Outcomes and clinical characteristics of the compassionate use of plitidepsin in COVID-19 patients with solid tumours, haematological malignancies or anti-CD20 antibody treatment.

OBJECTIVE: To study the effect of plitidepsin antiviral treatment in immunocompromised COVID-19 patients with underlying haematological malignancies or solid tumours, particularly those who have undergone anti-CD20 therapies. DESIGN: We conducted a retrospective observational study, involving 54 adults treated with plitidepsin on compassionate use as an antiviral drug. Our analysis compared outcomes between patients with solid tumours and those with haematological malignancies, and a cohort of cases treated or not with anti-CD20 monoclonal antibodies. RESULTS: Patients with a history of anti-CD20 therapies showed a prolonged time-to-negative RT-PCR for SARS-CoV-2 infection compared to non-treated patients (33 d (28;75) vs 15 (11;25); p = .002). Similar results were observed in patients with solid tumours in comparison to those with haematological malignancies (13 (10;16) vs 26 (17;50); p < .001). No serious adverse events were documented. CONCLUSIONS: Patients with haematological malignancies appear to be at a heightened risk for delayed SARS-CoV-2 clearance and subsequent clinical complications. These findings support plitidepsin as a well-tolerated treatment in this high-risk group. A phase II clinical trial (NCT05705167) is ongoing to evaluate plitidepsin as an antiviral drug in this population.KEY POINTSHaematological patients face an increased risk for severe COVID-19.Anti-CD20 therapies could increase fatal outcomes in COVID-19 patients.Persistent viral replication is increased in immunocompromised patients.Plitidepsin does not lead to new serious adverse events in immunocompromised patients.

Integrase strand transfer inhibitor resistance mediated by R263K plus E157Q in a patient with HIV infection treated with bictegravir/tenofovir alafenamide/emtricitabine: case report and review of the literature.

OBJECTIVES: The in vivo selection of E157Q plus R263K has not been reported in patients treated with coformulated bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). To the best of our knowledge, we hereby report the first case of high-grade INSTI resistance associated with the presence of these aminoacidic substitutions in a treatment-experienced HIV patient treated with BIC/FTC/TAF. METHODS: Clinical case report and review of the literature. RESULTS: A heavily treatment-experienced patient was switched to BIC/FTC/TAF due to drug-drug interactions after being diagnosed with disseminated Mycobacterium avium-intracellulare disease. He had been treated before with raltegravir with poor adherence. No mutations in the integrase gene were detected 1 year after finishing treatment with raltegravir. Months after being switched to BIC/FTC/TAF, and again with poor adherence documented, virological failure (VF) was detected. The polymorphic substitution E157Q and the resistance mutation R263K in the integrase gene were detected, as well as M184V, among other mutations in the reverse transcriptase gene. The patient is currently being treated with dolutegravir q12h plus boosted darunavir along with directly observed treatment, and for the first time in 20 years, plasmatic viral load values are below 100 copies/mL. CONCLUSIONS: This case illustrates that the combination of E157Q and R263K plus M184V can be selected in vivo in a clinical scenario of poor adherence with BIC/FTC/TAF, although it is a very rare phenomenon. Previous VF with first-generation integrase strand transfer inhibitors (INSTIs) should be kept in mind when switching patients to second-generation INSTIs.

Real Life Clinical Impact of Antimicrobial Stewardship Actions on the Blood Culture Workflow from a Microbiology Laboratory.

