Effectiveness of fosfomycin trometamol as oral step-down therapy for bacteraemic urinary tract infections due to MDR Escherichia coli: a post hoc analysis of the FOREST randomized trial.

BACKGROUND: Fosfomycin is a potentially attractive option as step-down therapy for bacteraemic urinary tract infections (BUTI), but available data are scarce. Our objective was to compare the effectiveness and safety of fosfomycin trometamol and other oral drugs as step-down therapy in patients with BUTI due to MDR Escherichia coli (MDR-Ec). METHODS: Participants in the FOREST trial (comparing IV fosfomycin with ceftriaxone or meropenem for BUTI caused by MDR-Ec in 22 Spanish hospitals from June 2014 to December 2018) who were stepped-down to oral fosfomycin (3 g q48h) or other drugs were included. The primary endpoint was clinical and microbiological cure (CMC) 5-7 days after finalization of treatment. A multivariate analysis was performed using logistic regression to estimate the association of oral step-down with fosfomycin with CMC adjusted for confounders. RESULTS: Overall, 61 patients switched to oral fosfomycin trometamol and 47 to other drugs (cefuroxime axetil, 28; amoxicillin/clavulanic acid and trimethoprim/sulfamethoxazole, 7 each; ciprofloxacin, 5) were included. CMC was reached by 48/61 patients (78.7%) treated with fosfomycin trometamol and 38/47 (80.9%) with other drugs (difference, -2.2; 95% CI: -17.5 to 13.1; P = 0.38). Subgroup analyses provided similar results. Relapses occurred in 9/61 (15.0%) and 2/47 (4.3%) of patients, respectively (P = 0.03). The adjusted OR for CMC was 1.11 (95% CI: 0.42-3.29, P = 0.75). No relevant differences in adverse events were seen. CONCLUSIONS: Fosfomycin trometamol might be a reasonable option as step-down therapy in patients with BUTI due to MDR-Ec but the higher rate of relapses would need further assessment.

Daily tenofovir disoproxil fumarate/emtricitabine and hydroxychloroquine for pre-exposure prophylaxis of COVID-19: a double-blind placebo-controlled randomized trial in healthcare workers.

OBJECTIVES: To assess the effect of hydroxychloroquine (HCQ) and Tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) as pre-exposure prophylaxis on COVID-19 risk. METHODS: EPICOS is a double-blind, placebo-controlled randomized trial conducted in Spain, Bolivia, and Venezuela. Healthcare workers with negative SARS-CoV-2 IgM/IgG test were randomly assigned to the following: daily TDF/FTC plus HCQ for 12 weeks, TDF/FTC plus HCQ placebo, HCQ plus TDF/FTC placebo, and TDF/FTC placebo plus HCQ placebo. Randomization was performed in groups of four. Primary outcome was laboratory-confirmed, symptomatic COVID-19. We also studied any (symptomatic or asymptomatic) COVID-19. We compared group-specific 14-week risks via differences and ratios with 95% CIs. RESULTS: Of 1002 individuals screened, 926 (92.4%) were eligible and there were 14 cases of symptomatic COVID-19: 220 were assigned to the TDF/FTC plus HCQ group (3 cases), 231 to the TDF/FTC placebo plus HCQ group (3 cases), 233 to the TDF/FTC plus HCQ placebo group (3 cases), and 223 to the double placebo group (5 cases). Compared with the double placebo group, 14-week risk ratios (95% CI) of symptomatic COVID-19 were 0.39 (0.00-1.98) for TDF + HCQ, 0.34 (0.00-2.06) for TDF, and 0.49 (0.00-2.29) for HCQ. Corresponding risk ratios of any COVID-19 were 0.51 (0.21-1.00) for TDF + HCQ, 0.81 (0.44-1.49) for TDF, and 0.73 (0.41-1.38) for HCQ. Adverse events were generally mild. DISCUSSION: The target sample size was not met. Our findings are compatible with both benefit and harm of pre-exposure prophylaxis with TDF/FTC and HCQ, alone or in combination, compared with placebo.

Incidence and predictors of sternal surgical wound infection in cardiac surgery: A prospective study.

Sternal surgical wound infection (SSWI) in cardiac surgery is associated with increased morbidity. We investigated the incidence of SSWI, the main germs implicated and predictors of SSWI. Prospective study including patients undergoing full median sternotomy between January 2017 and December 2019. Patients were followed-up for 3 months after hospital discharge. All sternal wound infections up to 90 days after discharge were considered SSWI. 1004 patients were included. During follow-up, 68 (6.8%) patients presented SSWI. Patients with SSWI had a higher incidence of postoperative renal failure (29.4% vs 17.1%, P = .007), a higher incidence of early postoperative reoperation for non-infectious causes (42.6% vs 9.1%, P < .001), longer ICU stay (3 [2-9] days vs 2 [2-4] days, P = .006), and longer hospital stay (24.5 [14.8-38.3] days vs 10 [7-18] days, P < .001). Gram-positive germs were presented in 49% of the cultures, and gram-negative bacteria in 35%. Early reoperation for non-infectious causes (OR 4.90, 95% CI 1.03-23.7), and a longer ICU stay (OR 1.37 95% CI 1.10-1.72) were independent predictors of SSWI. SSWI is rare but leads to more postoperative complications. The need for early reoperation because of non-infectious cause and a longer ICU stay were independently associated with SSWI.

Risk Factors of DAIR Failure and Validation of the KLIC Score: A Multicenter Study of Four Hundred Fifty-Five Patients.

