The 747-bp cfiA gene, which encodes a metallo-␤-lactamase, and the regions flanking cfiA in six imipenemresistant and four imipenem-susceptible Bacteroides fragilis strains isolated in Japan were analyzed by PCR and DNA sequencing. The nucleotide sequences of the cfiA genes (designated cfiA 1 to cfiA 10 ) of all 10 strains tested varied from that of the standard cfiA gene from B. fragilis TAL2480. However, putative proteins encoded by the cfiA variants contained conserved amino acid residues important for zinc binding and hairpin loop formation, suggesting that cfiA variants have the capability of producing metallo-␤-lactamases with full catalytic activities. PCR assay indicated that six metallo-␤-lactamase-producing, imipenem-resistant strains had an insertion mutation in the region immediately upstream of cfiA. Nucleotide sequencing of the PCRamplified fragments along with the upstream region of cfiA revealed that there were five new kinds of insertion sequence (IS) elements (designated IS612, IS613, IS614, IS615, and IS616, with a size range of 1,594 to 1,691 bp), of which only IS616 was found to be almost identical to IS1188, one of the IS elements previously identified in the upstream region of cfiA. These elements had target site duplications of 4 or 5 bp in length, terminal inverted repeats (14, 15, or 17 bp in size), and a large open reading frame encoding a putative transposase which is required for the transcription of IS elements. Each element was inserted such that the transcriptional direction of the transposase was opposite to that of cfiA. A computer-aided homology search revealed that, based on the homology of their putative transposases, the sizes of their terminal inverted repeat sequences, and their target site duplications, IS612, IS613, IS614, and IS615 belong to the IS4 family, which includes IS942, previously found in some drug-resistant B. fragilis strains, but that IS616 belongs to the IS1380 family. All the IS elements appear to have putative promoter motif sequences (the ؊7 region's TAnnTTTG motif and the ؊33 region's TTG or TG) in their end regions, suggesting that the IS elements provide a promoter for the transcription of cfiA upon insertion. These data provide additional proof that various IS elements may exist to provide a promoter to express the cfiA gene.Bacteroides fragilis is a strict anaerobe that inhabits the intestines of humans and is the most common anaerobe recovered from various infections, such as intra-abdominal infection, foot ulcer, and sepsis. This organism shows inherently poor susceptibility to most ␤-lactam antibiotics (10, 13, 30). Carbapenems such as imipenem (15), panipenem (18), meropenem (6), biapenem (36), CS-834 (12), and ertapenem (13, 11) are powerful antimicrobial agents with broad spectra that cover most aerobes and anaerobes, including B. fragilis.The existence of imipenem-resistant B. fragilis strains was reported nearly 2 decades ago (5), and these strains were found to produce metallo-␤-lactamase, which hydrolyzes the fourmembered-ring CON bond of...

The cfiA gene, encoding an imipenem-hydrolyzing metallo-β-lactamase produced by Bacteroides fragilis, and insertion-like elements were detected by PCR amplification withB. fragilis strains isolated in Japan. The cfiAgene was found in 1.9 and 4.1% of the imipenem-susceptible B. fragilis isolates collected from 1987 to 1988 and from 1992 to 1994, respectively. Insertion-like elements adjacent to thecfiA gene were found in all nine metallo-β-lactamase-producing imipenem-resistant strains tested but not in nine cfiA-positive strains with no detectable metallo-β-lactamase activity.

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Compatibilty of Bricef Dry Syrup (cefatrizine oral suspension) with mixed solutions which were often pre scribed in our hospital was investigated in terms of changes in external appearance pH and residual potency of cefatrizine (CFT). These changes were checked immediately after and 1, 3, 5, 7 and 14 days after mixing. The results showed lowering, to some extent, of CFT potency in relatively high pH region. Especially, when dry syrup was mxed with an alkaline solution, CFT potency reduced significantly within 24 hours at room temperature. These results suggest that careful attention should be paid to the above combination since a risk of incompatibility may be involved.Color of suspensions of a few preparations changed during the storage. The change in color should be avoided to prevent anxiety in patients, though its correlation with stability of CFT is not clear. In combiantions with other solutions, the change in appearance, pH and potency of CFT was small, suggesting that such combinations be clinically recommendable.

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