BACKGROUND: Accelerating the diagnosis of bacteremia is one of the biggest challenges in clinical microbiology departments. The fast establishment of a correct treatment is determinant on bacteremic patients' outcomes. Our objective was to evaluate the impact of antimicrobial therapy and clinical outcomes of a rapid blood culture workflow protocol in positive blood cultures with Gram-negative bacilli (GNB). METHODS: A quasi-experimental before-after study was performed with two groups: (i) control group (conventional work-protocol) and (ii) intervention group (rapid workflow-protocol: rapid identification by Matrix-Assisted Laser Desorption/Ionization-Time-Of-Flight (MALDI-TOF) and antimicrobial susceptibility testing (AST) from bacterial pellet without overnight incubation). Patients were divided into different categories according to the type of intervention over treatment. Outcomes were compared between both groups. RESULTS: A total of 313 patients with GNB-bacteremia were included: 125 patients in the control group and 188 in the intervention. The time from positive blood culture to intervention on antibiotic treatment decreased from 2.0 days in the control group to 1.0 in the intervention group (p < 0.001). On the maintenance of correct empirical treatment, the control group reported 2.0 median days until the clinical decision, while in the intervention group was 1.0 (p < 0.001). In the case of treatment de-escalation, a significant difference between both groups (4.0 vs. 2.0, p < 0.001) was found. A decreasing trend on the change from inappropriate treatments to appropriate ones was observed: 3.5 vs. 1.5; p = 0.12. No significant differences were found between both groups on 7-days mortality or on readmissions in the first 30-days. CONCLUSIONS: Routine implementation of a rapid workflow protocol anticipates the report of antimicrobial susceptibility testing results in patients with GNB-bacteremia, decreasing the time to effective and optimal antibiotic therapy.

Intestinal co-colonization with different carbapenemase-producing Enterobacterales isolates is not a rare event in an OXA-48 endemic area.

BACKGROUND: The current spread of carbapenemase-producing Enterobacterales (CPE) is a great concern. METHODS: We recovered 198 CPE from 162 patients admitted in our Hospital (March 2014-March 2016) during the R-GNOSIS European Project. Microbiological features and plasmid characteristics of CPE recovered from patients co-colonized with multiple CPE were studied. FINDINGS: Thirty patients (18.5%; CI 95%= 12.5%-24.5%) presented co-colonization with multiple CPE producing the same (CPE-SC) (15.4%) or a different carbapenemase (CPE-DC) (4.3%). OXA-48 (83.3%) was the most frequent carbapenemase, followed by VIM-1 (26.7%), NDM-1 (10%) and KPC-3 (3.3%). CPE-DC-patients had longer admissions [63 days (20-107)] than the other patients. Moreover, hospital stay until CPE detection was lower [9 days (5-14)] (p = 0.0052) in CPE-SC-patients than in those with a single colonization; 56% showed co-colonization in the first positive sample, although most of them had previous admissions and had received multiple antibiotic treatments. CPE were more frequently recovered in clinical samples from co-colonized [CPE-DC (28.6%), CPE-SC (24%)] patients than from patients with a single CPE (15.2%). Among CPE-SC-OXA-48 [80% (p = 0.11)], K. pneumoniae [88% (p = 0.006)] and E. coli [84% (p < 0.001)] were the most frequent species. In 60% of patients, K. pneumoniae and E. coli species were simultaneously recovered, frequently after a single OXA-48-K. pneumoniae colonization. High-risk clones (ST11, ST15, ST307) were detected in OXA-48-K. pneumoniae but a higher clonal diversity was found among E. coli. A frequent in-vivo cross-species plasmid transmission was shown, due to a dominant plasmid (IncL-pOXA-48), but also involving related or unrelated bla VIM-1-, bla NDM-1- and bla KPC-3-encoding plasmids. INTERPRETATION: CPE co-colonization status should be monitored during epidemiological surveillance cultures, as these patients might be at a higher risk for infection. FUNDING: European Commission Framework Programme 7 and Instituto de Salud Carlos III, Spain.

Outbreak of NDM-1+CTX-M-15+DHA-1-producing Klebsiella pneumoniae high-risk clone in Spain owing to an undetectable colonised patient from Pakistan.

