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            "entidad" => "Servicio de Microbiolog&#237;a&#44; Hospital Virgen del Castillo&#44; Yecla&#44; Murcia&#44; Spain"
            "etiqueta" => "f"
            "identificador" => "aff0030"
          ]
          6 => array:3 [
            "entidad" => "Servicio de Microbiolog&#237;a&#44; Hospital Rafael M&#233;ndez&#44; Lorca&#44; Murcia&#44; Spain"
            "etiqueta" => "g"
            "identificador" => "aff0035"
          ]
          7 => array:3 [
            "entidad" => "Unidad de Apoyo Metodol&#243;gico de la Fundaci&#243;n para la Formaci&#243;n e Investigaci&#243;n Sanitarias&#44; Murcia&#44; Spain"
            "etiqueta" => "h"
            "identificador" => "aff0040"
          ]
          8 => array:3 [
            "entidad" => "Centro de Salud Dr&#46; Antonio Garc&#237;a&#44; Molina de Segura&#44; Murcia&#44; Spain"
            "etiqueta" => "i"
            "identificador" => "aff0045"
          ]
        ]
        "correspondencia" => array:1 [
          0 => array:3 [
            "identificador" => "cor0005"
            "etiqueta" => "&#8270;"
            "correspondencia" => "Corresponding author&#46;"
          ]
        ]
      ]
    ]
    "titulosAlternativos" => array:1 [
      "es" => array:1 [
        "titulo" => "Sensibilidad de <span class="elsevierStyleItalic">Streptococcus pneumoniae</span> en ni&#241;osportadores sanos en Murcia &#40;Espa&#241;a&#41;"
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Streptococcus pneumoniae</span> &#40;SP&#41; is one of the most frequent aetiological agents in community-acquired infections in both children and adults&#46; It causes severe invasive disease&#44; such as sepsis&#44; meningitis and bacteraemic pneumonia&#44; as well as other&#44; less severe yet much more frequent processes such as otitis and sinusitis&#44; so it has a very high impact on public health and leads to extensive use of antibiotics&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">1</span></a> Our aim was to determine the susceptibility of SP to commonly used antibiotics in our geographical region&#44; as well as the relationship of its susceptibility to the analysed epidemiological factors&#44; with the purpose of contributing to a more rational use of antibiotics&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Materials and methods</span><p id="par0010" class="elsevierStylePara elsevierViewall">We conducted a cross-sectional multicentre study in children 1&#8211;4 years of age in the autonomous community of the Region of Murcia &#40;CARM&#41;&#46; In 2009&#44; the population of 1-year-old children in the CARM was 18&#44;479&#44; and the population of 4-year-old children was 17&#44;555 &#40;Instituto Nacional de Estad&#237;stica&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">2</span></a> The participants were children that attended check-ups in the context of the &#8220;Well-child programme&#8221; and selected by purposive sampling&#46; We included healthy children age 12 months &#40;10&#8211;14 months&#41; and 4 years &#40;3&#46;5&#8211;4&#46;5 years&#41; that may or may not have been vaccinated with the pneumococcal 7-valent conjugate vaccine &#40;PCV7&#41;&#46; We excluded children presenting with fever&#44; chronic diseases&#44; cystic fibrosis&#44; or that were immunosuppressed&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">In collaboration with the Asociaci&#243;n de Pediatr&#237;a Extrahospitalaria y Atenci&#243;n Primaria de la Regi&#243;n de Murcia &#40;Association of Out-of-Hospital Paediatrics and Primary Care of the Region of Murcia &#91;APERMAP&#93;&#41;&#44; we obtained the participation of 60 primary care paediatricians from all the health areas of the CARM except one that represents only 10&#37; of the population&#44; and of microbiologists working at the hospitals of each health area where the samples were collected&#46; One paediatrician was appointed coordinator for each participating hospital service area&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Data collection</span><p id="par0020" class="elsevierStylePara elsevierViewall">Data was collected over two periods&#44; the summer of 2009 and the winter of 2009&#8211;2010&#46; After verbally explaining the study&#44; we obtained informed consent and administered an epidemiological questionnaire that included the following data&#58; health care centre&#44; date of sample collection&#44; age&#44; sex&#44; pneumococcal vaccination status&#44; breastfeeding&#44; school enrolment&#47;child care attendance&#44; antibiotic use in the past month&#44; parental smoking and number of siblings&#46; The preferred approach was to collect this information from the medical records&#44; and it was completed by interviewing the parents whenever necessary&#46; The project was accepted by the Fundaci&#243;n para la Formaci&#243;n e Investigaci&#243;n Sanitarias de la Regi&#243;n de Murcia &#40;Foundation for Public Health Education and Research of the Region of Murcia &#91;FFIS&#93;&#41; and received a grant from the Proyectos Fundaci&#243;n Cajamurcia programme &#40;FFIS&#47;CM09&#47;037&#41;&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Microbiological sample management</span><p id="par0025" class="elsevierStylePara elsevierViewall">Samples of nasopharyngeal secretions were collected with a flexible nasal swab &#40;Deltalab&#44; AMIES<span class="elsevierStyleSup">&#174;</span> medium swab&#41; by the nursing staff in the paediatrics department of each centre&#46; They were sent to the corresponding health area hospital in transport medium and seeded in 5&#37; sheep blood agar plates with optochin disks&#46; They were incubated for 24&#8211;48<span class="elsevierStyleHsp" style=""></span>h in a 5&#37; to 10&#37; CO<span class="elsevierStyleInf">2</span> atmosphere at a temperature of 37<span class="elsevierStyleHsp" style=""></span>&#176;C&#46; <span class="elsevierStyleItalic">S&#46; pneumoniae</span> was identified by colony morphology&#44; susceptibility to optochin and solubility in bile salts&#46; After being identified&#44; pneumococcal strains were suspended in a skim milk medium &#40;Skim milk Difco<span class="elsevierStyleSup">&#174;</span>&#41; and stored at &#8722;80<span class="elsevierStyleHsp" style=""></span>&#176;C&#44; and then submitted to the referral hospital for susceptibility testing&#46; Later on&#44; they were sent for serotyping to the Laboratorio Nacional de Referencia de Neumococos &#40;National Reference Laboratory for Pneumococcus&#41; of the Instituto Carlos III in Madrid&#46; The penicillin and cefotaxime minimum inhibitory concentrations &#40;MICs&#41; were determined by the Etest method &#40;bioM&#232;rieux&#41; in blood agar plates&#46; For the rest of the antibiotics under study&#44; antimicrobial susceptibility was determined by the disc diffusion method in blood agar plates&#46; After reseeding the strain to