Emergence of Penicillin‐Nonsusceptible<i>Streptococcus pneumoniae</i>Clones Expressing Serotypes Not Present in the Antipneumococcal Conjugate Vaccine

Porat, Nurith; Arguedas, Adriano; Spratt, Brian G.; Trefler, Ronit; Brilla, Eduardo; Loaiza, Cecilia; Godoy, Dan; Bilek, Nicole; Dagan, Ron

doi:10.1086/425908

Cited by 112 publications

(54 citation statements)

References 34 publications

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“…Another possibility is serotype switch, 25 whereby pneumococcal strains express a new capsular serotype, possibly to evade host immunity. This phenomenon has been described between 15B and 15C, 26 19F and 23F, 27 9V and 11A, 28 and others. 25 Although serotype replacement has been a concern after the release of the conjugate pneumococcal vaccine, experts hoped that antibiotic resistance would decrease because resistance had been highly concentrated in PCV7 and PCV7 cross-reactive serotypes.…”

Section: Discussionsupporting

confidence: 58%

Post-PCV7 Changes in Colonizing Pneumococcal Serotypes in 16 Massachusetts Communities, 2001 and 2004

et al. 2005

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ABSTRACT. Objective. The introduction of heptavalent conjugate pneumococcal vaccine (PCV7) has raised concerns for replacement with nonvaccine serotypes in both invasive disease and asymptomatic carriage. Analysis of colonizing serotypes among healthy children in the community provides critical data on such changes.Methods. Nasopharyngeal specimens were obtained from children who were younger than 7 years during well-child or sick visits in primary care practices in 16 Massachusetts communities during 2001 and 2004. Susceptibility testing and serotyping were performed on isolated Streptococcus pneumoniae strains. Vaccination history with PCV7 was abstracted from the medical record.Results. Among colonizing pneumococcal isolates, PCV7 serotypes decreased from 36% to 14%, and non-PCV7 serotypes increased from 34% to 55%. Overall carriage did not change (26% to 23%); neither did carriage of potentially cross-reactive serotypes (30% to 31%). The most common non-PCV7 serotypes were serotypes 11, 15, and 29. There was a substantial increase in penicillin nonsusceptibility from 8% to 25% in non-PCV7 serotypes; 35% were highly resistant to penicillin. Penicillin nonsusceptibility increased from 45% to 56% among PCV7 serotypes while remaining stable among PCV7 potentially cross-reactive strains (51% vs 54%).Conclusions. Pneumococcal colonization has changed after the introduction of PCV7, both in serotype distribution and in patterns of antibiotic resistance. The frequency of nonvaccine strains has increased, and the proportion of nonvaccine isolates that are not susceptible to penicillin has tripled. This shift toward increased carriage of nonvaccine serotypes warrants vigilance for changes in the epidemiology of invasive pneumococcal disease. B efore the release of a conjugate vaccine for US children, Streptococcus pneumoniae caused invasive disease in 1 in 500 to 600 children who were younger than 2 years. 1 In addition, rising antibiotic resistance among pneumococcal strains was a major concern among public health officials. 2,3 By 1999, 38% of laboratory isolates in children who were younger than 2 years were nonsusceptible to penicillin, 4 with higher rates reported in local areas. [5][6][7] In February 2000, heptavalent pneumococcal conjugate vaccine (PCV7) was released to provide immunity to the 7 serotypes responsible for 85% of pediatric invasive pneumococcal disease 8 and 78% of penicillin-nonsusceptible S pneumoniae (PNSP) isolates in children. 9 Prelicensure trials showed a 90% reduction in invasive disease 10 and a 23% reduction in all-cause pneumonia in the first 2 years of life. 11 Postlicensure studies have also shown declines in invasive pneumococcal disease from 188 per 100 000 to 59 cases per 100 000 in US children who are younger than 2 years. 4,12 Despite the success of PCV7 in reducing invasive disease, critical questions remain about the changing pneumococcal reservoir. Some trials of immunization with PCV7 have shown a 50% to 65% decrease in carriage of vaccine serotypes [13][14][15] and have rai...

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Section: Discussionsupporting

confidence: 58%

Post-PCV7 Changes in Colonizing Pneumococcal Serotypes in 16 Massachusetts Communities, 2001 and 2004

et al. 2005

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“…It is not known whether NTHi isolates that express b-lactamases (responsible for resistance to b-lactam antibiotics such as penicillins, cephamycins and carbapenems) are phylogenetically related. Various studies of Streptococcus pneumoniae have shown phylogenetic relationships among antibiotic-resistant strains (Beall et al, 2006;Hanage et al, 2009;Porat et al, 2004;Xu et al, 2009). In this study, we explored whether or not NTHi shows genetic relatedness in relation to b-lactamase enzyme production.…”

Section: Introductionmentioning

confidence: 99%

Phylogenetic relatedness and diversity of non-typable Haemophilus influenzae in the nasopharynx and middle ear fluid of children with acute otitis media