Background: Debridement, antibiotic agents, and implant retention (DAIR) is a currently accepted approach for the treatment of early prosthetic joint infections (PJI). The success of a DAIR procedure has shown variable results throughout the published literature. Scoring systems such as the Kidney, Liver, Index surgery, Cemented prosthesis, and C-reactive protein value (KLIC) score for the selection of patients that are likely to benefit from DAIR have proved to be helpful in decision making. Our study aims to further validate the KLIC score using a large external multicentric cohort and to evaluate other risk factors for failure. Patients and Methods: A retrospective analysis of patients with an early acute PJI who were treated with DAIR and recorded in a database of eight Spanish university hospitals was performed. According to pre-operative variables of the KLIC study, patients were categorized into five groups: group A, ≤2 points; group B, 2.5-3.5 points; group C, 4-5 points; group D, 5.5-6.5 points; and group E, ≥7 points. Failure rates were compared between groups at 60 days and after 60 days of DAIR. Further variables for risk of failure were also analyzed. Results: A total of 455 patients with early acute PJI were included in the analyses. At 60 days, patients presenting with pre-operative elevated C-reactive protein serum levels, Staphylococcus aureus, and polymicrobial infections were associated with failure. Failure rates recorded were 12% for group A (n = 210), 18% for group B (n = 83), 26% for group C (n = 89), 24% for group D (n = 66), and 0% for group E (n = 7). Univariable analysis between consecutive groups of the KLIC score showed no differences for failure before 60 days of the DAIR procedure. Scheduled surgery and having the procedure performed by a specialized unit were also identified as important factors for DAIR success. Conclusions: Our results suggest the KLIC score was not useful for predicting failure in our cohort. Furthermore, our results indicate a specialized unit should conduct DAIR procedures.

Effectiveness of Fosfomycin for the Treatment of Multidrug-Resistant Escherichia coli Bacteremic Urinary Tract Infections: A Randomized Clinical Trial.

Importance: The consumption of broad-spectrum drugs has increased as a consequence of the spread of multidrug-resistant (MDR) Escherichia coli. Finding alternatives for these infections is critical, for which some neglected drugs may be an option. Objective: To determine whether fosfomycin is noninferior to ceftriaxone or meropenem in the targeted treatment of bacteremic urinary tract infections (bUTIs) due to MDR E coli. Design, Setting, and Participants: This multicenter, randomized, pragmatic, open clinical trial was conducted at 22 Spanish hospitals from June 2014 to December 2018. Eligible participants were adult patients with bacteremic urinary tract infections due to MDR E coli; 161 of 1578 screened patients were randomized and followed up for 60 days. Data were analyzed in May 2021. Interventions: Patients were randomized 1 to 1 to receive intravenous fosfomycin disodium at 4 g every 6 hours (70 participants) or a comparator (ceftriaxone or meropenem if resistant; 73 participants) with the option to switch to oral fosfomycin trometamol for the fosfomycin group or an active oral drug or parenteral ertapenem for the comparator group after 4 days. Main Outcomes and Measures: The primary outcome was clinical and microbiological cure (CMC) 5 to 7 days after finalization of treatment; a noninferiority margin of 7% was considered. Results: Among 143 patients in the modified intention-to-treat population (median [IQR] age, 72 [62-81] years; 73 [51.0%] women), 48 of 70 patients (68.6%) treated with fosfomycin and 57 of 73 patients (78.1%) treated with comparators reached CMC (risk difference, -9.4 percentage points; 1-sided 95% CI, -21.5 to ∞ percentage points; P = .10). While clinical or microbiological failure occurred among 10 patients (14.3%) treated with fosfomycin and 14 patients (19.7%) treated with comparators (risk difference, -5.4 percentage points; 1-sided 95% CI, -∞ to 4.9; percentage points; P = .19), an increased rate of adverse event-related discontinuations occurred with fosfomycin vs comparators (6 discontinuations [8.5%] vs 0 discontinuations; P = .006). In an exploratory analysis among a subset of 38 patients who underwent rectal colonization studies, patients treated with fosfomycin acquired a new ceftriaxone-resistant or meropenem-resistant gram-negative bacteria at a decreased rate compared with patients treated with comparators (0 of 21 patients vs 4 of 17 patients [23.5%]; 1-sided P = .01). Conclusions and Relevance: This study found that fosfomycin did not demonstrate noninferiority to comparators as targeted treatment of bUTI from MDR E coli; this was due to an increased rate of adverse event-related discontinuations. This finding suggests that fosfomycin may be considered for selected patients with these infections. Trial Registration: ClinicalTrials.gov Identifier: NCT02142751.

Infected bone defects in the lower limb. Management by means of a two-stage distraction osteogenesis protocol.

INTRODUCTION: Although bone transport is generally accepted as the gold standard for the treatment of segmental septic bone defects, some aspects of its practical application are still open to debate. We present our results in this field and compare them with the series published so far. MATERIAL AND METHODS: We reviewed all our patients (2010-2018) that underwent a bone transport procedure in the lower limb due to a septic bone defect. We calculated the bone healing index (BHI), the external fixation index (EFI), the rate of complications and the clinical results. We statistically compared our results with 63 publications with a similar scope. RESULTS: Thirty-five patients (30 M/5F) with a mean age of 40 years and a mean follow-up of 45 months were included. Bone segment was 24 T/11F and mean defect was 8.4 cm (7.34 T/ 10.73F). Mean global BHI was 45.62 days/cm (48.16 T/40.09F). Mean EFI was 2.37 months/cm. Results were excellent in 9 patients, good in 23 and bad in 3. Bone graft was used in 60% of the cases. DISCUSSION: The size of our series is similar to previously published ones, although the mean age of our patients is higher and they present a larger bone defect. BHI of our series is similar to that of other series, although EFI is significantly higher. The number of complications is also in line with the existing literature. CONCLUSION: The use of a two-stage technique for managing segmental bone defects of septic origin in the lower extremity is a valid alternative. Our series shows results comparable to the current literature.

