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-G s, 68.0% as Pen-G ir and 6.1% as Pen-G r. 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 ( 1a w/ 2x w/ 2b w). Of those 64 isolates with 1a w/ 2x w/ 2b w, the minimum inhibitory concentration (MIC) of PEN-G was ≤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 ≤0.03 mg/l, there were 85 Pen-G s, 184 Pen-G ir and three Pen-G r isolates. Three strains for which the MIC of LVX was ≥4.0 mg/l included one Pen-G s and two Pen-G ir isolates. The MICs of CLR correlated significantly with those of AZM. The MIC of CLR was ≥1 mg/l for 216 isolates, and the MIC of AZM was ≥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.