Here we describe an outbreak due to NDM-1+CTX-M-15+DHA-1-producing Klebsiella pneumoniae (NDM-1-Kp) in Spain related to a patient previously admitted to a healthcare centre in an endemic area (Pakistan). Nine colonised patients were detected in the Neurosurgery ward between September 2015 and February 2016 during the R-GNOSIS European Project. NDM-1-Kp isolates from clinical samples were also recovered in three of these patients. Surveillance culture at admission was negative in the index case, but NDM-1-Kp colonisation was detected 27 days later after receiving antibiotic treatment. Co-colonisation with a second NDM-1-Kp isolate was identified in this patient 61 days post-admission. Overall length of stay (LOS = 75 days) (P < 0.01) and LOS until carbapenemase detection (LOS-1 = 36 days) was longer in NDM-1-Kp carriers than in patients with other carbapenemase-producing Enterobacterales. Intervention strategies were implemented after the outbreak declaration and NDM-1-Kp transmission was contained. Among the NDM-1-Kp isolates, two clones [ST437 (index case and Patient 2) and ST101 (index case and Patients 3-9)] with different IncFIB NDM-1-containing plasmids were identified. Whole-genome sequencing revealed a high content of antimicrobial resistance genes in both isolates in addition to a large number of virulence factors. Colonisation with other epidemic (OXA-48-ST11-K. pneumoniae and VIM-1-ST54-K. pneumoniae) and non-epidemic (VIM-1-ST908-K. pneumoniae and VIM-ST431-Escherichia coli) clones was also detected in two NDM-1 carriers. Implementation of adequate infection control measures and uninterrupted active surveillance programmes for detecting patients with a low colonisation status are crucial to prevent the introduction and dissemination of NDM-type enzymes in our region.

Hypermucoviscous Klebsiella pneumoniae: A challenge in community acquired infection.

In 1986, a new syndrome was described in Taiwan secondary to hypervirulent K. pneumoniae (hvKP), and its main feature was the ability to cause severe infection in young and immunocompetent hosts. Their virulence is explained by the efficient acquisition of iron and an increase in capsule production, which confer the characteristic hypermucoviscous phenotype. Most of these cases have been described in Asia and subsequently spread to America and Europe, where their prevalence is much lower. We present four cases of bacteremia and liver abscesses secondary to hypervirulent K. pneumoniae, two of them associated with endophthalmitis. K. pneumoniae isolates recovered from two of the patients belonged to capsular serotype K1 (genes wzx_K1 and magA), while the other two were K2 (gene wzy_K2). Both of the K1 isolates were classified into a ST23, and isolates of serotype K2 belonged to the ST375 and ST881 clones. In Europe, hvKP isolates are less frequently recovered, mostly associated with Asian citizens or travelers, which was not the case in our patients. K1 capsular serotype is a major cause of primary liver abscess and secondary septic embolus, and K2 is associated with secondary liver abscess. Although these hypervirulent variants usually affect immunocompetent patients as in our cases, diabetes mellitus is a major risk factor for the most invasive cases, with concomitant poor prognosis. Identification of hypervirulent K. pneumoniae serotypes K1 and K2 should be considered as part of the microbiological diagnosis of community-acquired liver abscess due to their clinical implications.

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.

The what, when and how in performing and interpreting microbiological diagnostic tests in skin and soft tissue infections.

PURPOSE OF REVIEW: To summarize and classify the most recent and relevant microbiological studies for each type of skin and soft tissue infection (SSTI). RECENT FINDINGS: Following Infectious Diseases Society of America and Food and Drug Administration classifications of SSTIs, we differentiate between two large groups, the superficial or uncomplicated infections and the complicated infections with deep involvement. It is not usually necessary to obtain microbiological samples in uncomplicated infections, except in cases of recurrences or for epidemiological control purposes. In the case of complicated infections, the samples are of two different types: those obtained from the affected area (surgical samples, punctures of abscesses or swabs) and systemic samples (i.e. blood cultures). The clinical condition also determines the type of samples to be obtained. In cases of systemic involvement, blood cultures are mandatory. For immunocompromised patients, who may present atypical infections, detection of antigens, serologies or molecular biology techniques may be helpful. The rapid diagnosis is currently the goal to be pursued by implementing techniques such as matrix assisted laser desorption ionization-time of flight, commercial real-time PCR or the promising metagenomics. SUMMARY: Microbiological diagnosis is one of the cornerstones of the management of SSTIs. Prompt obtaining and processing of the necessary samples, depending on the clinical situation of the patient, is of relevance in the decision-making process. Rapid and fluid reporting of the results (identification, mechanisms of resistance and antibiogram) will improve the management of these patients.

