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Objectives To evaluate the efficacy of oral colistin-neomycin in preventing multidrug-resistant Enterobacterales (MDR-E) infections in solid organ transplant (SOT) recipients. Methods Multicentre, open-label, parallel-group, controlled trial with balanced (1:1) randomization in five transplant units. SOT recipients were screened for MDR-E intestinal colonization (extended-spectrum β-lactamase or carbapenemase producing) before transplantation and +7 and + 14 days after transplantation and assigned 1:1 to receive treatment with colistin sulfate plus neomycin sulfate for 14 days (decolonization treatment (DT) group) or no treatment (no decolonization treatment (NDT) group). The primary outcome was diagnosis of an MDR-E infection. Safety outcomes were appearance of adverse effects, mainly diarrhoea, rash, nausea and vomiting. Patients were monitored weekly until 30 days after treatment. Intention-to-treat analysis was performed. Results MDR-E rectal colonization was assessed in 768 SOT recipients; 105 colonized patients were included in the clinical trial, 53 receiving DT and 52 NDT. No significant decrease in the risk of infection by MDR-E was observed in the DT group (9.4%, 5/53) compared to the NDT group (13.5%, 7/52) (relative risk 0.70; 95% confidence interval 0.24–2.08; p 0.517). Four patients (5.6%), three (5.6%) in the DT group and one (1.9%) in the NDT group, developed colistin resistance. Twelve patients (22.7%) in the DT group had diarrhoea, eight related to treatment (15.0%); one patient (1.8%) developed skin rash and another (1.8%) nausea and vomiting. Two patients (3.8%) in the NDT group developed diarrhoea. Conclusions DT does not reduce MDR-E infections in SOT. Colistin resistance and adverse effects such as diarrhoea are a potential issue that must be taken seriously.

Introduction Eikenella corrodens (EC) is part of the normal microbiota of the oropharynx and a recognised opportunistic pathogen. It is mainly involved in head and neck infections, but it has also been identified as a cause of pleuropulmonary and intraabdominal infections. Its identification could be difficult due to its fastidious growth requirements, especially in the context of polymicrobial infection and is probably underreported. Methods We carried out a retrospective 5-year review of clinical charts and laboratory database. Results We describe the clinical and microbiological characteristics of 9 deep-seated infections caused by EC, diagnosed in locations different from the head and neck. Conclusion EC deep-seated infections are often found in patients with comorbid conditions and a history of interventional procedures. Due to the characteristic torpid evolution of EC abscesses, imaging to assess the necessity of debridement and avoid early cessation of antibiotics is necessary.

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

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) (P0.01) 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.

Resumen El uso de los dispositivos semicriticos reutilizables se ha extendido en la practica medica actual tanto con fines diagnosticos como terapeuticos. Sin embargo, la reutilizacion de estos instrumentos conlleva el riesgo de una transmision cruzada de microorganismos de un paciente a otro. El proceso de limpieza y desinfeccion de estos dispositivos es complejo, largo, caro y muy sensible a que se produzcan fallos. En el presente documento se analizan los aspectos epidemiologicos de las infecciones asociadas a la reutilizacion de los dispositivos semicriticos, y el papel del laboratorio de Microbiologia en la monitorizacion del proceso de limpieza y desinfeccion de los mismos a traves de los controles microbiologicos. Se revisan las recomendaciones de diferentes sociedades cientificas sobre la pertinencia de dichos controles y se establecen recomendaciones especificas para la toma y el procesamiento de las muestras, la interpretacion de los resultados y las medidas a tomar en funcion de los resultados obtenidos.