Risk factors for methicillin-resistant Staphylococcus aureus and extended-spectrum Beta-lactamase-producing Enterobacterales in patients with diabetic foot infections requiring hospital admission / Factores de riesgo de infección por Staphylococcus aureus resistente a meticilina y enterobacterias productoras de betalactamasas en infecciones de pie diabético que requieren hospitalización

OBJETIVO: Staphylococcus aureus resistente a meticilina (MRSA) y las enterobacterias productoras de betalactamasas (ESBL-E) pueden complicar el tratamiento de las infecciones del pie del diabético (DFIs). El objetivo de este estudio fue determinar los factores de riesgo de las infecciones por estos microorganismos en el pie del diabético. MATERIAL Y MÉTODOS: Estudio observacional prospectivo de 167 pacientes consecutivos con infecciones del pie del diabético. El diagnóstico y gravedad de las infecciones se basó en la guía de la Infectious Disease Society of America (IDSA). Para identificar los factores de riesgo de las infecciones por MRSA y (ESBL-E) se llevó a cabo mediante un estudio multivariante. RESULTADOS: S. aureus fue el microorganismo más aislado (n= 82; 37,9 %) seguido por Escherichia coli (n= 40; 18,5%). El 57,3% de S. aureus fueron MRSA y el 70% de Klebsiella pneumoniae y el 25% de E. coli eran productores ESBL, respetivamente. Los factores de riesgo independientes de las infecciones por MRSA fueron las úlceras profundas [OR 8,563; IC 95% (1,068-4,727)], uso previo de fluoroquinolonas [OR 2,78; IC 95% (1,156-6,685)] y la vasculopatía periférica [OR 2,47; IC 95% (1.068-4.727)], mientras que para las infecciones por (ESBL-E) lo fueron osteomielitis [OR 6,351; 95% IC 95% (1,609-25,068)] y el uso previo de cefalosporinas [OR 5,824; IC 95% (1,517-22,361)]. CONCLUSIONES: MRSA y ESBL-E han adquirido una gran relevancia clínica en las DFIs. La disponibilidad de sus factores de riesgo es muy conveniente para elegir el tratamiento empírico en las formas graves

PURPOSE: Methicillin-resistant Staphylococcus aureus (MRSA) and extended-spectrum Beta-lactamase-producing Enterobacterales (ESBL-E) may complicate the treatment of diabetic foot infections (DFIs). The aim of this study was to determine the risk factors for these pathogens in DFIs. MATERIAL AND METHODS: This was a prospective observational study of 167 consecutive adult patients with DFIs. The diagnosis and severity of DFIs were based on the Infectious Disease Society of America (IDSA) classification system. Multivariate analyses were performed in order to identify risk factors for MRSA and ESBL-E infections. RESULTS: S. aureus was the most isolated pathogen (n=82, 37.9 %) followed by Escherichia coli (n= 40, 18.5%). MRSA accounted for 57.3% of all S. aureus and 70% of Klebsiella pneumoniae and 25% of E. coli were ESBL producers, respectively. Deep ulcer [OR 8,563; 95% CI (1,068-4,727)], previous use of fluoroquinolones [OR 2,78; 95% CI (1,156-6,685)] and peripheral vasculopathy [OR 2,47; 95% CI (1.068-4.727)] were the independent predictors for MRSA infections; and osteomyelitis [OR 6,351; 95% CI (1,609-25,068)] and previous use of cephalosporins [OR 5,824; 95% CI (1,517-22,361)] for ESBL-E infections. CONCLUSIONS: MRSA and ESBL-E have adquired a great clinical relevance in DFIs. The availability of their risk factors is very convenient to choose the empirical treatment in severe forms

Comparison of Predictors and Mortality Between Bloodstream Infections Caused by ESBL-Producing Escherichia coli and ESBL-Producing Klebsiella pneumoniae.

OBJECTIVETo compare the epidemiology, clinical characteristics, and mortality of patients with bloodstream infections (BSI) caused by extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli (ESBL-EC) versus ESBL-producing Klebsiella pneumoniae (ESBL-KP) and to examine the differences in clinical characteristics and outcome between BSIs caused by isolates with CTX-M versus other ESBL genotypesMETHODSAs part of the INCREMENT project, 33 tertiary hospitals in 12 countries retrospectively collected data on adult patients diagnosed with ESBL-EC BSI or ESBL-KP BSI between 2004 and 2013. Risk factors for ESBL-EC versus ESBL-KP BSI and for 30-day mortality were examined by bivariate analysis followed by multivariable logistic regression.RESULTSThe study included 909 patients: 687 with ESBL-EC BSI and 222 with ESBL-KP BSI. ESBL genotype by polymerase chain reaction amplification of 286 isolates was available. ESBL-KP BSI was associated with intensive care unit admission, cardiovascular and neurological comorbidities, length of stay to bacteremia >14 days from admission, and a nonurinary source. Overall, 30-day mortality was significantly higher in patients with ESBL-KP BSI than ESBL-EC BSI (33.7% vs 17.4%; odds ratio, 1.64; P=.016). CTX-M was the most prevalent ESBL subtype identified (218 of 286 polymerase chain reaction-tested isolates, 76%). No differences in clinical characteristics or in mortality between CTX-M and non-CTX-M ESBLs were detected.CONCLUSIONSClinical characteristics and risk of mortality differ significantly between ESBL-EC and ESBL-KP BSI. Therefore, all ESBL-producing Enterobacteriaceae should not be considered a homogeneous group. No differences in outcomes between genotypes were detected.CLINICAL TRIALS IDENTIFIERClinicalTrials.gov. Identifier: NCT01764490.Infect Control Hosp Epidemiol 2018;39:660-667.