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.

Diagnosis and antimicrobial treatment of invasive infections due to multidrug-resistant Enterobacteriaceae. Guidelines of the Spanish Society of Infectious Diseases and Clinical Microbiology / / Diagnóstico y tratamiento de las infecciones invasivas causadas por Enterobacteriaceae multirresistentes. Guía de la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica

The spread of multidrug-resistant Enterobacteriaceae related to the production of extended-spectrum beta-lactamases and carbapenemases is a serious public health problem worldwide. Microbiological diagnosis and therapy of these infections are challenging and controversial. Clinically relevant questions were selected and the literature was reviewed for each of them. The information from the selected articles was extracted and recommendations were provided and graded according to the strength of the recommendations and quality of the evidence. The document was opened to comments from the members from the Spanish Society of Infectious Diseases and Clinical Microbiology, which were considered for inclusion in the final version. Evidence-based recommendations are provided for the use of microbiological techniques for the detection of extended-spectrum beta-lactamases and carbapenemases in Enterobacteriaceae, and for antibiotic therapy for invasive/severe infections caused by these organisms. The absence of randomised controlled trials is noteworthy; thus, recommendations are mainly based on observational studies (that have important methodological limitations), pharmacokinetic and pharmacodynamics models, and data from animal studies. Additionally, areas for future research were identified

La diseminación de Enterobacteriaceae multirresistentes en relación con la producción de beta-lactamasas de espectro extendido y carbapenemasas es un importante problema de salud pública en todo el mundo. Tanto el diagnóstico microbiológico como el tratamiento de estas infecciones son complicados y controvertidos. Los autores seleccionaron preguntas clínicamente relevantes, realizándose una revisión de la literatura para cada una de ellas; se obtuvo información de los artículos seleccionados y se realizaron recomendaciones que se clasificaron de acuerdo con la fuerza de la recomendación y la calidad de la evidencia. El documento estuvo abierto para los comentarios de los socios de la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica, los cuales se consideraron para su inclusión en la versión final. Se proporcionan recomendaciones basadas en la evidencia para el uso de técnicas microbiológicas cara a la detección de beta-lactamasas de espectro extendido y carbapenemasas en Enterobacteriaceae, y para el tratamiento antimicrobiano de las infecciones graves o invasivas causadas por estos microorganismos. Es llamativa la ausencia de ensayos aleatorizados, por lo que las recomendaciones se basan principalmente en estudios observacionales que tienen importantes limitaciones metodológicas, modelos farmacocinéticos y farmacodinámicos, y datos de estudios en animales. Además, se identificaron áreas prioritarias para la investigación futura

Executive summary of the diagnosis and antimicrobial treatment of invasive infections due to multidrug-resistant Enterobacteriaceae. Guidelines of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) / / Resumen ejecutivo del diagnóstico y tratamiento de infecciones invasivas causadas por Enterobacteriaceae multirresistentes. Guía de la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica (SEIMC)

The spread of multidrug-resistant Enterobacteriaceae related to the production of extended-spectrum beta-lactamases (ESBL) and carbapenemases is a serious public health problem worldwide. Microbiological diagnosis and therapy of these infections are challenging and controversial. After the selection of clinically relevant questions, this document provides evidence-based recommendations for the use of microbiological techniques for the detection of ESBL- and carbapenemase-producing Enterobacteriaceae, and for antibiotic therapy for invasive infections caused by these organisms. The absence of randomized-controlled trials is noteworthy, thus recommendations are mainly based on observational studies, that have important methodological limitations, pharmacokinetic and pharmacodynamics models, and data from animal studies. Additionally, areas for future research were identified