be analysed twice in blood agar&#44; an inoculum suspension was prepared and adjusted to the turbidity of a 0&#46;5 McFarland standard&#46; A swab was dipped in the suspension and squeezed against the walls of the tube&#44; and then used to distribute the suspension in three directions on blood agar to obtain a spread plate&#46; After allowing a few minutes for drying&#44; Etest strips for penicillin and cefotaxime were placed on the agar&#46; Disks for the rest of the antibiotics under study &#40;erythromycin&#44; clindamycin&#44; vancomycin&#44; linezolid&#44; rifampicin and levofloxacin&#41; were placed in another spread plate prepared by the same method&#46; Both plates were incubated in a 5&#8211;10&#37; CO<span class="elsevierStyleInf">2</span> atmosphere at 37<span class="elsevierStyleHsp" style=""></span>&#176;C for 24<span class="elsevierStyleHsp" style=""></span>h&#46; We classified strains into susceptible&#44; intermediate or resistant following the updated 2013 recommendations of the Clinical and Laboratory Standards Institute&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">3</span></a><span class="elsevierStyleItalic">SP</span> ATCC 49619 was the control strain&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Statistical analysis</span><p id="par0030" class="elsevierStylePara elsevierViewall">We estimated the minimum sample size at 318 children for each of the four groups&#44; assuming that 30&#37; of the children were carriers&#44; with an accuracy of 5&#37; for a confidence level of 95&#37;&#46; We compared the means using Student&#39;s <span class="elsevierStyleItalic">t</span> test&#46; We analysed the association between qualitative variables with Pearson&#39;s chi square test&#46; We performed a multivariate logistic regression analysis to identify factors associated with resistance that included all variables that reached or approximated statistical significance in the univariate analysis&#46; We performed the same statistical analysis in children 1 year of age stratifying by child care attendance&#46; All results were considered significant for <span class="elsevierStyleItalic">&#945;</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#46;</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Results</span><p id="par0035" class="elsevierStylePara elsevierViewall">The study included 1562 children&#59; 729 were 1 year of age &#40;387 in the summer&#44; 342 in the winter&#41; and 833 were 4 years old &#40;445 in the summer&#44; 388 in the winter&#41;&#46; Out of all the included children&#44; 61&#46;7&#37; &#40;964&#47;1562&#41; had received at least one dose of the PCV7 vaccine and 58&#37; &#40;905&#47;1562&#41; had received two or more doses&#46; The total percentage of nasal carriers was 24&#46;6&#37; &#40;205&#47;832&#41; in the summer and 38&#46;9&#37; &#40;284&#47;730&#41; in the winter &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41;&#44; and the mean value for the entire cohort under study was 31&#46;3&#37; &#40;489&#47;1&#46;562&#41;&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">We lost 122 of the 489 isolates due to various circumstances &#40;freezer malfunction&#44; contamination&#44; lysis during sample transport&#44; etc&#46;&#41; so the antibiogram was performed in 367&#46; Another 24 isolates were lost in the transfer to the Laboratorio Nacional de Referencia de Neumococos&#44; so 343 were serotyped&#46; Thus&#44; we will refer to two figures in our susceptibility analysis&#44; 343 when discussing the serotyped isolates&#44; and 367 when referring to isolates tested for antimicrobial susceptibility&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">We recovered 44 isolates &#40;12&#46;8&#37;&#41; covered by the PCV7 vaccine that corresponded to 4 serotypes&#58; 16 isolates each of serotypes 14 and 23F&#44; 10 isolates of serotype 19F and 6 of serotype B2&#46; Another 83 isolates &#40;24&#46;2&#37;&#41; corresponded to the 6 additional serotypes covered by the PCV13 vaccine&#44; with predominance of serotypes 6A and 19A&#44; with 36 and 31 isolates&#44; respectively&#46; Two hundred and sixteen isolates &#40;63&#37;&#41; were not covered by either vaccine&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the rate of penicillin resistance by route of administration and the disease being treated&#46; Of the 367 isolates&#44; those that met the criteria for nonmeningeal infection treated with oral penicillin V included 103 resistant isolates &#40;28&#37;&#41;&#44; 101 with intermediate resistance &#40;MIC&#44; 0&#46;12&#8211;1<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#41; and two with high-level resistance &#40;MIC&#44; 2<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#41;&#46; All the isolates that met the criteria for nonmeningeal infection treated with parenteral penicillin were susceptible&#46; The main serotypes associated with resistance can be seen in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#44; with the highest percentages being found for serotypes 14 &#40;87&#46;5&#37;&#41;&#44; 35B &#40;71&#46;4&#37;&#41;&#44; 19A &#40;54&#46;8&#37;&#41;&#44; 15A &#40;44&#37;&#41; and 19F &#40;37&#46;5&#37;&#41;&#46; The percentage of resistance in the serotypes covered by the PCV7 was 54&#37;&#44; while it was 18&#46;4&#37; for the remaining serotypes &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41;&#46; The multivariate analysis &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41; showed that being a vaccine serotype &#40;VT&#41; carrier &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;004&#41; and having used antibiotics within the past month &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41; were risk factors for penicillin resistance for the entire sample&#44; while attending a child care centre was a risk factor for one-year-old children &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;049&#41; and age 4 years was a protective factor compared to age 1 year &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;048&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">As for susceptibility for cefotaxime&#44; the MIC of 22 &#40;6&#37;&#41; of the 367 isolates was greater than 0&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#44; and of these 22&#44; 63&#46;6&#37; corresponded to VTs &#40;10 were serotype 14&#41;&#46; We found two isolates with high-level resistance to cefotaxime with the breakpoints for meningeal infection &#40;MIC<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#41; that corresponded to serotypes 14 and 19&#46; We did not detect any isolates with a MIC above 2<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#46; The risk factors for bacterial resistance identified by the multivariate analysis &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41; were VT carriage &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41; and antibiotic use in the past month &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41;&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">The rate of erythromycin resistance was 45&#46;8&#37; &#40;168&#47;367&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; When it came to specific serogroups &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#44; the rate was higher than 75&#37; in 15A&#44; 11A and 14&#44; and higher than 60&#37; in 19A&#44; 19F and 23A&#46; The percentage of resistant isolates of VTs was 68&#46;5&#37;&#44; while it was 40&#46;8&#37; for isolates of nonvaccine serotypes &#40;NVTs&#41; &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41;&#46; Of the 264 penicillin-susceptible pneumococci&#44; we considered 99 &#40;37&#46;5&#37;&#41; resistant to erythromycin&#44; with a predominance of serotypes 15A&#44; 11A&#44; 19A&#44; 23A&#44; 6A and 6C&#46; We found statistically significant differences when we compared erythromycin resistance in penicillin-susceptible versus nonsusceptible isolates &#40;37&#46;5&#37; and 67&#37;&#44; respectively&#41;&#44; which was higher in nonsusceptible isolates &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;003&#41;&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Resistance to clindamycin was detected in 110 strains &#40;29&#46;9&#37;&#41;&#44; with predominance of serotypes 19F &#40;10 isolates&#41; and 33F &#40;7 isolates&#41;&#44; all the isolates of which were resistant&#59; and serotype 15A&#44; with resistance found in 72&#37; of the isolates &#40;18&#47;25&#41;&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">As for combined antibiotic resistance&#44; 69 strains &#40;18&#46;8&#37;&#41; were resistant to penicillin and erythromycin&#44; and 45 &#40;12&#46;3&#37;&#41; were multidrug-resistant &#40;resistance to 3 or more antibiotics&#41;&#46; The predominant serotypes in both cases were 19A&#44; 15A and 14&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">We did not find resistance to any of the other antibiotics under study &#40;linezolid&#44; levofloxacin&#44; rifampicin and vancomycin&#41; in any of the isolates&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Discussion</span><p id="par0080" class="elsevierStylePara elsevierViewall">We conducted this study eight years after the PCV7 was introduced in Spain&#44; and in consideration of the impending marketing of the new 10- and 13-valent conjugate vaccines&#46; We wanted to determine the susceptibility to commonly used antibiotics of the circulating pneumococcal strains in the population of healthy children&#44; as well as the influence of the epidemiological factors under study&#44; as respiratory infections caused by SP &#40;otitis&#44; sinusitis&#44; pneumonia&#41; result in a high use of antibiotics&#44; especially at the primary care level&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">The inappropriate use of antibiotics is an important public health problem&#44; as it has been associated with an increase in bacterial resistances&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">1</span></a> Spain is one of the countries with the highest use of antibiotics and the highest rates of resistance in Europe&#46;<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">1&#44;4</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">The mechanism of penicillin resistance is based on alterations in penicillin-binding proteins &#40;PBPs&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">5</span></a> These alterations lead to various degrees of resistance&#44; from very low levels in susceptible strains&#44; to intermediate- or high-level resistance&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">5</span></a> Two mechanisms of macrolide resistance have been reported&#46; The MLS<span class="elsevierStyleInf">B</span> phenotype involves the enzymatic modification of the ribosomal target &#40;changes in the <span class="elsevierStyleItalic">ermB</span> gene that encodes the production of methylases that methylate the 23S subunit of rRNA&#44; preventing macrolide binding to the target&#41;&#46; This mechanism results in cross-resistance to all macrolides &#40;14-&#44; 15- and 16-membered&#41;&#44; lincosamides and streptogramins&#46; This is the most prevalent phenotype in Spain and it may have a constitutive or an inducible expression&#46; The M phenotype consists in an active antibiotic efflux system &#40;<span class="elsevierStyleItalic">mef</span>&#40;E&#41; gene&#41;&#46; This mechanism confers resistance to 14- and 15-membered macrolides&#44; lincosamides and streptogramins&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">5</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">The patterns of resistance vary widely between countries&#44; and they evolve through time&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">1</span></a> Spain&#44; along with France&#44; has had the highest rates of resistance in Europe&#44;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">4</span></a> and there has been a decline in penicillin resistance in recent years&#46; The factors associated with these changes are a decrease in the use of antibiotics&#44; the introduction of the new vaccines&#44; and other factors that are less understood&#44; such as the expansion of existing clones&#46;<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">1&#44;6&#8211;9</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">When it came to penicillin in meningeal infections&#44; our study found that 28&#37; of the strains were nonsusceptible &#40;MIC<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#46;06<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#41;&#44; figures that were similar to those in some studies conducted in Spain<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">8</span></a> and lower than the figures reported in other studies in Spain and abroad&#46;<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">6&#44;9&#8211;11</span></a> Consistent with the reports of other authors&#44; when we applied the criteria for meningeal infection and parenteral penicillin &#40;resistance&#44; MIC<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>2<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#41;&#44; 100&#37; of pneumococci were susceptible&#46;<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">10&#44;12&#44;13</span></a> The rates of resistance were higher in VT strains &#40;54&#37; in our study&#41; than in NVS strains &#40;18&#37;&#41;&#44; consistent with the existing literature&#46;<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">1&#44;7&#44;9</span></a> Thus&#44; there was a significant decrease in penicillin resistance compared to studies conducted in Spain before the introduction of conjugate vaccines &#40;64&#37;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">14</span></a> and 68&#37;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">15</span></a>&#41; or in the