Browsing by Author "Fenoll, Asuncion"
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Publication Actividad de cefpodoxima y otros betalactámicos orales frente a Haemophilus influenzae y Streptococcus pneumoniae con distinta sensibilidad a la penicilina(Sociedad Española de Quimioterapia (SEQ), 2006-03) Fenoll, Asuncion; Robledo, Olga; Lerma, M; Giménez, M J; Cebrián, L; Casal, Julio; Aguilar, L; Gómez-Lus, M L[ES] Estudiamos la influencia de la producción de betalactamasas en Haemophilus influenzae y del grado de sensibilidad a la penicilina en Streptococcus pneumoniae sobre la actividad intrínseca de distintos betalactámicos orales. Realizamos tres subestudios: 1) un estudio general de sensibilidad, analizando 550 aislamientos consecutivos recibidos en el Laboratorio de Referencia de Neumococos durante los meses de febrero y marzo de 2005; 2) un estudio de la influencia de la sensibilidad a la penicilina sobre la actividad del resto de los betalactámicos, analizando la sensibilidad de 251 cepas sensibles a la penicilina (CMI ≤0,06 mg/l), 165 cepas con resistencia intermedia (CMI 0,12-1mg/l) y 139 resistentes (CMI ≥2 mg/l), elegidas aleatoriamente entre todos los aislamientos recibidos durante el año 2005; y 3) un estudio desensibilidad de H. influenzae, analizando 150 cepas recibidas por el Instituto Valenciano de Microbiología a lo largo del año 2005. El 71% de las cepas de S. pneumoniae fueron sensibles a la penicilina, el 21% presentaron baja resistencia o resistencia intermedia, y un 8% altaresistencia. La tasa de producción de betalactamasas fue del 18,6% en H. influenzae. El 3% de las cepas no productoras de betalactamasas fueron no sensibles a la ampicilina. La cefpodoxima y la cefixima presentaron la mayor actividad intrínseca frente a H. influenzae, mientras que frente a S. pneumoniae ésta correspondió a la amoxicilina y la cefpodoxima. Mientras que el 100% de las cepas de H. influenzae fueron sensibles a las cefalosporinas orales y a amoxicilina-ácido clavulánico, el aumento de la resistencia a la penicilina en S. pneumoniae afectó en mayor grado a la actividad de la cefixima, el cefaclor y la cefuroxima que a la amoxicilina y la cefpodoxima. [EN] his study explores the influence on the intrinsic activity of different oral beta-lactams of beta-lactamase production in Haemophilus influenzae and penicillin resistance in Streptococcus pneumoniae. Three substudies were performed: a) a general susceptibility study, analyzing 550 strains received by the Spanish Laboratorio de Referencia de Neumococos throughout February and March 2005; b) a study on the influence of penicillin resistance on the activity of beta-lactams, analyzing 251 penicillin-susceptible strains (MICor=2 mg/l) randomly chosen among those received by the Spanish Laboratorio de Referencia de Neumococos throughout 2005; and c) an H. influenzae susceptibility study analyzing 150 strains received by Instituto Valenciano de Microbiologia throughout 2005. A total of 71% of S. pneumoniae strains were susceptible to penicillin, 21% exhibited intermediate resistance and 8% strains presented full resistance. H. influenzae beta-lactamase production rate was 18.6%. Of the non-beta-lactamase-producing strains, 3% were not susceptible to ampicillin. Cefpodoxime and cefixime exhibited the highest intrinsic activity against H. influenzae, while amoxicillin and cefpodoxime were the most active compounds against S. pneumoniae. All H. influenzae strains were susceptible to oral cephalosporins and amoxicillin/clavulanic acid. The increase in penicillin resistance in S. pneumoniae influenced cefixime, cefaclor and cefuroxime to a higher degree than amoxicillin and cefpodoxime.Publication Changes in fluoroquinolone-resistant Streptococcus pneumoniae after 7-valent conjugate vaccination, Spain(Centers for Disease Control and Prevention (CDC), 2009-06) de la Campa, Adela G; Ardanuy, Carmen; Balsalobre-Arenas, Maria Luz; Pérez-Trallero, Emilio; Marimón, Jose M; Fenoll, Asuncion; Liñares, Josefina; Ministerio de Ciencia e Innovación (España); Comunidad de