Antimicrobial activity of ceftolozane-tazobactam against Enterobacterales and Pseudomonas aeruginosa recovered during the Study for Monitoring Antimicrobial Resistance Trends (SMART) program in Spain (2016-2018).

OBJECTIVE: To analyse the susceptibility to ceftolozane-tazobactam and comparators in Enterobacterales and Pseudomonas aeruginosa isolates recovered from intraabdominal (IAI), urinary (UTI), respiratory (RTI) and bloodstream infection (BSI) in the SMART (Study for Monitoring Antimicrobial Resistance Trends) study. METHODS: The susceptibility of 5,351 isolates collected in 11 Spanish hospitals (2016-2018) were analysed (EUCAST-2020 criteria) by broth microdilution and were phenotypically studied for the presence of extended-spectrum beta-lactamases (ESBL). Ceftolozane-tazobactam and/or carbapenem resistant isolates were genetically characterized for ESBL and carbapenemases. RESULTS: Escherichia coli was the most frequent pathogen (49.3% IAI, 54.9% UTI, 16.7% RTI and 50% BSI), followed by Klebsiella pneumoniae (11.9%, 19.1%, 13.1% and 15.4%, respectively). P. aeruginosa was isolated in 9.3%, 5.6%, 32% and 9%, respectively. The frequency of isolates with ESBLs (2016-2017) was: 30.5% K. pneumoniae, 8.6% E. coli, 2.3% Klebsiella oxytoca and 0.7% Proteus mirabilis. Ceftolozane-tazobactam was very active against non-ESBL-(99.3% susceptible) and ESBL-(95.2%) producing E. coli being less active against K. pneumoniae (98% and 43.1%, respectively) isolates. CTX-M-15 was the most prevalent ESBL in E. coli (27.5%) and K. pneumoniae (51.9%) frequently associated with OXA-48-like carbapenemase. Overall, 93% of P. aeruginosa isolates were susceptible to ceftolozane-tazobactam, preserving this activity (>75%) in isolates resistant to other beta-lactams except in those resistant to meropenen or ceftazidime-avibactam. GES-5, PER-1, VIM-1/2 were the most prevalent enzymes in isolates resistant to ceftolozane-tazobactam. CONCLUSIONS: Ceftolozane-tazobactam showed high activity rates against isolates recovered in the SMART study although it was affected in K. pneumoniae and P. aeruginosa isolates with ESBL and/or carbapenemases.

Antimicrobial susceptibility trends and evolution of isolates with extended spectrum ß-lactamases among Gram-negative organisms recovered during the SMART study in Spain (2011-2015).

OBJECTIVE: The SMART (Study for Monitoring Antimicrobial Resistance Trends) surveillance study monitors antimicrobial susceptibility and extended spectrum ß-lactamases (ESBLs) in Gram-negative bacilli recovered from intra-abdominal infections (IAI). METHODS: Antimicrobial susceptibility of 5,343 isolates from IAI recovered in 11 centres during the 2011-2015 SMART-Spain program was analysed by standard microdilution (EUCAST criteria) and compared with that from 2002-2010. ESBLs were phenotypically detected. RESULTS: Escherichia coli, the most common isolate, significantly decreased in community acquired IAI (60.9% 2002-2010 vs. 56.1% 2011-2015, P=0.0003). It was followed in prevalence by Klebsiella pneumoniae that increased both in the community (8.9% vs. 10.8%, P=0.016) and nosocomial (9.2% vs. 10.8%, P=0.029) IAI and P. aeruginosa, which significantly increased in community acquired IAI (5.6% vs. 8.0%, P=0.0003). ESBLs were more prevalent in K. pneumoniae (16.3%) than in E. coli (9.5%) of nosocomial origin and were more frequently isolated from elderly patients (>60 years). Considering all Enterobacteriaceae, ertapenem (92.3-100%) and amikacin (95.5%-100%) were the most active antimicrobials. Ertapenem activity, unlike amoxicillin-clavulanate or piperacillin-tazobactam, remained virtually unchanged in ESBL (100%) and non-ESBL (98.8%) E. coli producers. Its activity decreased in ESBL-K. pneumoniae (74.7%) but was higher than that of amoxicillin-clavulanate (14.0%) and piperacillin-tazobactam (24.0%). Interestingly, ertapenem susceptibility was maintained in >60% of ESBL isolates that were resistant to amoxicillin-clavulanate, piperacillin-tazobactam or fluoroquinolones. CONCLUSIONS: SMART-Spain results support current guidelines which include ertapenem as empiric treatment in mild-moderate community-acquired IAI, particularly with ESBL producers. These recommendations will need to be updated with the recently introduction of new antimicrobials.

