Efficacy and safety of a structured de-escalation from antipseudomonal ß-lactams in bloodstream infections due to Enterobacterales (SIMPLIFY): an open-label, multicentre, randomised trial.

BACKGROUND: De-escalation from broad-spectrum to narrow-spectrum antibiotics is considered an important measure to reduce the selective pressure of antibiotics, but a scarcity of adequate evidence is a barrier to its implementation. We aimed to determine whether de-escalation from an antipseudomonal ß-lactam to a narrower-spectrum drug was non-inferior to continuing the antipseudomonal drug in patients with Enterobacterales bacteraemia. METHODS: An open-label, pragmatic, randomised trial was performed in 21 Spanish hospitals. Patients with bacteraemia caused by Enterobacterales susceptible to one of the de-escalation options and treated empirically with an antipseudomonal ß-lactam were eligible. Patients were randomly assigned (1:1; stratified by urinary source) to de-escalate to ampicillin, trimethoprim-sulfamethoxazole (urinary tract infections only), cefuroxime, cefotaxime or ceftriaxone, amoxicillin-clavulanic acid, ciprofloxacin, or ertapenem in that order according to susceptibility (de-escalation group), or to continue with the empiric antipseudomonal ß-lactam (control group). Oral switching was allowed in both groups. The primary outcome was clinical cure 3-5 days after end of treatment in the modified intention-to-treat (mITT) population, formed of patients who received at least one dose of study drug. Safety was assessed in all participants. Non-inferiority was declared when the lower bound of the 95% CI of the absolute difference in cure rate was above the -10% non-inferiority margin. This trial is registered with EudraCT (2015-004219-19) and ClinicalTrials.gov (NCT02795949) and is complete. FINDINGS: 2030 patients were screened between Oct 5, 2016, and Jan 23, 2020, of whom 171 were randomly assigned to the de-escalation group and 173 to the control group. 164 (50%) patients in the de-escalation group and 167 (50%) in the control group were included in the mITT population. 148 (90%) patients in the de-escalation group and 148 (89%) in the control group had clinical cure (risk difference 1·6 percentage points, 95% CI -5·0 to 8·2). The number of adverse events reported was 219 in the de-escalation group and 175 in the control group, of these, 53 (24%) in the de-escalation group and 56 (32%) in the control group were considered severe. Seven (5%) of 164 patients in the de-escalation group and nine (6%) of 167 patients in the control group died during the 60-day follow-up. There were no treatment-related deaths. INTERPRETATION: De-escalation from an antipseudomonal ß-lactam in Enterobacterales bacteraemia following a predefined rule was non-inferior to continuing the empiric antipseudomonal drug. These results support de-escalation in this setting. FUNDING: Plan Nacional de I+D+i 2013-2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases; Spanish Clinical Research and Clinical Trials Platform, co-financed by the EU; European Development Regional Fund "A way to achieve Europe", Operative Program Intelligence Growth 2014-2020.

Comparison of dalbavancin with standard of care in the management of infective endocarditis: efficacy, safety, and cost analysis.

OBJECTIVES: Due to its long half-life, dalbavancin offers benefits for long-duration treatments, especially osteoarticular and infective endocarditis (IE). We evaluated the efficacy and costs of IE treatment, comparing dalbavancin with standard of care (SOC). METHODS: Retrospective multicenter cohort study of adult patients with Gram-positive cocci definite IE. Dalbavancin was used as a sequential therapy before discharge. Efficacy was a combined variable of clinical cure and absence of recurrence in 12-month follow-up. Length of hospital stay and the associated costs were analyzed in both groups of treatment. RESULTS: Twenty-two patients received dalbavancin and 47 SOC. The efficacy was similar between the groups (dalbavancin 18 [72%] vs SOC 44 [94%], P = 0.198). Hospital stay was shorter in the dalbavancin group (dalbavancin 22 days [16-34] vs SOC 37 days [23-49], P = 0.001), especially in those with E. faecalis IE (dalbavancin 30 days [20-36] vs SOC 65 days [46-74], P <0.001). A reduction of cost was observed between both groups (dalbavancin, 12,206 € [8998-17,283] vs SOC 16,249 € [11,496-22,367], P = 0.032). CONCLUSION: Dalbavancin could be a safe and effective option in the sequential treatment of patients with IE. Also, a cost reduction was detected, due to a significant shortness of hospital stay.