Madrid (España)Among 4,215 Streptococcus pneumoniae isolates obtained in Spain during 2006, 98 (2.3%) were ciprofloxacin resistant (3.6% from adults and 0.14% from children). In comparison with findings from a 2002 study, global resistance remained stable. Low-level resistance (30 isolates with MIC 4-8 microg/mL) was caused by a reserpine-sensitive efflux phenotype (n = 4) or single topoisomerase IV (parC [n = 24] or parE [n = 1]) changes. One isolate did not show reserpine-sensitive efflux or mutations. High-level resistance (68 isolates with MIC >or=16 microg/mL) was caused by changes in gyrase (gyrA) and parC or parE. New changes in parC (S80P) and gyrA (S81V, E85G) were shown to be involved in resistance by genetic transformation. Although 49 genotypes were observed, clones Spain9V-ST156 and Sweden15A-ST63 accounted for 34.7% of drug-resistant isolates. In comparison with findings from the 2002 study, clones Spain14-ST17, Spain23F-ST81, and ST8819F decreased and 4 new genotypes (ST9710A, ST57016, ST43322, and ST71733) appeared in 2006.Publication Decrease of invasive pneumococcal disease (IPD) in adults after introduction of pneumococcal 13-valent conjugate vaccine in Spain(Public Library of Science (PLOS), 2017) Càmara, Jordi; Marimón, José María; Cercenado, Emilia; Larrosa, Nieves; Quesada, María Dolores; Fontanals, Dionísia; Cubero, Meritxell; Pérez-Trallero, Emilio; Fenoll, Asuncion; Liñares, Josefina; Ardanuy, Carmen; Centro de Investigación Biomedica en Red - CIBER; Instituto de Salud Carlos III; Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)A prospective laboratory-based multicenter study that collected all adult invasive pneumococcal disease (IPD) episodes from 6 Spanish hospitals before (2008-2009) and after (2012-2013). The 13-valent pneumococcal conjugate vaccine (PCV13) licensure was conducted in order to analyze the impact of PCV13 introduction for children on adult IPD. A total of 1558 IPD episodes were detected. The incidence of IPD decreased significantly in the second period by -33.9% (95% CI, -40.3% to -26.8%). IPD due to PCV7 serotypes (-52.7%; 95% CI, -64.2% to -37.5%) and to PCV13 additional serotypes (-55.0% 95% CI, -62.0% to -46.7%) significantly decreased whereas IPD due to non-PCV13 serotypes remained stable (1.0% 95% CI, -12.9% to 17.2%). IPD due to all PCV13 additional serotypes significantly declined with the exception of serotype 3 (-11.3%; 95%CI -35.0% to 21.1%). IPD due to two non-PCV13 serotypes varied: serotype 6C that rose (301.6%; 95%CI, 92.7% to 733.3%, p<0.001), related to the expansion of ST3866C, and serotype 8 that decreased (-34.9%, 95%CI, -57.1 to -1.2, p = 0.049), related to a decline of the ST638. The recombinant clone ST652111A (variant of ST1569V) increased in frequency. The decrease of serotype 19A IPD was linked to a fall in those antibiotic susceptible clones. In the last period, rates of penicillin- and cefotaxime-resistance remained under 10% and 4%, respectively. Adult IPD decreased after the PCV13 introduction in Spain due to herd protection. The spread of multidrug resistant clones (ST3866C, ST652111A) related to non-PCV13 serotypes needs further surveillance.Publication Disease isolates of Streptococcus pseudopneumoniae and non-typeable S. pneumoniae presumptively identified as atypical S. pneumoniae in Spain(Public Library of Science (PLOS), 2013-02-21) Rolo, Dora; S Simões, Alexandra; Domenech, Arnau; Fenoll, Asuncion; Liñares, Josefina; de Lencastre, Hermínia; Ardanuy, Carmen; Sá-Leão, Raquel; Ministerio de Ciencia e Innovación (España); Instituto de Salud Carlos III; Fundação para a Ciência e Tecnologia (Portugal)We aimed to obtain insights on the nature of a collection of isolates presumptively identified as atypical Streptococcus pneumoniae recovered from invasive and non-invasive infections in Spain. One-hundred and thirty-two isolates were characterized by: optochin susceptibility in ambient and CO(2)-enriched atmosphere; bile solubility; PCR-based assays targeting pneumococcal genes lytA, ply, pspA, cpsA, Spn9802, aliB-like ORF2, and a specific 