Influencia de la protocolización del tratamiento inicial con corticoides en la estancia y costo de las neumonías adquiridas en la comunidad. Estudio prospectivo 2015 / Influence of initial protocolized treatment with steroids in length of stay and costs of community acquired pneumonia

Objetivos. Valorar el impacto que la inclusión inicial de corticoides en el protocolo de tratamiento de un paciente con neumonía de la comunidad (NAC) puede tener en la estancia y costo de los procesos en enfermos ingresados con este diagnóstico en un hospital clínico universitario. Pacientes y métodos. Estudio prospectivo de los pacientes ingresados con el diagnóstico de NAC en los Servicios de Medicina Interna e Infecciosas durante los meses de enero a marzo de 2015; los pacientes se clasificaron en Grupo I, en caso de haber recibido esteroides desde el diagnóstico del proceso neumónico y hasta la finalización del tratamiento antibiótico y en Grupo II, si no habían recibido esteroides; la administración o no de esteroides fue realizada según la práctica clínica de cada médico responsable del paciente. Se valoró el costo según el GRD de NAC. Resultados. La edad < de 65 años es más frecuente en el grupo I que en el II, siendo el único factor diferencial entre ambas cohortes con significación estadística (p<0,05). En el análisis bivariado, las estancias medias del grupo I (5,37 vs 8,88 días) fueron significativamente menores (p<0,0005) y también lo fueron los costes (2.361 euros vs 3.907 euros) (p<0,0005). En el estudio multivariado se asociaron de forma independiente los costes altos (>3.520 euros) a los pacientes con EPOC (OR=2,602; IC95% 1,074-6,305) y al grupo II (pacientes que no habían recibido esteroides) (OR=6,2; p=0,007). Conclusiones. El no utilizar corticoides en el tratamiento de los pacientes con neumonías comunitarias se asoció, junto con el ser EPOC a un mayor coste del ingreso, valorado por el GRD/estancia diaria (AU)

Objective. The aim of the study was to analyze the impact of steroid treatment in patients with community acquired pneumonia (CAP), both in length of stay and economical cost of admission at a clinical university hospital. Patients and methods. Prospective study of admitted patients with the diagnosis of CAP, both in Internal Medicine and Infectious diseases department. The study was conducted from January to march 2015; patients receiving steroids from diagnosis to end of antibiotic treatment were classified as group I; otherwise, they were considered in group II. Administration of steroids was done according to the criteria of the responsible. Cost was stablished according to CAP Diagnostic Related Group (DRG). Results. Prevalence of patients younger than 65 year old was higher in group I (p<0.05). In bivariate analyses, mean admission time was lower in group I (5.37 vs 8.88 days) (p<0.0005) and also economical cost (2,361 euros vs 3,907 euros) (p<0.0005). In multivariate analysis, factors independently associated to higher cost (>3,520 euros) were COPD (OR=2.602; 95% CI 1.074-6.305) and group II (patients with no steroids) (OR=6.2; p=0,007). Conclusions. No administration of steroids in patients with CAP was associated, together with COPD, with higher economical cost (evaluated by DRG/length of stay) (AU)

Geographical variation in therapy for bloodstream infections due to multidrug-resistant Enterobacteriaceae: a post-hoc analysis of the INCREMENT study.

We describe regional differences in therapy for bloodstream infection (BSI) caused by extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-E) or carbapenemase-producing Enterobacteriaceae (CPE). Patients (n = 1482) in 12 countries from an observational study of BSI caused by ESBL-E or CPE were included. Multivariate logistic regression was used to calculate adjusted odds ratios (aORs) for the influence of country of recruitment on empirical use of ß-lactam/ß-lactamase inhibitors (BLBLIs) or carbapenems, targeted use of BLBLIs for ESBL-E and use of targeted combination therapy for CPE. Compared with Spain, BLBLI use for empirical therapy was least likely in sites from Israel (aOR 0.34, 95% CI 0.14-0.81), Greece (aOR 0.49, 95% CI 0.26-0.94) and Canada (aOR 0.31, 95% CI 0.11-0.88) but more likely in Italy (aOR 1.58, 95% CI 1.11-2.25) and Turkey (aOR 2.09, 95% CI 1.14-3.81). Empirical carbapenem use was more likely in sites from Taiwan (aOR 1.73, 95% CI 1.03-2.92) and USA (aOR 1.89, 95% CI 1.05-3.39) and less likely in Italy (aOR 0.44, 95% CI 0.28-0.69) and Canada (aOR 0.10, 95% CI 0.01-0.74). Targeted BLBLIs for ESBL-E was more likely in Italian sites. Treatment at sites within Israel, Taiwan, Turkey and Brazil was associated with less combination therapy for CPE. Although this study does not provide precise data on the relative prevalence of ESBL-E or CPE, significant variation in therapy exists across countries even after adjustment for patient factors. Better understanding of what influences therapeutic choices for these infections will aid antimicrobial stewardship efforts.

Diseño y puesta en marcha de un protocolo de tratamiento antimicrobiano domiciliario endovenoso en atención primaria: experiencia en un hospital de segundo nivel / Design and implementation of an outpatient parenteral antimicrobial therapy program in primary care: the experience at a second level hospital

