Characteristics of pneumococci causing disease in adults in Portugal in a time of private use of pneumococcal conjugate vaccines in children

Invasive pneumococcal disease (IPD) and non-invasive pneumococcal pneumonia (NIPP) are important causes of morbidity and mortality worldwide, particularly among young children, the elderly and the immunocompromised. Two types of vaccines are available to prevent pneumococcal disease, but these target a limited number of the 97 pneumococcal serotypes described so far. One type is a strictly polysaccharide-based vaccine, which includes 23 serotypes and is primarily indicated for adults (23-valent pneumococcal polysaccharide vaccine, PPV23, targeting serotypes 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F and 33F). The other type are pneumococcal conjugate vaccines (PCVs). Three PCVs have been licensed to date: a 7-valent formulation (PCV7), which covers serotypes 4, 6B, 9V, 14, 18C, 19F and 23F; a 10-formulation (PCV10), which includes all serotypes of PCV7, plus serotypes 1, 5 and 7F; and a 13-valent formulation (PCV13), which targets all serotypes of PCV10 and also serotypes 3, 6A and 19A. PCV7 became available in the USA in 2000 and in Europe in 2001. Several studies reported that the use of PCV7 in children was followed by decreases in the incidence of PCV7-type IPD in children. Since PCV7 reduced colonization due to the vaccine serotypes and because children are the main reservoirs of pneumococci in the community, PCV7 serotypes became less transmitted from children to the remaining population, with this resulting in decreases in the incidence of PCV7-type IPD also in non-vaccinated people, including adults (herd protection). However, at the same time, increases in the incidence of IPD due to particular non-PCV7 serotypes occurred in children and adults. In Portugal, PCV7 was used in children between 2001 and 2009, but was not included in the national immunization program. The uptake of PCV7 was initially low (43% in 2004), but increased steadily (75% in 2008). In mid-2009 and early-2010, PCV10 and PCV13, respectively, became available for children, with PCV13 replacing PCV7. PCV10 and PCV13 were given through the private market until June 2015, when PCV13 was included in the national immunization program for children. During the availability of PCV10 and PCV13 outside the national immunization program, PCV13 was the most frequently used PCV. Even though PPV23 and PCV13 are also available for adults, in Portugal, adult pneumococcal vaccination is estimated to be low. The studies presented in this thesis aimed to evaluate the characteristics of pneumococci causing adult IPD and adult NIPP in Portugal in a time of private PCVs use in children in the country. The isolates were collected by an epidemiological surveillance network, in work since 1999, which includes several laboratories throughout the country. All isolates analyzed were collected from adult patients (≥ 18 yrs). For the characterization of adult IPD isolates we determined the serotype and antimicrobial susceptibility of isolates responsible for adult IPD between 2009 and 2014 (n = 2428). The results were compared with previously published data from the same network (1999-2008, n = 2182). Adult IPD isolates were also characterized by Multi Locus Sequence Typing (MLST) and regarding the presence and type of two pilus islands (PI-1 and PI-2). For this characterization, 50% of adult IPD isolates recovered from 2008 to 2011 (n = 871), from each serotype, were randomly chosen. For the characterization of adult NIPP isolates, we determine the serotype and antimicrobial susceptibility of a collection of isolates responsible for adult NIPP between 1999 and 2015 (n = 2735). Previous studies from this epidemiological surveillance network, which analyzed the serotypes of adult IPD isolates recovered between 1999 and 2008, found that in Portugal there was a significant decrease in the proportion of PCV7 serotypes in adult IPD in the post-PCV7 period (from 30.3% in 1999-2003 to 16.4% in 2008, p < 0.001), accompanied by increases in the proportion of specific non-PCV7 serotypes (serotypes 1, 7F