16S rRNA region; multilocus sequence analysis; and antimicrobial susceptibility. By multilocus sequence analysis, 61 isolates were S. pseudopneumoniae, 34 were pneumococci, 13 were S. mitis, and 24 remained unclassified as non-pneumococci. Among S. pseudopneumoniae isolates, 51 (83.6%) were collected from respiratory tract samples; eight isolates were obtained from sterile sources. High frequency of non-susceptibility to penicillin (60.7%) and erythromycin (42.6%) was found. Only 50.8% of the S. pseudopneumoniae isolates displayed the typical optochin phenotype originally described for this species. None harbored the cpsA gene or the pneumococcal typical lytA restriction fragment length polymorphism. The Spn9802 and the specific 16S rRNA regions were detected among the majority of the S. pseudopneumoniae isolates (n = 59 and n = 49, respectively). The ply and pspA genes were rarely found. A high genetic diversity was found and 59 profiles were identified. Among the S. pneumoniae, 23 were capsulated and 11 were non-typeable. Three non-typeable isolates, associated to international non-capsulated lineages, were recovered from invasive disease sources. In conclusion, half of the atypical pneumococcal clinical isolates were, in fact, S. pseudopneumoniae and one-fourth were other streptococci. We identified S. pseudopneumoniae and non-typeable pneumococci as cause of disease in Spain including invasive disease.Publication Emergence of Amoxicillin-Resistant Variants of Spain9V-ST156 Pneumococci Expressing Serotype 11A Correlates with Their Ability to Evade the Host Immune Response(Public Library of Science (PLOS), 2015) Aguinagalde, Leire; Corsini, Bruno; Domenech, Arnau; Domenech Lucas, Mirian; Cámara, Jordi; Ardanuy, Carmen; García, Ernesto; Liñares, Josefina; Fenoll, Asuncion; Yuste, Jose EnriqueCapsular switching allows pre-existing clones of Streptococcus pneumoniae expressing vaccine serotypes to escape the vaccine-induced immunity by acquisition of capsular genes from pneumococci of a non-vaccine serotype. Here, we have analysed the clonal composition of 492 clinical isolates of serotype 11A causing invasive disease in Spain (2000-2012), and their ability to evade the host immune response. Antibiograms, serotyping and molecular typing were performed. The restriction profiles of pbp2x, pbp1a and pbp2b genes were also analysed. Interaction with the complement components C1q, C3b, C4BP, and factor H was explored whereas opsonophagocytosis assays were performed using a human cell line differentiated to neutrophils. Biofilm formation and the polymorphisms of the major autolysin LytA were evaluated. The main genotypes of the 11A pneumococci were: ST62 (447 isolates, 90.6%), followed by ST6521 (35 isolates, 7.3%) and ST838 (10 isolates, 2.1%). Beta lactam resistant serotype 11A variants of genotypes ST838 and ST6521 closely related to the Spain9V-ST156 clone were first detected in 2005. A different pattern of evasion of complement immunity and phagocytosis was observed between genotypes. The emergence of one vaccine escape variant of Spain9V-ST156 (ST652111A), showing a high potential to avoid the host immune response, was observed. In addition, isolates of ST652111A showed higher ability to produce biofilms than ST83811A or ST6211A, which may have contributed to the emergence of this PEN-resistant ST652111A genotype in the last few years. The emergence of penicillin-resistant 11A invasive variants of the highly successful ST156 clonal complex merits close monitoring.Publication Emerging, Non-PCV13 Serotypes 11A and 35B of Streptococcus pneumoniae Show High Potential for Biofilm Formation In Vitro(Public Library of Science (PLOS), 2015-04-30) Domenech Lucas, Mirian; Damián, Diana; Ardanuy, Carmen; Liñares, Josefina; Fenoll, Asuncion; García, Ernesto; Ministerio de Economía y Competitividad (España); Instituto de Salud Carlos IIIBACKGROUND: Since the use of pneumococcal conjugate vaccines PCV7 and PCV13 in children became widespread, invasive pneumococcal disease (IPD) has dramatically decreased. Nevertheless, there