Introducción. Los programas de tratamiento antimicrobiano domiciliario endovenoso (TADE) suponen una buena opción asistencial para una gran variedad de enfermedades infecciosas. Nuestro objetivo fue diseñar e implementar un programa TADE en el área de influencia de un hospital de segundo nivel, en el que no se dispone de una Unidad de Hospitalización a domicilio (UHD), siendo necesario la estrecha colaboración entre los equipos de atención hospitalaria y primaria, describir la cohorte de pacientes, analizar las pautas de tratamiento antimicrobiano y evaluar los factores de riesgo asociados al reingreso y la mortalidad. Métodos. Estudio de cohortes prospectivo de los pacientes incluidos en el TADE entre el 1 de Enero de 2012 al 31 mayo de 2015. Resultados. Se registraron un total de 98 episodios. La edad media fue 66 años. La comorbilidad más frecuente fue la inmunosupresión (33,67%), con una media global del índice de Charlson de 5,21 ± 3,09. El foco de infección más frecuente fue el respiratorio (33,67%). Se consiguió aislamiento microbiológico en 58 pacientes (59,18%), siendo Escherichia coli el más frecuentemente aislado (25%). La media de días de administración de antimicrobianos fue 10,42 (± 6,02 DE, rango 2-40), siendo los carbapenémicos (43,48%) los más usados. Ochenta y seis pacientes (87,75%) cumplimentaron el tratamiento. Treinta y dos pacientes (32,65%) reingresaron en los siguientes 30 días al alta y siete (7,14%) fallecieron. Se encontró asociación estadísticamente significativa con el reingreso con las variables edad (p = 0,03), portador de reservorios (p = 0,04) e interrupción del tratamiento RI (p<0,05). Conclusiones. Este programa es pionero en España en la administración de TADE sin el soporte de una UHD, lo que podría permitir optimizar la red de recursos hospitalarios y de Atención Primaria disponibles. No obstante, los datos del proyecto piloto son pobres en optimización de la elección del antibiótico, secuenciación, desescalamiento y duración (AU)

Introduction. Outpatient parenteral antimicrobial therapy (OPAT) programs are a good assistance option in a wide variety of infectious diseases. Our aim was to design and implement an OPAT program in the area of influence of a second-level hospital, with no Home Hospitalization Service available, being necessary close collaboration between hospitalization and Primary Care teams, describe our cohort, analyse the antimicrobial treatment indicated and evaluate the prognostic and risk factors associated with readmission and mortality. Material and methods. Prospective study cohorts of patients admitted to the OPAT programme, from 1 January 2012 to 31 May 2015. Results. During the period of study a total of 98 episodes were recorded. The average age of the cohort was 66 years. The most frequent comorbidity was immunosuppression (33.67 %), with an overall average of Charlson index of 5.21 ± 3.09. The most common source of infection was respiratory (33.67 %). Microbiological isolation was achieved in fifty-eight patients (59.18 %) being Escherichia coli the most frequently isolated (25%). The average number of days of antibiotics administration at home was 10.42 ± 6.02 (SD), being carbapenems (43.48%) the more administered. Eighty-six patients (87.75%) completed the treatment successfully. Thirty-two patients (32.65%) were readmitted within 30 days after being discharged and seven patients (7.14%) died. A statistically significant association was only found in the readmission with variables: elderly patients (p=0.03), being carriers of Porth-a-Cath (p=0.04) and treatment termination related with infection (p<0.05). Conclusions. This is the first programme of OPAT administration not dependent on Home Hospitalization Service in Spain, which could allow to optimize the hospital and primary care resources available. Nevertheless this pilot study results are poor in terms of optimization of antibiotics choice, transition to oral administration, de-escalation and duration (AU)

Development and validation of the INCREMENT-ESBL predictive score for mortality in patients with bloodstream infections due to extended-spectrum-ß-lactamase-producing Enterobacteriaceae.

Background: Bloodstream infections (BSIs) due to ESBL-producing Enterobacteriaceae (ESBL-E) are frequent yet outcome prediction rules for clinical use have not been developed. The objective was to define and validate a predictive risk score for 30 day mortality. Methods: A multinational retrospective cohort study including consecutive episodes of BSI due to ESBL-E was performed; cases were randomly assigned to a derivation cohort (DC) or a validation cohort (VC). The main outcome variable was all-cause 30 day mortality. A predictive score was developed using logistic regression coefficients for the DC, then tested in the VC. Results: The DC and VC included 622 and 328 episodes, respectively. The final multivariate logistic regression model for mortality in the DC included age >50 years (OR = 2.63; 95% CI: 1.18-5.85; 3 points), infection due to Klebsiella spp. (OR = 2.08; 95% CI: 1.21-3.58; 2 points), source other than urinary tract (OR = 3.6; 95% CI: 2.02-6.44; 3 points), fatal underlying disease (OR = 3.91; 95% CI: 2.24-6.80; 4 points), Pitt score >3 (OR = 3.04; 95 CI: 1.69-5.47; 3 points), severe sepsis or septic shock at presentation (OR = 4.8; 95% CI: 2.72-8.46; 4 points) and inappropriate early targeted therapy (OR = 2.47; 95% CI: 1.58-4.63; 2 points). The score showed an area under the receiver operating curve (AUROC) of 0.85 in the DC and 0.82 in the VC. Mortality rates for patients with scores of < 11 and ≥11 were 5.6% and 45.9%, respectively, in the DC, and 5.4% and 34.8% in the VC. Conclusions: We developed and validated an easy-to-collect predictive scoring model for all-cause 30 day mortality useful for identifying patients at high and low risk of mortality.

Use of antibiotics at a University Clinic Hospital: effect of protocolized antibiotic treatment in the evolution of hospital patients with infections.