and 19A). When analyzing adult IPD data from 2009 to 2014, we found further changes in the serotype distribution of pneumococci causing adult IPD. Comparing adult IPD isolates recovered in 2009-2011 with those recovered in 2012- 2014, a new but small decrease in the representation of PCV7 serotypes in adult IPD was noted (from 19% to 14%, p = 0.003). In what concerns the overall proportion of PCV13 serotypes, it peaked in 2008 (70%) and then started a significant and gradual decline until 2014 (38%, p < 0.001), the last year analyzed. Since PCV10 and PCV13 became available in Portugal only in mid-2009 and early-2010, respectively, the initial decline in the overall proportion of PCV13 serotypes was independent of childhood vaccination. The PCV13 serotypes that decreased the most from 2008 to 2011 were serotypes 1 (from 10.7% in 2009 to 4.1% in 2011, p < 0.001) and 5 (from 2.0% in 2008 to 0% in 2011, p = 0.003). The early decreases of these two serotypes may be associated with long term fluctuations and outbreaks, described elsewhere. Other serotypes, instead, decreased when a herd effect with the use of PCV13 in children was expected. This was the case of serotype 7F (from 8.2% in 2012 to 2.7% in 2014, p < 0.001) and 19A (from 9.7% in 2012 to 5.6% in 2014, p = 0.027). In the post-PCV13 period, there were also significant increases in some of the serotypes not covered by PCV13 (i.e. serotypes 8, 15A, 20 and 22F). In what concerns antimicrobial resistance, and considering current Clinical Laboratory Standards Institute (CLSI) breakpoints, in 2012-2014, o.5% of the isolates were considered penicillin non-susceptible pneumococci (PNSP) and 17% erythromycin resistant pneumococci (ERP). Regarding the characterization of adult IPD isolates by MLST we found high genetic diversity, with 206 different sequence types (STs) detected. The STs represented 80 different clonal complexes (CCs), but the six more frequent CCs accounted for half of the isolates (CC156, CC191, CC180, CC306, CC62 and CC230). Most of the STs detected related to STs described in other countries. We found the changes in serotypes occurring in adult IPD following PCV7 use in children were mostly driven by the expansion of previously circulating clones or to decreases in most of the lineages expressing a given serotype. Concerning the presence and type of PI-1 and PI-2, only a small proportion of isolates was positive for any of the PIs (31.9%). Most of the isolates expressing PCV7 serotypes presented PI-1 (87.9%), while PI-2 positive isolates were mainly found among isolates expressing serotypes 1 and 7F, which are serotypes included in PCV10 and PCV13. In what concerns the characterization of adult NIPP isolates, we found significant declines in the proportion of vaccines serotypes following the use of PCVs in children, although these declines were less marked than those occurring in adult IPD. In adult NIPP, the proportion of PCV7 serotypes declined from 31% in 1999-2003 to 11% in 2011 (p < 0.001), while the overall proportion of PCV13 serotypes declined from 44% in 2010 to 30% in 2015 (p < 0.001). When considering the 2012-2015 period, and according to current CLSI breakpoints, 1% of adult NIPP isolates were PNSP and 21.7% were ERP. Comparison of NIPP serotypes with IPD serotypes identified associations of several serotypes with either disease presentation. The studies presented in this thesis showed that in Portugal in the time of PCVs use in children outside the national immunization program there were several changes in the characteristics of pneumococci causing disease in adults. While some of the changes suggested herd protection with the use of PCVs in children, others were independent. The inclusion of PCV13 in the national immunization program for children in June 2015 may be further reducing the importance of PCV13 serotypes in adult IPD and adult NIPP. However, increases of particular non-PCV13 serotypes in adult IPD are concerning and should be monitored. Continued IPD and NIPP epidemiological surveillance is important due to different serotype distribution and dynamics of pneumococci causing each disease presentation