Computing thickness of irregularly-shaped thin walls using a locally semi-implicit scheme with extrapolation to solve the Laplace equation: Application to the right ventricle.

Cardiac Magnetic Resonance (CMR) Imaging is currently considered the gold standard imaging modality in cardiology. However, it is accompanied by a tradeoff between spatial resolution and acquisition time. Providing accurate measures of thin walls relative to the image resolution may prove challenging. One such anatomical structure is the cardiac right ventricle. Methods for measuring thickness of wall-like anatomical structures often rely on the Laplace equation to provide point-to-point correspondences between both boundaries. This work presents limex, a novel method to solve the Laplace equation using ghost nodes and providing extrapolated values, which is tested on three different datasets: a mathematical phantom, a set of biventricular segmentations from CMR images of ten pigs and the database used at the RV Segmentation Challenge held at MICCAI'12. Thickness measurements using the proposed methodology are more accurate than state-of-the-art methods, especially with the coarsest image resolutions, yielding mean L1 norms of the error between 43.28% and 86.52% lower than the second-best methods on the different test datasets. It is also computationally affordable. Limex has outperformed other state-of-the-art methods in classifying RV myocardial segments by their thickness.

Cloxacillin plus fosfomycin versus cloxacillin alone for methicillin-susceptible Staphylococcus aureus bacteremia: a randomized trial.

Treatment failure occurs in about 25% of patients with methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. We assessed whether cloxacillin plus fosfomycin achieves better treatment success than cloxacillin alone in hospitalized adults with MSSA bacteremia. We conducted a multicenter, open-label, phase III-IV superiority randomized clinical trial. We randomly assigned patients (1:1) to receive 2 g of intravenous cloxacillin alone every 4 h or with 3 g of intravenous fosfomycin every 6 h for the initial 7 days. The primary endpoint was treatment success at day 7, a composite endpoint with the following criteria: patient alive, stable or with improved quick Sequential Organ Failure Assessment score, afebrile and with negative blood cultures for MSSA, adjudicated by an independent committee blinded to treatment allocation. We randomized 215 patients, of whom 105 received cloxacillin plus fosfomycin and 110 received cloxacillin alone. We analyzed the primary endpoint with the intention-to-treat approach in 214 patients who received at least 1 day of treatment. Treatment success at day 7 after randomization was achieved in 83 (79.8%) of 104 patients receiving combination treatment versus 82 (74.5%) of 110 patients receiving monotherapy (risk difference 5.3%; 95% confidence interval (CI), -5.95-16.48). Secondary endpoints, including mortality and adverse events, were similar in the two groups except for persistent bacteremia at day 3, which was less common in the combination arm. In a prespecified interim analysis, the independent committee recommended stopping recruitment for futility prior to meeting the planned randomization of 366 patients. Cloxacillin plus fosfomycin did not achieve better treatment success at day 7 of therapy than cloxacillin alone in MSSA bacteremia. Further trials should consider the intrinsic heterogeneity of the infection by using a more personalized approach. ClinicalTrials.gov registration: NCT03959345 .

Randomized Clinical Trial of the Need for Antibiotic Treatment for Low-Risk Catheter-Related Bloodstream Infection Caused by Coagulase-Negative Staphylococci.

