Katsuhiko Sunaoshi

Serotype and antibiotic resistance of isolates from patients with invasive pneumococcal disease in Japan

Invasive pneumococcal disease (IPD) is of concern in Japan, where the heptavalent pneumococcal conjugate vaccine (PCV7) is unavailable. We determined serotypes, genotypes indicating beta-lactam resistance, and antibiotic susceptibilities of 496 isolates from normally sterile sites in patients (193 children, 303 adults) from 186 institutions between August 2006 and July 2007. Disease presentations included sepsis (46.2%), pneumonia (31.5%), and meningitis (17.5%). Mortality was 1.4% in children and 22.1% in adults, many of whom had underlying diseases. In children, serotype 6B (22.5%) was followed by 19F (14.1%), and 14 (13.1%); potential coverages of PCV7 and PCV13 were 75.4% and 93.7%, respectively. In adults, serotype 12F (14.3%) was followed by 3 (11.3%), and 6B (10.3%); 23-valent polysaccharide vaccine (PPV23) coverage was 85.4%. Most serotype 12F strains were gPISP, with pbp2b gene alteration; carbapenem had an excellent MIC90. PCV7 is recommended for children and PPV23 for adults to increase prevention against IPD.

Capsular Type and Antibiotic Resistance in Streptococcus agalactiae Isolates from Patients, Ranging from Newborns to the Elderly, with Invasive Infections

ABSTRACT Streptococcus agalactiae isolates (n = 189) from patients with invasive infections were analyzed for capsular type by PCR, for antimicrobial susceptibility, and for the presence of resistance genes. In contrast to the predominance of capsular type III in children, types Ib and V were most common among adults. All 45 levofloxacin-resistant strains had two amino acid substitutions, Ser81Leu in the gyrA gene and Ser79Phe in the parC gene, and showed similar pulsed-field gel electrophoresis patterns.

Clinical aspects of invasive infections with Streptococcus dysgalactiae ssp. equisimilis in Japan: differences with respect to Streptococcus pyogenes and Streptococcus agalactiae infections

Streptococcus dysgalactiae ssp. equisimilis (SDSE) is increasingly being identified as a pathogen responsible for invasive and non-invasive infections. We compared the clinical features of invasive SDSE infections with those of invasive infections caused by Streptococcus pyogenes (group A streptococcus (GAS)) and Streptococcus agalactiae (group B streptococcus (GBS)). Active surveillance for invasive SDSE, GAS and GBS was maintained over 1 year at 142 medical institutions throughout Japan. Clinical information was collected together with isolates, which were characterized microbiologically. Two hundred and thirty-one invasive SDSE infections were identified, 97 other patients had infections with GAS, and 151 had infections with GBS. The median age of the SDSE patients was 75 years; 51% were male and 79% had underlying diseases. Forty-two SDSE patients (19%) presented to the emergency department. Among the 150 patients (65%) for whom follow-up was completed, 19 (13%) died and eight (5%) had post-infective sequelae (poor outcome). Insufficient white blood cell responses (<5000 cells/microL) and thrombocytopenia on admission each suggested significantly higher risk of poor outcome (ORs 3.6 and 4.5, respectively). Of 229 isolates, 55 (24%) showed an stG6792 emm type, which was significantly associated with poor outcome (OR 2.4). Clinical manifestations of invasive SDSE infections were distinct from those of invasive GBS infections. Primary-care doctors should consider invasive SDSE infections when treating elderly patients.

Distribution of emm type and antibiotic susceptibility of group A streptococci causing invasive and noninvasive disease.

