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Biomedical subjects

B E Murray

Publications and source records attributed to B E Murray.

At least 127 records · Page 7Linked to original sources

Molecular epidemiology of Shigella infection in Central Australia.

Shigellosis is endemic in Central Australia and the infections are predominantly due to Shigella flexneri 6, Shigella flexneri 2a and Shigella sonnei. Plasmid profiles of isolates collected from 1985-9, suggested that infections caused by Shigella flexneri 6 were predominantly due to a single clone, whereas those caused by Shigella flexneri 2a and Shigella sonnei were due to several genetically diverse strains, although strains with identical plasmid profiles were found in widely separated geographical areas and in different years.

Australia↗

Comparison of enterococcal and staphylococcal beta-lactamase plasmids.

In Staphylococcus aureus, beta-lactamase (Bla) is typically associated with transducible plasmids that also encode metal resistance or with the more recently described conjugative, gentamicin resistance plasmids. The beta-lactamase gene of Enterococcus faecalis, which has been shown to be highly homologous to bla from the S. aureus plasmid p1258, is also encoded on conjugative, gentamicin resistance plasmids. To determine if the enterococcal Bla-encoding plasmids are similar to those from staphylococci, Bla-encoding plasmids from both species were compared by restriction endonuclease digestion followed by hybridization to Bla and gentamicin resistance gene probes and to one of the enterococcal Bla-encoding plasmids. Although similarities were noted in the restriction endonuclease digestion patterns among the transducible staphylococcal plasmids (pI524, pI258, and pII147) and among the conjugative Gmr staphylococcal plasmids, neither of these restriction patterns was similar to those of the enterococcal plasmids. Although the enterococcal plasmids showed extensive similarities by hybridization, the staphylococcal plasmids showed little or no similarity to the enterococcal plasmids except for bla and the gentamicin resistance genes. Whether enterococci acquired a different type of Bla-encoding plasmid or whether bla was acquired by transposition or by homologous recombination into enterococcal plasmids is unknown.

DNA Probes↗

The association of Shiga toxin and other cytotoxins with the neurologic manifestations of shigellosis.

The neurologic symptoms in human shigellosis have often been attributed to Shiga toxin, although its exact role has not been determined. By use of a [3H] thymidine-labeled HeLa cell assay, cytotoxic activity was demonstrated in stool but not cerebrospinal fluid or serum from five patients with shigellosis presenting with seizures or encephalopathy. Bacterial isolates produced 16.0-88.2 CD50 (50% cytotoxic dose) of cytotoxin/mg of protein. The toxin activity in stool and the cytotoxic activity of the isolates were not neutralized by antiserum to purified Shiga toxin. DNA hybridization studies showed that Shigella isolates from these patients lacked the structural genes for Shiga toxin. The cytotoxin produced was also distinct from Shiga-like toxins I and II. Sonicates of the Shigella strains injected intraperitoneally into mice caused lethargy and lethality. The toxin activity was heat-labile and sensitive to trypsin, indicating that its active component is protein. Ultrafiltration and gel filtration chromatography showed a molecular mass of 100-125 kDa. Thus Shiga toxin production is not essential for the development of neurologic manifestations of shigellosis; other toxic products may play a role.

Animals↗

Comparative in vitro activities of amoxicillin-clavulanic acid, cefuroxime, cephalexin, and cephalothin against trimethoprim-resistant Escherichia coli isolated from stools of children attending day-care centers.

A high prevalence of fecal colonization with trimethoprim-resistant Escherichia coli was found in diapered children attending day-care centers in Houston, Tex. In the present study, 100 isolates of E. coli resistant to multiple antibiotics, including trimethoprim (100%), sulfisoxazole (100%), streptomycin (94%), and ampicillin (87%), were obtained over a 5-month period from stool samples of diapered children attending four day-care centers and tested for their susceptibilities to amoxicillin-clavulanic acid, cefuroxime, cephalexin, and cephalothin. The MICs for 50 and 90% of strains tested were 16 and 32 micrograms/ml, respectively, for amoxicillin-clavulanic acid, 4 and 16 micrograms/ml, respectively, for cefuroxime, 4 and 64 micrograms/ml, respectively, for cephalexin, and 32 and greater than 64 micrograms/ml, respectively, for cephalothin. Although all three oral beta-lactams tested were generally active at concentrations likely to be achieved in urine, cefuroxime and cephalexin were more potent and are thus more likely to be inhibitory at the concentrations needed for systemic infections.