According to clinical guidelines, the management of catheter-related bloodstream infections (CRBSI) due to coagulase-negative staphylococci (CoNS) includes catheter removal and antibiotic treatment for 5 to 7 days. However, in low-risk episodes, it remains uncertain whether antibiotic therapy is necessary. This randomized clinical trial aims to determine whether the non-administration of antibiotic therapy is as safe and effective as the recommended strategy in low-risk episodes of CRBSI caused by CoNS. With this purpose, a randomized, open-label, multicenter, non-inferiority clinical trial was conducted in 14 Spanish hospitals from 1 July 2019 to 31 January 2022. Patients with low-risk CRBSI caused by CoNS were randomized 1:1 after catheter withdrawal to receive/not receive parenteral antibiotics with activity against the isolated strain. The primary endpoint was the presence of any complication related to bacteremia or to antibiotic therapy within 90 days of follow-up. The secondary endpoints were persistent bacteremia, septic embolism, time until microbiological cure, and time until the disappearance of a fever. EudraCT: 2017-003612-39 INF-BACT-2017. A total of 741 patients were assessed for eligibility. Of these, 27 were included in the study; 15 (55.6%) were randomized to the intervention arm (non-antibiotic administration) and 12 (44.4%) to the control arm (antibiotic therapy as per standard practice). The primary endpoint occurred in one of the 15 patients in the intervention group (septic thrombophlebitis) and in no patients in the control group. The median time until microbiological cure was 3 days (IQR 1-3) in the intervention arm and 1.25 days (IQR 0.5-2.62) in the control arm, while the median time until fever resolution was zero days in both arms. The study was stopped due to the insufficient number of recruited patients. These results seem to indicate that low-risk CRBSI caused by CoNS can be managed without antibiotic therapy after catheter removal; efficacy and safety are not affected.

The Use and Effectiveness of Ceftazidime-Avibactam in Real-World Clinical Practice: EZTEAM Study.

INTRODUCTION: Ceftazidime-avibactam has proven activity against multidrug-resistant (MDR) bacteria in clinical trials and real-world studies. This study was conducted to describe the patterns of use of ceftazidime-avibactam (including indications and associated antibiotics), and the effectiveness and safety of ceftazidime-avibactam in real-world clinical practice. METHODS: This non-interventional medical chart review study was conducted in 11 countries across the European and Latin American (LATAM) regions. Consecutive patients treated in clinical practice with at least one dose of ceftazidime-avibactam for an approved indication per country label since 01 January 2018 (or launch date in the country if posterior) were enrolled. Effectiveness analyses were conducted in patients treated with ceftazidime-avibactam for at least 72 h. RESULTS: Of the 569 eligible patients enrolled, 516 (90.7%) were treated for at least 72 h (354 patients from Europe and 162 patients from LATAM); 390 patients (75.7%) had switched from another antibiotic line for Gram-negative coverage. Infection sources were intra-abdominal, urinary, respiratory, bloodstream infections, and other infections (approximately 20% each). K. pneumoniae was the most common microorganism identified in the latest microbiological evaluation before starting ceftazidime-avibactam (59.3%). Two-thirds of microorganisms tested for susceptibility were MDR, of which 89.3% were carbapenem-resistant. The common MDR mechanisms for K. pneumoniae were carbapenemase (33.9%), oxacillinase 48 (25.2%), extended-spectrum beta-lactamase (21.5%), or metallo-beta-lactamase (14.2%) production. Without prior patient exposure, 17 isolates (mostly K. pneumoniae) were resistant to ceftazidime-avibactam. Treatment success was achieved in 77.3% of patients overall (88.3% among patients with urinary infection), regardless of first or second treatment line. In-hospital mortality rate was 23.1%. Adverse events were reported for six of the 569 patients enrolled. CONCLUSION: This study provides important real-world evidence on treatment patterns, effectiveness, and safety of ceftazidime-avibactam in clinical practice through its recruitment in the European and LATAM regions. Ceftazidime-avibactam is one of the antibiotics to consider for treatment of MDR bacteria. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03923426.

Conventional Hospitalization versus Sequential Outpatient Parenteral Antibiotic Therapy for Staphylococcus aureus Bacteremia: Post-Hoc Analysis of a Multicenter Observational Cohort.

It is not known whether sequential outpatient parenteral antimicrobial (OPAT) is as safe and effective as conventional hospitalization in patients with S. aureus bacteremia (SAB). A post-hoc analysis of the comparative effectiveness of conventional hospitalization versus sequential OPAT was performed in two prospective Spanish cohorts of patients with S. aureus bacteremia. The PROBAC cohort is a national, multicenter, prospective observational cohort of patients diagnosed in 22 Spanish hospitals between October 2016 and March 2017. The DOMUS OPAT cohort is a prospective observational cohort including patients from two university hospitals in Seville, Spain from 2012 to 2021. Multivariate regression was performed, including a propensity score (PS) for receiving OPAT, stratified analysis according to PS quartiles, and matched pair analyses based on PS. Four hundred and thirteen patients were included in the analysis: 150 in sequential OPAT and 263 in the full hospitalization therapy group. In multivariate analysis, including PS and center effect as covariates, 60-day treatment failure was lower in the OPAT group than in the full hospitalization group (p < 0.001; OR 0.275, 95%CI 0.129−0.584). In the PS-based matched analyses, sequential treatment under OPAT was not associated with higher 60-day treatment failure (p = 0.253; adjusted OR 0.660; % CI 0.324−1.345). OPAT is a safe and effective alternative to conventional in-patient therapy for completion of treatment in well-selected patients with SAB, mainly those associated with a low-risk source and without end-stage kidney disease.