Background The anaerobic infection management is usually based on empirical treatment because anaerobic culture techniques take a long time due to their fastidious nature. The aim of this study was to analyze the etiological profile of severe anaerobic infections and AST data from clinical anaerobic bacteria isolated in a tertiary hospital in Madrid (Spain). Material and methods A consecutive study was carried out over 19 months in Ramon y Cajal Universitary Hospital, Madrid. Clinical samples were processed in appropriate anaerobic media and incubated using Anoxomat system. Identification was performed by MALDI-TOF. AST were determined with gradient diffusion method using EUCAST (penicillin, co-amoxiclav, imipenem, clindamycine and metronidazole) or CLSI (cefoxitin) breakpoints. Results During the period of study, 503 anaerobic microorganisms isolated from 424 clinical samples were included. Twenty-six percent of the cultures were monomicrobial, while 70.0% also contained aerobic bacteria. The most common source of infection was abscesses (26%), while blood infections represented the 11%. Anaerobic gram-negative bacilli were predominant (41%), being Bacteroides fragilis (13%) the most prevalent overall; anaerobic gram-positive bacilli represented 35%, anaerobic gram-positive cocci 19% and anaerobic gram-negative cocci 5%. Metronidazole and imipenem were the most effective agents tested against anaerobic bacteria, while clindamycin presented higher resistance rates. Conclusion Antimicrobial susceptibility surveillance of anaerobic bacteria should be performed to monitor changes in resistance patterns and to be able to optimize empiric antimicrobial treatment. Reliable species identification and quick reporting of results would guide clinicians to select the optimal antimicrobial therapy.

Objective To describe a clonal outbreak due to vancomycin-resistant Enterococcus faecium (VREF) in the nephrology and renal transplant unit of a tertiary teaching hospital in Barcelona, Spain, and to highlight how active patient and environment surveillance cultures, as well as prompt and directed intervention strategies, mainly environmental, helped to successfully bring it under control. Patients and methods A study was conducted on patients admitted to the nephrology ward with any culture positive for VREF over a 6-month period (August 2012–January 2013). Based on the identification of a clonal link between the isolates, weekly rectal screening using swabs was implemented for all patients, as well as environmental cultures and cleaning of medical equipment and the ward. VREF isolates were identified by MicroScan and confirmed by Etest. Bacterial identification was confirmed by MALDI-TOF MS. The presence of van genes, and esp and hyl virulence genes was determined using PCR. The clonal relationship between the isolates was studied first with DiversiLab (bioMerieux), and then by PFGE-Smal and MLST. A two-tier sequence of infection control measures was implemented. Results During the study period, VREF was isolated from 13 patients. All cases were colonized with no criteria for infection. VREF isolates were also extensively recovered from the environment and medical equipment. Isolates carried the vanA gene, and were multidrug-resistant, including high-level resistance (MIC >16 mg/L) to vancomycin and teicoplanin. Molecular analysis showed that all VREF isolates belonged to sequence type 17 (ST17) carrying hyl virulence genes. After implementing infection control measures in a two-tier sequence, and reinforcing particularly environmental and medical equipment cleaning, no further cases were detected in the follow-up year. Conclusion A clonal outbreak of VREF-ST17 involving only colonization is reported. The prompt implementation of aggressive infection control measures in patients and the environment was effective in controlling the outbreak and avoided the potential emergence of infection among patients.

Performance of the CHROMagar mSuperCARBA media was assessed in both well-characterized carbapenem-resistant Enterobacteriaceae ( n =52) and routine surveillance rectal swab specimens ( n =211). Limit of detection ranged between 10 1 and 10 2 CFU/mL except for OXA-48 producers with low-carbapenem MICs (10 6 CFU/mL). High sensitivity (100%) and specificity (100%) were obtained with rectal swabs.

The emergence and spread of carbapenemase-producing Enterobacteriaceae (CPE), as the current paradigm of extensive drug-resistance and multi-drug resistance to antibiotics, is a serious threat to patient health and public health. The increase in OXA-48- and VIM-1-producing Klebsiella pneumoniae isolates represents the greatest impact of CPE in Spain. This evidence has lead the members of a representative panel of the Spanish Study Groups of Nosocomial Infections and Mechanisms of Action and Resistance to Antimicrobials of the Spanish Society of Clinical Microbiology and Infectious Diseases (GEIH/GEMARA-SEIMC) to make a position statement expressing the need for: (i) definitive and coordinated action by all health professionals and authorities involved, and (ii) an adaptation of health systems to facilitate their early control and minimize their impact.

