Antibiotic resistance. Epidemiology and therapeutics.
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Cross Infection↗
Biomedical subjects
F P Tally
Publications and source records attributed to F P Tally.
Escherichia coli chromosomal mutations that permit direct cloning of the Bacteroides fragilis metallo-beta-lactamase gene, ccrA.
The class B, metallo-beta-lactamase genes ccrA (carbapenem- and cephamycin resistance) from three Bacteroides fragilis isolates--QMCN3, QMCN4, and TAL3636--were cloned and expressed in Escherichia coli. Cloning of the genes, by selecting for ampicillin resistance, was facilitated by two classes of Escherichia coli chromosomal mutations which resulted in at least a 5-10-fold increase in metallo-beta-lactamase enzymatic activity. The observed increase in enzymatic activity is due to either increased translation of the ccrA gene or an effect on localization or stability of the protein. Comparison of the DNA sequences of the three ccrA genes revealed that their protein-coding sequences shared greater than 97% DNA sequence identity. However, the 5' upstream sequence for the TAL3636 ccrA gene was unrelated to that of the other two genes.
Amino Acid Sequence↗
Molecular basis of tetracycline action: identification of analogs whose primary target is not the bacterial ribosome.
Tetracycline analogs fell into two classes on the basis of their mode of action. Tetracycline, chlortetracycline, minocycline, doxycycline, and 6-demethyl-6-deoxytetracycline inhibited cell-free translation directed by either Escherichia coli or Bacillus subtilis extracts. A second class of analogs tested, including chelocardin, anhydrotetracycline, 6-thiatetracycline, anhydrochlortetracycline, and 4-epi-anhydrochlortetracycline, failed to inhibit protein synthesis in vitro or were very poor inhibitors. Tetracyclines of the second class, however, rapidly inhibited the in vivo incorporation of precursors into DNA and RNA as well as protein. The class 2 compounds therefore have a mode of action that is entirely distinct from the class 1 compounds, such as tetracycline that are used clinically. Although tetracyclines of the second class entered the cytoplasm, the ability of these analogs to inhibit macromolecular synthesis suggests that the cytoplasmic membrane is their primary site of action. The interaction of class 1 and class 2 tetracyclines with ribosomes was studied by examining their effects on the chemical reactivity of bases in 16S rRNA to dimethyl sulfate. Class 1 analogs affected the reactivity of bases to dimethyl sulfate. The response with class 2 tetracyclines varied, with some analogs affecting reactivity and others (chelocardin and 4-epi-anhydrotetracycline) not.
Bacteria↗
Microbiology and antibiotic resistance in odontogenic infections.
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Bacteria, Anaerobic↗
Candidal meningitis following bacterial meningitis.
Patients with bacterial meningitis and posttraumatic and/or postsurgical access to the CSF are at risk for superinfection with Candida species. Patients who are not improving on appropriate antimicrobial chemotherapy for bacterial meningitis or are deteriorating after initial improvement should have a CSF reexamination for Candida superinfection.
Adult↗
Imipenem resistance in Bacteroides distasonis mediated by a novel beta-lactamase.
Imipenem is a highly active drug against the Bacteroides fragilis group of organisms. On the basis of a nationwide survey of over 500 isolates, it was found that the frequency of imipenem resistance was less than 0.1%. We have a highly resistant Bacteroides distasonis isolate, TAL7860, for which the following MICs (micrograms per milliliter) were determined by agar dilution: cefoxitin, greater than 128; moxalactam, greater than 128; piperacillin, greater than 128; imipenem, 16; and SCH34343, 16. Resistance was shown to involve both a beta-lactamase and an outer membrane permeability barrier. beta-Lactamase kinetics studies with several beta-lactams, including imipenem, revealed similar hydrolytic efficiency in comparison with those found for the B. fragilis strains. An imipenem outer membrane permeability barrier was detected for TAL7860, which was approximately sixfold more effective for B. fragilis TAL3636 and TAL2480. Significant inhibition of nitrocefin destruction was also shown with sulbactam and clavulanic acid at 10 mumol and dithiothreitol at 10 mM. No inhibition was seen with 10 mM EDTA. Differences in physicochemical properties and inhibition studies suggest that this beta-lactamase is different from the imipenem-inactivating metallo-beta-lactamase previously described in B. fragilis. We demonstrated a significant permeability barrier to clavulanic acid and sulbactam, which resulted in loss of synergism between these clinically employed beta-lactamase inhibitors and beta-lactam drugs. The novel beta-lactamase activity in conjunction with a limited permeability in TAL7860 resulted in resistance to all commonly employed beta-lactams, including the newest and most potent beta-lactam drugs.
Bacterial Proteins↗
Comparative activities of newer beta-lactam agents against members of the Bacteroides fragilis group.