Risk factors for Gram-negative bacterial infection of cardiovascular implantable electronic devices: multicentre observational study (CarDINe Study).

BACKGROUND: Infections of cardiovascular implantable electronic devices (CIED) are mainly due to Gram-positive bacteria (GPB). Data about Gram-negative bacteria CIED (GNB-CIED) infections are limited. This study aimed to investigate risk factors, clinical and diagnostic characteristics, and outcome of patients with GNB-CIED. METHODS: A multicentre, international, retrospective, case-control-control study was performed on patients undergoing CIED implantation from 2015 to 2019 in 17 centres across Europe. For each patient diagnosed with GNB-CIED, one matching control with GPB-CIED infection and two matching controls without infection were selected. RESULTS: A total of 236 patients were enrolled: 59 with GNB-CIED infection, 59 with GPB-CIED infection and 118 without infection. No between-group differences were found regarding clinical presentation, diagnostic and therapeutic management. A trend toward a higher rate of fluorodeoxyglucose positron emission computed tomography (FDG PET/CT) positivity was observed among patients with GNB than in those with GPB-CIED infection (85.7% vs. 66.7%; P = 0.208). Risk factors for GNB-CIED infection were Charlson Comorbidity Index Score (relative risk reduction, RRR = 1.211; P = 0.011), obesity (RRR = 5.122; P = 0.008), ventricular-pacing ventricular-sensing inhibited-response pacemaker implantation (RRR = 3.027; P = 0.006) and right subclavian vein site of implantation (RRR = 5.014; P = 0.004). At 180-day survival analysis, GNB-CIED infection was associated with increased mortality risk (HR = 1.842; P = 0.067). CONCLUSIONS: Obesity, high number of comorbidities and right subclavian vein implantation site were associated with increased risk of GNB-CIED infection. A prompt therapeutic intervention that may be guided using FDG PET/CT is suggested in patients with GNB-CIED infection, considering the poorer outcome observed in this group.

Antimicrobial stewardship in hospitals: Expert recommendation guidance document for activities in specific populations, syndromes and other aspects (PROA-2) from SEIMC, SEFH, SEMPSPGS, SEMICYUC and SEIP.

In 2012, The Spanish Societies of Infectious Diseases and Clinical Microbiology (SEIMC), Hospital Pharmacy (SEFH), and Preventive Medicine, Public Health and Healthcare Management (SEMPSGS) lead a consensus document including recommendations for the implementation of antimicrobial stewardship (AMS) programs (AMSP; PROA in Spanish) in acute care hospitals in Spain. While these recommendations were critical for the development of these programs in many centres, there is a need for guidance in the development of AMS activities for specific patient populations, syndromes or other specific aspects which were not included in the previous document or have developed significantly since then. The objective of this expert recommendation guidance document is to review the available information about these activities in these patient populations or circumstances, and to provide guidance recommendations about them. With this objective the SEIMC, SEFH, SEMPSPGS, the Spanish Society of Intensive Care Medicine (SEMICYUC) and the Spanish Pediatric Infectious Disease Society (SEIP) selected a panel of experts who chose the different aspects to include in the document. Because of the lack of high-level evidence in the implementation of the activities, the panel opted to perform a narrative review of the literature for the different topics for which recommendations were agreed by consensus. The document was open to public consultation for the members of these societies for their comments and suggestions, which were reviewed and considered by the panel.