Kaur

Chang

et al. 2011

Journal of Medical Microbiology

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The phylogenetic relationships of non-typable Haemophilus influenzae (NTHi) strains prospectively isolated from healthy children and children with acute otitis media (AOM) were analysed using multilocus sequence typing (MLST). A total of 165 NTHi isolates were collected over a 3.5 year time frame during 2006 through 2009. The strains were tested for b-lactamase production; 28.5 % were positive. Seventy different NTHi sequence types (STs) were identified of which 29 (41.4 %) were novel. NTHi strains did not show any phylogenetic grouping or clustering among asymptomatic colonizing strains or strains that caused AOM, or based on b-lactamase enzyme production. Evaluation of triplets and other siblings over time demonstrated relatively frequent genetic exchanges in NTHi isolates in vivo in a short time frame and subsequent transfer among children in a family. Comparison of the MLST STs isolated at different time points showed that in~85 % of the nasopharynx (NP) colonizations, NTHi strains cleared from the host within 3 months, that sequential colonization in the same child involved different strains in all cases except one, and that NP and middle ear isolates were identical STs in 84 % of cases. In this first study of its type to our knowledge, we could not identify predominant MLST types among strains colonizing the NP versus those causing AOM or expressing a b-lactamase enzyme conferring penicillin resistance in children. INTRODUCTIONNon-typable Haemophilus influenzae (NTHi) is an important human-specific pathogen colonizing the nasopharynx (NP) of the upper respiratory tract (Faden et al., 1995; Murphy et al., 2009). NTHi strains are rarely associated with invasive disease in children, but they are associated with respiratory tract infections in both children and adults (Murphy, 2003;Kyd & Cripps, 1999). NP colonization with NTHi is an important risk factor for developing disease (Faden et al., 1997). Children frequently NP-colonized by NTHi are more likely to develop acute otitis media (AOM) than less frequently colonized children (Faden et al., 1997; Harabuchi et al., 1994). Simultaneous detection of multiple isolates of NTHi from the same sample has been reported among aboriginal children with otitis media (Smith-Vaughan et al., 1996), among otitis-prone children in day care centres (St Sauver et al., 2000) and in cystic fibrosis patients (Bandi et al., 2001; Murphy et al., 1999), which may result from inadequate clearance of colonizing bacteria, exposure to multiple circulating strains or in vivo genetic recombinations in a specific host. It is not known whether NTHi isolates that express b-lactamases (responsible for resistance to b-lactam antibiotics such as penicillins, cephamycins and carbapenems) are phylogenetically related. Various studies of Streptococcus pneumoniae have shown phylogenetic relationships among antibiotic-resistant strains (Beall et al., 2006;Hanage et al., 2009;Porat et al., 2004;Xu et al., 2009). In this study, we explored whether or not NTHi shows genetic relatedness in relation...

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“…17,18,26,36,37,[42][43][44] Although this phenomenon has been evidenced in several studies, the benefits of the use of conjugate vaccines are greater than the risk of infections by PS not included in the vaccine or by other less pathogenic bacteria and with less resistance to antibiotics. The increased prevalence of H.…”

Section: Impact Of Pnc7 Vaccine On Replacement By Nonvaccination Seromentioning

confidence: 99%

“…[35][36][37] The appearance of serotype 19 A, which over the last 5 years grew in importance among invasive and non-invasive diseases, is an exception to this rule. 43,44 Of all the ST included in Pnc7 vaccine, the ST 19F is the one that induces least response. At present, it is known that this vaccine does not give cross-protection against ST 19A.…”

Section: Impact Of Pnc7 Vaccine On Replacement By Nonvaccination Seromentioning

confidence: 99%

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Impacto da vacina conjugada contra Streptococcus pneumoniae em doenças invasivas

Bricks¹,

Berezin²

2006

J. Pediatr. (Rio J.)

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. Articles retrieved with the keywords Streptococcus pneumoniae, pneumococcal diseases, conjugate vaccine, antimicrobial resistance and meningitis were reviewed. Summary of the findings:The introduction of heptavalent pneumococcal conjugate vaccine caused a dramatic reduction in the incidence of invasive pneumococcal diseases in American children, reduced antibiotic use and the number of medical visits due to otitis media and pneumonia by children. The incidence of invasive pneumococcal diseases caused by resistant strains declined in immunized children, adults and elderly individuals. In Brazil, the mortality rate of pneumococcal meningitis is very high and the resistance to antibiotics has increased over the last 5 years.Conclusions: Heptavalent pneumococcal conjugate vaccine can benefit not only children, but the entire community and should be included in the Brazilian routine immunization schedule.J Pediatr (Rio J). 2006;82(3 Suppl):S67-74: Streptococcus pneumoniae, pneumococcal disease, conjugate vaccines, pneumonia, meningitis, antimicrobial resistance.

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Emergence of Penicillin‐NonsusceptibleStreptococcus pneumoniaeClones Expressing Serotypes Not Present in the Antipneumococcal Conjugate Vaccine

Cited by 112 publications

References 34 publications

Post-PCV7 Changes in Colonizing Pneumococcal Serotypes in 16 Massachusetts Communities, 2001 and 2004

Post-PCV7 Changes in Colonizing Pneumococcal Serotypes in 16 Massachusetts Communities, 2001 and 2004

Phylogenetic relatedness and diversity of non-typable Haemophilus influenzae in the nasopharynx and middle ear fluid of children with acute otitis media

Impacto da vacina conjugada contra Streptococcus pneumoniae em doenças invasivas

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