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Resumen Antecedentes y objetivo Las deficiencias predominantemente de anticuerpos constituyen, en la actualidad, el grupo de inmunodeficiencias primarias (IDP) mas prevalente en adultos. Son enfermedades complejas desde el punto de vista clinico, catalogadas como minoritarias y que tienen a menudo un retraso inaceptable en su diagnostico. El objetivo de este estudio fue evaluar si un mejor conocimiento de estas entidades podia conllevar un incremento en el numero de diagnosticos, una reduccion en el intervalo al diagnostico y, por ende, una disminucion en la carga de enfermedad al diagnostico. Pacientes y metodos Se diseno un estudio de intervencion casi experimental y Unicentro, que incluyo dos periodos, periodo 1 preintervencion (1986-2008) y periodo 2 postintervencion (2009-2018). Se efectuo un estudio descriptivo comparativo de diversas variables en ambos periodos. Resultados Se incluyeron 116 pacientes [27 (23,3%) en el periodo 1 y 89 (76,7%) en el periodo 2]. La tasa de incidencia aumento de forma significativa (0,204 y 1,236/100.000 habs./ano; P Conclusiones Dadas las complicaciones potencialmente graves de los pacientes con diagnostico tardio de IDP, es necesaria la creacion de unidades multidisciplinarias especializadas, la unificacion de protocolos asistenciales y el diseno de intervenciones para la divulgacion de esta entidad.

Healthcare-related Legionnaires’ disease has a devastating impact on high risk patients, with a case fatality rate of 30-50%. Legionella prevention and control in hospitals is therefore crucial. To control Legionella water colonisation in a hospital setting we evaluated the effect of pipeline improvements and temperature increase, analysing 237 samples over a two-year period (first year: 129, second year: 108). In the first year, 25.58% of samples were positive for Legionella and 16.67% for amoeba. Assessing the distance of the points analysed from the hot water tank, the most distal points presented higher proportion of Legionella colonisation and lower temperatures (nearest points: 6.4% colonised, and temperature 61.4°C; most distal points: 50% and temperature 59.1°C). After the first year, the hot water system was repaired and the temperature stabilised. This led to a dramatic reduction in Legionella colonisation, which was negative in all the samples analysed; however, amoeba colonisation remained stable. This study shows the importance of keeping the temperature stable throughout the circuit, at around 60°C. Special attention should be paid to the most distal points of the circuit; a fall in temperature at these weak points would favour the colonisation and spread of Legionella, because amoeba (the main Legionella reservoir) are not affected by temperature.

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.

High-dose of IVIG show immunomodulatory properties that may be useful for controlling the hyperinflammatory status observed in COVID-19 patients., The use of high-dose of intravenous immunoglobulins (IVIGs) as immunomodulators for the treatment of COVID-19–affected individuals has shown promising results. IVIG reduced inflammation in these patients, who progressively restored respiratory function. However, little is known about how they may modulate immune responses in COVID-19 individuals. Here, we have analyzed the levels of 41 inflammatory biomarkers in plasma samples obtained at day 0 (pretreatment initiation), 3, 7, and 14 from five hospitalized COVID-19 patients treated with a 5-d course of 400 mg/kg/d of IVIG. The plasmatic levels of several cytokines (Tumor Necrosis Factor, IL-10, IL-5, and IL-7), chemokines (macrophage inflammatory protein-1α), growth/tissue repairing factors (hepatic growth factor), complement activation (C5a), and intestinal damage such as Fatty acid–binding protein 2 and LPS-binding protein showed a progressive decreasing trend during the next 2 wk after treatment initiation. This trend was not observed in IVIG-untreated COVID-19 patients. Thus, the administration of high-dose IVIG to hospitalized COVID-19 patients may improve their clinical evolution by modulating their hyperinflammatory and immunosuppressive status.

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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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.

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.

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.