has been a rise in incidence of Streptococcus pneumoniae non-vaccine serotypes (NVT) colonising the human nasopharynx. Nasopharyngeal colonisation, an essential step in the development of S. pneumoniae-induced IPD, is associated with biofilm formation. Although the capsule is the main pneumococcal virulence factor, the formation of pneumococcal biofilms might, in fact, be limited by the presence of capsular polysaccharide (CPS). METHODOLOGY/PRINCIPAL FINDINGS: We used clinical isolates of 16 emerging, non-PCV13 serotypes as well as isogenic transformants of the same serotypes. The biofilm formation capacity of isogenic transformants expressing CPSs from NVT was evaluated in vitro to ascertain whether this trait can be used to predict the emergence of NVT. Fourteen out of 16 NVT analysed were not good biofilm formers, presumably because of the presence of CPS. In contrast, serotypes 11A and 35B formed ≥45% of the biofilm produced by the non-encapsulated M11 strain. CONCLUSIONS/SIGNIFICANCE: This study suggest that emerging, NVT serotypes 11A and 35B deserve a close surveillance.Publication Fluoroquinolone Resistance in Penicillin-resistantStreptococcus pneumoniaeClones, Spain(Centers for Disease Control and Prevention (CDC), 2004-10) de la Campa, Adela G; Balsalobre-Arenas, Maria Luz; Ardanuy, Carmen; Fenoll, Asuncion; Pérez-Trallero, Emilio; Liñares, Josefina; Instituto de Salud Carlos III; Ministerio de Ciencia y Tecnología (España)Among 2,882 Streptococcus pneumoniae sent to the Spanish Reference Laboratory during 2002, 75 (2.6%) were ciprofloxacin-resistant. Resistance was associated with older patients (3.9% in adults and 7.2% in patients > or =65 years of age), with isolation from noninvasive sites (4.3% vs. 1.0%), and with penicillin and macrolide resistance. Among 14 low-level resistant (MIC 4-8 microg/mL) strains, 1 had a fluoroquinolone efflux phenotype, and 13 showed single ParC changes. The 61 high-level ciprofloxacin-resistant (MIC > or =16 microg/mL) strains showed either two or three changes at ParC, ParE, and GyrA. Resistance was acquired either by point mutation (70 strains) or by recombination with viridans streptococci (4 strains) at the topoisomerase II genes. Although 36 pulsed-field gel electrophoresis patterns were observed, 5 international multiresistant clones (Spain23F-1, Spain6B-2, Spain9V-3, Spain14-5 and Sweden15A-25) accounted for 35 (46.7%) of the ciprofloxacin-resistant strains. Continuous surveillance is needed to prevent the dissemination of these clones.Publication Fluoroquinolone-resistant pneumococci: dynamics of serotypes and clones in Spain in 2012 compared with those from 2002 and 2006(American Society for Microbiology (ASM), 2014) Domenech, Arnau; Tirado-Velez, JM; Fenoll, Asuncion; Ardanuy, Carmen; Yuste, Jose Enrique; Liñares, Josefina; de la Campa, Adela G; Ministerio de Ciencia y Tecnología (España); Instituto de Salud Carlos III; Centro de Investigación Biomedica en Red - CIBER; Societat Catalana de Malalties Infeccioses i Microbiologia ClínicaIn Spain, rates of ciprofloxacin resistance in pneumococci were low during the last decade (2.6% in 2002 and 2.3% in 2006). In 2012, the rate remained at 2.3%, equivalent to 83 of 3,621 isolates. Of the 83 resistant isolates, 15 showed a low level (MIC of 4 to 8 μg/ml) and 68 a high level (MIC of 16 to 128 μg/ml) of ciprofloxacin resistance. Thirteen low-level-resistant isolates had single changes in ParC, one had a single ParE change, and one did not present any mutations. High-level-resistant isolates had GyrA changes plus additional ParC and/or ParE changes: 51, 15, and 2 isolates had 2, 3, or 4 mutations, respectively. Although 24 different serotypes were observed, 6 serotypes accounted for 51.8% of ciprofloxacin-resistant isolates: 8 (14.5%), 19A (10.8%), 11A (7.2%), 23A (7.2%), 15A (6.0%), and 6B (6.0%). A decrease in pneumococcal 7-valent conjugate vaccine (PCV7) serotypes was observed from 2006 (35.7%) to 2012 (16.9%), especially of serotype 14 (from 16.3% to 2.4%; P<0.001). In comparison with findings in 2006, multidrug