early years of PCV7 use&#44; and it was associated with this vaccine and with the decrease in antibiotic use&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">9&#44;16</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">As was seen in other studies&#44; VT carriage&#44;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">9&#44;10</span></a> younger age&#44;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">11</span></a> child care attendance and antibiotic use in the previous month<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">1&#44;10</span></a> were associated with resistance&#46; Serotype 14 among the PCV7 VTs&#44; 19A among the 13-valent VTs&#44; and serotypes 15A and 35B had the highest rates of penicillin resistance&#44; similar to what has been observed in other studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">1&#44;10</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">Ninety-four percent and 99&#46;4 percent were susceptible to cefotaxime in meningeal and nonmeningeal infections&#44; respectively&#44; consistent with other reports&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">10</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">When it comes to macrolides&#44; resistance to erythromycin has been associated with penicillin resistance&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">1</span></a> We also observed this association in our study&#46; We found a very high percentage of resistance to erythromycin of 45&#46;8&#37;&#44; similar to that of a study conducted before the introduction of the PCV7<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">14</span></a> and higher than the rates reported in other Spanish studies before and after the introduction of this vaccine&#46; This resistance is strongly associated with a widespread use of macrolides&#46;<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">1&#44;7&#44;9&#44;14</span></a> We also found an association between macrolide resistance and VTs&#44; similar to what has been observed by other authors&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">9</span></a> The literature describes an initial decrease in resistance following the introduction of the PCV7 due to a reduction in the prevalence of VTs&#44; and a subsequent increase in resistance due to the emergence of NVTs such as 19A with high rates of resistance&#46;<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">1&#44;11&#44;13</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">We found resistance to more than one antibiotic in 69 strains &#40;18&#46;8&#37;&#41;&#44; which did not diverge significantly from previous reports&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">8</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">We found a percentage of clindamycin resistance of 29&#46;9&#37;&#46; In this study we did not determine the macrolide resistance phenotype&#44; but the seemingly better performance of clindamycin compared to macrolides could be due to the presence of strains with inducible MLS<span class="elsevierStyleInf">B</span> phenotypes or M phenotypes&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">The rates of multi-drug resistance &#40;to 3 or more antibiotics&#41; in Europe&#44; while widely variable&#44; are of approximately 15&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">1</span></a> In our study we found multi-drug resistance in 45 isolates &#40;12&#46;3&#37;&#41;&#44; a proportion close to the European mean&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">In nonmeningeal infections&#44; the change in the affinity of PBPs that confers a degree of resistance to some isolates can be overcome by higher concentrations of penicillin&#46;<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">5&#44;16&#44;17</span></a> Therefore&#44; in regions like ours&#44; with a low prevalence of pneumococcal high-level penicillin resistance &#40;MIC<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>2<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#41;&#44; amoxicillin may be used as the first-line agent in appropriately vaccinated children with mild to moderate disease with a suspected pneumococcal aetiology&#44; such as pneumonia&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">18</span></a> Parenteral penicillin or ampicillin can be used in patients that require admission to the hospital&#46;<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">16&#44;18</span></a> This strategy may also be used in the outpatient management of acute otitis media&#44; as doses of 80&#8211;90<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;day yield middle ear fluid amoxicillin levels that meet pharmacokinetic and pharmacodynamics parameters&#44; with times with concentrations above the MIC that allow the treatment of infections by all intermediately-resistant pneumococci &#40;MIC&#44; 0&#46;12&#8211;1&#46;0<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#41; and many highly-resistant pneumococci &#40;MIC<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>2<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">19</span></a> Similarly&#44; in cases of acute sinusitis&#44; high doses of amoxicillin can achieve adequate concentrations in nasal secretions to overcome resistance attributable to alterations in PBPs&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">20</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall">Third-generation cephalosporins are an excellent option for treating nonmeningeal infections in patients with incomplete vaccination&#44; in areas with a high prevalence of penicillin-resistance pneumococcus &#40;MIC<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>2<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#41; and in severe forms of disease&#44; such as empyema&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">18</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">Whenever a pneumococcal aetiology is suspected in meningeal infections&#44; the patient should be treated with cefotaxime and vancomycin due to their synergistic effect until the causative agent is identified and its susceptibility determined&#44; as 6&#37; of the isolates had intermediate resistance to cefotaxime and two isolates had a MIC of 2<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#44; and both of these circumstances were associated with treatment failure when the patient was treated with cefotaxime or ceftriaxone as monotherapy&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">21</span></a></p><p id="par0150" class="elsevierStylePara elsevierViewall">The use of macrolides in respiratory tract infections should be restricted given the high rate of resistance to these agents&#44; and it should only be considered in cases of suspected atypical pneumonia <a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">18</span></a> or of uncomplicated disease in patients