Amoxicillin↗

Molecular epidemiology of beta-lactamase-producing enterococci.

Plasmids from the first six reported beta-lactamase-producing (Bla+) enterococci were compared for genetic relatedness. Bla+ enterococcal plasmids from strains isolated in Houston, Tex.; Philadelphia, Pa.; Connecticut; and Pittsburgh, Pa., had heterogeneous HaeIII and MspI-ClaI restriction endonuclease digestion patterns. A staphylococcal beta-lactamase probe hybridized to all six Bla+ enterococcal plasmids, but hybridization was detected on different HaeIII and MspI-ClaI fragments of the six plasmids. An enterococcal gentamicin resistance (Gmr) probe hybridized to a common 3.9-kilobase HaeIII fragment from the five Gmr plasmids. The Houston plasmid was cross-hybridized to the other five strains, and moderate to extensive homology was demonstrated. Bla+ enterococcal plasmids from a broad geographic range are heterogeneous with respect to size and restriction endonuclease digestion patterns but contain homologous genetic material, including Bla+ and Gmr determinants.

Conjugation, Genetic↗

Emergence of resistant fecal Escherichia coli in travelers not taking prophylactic antimicrobial agents.

Fecal specimens from individuals traveling to Mexico were examined before, during, and after travel for the presence of Escherichia coli resistant to ampicillin, chloramphenicol, gentamicin, kanamycin, streptomycin, sulfonamides, trimethoprim (TMP), and TMP-sulfamethoxazole (TMP-SMX). None of these individuals took prophylactic antibiotics, although 4 of 13 took short courses of an antimicrobial agent for therapy of traveler's diarrhea. With an average of 9.3 E. coli per sample, resistance to all agents tested except gentamicin was shown to increase during the time in Mexico (P less than 0.001 to P less than 0.05). For example, no TMP-resistant (Tmpr) E. coli isolates were found by this method before travel, whereas 57% of the individuals had Tmpr and Tmpr-Smxr E. coli by the final week in Mexico. This increase in resistance occurred regardless of whether an individual took a short course of antimicrobial therapy. This study shows that travel itself, even without the use of prophylactic or therapeutic antimicrobial agents, is associated with the acquisition of resistant E. coli. Travel to developing nations may rival other sources of resistant organisms.

Anti-Bacterial Agents↗

Mobilization of the gentamicin resistance gene in Enterococcus faecalis.

Enterococcus faecalis plasmid pBEM10 (a conjugative plasmid encoding beta-lactamase production and gentamicin resistance [Gmr]) was made transfer deficient by using Tn917. Relocation of the Gmr determinant into two sites on pCF10 was observed. Restriction analysis revealed insertion of a common 2.5-kilobase-pair HindIII and a 3.9-kilobase-pair HaeIII fragment encoding Gmr, suggesting that this determinant resides on a transposon similar to Tn4001.

DNA Probes↗

Evidence for a staphylococcal-like mercury resistance gene in Enterococcus faecalis.

We investigated mercury resistance (Hgr) in 52 clinical isolates of Enterococcus faecalis from two different geographical regions. Eleven of the 52 strains were resistant to HgCl2, and plasmids from these enterococci hybridized with a staphylococcal mercury resistance gene probe. Hgr from 5 of the 11 transferred at frequencies ranging from approximately 2 X 10(-7) to 2 X 10(-3).

Conjugation, Genetic↗

Risk factors for fecal colonization with trimethoprim-resistant and multiresistant Escherichia coli among children in day-care centers in Houston, Texas.

