BackgroundA class of methicillin-resistant Staphylococcus aureus (MRSA) shows resistance to vancomycin only in the presence of ß-lactam antibiotics (BIVR). This type of vancomycin resistance is mainly attributable to the rapid depletion of free vancomycin in the presence of ß-lactam antibiotics. This means that ß-lactam antibiotics remain active or intact in BIVR culture, although most MRSA cells are assumed to produce ß-lactamase. We hypothesised that the BIVR cells either did not harbour the ß-lactamase gene, blaZ, or the gene was quiescent. We tested this hypothesis by determining ß-lactamase activity and conducting PCR amplification of blaZ.ResultsFive randomly selected laboratory stock BIVR strains showed an undetectable level of ß-lactamase activity and were blaZ-negative. Five non-BIVR stock strains showed an average ß-lactamase activity of 2.59 ± 0.35 U. To test freshly isolated MRSA, 353 clinical isolates were collected from 11 regionally distant hospitals. Among 25 BIVR strains, only 16% and 8% were blaZ positive and ß-lactamase-positive, respectively. In contrast, 95% and 61% of 328 non-BIVR strains had the blaZ gene and produced active ß-lactamase, respectively. To know the mechanism of low ß-lactamase activity in the BIVR cells, they were transformed with the plasmid carrying the blaZ gene. The transformants still showed a low level of ß-lactamase activity that was several orders of magnitude lower than that of blaZ-positive non-BIVR cells. Presence of the ß-lactamase gene in the transformants was tested by PCR amplification of blaZ using 11 pairs of primers covering the entire blaZ sequence. Yield of the PCR products was consistently low compared with that using blaZ-positive non-BIVR cells. Nucleotide sequencing of blaZ in one of the BIVR transformants revealed 10 amino acid substitutions. Thus, it is likely that the ß-lactamase gene was modified in the BIVR cells to downregulate active ß-lactamase production.ConclusionsWe concluded that BIVR cells gain vancomycin resistance by the elimination or inactivation of ß-lactamase production, thereby preserving ß-lactam antibiotics in milieu, stimulating peptidoglycan metabolism, and depleting free vancomycin to a level below the minimum inhibitory concentration of vancomycin.

We surveyed pediatrics bacterial meningitis epidemiology from January 2007 to December 2008 in Japan, with the following results: Cases numbered 287-160 male and 127 female-equivalent to 1.54-1.62 of 1,000 pediatric hospitalization per year. Children under 1-year-old accounted for the highest number of cases, which decreased with increasing age. Haemophilus influenzae was the most common cause of infection, followed by Streptococcus pneumoniae, group B streptococcus (GBS), and Escherichia coli. GBS and E. coli were major pathogens in children under 4 months of age, while H. influenzae and S. pneumoniae mainly accounted for those over 4 months of age. Susceptibility tests showed that 51% of H. influenzae isolates and 56.5% of S. pneumoniae isolates in 2008 were drug-resistant. Ampicillin combined with cephem antibiotics effective against GBS, E. coli, and Listeria, were mainly used to initially treat those under 4 months of age. In those over 4 months of age, carbapenem antibiotics are effective against PRSP and cephem antibiotics against H. influenza.

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We analyzed 218 strains of methicillin-resistant Staphylococcus aureus (MRSA) isolated from the septicemia patients in a geriatric hospital for 25 years. These strains were classified into 11 major DNA types, A through K, and 27 minor types. The strains belonging to group A and B isolated before 1990 were susceptible to imipenem (IPM), fluoroquinolone, and most other antibiotics tested, except that they were markedly resistant to gentamicin. Strains mostly isolated in 1985 and thereafter were classified into group C through K, and they were mainly resistant to IPM, fluoroquinolones, and clindamycin. Analysis of the MRSA marker gene, staphylococcal cassette chromosome mec (SCCmec), of these strains revealed that the strains in groups A and B had mainly type IV and type I, respectively, and that strains in groups C through J had mainly type II. These results suggested that the strains holding type II SCCmec were resistant to IPM, fluoroquinolone, and clindamycin and they were dominant-resistant type after late 1980s. The antibiotic resistance profiles of MRSA dramatically changed during late 1980s, and these were correlated with the SCCmec types. The lesson from this study would be that consistent execution of surveillance study is needed to update the resistant profiles.