resistance was greater in 2012 (P=0.296), mainly due to the increased presence and/or emergence of clonal complexes associated with non-PCV7 serotypes: CC63 expressing serotypes 8, 15A, and 19A; CC320 (with serotype 19A); and CC42 (with serotype 23A). Although rates of ciprofloxacin resistance remained low and stable throughout the last decade, changes in serotype and genotype distributions were observed in 2012, notably the expansion of a preexisting multidrug-resistant clone, CC63, and the emergence of the CC156 clone expressing serotype 11A.Publication Genetic characterization of optochin-susceptible viridans group streptococci(American Society for Microbiology (ASM), 2003-10) Martin-Galiano, Antonio Javier; Balsalobre-Arenas, Maria Luz; Fenoll, Asuncion; de la Campa, Adela G; Instituto de Salud Carlos III; Comunidad de Madrid (España); Ministerio de Ciencia y Tecnología (España)Two clinical isolates of viridans group streptococci (VS) with different degrees of susceptibility to optochin (OPT), i.e., fully OPT-susceptible (Opt(s)) VS strain 1162/99 (for which the MIC was equal to that for Streptococcus pneumoniae, 0.75 micro g/ml) and intermediate Opt(s) VS strain 1174/97 (MIC, 6 micro g/ml) were studied. Besides being OPT susceptible, they showed characteristics typical of VS, such as bile insolubility; lack of reaction with pneumococcal capsular antibodies; and lack of hybridization with rRNA (AccuProbe)-, lytA-, and pnl-specific pneumococcal probes. However, these VS Opt(s) strains and VS type strains hybridized with ant, a gene not present in S. pneumoniae. A detailed characterization of the genes encoding the 16S rRNA and SodA classified isolates 1162/99 and 1174/97 as Streptococcus mitis. Analysis of the atpCAB region, which encodes the c, a, and b subunits of the F(0)F(1) H(+)-ATPase, the target of optochin, revealed high degrees of similarity between S. mitis 1162/99 and S. pneumoniae in atpC, atpA, and the N terminus of atpB. Moreover, amino acid identity between S. mitis 1174/97 and S. pneumoniae was found in alpha helix 5 of the a subunit. The organization of the chromosomal region containing the atp operon of the two Opt(s) VS and VS type strains was spr1284-atpC, with spr1284 being located 296 to 556 bp from atpC, whereas in S. pneumoniae this distance was longer than 68 kb. In addition, the gene order in S. pneumoniae was IS1239-74 bp-atpC. The results suggest that the full OPT susceptibility of S. mitis 1162/99 is due to the acquisition of atpC, atpA, and part of atpB from S. pneumoniae and that the intermediate OPT susceptibility of S. mitis 1174/97 correlates with the amino acid composition of its a subunit.Publication Immunization with LytB protein of Streptococcus pneumoniae activates complement-mediated phagocytosis and induces protection against pneumonia and sepsis(Elsevier, 2016) Ruiz, Susana; Domenech, Mirian; Antequera, María Luisa; García, Pedro; García, Ernesto; Corsini, Bruno; Aguinagalde, Leire; Fenoll, Asuncion; Yuste, Jose Enrique; Ministerio de Economía y Competitividad (España); Centro de Investigación Biomedica en Red - CIBER; National Council for Scientific and Technological Development (Brasil)The cell wall glucosaminidase LytB of Streptococcus pneumoniae is a surface exposed protein involved in daughter cell separation, biofilm formation and contributes to different aspects of the pathogenesis process. In this study we have characterized the antibody responses after immunization of mice with LytB in the presence of alhydrogel as an adjuvant. Enzyme-linked immunosorbent assays measuring different subclasses of immunoglobulin G, demonstrated that the antibody responses to LytB were predominantly IgG1 and IgG2b, followed by IgG3 and IgG2a subclasses. Complement-mediated immunity against two different pneumococcal serotypes was investigated using sera from immunized mice. Immunization with LytB increased the recognition of S. pneumoniae by complement components C1q and C3b demonstrating that anti-LytB antibodies trigger activation of the classical pathway. Phagocytosis assays