La diseminación de Enterobacteriaceae multirresistentes en relación con la producción de beta-lactamasas de espectro extendido (BLEE) y carbapenemasas es un importante problema de salud pública en todo el mundo. Tanto el diagnóstico microbiológico como el tratamiento de estas infecciones son complicados y controvertidos. Tras una selección de preguntas clínicamente relevantes, este documento proporciona recomendaciones basadas en la evidencia para el uso de técnicas microbiológicas para la detección de Enterobacteriaceae productoras de BLEE y carbapenemasas, y para el tratamiento antibiótico de las infecciones invasivas causadas por estos microorganismos. Es llamativa la ausencia de ensayos aleatorizados controlados, por lo que las recomendaciones se basan principalmente en estudios observacionales con importantes limitaciones metodológicas, modelos farmacocinéticos y farmacodinámicos y estudios en animales. Además, se han identificado áreas prioritarias de investigación futura

Impact of virulence genes on sepsis severity and survival in Escherichia coli bacteremia.

Extraintestinal pathogenic Escherichia coli (ExPEC) are a frequent cause of bacteremia and sepsis, but the role of ExPEC genetic virulence factors (VFs) in sepsis development and outcome is ill-defined. Prospective study including 120 adult patients with E. coli bacteremia to investigate the impact of bacterial and host factors on sepsis severity and mortality. Patients' clinical and demographic data were registered. Phylogenetic background of E. coli isolates was analyzed by SNP pyrosequencing and VFs by PCR. The E. coli isolates presented an epidemic population structure with 6 dominant clones making up to half of the isolates. VF gene profiles were highly diverse. Multivariate analysis for sepsis severity showed that the presence of cnf and blaTEM genes increased the risk of severe illness by 6.75 (95% confidence interval [CI] 1.79-24.71) and 2.59 (95% CI 1.04-6.43) times respectively, while each point in the Pitt score increased the risk by 1.34 (95% CI 1.02-1.76) times. Multivariate analysis for mortality showed that active chemotherapy (OR 17.87, 95% CI 3.35-95.45), McCabe-Jackson Index (OR for rapidly fatal category 120.15, 95% CI 4.19-3446.23), Pitt index (OR 1.78, 95% CI 1.25-2.56) and presence of fyuA gene (OR 8.05, 95% CI 1.37-47.12) were associated to increased mortality while the presence of P fimbriae genes had a protective role (OR 0.094, 95%IC 0.018-0.494). Bacteremic E. coli had a high diversity of genetic backgrounds and VF gene profiles. Bacterial VFs and host determinants had an impact on disease evolution and mortality.

Diagnosis and antimicrobial treatment of invasive infections due to multidrug-resistant Enterobacteriaceae. Guidelines of the Spanish Society of Infectious Diseases and Clinical Microbiology.

The spread of multidrug-resistant Enterobacteriaceae related to the production of extended-spectrum ß-lactamases and carbapenemases is a serious public health problem worldwide. Microbiological diagnosis and therapy of these infections are challenging and controversial. Clinically relevant questions were selected and the literature was reviewed for each of them. The information from the selected articles was extracted and recommendations were provided and graded according to the strength of the recommendations and quality of the evidence. The document was opened to comments from the members from the Spanish Society of Infectious Diseases and Clinical Microbiology, which were considered for inclusion in the final version. Evidence-based recommendations are provided for the use of microbiological techniques for the detection of extended-spectrum ß-lactamases and carbapenemases in Enterobacteriaceae, and for antibiotic therapy for invasive/severe infections caused by these organisms. The absence of randomised controlled trials is noteworthy; thus, recommendations are mainly based on observational studies (that have important methodological limitations), pharmacokinetic and pharmacodynamics models, and data from animal studies. Additionally, areas for future research were identified.