Conjugate vaccine serotypes persist as major causes of non-invasive pneumococcal pneumonia in Portugal despite declines in serotypes 3 and 19A (2012-2015)

Copyright: © 2018 Hora ́cio et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Non-invasive pneumococcal pneumonia (NIPP) is a frequent cause of morbidity and mortality worldwide. The 13-valent pneumococcal conjugate vaccine (PCV13) was included in the national immunization program of children living in Portugal in 2015. Until then, PCV7 (since late 2001) and PCV13 (since early 2010) were given through the private market. We determined the serotype distribution and antimicrobial susceptibility of isolates causing adult NIPP in 2012-2015 and compared the results with previously published data (2007-2011). There were 50 serotypes among the 1435 isolates. The most common were serotypes: 3 (14%), 11A (8%), 19F (6%), 23A (5%), 6C (5%), 19A (4%), 23B (4%), 9N (4%) and non-typable isolates (4%). When considering data since the availability of PCV13 for children in the private market, the proportion of PCV13 serotypes declined from 44.0% in 2010 to 29.7% in 2015 (p < 0.001), mainly due to early decreases in the proportions of serotypes 3 and 19A. In contrast, during the same period, PCV7 serotypes (11.9% in 2012-2015) and the serotypes exclusive of the 23-valent polysaccharide vaccine (26.0% in 2012-2015), remained relatively stable, while non-vaccine types increased from 27.0% in 2010 to 41.9% in 2015 (p<0.001). According to the Clinical and Laboratory Standards Institute (CLSI) breakpoints, penicillin non-susceptible and erythromycin resistant isolates accounted for 1% and 21.7%, respectively, of the isolates recovered in 2012-2015, with no significant changes seen since 2007. Comparison of NIPP serotypes with contemporary invasive disease serotypes identified associations of 19 serotypes with either disease presentation. The introduction of PCV13 in the national immunization program for children from 2015 onwards may lead to reductions in the proportion of NIPP due to vaccine serotypes but continued NIPP surveillance is essential due to a different serotype distribution from invasive disease.ANH was supported by a grant from Fundação para a Ciência e Tecnologia, Portugal SFRH/BD/81205/2011. This work was partly supported by Fundação para a Ciência e a Tecnologia, Portugal (PTDC/DTP-EPI/1555/2014), LISBOA-01-0145-FEDER-007391, project cofunded by FEDER, through POR Lisboa 2020 - Programa Operacional Regional de Lisboa, PORTUGAL 2020 and Fundação para a Ciência e a Tecnologia, and an unrestricted Investigator initiated project from Pfizer.info:eu-repo/semantics/publishedVersio

Non-invasive Pneumococcal pneumonia in Portugal : serotype distribution and antimicrobial resistance

Copyright: © 2014 Horácio et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.There is limited information on the serotypes causing non-invasive pneumococcal pneumonia (NIPP). Our aim was to characterize pneumococci causing NIPP in adults to determine recent changes in serotype prevalence, the potential coverage of pneumococcal vaccines and changes in antimicrobial resistance. Serotypes and antimicrobial susceptibility profiles of a sample of 1300 isolates recovered from adult patients (≥18 yrs) between 1999 and 2011 (13 years) were determined. Serotype 3 was the most frequent cause of NIPP accounting for 18% of the isolates. The other most common serotypes were 11A (7%), 19F (7%), 19A (5%), 14 (4%), 22F (4%), 23F (4%) and 9N (4%). Between 1999 and 2011, there were significant changes in the proportion of isolates expressing vaccine serotypes, with a steady decline of the serotypes included in the 7-valent conjugate vaccine from 31% (1999-2003) to 11% (2011) (P<0.001). Taking together the most recent study years (2009-2011), the potential coverage of the 13-valent conjugate vaccine was 44% and of the 23-valent polysaccharide vaccine was 66%. While erythromycin resistance increased from 8% in 1999-2003 to 18% in 2011 (P<0.001), no significant trend was identified for penicillin non-susceptibility, which had an average value of 18.5%. The serotype distribution found in this study for NIPP was very different from the one previously described for IPD, with only two serotypes in common to the ones responsible for half of each presentation in 2009-2011 - serotypes 3 and 19A. In spite of these differences, the overall prevalence of resistant isolates was similar in NIPP and in IPD.A.N. Horácio was supported by grant SFRH/BD/81205/2011, from Fundação para a Ciência e Tecnologia, Portugal. This work was partially supported by Fundação para a Ciência e Tecnologia, Portugal (PTDC/DTP-EPI/1759/2012) and unrestricted research grants from Pfizer and GlaxoSmithKline.info:eu-repo/semantics/publishedVersio

Serotype 3 Remains the Leading Cause of Invasive Pneumococcal Disease in Adults in Portugal (2012-2014) Despite Continued Reductions in Other 13-Valent Conjugate Vaccine Serotypes