Documento de opinión de expertos para la mejora de la cobertura vacunal frente a la gripe estacional / Expert opinion on strategies to improve vaccination coverage against seasonal influenza

La gripe estacional sigue siendo un importante problema de salud pública, y la vacuna antigripal es la medida más efectiva para su prevención. En nuestro país, los datos de coberturas vacunales de las últimas temporadas muestran unas tasas de vacunación muy por debajo de los objetivos marcados por los organismos oficiales. Tras la pandemia de la COVID19, las coberturas vacunales para la gripe han experimentado una notable mejoría. Dado que resulta imperativo alcanzar y mantener unas elevadas tasas de vacunación con el fin de evitar el impacto clínico y económico de la gripe, un grupo multidisciplinar de expertos en el área de las vacunas hemos analizado cómo afectan las bajas coberturas en nuestro país y hemos diseñado una serie de medidas para incrementar la cobertura vacunal de la gripe, especialmente en los colectivos definidos como prioritarios. (AU)

Seasonal flu continues to be a major public health concern, and the influenza vaccine remains the most effective preventive measure. In Spain, vaccination coverage data from previous seasons show vaccination rates well below official targets; however, these figures improved significantly after the COVID-19 pandemic. Given the importance of achieving and maintaining high vaccination rates in order to avoid the clinical and economic impact of influenza, our multidisciplinary group of experts on vaccines analyzed the impact of low vaccination rates in Spain and drafted a series of measures to boost influenza vaccination coverage, particularly among priority groups. (AU)

Cerebrospinal fluid drainage-related ventriculitis due to multidrug-resistant microorganisms.

INTRODUCTION: The aim of the study was to analyze the clinical and microbiological characteristics of adult patients with cerebrospinal fluid (CSF) drainage-related ventriculitis. METHODS: Retrospective study from January 2010 to June 2019 performed in the Complexo Hospitalario Universitario de Vigo (Spain). Cases of CSF drainage-related ventriculitis in patients ≥18-year-old were gathered. Clinical characteristics of patients, type of drainage devices, management and microbiological isolates were analyzed. RESULTS: Ninety-one episodes of CSF drainage-related ventriculitis were identified. The most frequent organisms isolated were Gram-positive cocci (65%), mainly Staphylococcus epidermidis (48%). Multidrug-resistant microorganisms were detected in 21 episodes (23%). In multivariate analysis, the independent factors related with multidrug-resistant ventriculitis were the length of hospital stay >14 days (HR 6.7; 95%CI 1.75-25.86, p=0.006) and previous antimicrobial therapy (HR 5.58; 95%CI 1.44-21.65, p=0.013). CONCLUSIONS: Our study shows a large number of drainage-related ventriculitis episodes caused by multidrug-resistant organisms and reinforce the importance of a judicious use of antibiotics.

Cerebrospinal fluid drainage-related ventriculitis due to multidrug-resistant microorganisms / Ventriculitis asociadas a dispositivos de drenaje de líquido cefalorraquídeo causadas por microorganismos multirresistentes

Introduction: The aim of the study was to analyze the clinical and microbiological characteristics of adult patients with cerebrospinal fluid (CSF) drainage-related ventriculitis. Methods: Retrospective study from January 2010 to June 2019 performed in the Complexo Hospitalario Universitario de Vigo (Spain). Cases of CSF drainage-related ventriculitis in patients ≥18-year-old were gathered. Clinical characteristics of patients, type of drainage devices, management and microbiological isolates were analyzed. Results: Ninety-one episodes of CSF drainage-related ventriculitis were identified. The most frequent organisms isolated were Gram-positive cocci (65%), mainly Staphylococcus epidermidis (48%). Multidrug-resistant microorganisms were detected in 21 episodes (23%). In multivariate analysis, the independent factors related with multidrug-resistant ventriculitis were the length of hospital stay >14 days (HR 6.7; 95%CI 1.75–25.86, p=0.006) and previous antimicrobial therapy (HR 5.58; 95%CI 1.44–21.65, p=0.013). Conclusions: Our study shows a large number of drainage-related ventriculitis episodes caused by multidrug-resistant organisms and reinforce the importance of a judicious use of antibiotics.(AU)