Sentinel surveillance of invasive candidiasis in Spain: epidemiology and antifungal susceptibility.

In order to know the epidemiology and the changes of antifungal resistance in invasive candidiasis (IC) we carried out this prospective study of Candida strains belonging to patients admitted to 26 Spanish hospitals from June 2011 to June 2012 diagnosed with IC. Clinical information and the identity of the Candida species were collected and antifungal susceptibility was tested using broth microdilution in five agents: amphotericin B, fluconazole, voriconazole, caspofungin and anidulafungin. A total of 705 cases-isolates were documented. Most of the patients suffered from candidemia and several underlying diseases and more than half of them were neutropenic or under immunosuppressive therapy, factors associated with higher mortality. Thirty percent of global mortality was documented. C. albicans was the most frequently isolated species, although an increase of non-C. albicans species was observed. Resistance to fluconazole was of 3.4%, lower than in previous years (6.3%). C. parapsilosis presented a higher MIC90 of echinocandins compared to other species.

First field results on the use of stallion sex-sorted semen in a large-scale embryo transfer program.

Flow cytometry sex-sorting technology was developed in 1989. However, it is only the bovine species in which offspring of the desired sex are obtained at a commercial level. The aim of the present work was to evaluate efficiency parameters when using fresh sexed semen in a large-scale equine commercial embryo transfer program. During the 2009, 2010 and 2011 breeding seasons, 938 synchronized cycles were artificially inseminated. One hundred (10.6%) mares failed to ovulate, and for the remaining 838 useable cycles, 887 doses of sexed semen were used, representing 1.06 doses per cycle. In general, 435 (51.9%) out of 838 flushing performed resulted in the recovery of at least one embryo and 496 (59.1%) embryos were recovered, including twins and triplets. Pregnancy rate at 25 days achieved 81.5% (one embryo transferred per recipient). Embryo recovery rate was not statistically different either between preovulatory and postovulatory artificially inseminated mares or when increased quantities of sexed sperm per dose were used (15-45 million) (P > 0.05). A broad variation in embryo recovery rate was observed between the different stallions used in this study. Sex accuracy of the sex sorting assessed by ultrasound fetal sex determination was 90.3%. Finally, overall efficiency (female embryo pregnancies per useable cycles) was 39% (325/838), meaning that to obtain a female pregnancy of at least 75 days it was necessary to perform 2.5 flushing.

Validation of the PCR-dHPLC method for rapid identification of Candida glabrata phylogenetically related species in different biological matrices.

Since two new species phylogenetically related to Candida glabrata with slightly different phenotypes and antifungal susceptibility profiles have been described, it seems to be necessary from clinical point of view, to develop a rapid and accurate identification system in order to distinguish between these three fungal species. We studied the performance of denaturing high performance liquid chromatography (dHPLC) as a faster (less than 7 min) and alternative novel technique for simultaneous analysis of Candida species in different biological matrices. The analyses show the good low limit of detection (LLOD) in all biological matrices studied (5.16-9.56 ngµL(-1), 4.14-4.70 ng µL(-1) and 3.99-4.66 ng µL(-1) for Candida bracarensis, Candida nivariensis and C. glabrata, respectively). 180 Candida isolates were analyzed in order to demonstrate the method suitability for screening analysis to identify C. glabrata and its cryptic species (C. bracarensis and C. nivariensis) in clinical routine.