Since 2010 the 13-valent pneumococcal conjugate vaccine (PCV13) replaced the 7-valent vaccine (PCV7) as the leading pneumococcal vaccine used in children through the private sector. Although, neither of the PCVs were used significantly in adults, changes in adult invasive pneumococcal disease (IPD) were expected due to herd protection. We characterized n = 1163 isolates recovered from IPD in adults in 2012-2014 with the goal of documenting possible changes in serotype prevalence and antimicrobial resistance. Among the 54 different serotypes detected, the most frequent, accounting for half of all IPD, were serotypes: 3 (14%), 8 (11%), 19A (7%), 22F (7%), 14 (6%), and 7F (5%). The proportion of IPD caused by PCV7 serotypes remained stable during the study period (14%), but was smaller than in the previous period (19% in 2009-2011, p = 0.003). The proportion of IPD caused by PCV13 serotypes decreased from 51% in 2012 to 38% in 2014 (p < 0.001), mainly due to decreases in serotypes 7F and 19A. However, PCV13 serotype 3 remained relatively stable and the most frequent cause of adult IPD. Non-PCV13 serotypes continued the increase initiated in the late post-PCV7 period, with serotypes 8 and 22F being the most important emerging serotypes. Serotype 15A increased in 2012-2014 (0.7% to 3.5%, p = 0.011) and was strongly associated with antimicrobial resistance. However, the decreases in resistant isolates among serotypes 14 and 19A led to an overall decrease in penicillin non-susceptibility (from 17 to 13%, p = 0.174) and erythromycin resistance (from 19 to 13%, p = 0.034). Introduction of PCV13 in the NIP for children, as well as its availability for adults may further alter the serotypes causing IPD in adults in Portugal and lead to changes in the proportion of resistant isolates.info:eu-repo/semantics/publishedVersio

ENDOVASCULAR MANAGEMENT OF LIFE-THREATENING CAROTID BLOWOUT SYNDROME AFTER OSTEORADIONECROSIS OF THE MANDIBULA — A CASE REPORT AND LITERATURE REVIEW

Aim: Carotid blowout syndrome is a rare but devastating complication of head and neck malignancy, and is associated with a reported mortality and neurologic morbidity of 40% and 60% respectively. The aim of this case report is to present our experience with a single case of massive haemorrhage from the internal carotid artery (ICA) in a previously irradiated neck treated with a stentgraft, hence maintaining carotid artery patency. Methods: Relevant medical data were collected and literature review was performed. Results: The patient is a 61-year-old male with a previous history of head and neck cancer submitted to radical surgery and chemo and radiotherapy. Seven years later, the patient was diagnosed with osteoradionecrosis of the mandibula and submitted to surgery. Hospital stay was prolonged due to local infection and suture dehiscence with carotid artery exposure. No previous episodes of sentinel bleeding were registered. Life-threatening haemorrhage from the surgical wound started acutely. Under manual compression, the patient was rushed to the angiography suite and the diagnostic angiography ascertained active bleeding from the ICA. A stentgraft Atrium Advanta V12 (Maquet Getinge group, Hudson, NH, USA) was deployed maintaining ICA patency. The patient was subsequently submitted to surgical reconstruction and had an uneventful recovery. Discussion: Management of acute carotid blow syndrome is critical, often requiring a multidisciplinary approach. Stentgraft placement is a highly feasible and effective approach with lower morbimortality rates when compared to surgical repair/ ligation or endovascular embolization. However long term results with patency rates are currently lacking

Personality and attachment in the homeless: a systematic review

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2022Introdução: As pessoas em situação de sem-abrigo apresentam uma elevada prevalência de psicopatologia, incluindo perturbações da personalidade. Dada a associação entre perturbações da personalidade e vinculação, e a potencial importância destes dois temas na compreensão das pessoas sem-abrigo, o objetivo deste estudo foi o de rever todos os artigos que analisaram as perturbações da personalidade e a vinculação nas pessoas sem-abrigo. Métodos: Nesta revisão usaram-se critérios de inclusão amplos, de modo a incluir todos os estudos sobre vinculação nos sem abrigo e todos os estudos sobre personalidade nos sem-abrigo, que tenham avaliado a distribuição de pelo menos três perturbações da personalidade. Um total de 213 estudos foram analisados por título e resumo, dos quais 63 foram escolhidos para leitura do texto completo. Destes, 14 artigos obedeceram aos critérios de inclusão, tendo sido incluídos nesta revisão sistemática. Resultados: Dos 14 artigos incluídos, seis estudos avaliaram as perturbações da personalidade e oito estudos avaliaram a vinculação. As perturbações da personalidade revelaram-se muito frequentes nas pessoas sem-abrigo, ocorrendo em 64% a 79% das amostras. As perturbações da personalidade paranoide, borderline, evitante e anti-social foram as mais comummente identificadas, embora as suas frequências tenham variado entre os estudos. Os artigos sobre vinculação diferiram nos métodos usados e nos resultados obtidos. Ainda assim, observou-se uma predominância dos estilos de vinculação insegura nas pessoas sem-abrigo (62% a 100% das amostras). Conclusões: A elevada prevalência das perturbações da personalidade e dos estilos de vinculação insegura nos sem-abrigo pode ter um impacto negativo nas estratégias de intervenção planeadas para ajudar estas pessoas. Esta revisão sistemática demonstrou que a literatura disponível sobre as perturbações da personalidade e a vinculação nos sem-abrigo é escassa, e que mais estudos são necessários sobre estes dois temas.Background: Homeless people present high rates of psychopathology, including personality disorders. Given the link between personality disorders and attachment and the potential importance of these two traits for understanding homeless populations, our aim was to review all studies focusing on personality disorders and attachment in the homeless. Methods: We used broad inclusion criteria to include all studies focusing on attachment and on at least three personality disorders in the homeless. Overall, 213 studies were screened through title and abstract. Of these, 63 were chosen for full-text assessment. A total of 14 articles met eligibility criteria and were included. Results: Six studies evaluated personality in the homeless and eight studies focused on attachment in the homeless. In general, reports suggest personality disorders are highly frequent in the homeless, with frequencies ranging between 64% and 79% for any personality disorder. The most common personality diagnoses were paranoid, borderline, avoidant and antisocial personality disorders, but their frequencies varied greatly between studies. Attachment reports differed in the methods used and presented diverse results and correlates. Even so, insecure types of attachment dominated in the homeless in the few studies showing this analysis (accounted for 62% to 100% of the samples). Conclusions: The high prevalence of personality disorders and insecure types of attachment in the homeless may impact intervention strategies for the homeless. The available literature focusing on attachment and the full assessment of personality disorders in the homeless is scarce. The present review supports the need for more research on these two topics

