Search PubMed⌕ Search

Biomedical subjects

K Bush

Publications and source records attributed to K Bush.

At least 55 records · Page 3Linked to original sources
PubMed1997

Antimicrobial resistance in anaerobes.

The development of antibiotic resistance in anaerobic bacteria has a tremendous impact on the selection of antimicrobial agents for empirical therapy. Susceptibility studies have documented the emergence of antimicrobial resistance and indicate distinct differences in resistance patterns related to individual hospitals, geographic regions, and antibiotic-prescribing regimens. Resistance to beta-lactam drugs, clindamycin, tetracyclines, and 5-nitroimidazoles (metronidazole) has been observed. The prime mechanism for resistance to beta-lactam agents is the production of beta-lactamases. Resistance to clindamycin is mediated by modification of the ribosome. Tetracycline resistance is mediated by both tetracycline efflux and ribosomal protection. 5-Nitroimidazole resistance appears to be caused by a combination of decreased antibiotic uptake and decreased nitroreductase activity. The level of chloramphenicol susceptibility remains quite high, whereas uniform resistance to aminoglycosides and quinolones is observed. Understanding the mechanisms of resistance is critical for both informed selection of antimicrobial therapy and the design of new antimicrobial agents.

Bacteria, Anaerobic↗
PubMed1997

Imipenem resistance in Klebsiella pneumoniae is associated with the combination of ACT-1, a plasmid-mediated AmpC beta-lactamase, and the foss of an outer membrane protein.

Six Escherichia coli and 12 Klebsiella pneumoniae isolates from a single hospital expressed a common beta-lactamase with a pI of approximately 9.0 and were resistant to cefoxitin and cefotetan (MIC ranges, 64 to > 128 and 16 to > 128 micrograms/ml, respectively). Seventeen of the 18 strains produced multiple beta-lactamases. Most significantly, three K. pneumoniae strains were also resistant to imipenem (MICs, 8 to 32 micrograms/ml). Spectrophotometric beta-lactamase assays with purified enzyme indicated hydrolysis of cephamycins, in addition to cephaloridine and benzylpenicillin. The 4ene encoding the pI 9.0 beta-lactamase (designated ACT-1 for AmpC type) was cloned and sequenced, which revealed an ampC-type beta-lactamase gene that originated from Enterobacter cloacae and that had 86% sequence homology to the P99 beta-lactamase and 94% homology to the partial sequence of MIR-1. Southern blotting revealed that the gene encoding ACT-1 was on a large plasmid in some of the K. pneumoniae strains as well as on the chromosomes of all of the strains, suggesting that the gene is located on an easily mobilized element. Outer membrane protein profiles of the K. pneumoniae strains revealed that the three imipenem-resistant strains were lacking a major outer membrane protein of approximately 42 kDa which was present in the imipenem-susceptible strains. ACT-1 is the first plasmid-mediated AmpC-type beta-lactamase derived from Enterobacter which has been completely sequenced. This work demonstrates that in addition to resistance to cephamycins, imipenem resistance can occur in K. pneumoniae when a high level of the ACT-1 beta-lactamase is produced in combination with the loss of a major outer membrane protein.

Amino Acid Sequence↗
PubMed1997

Antibacterial activity of BMS-180680, a new catechol-containing monobactam.

The in vitro activities of a new catechol-containing monobactam, BMS-180680 (SQ 84,100), were compared to those of aztreonam, ceftazidime, imipenem, piperacillin-tazobactam, ciprofloxacin, amikacin, and trimethoprim-sulfamethoxazole. BMS-180680 was often the most active compound against many species of the family Enterobacteriaceae, with MICs at which 90% of the isolates were inhibited (MIC90s) of < or = 0.5 microg/ml for Escherichia coli, Klebsiella spp., Citrobacter diversus, Enterobacter aerogenes, Serratia marcescens, Proteus spp., and Providencia spp. BMS-180680 had moderate activities (MIC90s of 2 to 8 microg/ml) against Citrobacter freundii, Morganella morganii, Shigella spp., and non-E. aerogenes Enterobacter spp. BMS-180680 was the only antibiotic evaluated that was active against >90% of the Pseudomonas aeruginosa (MIC90, 0.25 microg/ml), Burkholderia cepacia, and Stenotrophomonas maltophilia (MIC90s, 1 microg/ml) strains tested. BMS-180680 was inactive against most strains of Pseudomonas fluorescens, Pseudomonas stutzeri, Pseudomonas diminuta, and Burkholderia pickettii. BMS-180680 was moderately active (MIC90s of 4 to 8 microg/ml) against Alcaligenes spp. and Acinetobacter lwoffii and less active (MIC90, 16 microg/ml) against Acinetobacter calcoaceticus-Acinetobacter baumanii complex. BMS-180680 lacked activity against gram-positive bacteria and anaerobic bacteria. Both tonB and cir fiu double mutants of E. coli had greatly decreased susceptibility to BMS-180680. Of the TEM, PSE, and chromosomal-encoded beta-lactamases tested, only the K1 enzyme hydrolyzed BMS-180680 to any measurable extent. Like aztreonam, BMS-180680 bound preferentially to penicillin-binding protein 3. The MICs of BMS-180680 were not influenced by the presence of hematin or 5% sheep blood in the test medium or with incubation in an atmosphere containing 5% CO2. BMS-180680 MICs obtained under strict anaerobic conditions were significantly higher than those obtained in ambient air.