Nationwide sentinel surveillance of bloodstream Candida infections in 40 tertiary care hospitals in Spain.

Candidemia studies have documented geographic differences in rates and epidemiology, underscoring the need for surveillance to monitor trends. We conducted prospective candidemia surveillance in Spain to assess the incidence, species distribution, frequency of antifungal resistance, and risk factors for acquiring a Candida infection. Prospective laboratory-based surveillance was conducted from June 2008 to June 2009 in 40 medical centers located around the country. A case of candidemia was defined as the isolation of a Candida species from a blood culture. Incidence rates were calculated per 1,000 admissions. Antifungal susceptibility tests were performed by using broth microdilution assay according to the guidelines of the Clinical and Laboratory Standards Institute. We detected 984 cases, for an overall incidence of 1.09 cases per 1,000 admissions. The crude mortality was 20.20%. Candida albicans was the most common species (49.08%), followed by C. parapsilosis (20.73%), C. glabrata (13.61%), and C. tropicalis (10.77%). Overall, decreased susceptibility to fluconazole occurred in 69 (7.01%) incident isolates. Antifungal resistance was rare, and a moderate linear correlation between fluconazole and voriconazole MICs was observed. This is the largest multicenter candidemia study conducted to date and shows the substantial morbidity and mortality of candidemia in Spain.

Vacunas frente al virus del papiloma humano: actualización / Vaccine against human papillomavirus: Up-date

La vacunación frente al virus del papiloma humano (VPH) constituye una herramienta preventiva muy novedosa y de un gran impacto en la prevención primaria oncológica. El flujo de información es continuo y requiere una permanente puesta al día. Inmunogenicidad, eficacia, seguridad y eficiencia de las dos vacunas disponibles, Cervarix®, bivalente VPH 16/18, y Gardasil®, tetravalente 6/11/16/18, son actualizadas y discutidas en esta revisión (AU)

Vaccination against human papillomavirus (HPV) is a recently developed preventive tool with a major impact on primary cancer prevention. Because of the pace at which new data appear, a constant effort is required to keep up to date. The present review discusses and provides an update on the immunogenicity, efficacy, safety and efficiency of the two currently available vaccines, Cervarix®, a bivalent vaccine for the prevention of HPV 16- and 18-associated cervical cancer, and Gardasil®, a tetravalent vaccine against HPV types 6, 11, 16, and 18 (AU)

Characterization of hepatitis B virus genotypes in chronically infected patients

Las mutaciones genómicas presentes durante la transcripción reversa del virus de la hepatitis B (VHB) podrían explicar su variabilidad genéticay ser la causa de la existencia de ocho genotipos distintos que presentan una distribución geográfica diferente. Los objetivos principalesdel presente trabajo fueron determinar la prevalencia de los genotipos del virus de la hepatitis B en pacientes con hepatitis crónica B y buscarla relación entre los genotipos y los factores de riesgo de transmisión con respecto al estado del HBeAg. Se analizaron 14 muestras desuero utilizando el kit INNO-LIPA HBV Genotyping assay. El genotipo D fue el más prevalente (64,3%), seguido del genotipo A (28,6%). Enuna muestra se detectó una coinfección (genotipos D/E) que fue confirmada mediante secuenciación. Todos los pacientes, excepto uno, presentaronHBeAg negativo y anti-HBe positivo. Con respecto a los factores de riesgo de transmisión del VHB, en la mitad de los casos se desconocían;en la otra mitad se observaron transmisiones sexuales, mediante transfusión, verticales e intrafamiliares. Estos resultados demuestranque el genotipo D es el más prevalente en nuestro hospital, seguido del genotipo A. Por otra parte, no hemos encontrado relación entreel estado del HBeAg y el genotipo implicado en la infección(AU)