showed that serum containing antibodies to LytB stimulates neutrophil-mediated phagocytosis against S. pneumoniae. Animal models of infection including invasive pneumonia and sepsis were performed with two different clinical isolates. Vaccination with LytB increased bacterial clearance and induced protection demonstrating that LytB might be a good candidate to be considered in a future protein-based vaccine against S. pneumoniae.Publication Increase in serotype 19A prevalence and amoxicillin non-susceptibility among paediatric Streptococcus pneumoniae isolates from middle ear fluid in a passive laboratory-based surveillance in Spain, 1997-2009(BioMed Central (BMC), 2011-09-12) Fenoll, Asuncion; Aguilar, Lorenzo; Vicioso-Perez, Maria Dolores; Gimenez, Maria-Jose; Robledo, Olga; Granizo, Juan-Jose; Fundación Pfizer; RETICS-Investigación en Patología Infecciosa (REIPI-ISCIII) (España)BACKGROUND: Conjugate vaccines, such as the 7-valent conjugate vaccine (PCV7), alter serotype nasopharyngeal carriage, potentially increasing cases of otitis media by non-vaccine serotypes. METHODS: All paediatric middle ear fluid (MEF) isolates received in the Spanish Reference Laboratory for Pneumococci through a passive, laboratory-based surveillance system from January 1997 to June 2009 were analysed. Data from 1997 to 2000 were pooled as pre-vaccination period. Trends over time were explored by linear regression analysis. RESULTS: A total of 2,077 isolates were analysed: 855 belonging to PCV7 serotypes, 466 to serotype 19A, 215 to serotype 3, 89 to serotype 6A and 452 to other serotypes (< 40 isolates each). Over time, there has been a decreasing trend for PCV7 serotypes (R(2) = 0.944; p < 0.001, with significant decreasing trends for serotypes 19F, 14, 23F and 9V), and increasing trends for serotype 19A (R(2) = 0.901; p < 0.001), serotype 3 (R(2) = 0.463; p = 0.030) and other non-PCV7 serotypes (R(2) = 0.877; p < 0.001), but not for serotype 6A (R(2) = 0.311; p = 0.094). Considering all isolates, amoxicillin non-susceptibility showed an increasing trend (R(2) = 0.528; p = 0.017). Regarding serotype 19A, increasing trends in non-susceptibility to penicillin (R(2) = 0.726; p = 0.001), amoxicillin (R(2) = 0.804; p < 0.001), cefotaxime (R(2) = 0.546; p = 0.005) and erythromycin (R(2) = 0.546; p = 0.009) were found, with amoxicillin non-susceptibility firstly detected in 2003 (7.4%) and increasing up to 38.0% in 2009. In PCV7 serotypes (which prevalence decreased from 70.7% during 1997-2000 to 10.6% in 2009) amoxicillin non-susceptibility rates showed an increasing trend (R(2) = 0.702; p = 0.002). However, overall, amoxicillin non-susceptibility (≈25% in 2008-9) could be mainly attributed to serotype 19A (> 35% isolates) since PCV7 strains represented < 11% of total clinical isolates. CONCLUSIONS: In contrast to reports on invasive pneumococcal strains, in MEF isolates the reduction in the prevalence of PCV7 serotypes was not associated with decreases in penicillin/erythromycin non-susceptibility. The high prevalence of serotype 19A among paediatric MEF isolates and the amoxicillin non-susceptibility found in this serotype are worrisome since amoxicillin is the most common antibiotic used in the treatment of acute otitis media. These data suggest that non-PCV7 serotypes (mainly serotype 19A followed by serotypes 3 and 6A) are important etiological agents of acute otitis media and support the added value of the broader coverage of the new 13-valent conjugate vaccine.Publication Indirect effects of paediatric conjugate vaccines on invasive pneumococcal disease in older adults(Elsevier, 2019-09) Ciruela, Pilar; Broner, Sonia; Izquierdo, Conchita; Pallarés, Román; Muñoz-Almagro, Carmen; Hernández, Sergi; Grau, Imma; Domínguez, Angela; Jané, Mireia; The Catalan Working Group on Invasive Pneumococcal Disease; Fenoll, Asuncion; Unión Europea. European Centre for Disease Prevention and Control (ECDC); Centro de Investigación Biomédica en Red - CIBERESP (Epidemiología y Salud Pública)OBJECTIVES: The aim of this study was to assess the indirect