Aim: To compare the discriminatory power of pulsed-field gel electrophoresis (PFGE) and sequence-based typing (SBT) in Legionella outbreaks for determining the infection source. Materials & methods: Twenty-five investigations of Legionnaires’ disease were analyzed by PFGE, SBT and Dresden monoclonal antibody. Results: The results suggested that monoclonal antibody could reduce the number of Legionella isolates to be characterized by molecular methods. The epidemiological concordance PFGE–SBT was 100%, while the molecular concordance was 64%. Adjusted Wallace index (AW) showed that PFGE has better discriminatory power than SBT (AWSBT→PFGE = 0.767; AWPFGE→SBT = 1). The discrepancies appeared mostly in sequence type (ST) 1, a worldwide distributed ST for which PFGE discriminated different profiles. Conclusion: SBT discriminatory power was not sufficient verifying the infection source, especially in worldwide distributed STs, which were classified into different PFGE patterns.

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.

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.

Resumen Introduccion Legionella pneumophila (L. pneumophila) fue aislada en tres torres de refrigeracion implicadas en tres brotes de legionelosis comunitaria. En cada una de ellas se encontraron cepas con dos subtipos diferentes de ADN cromosomico. Sin embargo, solo uno de ellos era identico al de las cepas clinicas. Para intentar entender porque solo una de las cepas ambientales produjo los casos clinicos investigamos la virulencia intrinseca de estas cepas. Metodos Se seleccionaron 6 cepas de L. pneumophila sg.1: dos cepas (A1 y B1) procedentes de la torre de refrigeracion 1, dos cepas (A2 y B2) de la torre 2 y dos cepas (A3 y B3) de la torre 3. Las cepas A presentaban un perfil de ADN cromosomico identico a la cepa clinica aislada en los individuos afectados en cada uno de los brotes de legionelosis. La cepa B presentaba un perfil cromosomico diferente. Se realizaron ensayos de replicacion en macrofagos, se determino la presencia del epitopo reconocido por MAb 3/1 y se estudio la cinetica de crecimiento en medio BCYE. Las cepas se tipificaron mediante electroforesis en campo pulsante. Resultados Las cepas A no presentaron mayor grado de virulencia, sin embargo, fueron capaces de crecer y sobrevivir mejor que las cepas B en medio BCYE. Conclusiones Estos resultados sugieren que las cepas mejor adaptadas al medio conseguiran desplazar a las demas y seran capaces de propagarse e infectar a los humanos. La adaptacion a las condiciones ambientales podria desempenar un papel importante en la patogenia de cada cepa.

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.

Fundamento y objetivo En el ano 2001 tuvo lugar en Murcia un brote de enfermedad del legionario (EL) con una de las tasas de mortalidad mas bajas conocidas. Los objetivos de este estudio fueron describir la presentacion clinica y los resultados de los estudios molecular y de virulencia de los aislamientos clinicos de Legionella para correlacionar la baja mortalidad de la serie con la virulencia de la cepa. Pacientes y metodo Estudio prospectivo y descriptivo de un brote de EL en un subgrupo de 86 pacientes. Se analizan datos demograficos, factores de riesgo y evolucion clinica. Se ha practicado subtipificacion molecular mediante electroforesis en campo pulsatil y estudio de citopatogenicidad de los aislamientos clinicos y se han comparado con los de aislamientos procedentes de otros brotes. Resultados La edad media fue de 58,2 anos, con predominio del sexo masculino (77,9%). El tabaquismo fue el factor de riesgo mas frecuente (71,7%). El 70,2% de los pacientes presentaba enfermedades de base. Las manifestaciones clinicas, los datos de laboratorio y la radiologia fueron compatibles con un cuadro de neumonia atipica. La mortalidad fue del 3,2%. Todos los aislamientos clinicos de Legionella pneumophila mostraron el mismo subtipo molecular. En el estudio de citopatogenicidad, las cepas de Legionella procedentes del brote se incluyeron dentro del grupo de menor virulencia. Conclusiones En este subgrupo de pacientes predominaron el sexo masculino, el tabaquismo, la presentacion clinica compatible con neumonia atipica y la baja mortalidad. La baja virulencia de este genotipo molecular de L. pneumophila podria ser causante, en parte, de la baja mortalidad observada en el brote de Murcia.

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.