In a previous study, we found fecal colonization with multiresistant Escherichia coli exhibiting high-level trimethoprim resistance in 19% of diapered children attending six day-care centers in Houston, Tex. To examine the potential risk factors associated with this finding, we conducted cross-sectional studies among 203 children attending 12 day-care centers, 51 children attending a well-child clinic (controls), and 64 medical students. The prevalence of fecal colonization with trimethoprim-resistant E. coli among children attending day-care centers (30%) was higher (P less than 0.001) than among control children (6%) or medical students (8%). The prevalence of colonization among the children attending the 12 centers ranged from 0 to 59% and was correlated with the number of diapered children enrolled (r = 0.73; P less than 0.01). In a case control study among the day-care center children, significant risk factors were an age of less than 12 months and attendance at a center with an enrollment of over 40 diapered children (odds ratios of 2.2 and 3.5, respectively); ethnicity, duration of attendance, and prior antibiotic administration were not associated with colonization. Plasmid analysis of 60 of the day-care center strains revealed 22 profiles, each of which was unique to a given day-care center. Transmission and carriage of trimethoprim-resistant strains for as long as 6 months was documented in one center studied on three occasions. Given the documented transmission of enteric pathogens among diapered children attending day-care centers and their spread into family members, it is likely that day-care centers are an important community reservoir of plasmid-associated antibiotic-resistant E. coli.

Adolescent↗

The life and times of the Enterococcus.

Enterococci are important human pathogens that are increasingly resistant to antimicrobial agents. These organisms were previously considered part of the genus Streptococcus but have recently been reclassified into their own genus, called Enterococcus. To date, 12 species pathogenic for humans have been described, including the most common human isolates, Enterococcus faecalis and E. faecium. Enterococci cause between 5 and 15% of cases of endocarditis, which is best treated by the combination of a cell wall-active agent (such as penicillin or vancomycin, neither of which alone is usually bactericidal) and an aminoglycoside to which the organism is not highly resistant; this characteristically results in a synergistic bactericidal effect. High-level resistance (MIC, greater than or equal to 2,000 micrograms/ml) to the aminoglycoside eliminates the expected bactericidal effect, and such resistance has now been described for all aminoglycosides. Enterococci can also cause urinary tract infections; intraabdominal, pelvic, and wound infections; superinfections (particularly in patients receiving expanded-spectrum cephalosporins); and bacteremias (often together with other organisms). They are now the third most common organism seen in nosocomial infections. For most of these infections, single-drug therapy, most often with penicillin, ampicillin, or vancomycin, is adequate. Enterococci have a large number of both inherent and acquired resistance traits, including resistance to cephalosporins, clindamycin, tetracycline, and penicillinase-resistant penicillins such as oxacillin, among others. The most recent resistance traits reported are penicillinase resistance (apparently acquired from staphylococci) and vancomycin resistance, both of which can be transferred to other enterococci. It appears likely that we will soon be faced with increasing numbers of enterococci for which there is no adequate therapy.

Drug Resistance, Microbial↗

Comparison of genomic DNAs of different enterococcal isolates using restriction endonucleases with infrequent recognition sites.

Epidemiologic evaluation of enterococci has been limited by the lack of a simple and effective method for comparing strains. In this study, we have compared chromosomal restriction endonuclease digestion patterns of 27 isolates of Enterococcus faecalis from three different locations by using pulsed-field electrophoresis of large chromosomal fragments (14 to 1,000 kilobases). All but two isolates generated a clear, evaluable pattern with a single lysis and digestion, and the remaining two were visualized when a larger quantity of bacteria was used. All isolates from different locations generated different restriction patterns, as did most isolates within a single location; there was also evidence of spread of strains between individuals in each location. The ease with which this analysis can be performed, together with the clarity and polymorphism seen in the patterns, suggests that this technique will be very useful for epidemiological evaluations of nosocomial enterococcal infections.

DNA Restriction Enzymes↗

Quinolones and the gastrointestinal tract.

A number of studies have evaluated the efficacy of the new fluoroquinolones for therapy of bacterial enteric diseases and for prevention of gram-negative sepsis in granulocytopenic patients. The success of the quinolones in these settings is related to several special features of these agents, including their spectrum of activity and high fecal levels, which are in turn reflected in their effect on the gastrointestinal flora. Other factors that are important, particularly for invasive disease such as typhoid fever and shigellosis, include good intracellular and bowel wall penetration, and lymph node and systemic drug concentrations many times higher than the MICs of the causative organisms. This article reviews the factors that contribute to the changes in fecal flora, and the results of clinical studies in patients with diarrhea, granulocytopenic patients, and patients with selected other infections of, or related to, the gastrointestinal tract.