Anti-Bacterial Agents↗
PubMed1997

Penicillin-binding proteins and induction of AmpC beta-lactamase.

In competition assays for radiolabeled penicillin, penicillin-binding proteins (PBPs) 4, 7a, and 7b showed very high affinities for strong inducers of AmpC beta-lactamase. Loss of PBP 4 resulted in diminished inducibility. This suggests that if PBPs are involved in induction of AmpC beta-lactamase, there is probably a redundancy in function among the different PBPs.

Bacterial Proteins↗
PubMed1997

The evolution of beta-lactamases.

beta-lactamases, the enzymes often associated with resistance to beta-lactam antibiotics, are found in most bacterial species. Although these enzymes protected bacteria from naturally occurring beta-lactams long before the introduction of synthetic antimicrobial agents, the numbers and varieties of beta-lactamases have increased dramatically with the introduction of modern penicillins and cephalosporins. Over the past twenty years it has become apparent that families of beta-lactamases have been selected as the result of antimicrobial usage. Outbreaks of beta-lactam-resistant bacteria can be traced to the introduction of specific classes of beta-lactams or to the introduction of a specific agent. Many of the most serious epidemics can be related to transferable beta-lactamase genes that are harboured on multidrug-resistant plasmids. The separation of beta-lactamases into three major functional groups or four structural classes has been proposed. Stepwise selection of variants within several of these classes has been documented both in the clinical setting and in the laboratory, e.g. the extended-spectrum (TEM and SHV) beta-lactamases and the inhibitor-resistant (TEM) beta-lactamases. Close relationships among the recently described plasmid-mediated 'cephamycinases' and the common chromosomal cephalosporinases have been identified. Carbapenem-hydrolysing metallo-beta-lactamases with broad spectrum hydrolysing activity have become serious concerns as they begin to be described on plasmids. Factors contributing to selection of beta-lactam-resistant strains include decreased outer membrane permeability and increased beta-lactamase production.

Bacteria↗
PubMed1996

Crystal structure of the wide-spectrum binuclear zinc beta-lactamase from Bacteroides fragilis.

BACKGROUND: The metallo-beta-lactamase from Bacteroides fragilis hydrolyzes a wide range of beta-lactam antibiotics, and is not clinically susceptible to any known beta-lactamase inhibitors. B. fragilis is associated with post-surgery hospital infections, and there has been a recent report of plasmid-mediated dissemination of the enzyme. Effective inhibitors are therefore urgently needed. Knowledge of the three-dimensional structure will aid in the drug design effort. RESULTS: The crystal structure of the enzyme has been determined by using multiwavelength anomalous diffraction at the zinc absorption edge and refined to 1.85 A resolution. The structure is a four-layer alpha/beta/beta/alpha molecule. The active site, found at the edge of the beta sandwich contains a binuclear zinc center with several novel features. One zinc is tetrahedrally coordinated, the other has a trigonal bipyramidal coordination; a water/hydroxide molecule serves as a ligand for both metals. The residues that coordinate the two zincs are invariant in all metallo-beta-lactamases that have been sequenced, except for two conservative replacements. Despite the existence of the pattern for binuclear zinc binding, the reported structure of the Bacillus cereus enzyme contains only a single zinc. CONCLUSIONS: Structural analysis indicates that affinity for the penta-coordinated zinc can be modulated by neighboring residues, perhaps explaining the absence of the second zinc in the B. cereus structure. Models of bound substrates suggest that the active-site channel can accommodate a wide variety of beta-lactams. We propose that the zinc cluster prepares an hydroxide, probably the hydroxide that ligates both zincs, for nucleophilic attack on the carbonyl carbon atom of the beta-lactam. The resulting negatively charged tetrahedral intermediate implicated in catalysis is stabilized by an oxyanion hole formed by the side chain of the invariant Asn 193 and the tetrahedral zinc.