with type 1 beta-lactam hypersensitivity&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">22</span></a></p><p id="par0155" class="elsevierStylePara elsevierViewall">The main strengths of this study are the time when it was conducted&#44; just prior to the introduction of new vaccines to the market&#44; and the number of samples collected&#44; despite the excessive number of samples lost&#46; However&#44; as it usually occurs in this type of study&#44; there was no randomisation since participation was voluntary&#44; so the sample may not be fully representative&#46; We did not collect data on the dosage and duration of previous antibiotic therapy and we did not assess for multiple colonisation&#44; which may have biased the final results&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Conclusions</span><p id="par0160" class="elsevierStylePara elsevierViewall">With the ultimate end of improving the use of antibiotics&#44; our data support the use of high-dose oral amoxicillin in most mild to moderate respiratory tract bacterial infections&#44; such as otitis&#44; sinusitis and community-acquired pneumonia&#44; while in patients that require parenteral antibiotherapy&#44; penicillin and ampicillin would be the first-line therapy for uncomplicated nonmeningeal pneumococcus infections&#46; We found a high rate of macrolide resistance&#44; so the use of these agents should be restricted to very specific situations&#46; We observed the highest rates of resistance in serotypes 14&#44; 19A and 15A&#46; Being a VT carrier&#44; antibiotic use within the past month&#44; age 1 year compared to 4 years&#44; and child care attendance were risk factors for penicillin resistance&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Funding</span><p id="par0165" class="elsevierStylePara elsevierViewall">This project was accepted by the <span class="elsevierStyleGrantSponsor" id="gs1">Fundaci&#243;n para la Formaci&#243;n e Investigaci&#243;n Sanitarias de la Regi&#243;n de Murcia</span> &#40;FFIS&#41; and received a grant from the <span class="elsevierStyleGrantSponsor" id="gs2">Proyectos Fundaci&#243;n Cajamurcia program</span> &#40;FFIS&#47;CM09&#47;037&#41;&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Conflicts of interest</span><p id="par0170" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare&#46;</p></span></span>"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction and objectives</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Streptococcus pneumoniae</span> &#40;SP&#41; is a human pathogen that involves a high use of antibiotics&#46; The objective of the study was to determine the susceptibility to commonly used antibiotics and their associated risk factors&#44; in order to promote rational use of antibiotics&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Patients and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">In a multicentre study was conducted in summer 2009 and winter 2010 on children attending paediatric clinics in the Region of Murcia&#46; A nasopharyngeal sample was collected and an epidemiological questionnaire was completed&#46; The study included 1562 children aged 1 and 4 years old&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Almost one-third &#40;31&#46;3&#37;&#44; 489&#47;1562&#41; of children were nasal carriers&#46; A sensitivity study was carried out on 376 isolates&#44; of which 343 were serotyped&#46; Almost two-thirds &#40;61&#46;7&#37;&#44; 964&#47;1562&#41; of children had received at least one dose of PCV7 &#40;heptavalent pneumococcal conjugate vaccine&#41;&#44; and 12&#46;8&#37; &#40;44&#47;343&#41; of the isolates belonged to PCV7 serotypes&#46; The prevalence rates of penicillin resistance &#40;meningitis infections criteria CMI<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#46;06<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#41; were 28&#46;1&#37;&#59; however&#44; this percentage was 54&#37; in PCV7 serotypes&#46; None of the isolates had &#40;MIC<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>2<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#41;&#44; so prevalence rates of susceptibility with non-meningitis infections criteria were 100&#37;&#46; There was a high percentage of erythromycin resistance &#40;45&#46;7&#37;&#41;&#46; The factors favouring resistance to penicillin and cefotaxime were the consumption of antibiotics in the previous month and the carrying of vaccine serotypes&#46; On the other hand&#44; the age of 4 years old was a protective factor of resistance&#46; The 14&#44; 35B&#44; 19A&#44; 15A&#44; and 19F serotypes were less susceptible to penicillin&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Both oral amoxicillin given to outpatients and intravenous penicillin or ampicillin to hospitalized patients are excellent options for the treatment of non-meningeal infections&#44; as seen with pneumonia in these kinds of environments&#44; where there is low incidence of isolates highly resistant to penicillin &#40;CMI<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>2<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#41;&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducci&#243;n y objetivos</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Streptococcus pneumoniae</span> &#40;SP&#41; es un pat&#243;geno que causa un elevado consumo de antibi&#243;ticos&#46; Objetivos&#58; conocer la sensibilidad a antibi&#243;ticos de uso habitual&#44; los factores epidemiol&#243;gicos asociados y favorecer el uso racional de antibi&#243;ticos&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Pacientes y m&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">En verano del 2009 y el invierno del 2010 realizamos un estudio multic&#233;ntrico en Atenci&#243;n Primaria &#40;AP&#41;&#46; Se recogi&#243; una muestra nasofar&#237;ngea y se cumpliment&#243; una encuesta epidemiol&#243;gica en 1&#46;562 ni&#241;os de 1 y 4 a&#241;os&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">El 31&#44;3&#37; &#40;489&#47;1&#46;562&#41; eran portadores nasales &#40;PN&#41;&#46; Se realiz&#243; un estudio de sensibilidad en 376 aislados&#44; y se serotipificaron 343&#46; El 61&#44;7&#37; &#40;964&#47;1&#46;562&#41; hab&#237;an recibido al menos una dosis de vacuna antineumoc&#243;cica conjugada heptavalente &#40;PCV7&#41;&#46; El 12&#44;8&#37; &#40;44&#47;343&#41; correspond&#237;a a serotipos vacunales &#40;SV&#41;&#46; La resistencia a penicilina &#40;criterio meningitis CMI<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#44;06<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#41; fue del 28&#37;&#44; siendo del 54&#37; para los SV&#46; Para infecciones no men&#237;ngeas&#44; el 100&#37; de los aislados eran sensibles a penicilina parenteral &#40;CMI &#8804;<span class="elsevierStyleHsp" style=""></span>2<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#41;&#46; Existe un alto nivel de resistencias para