Introducción: El objetivo del estudio fue analizar las características clínicas y microbiológicas de pacientes adultos con ventriculitis asociada a dispositivos de drenaje de líquido cefalorraquídeo (VaD-LCR). Métodos: Estudio retrospectivo entre enero de 2010 y junio de 2019 realizado en el Complexo Hospitalario Universitario de Vigo (España). Se recogieron los casos de VaD-LCR y se analizaron las características clínicas, los tipos de drenaje, el tratamiento y los aislamientos microbiológicos. Resultados: Se identificaron 99 episodios de VaD-LCR. Los microorganismos más frecuentemente aislados fueron los cocos grampositivos (65%), principalmente Staphylococcus epidermidis (48%). Se detectaron microorganismos multirresistentes en 21 episodios (23%). En el análisis multivariante, los factores asociados con VaD-LCR por cepas multirresistentes fueron la estancia hospitalaria >14días (HR: 6,7; IC95%: 1,75-25,86; p=0,006) y el uso previo de antibióticos (HR: 5,58; IC95%: 1,44-21,65; p=0,013). Conclusiones: En nuestro estudio la tasa de VaD-LCR causada por bacterias multirresistentes fue elevada. Estos datos refuerzan la importancia del uso adecuado de antibióticos.(AU)

Oral sequential therapy in the treatment of post-surgical epidural abscess and subdural empyema.

PURPOSE: The management of post-surgical subdural empyema and subdural abscess is not standardised. The objective was to analyse the efficacy and safety of oral sequential therapy (OST). METHODS: Retrospective observational study in a tertiary hospital in Vigo (Spain). We included adult patients with subdural abscess or epidural empyema with microbiological isolation. Clinical and demographic variables, isolated microorganisms and treatment regimens were included, as well as mortality and adverse effects during the follow-up period. RESULTS: Thirty patients were reviewed, two died due to causes other than infection. Six-month recurrence rate was 2/28 and all other patients (26/28) had clinical cure at the end of the treatment. The commonest isolated microorganisms were Gram-positive, especially Staphylococcus aureus. The most widely used oral antibiotic was trimethoprim-sulfamethoxazole (80%). No side effects related to oral treatment were observed. CONCLUSION: After adequate source control, OST can be a safe practice in the management of post-surgical epidural abscess and subdural empyema.

Clinical characteristics, aetiology and mortality/recurrence risk factors of acute cholangitis in patients with and without biliary stent.

OBJECTIVES: Acute cholangitis is one of the most frequent complications in patients carrying biliary stents. The aim of our study is to analyze the demographic and clinical characteristics, as well as the microbiological profile and evolution of patients with acute bacteremic cholangitis, comparing them based upon they were or not biliary stent carriers. METHODS: We performed a retrospective analysis of all consecutive patients over 18 years-old with a stent placement in our center between 2008 and 2017 were included. We compared them with our prospective cohort of patients with a diagnosis of acute bacteremic cholangitis. Primary outcome was 30-day mortality. Secondary outcome was clinical cure at day 7, 14-day mortality and 90-day recurrence. RESULTS: Two hundred and seventy-three patients were analyzed, including 156 in the stent-related (SR) and 117 in the stent not-related (SNR) group, respectively. Stent-related colangitis patients were younger, with more comorbidities and with a greater severity of infection. Escherichia coli and Klebsiella pneumonia were the most frequent isolation. Enterococcus spp. was the third most frequent isolation in SR group but were uncommon in SNR patients; where E. coli was the most prevalent microorganism. Septic shock (HR 3.44, 95% [CI 1.18-8.77]), inadequate empirical treatment (HR 2.65, 95% CI [1.38-.7.98]) and advanced neoplasia (HR 2.41, 95% CI [1.55-6.44]) were independent 30-day mortality risk factors. The 90-day recurrence rate significantly higher in those patients with stent-related cholangitis (29% vs. 13%, p=0.016) and stent replacement was associated with lower recurrence rate (HR 0.38, 95% CI [0.11-0.77]). CONCLUSIONS: Clinical and microbiological profile, as well as outcome of patients with SR and SNR cholangitis were different. In SR group, recurrence rate was high and stent replacement was associated with a lower risk.