Genomic mutations occurring during reverse transcription of hepatitis B virus (HBV) could explain its genetic diversity and account for 8genetically distinct genotypes that are geographically distributed quite differently. The main objectives of this study were to determine theprevalence of hepatitis B virus genotypes in patients with chronic hepatitis B and to see if there was a relationship between genotypes andrisk factors for transmission based on HBeAg status. A total of 14 serum samples were analyzed using INNO-LIPA HBV genotyping assay.Genotype D was the most prevalent (64.3%) followed by genotype A (28.6%). There was one case of co-infection (D/E genotypes) that wasconfirmed by PCR sequencing. All patients except one were HBeAg-negative and anti-HBe-positive. The risk factors for HBV transmission wereunknown in half of the cases; in the other half, sexual, transfusion, maternal or interfamilial transmission were observed. The results showthat genotype D is the most prevalent genotype in our hospital, followed by genotype A. On the other hand, no relationship was found betweenHBeAg status and genotype(AU)

Repercusión en los pacientes de las resistencias de los microorganismos / No disponible

No disponible

Characterization of hepatitis B virus genotypes in chronically infected patients.

Genomic mutations occurring during reverse transcription of hepatitis B virus (HBV) could explain its genetic diversity and account for 8 genetically distinct genotypes that are geographically distributed quite differently. The main objectives of this study were to determine the prevalence of hepatitis B virus genotypes in patients with chronic hepatitis B and to see if there was a relationship between genotypes and risk factors for transmission based on HBeAg status. A total of 14 serum samples were analyzed using INNO-LIPA HBV genotyping assay. Genotype D was the most prevalent (64.3%) followed by genotype A (28.6%). There was one case of co-infection (D/E genotypes) that was confirmed by PCR sequencing. All patients except one were HBeAg-negative and anti-HBe-positive. The risk factors for HBV transmission were unknown in half of the cases; in the other half, sexual, transfusion, maternal or interfamilial transmission were observed. The results show that genotype D is the most prevalent genotype in our hospital, followed by genotype A. On the other hand, no relationship was found between HBeAg status and genotype.

[Patterns of susceptibility to antibiotics of Enterobacteriaceae causing intra-abdominal infection in Spain: SMART 2003 study outcomes]. / Patrones de sensibilidad a antimicrobianos de Enterobacteriaceae causantes de infecciones intraabdominales en España: resultados del estudio SMART 2003.

SMART (Study for Monitoring Antimicrobial Resistance Trends) is an ongoing global antimicrobial surveillance program focused on clinical isolates from intra-abdominal infections. The objective of this subanalysis was to assess antimicrobial susceptibility patterns among Entero-bacteriaceae recovered at 13 participating Spanish sites during 2003. Antimicrobial susceptibility testing was performed using broth microdilution techniques according to the CLSI (formerly NCCLS) guidelines for MIC testing. The presence of extended-spectrum beta-lactamases (ESBL) was confirmed in isolates with a MIC of ceftriaxone, ceftazidime, or cefepime>or=2 mg/l by comparing cefepime MICs with and with-out clavulanate. A total of 981 Enterobacteriaceae recovered from 840 patients were tested, of which 398 (41%) were community-acquired. Escherichia coli was the most common isolate (571 isolates; 58%), followed by Klebsiella spp. (153; 16% Enterobacter spp. (97; 10%), and Proteus spp. (63; 6%). A total of 191 isolates (19%) from 176 patients produced inducible beta-lactamases. The carbapenems and amikacin were the most consistently active agents against the Enterobacteriaceae (susceptibility>or=99%). Resistance rates for ceftazidime, cipro-floxacin, and levofloxacin exceeded 10%. ESBLs were detected phenotypically in 61 (6%) isolates, being the most common E. coli (61%), Klebsiella spp. (20%), and Enterobacter spp. (8%). Antimicrobial resistance among Enterobacteriaceae isolated from intra-abdominal infections is a problem in Spain. A significant proportion of inducible beta-lactamase and ESBL-producing Enterobacteriaceae causing intra-abdominal infection were acquired in the community. The carbapenems ertapenem, imipenem and meropenem and the aminoglycoside amikacin were highly active in vitro against Enterobacteriaceae isolated from intra-abdominal sites, including ESBL-producing organisms.