OBJECTIVES: To analyse factors associated to "failure" in patients under antibiotic (AB) treatment at a third level hospital. PATIENTS AND METHODS: All patients receiving an AB treatment along April 2012 were prospectively observed and factors associated to failure were analyzed. Failure was defined as clinical or microbiological failure, relapse or death. Statistically significance was established as p<0.05. RESULTS: 602 of 1,265 admitted patients during the study month included an AB in their medical prescriptions, being 178 considered as prophylactic AB prescriptions, 342 empirical treatments and 82 directed treatments as empiric treatments. Ceftriaxone and levofloxacin were the most used AB; choice of empirical and directed treatments were in line with protocols in 71% (242 of 342 cases) and 67% (55 of 82), respectively. Of all the patients receiving antibiotics for therapy (n=424), 402 had infection criteria (in 22 cases antibiotic treatment was deemed unnecessary since the patient showed no infectious process). Of these, 292 (72%) showed a good evolution, while the others were considered as failed therapies, either because of microbiological persistence in 49 (12.8%), relapse in 31 (7.71%) and death in en 30 (7.46%). Factors associated to "failure" were Charlson score ≥3 (OR 3.35; 95%CI 1.602-7.009); empirical and/or directed treatment not in keeping with the protocol (OR 5.68; 95%CI 2.898-11.217); and infection by ESBL and/or ciprofloxacin resistant E. coli (OR 4.43; 95%CI 1.492-13.184). CONCLUSIONS: A high rate of AB prescriptions in admitted patients correspond to empirical infection treatment, being ceftriaxone and levofloxacin the most used AB. Inadequate empirical and/or directed treatment is associated to clinical or microbiological failure and death.

Use of antibiotics at a University Clinic Hospital: effect of protocolized antibiotic treatment in the evolution of hospital patients with infections / Uso de antibióticos en un hospital clínico universitario: efecto del tratamiento antibiótico protocolizado en la evolución de pacientes hospitalizados con infección

Objectives. To analyse factors associated to 'failure' in patients under antibiotic (AB) treatment at a third level hospital. Patients and methods. All patients receiving an AB treatment along April 2012 were prospectively observed and factors associated to failure were analyzed. Failure was defined as clinical or microbiological failure, relapse or death. Statistically significance was established as p<0.05 Results. 602 of 1,265 admitted patients during the study month included an AB in their medical prescriptions, being 178 considered as prophylactic AB prescriptions, 342 empirical treatments and 82 directed treatments as empiric treatments. Ceftriaxone and levofloxacin were the most used AB; choice of empirical and directed treatments were in line with protocols in 71% (242 of 342 cases) and 67% (55 of 82), respectively. Of all the patients receiving antibiotics for therapy (n=424), 402 had infection criteria (in 22 cases antibiotic treatment was deemed unnecessary since the patient showed no infectious process). Of these, 292 (72%) showed a good evolution, while the others were considered as failed therapies, either because of microbiological persistence in 49 (12.8%), relapse in 31 (7.71%) and death in en 30 (7.46%). Factors associated to 'failure' were Charlson score ≥3 (OR 3.35; 95%CI 1.602-7.009); empirical and/or directed treatment not in keeping with the protocol (OR 5.68; 95%CI 2.898-11.217); and infection by ESBL and/or ciprofloxacin resistant E. coli (OR 4.43; 95%CI 1.492-13.184). Conclusions. A high rate of AB prescriptions in admitted patients correspond to empirical infection treatment, being ceftriaxone and levofloxacin the most used AB. Inadequate empirical and/or directed treatment is associated to clinical or microbiological failure and death (AU)

Objetivos. Analizar los factores asociados a fracaso en los pacientes que están recibiendo tratamiento antibiótico en un hospital de tercer nivel. Pacientes y métodos. Todos los pacientes que recibieron algún tratamiento antibiótico durante el mes de Abril de 2012 se siguieron de forma prospectiva y se analizaron los factores asociados a fracaso. El fracaso fue definido como clínico o microbiológico, recaída o muerte. La significación estadística fue establecida con una p<0,05. Resultados. 602 de los 1.265 pacientes ingresados durante el mes de estudio llevaban al menos un antibiótico entre sus prescripciones médicas, correspondiendo en 178 de los casos a profilaxis antibiótica, 342 a tratamientos antibióticos empíricos y 82 a tratamientos dirigidos. Los antibióticos más utilizados fueron ceftriaxona y levofloxacino; la elección del tratamiento antibiótico tanto empírico como dirigido se hizo de acuerdo a los protocolos correspondientes en el 71% (242 de 342 casos) y el 67% (55 de 82 casos), respectivamente. De todos los pacientes que recibieron antibióticos como tratamiento (n=424), 402 tenían criterios de infección (en 22 casos el tratamiento se consideró innecesario dado que el paciente no presentaba proceso infeccioso alguno). De estos, 292 (72%) evolucionaron favorablemente, mientras los otros fueron considerados fallos terapéuticos, bien por persistencia microbiológica en 49 casos (12,8%), recaída en 31 casos (7,71%) y muerte en 30 (7,46%). Los factores asociados a 'fracaso' fueron un índice de Charlson ≥3 (OR 3,35; 95%CI 1,602-7,009); el tratamiento antibiótico empírico o dirigido no ajustado a protocolo (OR 5,68; 95%CI 2,898-11,217); y la infección por E. coli BLEE y/o resistente a ciprofloxacino (OR 4,43; 95%CI 1,492-13,184). Conclusiones. Un alto porcentaje de los antibióticos prescritos en pacientes hospitalizados corresponde a tratamientos empíricos, siendo ceftriaxona y levofloxacino los antibióticos más usados. El tratamiento inadecuado, tanto empírico como dirigido, se asocia con fracaso clínico o microbiológico y con un mayor riesgo de muerte (AU)

La leishmaniasis visceral en la región de Murcia: estudio multicéntrico 1997-2013 / Visceral leishmaniasis in Murcia: Multicentric study 1997-2013

