High Prevalence of &lt;i&gt;Streptococcus pneumoniae&lt;/i&gt; with Mutations in &lt;i&gt;pbp1a&lt;/i&gt;, &lt;i&gt;pbp2x&lt;/i&gt;, and &lt;i&gt;pbp2b&lt;/i&gt; Genes of Penicillin-Binding Proteins in the Nasopharynx in Children in Japan

Hotomi, Muneki; Billal, Dewan S.; Shimada, Jun; Suzumoto, Masaki; Yamauchi, Kazuma; Fujihara, Kazuo; Yamanaka, Noboru

doi:10.1159/000091276

Cited by 12 publications

(16 citation statements)

References 60 publications

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“…Extreme diversity of distribution in pneumococcal serotypes is a common phenomenon and is of great concern for researchers in this field. As documented in previous reports, penicillin-resistant strains were frequently identified among children Յ3 years old (11). The serotype distributions among Japanese children with AOM were similar to those reported for children from the United States and Europe (2,10,15,18).…”

supporting

confidence: 85%

Serotype Distribution and Penicillin Resistance of Streptococcus pneumoniae Isolates from Middle Ear Fluids of Pediatric Patients with Acute Otitis Media in Japan

Hotomi

Billal

Kamide³

et al. 2008

J Clin Microbiol

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Out of 175 pneumococcal isolates from middle ear fluids, 26.3% were penicillin-resistant S. pneumoniae (PRSP). Serotypes 19F and 23F occurred most frequently among PRSP strains. The 7-valent pneumococcal conjugate vaccine (PCV) showed better coverage of PRSP strains (87.0%). The 7-valent PCV may reduce the prevalence of PRSP in Japan.Acute otitis media (AOM) is one of the leading infectious diseases caused by Streptococcus pneumoniae (3, 9). In recent decades, penicillin-resistant S. pneumoniae (PRSP) has evolved into a global problem, especially with AOM (7,12,18,21). The 7-valent pneumococcal conjugate vaccine (PCV) introduced in the United States and Europe has reduced the incidences of invasive pneumococcal disease and AOM (8,13,17,25,26). Nasopharyngeal carriage and transmission in children were also reduced (24). However, in Japan, use of the 7-valent PCV has not yet been licensed, and little is known about the distribution of pneumococcal serotypes. Prior to the introduction of 7-valent PCV in Japan, it is important to determine the distribution of pneumococcal serotypes in Japan as well as the prevalence of antimicrobial-resistant pneumococci associated with AOM. In this study, we evaluated the distribution of pneumococcal serotypes among children with AOM and determined the serotype coverage of pneumococcal vaccine formulas in Japan.(This paper was presented at the 108th General Meeting of the American Society for Microbiology, Boston, MA, 1 to 5 June 2008.)One hundred seventy-five pneumococcal isolates were collected randomly from middle ear fluids of 175 children with AOM at outpatient clinics in different regions of Japan during nationwide surveillance from February 2006 to June 2007. The range and quartiles of the ages of the subjects were 1 to 127, 12.8 (25th percentile), 17.0 (median), and 42.3 (75th percentile) months. Susceptibilities to penicillin G (PCG) were tested, and breakpoints were defined according to the Clinical and Laboratory Standards Institute (CLSI) (6). All isolates were serotyped or serogrouped by the capsular quelling method with pneumococcal capsule-specific antisera (Statens Serum Institut, Copenhagen, Denmark) as recommended by the manufacturer. The chi-square test and Fisher's exact test were used for categorical variables to test for significant differences between groups with Prism 4 (GraphPad Software, Inc.). A P value of Ͻ0.05 was considered statistically significant.Out of 175 pneumococcal isolates, 63 (36.0%), 66 (37.7%), and 46 (26.3%) were penicillin-susceptible S. pneumoniae (PSSP), penicillin-intermediate-resistant S. pneumoniae (PISP), and PRSP, respectively (Table 1). The predominant serotype was 19F (19.4%), followed by 23F (14.9%), 14 (11.4%), 6B (11.4%), 6A (9.1%), and 3 (9.1%). The distribution of S. pneumoniae serotypes among PCGsusceptible strains was significantly different from that among PCG-resistant strains (P Ͻ 0.01). Serotype 3 was the most prevalent PSSP serotype (odds ratio [OR], 78.2; 95% confidence interval [CI], 4.6 to 1,330; P Ͻ 0.01), while s...

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supporting

confidence: 85%

Serotype Distribution and Penicillin Resistance of Streptococcus pneumoniae Isolates from Middle Ear Fluids of Pediatric Patients with Acute Otitis Media in Japan

Hotomi

Billal

Kamide³

et al. 2008

J Clin Microbiol

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“…Polymerase chain reaction (PCR) analysis was conducted for all strains collected and stored in 2003, 2005, 2007, 2009, and 2012 to determine the β-lactam resistance genotype by detecting PBP gene mutations on pbp1a , pb2b , and pbp2x [3,4,8,11]. All 379 strains genetically identified as S. pneumoniae on the basis of the detection of S. pneumoniae -specific autolysin gene ( lytA ) were included in the study.…”

Section: Methodsmentioning

confidence: 99%

“…The resistance genotypes of isolates were classified into the following 3 groups on the basis of their β-lactam resistance genotype as previously reported [3,4,8,11]: gPSSP, gPISP, and gPRSP. Briefly, gPSSP was defined as detecting no mutations on any of the above 3 genes.…”