The key points of this review are the increasingly recognized risk of home-acquired Legionnaires' disease; the significance and potential pathogenic role of other species of Legionella spp., different from L. pneumophila, and of other microorganisms that are phylogenetically close to Legionella and that have been named as Legionella-like amoebal pathogens; the breakthrough in the diagnosis of the disease caused by new commercially available urine antigen detection tests; the controversy over sensitivity and specificity of serological diagnostic methods; the recognition of a variety of possible mixed infections, particularly in the immunocompromised population; and new and controversial aspects of the therapeutic approach to legionellosis.During the last year a number of articles have provided clinically relevant insights into our knowledge of Legionnaires' disease. In view of the fact that Legionella spp. have progressively become recognized as relatively common causative agents of both community-acquired and nosocomial legionellosis, this is an opportune moment for this review.If domestic aquatic reservoirs were eventually confirmed as significant agents of transmission of legionellosis, the adoption of preventive measures would then be crucial. The progressive identification of other species, different from L. pneumophila, as causative agents of pneumonia should both encourage microbiologists and clinicians to improve their diagnostic methodology and increase the awareness of these infections. Finally, the awareness of mixed infections, probably far more severe and perhaps not so uncommon as previously thought, has important clinical connotations for both the diagnostic and the therapeutic approach to legionellosis in the immunosuppressed host, particularly in those cases of delayed clinical resolution.

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%.

The concentrations of Legionella pneumophila in cooling towers may vary considerably over short periods of time, producing significant fluctuations throughout the year. Despite genetic variability, in small geographical areas the same indistinguishable pulsed-field gel electrophoresis patterns may be shared among different cooling towers and persist over time.

Copper and silver ionization is a well-recognized disinfection method to control Legionella species in water distribution systems in hospitals. These systems may also serve as a potential indoor reservoir for fungi. The prevalence of fungi was significantly lower in ionized than in nonionized water samples from health care facilities. The clinical consequences of this finding require further investigation.

Fundamento y objetivo El choque termico es un metodo de desinfeccion frente a Legionella en circuitos de agua sanitaria. En enero de 1996 se produjo un brote de legionelosis nosocomial (LN) en el Hospital Germans Trias i Pujol. El objetivo de este estudio fue evaluar el impacto ambiental y clinico de un choque termico. Material y metodo Recogida diaria de muestras de agua de puntos centrales y de consumo 3 dias antes del choque termico y los 15 dias posteriores. Vigilancia clinica de LN durante 30 dias consecutivos tras el choque termico. Resultados Tras el choque termico, el inoculo de Legionella pneumophila en puntos centrales disminuyo, pero aumento a partir del dia 11 y alcanzo su valor maximo a los 15 dias. No se detecto L. pneumophila en puntos de consumo a los 4 dias. Sin embargo, a partir del dia 7, hubo recolonizacion, que alcanzo el 66% el dia 9. No se detectaron casos clinicos de LN durante el periodo de estudio. Conclusiones El choque termico es un metodo de desinfeccion, eficaz pero transitorio, que permite actuar de forma inmediata ante un brote de LN.

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.

Subtyping isolates may be useful for epidemiological studies of methicillin-resistant-Staphylococcus aureus (MRSA) outbreaks. Among subtyping methods, DNA-based techniques have been applied very effectively for this purpose. An outbreak of MRSA infections took place in one hospital in Barcelona early during 1991. From the beginning of the outbreak to December 92, 70 MRSA isolates from different patients and sources were collected. All strains were evaluated by restriction endonuclease analysis of plasmid DNA (REAP) and macrorestriction endonuclease analysis of genomic DNA using Sma I and pulsed-field-gel-electrophoresis (PFGE). Plasmid screening and REAP using Hind III demonstrated two plasmid subtypes: subtype A showing a large plasmid, and subtype B showing the same large plasmid plus a smaller one. Subtypes A and B corresponded to the more recent and older isolates, respectively, suggesting the loss of the small plasmid during the epidemic. PFGE using Sma I displayed two closely related profiles (PFGE subtype A and A'; CS = 0.90). These subtypes were different from those subtypes exhibited from 4 methicillin-susceptible-Staphylococcus aureus (MSSA) isolates from the same hospital and from 2 epidemiologically unrelated MRSA isolates. Almost all isolates showing PFGE subtype A preceded those isolates showing PFGE subtype A'. This fact and the similarity between both subtypes suggested minor chromosomal DNA rearrangement during the outbreak from a unique strain. While PFGE using Sma I is a useful tool in evaluation of clonal dissemination, our data suggest epidemic or local outbreaks may need several methods to best delineate the source and spread of MRSA strains. The reproducibility and discriminatory power of REAP makes it a useful adjunct in this context.