Introducción: La prevalencia de la leishmaniasis visceral (LV), una parasitosis endémica en la cuenca mediterránea, puede verse afectada por movimientos migratorios. Objetivo: El objetivo de este estudio fue analizar los casos de LV valorados en hospitales de la región de Murcia. Material y métodos: Se trata de un estudio retrospectivo multicéntrico de los casos de LV diagnosticados y tratados en los diferentes hospitales de nuestra región, que se agruparon en 2 cohortes: período A (pA), el comprendido entre los años 1997 y 2005, y período B (pB), el transcurrido entre 2006 y 2013. Resultados: Se analizaron 97 casos de LV (75% fueron hombres y la edad media fue de 35 años), 36 en pA y 61 en pB; el 11% de los pacientes procedían de otros países en pA y el 22% en pB (subsaharianos en 10 casos); el 55% tenían algún tipo de inmunosupresión (80% de ellos estaban diagnosticados de infección por VIH). Las manifestaciones más frecuentes fueron: fiebre (85%) y astenia (66%). La duración media de los síntomas antes de la primera consulta fue de 47 días, y el tiempo medio transcurrido entre esta primera consulta y la realización de la prueba diagnóstica, de 13 días. El hallazgo más común en la exploración física fue la esplenomegalia (89%), mientras que la trombocitopenia fue el hallazgo de laboratorio más constante (78%). El diagnóstico se confirmó con la detección de amastigotes y/o PCR del aspirado medular en el 61% de los casos; en el 39% restante el aspirado fue negativo y fue necesario el estudio de otras muestras (biopsia de médula ósea, ganglio linfático, laringe, colon, parótida y amígdala, PCR en sangre, serología o inmunocromatografía en orina). El tratamiento más usado fue anfotericina B liposomal (71%), seguida de glucantime (27%) y anfotericina B complejo lipídico (1%); en un caso no se pudo averiguar el tratamiento administrado. Se objetivaron 16 recidivas, 11 de ellas en pacientes con sida. Conclusiones: Aun a riesgo de sesgos propios de estudios retrospectivos y a pesar del mejor control de la infección VIH, observamos en nuestra región un aumento en la frecuencia de casos de LV, probablemente favorecido por el aumento del número de inmigrantes.

Introduction: The prevalence of visceral leishmaniasis (VL), an endemic parasitic infection in the Mediterranean basin, can be affected by migratory movements. Objective: To analyze VL cases evaluated at several hospitals in the Murcia region. Methods: Retrospective, multicentric study of VL cases; patients were grouped into two time periods: period A (pA: 1997-2005) and period B (pB: 2006-2013). Results: A total of 97 VL cases were analyzed (75% men, mean age 35 years), 36 of them in pA and 61 in pB; 11% and 22% of the patients were foreigners in pA and pB, respectively (10 from sub-Saharan Africa); 55% suffered from some type of immunosuppression (80% HIV). The most common clinical manifestations were fever (85%) and asthenia (66%). The mean duration of symptoms before the first medical contact was 47 days and the average time between the first contact and the microbiological confirmation was 13 days. The most common finding on physical examination was splenomegaly (89%), whereas thrombocytopenia was the most frequent laboratory finding (78%). Diagnoses were confirmed by detection of amastigotes and/or PCR of bone marrow aspiration (BMA) in 61%; in the remaining 39% of cases, BMA was negative and additional samples were necessary (bone marrow, lymph node, larynx, colon, parotid and amygdala biopsy, PCR of blood samples, serology or urine antigen detection). The most commonly used treatment was liposomal amphotericin B (71%), followed by glucantime (27%) and amphotericin B lipid complex (1%). A total of 16 recurrent cases (11 in AIDS patients), were bserved. Conclusions: Although this is a retrospective study and despite better control of HIV infection, we have observed an increase in the frequency of VL cases in our region, which is probably related to migratory flows.

[Study of a cohort of patients with Enterococcus spp. Bacteraemia. Risk factors associated to high-level resistance to aminoglycosides]. / Estudio de una cohorte de pacientes con bacteriemias por Enterococcus spp. Factores de riesgo para resistencia de alto nivel a aminoglicósidos.

OBJECTIVES: To analyze a cohort of patients with Enterococcus sp. bacteraemia. PATIENTS AND METHODS: Retrospective and observational study of a cohort of non-pediatric in-patients with Enterococcus spp. bacteraemia (June 2007-September 2009). Data collection from clinical records was done according to a standard protocol. We analyzed epidemiological, clinical and microbiological data. Treatment with glycopeptides in non allergic patients or in case of betalactam susceptibility (ampicillin) was considered "optimizable". RESULTS: Three were 106 cases of bacteraemia (2.2/1000 admitted patients; 84% E. faecalis); 83% had an underlying condition; 88% nosocomial or health related cases. Urinary infection was present in 20% and primary bacteraemia in 47%. High level resistance to gentamicin (HLRG) was present in 60%; there was no vancomycin or linezolid resistance. Most frequent empiric treatments were penicillin-betalactamase inhibitor (25%) and glycopeptides (22%). Most frequent definitive treatment was glycopeptides (34%), being "optimized" 21% and 44% of empiric and definitive treatments, respectively. Mortality was 23% (related, 14%). In the multivariate analysis, risk factors associated with HLRG were nosocomial acquired infection (OR 6.083; 95CI% 1.428-25.915) and no-abdominal origin (OR 6.006; 95CI%1.398-25.805). In multivariate analysis, independent risk factors for mortality were: Pitt > 3 (OR 14.405; 95CI%2.236-92.808) and active empiric treatment (OR 8.849; 95CI% 1.101-71.429). Incidence in previous cohort was similar but HLRG rate has increased. CONCLUSIONS: Risk factors associated with HLRG were nosocomial acquired infection and no-abdominal origin. Risk factors for mortality were initial clinical severity and having received active empiric treatment. HLRG rate has increased.

