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Biomedical subjects

F W Goldstein

Publications and source records attributed to F W Goldstein.

At least 91 records · Page 5Linked to original sources

Cross-resistance to nalidixic acid, trimethoprim, and chloramphenicol associated with alterations in outer membrane proteins of Klebsiella, Enterobacter, and Serratia.

We studied in vitro mutants of Klebsiella, Enterobacter, and Serratia cross-resistant to nalidixic acid, trimethoprim, and chloramphenicol that were similar to mutants found in vivo. The sole mechanism for this type of resistance appeared to be a reduction in permeability of the cell envelope. The mutants had significantly lower rates of uptake of glucose and chloramphenicol, but binding of chloramphenicol to ribosomes was normal. In addition, the amounts of dihydrofolate reductase were similar in both wild-type and cross-resistant mutants of Klebsiella. Examination of the bacterial outer membrane revealed that the amount of at least one major protein, with a molecular size of approximately 40 kilodaltons, was decreased in the mutants. Therefore the resistance seemed likely to be due to the reduction in quantity of these outer membrane proteins, possibly porins, in the mutant bacteria.

Anti-Bacterial Agents↗

[Resistance of enterobacteria to the sulfonamide-trimethoprim combination. Course during the last 10 years].

From january 1972 to december 1981, nearly 54.000 strains of enterobacteria isolated from clinical specimens were tested for susceptibility to the trimethoprim-sulfamide combination (co-trimoxazole). During that period, the overall resistance to trimethoprim increased from 17.9% to 32.7%, and there was a fourfold increase in the number of strains exhibiting high level resistance; 246 trimethoprim-resistant plasmids were transferred into E. coli K 12. The number and frequency of the other resistance markers co-transferred with trimethoprim are constantly increasing and as a result, more and more antibiotics are likely to be responsible for the selection of trimethoprim-resistant plasmids. In contrast, the proportion of trimethoprim-resistant mutants decreased from 11% to 5%. The use of co-trimoxazole in France may explain this low incidence.

Drug Resistance, Microbial↗

Transferable plasmid-mediated antibiotic resistance in Acinetobacter.

Acinetobacter calcoaceticus strain BM2500 was resistant to ampicillin, aminoglycoside-aminocyclitols, chloramphenicol, sulfonamides, and high levels of trimethoprim. Resistance to ampicillin was due to the presence of a beta-lactamase (TEM-1) and the aminoglycoside-aminocyclitol resistance was mediated by phosphotransferase (APH(3')(5")I) and adenylyltransferase (AAD(3)(9] activities. The resistance genes were carried by a 167 kilobase plasmid, pIP1031, belonging to incompatibility group 6-C; the plasmid was self-transferable, at extremely low frequency, to Escherichia coli by conjugation. Plasmid pIP1031 DNA was analyzed by agarose gel electrophoresis following restriction endonuclease digestion, by nucleic acid hybridization, and by CsCl analytical density gradient ultracentrifugation. The results support the hypothesis that plasmid pIP1031 may have been acquired recently by strain BM2500.

Acinetobacter↗

Activity of imipenem on aerobic bacteria.

Imipenem is a new carbapenem antibiotic with a broad spectrum of activity on Gram-positive and Gram-negative bacteria. It is a potent inhibitor of plasmid- and chromosomally-mediated beta-lactamases. The purpose of this study was to evaluate the in vitro activity of imipenem on clinical isolates classified according to their susceptibility to beta-lactam antibiotics. On penicillin G-susceptible bacteria, imipenem is comparable to penicillin. On streptococci, pneumococci, Staphylococcus aureus and Listeria the MICs were 0.02 to 0.06 mg/l. On gonococci, MICs were 0.04 to 0.25 mg/l. Gram-negative bacteria susceptible to beta-lactam antibiotics or naturally resistant to certain of them (e.g. Klebsiella pneumoniae resistant to ampicillin and carbenicillin) were highly susceptible to imipenem with MICs from 0.06 to 0.5 mg/l. It was slightly less active on Haemophilus influenzae, compared to ampicillin. On beta-lactam-resistant bacteria, imipenem maintained a remarkable activity. For penicillin-resistant pneumococci (MIC 16 mg/l) the imipenem MIC was 1 mg/l. Imipenem was equally effective on beta-lactamase-producing and non-producing Haemophilus influenzae and gonococci. Among 12 Nocardia asteroides tested, 11 had MIC less than 1 mg/l. When tested at 30 degrees, the MIC of imipenem for oxacillin-resistant Staphylococcus aureus ranged from 8 to 64 mg/l in contrast to 0.03 to 0.06 mg/l for oxacillin-sensitive isolates. Eighteen strains of enterococci (17 faecium, 2 faecalis) resistant to ampicillin (MIC 128 mg/l) were more resistant to imipenem (MIC 16 to 256 mg/l). Imipenem was very active on beta-lactam-resistant Gram-negative bacteria, including multiply-resistant Salmonella typhi., with MICs in a range from 0.06 to 4 mg/l).(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Bacterial Agents↗

Susceptibility of Nocardia asteroides to 46 antibiotics, including 22 beta-lactams.

