not included. Patients with previous immunosuppressive therapy or transplant recipients were excluded from the former group. In the HIV group, the mean CD4 cell count was 347.5/μL, plasma viral load was undetectable in 50% of the patients, and only one patient (7%) was receiving cotrimoxazole as prophylaxis against Pneumocystis carinii at the time of pneumonia. No differences were observed in the two groups with respect to community or nosocomial acquisition, delay in the initiation of appropriate treatment, the use of macrolides or fluoroquinolones, and Fine score in cases of community-acquired LD. Results Univariate analysis showed that time to apyrexia was longer, and respiratory symptoms, bilateral infiltrates in chest radiograph, hyponatremia, increase in aspartate aminotransferase and creatine phosphokinase (CK), and respiratory failure were more frequent in the HIV group. Mortality was greater in patients with HIV, achieving a statistically significant value of 20%; however, multivariate analysis only confirmed these differences with respect to the increase in CK. Conclusions LD has a more severe clinical presentation and worse evolution in patients with HIV.

Since 1990 a clone of gentamicin and methicillin-resistant Staphylococcus aureus (MRSA) has remained endemic in our hospital, but since January 1996 a gentamicin-sensitive strain has progressively replaced the previous clone. We characterized the phenotypic and molecular pattern of the MRSA strains isolated in our hospital in 1996 and compared prospectively the epidemiological, clinical and evolutionary characteristics of ninety patients infected or colonized by gentamicin-sensitive MRSA (GS-MRSA) (49) and by gentamicin-resistant MRSA (GR-MRSA) (41). Finally we studied the variation of aminoglycoside consumption in our hospital from 1989 to 1996. We observed two antibiotypes (GS-MRSA and GR-MRSA) corresponding to two major chromosomal patterns. Patients with GS-MRSA usually acquired the infection 72 hours after hospital admission. No significant differences were observed in epidemiological characteristics, clinical presentation and evolution between patients with GS-MRSA and GR-MRSA. Since 1989 aminoglycoside intake in our hospital has decreased by 46%.

Background Hospital-acquired pneumonia (HAP) is one of the leading nosocomial infections and is associated with high morbidity and mortality. Numerous studies on HAP have been performed in intensive care units (ICUs), whereas very few have focused on patients in general wards. This study examined the incidence of, risk factors for, and outcomes of HAP outside the ICU. Methods An incident case-control study was conducted in a 600-bed hospital between January 2006 and April 2008. Each case of HAP was randomly matched with 2 paired controls. Data on risk factors, patient characteristics, and outcomes were collected. Results The study group comprised 119 patients with HAP and 238 controls. The incidence of HAP outside the ICU was 2.45 cases per 1,000 discharges. Multivariate analysis identified malnutrition, chronic renal failure, anemia, depression of consciousness, Charlson comorbidity index ≥3, previous hospitalization, and thoracic surgery as significant risk factors for HAP. Complications occurred in 57.1% patients. The mortality attributed to HAP was 27.7%. Conclusions HAP outside the ICU prevailed in patients with malnutrition, chronic renal failure, anemia, depression of consciousness, comorbidity, recent hospitalization, and thoracic surgery. HAP in general wards carries an elevated morbidity and mortality and is associated with increased length of hospital stay and increased rate of discharge to a skilled nursing facility.