A nationwide susceptibility survey of 557 isolates of the Bacteroides fragilis group was continued in 1986. The most active beta-lactam drugs were imipenem and ticarcillin-clavulanic acid, which had 0.2 and 1.7% resistance, respectively. The rank order of activity of beta-lactam drugs was imipenem, ticarcillin-clavulanic acid, cefoxitin, piperacillin, moxalactam, ceftizoxime, cefotetan, cefotaxime, cefoperazone, and ceftazadime.
Anti-Bacterial Agents↗
Cloning and sequencing of the class B beta-lactamase gene (ccrA) from Bacteroides fragilis TAL3636.
Bacteroides fragilis TAL3636 produces a class B, Zn2(+)-requiring beta-lactamase. The gene, ccrA, was cloned and expressed in Escherichia coli. The gene was sequenced and shown to share greater than 33% identity with the metalloenzyme from Bacillus cereus 569/H.
Amino Acid Sequence↗
R-plasmid mediated transfer of beta-lactam resistance in Bacteroides fragilis.
We described plasmid mediated transfer of resistance to beta-lactam antibiotics between Bacteroides fragilis strains. Ampicillin-resistance was transferred from B. fragilis strain GAI-10150 to a B. fragilis strain JC-101 with a frequency of 10(-6)/input donor by a filter mating technique. A common plasmid band, named pBFKW1, was found in both the donor and the transconjugants. The plasmid was purified by an ethidium bromide-CsCl ultracentrifugation. The molecular size of the plasmid pBFKW1 which seemed to encode the beta-lactam resistance and beta-lactamase production was estimated ca. 40 kb by the analysis of endonuclease digest. Substrate profile of the enzymes derived from the donor and a transconjugant were of cephalosporinase character.
Ampicillin Resistance↗
In-vitro susceptibility of the Bacteroides fragilis group and the inoculum effect of newer beta-lactam antibiotics on this group of organisms.
The susceptibility and inoculum effect of 190 selected Bacteroides fragilis group isolates were determined with six beta-lactam antibiotics by two different methods: agar dilution and broth microdilution. The results were analysed by species within this group of pathogens. The evaluation showed that imipenem had superior activity and was very stable to increased inoculum concentration. Cefoxitin and piperacillin exhibited very good activity and very small inoculum effect; latamoxef showed stability to changes in the inoculum concentration but only intermediate activity; while ceftizoxime and cefoperazone exhibited a marked inoculum effect and relatively poor activity. Resistance among the species was as follows: B. distasonis greater than B. thetaiotaomicron greater than B. ovatus greater than B. fragilis. The inoculum effect was higher when tests were performed in broth rather than in agar. In general, the effect was more pronounced among B. ovatus and less among B. distasonis isolates.
Anti-Bacterial Agents↗
Recurrent tonsillitis: histologic and bacteriologic evaluation.
Histologic and bacteriologic evaluations of tonsils removed at surgery from ten patients with a diagnosis of recurrent tonsillitis were performed. The bacteriology was complex, with an average of 6.3 aerobic bacteria and 3.3 anaerobic bacteria isolated from each patient. Histologic sections revealed chronic cryptitis, with intact tonsillar architecture. These findings provide a possible explanation for the failure of commonly used antibiotic regimens to eradicate recurrent infection from this site.
Adolescent↗
Prospective study comparing imipenem-cilastatin with clindamycin and gentamicin for the treatment of serious surgical infections.
Surgical infection remains a leading cause of hospital morbidity and mortality. We compared the efficacy and toxicity of imipenem-cilastatin sodium in 32 patients with that of clindamycin phosphate and gentamicin sulfate in 25 patients. In the imipenem-cilastatin group, 87.5% had a favorable outcome, with a 12.5% failure rate and 13 adverse reactions. In the clindamycin-gentamicin group, 80% had a favorable outcome, with a 20% failure rate and ten adverse reactions. Two significant superinfections with Pseudomonas and Candida were noted in patients treated with impenem-cilastatin. Each group had one case of Clostridium difficile-associated colitis. Cost analysis showed no differences between treatment arms, except in the appendicitis subgroup. For serious surgical infections, single-agent therapy with imipenem-cilastatin appears to be as efficacious as combination therapy with clindamycin and gentamicin.
Adolescent↗
A prospective double-blind evaluation of penicillin versus clindamycin in the treatment of odontogenic infections.
In a prospective, double-blind trial, penicillin and clindamycin were compared in treatment of moderate to severe orofacial infections of odontogenic origin, which yielded pus on aspiration. Among 27 patients randomized to receive penicillin, 22 (81%) had a successful outcome, and five (19%) were improved. In the 28 clindamycin-treated patients, 23 (82%) had a successful outcome, and five (18%) were improved. No failures were noted in either group. One patient who was receiving penicillin and two who were receiving clindamycin developed diarrhea. Bacteriologic results showed an average of 6.1 organisms per culture (2.5 aerobes and 3.6 anaerobes). Resistance rates for anaerobic isolates were 8.9% to penicillin and 1.9% to clindamycin. It was concluded that penicillin and clindamycin produce similar good results in treating odontogenic infection when the rate of penicillin resistance among oral anaerobic bacteria is at a relatively low level.