Executive summary of the diagnosis and antimicrobial treatment of invasive infections due to multidrug-resistant Enterobacteriaceae. Guidelines of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC).

The spread of multidrug-resistant Enterobacteriaceae related to the production of extended-spectrum ß-lactamases (ESBL) and carbapenemases is a serious public health problem worldwide. Microbiological diagnosis and therapy of these infections are challenging and controversial. After the selection of clinically relevant questions, this document provides evidence-based recommendations for the use of microbiological techniques for the detection of ESBL- and carbapenemase-producing Enterobacteriaceae, and for antibiotic therapy for invasive infections caused by these organisms. The absence of randomized-controlled trials is noteworthy, thus recommendations are mainly based on observational studies, that have important methodological limitations, pharmacokinetic and pharmacodynamics models, and data from animal studies. Additionally, areas for future research were identified.

Conocimiento y percepciones de los médicos residentes españoles sobre el uso de antibióticos y sus resistencias: resultados de una encuesta multicéntrica / Knowledge and perceptions of junior and senior Spanish resident doctors about antibiotic use and resistance: Results of a multicenter survey

Antecedentes La resistencia a los antibióticos ha sido reconocida como un problema a nivel mundial. Nuestro objetivo fue conocer las percepciones de los médicos residentes españoles, respecto al uso de antibióticos y la resistencia a los mismos. Métodos Estudio descriptivo transversal mediante encuesta on-line, a todos los médicos residentes de 5 hospitales terciarios, realizada entre septiembre y noviembre de 2010. Se envió un enlace a la encuesta a través de correo electrónico a 844 médicos residentes. El cuestionario evalúa las características demográficas, el conocimiento de los residentes sobre algunos microorganismos de relevancia clínica conocida, sus hábitos en el proceso de prescripción de antibióticos y sus percepciones sobre las actividades encaminadas a mejorar el uso de antimicrobianos. Resultados Se recibieron 279 respuestas que corresponden al 33,05% de todos los residentes encuestados. La tasa de respuesta fue mayor entre los residentes de los primeros años que entre los residentes de los últimos años (39,95% vs 26,12%, p<0,05). Los residentes de todos los hospitales, especialidades y grado de experiencia, en su mayoría consideran que la resistencia antimicrobiana es un problema importante a nivel nacional (94,3%), en su institución (91,3%) y para su práctica diaria (83,8%). Los residentes consideran su formación respecto a los antibióticos insuficiente, aunque, hasta el 86,5% había recetado antibióticos en el último mes. Preferían la disponibilidad de guías locales de uso de antibióticos (65%), sesiones de enseñanza específicas, equipos de gestión de antimicrobianos o mayor facilidad de acceso a la asesoría de s (..) (AU)

Background Antibiotic resistance has been recognized as a worldwide problem. Our aim was to assess the perceptions of Spanish residents about antibiotic use and resistance. Methods An online cross-sectional survey was conducted on all resident doctors in five teaching hospitals (September to November 2010). A link to the questionnaire was e-mailed to 844 doctors. The questionnaire collected demographical characteristics, residents’ knowledge about microorganisms of known clinical relevance, their habits in the antibiotic prescription process, and their perceptions on the activities aimed to improve antibiotic use. Results We received 279 responses corresponding to 33.05% of all targeted residents. The response rate was higher among junior than among senior residents (39.95% vs. 26.12%; p<0.05). Residents of all hospitals, specialties and seniority mostly considered that antimicrobial resistance was a significant problem at national level (94.3%), at their institution (91.3%), and for their daily practice (83.8%). Residents considered their training regarding antibiotics insufficient, although up to 86.5% had prescribed antibiotics in the last month. They preferred the availability of local antibiotic guidelines (65%), specific teaching sessions, specific antimicrobial management teams or readily accessible advice from a group or an infectious diseases specialist, to improve antibiotic prescribing, rather than other restrictive interventions. Conclusions Most residents at the hospitals surveyed believed that antibiotic resistance was a serious problem. The results of this survey provided very important information to optimize adherence to Antimicrobial Stewardship Programs (ASPs). Educational strategies and non-restrictive aids are the most valuable interventions, which ASPs should capitalize on to improve antimicrobial prescription (AU)

Infections caused by OXA-48-producing Klebsiella pneumoniae in a tertiary hospital in Spain in the setting of a prolonged, hospital-wide outbreak.