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. Keywords: Hypermucoviscous Klebsiella pneumoniae, Liver abscess, Community acquired infection, MLST

Methicillin -resistant Staphylocccus aureus (MRSA) and multirresistant entorococci are still problematic in nosocomial infections and new challenges have emerged for their containment. MRSA has increased the multiresistant profile; it has been described vancomycin and linezolid resistant isolates and isolates with decreased daptomycin susceptibility. Moreover, new clones (ST398) have emerged, initially associated with piggeries, and new mec variants (mecC) with livestock origin that escape to the detection with current molecular methods based on mecA gene have been detected. In enterococci, linzeolid resistant isolates and isolates with deceased susceptibility to daptomycin have been described. Moreover, ampicillin resistant Enterococcus faecium due to β-lactamase production has been recently found in Europe. Control of MRSA isolates and multiresistant enteroccocci should combined antibiotic stewardship strategies and epidemiological measures, including detection of colonized patients in order to reduce colonization pressure and their transmission.

Hospitals are considered an excellent compartment for the selection of resistant and multi-drug resistant (MDR) bacteria. The overuse and misuse of antimicrobial agents are considered key points fuelling this situation. Antimicrobial stewardship programs have been designed for better use of these compounds to prevent the emergence of resistant microorganisms and to diminish the upward trend in resistance. Nevertheless, the relationship between antibiotic use and antimicrobial resistance is complex, and the desired objectives are difficult to reach. Various factors affecting this relationship have been advocated including, among others, antibiotic exposure and mutant selection windows, antimicrobial pharmacodynamics, the nature of the resistance (natural or acquired, including mutational and that associated with horizontal gene transfer) and the definition of resistance. Moreover, antimicrobial policies to promote better use of these drugs should be implemented not only in the hospital setting coupled with infection control programs, but also in the community, which should also include animal and environmental compartments. Within hospitals, the restriction of antimicrobials, cycling and mixing strategies and the use of combination therapies have been used to avoid resistance. Nevertheless, the results have not always been favorable and resistant bacteria have persisted despite the theoretical benefits of these strategies. Mathematical models as well as microbiological knowledge can explain this failure, which is mainly related to the current scenario involving MDR bacteria and overcoming the fitness associated with resistance. New antimicrobials, rapid diagnostic and antimicrobial susceptibility testing and biomarkers will be useful for future antimicrobial stewardship interventions.

Co-resistance involves transfer of several genes into the same bacteria and/or the acquisition of mutations in different genetic loci affecting different antimicrobials whereas pleiotropic resistance implies the same genetic event affecting several antimicrobials. There is an increasing prevalence of isolates with co-resistance which are over-represented within the so-called high-risk clones. Compensatory events avoid fitness cost of co-resistance, even in the absence of antimicrobials. Nevertheless, they might be selected by different antimicrobials and a single agent might select co-resistant isolates. This process, named as co-selection, is not avoided with cycling or mixing strategies of antimicrobial use. Co-resistance and co-selection processes increase the opportunity for persistence of the bacteria and resistance genes and should be considered when designing strategies for decreasing antimicrobial resistance.

Resumen Introduccion En julio de 2005 se aislo el primer Enterococcus faecium resistente a vancomicina (EFRV) genotipo vanA en el Hospital Universitario de Canarias en un paciente trasplantado renal ingresado en la Unidad de Nefrologia. En los meses siguientes se aislo EFVR en otros 15 pacientes trasplantados renales ingresados en la misma unidad. Nuestro objetivo fue estudiar este primer brote de EFVR vanA en el Hospital Universitario de Canarias y el vinculo epidemiologico con los aislamientos de EFVR vanA encontrados tambien en otros 2 hospitales universitarios ubicados en las Islas Canarias. Material y metodos Se estudiaron mediante metodos microbiologicos y moleculares un total de 22 aislamientos de EFRV y las historias clinicas de los 22 pacientes de los que se aislaron. Resultados y conclusiones Se confirmo mediante electroforesis de campo pulsante que los aislamientos del brote pertenecian a una misma clona y, a su vez, se confirmo el vinculo epidemiologico con los primeros aislamientos en los otros 2 hospitales universitarios relacionando los resultados moleculares con los datos epidemiologicos. Todos los aislamientos pertenecian a la secuencia tipo ST18 mediante multilocus sequence typing, asociado al complejo clonal 17. El complejo clonal 17 es un linaje que comprende una poblacion policlonal que se ha adaptado bien al ambiente hospitalario y que se aisla en los 5 continentes.