Agranulocytosis↗

Escherichia coli O114:nonmotile as a pathogen in an outbreak of severe diarrhea associated with a day care center.

Five infants from a day care center developed severe diarrhea associated with enteropathogenic Escherichia coli O114:nonmotile (EPEC O114:NM) and required hospitalization. Five additional cases of diarrhea associated with EPEC O114:NM subsequently occurred, four in hospital contacts of the patients and one in a household contact. Biochemically, all EPEC O114:NM isolates were sorbitol nonfermenters. All isolates produced low concentrations of cytotoxin with a mean of 10(1.23) CD50/mg of protein. Cytotoxin was not neutralized with antibody to Shiga-like toxin I or II. Heat-labile and heat-stable enterotoxins were not present by gene probe analysis. Stool isolates from 9 of 10 hospitalized infants were positive for EPEC adherence factor by colony blot DNA probe analysis. The severity of the disease, sorbitol nonfermentation, and presence of enteroadherence are unusual features of this organism.

Child Day Care Centers↗

Hemolytic uremic syndrome and diarrhea in Argentine children: the role of Shiga-like toxins.

Shiga-like toxin-producing Escherichia coli have been associated with hemorrhagic colitis and the hemolytic uremic syndrome (HUS). Because Argentina has the highest reported frequency of HUS in the world, Argentine children were prospectively studied during the HUS seasons for evidence of Shiga-like toxin-related diseases. On the basis of serology, fecal cytotoxin neutralization, stool cultures, and DNA hybridization of colony lysates, most children with HUS had evidence of infection with Shiga-like toxin-producing organisms. Children with spring-summer diarrhea also commonly (32%, confidence interval 18%-46%) had clear-cut evidence of such infection. No controls (children without gastrointestinal, renal, or hemolytic disease) had free fecal cytotoxin, positive cultures for E. coli O157:H7, or DNA probe-positive organisms; 20% of them had low serum titers of antibodies to Shiga-like toxins. E. coli O157:H7 was not common in either HUS or diarrhea patients. The high frequency of Shiga-like toxin-induced diarrhea in young children in Argentina probably explains the high incidence of HUS in this country and suggests that HUS is a relatively uncommon complication of Shiga-like toxin-related disease.

Argentina↗

Treatment of experimental endocarditis caused by a beta-lactamase-producing strain of Enterococcus faecalis with high-level resistance to gentamicin.

Several antimicrobial regimens were evaluated in the treatment of experimental enterococcal endocarditis due to a beta-lactamase-producing, highly gentamicin-resistant strain of Enterococcus faecalis. Ampicillin alone cleared bacteremia in the majority of rats and reduced titers of bacteria within vegetations (6.84 versus 8.80 log10 CFU/g in controls) but did not sterilize valves. Ampicillin-sulbactam combinations, vancomycin, daptomycin, and imipenem each reduced residual bacterial titers within vegetations to 4.01 log10 CFU/g or less; in 26 to 43% of animals receiving 5 days of therapy, titers of bacteria were reduced to undetectable levels. In a separate experiment, rats received ampicillin-sulbactam, daptomycin, or vancomycin for 10 days and were then observed for 10 days after termination of therapy for evidence of relapse. In surviving rats, valves remained sterile in four of five rats treated with ampicillin-sulbactam, in five of seven treated with daptomycin, but in only one of eight receiving vancomycin.

Animals↗

Problems and mechanisms of antimicrobial resistance.

Despite mankind's continuing efforts to find better and more powerful antimicrobial agents, bacteria continue to find ways to resist these agents. Recent examples include the emergence of plasmid-mediated resistance to third generation cephalosporins in E. coli, K. pneumoniae and Salmonella; the emergence of plasmid-mediated beta-lactamase in E. faecalis; the appearance of ciprofloxacin resistance among methicillin-resistant staphylococci; and, perhaps most threatening, the appearance of vancomycin resistance in E. faecalis and E. faecium, at least some of which is plasmid mediated. These examples demonstrate the continuing need for studies of resistance and for new compounds, and the need for new stategies in managing bacterial infections.

Anti-Bacterial Agents↗