A Case of Penicillin-Resistant Pneumococcal Pneumonia and Penicillin-Binding Proteins of the Clinical Isolates

We experienced a case of a 68-year-old female with β-lactam antibiotics including penicillin G (PCG) resistant pneumococcal pneumonia, leading to death during the treatment with ceftizoxime (CZX). We reported the clinical course and the mechanism of resistance of isolated bacteria. The present case is the first in Japan. Minimum inhibitory concentration (MIC) against Streptococcus pneumoniae 88031 isolated from the present case was 1.56μg/ml in PCG and 6.25μg/ml in CZX, showing PCG resistance. The isolate was no β-lactamase production and serotype 23. The drug susceptibility in 34 strains of S. pneumoniae which were isolated as causative organism of respiratory infection in our department in 1988 was studied. PCG high resistant strain (PCGMIC>1.56μg/ml) was only observed in the isolated strain in the present case and PCG low sensitive strains (PCG MIC=0.1-1.0μg/ml) were observed in 3 strains (8.8%). The CZX resistance was observed only in the present case. The detection of penicillin-binding protein (PBP) and binding affinity of μ-lactam antibiotics were studied using PCG sensitive strain, S. pneumoniae type I (preserved strain PCG MIC=0.05μg/ml, CZX MIC=0.1μg/ml, CMX MIC=0.025μg/ml) and PCG resistant strain, S. pneumoniae 88031. The result obtained showed that PBP1a, detected in sensitive strain type I, was not detected in resistant strain 88031 and PBP1b was increased. The binding of 14C-PCG of PCG resistant strain to PBP1b showed lower affinity for CZX and CMX than PCG sensitive strain. From the above observation, it was suggested that the decrease in drug sensitivity of β-lactam antibiotics resistant S. pneumonia 88031 was caused by the variation of PBP1b.