Patrones de sensibilidad a antimicrobianos de Enterobacteriaceae causantes de infecciones intraabdominales en España: resultados del estudio SMART 2003 / Patterns of susceptibility to antibiotics of Enterobacteriaceae causing intra-abdominal infections in Spain: SMART 2003 study outcomes

El estudio SMART ( Study for Monitoring Antimicrobial Resistance Trends ) es un programa mundial de vigilancia de la resistencia a los antimicrobianos de microorganismos aislados de infecciones intraabdominales. En este subanálisis se evaluó el patrón de sensibilidad de las enterobacterias recogidas en los 13 centros españoles participantes en el año 2003. Se determinaron las CMI de diferentes antimicrobianos por el método de microdilución en caldo siguiendo las recomendaciones del CLSI (antes NCCLS). Se confirmó la presencia de betalactamasas de espectro extendido (BLEE) en aquellas cepas frente a las cuales las CMI de ceftriaxona, ceftazidima y cefepima eran ≥2 mg/l mediante la comparación de las CMI de cefepima con o sin ácido clavulánico (10 mg/l). Se evaluaron 981 enterobacterias de 840 pacientes. De ellas, 398 (41%) eran de adquisición comunitaria. Escherichia coli fue el aislamiento más frecuente (571 cepas; 58%), seguida por Klebsiella spp. (153 cepas; 16%), Enterobacter spp. (97 cepas; 10%) y Proteus spp. (63 cepas; 6%). Un total de 191 cepas procedentes de 176 pacientes eran productoras de betalactamasas inducibles (19%). Los carbapenémicos y la amikacina fueron los antibióticos más activos frente a las enterobacterias (sensibilidad ≥99%). La resistencia a ceftazidima, ciprofloxacino y levofloxacino fue superior al 10%. Se detectaron BLEE fenotípicamente en 61 (6%) de los aislamientos, siendo más frecuentes en E. coli (61%), Klebsiella spp. (20%) y Enterobacter spp. (8%). La resistencia entre las enterobacterias aisladas de infecciones intraabdominales constituye un problema en España. Una proporción significativa de las productoras de BLEE o de betalactamasas inducibles proceden de la comunidad. Los carbapenémicos ertapenem, imipenem y meropenem, y el aminoglucósido amikacina, son muy activos in vitro frente a las enterobacterias aisladas de focos intraabdominales, incluyendo aquéllas productoras de BLEE

SMART (Study for Monitoring Antimicrobial Resistance Trends) is an ongoing global antimicrobial surveillance program focused on clinical isolates from intra-abdominal infections. The objective of this subanalysis was to assess antimicrobial susceptibility patterns among Enterobacteriaceae recovered at 13 participating Spanish sites during 2003. Antimicrobial susceptibility testing was performed using broth microdilution techniques according to the CLSI (formerly NCCLS) guidelines for MIC testing. The presence of extended-spectrum beta-lactamases (ESBL) was confirmed in isolates with a MIC of ceftriaxone, ceftazidime, or cefepime >2 mg/l by comparing cefepime MICs with and without clavulanate. A total of 981 Enterobacteriaceae recovered from 840 patients were tested, of which 398 (41%) were community-acquired. Escherichia coli was the most common isolate (571 isolates; 58%), followed by Klebsiella spp. (153; 16%), Enterobacter spp. (97; 10%), and Proteus spp. (63; 6%). A total of 191 isolates (19%) from 176 patients produced inducible beta-lactamases. The carbapenems and amikacin were the most consistently active agents against the Enterobacteriaceae (susceptibility >99%). Resistance rates for ceftazidime, ciprofloxacin, and levofloxacin exceeded 10%. ESBLs were detected phenotypically in 61 (6%) isolates, being the most common E. coli (61%), Klebsiella spp. (20%), and Enterobacter spp. (8%). Antimicrobial resistance among Enterobacteriaceae isolated from intra-abdominal infections is a problem in Spain. A significant proportion of inducible beta-lactamase and ESBL-producing Enterobacteriaceae causing intra-abdominal infection were acquired in the community. The carbapenems ertapenem, imipenem and meropenem and the aminoglycoside amikacin were highly active in vitro against Enterobacteriaceae isolated from intra-abdominal sites, including ESBL-producing organisms

