Antibiotic Susceptibility in Relation to Penicillin-Binding Protein Genes and Serotype Distribution of Streptococcus pneumoniae Strains Responsible for Meningitis in Japan, 1999 to 2002

Abstract

The antibiotic susceptibilities, genotypes of penicillin (PEN)-binding protein genes (pbp), and serotype distributions of Streptococcus pneumoniae isolates from meningitis patients were investigated by a nationwide surveillance group in Japan between 1999 and 2002. We analyzed 146 isolates from children (<17 years old) and 73 from adults (>18 years old). Isolates with or without abnormal pbp1a, pbp2x, or pbp2b genes identified by PCR were classified into six genotype patterns and 90% MIC (MIC 90 ) values for PEN: (i) strains with three normal genes (17.2% of isolates; MIC 90 , 0.031 g/ml); (ii) strains with abnormal pbp2x (22.1%, 0.063 g/ml); (iii) strains with abnormal pbp2b (1.0%, 0.125 g/ml); (iv) strains with abnormal pbp2x and pbp2b (7.4%, 0.25 g/ml); (v) strains with abnormal pbp1a and pbp2x (12.7%, 0.25 g/ml); and (vi) strains with three abnormal PBP genes (39.7%, 4 g/ml), which are termed genotypic PEN-resistant S. pneumoniae (gPRSP). Panipenem, a carbapenem, showed an excellent MIC 90 (0.125 g/ml) against gPRSP, followed by meropenem and vancomycin (0.5 g/ml), cefotaxime and ceftriaxone (1 g/ml), and ampicillin (4 g/ml). Strains of gPRSP were significantly more prevalent in children (45.2%) than in adults (27.4%). The most frequent serotypes were 6B, 19F, 23F, 6A, and 14 in children and 23F, 22, 3, 10, 6B, and 19F in adults. Serotypes 6B, 6A, 19F, 23F, and 14 predominated among gPRSP. In children, 7-and 11-valent pneumococcal conjugate vaccines would cover 76.2 and 81.3% of isolates, respectively, although coverage would be lower in adults (43.9 and 56.0%, respectively). These findings suggest the need for early introduction of pneumococcal conjugate vaccines and continuous bacteriological surveillance for meningitis.Streptococcus pneumoniae is a common etiologic agent of serious invasive infections, with high morbidity and mortality in children and adults, such as meningitis, septicemia, and pneumonia (23, 29). The evolution of strains of S. pneumoniae resistant to penicillin G (PEN) and broad-spectrum cephalosporin antibiotics has created difficulties worldwide in selecting an appropriate chemotherapeutic agent (2).Surveillance studies of antibiotic susceptibility, serotype distribution of causative strains, and mortality rate in meningitis have been carried out nationwide in many countries (8,11,15,20,21,28,33,36,39,43).In Japan, prevalence of PEN-resistant S. pneumoniae (PRSP) among clinical isolates from acute otitis media and respiratory tract infections (RTIs) has been increasing rapidly, especially in younger children (40,41). In parallel with overall increases in incidence of PRSP, meningitis caused by PRSP is being reported increasingly throughout Japan (4). As investigators in that country, we felt that nationwide surveillance had become crucial given increasing isolation of resistant strains that could cause meningitis, including PRSP, as well as ampicillin (AMP)-and cephalosporin-resistant strains of Haemophilus influenzae type b, the most frequent etiologic agent of bacterial meningitis. I...

Non-Antibiotic Treatment for Pediatric Outpatients With Common Cold Inhibits the Emergence of Drug Resistant Pneumococci

“…19) . Currently, it is known that the prevalence of those strains is very high as recent reports showed the rate is higher than 80% 20,21) . Other reports also mentioned that the rate of macrolide -resistant strains has increased and that the rate is higher than 80% 22) .…”

Correlation between Substitutions in Penicillin‐Binding Protein 1 and Amoxicillin Resistance in Helicobacter pylori

“…PBPs are peptidoglycan synthase and have transpeptidase activity at the C-terminal region. It was previously shown that amino acid substitutions in or around the penicillinbinding motifs (SXXK, SXN, and KTG) in the transpeptidase region of PBPs result in β-lactam resistance due to reduced affinity to β-lactams in Streptococcus pneumoniae and Haemophilus influenzae (20,24). In H. pylori, PBP1, PBP2, and PBP3 have been found as high-molecular PBPs and PBP4 and other several PBPs are found as low-molecular PBPs (11).…”

128 Substitutions in Penicillin-Binding Protein 1 in Amoxicillin-Resistant Helicobacter pylori Strains Isolated from Korean Patients

“…Contribution of PBP mutation in the development of b-lactam resistance of gram-negative bacilli had been investigated in the Streptococcus pneumoniae, Hemophilus influenaze, and Proteus mirabilis. [21][22][23] In these species the amino acid substitution in close to the penicillin-binding motifs (SXXK, SXN, and KTG) of PBPs was associated with development of b-lactam resistance. Regarding H. pylori, amino acid substitution in penicillin-binding motifs SAIK (368 to 371), SLN (433 to 435), and KTG (555 to 557) was known to be related with development of b-lactam resistance.…”