Antagonism in sulphonamide sensitivity testing [proceedings].
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Biomedical subjects
Publications and source records attributed to S G Amyes.
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In a minimal medium, trimethoprim is merely bacteriostatic on the prototroph Escherichia coli 114. The drug was bactericidal when the amino acids methionine and glycine, plus a purine or purine nucleoside, were also present. This response could be reversed completely when thymine and lysine were added to the culture. Methionine, glycine, and the purine are thought to maintain the integrity of the tetrahydrofolate pool under trimethoprim treatment and prevent the thymidylate synthetase reaction. Thus, the organism behaves phenotypically as a thymineless mutant. The mechanisms by which thymine and lysine reverse the bactericidal effect of trimethoprim in a minimal medium containing methionine, glycine, and adenine is discussed.
Ampicillin and its derivatives are the most widely used beta-lactam antibiotics throughout the world. Ampicillin resistance in Gram-negative bacteria is usually manifested by plasmid-encoded beta-lactamases, which hydrolyse the beta-lactam ring of the antibiotic. There are at least 30 different plasmid-encoded beta-lactamases but almost all of them are found very infrequently. The one exception is the TEM-1 beta-lactamase which is found wherever transferable ampicillin resistance emerges and accounts for over 50% of all plasmid encoded ampicillin resistance. In India, the incidence of ampicillin resistance is high (82%) and, amongst Escherichia coli, a significant proportion of the plasmid-encoded beta-lactamases are different from those found in the United Kingdom. Although many Gram-negative species are able to accept the TEM-1 beta-lactamase, certain species have a pre-disposition to their own plasmid beta-lactamase types.
The incidence of trimethoprim resistance amongst enterobacterial strains responsible for significant bacteriuria in patients attending general practitioners in Edinburgh was 11.4%. Two-thirds of these resistant strains were highly resistant to trimethoprim. Trimethoprim resistance was more prevalent in bacteria isolated from men and from elderly patients. Less than half of the highly resistant strians possessed trimethoprim resistance plasmids; however, amongst those that did, one plasmid predominated. This plasmid was identical with the most successful trimethoprim resistance plasmid in hospital enterobacterial isolates at that time.
In this study, the relationship between gyrA mutations and ciprofloxacin minimum inhibitory concentration (MIC) values was investigated in Escherichia coli strains. For this purpose, ciprofloxacin MIC values of 46 E. coli strains, isolated from out-patients and hospitalized patients, were determined by the agar dilution method. The "Quinolone Resistance Determining Region" (QRDR) of gyrA gene was amplified and restricted by Hinf-I enzyme. Ser-83 mutation was observed in all strains that have ciprofloxacin MIC values of 0.062 mg/L and higher. Afterwards, eight strains, that were found susceptible (MIC < 1 mg/L, n: 1), intermediate (MIC: 1-4 mg/L, n: 1) and high level resistant (MIC > 4 mg/L, n: 6) to ciprofloxacin, were chosen and mutations in QRDRs of these strains investigated by DNA sequence analysis. Ser 83 Leu mutation was found in all the chosen strains and Asp 87 Tyr or Asp 87 Asn mutations were also observed except the ciprofloxacin susceptible (MIC: 0.062 mg/L) one. In addition, base substitutions that don't lead to aminoacid changes were detected. The strain in which only Ser 83 Leu mutation was observed, showed high level nalidixic acid resistance (MIC > 256 mg/L). This fact was in favour of that, one mutation is enough to develop high level resistance to nalidixic acid. It was concluded that high level ciprofloxacin resistance requires at least two mutations in the QRDR of gyrA gene.
Of 320 patients surveyed in a general hospital's medical wards during a 6-month period in 1981, 18 (5.6%) harboured enterobacteria which contained resistance plasmids conferring resistance to trimethoprim (Tp). At the beginning of the study period, Tp-containing therapy was not the first choice for treatment of infections caused by these bacteria and the incidence of plasmid-determined resistance was 10%. When Tp alone was used as the first choice of treatment of urinary tract infections and the use of this antimicrobial was correspondingly increased, the proportion of strains that contained Tp resistance plasmids (R-plasmids) decreased to 4%. Relatively more patients with Tp-resistant strains in the bowel had significant bacteriuria compared with those without Tp-resistant organisms. The continuing occurrence of Tp-R-plasmid containing strains in the gut was associated with continuing antimicrobial therapy; the strains generally disappeared after antimicrobial therapy was stopped.