Clinical characteristics, aetiology and mortality/recurrence risk factors of acute cholangitis in patients with and without biliary stent / Características clínicas, etiología y factores de riesgo de mortalidad/recidiva de la colangitis bacteriana aguda en pacientes con y sin stent biliar

Objectives: Acute cholangitis is one of the most frequent complications in patients carrying biliary stents. The aim of our study is to analyze the demographic and clinical characteristics, as well as the microbiological profile and evolution of patients with acute bacteremic cholangitis, comparing them based upon they were or not biliary stent carriers. Methods: We performed a retrospective analysis of all consecutive patients over 18 years-old with a stent placement in our center between 2008 and 2017 were included. We compared them with our prospective cohort of patients with a diagnosis of acute bacteremic cholangitis. Primary outcome was 30-day mortality. Secondary outcome was clinical cure at day 7, 14-day mortality and 90-day recurrence. Results: Two hundred and seventy-three patients were analyzed, including 156 in the stent-related (SR) and 117 in the stent not-related (SNR) group, respectively. Stent-related colangitis patients were younger, with more comorbidities and with a greater severity of infection. Escherichia coli and Klebsiella pneumonia were the most frequent isolation. Enterococcus spp. was the third most frequent isolation in SR group but were uncommon in SNR patients; where E. coli was the most prevalent microorganism. Septic shock (HR 3.44, 95% [CI 1.18–8.77]), inadequate empirical treatment (HR 2.65, 95% CI [1.38–.7.98]) and advanced neoplasia (HR 2.41, 95% CI [1.55–6.44]) were independent 30-day mortality risk factors. The 90-day recurrence rate significantly higher in those patients with stent-related cholangitis (29% vs. 13%, p=0.016) and stent replacement was associated with lower recurrence rate (HR 0.38, 95% CI [0.11–0.77]). Conclusions: Clinical and microbiological profile, as well as outcome of patients with SR and SNR cholangitis were different. In SR group, recurrence rate was high and stent replacement was associated with a lower risk.(AU)

Objetivos: La colangitis aguda es una de las complicaciones más frecuentes en los pacientes portadores de stents biliares. El objetivo de nuestro estudio es analizar las características demográficas y clínicas, así como el perfil microbiológico y la evolución de los pacientes con colangitis bacteriana aguda, comparándolos en función de si eran o no portadores de stents biliares. Métodos: Se realizó un análisis retrospectivo de todos los pacientes consecutivos mayores de 18 años con un stent colocado en nuestro centro entre 2008 y 2017. Los comparamos con nuestra cohorte prospectiva de pacientes con diagnóstico de colangitis bacteriana aguda. El criterio principal de valoración fue la mortalidad a los 30 días. Los criterios secundarios de valoración fueron la curación clínica el día 7, la mortalidad a los 14 días y la recidiva a los 90 días. Resultados: Se analizaron 273 pacientes, incluyendo 156 en el grupo relacionado con el stent (RS) y 117 en el grupo no relacionado con el stent (NRS). Los pacientes con colangitis RS eran más jóvenes, con más enfermedades concomitantes y con una mayor intensidad de la infección. Las cepas aisladas más frecuentes fueron Escherichia coli y Klebsiellapneumoniae. Enterococcus spp. fue la tercera cepa aislada más frecuente en el grupo RS, pero no fue frecuente en los pacientes NRS, en los que E. coli fue el microorganismo más prevalente. El choque septicémico (HR: 3,44; IC del 95%: 1,18-8,77), el tratamiento empírico inadecuado (HR: 2,65; IC del 95%: 1,38-7,98) y la neoplasia avanzada (HR: 2,41; IC del 95%: 1,55-6,44) fueron factores de riesgo de mortalidad a los 30 días independientes. La tasa de recidiva a los 90 días fue significativamente más elevada en aquellos pacientes con colangitis RS (29 frente al 13%; p=0,016) y el reemplazo del stent se asoció a una menor tasa de recidiva (HR: 0,38; IC del 95%: 0,11-0,77).(AU)

Multicentre, randomised, open-label, phase IV-III study to evaluate the efficacy of cloxacillin plus fosfomycin versus cloxacillin alone in adult patients with methicillin-susceptible Staphylococcus aureus bacteraemia: study protocol for the SAFO trial.

INTRODUCTION: Methicillin-susceptible Staphylococcus 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 against S. 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.

Long-term antibiotic therapy in patients with surgery-indicated not undergoing surgery infective endocarditis.

