Multidrug-resistant pneumococci (serotype 8) causing invasive disease in HIV+ patients

Sanz, Juan Carlos; Cercenado, Emilia; Marı́n, Mercedes; Ramos, Belén; Ardanuy, Carmen; Rodríguez-Avial, Iciar; Bouza, Emilio

doi:10.1111/j.1469-0691.2011.03495.x

Cited by 24 publications

(32 citation statements)

References 17 publications

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“…All serotype 8 isolates were associated with genotype CC63, suggesting a capsular switching event. This clone expressing serotype 8 was first detected in the 2006 study (18), and it was disseminated in the Madrid area, mainly among HIV-positive patients, with one isolate showing FQ resistance and a ParC S79F amino acid substitution (26,41). In the present series, eight CC63-serotype 8 isolates were also isolated from patients at hospitals in Madrid, a fact that could explain the frequency of this serotype among Cip r pneumococci in 2012.…”

Section: Discussionmentioning

confidence: 64%

Fluoroquinolone-Resistant Pneumococci: Dynamics of Serotypes and Clones in Spain in 2012 Compared with Those from 2002 and 2006

Domenech

Tirado-Vélez

Fenoll

et al. 2014

Antimicrob Agents Chemother

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Section: Discussionmentioning

confidence: 64%

Fluoroquinolone-Resistant Pneumococci: Dynamics of Serotypes and Clones in Spain in 2012 Compared with Those from 2002 and 2006

Domenech

Tirado-Vélez

Fenoll

et al. 2014

Antimicrob Agents Chemother

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“…Although we have no explanation for this decrease, it could be partially due to the existence of an outbreak of IPD due to Serotype 8-ST63 among young adults (mainly HIV-infected patients) in the region of Madrid over the 2004–2009 period (pre-PCV13); in fact among non-PCV13 serotypes, only serotype 8 IPD decreased [27,28]. As expected, a reduction of incidence was observed for all PCV13 additional serotypes (1, 3, 5, 6A, 7F and 19A) with the exception of serotype 3, which remained stable (-11.3%, 95%CI -35.0% to 21.1%, p = 0.477).…”

Section: Discussionmentioning

confidence: 99%

Decrease of invasive pneumococcal disease (IPD) in adults after introduction of pneumococcal 13-valent conjugate vaccine in Spain

et al. 2017

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A prospective laboratory-based multicenter study that collected all adult invasive pneumococcal disease (IPD) episodes from 6 Spanish hospitals before (2008–2009) and after (2012–2013). The 13-valent pneumococcal conjugate vaccine (PCV13) licensure was conducted in order to analyze the impact of PCV13 introduction for children on adult IPD. A total of 1558 IPD episodes were detected. The incidence of IPD decreased significantly in the second period by -33.9% (95% CI, -40.3% to -26.8%). IPD due to PCV7 serotypes (-52.7%; 95% CI, -64.2% to -37.5%) and to PCV13 additional serotypes (-55.0% 95% CI, -62.0% to -46.7%) significantly decreased whereas IPD due to non-PCV13 serotypes remained stable (1.0% 95% CI, -12.9% to 17.2%). IPD due to all PCV13 additional serotypes significantly declined with the exception of serotype 3 (-11.3%; 95%CI -35.0% to 21.1%). IPD due to two non-PCV13 serotypes varied: serotype 6C that rose (301.6%; 95%CI, 92.7% to 733.3%, p<0.001), related to the expansion of ST3866C, and serotype 8 that decreased (-34.9%, 95%CI, -57.1 to -1.2, p = 0.049), related to a decline of the ST638. The recombinant clone ST652111A (variant of ST1569V) increased in frequency. The decrease of serotype 19A IPD was linked to a fall in those antibiotic susceptible clones. In the last period, rates of penicillin- and cefotaxime-resistance remained under 10% and 4%, respectively. Adult IPD decreased after the PCV13 introduction in Spain due to herd protection. The spread of multidrug resistant clones (ST3866C, ST652111A) related to non-PCV13 serotypes needs further surveillance.

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“…ST8 is part of the polysaccharide vaccine Pneumovax 23, but is not included in conjugate vaccines such as Prevnar 13. Many clinical ST8 isolates are broadly resistant to antibiotics such that vaccination to prevent rather than fight ST8 infections is advisable (12, 13). The combination of AGA, glycan microarrays and mAb reverse engineering produced semisynthetic glycoconjugate vaccines against ST8 that were combined with Prevnar 13 to form experimental 14-valent vaccines.…”

Section: Introductionmentioning

confidence: 99%

A semisynthetic Streptococcus pneumoniae serotype 8 glycoconjugate vaccine

et al. 2017

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Glycoconjugate vaccines based on capsular polysaccharides (CPSs) of pathogenic bacteria such as Streptococcus pneumoniae successfully protect from disease, but suffer from incomplete coverage, are troublesome to manufacture from isolated CPSs and lack efficacy against certain serotypes. Defined, synthetic oligosaccharides are an attractive alternative to isolated CPSs but require the identification of immunogenic and protective oligosaccharide antigens. Here, we describe a medicinal chemistry strategy based on a combination of automated glycan assembly (AGA), glycan microarray-based monoclonal antibody (mAb) reverse engineering and immunological evaluation in vivo to uncover a protective glycan epitope (glycotope) for S. pneumoniae serotype 8 (ST8). All four tetrasaccharide frameshifts of ST8 CPS were prepared by AGA and used in glycan microarray experiments to identify the glycotopes recognized by antibodies against ST8. One tetrasaccharide frameshift that was preferentially recognized by a protective, CPS-directed mAb was conjugated to the carrier protein CRM197. Immunization of mice with this semisynthetic glycoconjugate followed by generation and characterization of a protective mAb identified protective and non-protective glycotopes. Immunization of rabbits with semisynthetic ST8 glycoconjugates containing protective glycotopes induced an antibacterial immune response. Co-formulation of ST8 glycoconjugates with the marketed 13-valent glycoconjugate vaccine Prevnar 13 yielded a potent 14-valent S. pneumoniae vaccine. Our strategy presents a facile approach to develop efficient semisynthetic glycoconjugate vaccines.

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Multidrug-resistant pneumococci (serotype 8) causing invasive disease in HIV+ patients

Cited by 24 publications

References 17 publications

Fluoroquinolone-Resistant Pneumococci: Dynamics of Serotypes and Clones in Spain in 2012 Compared with Those from 2002 and 2006

Fluoroquinolone-Resistant Pneumococci: Dynamics of Serotypes and Clones in Spain in 2012 Compared with Those from 2002 and 2006

Decrease of invasive pneumococcal disease (IPD) in adults after introduction of pneumococcal 13-valent conjugate vaccine in Spain

A semisynthetic Streptococcus pneumoniae serotype 8 glycoconjugate vaccine

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