eritromicina &#40;45&#44;8&#37;&#41;&#46; Fueron factores favorecedores de resistencia haber tomado antibi&#243;ticos el mes previo y ser portador de SV tanto para penicilina como para cefotaxima y la edad de 4 a&#241;os un factor de protecci&#243;n&#46; Los serotipos 14&#44; 35B&#44; 19A&#44; 15A y 19F fueron los menos susceptibles a penicilina&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">La amoxicilina por v&#237;a oral para pacientes ambulatorios y la penicilina o ampicilina por v&#237;a intravenosa para pacientes ingresados son excelentes opciones para el tratamiento de infecciones neumoc&#243;cicas no men&#237;ngeas&#44; en entornos como el nuestro&#44; con una baja incidencia de aislados con alto nivel de resistencia a penicilina &#40;CMI<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>2<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#41;&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Please cite this article as&#58; Alfayate-Migu&#233;lez S&#44; Ruiz G&#243;mez J&#44; Sanchez-Solis de Querol M&#44; Guerrero G&#243;mez C&#44; C&#225;mara Sim&#243;n M&#44; Ortiz Romero MM&#44; et al&#46; Sensibilidad de <span class="elsevierStyleItalic">Streptococcus pneumoniae</span> en ni&#241;osportadores sanos en Murcia &#40;Espa&#241;a&#41;&#46; An Pediatr &#40;Barc&#41;&#46; 2015&#59;83&#58;183&#8211;190&#46;</p>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0020">The participating paediatricians are detailed in <a class="elsevierStyleCrossRef" href="#sec0055">Appendix A</a>&#46;</p>"
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            "apendice" => "<p id="par0175" class="elsevierStylePara elsevierViewall">Hospital Universitario &#40;University Hospital &#91;HU&#93;&#41; Virgen de Arrixaca&#58; &#193;ngela Casquet Barcel&#243;&#44; Guillermo Nieves Gonz&#225;lez&#44; Jos&#233; M&#46; Calder&#243;n S&#225;nchez&#44; Luisa Camps Mart&#237;nez&#44; Nadia Sayed Sancho&#44; M&#46; &#193;ngeles Chumilla Valderas&#44; Joaquina Villalobos P&#233;rez&#44; M&#46; Matilde Cuenca G&#243;mez&#44; Fuensanta Costa Guirao&#44; Bego&#241;a Pelegrin L&#243;pez&#44; Rosario Hurtado del Cerro&#44; Jos&#233; Saura S&#225;nchez Parra&#44; Francisco Espa&#241;a&#44; Inmaculada Mart&#237;nez Artero&#46;</p> <p id="par0180" class="elsevierStylePara elsevierViewall">HU Morales Meseguer&#58; Antonio Iofr&#237;o de Arce&#44; Luisa M&#46; Garc&#237;a Sandoval&#44; Jes&#250;s Meca Garrido&#44; Enrique Guti&#233;rrez&#44; Beatriz Garnica Mart&#237;nez&#44; Rosa M&#46; P&#233;rez Tom&#225;s&#44; Esperanza Moreno Gom&#225;riz&#44; M&#46; Dolores Hern&#225;ndez-Gil&#44; M&#46; Jos&#233; Vicente Fern&#225;ndez&#46;</p> <p id="par0185" class="elsevierStylePara elsevierViewall">HU Reina Sof&#237;a&#58; Gonzalo Sanz Mateo&#44; Fuensanta Alem&#225;n Lorca&#44; Al&#237; Ghandour Houmani&#44; Enrique L&#243;pez Conesa&#44; Silvia Mart&#237;nez Garc&#237;a&#44; Cristina Ca&#241;avate Gonz&#225;lez&#44; Mercedes Guti&#233;rrez P&#233;rez&#44; and Antonio Lao Garc&#237;a&#46;</p> <p id="par0190" class="elsevierStylePara elsevierViewall">HU Los Arcos-Mar Menor&#58; Rosa M&#46; S&#225;nchez Andrada&#44; Isabel Cascales Barcel&#243;&#44; Mar&#237;a Vera Lorente&#44; Maria Teresa Jos&#233; Hernang&#243;mez Cuesta&#44; Monserrat Mart&#237;nez L&#243;pez&#44; Josefina Mart&#237;nez Garre and Jose Maria Ojeda Escuriet&#46;</p> <p id="par0195" class="elsevierStylePara elsevierViewall">HU Rafael M&#233;ndez&#58; Sebasti&#225;n Lorente Garc&#237;a&#44; Francisco P&#233;rez Navarro&#44; Carmen Nelia Vicente de Jim&#233;nez&#44; Manuel Garc&#237;a Moreno&#44; Teresa Dom&#237;nguez Rodr&#237;guez&#44; Juan Francisco Soriano Ibarra and Francisco Jaldo Alba&#46;</p> <p id="par0200" class="elsevierStylePara elsevierViewall">HU Santa Luc&#237;a&#58; M&#46; Pilar Espejo Garc&#237;a&#44; M&#46; Paz Ortu&#241;o del Moral&#44; Lorena Conesa Hern&#225;ndez&#44; M&#46; Dolores Rosique Conesa&#44; Clara Ferr&#225;ndez Garc&#237;a&#44; Gloria Heredero Garc&#237;a&#44; Javier Pe&#241;alver Manrrubia&#44; M&#46; Teresa F&#225;brega Valverde&#44; M&#46; Eugenia Serna de Miquel&#44; Eva Rodr&#237;guez Mart&#237;nez&#44; Ana Gonz&#225;lez Pacanowska&#44; Teresa Vidal Vidal&#46;</p> <p id="par0205" class="elsevierStylePara elsevierViewall">HU Yecla-Altiplano&#58; Juan Jos&#233; Vigueras Abell&#225;n&#44; M&#46; Eugenia Fuentes Sebasti&#225;n&#44; Josefina Romero Ortiz&#44; Luc&#237;a Gonz&#225;lez-Moro Azor&#237;n&#44; Jos&#233; M&#46; Ib&#225;&#241;ez Garc&#237;a and V&#237;ctor S&#225;nchez Qui&#241;ones&#46;</p>"
            "etiqueta" => "Appendix A"
            "titulo" => "Participating paediatricians&#58;"
            "identificador" => "sec0055"
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          "leyenda" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">MIC mg&#47;L&#58; minimum inhibitory concentration&#46;</p>"
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                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Susceptible&#47;Number of isolates&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Intermediate&#47;Number of isolates&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Resistant&#47;Number of isolates&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">&#37; Nonsusceptible&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleItalic">Pneumococcus 367</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Parenteral penicillin&#44; meningeal infection &#40;MIC&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8804;0&#46;06264&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8805;0&#46;12103&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">28&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Parenteral penicillin&#44; nonmeningeal infection &#40;MIC&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8804;2367&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">40&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8805;80&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Oral penicillin &#40;penicillin v&#41; &#40;MIC&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8804;0&#46;06264&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;12&#8211;1101&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8805;22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">28&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Cefotaxime&#44; meningeal infection &#40;MIC&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8804;0&#46;5345&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">120&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8805;22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Cefotaxime&#44; nonmeningeal infection &#40;MIC&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8804;1365&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8805;40&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Erythromycin &#40;MIC&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;0&#46;25199&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#62;1168&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">45&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab940488.png"