Estudio de una cohorte de pacientes con bacteriemias por Enterococcus spp. Factores de riesgo para resistencia de alto nivel a aminoglicósidos / Study of a cohort of patients with Enterococcus spp. Bacteraemia. Risk factors associated to high-level resistance to aminoglycosides

Objetivos. Analizar una cohorte de pacientes con bacteriemia enterocócica. Pacientes y métodos. Estudio retrospectivo-observacional de adultos ingresados con aislamiento de Enterococcus spp en hemocultivos (Junio 2007-Septiembre 2009). Se revisaron las historias clínicas siguiendo un protocolo que consideraba variables epidemiológicas, clínicas y microbiológicas. El tratamiento con glicopéptidos en pacientes no alérgicos o cepas sin resistencia a ampicilina se consideró “optimizable”. Resultados. Se detectaron 106 episodios (2/1000 pacientes ingresados; 84% E. faecalis); 83% presentaban comorbilidad de base; 88% de adquisición nosocomial/asociada a cuidados sanitarios. El foco fue urinario en 20% y desconocido en 47%; 60% tenían resistencia de alto nivel a gentamicina (RANG); no hubo cepas resistentes a vancomicina o linezolid. Los tratamientos empíricos más usados fueron penicilina-inhibidor de betalactamasas (25%) y glicopéptidos (22%). En el tratamiento definitivo el antibiótico más usado fue glicopéptido (34%), considerándose “optimizado” 21% de tratamientos empíricos y 44% de definitivos. La mortalidad global fue 23% (relacionada 14%). Se asociaron a RANG: adquisición nosocomial (OR 6,083; IC95% 1,428-25,915) y no tener foco abdominal (OR 6,006; IC95%1,398-25.805). Se asociaron a mayor mortalidad la gravedad clínica inicial (Pitt > 3) (OR 14,405; IC95%2,236-92,808) y haber recibido un tratamiento empírico activo (OR 8,849; IC95% 1,101-71,429). La incidencia de la serie histórica fue similar y aumentó el porcentaje de RANG en la cohorte más reciente. Conclusiones. La adquisición nosocomial y el no tener foco abdominal se asociaron a RANG; la gravedad clínica inicial y recibir tratamiento empírico activo (que no optimizado) se asociaron a mayor mortalidad. Apreciamos un aumento en el porcentaje de RANG (AU)

Objectives. To analyze a cohort of patients with Enterococcus sp. bacteraemia. Patients and methods. Retrospective and observational study of a cohort of non-pediatric in-patients with Enterococcus spp. bacteraemia (June 2007-September 2009). Data collection from clinical records was done according to a standard protocol. We analyzed epidemiological, clinical and microbiological data. Treatment with glycopeptides in non allergic patients or in case of betalactam susceptibility (ampicillin) was considered “optimizable”. Results. Three were 106 cases of bacteraemia (2.2/1000 admitted patients; 84% E. faecalis); 83% had an underlying condition; 88% nosocomial or health related cases. Urinary infection was present in 20% and primary bacteraemia in 47%. High level resistance to gentamicin (HLRG) was present in 60%; there was no vancomycin or linezolid resistance. Most frequent empiric treatments were penicillin-betalactamase inhibitor (25%) and glycopeptides (22%). Most frequent definitive treatment was glycopeptides (34%), being “optimized” 21% and 44% of empiric and definitive treatments, respectively. Mortality was 23% (related, 14%). In the multivariate analysis, risk factors associated with HLRG were nosocomial acquired infection (OR 6.083; 95CI% 1.428-25.915) and no-abdominal origin (OR 6.006; 95CI%1.398-25.805). In multivariate analysis, independent risk factors for mortality were: Pitt > 3 (OR 14.405; 95CI%2.236-92.808) and active empiric treatment (OR 8.849; 95CI% 1.101-71.429).). Incidence in previous cohort was similar but HLRG rate has increased. Conclusions. Risk factors associated with HLRG were nosocomial acquired infection and no-abdominal origin. Risk factors for mortality were initial clinical severity and having received active empiric treatment. HLRG rate has increased (AU)

When is coagulase-negative Staphylococcus bacteraemia clinically significant?

BACKGROUND: Coagulase-negative staphylococci (CoNS) are common contaminants in blood cultures (BC). A prospective study of patients with ≥ 2 blood culture sets and at least 1 positive CoNS BC was performed to develop an algorithm to assist in determining the clinical significance of CoNS bacteraemia. METHODS: A single reviewer examined the medical records of patients with CoNS bacteraemia (January-June 2010). The determination of clinical significance was made according to CDC/NHSN (US Centers for Disease Control and Prevention/National Healthcare Safety Network) criteria. To explore risk factors associated with clinical significance, a multivariate analysis was performed. The performances of various algorithms were then compared. An algorithm to assist in determining clinical significance was developed. RESULTS: Two hundred and sixty-nine cases were included; 97 (36%) were considered clinically significant bacteraemia (CSB). Predictors of CSB in the multivariate analysis were: time to positivity < 16 h (odds ratio (OR) 4.540, 95% confidence interval (CI) 1.734-11.884), identification of Staphylococcus epidermidis (OR 4.273, 95% CI 2.124-5.593), central venous catheter (OR 4.932, 95% CI 2.467-9.858), > 2 CoNS-positive bottles from different BC sets (OR 1.957, 95% CI 1.401-2.733), and Charlson score ≥ 3 (OR 2.102, 95% CI 1.078-4.099). The algorithm with best sensitivity (62%) and specificity (93%) for determining clinical significance of CoNS included Charlson score ≥ 3, Pitt score ≥ 1, neutropenic patients, presence of central venous catheter, identification of S. epidermidis, and time to positivity < 16 h. The positive predictive value was 83% and the negative predictive value was 81% (likelihood ratio 8.87). CONCLUSION: The use of this algorithm could potentially reduce the misclassification of nosocomial bloodstream infections and inappropriate antibiotic treatment in patients for whom a positive CoNS does not represent a CSB.