Orogenital transmission of Neisseria meningitidis serogroup C confirmed by genotyping techniques.

Urethritis caused by Neisseria meningitidis in heterosexual patients is presumed to occur via orogenital contact, but confirmation has not been possible in most cases. Presented here is a case of urethritis caused by N. meningitidis, serogroup C, and the isolation of the same microorganism from the nasopharynx and endocervix of the patient's sexual partner. The similarity of the urethral and nasopharyngeal isolates' electrophoretic patterns, obtained using pulsed-field gel electrophoresis, proves the infection was transmitted via orogenital contact.

Infección pulmonar por Nocardia nova / Pulmonary infection due to nocardia nova

No disponible

Variabilidad del virus de la hepatitis C e inhibición de las rutas del interferón / Hepatitis C virus variability and interferon-mediated pathway inhibition

El presente estudio tiene como objetivo principal determinar la hipotética relación entre la variabilidad de la región PePHD (relacionada con la codificación de un pseudosustrato para una enzima viral) del virus de la hepatitis C y la evolución de la terapia con interferón, con el fin de determinar si la aparición de mutaciones en esta región es el factor determinante de la respuesta al tratamiento. El valor que expresa la variabilidad es la detección de un elevado número de cuasiespecies. Para ello se emplearon técnicas ya utilizadas en estudios anteriores, como la transcripción inversa, la doble amplificación (RT-PCR anidada) y SSCP (Single-Strand Conformation Polymorphism). Se analizaron 24 enfermos, todos ellos infectados crónicamente por el virus de la hepatitis C. Se clasificaron en tres grupos diferentes dependiendo de la respuesta a la terapia: 8 pacientes con respuesta sostenida, 8 pacientes con respuesta parcial y 8 pacientes no respondedores. Todos los casos analizados presentaron un grado de heterogeneidad bajo. Este resultado se obtuvo independientemente de otros factores relacionados con la falta de respuesta, como son la edad y el sexo de los pacientes o el genotipo del virus. El hecho de que la secuencia sea tan poco variable indica que es una región funcionalmente importante para la persistencia viral. Se necesitan estudios más profundos para determinar el papel que realmente tiene esta región en las interacciones de la célula y el virus (AU)

[Hepatitis C virus variability and interferon-mediated pathway inhibition]. / Variabilidad del virus de la hepatitis C e inhibicion de las rutas del interferon.

The most important aim of this study was to describe the hypothetical relationship between the PePHD region variability (related to the synthesis of a cellular enzyme pseudosubstrate) of the hepatitis C virus and the response of patients to interferon therapy. This interaction could be a determining factor in the antiviral effect of interferon. All samples (from 24 patients with chronic hepatitis C infection) were analyzed using a previously described method based on RT-PCR and nested PCR mediated by single-strand conformation polymorphism assay (SSCP). The patients were divided into three groups with respect to the response to therapy: 8 patients with sustained response, 8 patients with transient response and 8 nonresponders. In all samples a low genetic heterogeneity pattern was detected, which was independent of other factors involved in the lack of response to treatment, such as age, sex or viral genotype. This genetic homogeneity is an indirect indication of the importance of the region on viral persistence. However, more studies are needed to evaluate the real role of this sequence on the interaction between cells and the virus.