Fundamento y objetivo: La neumonia por Legionella es poco frecuente en pacientes infectados por el virus de la inmunodeficiencia humana (VIH), en los que, sin embargo, adquiere especial gravedad. Se analizan las caracteristicas clinicas y la situacion inmunitaria de los enfermos infectados por el VIH con legionelosis. Pacientes y metodo: Se revisaron las historias clinicas de los pacientes infectados por el VIH y diagnosticados de legionelosis desde 1983 hasta diciembre de 2003, y se comparo la incidencia de neumonia nosocomial por Legionella en pacientes infectados y no infectados por el VIH entre 1997 y 2000. Resultados: Se incluyo en el estudio a 18 enfermos, de los que el 72,2% fueron diagnosticados mediante deteccion del antigeno de Legionella pneumophila serogrupo 1 en orina. La incidencia de neumonia nosocomial por Legionella en pacientes infectados y no infectados por el VIH fue de 0,3 y 0,25/1.000 ingresos/ano, respectivamente (p = 0,42). El 83,3% de los pacientes recibieron tratamiento antibiotico adecuado a su llegada al servicio de urgencias. La mediana del recuento de linfocitos CD4+ fue de 340,5/µl, el 53,8% tuvo una carga viral indetectable y un 64,7% tomaba farmacos antirretrovirales. Un 72,2% eran fumadores, el 38,8% tenia cancer y el 16,7% recibia quimioterapia. El 93,8% presento tos; el 75%, dificultad respiratoria; el 62,5%, algun sintoma extrarrespiratorio; el 76,5%, incremento de la aspartatoaminotransferasa; el 50%, incremento de la creatincinasa, y el 56,3%, hiponatremia. El 50% presento infiltrados pulmonares bilaterales; el 83,3%, insuficiencia respiratoria, y el 22,2% fallecio. Conclusiones: A pesar de que la legionelosis no es mas frecuente en pacientes infectados por el VIH, la gravedad clinica en este contexto hace pensar que podria tratarse de una infeccion oportunista.

Fundamento El uso del tratamiento antirretroviral de gran actividad (TARGA) (highly active antiretroviral therapy) ha conducido probablemente a la reduccion de las infecciones hematogenas en pacientes infectados por el virus de la inmunodeficiencia humana (VIH). Pacientes y metodo Se han estudiado todas las infecciones hematogenas, incluidas micobacteriemias y fungemias, ocurridas en pacientes infectados por el VIH y se han estratificado en dos periodos ( I: 1995-1996, y II: 1997-1998) para evaluar los cambios atribuibles al TARGA. Resultados Se atendieron 226 episodios (incidencia: 38,8 en el periodo I y 15,3 en el periodo II; p Conclusiones La infeccion hematogena en pacientes infectados por el VIH ha disminuido de forma significativa tras el uso generalizado del TARGA.

To determine the prevalence of and risk factors for methicillin-resistantStaphylococcus aureus(MRSA) carriage at the time of admission to our hospital, we screened the medical records of 1,128 patients for demographic and clinical data. The antimicrobial resistance pattern and genotype of MRSA isolates were studied. The prevalence of MRSA carriage at hospital admission was 1.4%. Older patients and patients previously admitted to healthcare centers were the most likely to have MRSA carriage at admission.

We evaluated the impact of the copper-silver ionization system in a hospital where hyperendemic nosocomial legionellosis and was present and all previous disinfection measures had failed. After implementation of the copper-silver ionization system, environmental colonization with Legionella species decreased significantly, and the incidence of nosocomial legionellosis decreased dramatically, from 2.45 to 0.18 cases per 1000 patient discharges.

The aim of this prospective study was to compare patient characteristics, clinical data, and evolution of Legionella pneumophila pneumonia according to the duration of Legionella urinary antigen excretion. Urine samples from 61 patients with Legionella pneumonia diagnosed by detection of urinary antigen were obtained periodically until urinary antigen could no longer be detected. Cases were divided into two groups based on the duration of urinary antigen excretion: group I (46 patients,60 days) and group II (15 patients,or=60 days). Groups were compared for patient characteristics, clinical data, and evolution of pneumonia. Antigen excretionor=60 days was observed significantly more frequently in immunosuppressed patients ( P=0.001) in whom the time to apyrexia was72 h ( P=0.002), although only the time to apyrexia remained significant on multivariate analysis ( P=0.006). In conclusion, the duration of Legionella urinary antigen excretion was60 days in most patients but was longer in immunosuppressed patients with a longer time to defervescence of fever.