OBJECTIVES: We describe clinical and microbiological features of infections caused by OXA-48-producing Klebsiella pneumoniae (O48KP) in the setting of a prolonged, hospital-wide outbreak detected in January 2011. METHODS: Clinical, demographic and microbiological data of patients with growth of O48KP in clinical specimens were collected until December 2011. PCR was used to detect carbapenemase and ß-lactamase genes. The genetic relationships were determined by automated repetitive-sequence-based PCR. RESULTS: Seventy-one patients with clinically guided cultures showing growth of O48KP were identified. Nine were considered to be colonizing rather than causing infection. The most frequent source of infection was the urinary tract (22/62), followed by surgical site infections (17/62). Blood cultures were positive in 23/62 patients. Many patients had significant comorbidity and prolonged hospital stays. In-hospital mortality among patients with O48KP infections was 43.5%. The MIC(90)s of ertapenem, imipenem and meropenem were >32, 16 and 16 mg/L, respectively. No single antimicrobial was active against all the isolates. The antibiotics most active against O48KP were amikacin (97.2% susceptible), colistin (90.1%), tigecycline (73%) and fosfomycin (66.2%). Although eight clones were identified, a predominant clone caused 73.2% of the infections. Multilocus sequence typing (MLST) of the predominant clone gave sequence type (ST) 405 and bla(TEM-1), bla(SHV-76), bla(CTX-M-15) and bla(OXA-1) genes and the insertion sequence IS1999 of the Tn1999 transposon were associated with bla(OXA-48) in this clone. CONCLUSIONS: To our knowledge, this is the largest reported series of infections caused by O48KP in the setting of a single-centre outbreak and provides further input on the clinical relevance of infections caused by O48KP and the difficulties associated with its detection and control.

Knowledge and perceptions of junior and senior Spanish resident doctors about antibiotic use and resistance: results of a multicenter survey.

BACKGROUND: Antibiotic resistance has been recognized as a worldwide problem. Our aim was to assess the perceptions of Spanish residents about antibiotic use and resistance. METHODS: An online cross-sectional survey was conducted on all resident doctors in five teaching hospitals (September to November 2010). A link to the questionnaire was e-mailed to 844 doctors. The questionnaire collected demographical characteristics, residents' knowledge about microorganisms of known clinical relevance, their habits in the antibiotic prescription process, and their perceptions on the activities aimed to improve antibiotic use. RESULTS: We received 279 responses corresponding to 33.05% of all targeted residents. The response rate was higher among junior than among senior residents (39.95% vs. 26.12%; p<0.05). Residents of all hospitals, specialties and seniority mostly considered that antimicrobial resistance was a significant problem at national level (94.3%), at their institution (91.3%), and for their daily practice (83.8%). Residents considered their training regarding antibiotics insufficient, although up to 86.5% had prescribed antibiotics in the last month. They preferred the availability of local antibiotic guidelines (65%), specific teaching sessions, specific antimicrobial management teams or readily accessible advice from a group or an infectious diseases specialist, to improve antibiotic prescribing, rather than other restrictive interventions. CONCLUSIONS: Most residents at the hospitals surveyed believed that antibiotic resistance was a serious problem. The results of this survey provided very important information to optimize adherence to Antimicrobial Stewardship Programs (ASPs). Educational strategies and non-restrictive aids are the most valuable interventions, which ASPs should capitalize on to improve antimicrobial prescription.