Infecção pneumocócica invasiva no adulto em Portugal em 2008 e 2009

Tese de mestrado. Biologia (Microbiologia Aplicada). Universidade de Lisboa, Faculdade de Ciências, 2011Streptococcus pneumoniae é um microrganismo patogénico do Homem, responsável por elevadas taxas de morbilidade e mortalidade em todo o mundo. A epidemiologia da infecção pneumocócica tem sido fundamental para avaliar a adaptação deste microrganismo à pressão imposta pela vacinação e uso de antibióticos. Esta tese teve como objectivo caracterizar feno e genotipicamente uma colecção de 425 estirpes de pneumococos responsável por infecção invasiva em adultos (18 a 64 anos de idade), em 2008 e 2009, em Portugal. Visto que no período em análise esteve disponível a vacina anti-pneumocócica conjugada 7-valente (PCV7), pretendeu-se ainda comparar estes resultados com os referentes ao período pré-vacinal de modo a avaliar o possível impacto da vacinação das crianças, na população pneumocócica que afecta os adultos. A caracterização fenotípica consistiu na serotipagem e determinação das taxas de susceptibilidade a diferentes classes de antimicrobianos, e a caracterização genotípica consistiu na determinação dos perfis de macrorestrição, obtidos por electroforese em gel de campo pulsado (PFGE), e perfis de Multi Locus Sequence Typing (MLST) e ainda na detecção da presença e distribuição das ilhas de patogenecidade que codificam para os pili tipo 1 (PI-1) e 2 (PI-2). Os serotipos 1, 3, 7F, 14 e 19A foram os mais frequentes, tendo provocado cerca de 50% das infecções. A não susceptibilidade à penicilina e eritromicina foi observada em 16,7% e em 14,6% das estirpes, respectivamente. Os complexos clonais CC306, CC156, CC191, CC62, CC180 e CC230 surgiram em aproximadamente metade das estirpes analisadas por MLST. As ilhas de patogenicidade PI-1 e PI-2 foram identificadas em 13,3% e em 28% das estirpes, respectivamente. Entre o período pré-vacinal e o analisado neste trabalho observou-se uma diminuição significativa da proporção de infecções provocadas pelo serotipo 4, um aumento significativo, para cerca do dobro, da não susceptibilidade à eritromicina e uma emergência de linhagens genéticas pré-existentes.Streptococcus pneumoniae is a human pathogen responsible for high rates of morbidity and mortality worldwide. The epidemiology of pneumococcal infections has been critical to evaluate the adaptation of this microorganism to the pressure imposed by vaccination and antimicrobial use. The aim of this thesis was to characterize pheno and genotypically a collection of 425 pneumococcal strains responsible for invasive pneumococcal disease in adults (with 18 to 64 years old), in 2008 and 2009, in Portugal. A pneumococcal 7-valent conjugate vaccine (PCV7) was available in this period and so, this thesis also aims to compare these results with the ones obtained in the pre-vaccine era, to evaluate the possible impact that vaccinating children with this vaccine might have had in the adult pneumococcal population. Phenotypic characterization consisted in serotyping and in antimicrobial susceptibility profiling of the bacterial isolates, while the genotypic characterization consisted in the determination of the macrorestriction profiles, obtained by Pulsed Field Gel Electrophoresis (PFGE), and Multi Locus Sequence Typing (MLST) profiles and also in the detection of the presence and distribution of the pathogenecity islands that encode pilus like structures, PI-1 and PI-2. Serotypes 1, 3, 7F, 14 and 19A were the most frequent, being responsible for almost 50% of all infections. Penicillin and erythromycin non-susceptibility were detected in 16,7% and 14,6% of the bacterial isolates, respectively. Clonal complexes CC306, CC156, CC191, CC62, CC180 and CC230 appeared in almost half of strains analyzed by MLST. Pathogenicity islands PI-1 and PI-2 were identified in 13,3% and 28% of all isolates. Between the pre-vaccine period and the one analyzed in this study, the proportions of serotype 4 infections have significantly decreased, erythromycin non-susceptibility has significantly doubled, and an emergence of the already existent genetic lineages occurred