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Susceptibility of <span class="elsevierStyleItalic">S&#46; pneumoniae</span> to penicillin&#44; cefotaxime and erythromycin&#46; Breakpoints applied&#58; CLSI 2013&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">ERYTHRO-R&#58; erythromycin-resistant&#59; PENI-NS&#58; penicillin-nonsusceptible&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Serotype&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Number of strains&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">PENI-NS and &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">ERYTHRO-R and &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">14 &#40;87&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">12 &#40;75&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">35B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10 &#40;71&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1 &#40;7&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">19A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">31&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">17 &#40;54&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">20 &#40;64&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">15A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11 &#40;44&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">21 &#40;84&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">19F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6 &#40;37&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10 &#40;62&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">6A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">36&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">9 &#40;25&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">15 &#40;41&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">23F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3 &#40;18&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7 &#40;43&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">11A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">17 &#40;80&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">6C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7 &#40;43&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">15B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5 &#40;31&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">23A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">9 &#40;64&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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        "descripcion" => array:1 [
          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Most frequent serotypes and resistance patterns in descending order of percentage of nonsusceptibility to penicillin&#46;</p>"
        ]
      ]
      2 => array:7 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:3 [
          "leyenda" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">BF&#44; breastfeeding&#59; F&#44; female&#59; M&#44; male&#59; VT&#44; vaccine serotype&#46;</p><p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Bold values are statistically significant&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col">Variable&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col">Resistance&#44; &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Univariate analysis</th><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Multivariate analysis</th></tr><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">OR &#40;95&#37; CI&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">P</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">OR &#40;95&#37; CI&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">P</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Sex M&#47;F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">24&#46;1&#47;22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;89 &#40;0&#46;54&#8211;1&#46;46&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;636&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Age 1&#47;4 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">27&#46;7&#47;19&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;86 &#40;0&#46;73&#8211;1&#46;02&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;073&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;59 &#40;0&#46;34&#8211;0&#46;996&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top"><span class="elsevierStyleBold">&#46;048</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Seasonality&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">21&#46;8&#47;24&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;16 &#40;0&#46;70&#8211;1&#46;92&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;566&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Vaccine doses<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>2&#46; Yes&#47;no&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">21&#46;9&#47;24&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;88 &#40;0&#46;53&#8211;1&#46;45&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;607&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Child care attendance<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> Yes&#47;no&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">31&#46;9&#47;18&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;48 &#40;0&#46;29&#8211;0&#46;80&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top"><span class="elsevierStyleBold">&#46;005</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top"><span class="elsevierStyleBold">0&#46;32 &#40;0&#46;10&#8211;0&#46;997&#41;</span><a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top"><span class="elsevierStyleBold">&#46;049</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">BF<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>3 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">23&#46;9&#47;22&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;10 &#40;0&#46;67&#8211;1&#46;82&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;708&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Antibiotic use in past month&#46; Yes&#47;no&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">52&#46;6&#47;19&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#46;63 &#40;2&#46;31&#8211;9&#46;30&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top"><span class="elsevierStyleBold">&#60;&#46;001</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#46;82 &#40;2&#46;36&#8211;9&#46;82&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top"><span class="elsevierStyleBold">&#60;&#46;001</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Parental