BACKGROUND: To date, there is little information regarding management of patients with infective endocarditis (IE) that did not undergo an indicated surgery. Therefore, we aimed to evaluate prognosis of these patients treated with a long-term antibiotic treatment strategy, including oral long term suppressive antibiotic treatment in five referral centres with a multidisciplinary endocarditis team. METHODS: This retrospective, multicenter study retrieved individual patient-level data from five referral centres in Spain. Among a total of 1797, 32 consecutive patients with IE were examined (median age 72 years; 78% males) who had not undergone an indicated surgery, but received long-term antibiotic treatment (LTAT) and were followed by a multidisciplinary endocarditis team, between 2011 and 2019. Primary outcomes were infection relapse and mortality during follow-up. RESULTS: Among 32 patients, 21 had IE associated with prostheses. Of the latter, 8 had an ascending aorta prosthetic graft. In 24 patients, a switch to long-term oral suppressive antibiotic treatment (LOSAT) was considered. The median duration of LOSAT was 277 days. Four patients experienced a relapse during follow-up. One patient died within 60 days, and 12 patients died between 60 days and 3 years. However, only 4 deaths were related to IE. CONCLUSIONS: The present study results suggest that a LTAT strategy, including LOSAT, might be considered for patients with IE that cannot undergo an indicated surgery. After hospitalization, they should be followed by a multidisciplinary endocarditis team.

Mortality-related factors in patients with OXA-48 carbapenemase-producing Klebsiella pneumoniae bacteremia.

ABSTRACT: Carbapenemase-producing Enterobacterales constitute a serious public health threat; however, information on the oxacilinasa (OXA-48)-type is limited. The objective of the study was to evaluate the risk factors associated with 14-day mortality for patients with bacteremia due to OXA-48 carbapenemase-producing Klebsiella pneumoniae.We conducted a retrospective, single-center observational study of adult patients with K. pneumoniae bacteremia, classifying the strains as carbapenem-susceptible K. pneumoniae (CSKp) and carbapenem-resistant K. pneumoniae (CRKp). All of the CRKp strains were the OXA-48-type.The study included 202 cases of bacteremia: 114 due to CSKp and 88 due to CRKp. The clinical cure rate was higher for the patients with CSKp (85% vs 69% for CSKp and CRKp, respectively; P = .010), while the 14-day mortality rate was lower (13% vs 30%, P = .005). An INCREMENT-CPE score ≥7 (HR 3.05, 95% CI 1.50-6.25, P = .002) was the only independent factor associated with 14-day mortality for the patients with Klebsiella spp. bacteremia. Other factors related to 14-day mortality were a rapidly fatal prognosis (McCabe) (HR 7.1, 95% CI 2.75-18.37, P < .001), dementia (HR 5.9, 95% CI 2.0-7.43, P = .001), and a high-risk source of infection (HR 2.7, 95% CI 1.06-6.82, P = .038).The most important factors associated with 14-day mortality for the patients with K. pneumoniae bacteremia was an INCREMENT-CPE score ≥7, dementia, a McCabe score indicating a rapidly fatal prognosis and a high-risk source of infection. We found no relationship between a poorer outcome and CRKp isolation or inadequate antibiotic therapy.

Cerebrospinal fluid drainage-related ventriculitis due to multidrug-resistant microorganisms.

INTRODUCTION: The aim of the study was to analyze the clinical and microbiological characteristics of adult patients with cerebrospinal fluid (CSF) drainage-related ventriculitis. METHODS: Retrospective study from January 2010 to June 2019 performed in the Complexo Hospitalario Universitario de Vigo (Spain). Cases of CSF drainage-related ventriculitis in patients ≥18-year-old were gathered. Clinical characteristics of patients, type of drainage devices, management and microbiological isolates were analyzed. RESULTS: Ninety-one episodes of CSF drainage-related ventriculitis were identified. The most frequent organisms isolated were Gram-positive cocci (65%), mainly Staphylococcus epidermidis (48%). Multidrug-resistant microorganisms were detected in 21 episodes (23%). In multivariate analysis, the independent factors related with multidrug-resistant ventriculitis were the length of hospital stay >14 days (HR 6.7; 95%CI 1.75-25.86, p=0.006) and previous antimicrobial therapy (HR 5.58; 95%CI 1.44-21.65, p=0.013). CONCLUSIONS: Our study shows a large number of drainage-related ventriculitis episodes caused by multidrug-resistant organisms and reinforce the importance of a judicious use of antibiotics.