Introduccion El desarrollo de un esquema de Multilocus sequence typing (MLST) para Enterococcus faecalis ha permitido conocer los primeros datos de su estructura poblacional y epidemiologia global. Se ha detectado la dispersion en Europa y America de dos complejos clonales (CC) de alto riesgo denominados CC2 y CC9 que estan especialmente adaptados al medio hospitalario. El objetivo de este trabajo ha sido definir la presencia de ambos CC en cepas de E. faecalis aisladas en Espana. Metodos Se han caracterizado por MLST 81 cepas de E. faecalis aisladas de diversos origenes y correspondientes a diferentes anos y regiones espanolas. Debido a su importancia clinica y epidemiologica se han incluido cepas representantes de cada uno de los brotes hospitalarios por E. faecalis resistente a vancomicina descritos en Espana. Resultados En el medio hospitalario se detecto la dispersion de CC2 y CC9. En estos CC se han agrupado las cepas de E. faecalis resistentes a vancomicina causantes de los brotes hospitalarios en La Coruna, Palma de Mallorca y Valencia, asi como cepas de origen hospitalario sensibles a la vancomicina. La utilizacion del indice de asociacion (I a ), que estima el equilibrio de ligamiento en la poblacion estudiada, revelo una estructura poblacional epidemica cuya variabilidad genetica es debida a procesos de recombinacion. Conclusion En Espana se han detectado los CC de alto riesgo CC2 y CC9, que han evolucionado localmente de forma diferente en funcion de la carga genetica del entorno. Las medidas de control de la infeccion deberian ir encaminadas a la deteccion de estos CC de alto riesgo, ya que su presencia en los hospitales podrian predecir tendencias futuras en cuanto a la adquisicion de determinadas resistencias como es el caso de la vancomicina.

Los antimicrobianos son fármacos distintos al resto. Su eficacia en la reducción de la morbilidad y la mor talidad es muy superior a la de otros grupos de medicamentos. Por otra parte, son los únicos fármacos con efectos ecológicos, de manera que su administración puede contribuir a la aparición y diseminación de resistencias microbianas. Finalmente, son utilizados por médicos de prácticamente todas las especialidades. La actual complejidad en el manejo de las enfermedades infecciosas y del aumento de las resistencias hace imprescindible el establecimiento de programas de optimización del uso de antimicrobianos en los hospitales (PROA). Este documento de consenso define los objetivos de los PROA (mejorar los resultados clínicos de los pacientes con infecciones, minimizar los efectos adversos asociados a la utilización de antimicrobianos, incluyendo aquí las resistencias, y garantizar la utilización de tratamientos coste-eficaces) y establece recomendaciones para su implantación en los hospitales españoles. Las líneas maestras de las recomendaciones son: la constitución de un equipo multidisciplinario de antibióticos, dependiente de la Comisión de Infecciones. Los PROA necesitan ser considerados programas institucionales de los hospitales donde se desarrollen. Deben incluir objetivos específicos y resultados cuantificables en función de indicadores, y basarse en la realización de actividades encaminadas a mejorar el uso de antimicrobianos, principalmente mediante actividades formativas y medidas no impositivas de ayuda a la prescripción. The antimicrobial agents are unique drugs for several reasons. First, their efficacy is higher than other drugs in terms of reduction of morbidity and mortality. Also, antibiotics are the only group of drugs associated with ecological effects, because their administration may contribute to the emergence and spread of microbial resistance. Finally, they are used by almost all medical specialties. Appropriate use of antimicrobials is very complex because of the important advances in the management of infectious diseases and the spread of antibiotic resistance. Thus, the implementation of programs for optimizing the use of antibiotics in hospitals (called PROA in this document) is necessary. This consensus document defines the objectives of the PROA (namely, to improve the clinical results of patients with infections, to minimise the adverse events associated to the use of antimicrobials including the emergence and spread of antibiotic resistance, and to ensure the use of the most cost-efficacious treatments), and provides recommendations for the implementation of these programs in Spanish hospitals. The key aspects of the recommendations are as follows. Multidisciplinary antibiotic teams should be formed, under the auspices of the Infection Committees. The PROA need to be considered as part of institutional programs and the strategic objectives of the hospital. The PROA should include specific objectives based on measurable indicators, and activities aimed at improving the use of antimicrobials, mainly through educational activities and interventions based more on training activities directed to prescribers than just on restrictive measures.