Section: Methodsmentioning

confidence: 99%

“…Those genotypes are described as gPRSP (genotypic penicillin-resistant S. pneumoniae ) or gPISP (genotypic penicillin-intermediate resistant S. pneumoniae ) depending on the number of mutations, as opposed to gPSSP (genotypic penicillin-susceptible S. pneumoniae ), having no mutations on PBP genes. Previous studies have reported the prevalence of gPRSP and gPISP in clinical isolates from the middle ear [5], cerebrospinal fluid [6], the upper respiratory tract [7,8], and the lower respiratory tract [9]. …”

Section: Introductionmentioning

confidence: 99%

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Ten-Year Trends and Clinical Relevance of the Antimicrobial Resistance Genotype in Respiratory Isolates of <b><i>Streptococcus pneumoniae</i></b>

Hagiwara

Baba²,

Shinohara³

et al. 2017

Chemotherapy

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Background: Antimicrobial resistance of Streptococcus pneumoniae, especially against β-lactam antibiotics, is a global concern. We aimed to analyze a 10-year trend in the antimicrobial resistance genotype of respiratory isolates of S. pneumoniae and to clarify whether resistance genotypes were correlated with phenotypic drug susceptibility, pathogenicity, and host clinical background. Methods: Respiratory isolates of S. pneumoniae from 2003 to 2012 were analyzed with polymerase chain reaction for the presence of β-lactam resistance gene mutations on pbp1a, pbp2x, and pbp2b. Sixty-eight strains isolated from different patients in 2012 were particularly analyzed for the association between genotypes and clinical data. Results: The 10-year trend analysis showed a recent increase in gPRSP (genotypic penicillin-resistant S. pneumoniae) with all 3 β-lactam resistance genes (from 21.7 to 35.3% in 3 years) and a steady level of gPSSP (genotypic penicillin-susceptible S. pneumoniae) without any β-lactam resistance genes (13.2% in 2012). This resistance trend in genotypes was more prominent than resistance phenotypes determined with a drug susceptibility test. The probability of being a causative pathogen did not differ in gPSSP (55.6%), gPISP (genotypic penicillin-intermediate resistant S. pneumoniae; 54.3%), and gPRSP (54.2%). There was no significant difference in the ratio of patients who presented with respiratory failure in respiratory infection caused by gPSSP, gPISP, or gPRSP. Host clinical characteristics including age and gender were not different among resistance genotypes. Conclusions: There was no difference in pathogenicity or clinical background between gPSSP, gPISP, and gPRSP. Antimicrobial resistance in respiratory isolates of S. pneumoniae was more prevalent in genotypes than in phenotypes.

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“…Streptococcus pneumoniae is a leading causative pathogen responsible for acute otitis media (AOM) that frequently colonizes the nasopharynx [3,6]. This pathogen has long been susceptible to penicillin, and AOM caused by pneumococci are easily improved by oral antimicrobial therapy.…”

Section: Introductionmentioning

confidence: 99%

Determination of pneumococcal serotypes/genotypes in nasopharyngeal secretions of otitis media children by multiplex PCR

et al. 2007

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The appropriate clinical applications of pneumococcal polysaccharide vaccines against recent increases in antimicrobial resistant Streptococcus pneumoniae (S. pneumoniae) urgently require accurate analytical methodologies for determining and characterizing the serotypes. The results of current immunological determinations of serotypes with anti-capsular polysaccharide-specific sera are difficult to interpret in terms of quellung changes of the pneumococci. In this study, we applied the multiplex PCR technique for the rapid identification of pneumococci and simultaneous rapid determinations of their serotypes and genotypes that directly correlated with antimicrobial susceptibilities from nasopharyngeal secretions (NPS). Serogroups 6, 19F and 23F were the predominant capsular types of S. pnuemoniae in the NPS samples. Strains of serotypes 19F and 23F frequently had mutations in pbp1a, pbp2x and pbp2b and expressed ermB and mefA; they also were mostly resistant to both penicillin G (PCG) and clarithromycin (CAM). Two NPS samples contained the strain of serotype 19F together with the strain of serotype 23F, although only the strain of serotype 19F was identified by a conventional bacterial culture. Pneumococci were identified in six NPS samples and their serotypes determined by the multiplex PCR, while a conventional bacterial culture failed to identify the pathogens. Our findings suggest that PCR-based serotyping and genotyping can provide an accurate and rapid distribution of pneumococcal serotypes and antimicrobial resistance. The relatively minor populations in the nasopharynx may be determined using molecular techniques.

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High Prevalence of <i>Streptococcus pneumoniae</i> with Mutations in <i>pbp1a</i>, <i>pbp2x</i>, and <i>pbp2b</i> Genes of Penicillin-Binding Proteins in the Nasopharynx in Children in Japan

Cited by 12 publications

References 60 publications

Serotype Distribution and Penicillin Resistance of Streptococcus pneumoniae Isolates from Middle Ear Fluids of Pediatric Patients with Acute Otitis Media in Japan

Serotype Distribution and Penicillin Resistance of Streptococcus pneumoniae Isolates from Middle Ear Fluids of Pediatric Patients with Acute Otitis Media in Japan

Ten-Year Trends and Clinical Relevance of the Antimicrobial Resistance Genotype in Respiratory Isolates of <b><i>Streptococcus pneumoniae</i></b>

Determination of pneumococcal serotypes/genotypes in nasopharyngeal secretions of otitis media children by multiplex PCR

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