Amino Acid Sequence↗
PubMed1996

Biochemical characterization of the carbapenem-hydrolyzing beta-lactamase AsbM1 from Aeromonas sobria AER 14M: a member of a novel subgroup of metallo-beta-lactamases.

AsbM1, a carbapenem-hydrolyzing beta-lactamase produced by Aeromonas sobria AER 14M, was purified chromatographically, with anion exchange chromatography performed in the absence of Zn2+. The molecular mass of AsbM1 was approximately 34,000; the isoelectric point was 9.1. AsbM1 had high hydrolytic specificity for carbapenems but low hydrolysis rates for penicillins and cephalosporins. AsbM1 was resistant to the commercially available beta-lactamase inhibitors but was inhibited by pCMB and the chelators EDTA and o-phenanthroline. Zinc, an activator for many metallo-beta-lactamases, inhibited AsbM1 with an IC50 of 8 microM. Analysis of the N-terminal sequence (27 amino acids) showed 26% similarity to the CphA metallo-beta-lactamase. Because of the high specificity for carbapenems and the sensitivity to inhibition by Zn2+, AsbM1 should be included in a new subgroup of metallo-beta-lactamases.

Aeromonas↗
PubMed1996

Outcome of cervical radiculopathy treated with periradicular/epidural corticosteroid injections: a prospective study with independent clinical review.

This prospective study with independent clinical review was set up to monitor the clinical outcome of patients when using serial periradicular/epidural corticosteroid injection techniques in managing cervical radiculopathy. Over a 10 year period, between 1986 and 1995, a consecutive series of 68 secondary referral patients presenting with cervical radiculopathy were entered into the study. There were 57 men (84%) and 11 women (16%) of average age 47 years (range 31-65 years). The average duration of symptoms prior to presentation was 2 months (range 1-12 months). All patients apart from one had neurological signs. Of the 64 patients (94%) who underwent imaging, relevant pathology thought to correlate with the clinical presentation was demonstrated in all but one patient. Serial periradicular/ epidural corticosteroid injections were used to control pain; an average of 2.5 injections was administered per patient (range 1-6). Patients underwent a final clinical examination when their pain had remained satisfactorily under control for an average of 7 months (range 1-23 months). They subsequently were reassessed, by an independent clinician, at an average of 39 months (range 4-112 months) after initial presentation, via a telephone interview. Despite the fact that all 68 patients were potential surgical candidates, they all made a satisfactory recovery without the need for surgical intervention. Forty-eight patients (76%) did not experience any arm pain, and of the 15 patients (24%) who did, this improved from 10 to an average of 2 (range 1-4) on a 10-point pain scale. Thus, patients with cervical radiculopathy make a satisfactory recovery with serial periradicular/epidural corticosteroid injections without the need for surgical intervention.

Adrenal Cortex Hormones↗
PubMed1996

Computed tomography artifacts associated with craniofacial fixation devices: an experimental study.

This study compares the artifacts caused by eight different craniofacial fixation devices in computed tomography (CT) images. Using a Teflon CT phantom model, part I of this study involved the quantitative evaluation of the X-ray absorption properties of each fixation device. Part II utilized a human cadaveric model to determine the degree to which the artifact interfered with the visualization of anatomic structures. In part I, each fixation device was secured to the surface of the phantom and then scanned. All artifacts were compared on the basis of standard deviation in CT number. The severity of the artifact was related to the physical size of the fixation device and its composition. Vitallium devices generated a greater degree of CT artifacts than titanium devices of comparable size. In part II, fixation devices were secured to the orbital rims of human cadaveric heads and then scanned. Visualization of specified anatomic structures was graded independently. The results revealed that titanium fixation devices did not cause significant bone or soft-tissue image degradation, whereas all vitallium fixation devices, except micro mesh and micro (1.0 mm) straight plates, generated an artifact that resulted in some image degradation. The extent of image degradation was related to the fixation device size. Only the thickest vitallium fixation device, mini fragmentation (2.0 mm), resulted in bony image degradation. The degree of soft-tissue image degradation decreased as the size of vitallium fixation devices decreased such that micro fragmentation (0.8 mm) and pan fixation (1.3 mm) devices interfered with soft-tissue visualization only in the immediate vicinity of the plate. The results of this study confirm the previous work of Sullivan and colleagues and Fiala and associates. The data indicate that when postoperative imaging is an important clinical consideration: (1) the fewest number of internal fixation devices should be used to achieve rigid bony fixation, (2) the proximity of fixation devices to the regions of interest should be considered at the time of fixation, (3) titanium implants produce less artifacts than vitallium implants of comparable size, and (4) vitallium micro mesh and micro (1.0 mm) straight fixation devices do not produce artifacts resulting in significant image degradation.