The primary aim of this study was to evaluate associated factors, clinical features and prognosis of healthcare-related infective endocarditis cases compared with community-acquired and intravenous drug user-related episodes. Changes in the distribution of healthcare-related infective endocarditis were also analysed over time in our setting.A prospective, observational, comparative study was performed. We included all the cases of infective endocarditis from January 2003 to June 2010, which were then classified into 2 groups: group 1: community-acquired and intravenous drug user origin, and group 2: nosocomial and non-nosocomial healthcare-related cases. The episodes were classified into 2 periods: period I: January/2003-June/2006 and period II: July/2006-June 2010. Univariate and multivariate analyses were performed.A total of 212 cases were included (group 1: 138, group 2: 74). The variables of age (risk ratio 1.026; 95%CI, 1.003 to 1.049), Charlson index (risk radio 1.242; 95%CI, 1.067 to 1.445), and previous heart surgery (risk ratio 2.522; 95%CI, 1.353 to 4.701) were independently associated with healthcare-related infective endocarditis on multivariate analysis. A non-significant increase was observed in healthcare-related cases of infective endocarditis in period II (40/104; 38.4% vs. 34/108; 31.4%).The recent increase in healthcare-related infective endocarditis seems to be associated with the use of invasive procedures in elderly patients with prosthetic cardiac valve, and those with a greater number of underlying diseases, especially patients with chronic renal failure on haemodialysis.

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.

The molecular epidemiology of clinical and environmental Legionella species isolates was studied in seven hospitals from 1989 to 2006. The number of environmental pulsed field gel electrophoresis (PFGE) patterns ranged from one to nine according to the hospital. Genomic PFGE pattern persistence was observed in 71% of the hospitals, even after 17 years in some hospitals, and the relationship between environmental and clinical isolates was established. The isolates associated with hospital-acquired Legionnaires' disease corresponded to the persistent environmental PFGE patterns of Legionella pneumophila in potable water supplies.

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 objective of this study was to compare epidemiological data and clinical presentation of community-acquired pneumonia (CAP) caused by Streptococcus pneumoniae, Legionella pneumophila or Chlamydia pneumoniae. From May 1994 to February 1996, 157 patients with S. pneumoniae (n = 68), L. pneumophila (n = 48) and C. pneumoniae (n = 41) pneumonia with definitive diagnosis, were prospectively studied. The following comparisons showed differences at a level of at least p0.05. Patients with S. pneumoniae pneumonia had more frequently underlying diseases (HIV infection and neoplasm) and those with C. pneumoniae pneumonia were older and had a higher frequency of chronic obstructive pulmonary disease (COPD), while L. pneumophila pneumonia prevailed in patients without comorbidity, but with alcohol intake. Presentation with cough and expectoration were significantly more frequent in patients with S. pneumoniae or C. pneumoniae pneumonia, while headache, diarrhoea and no response to betalactam antibiotics prevailed in L. pneumophila pneumonia. However, duration of symptomsor = 7 d was more frequent in C. pneumoniae pneumonia. Patients with CAP caused by L. pneumophila presented hyponatraemia and an increase in CK more frequently, while AST elevation prevailed in L. pneumophila and C. pneumoniae pneumonia. In conclusion, some risk factors and clinical characteristics of patients with CAP may help to broaden empirical therapy against atypical pathogens until rapid diagnostic tests are available.

Inhalation of contaminated aerosols is considered the most common route ofLegionellatransmission. The aim of this study was to determine whether contact with water contaminated byLegionellawas related to oropharyngeal colonization in immunosuppressed patients. Eighty-five oropharyngeal swabs (April 1996 to June 1996) were seeded on selective and nonselective buffered charcoal-yeast extract media.Legionellawas not isolated.

