Antibiotic Susceptibility Profiles of Bacteroides fragilis and Bacteroides thetaiotaomicron in Japan from 1990 to 1992

Susceptibilities to 16 antimicrobial agents were determined by measurement of MICs for 344 isolates of anaerobic bacteria recovered from patients with significant infections. Resistance rates varied among antimicrobial agents and the species tested. The ␤-lactams were more active in gram-positive than in gram-negative anaerobes. Resistance to meropenem was low (<1%). For ␤-lactam-␤-lactamase inhibitors, piperacillin-tazobactam was most active for all species (resistance, <6%). The rates of resistance to cefoxitin (31 to 65%) and clindamycin (50 to 70%) for non-Bacteroides fragilis species of the B. fragilis group were higher than those for B. fragilis (4% resistant to cefoxitin and 33% resistant to clindamycin). Among members of B. fragilis group, Bacteroides thetaiotaomicron was the most resistant to clindamycin (70%) and cefoxitin (65%). Rates of susceptibility to imipenem and metronidazole for B. fragilis continue to be high compared to those from a previous study 10 years ago. However, resistance to metronidazole was found recently in five strains of B. fragilis. We analyzed the genetic relationships among the metronidazole-resistant B. fragilis strains by pulsed-field gel electrophoresis. The metronidazole-resistant B. fragilis strains showed genotypic heterogeneity, excluding the dissemination of a single clone.

Section: Discussionmentioning

confidence: 99%

“…(12). h Peptostreptococcus species included P. anaerobius (10), P. magnus (15), P. micros (3), and unidentified Peptostreptococcus spp. (3).…”

Section: Discussionmentioning

confidence: 99%

High Incidence of Cefoxitin and Clindamycin Resistance among Anaerobes in Taiwan

Teng

Hsueh

Tsai

et al. 2002

“…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.…”

mentioning

confidence: 99%

New Insertion Sequence Elements in the Upstream Region of cfiA in Imipenem-Resistant Bacteroides fragilis Strains

Kato

Yamazoe

Han

et al. 2003

Self Cite

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...

“…Metalloenzymes that hydrolyze carbapenems have been found in both aerobic bacteria (3,10,11) and anaerobic bacteria (2); the gene for the metalloenzyme may be silent or expressed to various degrees, resulting in a wide range of carbapenem resistance levels (13). In Japan, this accounts for the 2 to 4% rate of resistance to imipenem (1,16), but these isolates are rarely found in the United States. The purpose of this study was to measure the efficacy of doripenem against a wide range of clinical anaerobic isolates and to compare its in vitro activities to those of other antimicrobial agents.…”

mentioning

confidence: 99%

In Vitro Activities of Doripenem and Comparator Agents against 364 Anaerobic Clinical Isolates

Wexler

Engel²,

Glass³

et al. 2005

The in vitro activities of doripenem against 364 anaerobic isolates were measured and compared to those of ertapenem, imipenem, meropenem, ceftriaxone, and levofloxacin. All of the carbapenems were active against nearly all Bacteroides fragilis group isolates. Doripenem was either comparable to or slightly less active than imipenem and meropenem against most isolates but more active than the other penems against Clostridium difficile. Doripenem appears to have excellent activity against a broad range of anaerobes.Doripenem, a 1-␤-methyl carbapenem being developed for the treatment of serious systemic bacterial infections, is resistant to hydrolysis by dihydropeptidase 1 (7). In aerobes, doripenem appears to have the advantages of both imipenem (in its activity against gram-positive cocci) and meropenem (in its activity against gram-negative organisms) (12). Metalloenzymes that hydrolyze carbapenems have been found in both aerobic bacteria (3, 10, 11) and anaerobic bacteria (2); the gene for the metalloenzyme may be silent or expressed to various degrees, resulting in a wide range of carbapenem resistance levels (13). In Japan, this accounts for the 2 to 4% rate of resistance to imipenem (1, 16), but these isolates are rarely found in the United States. The purpose of this study was to measure the efficacy of doripenem against a wide range of clinical anaerobic isolates and to compare its in vitro activities to those of other antimicrobial agents.Bacteria were clinical isolates collected from a wide range of infections throughout the United States or worldwide and identified at the Wadsworth Anaerobe Laboratory (5). MICs were determined by the CLSI (formerly NCCLS)-approved Wadsworth agar dilution technique (8). Antimicrobial agents were obtained from the following companies: doripenem (Shionogi & Co., Ltd., Osaka, Japan), imipenem and ertapenem (Merck, Rahway, NJ), meropenem (AstraZeneca, Waltham, MA), ceftriaxone (Hoffman La Roche, Nutley, NJ), and levofloxacin (Johnson and Johnson, Raritan, NJ). For analysis purposes, the bacteria tested were placed in species or genus groups with Ͼ5 isolates, and the MIC ranges, mean geometric MICs, MIC 50 s, and MIC 90 s were reported. Susceptible (intermediate) breakpoints are indicated in Table 1.Efflux inhibitor studies were performed by the spiral gradient endpoint system (19,20) by first depositing a uniform concentration of efflux inhibitor on 15 mm brucella blood agar plates (Anaerobe Systems), resulting in the following concentrations: carbonyl cyanide m-chlorophenylhydrazone (CCCP) (Sigma), 12.5 g/ml; CCCP, 25 g/ml; MC 207,110 (Sigma), 100 g/ml, reserpine (Sigma), 25 g/ml; and verapamil (Sigma), 100 g/ml. Doripenem was then deposited in the gradient mode, and MICs were determined. The concentrations of efflux inhibitors chosen were not inhibitory for the strains.Doripenem was active against almost all strains of the Bacteroides fragilis group of organisms. Doripenem had MICs of 16 g/ml for one strain and MICs of 8 g/ml for three additional strains. The MICs of the o...