Non-invasive pneumococcal pneumonia in Portugal--serotype distribution and antimicrobial resistance.

There is limited information on the serotypes causing non-invasive pneumococcal pneumonia (NIPP). Our aim was to characterize pneumococci causing NIPP in adults to determine recent changes in serotype prevalence, the potential coverage of pneumococcal vaccines and changes in antimicrobial resistance. Serotypes and antimicrobial susceptibility profiles of a sample of 1300 isolates recovered from adult patients (≥18 yrs) between 1999 and 2011 (13 years) were determined. Serotype 3 was the most frequent cause of NIPP accounting for 18% of the isolates. The other most common serotypes were 11A (7%), 19F (7%), 19A (5%), 14 (4%), 22F (4%), 23F (4%) and 9N (4%). Between 1999 and 2011, there were significant changes in the proportion of isolates expressing vaccine serotypes, with a steady decline of the serotypes included in the 7-valent conjugate vaccine from 31% (1999-2003) to 11% (2011) (P<0.001). Taking together the most recent study years (2009-2011), the potential coverage of the 13-valent conjugate vaccine was 44% and of the 23-valent polysaccharide vaccine was 66%. While erythromycin resistance increased from 8% in 1999-2003 to 18% in 2011 (P<0.001), no significant trend was identified for penicillin non-susceptibility, which had an average value of 18.5%. The serotype distribution found in this study for NIPP was very different from the one previously described for IPD, with only two serotypes in common to the ones responsible for half of each presentation in 2009-2011 - serotypes 3 and 19A. In spite of these differences, the overall prevalence of resistant isolates was similar in NIPP and in IPD

Antimicrobial resistance of the isolates responsible for non-invasive pneumococcal pneumonia in adults in Portugal, stratified by age groups (1999–2011).

a<p>PEN – penicillin; CTX – cefotaxime; LEV – levofloxacin; ERY – erythromycin; CLI – clindamycin; CHL – chloramphenicol; SXT – trimethoprim/sulphamethoxazole; TET – tetracycline. All isolates were susceptible to vancomycin and linezolid.</p>b<p>Non-susceptibitily to penicillin was determined using the CLSI breakpoints prior to 2008 <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0103092#pone.0103092-Clinical1" target="_blank">[20]</a>.</p

Serotype distribution of PNSP and ERP causing non-invasive pneumococcal pneumonia in adults in Portugal (1999–2011).

a<p>Only the serotypes that presented at least 10 non-susceptible isolates are shown.</p>b<p>Significant P-values after FDR correction are highlighted in bold.</p>c<p>Other serotypes found among PNSP: 6B (n = 8), non-typable (n = 7), 6A and 29 (n = 5, each), 23B and 24F (n = 3, each), 7C (n = 2), 1, 3, 4, 11A, 15B, 15F, 22F, 23A, 35A (n = 1, each).</p>d<p>NT – non typable.</p>e<p>Other serotypes found among ERP: 9V and 11A (n = 4, each), 3, 15B, 22F, 23A, 24F (n = 3, each), 6A (n = 2), 1, 7F, 8, 9N, 15F, 16F, 17F, 23B, 29, 33F and 35F (n = 1, each).</p