To determine the prevalence of macrolide antibiotic and levofloxacin resistance in infections with Streptococcus pyogenes (group A streptococcus or GAS), strains were collected from 45 medical institutions in various parts of Japan between October 2003 and September 2006. Four hundred and eighty-two strains from patients with GAS infections were characterized genetically. Strains were classified into four groups according to the type of infection: invasive infections (n=74) including sepsis, cellulitis and toxic-shock-like syndrome; acute otitis media (AOM; n=23); abscess (n=53); and pharyngotonsillitis (n=332). Among all strains, 32 emm types were identified; emm1 was significantly more common in invasive infections (39.2 %) and AOM (43.5 %) than in abscesses (3.8 %) or pharyngotonsillitis (10.2 %). emm12 and emm4 each accounted for 23.5 % of pharyngotonsillitis cases. Susceptibility of GAS strains to eight beta-lactam agents was excellent, with MICs of 0.0005-0.063 mug ml(-1). Macrolide-resistant strains accounted for 16.2 % of all strains, while the percentages of strains possessing the resistance genes erm(A), erm(B) and mef(A) were 2.5 %, 6.2 % and 7.5 %, respectively. Although no strains with high resistance to levofloxacin were found, strains with an MIC of 2-4 mug ml(-1) (17.4 %) had amino acid substitutions at either Ser-79 or Asp-83 in ParC. These levofloxacin-intermediately resistant strains included 16 emm types, but macrolide-resistant strains were more likely than others to represent certain emm types.

Molecular emm genotyping and antibiotic susceptibility of Streptococcus dysgalactiae subsp. equisimilis isolated from invasive and non-invasive infections

To analyse the characteristics of infections caused by Streptococcus dysgalactiae subsp. equisimilis, clinical isolates (n=145) were collected at 11 medical institutions between September 2003 and October 2005. These isolates belonged to Lancefield group A (n=5), group C (n=18) or group G (n=122). Among all isolates, 42 strains were isolated from sterile samples such as blood, synovial fluid and tissue specimens from patients who were mostly over 50 years with invasive infections, and included seven cases of streptococcal toxic shock syndrome and necrotizing fasciitis. In contrast, the remaining 103 were isolated mainly from patients of all age groups with non-invasive infections such as pharyngotonsillitis. These isolates were classified into 25 types based on emm genotyping. A significant difference in emm types was observed between isolates from invasive and non-invasive infections (P<0.001): stG485, stG6792 and stG2078 predominated among isolates from invasive infections. A phylogenetic tree of complete open reading frames of emm genes in this organism showed high homology with those of Streptococcus pyogenes, but not with those of other streptococci. The presence of five different clones was estimated based on DNA profiles of isolates from invasive infections obtained by PFGE. Genes for resistance to macrolides [erm(A), three isolates; erm(B), five isolates; mef(A), seven isolates] and levofloxacin (mutations in gyrA and parC, four isolates) were identified in this organism. These results suggest the need for further nationwide surveillance of invasive infections caused by S. dysgalactiae subsp. equisimilis.

Associations between capsular serotype, multilocus sequence type, and macrolide resistance in Streptococcus agalactiae isolates from Japanese infants with invasive infections

SUMMARY Streptococcus agalactiae (group B streptococcus; GBS) isolates (n = 150) from infants with invasive infections between 2006 and 2011 were analysed for capsular serotype, multilocus sequence type, and antibiotic susceptibility. In cases with late-onset disease (n = 115), primary meningitis was predominant (62.6%), but represented only 39.1% in cases with early-onset disease (n = 23). The most common serotype was III (58.7%), followed by Ia (21.3%) and Ib (12.7%). Sequence types (STs) of serotype III strains included ST17 (50.0%), ST19 (26.1%), ST335 (18.2%), ST27 (4.5%), and ST1 (1.1%). Predominant STs of serotypes Ia and Ib were ST23 (81.3%) and ST10 (84.2%), respectively. No penicillin-resistant strains were detected, but 22·0% of strains had mef(A/E), erm(A), or erm(B) genes, which mediate macrolide resistance. A new ST335, possessing an mef(A/E) gene belonging to clonal complex 19 gradually increased in frequency. Improved prevention of invasive GBS infections in infants requires timely identification, and ultimately vaccine development.

Molecular Characterization of Invasive Streptococcus dysgalactiae subsp. equisimilis, Japan

This infection is an increasing threat to aging populations.

Nonhemolytic Streptococcus pyogenes Isolates That Lack Large Regions of the sag Operon Mediating Streptolysin S Production

ABSTRACT Among nonhemolytic Streptococcus pyogenes (group A streptococcus) strains (n = 9) isolated from patients with pharyngitis or acute otitis media, we identified three deletions in the region from the epf gene, encoding the extracellular matrix binding protein, to the sag operon, mediating streptolysin S production.