Objective:To investigate the presence and clonal distribution ofLegionellaspecies in the water supply of 20 hospitals in Catalonia, Spain.Setting:20 hospitals in Catalonia, an area of 32,000 km2, located in northeast Spain.Methods:Environmental cultures of 186 points of potable water supply and 10 cooling towers were performed for the presence ofLegionellaspecies. Following filtration and acid treatment, the samples were seeded in selective MWY (modified Wadowsky Yee)-buffered charcoal yeast extract-a agar. All isolates obtained were characterized microbiologically and genotyped bySfilpulsed-field gel electrophoresis (PFGE).Results:73 of 196 water samples, representing 17 of the 20 hospitals included in the study, were positive forLegionella pneumophila(serogroups 1, 2-14, or both). The degree of contamination ranged from 200 to 74,250 colony-forming units/L. Twenty-five chromosomal DNA subtypes were detected by PFGE. A single DNA subtype was identified in 10 hospitals, 2 DNA subtypes were observed in 6 hospitals, and 1 hospital exhibited 3 different DNA subtypes. Each hospital had its ownLegionellaDNA subtype, which was not shared with any other hospitals.Conclusions:Legionellawas present in the water of most of the hospitals studied; each such hospital had a unique, dominant chromosomal DNA subtype. The verification of several genomic DNA restriction profiles in such a small geographic area demonstrates the great genetic diversity ofLegionellain the aquatic environment.

The aim of this study was to prospectively analyze the bacterial etiology of community-acquired pneumonia in adults in Spain. From May 1994 to February 1996, 392 episodes of CAP diagnosed in the emergency department of a 600-bed university hospital were studied. An etiological diagnosis based on noninvasive microbiological investigations was achieved in 228 cases (58%); 173 of these diagnoses were definitive and 55 probable. Streptococcus pneumoniae, which caused 23.9% of the episodes, was the predominant pathogen observed, followed by Chlamydia pneumoniae (13.5%) and Legionella pneumophila (12.5%). Other less frequent pathogens found were Haemophilus influenzae (2.3%), Pseudomonas aeruginosa (1.5%), Mycoplasma pneumoniae (1.3%), Coxiella burnetii (1%), Moraxella catarrhalis (2 cases), Nocardia spp. (2 cases), and Staphylococcus aureus (2 cases). Streptococcus pneumoniae was significantly more frequent in patients with underlying disease and/or age > or =60 years (28% vs. 13%, P = 0.002), while Legionella pneumophila was more frequent in patients below 60 years of age and without underlying disease (20% vs. 9%, P = 0.006). Likewise, Streptococcus pneumoniae and Legionella pneumophila were the most frequent etiologies in patients requiring admission to the intensive care unit, occurring in 29% and 26.3% of the patients, respectively. In addition to Streptococcus pneumoniae, other microorganisms such as Chlamydia pneumoniae and Legionella spp. should be seriously considered in adults with community-acquired pneumonia when initiating empiric treatment or ordering rapid diagnostic tests.

Summary Genotypic variability and clonal persistence are important concepts in molecular epidemiology as they facilitate the search for the source of sporadic cases or outbreaks of legionellosis. We studied the genotypic variability and persistence of Legionella pulsed-field gel electrophoresis (PFGE) patterns over time (period > 6 months) in 34 positive cooling towers from two different areas. In area A, radius of 70 km, 52 indistinguishable PFGE patterns were differentiated among the 27 cooling towers. In 13 cooling towers we observed ≥ 2 PFGE patterns. Each cooling tower had its own indistinguishable Legionella PFGE pattern which was not shared with any other cooling tower. In area B, radius of 1 km, 10 indistinguishable PFGE patterns were obtained from the seven cooling towers. In four, we observed ≥ 2 PFGE patterns. Three of these 10 indistinguishable PFGE patterns were shared by more than one cooling tower. In 27 of 34 cooling towers the same PFGE pattern was recovered after 6 months to up to 5 years of follow-up. The large genotypic diversity of Legionella observed in the cooling towers aids in the investigation of community outbreaks of Legionnaires' disease. However, shared patterns in small areas may confound the epidemiological investigation. The persistence of some PFGE patterns in cooling towers makes the recovery of the Legionella isolate causing the outbreak possible over time.

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.