Adult↗
Permeability to beta-lactams in Bacteroides fragilis.
Bacteroides fragilis strains TAL2480 and TAL3636 were used to assess outer membrane permeability to various beta-lactam compounds. These strains were chosen because they possess beta-lactamases capable of hydrolysing all commonly employed beta-lactams except monobactams. The beta-lactamases are located in the periplasmic space and could be released by sonication and osmotic shock. Permeability was calculated by the method of Zimmerman & Rosselet (1977, Antimicrobial Agents and Chemotherapy 12, 368-72). The rank order of permeative ability (from fastest to slowest) was as follows: cephaloridine, imipenem, cefotaxime, cefoxitin, cefoperazone, nitrocefin, cephalothin, and latamoxef. Our results showed that ionic charge, hydrophobicity, and molecular weight influenced beta-lactam drug uptake by B. fragilis. These results are similar to findings for Escherichia coli, where increased negative charge and increased molecular weight are associated with decreased drug uptake. However, unlike E. coli, increased drug hydrophobicity, for a given charge and molecular weight of the drug, was associated with increased uptake by B. fragilis.
Anti-Bacterial Agents↗
Antibiotic resistance in anaerobic bacteria.
An improved understanding of the mechanisms of resistance and transfer in Bacteroides fragilis has been gained over the past decade. B. fragilis resistance to most penicillins is largely due to production of chromosomal beta-lactamases, although recent findings indicate these micro-organisms can acquire novel beta-lactamases, which can even inactivate imipenem. Several of the beta-lactamases of B. fragilis are transferable. Most of our understanding of transferable antimicrobial resistance in Bacteroides spp. has been gained through studies of the clindamycin-erythromycin resistance determinant found on pBFTM10. This resistance is encoded on a transposon and is widely distributed among the naturally occurring clindamycin-resistant isolates. Recent studies have shown that DNA can be transferred from Escherichia coli to B. fragilis, from one B. fragilis to another, and from B. fragilis back to E. coli. Data from a large survey in the United States indicate that susceptibility patterns of B. fragilis differ in each of the eight participating centres. Overall, piperacillin and cefoxitin have been found to be the most active beta-lactam agents.
Anti-Bacterial Agents↗
Factors affecting the choice of antibiotics in mixed infections.
Mixed infections can occur anywhere in the body and, on the basis of the location of the infection, involve predictable species of anaerobic bacteria. Most of our knowledge of anaerobic mixed infection has come from the study of intra-abdominal infections. The mortality associated with intra-abdominal abscesses in a recent study was lower than in earlier studies, perhaps because of improvements in radiographic techniques for better localization of abscess and early drainage, improved management of nutrition, and the selection of appropriate antimicrobial agents. The efficacy of an antimicrobial agent depends on its ability to penetrate into an abscess and function under conditions of low pH, low Eh and in the presence of beta-lactamases. Some effective antibiotics include clindamycin/gentamicin, metronidazole/gentamicin, latamoxef, cefoxitin, piperacillin and imipenem.
Abscess↗
Activity of trospectomycin against Bacteroides fragilis and other Bacteroides species.
The in vitro activity of trospectomycin (U-63366; 6'-n-propyl spectinomycin pentahydrate sulfate) was evaluated against 189 clinical isolates of the Bacteroides fragilis group and 65 Bacteroides species isolates. At less than or equal to 8 micrograms/ml, the activity of trospectomycin compared favorably with those of clindamycin and cefoxitin against B. fragilis, Bacteroides distasonis, and Bacteroides vulgatus, and there was no cross resistance to these three drugs among the strains of the B. fragilis group. All the Bacteroides species were susceptible to trospectomycin. The results of this in vitro study indicate that trospectomycin possesses excellent activity against Bacteroides species.
Anti-Bacterial Agents↗
Susceptibility of the Bacteroides fragilis group in the United States: analysis by site of isolation.
An ongoing survey of the susceptibility of the Bacteroides fragilis group of bacteria was continued at New England Medical Center in 1984 and 1985. A total of 1,229 strains were obtained from eight centers in the United States. These results were compared with those for 1,847 isolates tested in 1981 through 1983. The most active beta-lactam drugs were imipenem and ticarcillin-clavulanic acid (Timentin), which had a less than 1% resistance rate. No metronidazole- or chloramphenicol-resistant isolates were found during the 5 years of the study. Isolates obtained from blood, perinatal, and bone sites of infection were more resistant to a variety of antimicrobial agents. Susceptibility patterns of the members of the B. fragilis group varied at the eight hospitals and among species. These data indicate the need for determining the susceptibility patterns for the B. fragilis group of organisms at each hospital.
Anti-Bacterial Agents↗