Artifacts↗
PubMed1996

Three-dimensional facial anthropometry using a laser surface scanner: validation of the technique.

Three-dimensional measurement and characterization of facial surface anatomy are fundamental to the objective analysis of facial deformity. However, existing clinical tools are inadequate. Recent innovations in laser scanning technology provide a potentially useful technique for accurate three-dimensional documentation of the face. The purpose of this study is to evaluate the reliability of interactive anthropometric landmark localization based on digitized three-dimensional facial images and to identify sources of error associated with the technique. Three-dimensional surface data were acquired using a commercially available laser scanning device (Cyberware 3030RGB digitizer), and all subsequent anthropometric analyses were performed interactively on the computer monitor. Four experimental conditions were studied, with 10 observations for each condition. A stable anthropomorphic model with prelabeled anatomic landmarks was scanned repeatedly under varying conditions of head inclination and position within the scanning gantry to determine the effect of these variables on the reliability of the technique. The scanning protocol was then repeated with the labels removed to evaluate the reliability of interactive localization of anthropometric landmarks on a digitized three-dimensional image. Optimal results were obtained with the head positioned in the center of the scanning gantry and with the Frankfort plane elevated 10 degrees from the horizontal. Under these circumstances, all 22 labeled landmarks were visualized and the variance in landmark localization was less than 0.6 mm in the x (horizontal), y (vertical), and z (depth) dimensions. Varying head position or inclination caused significant degradation of the digitized image. The variance of interactive landmark localization was analyzed in three dimensions. The reliability and the spatial orientation of variability were determined for each anthropometric point. These findings have direct implications for the clinical adaptation of this diagnostic tool for quantitative evaluation of facial surface anatomy.

Cephalometry↗
PubMed1996

Assessment and treatment of facial deformity resulting from radiation to the orbital area in childhood.

Children who receive radiation for malignant tumors in the orbital area frequently develop widespread craniofacial deformities. These affect the skull, orbit, maxilla, and mandible. When these patients seek treatment at a later age, they require careful assessment using cephalometrics and three-dimensional imaging. It is recommended that the four levels of skeletal deformity be corrected in a single procedure, that is frontotemporal expansion with repositioning of the skull base area, orbital expansion and repositioning together with maxillary and mandibular surgery. Bone grafts should be inlay rather than onlay and soft tissue should be supplied by free-tissue transfer. This counteracts any residual ischemia related to the previous radiation therapy. The second surgical stage is designed to reconstruct the socket and the eyelids to allow more satisfactory rehabilitation with an ocular prosthesis. In patients who have a globe present, the usual enophthalmos can be corrected by repositioning of the eye as part of the first procedure by reducing the anteroposterior dimensions of the socket. In bilateral cases, the deformity is hourglass in nature and requires correction in the frontal and temporal area with lateral displacement of the orbits. A bimaxillary procedure is also indicated. It is emphasized that to formulate a satisfactory operative plan an in-depth three-dimensional analysis of the deformity is mandatory.

Child↗
PubMed1996

TEM-28 from an Escherichia coli clinical isolate is a member of the His-164 family of TEM-1 extended-spectrum beta-lactamases.

TEM-28 (pI 6.1), expressed by an Escherichia coli clinical isolate, is a novel beta-lactamase which hydrolyzed ceftazidime, cefotaxime, and aztreonam with rates of 25, 1.1, and 5.6, respectively, relative to that for benzylpenicillin (100). The nucleotide sequence of blaTEM-28 differed from that of blaTEM-1 by two base changes, resulting in amino acid substitutions of Arg-164 to His and Glu-240 to Lys.

Drug Resistance, Microbial↗
PubMed1996

Characterization of IMI-1 beta-lactamase, a class A carbapenem-hydrolyzing enzyme from Enterobacter cloacae.