Twelve Nocardia asteroides isolates were tested for their susceptibility to 46 antibiotics by the agar dilution method. N-Formimidoyl thienamycin was the most active of 22 beta-lactam antibiotics, inhibiting 11 of the 12 strains at 1 microgram/ml. Penicillins, including ureidopenicillins, showed poor activity. Cefotaxime, ceftriaxone, and especially cefuroxime had the best activities of the cephalosporins tested. Among the other antibiotics, amikacin and minocycline, respectively, inhibited all of the strains tested at 0.5 and 4 micrograms/ml.

Aminoglycosides↗

Mechanism of transferable resistance to chloramphenicol in Haemophilus parainfluenzae.

A clinical isolate of Haemophilus parainfluenzae resistant to chloramphenicol and tetracycline transferred both cam and tet determinants to Escherichia coli K-12 during mixed cultivation on solid media irrespective of the selection employed. The doubly resistant transconjugant was found to contain levels of the enzyme chloramphenicol acetyltransferase (CAT) comparable to those found in R plasmid-bearing chloramphenicol-resistant enteric bacteria. Purification of CAT from the transconjugant was achieved by affinity chromatography, and the electrophoretically homogeneous protein was compared with previously characterized CAT variants specified by R plasmids. Although the CAT associated with cam from H. parainfluenzae was found to be distinct from the three types described previously, its N-terminal peptide amino acid sequence was identical with that determined for a type II CAT. Attempts to demonstrate covalently closed circular deoxyribonucleic acid in the H. parainfluenzae donor and the E. coli transconjugant were unsuccessful. The cam and tet determinants were nontransmissible from E. coli but could be cotransferred following the introduction of a suitable conjugative plasmid.

Cell-Free System↗

Human infections caused by thiamine- or menadione-requiring Staphylococcus aureus.

Stable dwarf forms of Staphylococcus aureus have been identified in clinical specimens as the sole or predominant isolate in eight cases. These organisms have been shown to be menadione or thiamine dependent, i.e., cultivation in the presence of one of these agents has permitted growth of colonies which appear typical of S. aureus. In vitro resistance to aminoglycosides was overcome by cultivation in the presence of menadione or thiamine. Menadione- or thiamine-requiring S. aureus can be considered as causative agents in severe human infections. Special care must be taken if they are to be identified in pathological specimens. Their antibiotic sensitivity testing should be done comparatively on supplemented and nonsupplemented media.

Aminoglycosides↗

Two distinct types of trimethoprim-resistant dihydrofolate reductase specified by R-plasmids of different compatibility groups.

R-Plasmids from a number of trimethoprim-resistant Escherichia coli and Citrobacter sp. were studied after transfer to E. coli K12 hosts. Each was found to specify a dihydrofolate reductase which was resistant to trimethoprim and Methotrexate, and which could be completely separated from the host chromosomal enzyme by gel filtration. Two distinct types of R-plasmid dihydrofolate reductases were identified. Type I enzymes, typified by the R483 enzyme previously described (Sköld, O., and Widh, A. (1974) J. Biol. Chem. 249, 4324-4325), are synthesized in amounts severalfold higher than the chromosomal enzyme. The 50% inhibitory concentrations (I50) of trimethoprim, Methotrexate, and aminopterin are increased several thousandfold over the corresponding values for the chromosomal enzyme. Type II R-plasmid dihydrofolate reductases are synthesized in about the same amount, or less, as the chromosomal enzyme, but are practically several hundredfold higher than those for the type I enzymes. Both types of R-plasmid dihydrofolate reductase showed little difference from the chromosomal enzyme in the binding of dihydrofolate, NADPH, folic acid, and 2,4-diaminopyrimidine.

Chromosomes, Bacterial↗

[Drug sensitivity of Haemophilus sp. and transfer of resistance into E. coli (author's transl)].

From June 1973 to July 1976, 742 strains of Haemophilus influenzae and parainfluenzae, isolated from clinical specimens, were routinely tested for in vitro sensitivity to twelve antibiotics: penicillin, ampicillin, cephalothin, streptomycin, kanamycin, gentamicin, chloramphenicol, tetracyclin, minocyclin, erythromycin, sulfamethoxazol, trimethoprim. 61 strains were found resistant to one or more of these antibiotics (ampicillin, kanamycin, chloramphenicol and tetracyclin). The MICs of 23 antibiotics were determined by the agar dilution method on most of the resistant strains and on 60 sensitive strains isolated during the same period and considered as control. 21 strains transferred their resistance determinants into E. coli K12; 23 plasmids were obtained isolated from these strains: 2 strains contained two different plasmids. 90% of the transconjugants were stable after repeated subcultures.

Anti-Bacterial Agents↗

[Trimethoprim resistance plasmids: transferability and incompatibility groups (author's transl)].

Over a three year period, 119 strains of enterobacteria isolated from patients have been found resistant to trimethoprim (TMP) and sulfonamides (Su); 11 strains were resistant to TMP only. MIC of TMP were between 32 and 2048 microng/ml. Three groups of strains are described: (1) thymineless variants (2 strains); (2) TMP resistance non-transferable into Escherichia coli K12 (95 strains); (3) TMP resistance transferable into E. coli K12 (33 strains). TMP marker and Su marker have been transferred independantly from 13 strains; they were cotransferred from 20 strains. The incompatibility group of 31 plasmids has been determined: 10 belong to the fi+ type, group FII; 21 belong to the fi--type, group 6, group 7, group 10, group N and group I1. Epidemiological implications of such a wide range of incompatibility groups among a small number of plasmids specifying TMP resistance are discussed.

Drug Resistance, Microbial↗