Morphological response of Bilophila wadsworthia to imipenem: correlation with properties of penicillin-binding proteins

Summanen, Paula; Wexler, Hannah M.; Lee, K.; Becker, Sonja; García, Manuel; Finegold, Sydney M.

doi:10.1128/aac.37.12.2638

Cited by 7 publications

(5 citation statements)

References 25 publications

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“…Others have reported higher MICs of carbapenems and other ␤-lactams for B. wadsworthia (4). We believe that this is due to the heavy haze seen on MIC plates; we have shown that the haze is composed of cell walldeficient forms (15). We do not know whether the cell wallactive forms can persist in vivo or whether they have any clinical significance.…”

mentioning

confidence: 67%

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

Wexler

Engel²,

Glass³

et al. 2005

Antimicrob Agents Chemother

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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...

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mentioning

confidence: 67%

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

Wexler

Engel²,

Glass³

et al. 2005

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…Further investigation of the action of -lactam antibiotics on cell wall structure was undertaken using imipenem. Inhibition of penicillin-binding proteins was found to be associated with spheroplast formation and 'hazy' growth on agar plates [7]. These distorted cells, however, were viable and able to return to normal morphology upon subculture.…”

Section: Antimicrobial Susceptibilitiesmentioning

confidence: 96%

“…Freeze-fracture electron micrographs show a relatively smooth cell membrane with few protruding structures [6]. Transmission electron micrographs display a Gram-negative cell wall with no obvious peptidoglycan layer [6,7]. By thermal melting point determination, Bilophila species are 39-40 mol% G + C [2].…”

Section: Characteristics Of the Organismmentioning

confidence: 99%

“…Similar to several other genera of anaerobes, such as Fusobacterium, agar dilution susceptibilities of Bilophila spp. occasionally exhibited a trailing 'haze' of growth that made endopoint determination difficult [5,7,16].…”

Section: Antimicrobial Susceptibilitiesmentioning

confidence: 99%

“…The organisms in the haze were found to be spheroplasts, often as large as 30 µm across, or eight times the diameter of the unaffected cell [5,7]. Triphenylte-trazolium chloride, a dye that is reduced to a red color by enzymes of viable bacteria, was used to clarify the endpoint determination [5].…”

Section: Antimicrobial Susceptibilitiesmentioning

confidence: 99%

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