effect of paediatric 13-valent pneumococcal conjugate vaccine (PCV13) vaccination on people ≥65 years of age with invasive pneumococcal disease (IPD) in Catalonia and to determine factors predictive of mortality. METHODS: During 2014-2016, 1285 IPD cases were reported to the Public Health Agency of Catalonia. The indirect effect of paediatric PCV13 vaccination was calculated by comparing the incidence rate (IR) in 2016 (PCV13 year) with that in 2009 (pre-PCV13). Predictors of mortality were determined using multivariate logistic regression. RESULTS: Comparing 2016 and 2009, IPD decreased by 19% (IR 40.1 and 32.5 per 100 000 person-years, respectively). PCV13 serotypes decreased by 57% (IR 23.7 and 10.1), while non-PCV13 serotypes increased by 36% (IR 16.4 and 22.4). During 2014-2016, the mortality rate was 17.5%, and mortality was associated with age ≥85 years (adjusted odds ratio (aOR) 2.91, 95% confidence interval (CI) 1.89, 4.48), meningitis (aOR 2.29, 95% CI 1.25, 4.19), non-focal bacteraemia (aOR 3.73, 95% CI 2.00, 6.94), and ≥1 high-risk condition (aOR 1.89, 95% CI 1.08, 3.32). PPV23non13 serotypes were associated with lower mortality than PCV13 serotypes (aOR 0.54, 95% CI 0.34, 0.86). CONCLUSIONS: The incidence of IPD in people ≥65 years of age decreased after the introduction of paediatric PCV13, and this was due to a reduction in PCV13 serotypes, although an increase in non-PCV13 serotypes was observed. Mortality was associated with age, meningitis, non-focal bacteraemia, ≥1 high-risk condition, and PCV13 serotypes.Publication Molecular characterization of disease-associated streptococci of the mitis group that are optochin susceptible(American Society for Microbiology (ASM), 2006-11) Balsalobre-Arenas, Maria Luz; Hernández-Madrid, Antonia; Llull, Daniel; Martin-Galiano, Antonio Javier; García, Ernesto; Fenoll, Asuncion; de la Campa, Adela G; Instituto de Salud Carlos III; NIH - National Institute of Dental and Craniofacial Research (NIDCR) (Estados Unidos)Eight optochin-susceptible (Opt(s)) alpha-hemolytic (viridans) streptococcus isolates were characterized at the molecular level. These isolates showed phenotypic characteristics typical of both viridans streptococci and Streptococcus pneumoniae. Comparison of the sequence of housekeeping genes from these isolates with those of S. pneumoniae, Streptococcus mitis, Streptococcus oralis, and Streptococcus pseudopneumoniae suggested that the Opt(s) isolates corresponded to streptococci of the mitis group. Besides, the Opt(s) streptococci were negative by a Gen-Probe AccuProbe pneumococcus test and hybridized with specific pneumococcal probes (lytA and ply) but also with ant, a gene not present in most S. pneumoniae strains. Moreover, the isolates were insoluble in 1% sodium deoxycholate but completely dissolved in 0.1% deoxycholate. Sequence analysis of the lytA gene revealed that the Opt(s) streptococci carried lytA alleles characteristic of those present in nonpneumococcal streptococci of the mitis group. The determination of the partial nucleotide sequence embracing the atp operon encoding the F(o)F(1) H(+)-ATPase indicated that the optochin susceptibility of the isolates was due to the acquisition of atpC, atpA, and part of atpB from S. pneumoniae by horizontal gene transfer.Publication Nationwide trends of invasive pneumococcal disease in Spain (2009-2019) in children and adults during the pneumococcal conjugate vaccine era.(Oxford University Press, 2020-09-29) Miguel, Sara de; Domenech Lucas, Mirian; Gonzalez-Camacho, Fernando; Sempere, Julio; Vicioso-Perez, Maria Dolores; Sanz, Juan Carlos; García Comas, Luis; Ardanuy, Carmen; Fenoll, Asuncion; Yuste, Jose Enrique; Ministerio de Economía, Industria y Competitividad (España)Introduction of pneumococcal conjugate vaccines (PCVs) has shown a marked reduction in the disease caused by vaccine serotypes in children providing herd protection to the elderly group. However, the emergence of non-vaccine serotypes is of great concern worldwide. This study includes national laboratory data from invasive