title: Alterations in penicillin binding protein gene of Streptococcus pneumoniae and their correlation with susceptibility patterns.
abstract: Penicillin binding protein (pbp) gene alterations of 328 clinical isolates of Streptococcus pneumoniae were examined for a correlation with their antibiotic-resistance. The frequency of penicillin G (PEN-G) resistance was determined to clarify susceptibility to several antibiotics, namely PEN-G, ampicillin, sulbactam/ampicillin, cefozopram, panipenem (PAPM), clarithromycin (CLR), azithromycin (AZM) and levofloxacin (LVX). Oligonucleotide primers for three pbp genes (pbp1a, pbp2x and pbp2b) were used to detect mutations in pbp. Of the strains, 25.9% were classified as Pen-Gs, 68.0% as Pen-Gir and 6.1% as Pen-Gr. The polymerase chain reaction product for wild-type pbp1a was found in 185 isolates, that for wild-type pbp2x was found in 66 isolates and that for wild-type pbp2b was found in 213 isolates. None of these three genes was detectable in 100 isolates while all of them were detected in 64 isolates (1aw/2xw/2bw). Of those 64 isolates with 1aw/2xw/2bw, the minimum inhibitory concentration (MIC) of PEN-G was < or =0.06 mg/l for 54 isolates and 0.12 mg/l for 10 isolates. Of the 272 strains for which the MIC of PAPM was < or =0.03 mg/l, there were 85 Pen-Gs, 184 Pen-Gir and three Pen-Gr isolates. Three strains for which the MIC of LVX was > or =4.0 mg/l included one Pen-Gs and two Pen-Gir isolates. The MICs of CLR correlated significantly with those of AZM. The MIC of CLR was > or =1 mg/l for 216 isolates, and the MIC of AZM was > or =1 mg/l for 244 of them. These data suggested that PAPM may be effective against S. pneumoniae infection, although acquisition of resistance should be considered. LVX also seemed to be effective against S. pneumoniae.
authors.affiliation: First Department of Medicine, Asahikawa Medical College, 2-1-1-1 Midorigaoka Higashi, Asahikawa 078-8510, Hokkaido, Japan. yohsaki@asahikawa-med.ac.jp
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Ohsaki
authors.forename: Mineji
authors.initials: M
authors.lastname: Tachibana
authors.forename: Kyoko
authors.initials: K
authors.lastname: Nakanishi
authors.forename: Shoko
authors.initials: S
authors.lastname: Nakao
authors.forename: Kumiko
authors.initials: K
authors.lastname: Saito
authors.forename: Eri
authors.initials: E
authors.lastname: Toyoshima
authors.forename: Maki
authors.initials: M
authors.lastname: Sato
authors.forename: Toru
authors.initials: T
authors.lastname: Takahashi
authors.forename: Shinobu
authors.initials: S
authors.lastname: Osanai
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Itoh
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Kikuchi
mesh_terms: D019881:Aminoacyltransferases; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D017963:Azithromycin / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D017291:Clarithromycin / Q000494:pharmacology; D024881:Drug Resistance, Bacterial / Q000235:genetics; D005798:Genes, Bacterial; D006602:Hexosyltransferases / Q000235:genetics*; D006801:Humans; D066298:In Vitro Techniques; D064704:Levofloxacin; D008826:Microbial Sensitivity Tests; D002267:Muramoylpentapeptide Carboxypeptidase / Q000235:genetics*; D009154:Mutation; D015242:Ofloxacin / Q000494:pharmacology; D010400:Penicillin G / Q000494:pharmacology; D010403:Penicillin Resistance / Q000235:genetics; D046915:Penicillin-Binding Proteins; D010458:Peptidyl Transferases / Q000235:genetics*; D011008:Pneumococcal Infections / Q000188:drug therapy / Q000382:microbiology; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D013845:Thienamycins / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002352:Carrier Proteins; D046915:Penicillin-Binding Proteins; D013845:Thienamycins; C072223:PBP 2x protein, Streptococcus; D064704:Levofloxacin; D017963:Azithromycin; D015242:Ofloxacin; D019881:Aminoacyltransferases; C478701:penicillin-binding protein 2b, Streptococcus; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase; D017291:Clarithromycin; D010400:Penicillin G; C039536:panipenem