smoking&#46; Yes&#47;no&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">24&#46;1&#47;22&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;09 &#40;0&#46;61&#8211;1&#46;92&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;777&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Number of siblings<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>2&#46; Yes&#47;no&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">17&#46;5&#47;24&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;67 &#40;0&#46;32&#8211;1&#46;39&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;284&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">VT carrier&#46; Yes&#47;No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">54&#46;5&#47;18&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&#46;32 &#40;2&#46;75&#8211;10&#46;32&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&#46;42 &#40;1&#46;79&#8211;23&#46;05&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;004&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "leyenda" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">BF&#44; breastfeeding&#59; F&#44; female&#59; M&#44; male&#59; VT&#44; vaccine serotype&#46;</p><p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">Bold values are statistically significant&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col">Variable&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col">Resistance&#44; &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Univariate analysis</th><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Multivariate analysis</th></tr><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">OR &#40;95&#37; CI&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">P</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">OR &#40;95&#37; CI&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">P</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Sex M&#47;F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&#46;11&#47;6&#46;42&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;05 &#40;0&#46;42&#8211;2&#46;45&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;904&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Age 1&#47;4 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&#46;59&#47;6&#46;80&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;23 &#40;0&#46;52&#8211;2&#46;92&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;637&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Seasonality&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&#46;28&#47;6&#46;25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;99 &#40;0&#46;42&#8211;2&#46;33&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;991&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Vaccine doses<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>2&#46; Yes&#47;no&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#46;29&#47;8&#46;92&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;46 &#40;0&#46;19&#8211;1&#46;09&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top"><span class="elsevierStyleBold">&#46;076</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;54 &#40;0&#46;20&#8211;1&#46;45&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;222&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Child care attendance<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a> Yes&#47;no&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&#46;44&#47;7&#46;81&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;68 &#40;0&#46;29&#8211;1&#46;59&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;374&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">BF<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>3 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&#46;38&#47;5&#46;18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;36 &#40;0&#46;58&#8211;3&#46;19&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;477&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Antibiotic use in past month&#46; Yes&#47;no&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">23&#46;26&#47;4&#46;01&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&#46;25 &#40;2&#46;95&#8211;17&#46;81&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top"><span class="elsevierStyleBold">&#60;&#46;001</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8&#46;02 &#40;3&#46;12&#8211;20&#46;62&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top"><span class="elsevierStyleBold">&#60;&#46;001</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Parental smoking&#46; Yes&#47;no&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">9&#46;78&#47;5&#46;09&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#46;02 &#40;0&#46;84&#8211;4&#46;84&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;114&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Number of siblings<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>2&#46; Yes&#47;no&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">17&#46;50&#47;24&#46;12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;13 &#40;0&#46;37&#8211;3&#46;45&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;829&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">VT carrier&#46; Yes&#47;no&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&#46;90&#47;6&#46;15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">16&#46;28 &#40;6&#46;51&#8211;40&#46;75&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top"><span class="elsevierStyleBold">&#60;&#46;001</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">12&#46;54 &#40;4&#46;43&#8211;35&#46;49&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;0001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:22 [
            0 => array:3 [
              "identificador" => "bib0115"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "<span class="elsevierStyleItalic">Streptococcus pneumoniae&#58;</span> epidemiology and risk factors&#44; evolution of antimicrobial resistance&#44; and impact of vaccines"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "J&#46;P&#46; Lynch III"
                            1 => "G&#46; George"
                            2 => "G&#46;G&#46; Zhanel"
                          ]
                        ]
                      ]
                    ]
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                    0 => array:2 [
                      "doi" => "10.1097/MCP.0b013e3283385653"
                      "Revista" => array:6 [
                        "tituloSerie" => "Curr Opin Pulm Med"
                        "fecha" => "2010"
                        "volumen" => "16"
                        "paginaInicial" => "217"
                        "paginaFinal" => "225"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20375783"
                            "web" => "Medline"
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                      ]
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