pneumococcal disease (IPD) cases affecting pediatric and adult population during 2009-2019. The impact of implementing different vaccine strategies for immunocompetent adults comparing Spanish regions using PCV13 vs regions using PPV23 vaccine was also analyzed for 2017-2019. The overall reductions of IPD cases by PCV13 serotypes in children and adults were 88% and 59% respectively during 2009-2019 with a constant increase of serotype 8 in adults since 2015. IPD cases by additional serotypes covered by PPV23 increased from 20% in 2009 to 52% in 2019. In children, serotype 24F was the most frequent in 2019 whereas in adults, serotypes 3 and 8 accounted for 36% of IPD cases. Introduction of PCV13 or PPV23 in the adult calendar of certain Spanish regions reduced up to 25% and 11% respectively the IPD cases by PCV13 serotypes, showing a decrease of serotype 3 when PCV13 was used. Use of PCV13 in children has shown a clear impact in pneumococcal epidemiology reducing the burden of IPD in children but also in adults by herd protection although the increase of serotype 8 in adults is worrisome. Vaccination with PCV13 in immunocompetent adults seems to control IPD cases by PCV13 serotypes including serotype 3.Publication Pneumococcal serotypes in children in 4 European countries(Centers for Disease Control and Prevention (CDC), 2010-09) Hanquet, Germaine; Kissling, Esther; Fenoll, Asuncion; George, Robert; Lepoutre, Agnes; Lernout, Tinne; Tarrago Asensio, David; Varon, Emmanuelle; Verhaegen, Jan; Instituto de Salud Carlos III; GlaxoSmithKline; SanofiAfter heptavalent pneumococcal conjugate vaccine (PCV7) was marketed in France, Spain, Belgium, and England and Wales (United Kingdom), invasive disease from non-PCV7 serotypes (NVT) increased. Adjusted serotype-specific incidences among children <15 years of age were compared between 1999-2002 (prevaccine) and 2005-2006 (postmarketing). Vaccine coverage increased to approximately 32%-48% in France, Spain, and Belgium but remained <1% in England and Wales. Serotype 1 incidence rose in all age groups and countries (incidence rate ratio [IRR] 1.3-4.2; p<0.004), independently of PCV7 use, but incidence of serotypes 7F and 19A increased most in France, Spain, and Belgium (IRR 1.9-16.9 in children <5 years; p<0.001), where PCV7 coverage was greater. Vaccine-induced replacement of PCV7 serotypes possibly contributed to NVT increases, as did secular trends. New vaccines targeting these serotypes are available, but serotype dynamics needs further exploration that accounts for underreporting and prevaccine trends.Publication Spread of Streptococcus pneumoniae serotype 8-ST63 multidrug-resistant recombinant Clone, Spain.(Centers for Disease Control and Prevention (CDC), 2014-11) Ardanuy, Carmen; de la Campa, Adela G; García, Ernesto; Fenoll, Asuncion; Calatayud, Laura; Cercenado, Emilia; Pérez-Trallero, Emilio; Bouza, Emilio; Liñares, Josefina; Ministerio de Ciencia e Innovación (España); Instituto de Salud Carlos III; PfizerSince 2004, a total of 131 isolates of Streptococcus pneumoniae multidrug-resistant invasive serotype 8 have been detected in Spain. These isolates showed resistance to erythromycin, clindamycin, tetracycline, and ciprofloxacin. All isolates were obtained from adult patients and shared a common genotype (sequence type [ST]63; penicillin-binding protein 1a [pbp1a], pbp2b, and pbp2x gene profiles; ermB and tetM genes; and a ParC-S79F change). Sixty-eight isolates that required a ciprofloxacin MIC ≥16 μg/mL had additional gyrA gene changes. Serotype 8-ST63 pbp2x sequences were identical with those of antimicrobial drug-susceptible serotype 8-ST53 isolates. Serotype 8-ST63 pbp2b sequences were identical with those of the multidrug-resistant Sweden 15A-ST63 clone. Recombination between the capsular locus and flanking regions of an ST53 isolate (donor) and an ST63 pneumococcus (recipient) generated the novel 15A-ST63 clone. One recombination point was upstream of pbp2x and another was within pbp1a. A serotype 8-ST63 clone was identified as a cause of invasive disease in Spain.