In 1984, a year prior to the U.S. approval of imipenem for clinical use, a wound isolate and a bile isolate of Enterobacter cloacae were obtained from two patients in a California hospital. These isolates were resistant to imipenem, penicillins, and inhibitor combinations; early cephalosporins such as cephalothin, cefamandole, and cefoxitin; and cefoperazone. However, they were susceptible (MICs, < 4 micrograms/ml) to cefotaxime, ceftriaxone, ceftazidime, and moxalactam. Both strains produced an apparent TEM-1 beta-lactamase; an inducible NmcA-type imipenem-hydrolyzing beta-lactamase, IMI-1, with a pl of 7.05; and an inducible beta-lactamase with a pI of 8.1, typical of an E. cloacae AmpC beta-lactamase. Purified IMI-1 hydrolyzed imipenem and benzylpenicillin at modest rates, but more slowly than cephaloridine. The enzyme was inhibited by clavulanic acid and tazobactam. EDTA did not inhibit the cephaloridine-hydrolyzing activity. The beta-lactamase gene encoding IMI-1, imiA1, was cloned from E. cloacae 1413B. Sequence analysis identified the imiA1 gene as encoding a class A serine beta-lactamase. Both the imiA1 DNA and encoded amino acid sequences shared greater than 95% identity with the NmcA gene and its encoded protein. DNA sequence analysis also identified a gene upstream of imiA1 that shares > 95% identity with nmcR and that may encode a regulatory protein. In conclusion, IMI-1, a carbapenem-hydrolyzing beta-lactamase inhibited by clavulanic acid, was identified as a group 2f, class A, carbapenem-hydrolyzing cephalosporinase.

Amino Acid Sequence↗
PubMed1995

A model for recording the microcirculatory changes associated with standardized electrical injury of skeletal muscle.

The rate of major limb amputation following high voltage electrical injury remains high despite a decrease in mortality rate. Several theories about the pathophysiology of electrical injury have been discussed in the literature and different clinical regimens have been attempted to decrease the high amputation rate. However, to date, the overall tissue response after electrical injury remains incompletely understood with nothing new to offer these unfortunate patients. We have developed a rat gracilis muscle intravital microscopy preparation in order to better understand the mechanisms of this injury. A standardized 40-V stimulation of 10-sec duration was applied to the anterior belly of the gracilis muscle which translated into a current load of 30 mA. The current density was 750 mA/cm2. Sequential intravital assessment of microcirculatory changes before injury, as well as 5, 15, 30, 60, 120, 180 and 240 min after injury was performed. Consistent findings included initial cessation of blood flow in many capillary beds, focal flow reversal, venous and arterial vascular spasm. Restitution of microvascular flow varied from several minutes to 1 hr and was preceded by vasodilation at 5-15 min following the injury (+16.9 microns from baseline at 15 min). Starting at 30 min progressive vasoconstriction was noted (-0.8 micron from baseline at 30 min, -31.3 microns from baseline at 4 hr). High resolution observation of neutrophil behavior showed an increase in the number of these cells adherent to venular endothelium in areas exhibiting circulatory disturbances (+11.4 cells at 5 min, +15 cells at 4 hr). The standardization of this model allows a quantitative method of evaluating the microcirculatory changes associated with electrical injury and of studying ways to prevent tissue damage. The microcirculatory changes induced by electrical injury were similar to those reported in ischemia-reperfusion injury of skeletal muscle.

Animals↗
PubMed1995

Biochemical comparison of imipenem, meropenem and biapenem: permeability, binding to penicillin-binding proteins, and stability to hydrolysis by beta-lactamases.

Biological activities of biapenem, imipenem, and meropenem were compared with respect to permeability into Gram-negative bacteria, binding to penicillin-binding proteins (PBPs), and hydrolysis by beta-lactamases. Permeability for the three carbapenems was similar when measured in Serratia marcescens S6 producing a carbapenem-hydrolyzing beta-lactamase. Penetration of the carbapenems was comparable with cephaloridine and faster than piperacillin or the extended spectrum cephalosporin cefotaxime. All the carbapenems bound most strongly to PBP 2 of Escherichia coli and Pseudomonas aeruginosa, and to PBP 1 of Staphylococcus aureus. In addition, biapenem showed strong affinity with PBP 1a of E. coli and PBP 1b of P. aeruginosa. Selected serine beta-lactamases, including the extended spectrum plasmid-mediated beta-lactamases, hydrolyzed these carbapenems at rates < 0.1% that of cephaloridine. Metallo-beta-lactamases hydrolysed the carbapenems at measurable rates, with enzymes from Bacteroides fragilis and Xanthomonas maltophilia hydrolyzing biapenem at lower Vmax values than meropenem or imipenem. In conclusion, all the carbapenems exhibited good rates of penetration, bound strongly to PBPs in both Gram-negative and Gram-positive bacteria, and were stable to most Group 1 and Group 2 serine beta-lactamases, but were hydrolyzed by metallo-beta-lactamases.

Bacteria↗