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Biomedical subjects

F O'Grady

Publications and source records attributed to F O'Grady.

At least 55 records · Page 3Linked to original sources

Factors governing the emergence of resistance to nalidixic acid in treatment of urinary tract infection.

Cultures of Escherichia coli were exposed to nalidixic acid in an in vitro model in which the conditions of drug-organism interaction resembled those of bacterial cystitis treatment. Results obtained in this way suggested that emergence of bacterial resistance should not be a major problem in treatment of uncomplicated urinary infection; such cases might indeed respond to a less intensive course of treatment than is usual. More prolonged, high-dosage therapy with nalidixic acid may be required for patients with more complicated infections if the risk of failure from the emergence of bacterial resistance is to be minimized.

Cystitis↗

Mecillinam.

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Azepines↗

Dual-action cephalosporin utilizing a novel therapeutic principle.

A new cephalosporin is described that overcomes, in a novel way, the general susceptibility of this group of agents to enterobacterial beta-lactamases. The new compound carries a substituent that is released on cleavage of the beta-lactam ring and then exhibits antibacterial activity in its own right. The possible therapeutic benefits of such an antibiotic are discussed.

Ampicillin↗

Activity and interaction of trimethoprim and sulphamethoxazole against Escherichia coli.

The activity of trimethoprim (TMP) and sulphamethoxazole (SMX), alone and in combination, against a sensitive strain of Escherichia coli was investigated in turbidimetric systems. In a static system in which the conditions of exposure of bacteria to drug resembled those of conventional minimum inhibitory concentration (MIC) titrations, both TMP and SMX exhibited antibacterial activity at concentrations well below the conventionally determined MIC, but regrowth occured at these concentrations during the overnight incubation period due to the emergence of adaptively resistant bacteria. Tests of combined drug action in the static turbidimetric system revealed even more synergic interaction than was apparent in conventional MIC tests. It is suggested that an important component of overall synergic interaction is the mutual suppression of adaptive "resistance" to the other agent. Studies in an in vitro model which simulates the hydrokinetic features of the urinary bladder showed that concentrations of TMP and SMX below the conventionally determined MIC inhibited the growth even of extremely dense bacterial populations so long as the concentration of drug was maintained. The response of cultures exposed to combinations of TMP and SMX in this system was so dominated by the effect of TMP that no synergic interaction with SMX was noted at concentrations of the drugs which are achievable in urine.

Drug Synergism↗

The in vitro activity of ceftezol (demethylcefazolin) against dense populations of Escherichia coli.

The activity of ceftezol was examined by continuous turbidimetric monitoring of dense populations of Escherichia coli exposed to the drug. Although ceftezol was found to be very active against strains of E. coli, its activity was consistently less than that of the closely related antibiotics, cefazolin. This difference was also found when strains of E. coli were examined in a dynamic system which simulates some of the conditions in which bacteria and drug interact in the treatment of bacterial cystitis. Evidence is presented that the difference in activity between the two cephalosporins resides in a differential ability to induce certain morphological changes in E. coli and in a differential rate of destruction by escherichial beta-lactamases.

Anti-Bacterial Agents↗

Global surveillance of antibiotic sensitivity of Vibrio cholerae.

Strains of Vibrio cholerae-1156 from various parts of the world-were examined by standardized antibiotic sensitivity tests in one centre, to determine the global incidence of antibiotic resistance in this organism and to assess the extent to which differences in methods of sensitivity testing might be responsible for discrepancies in the reported incidence of resistant strains. Of the strains examined, 1127 were fully sensitive to ampicillin, chloramphenicol, tetracycline, furazolidone, and three different sulphonamides, 27 showed stable and reproducible resistance to one or more of these agents, and 2 proved to contain a minority of cells with unstable, presumably plasmid-borne, resistance to chloram-phenicol. Unstable resistance to antibiotics may be common in V. cholerae but rarely recognized, and may account for some of the discrepancies in the reported incidence of resistant strains.

Anti-Bacterial Agents↗

Factors influencing the response of Escherichia coli to antibiotics in conditions prevailing in the infected urinary bladder.

The response of a sensitive strain of Escherichia coli to a variety of antibiotics was examined in an in vitro model which simulates the hydrokinetic features of the urinary bladder. Recovery of bacterial cultures from antibiotic effects was observed following exposure to bactericidal and bacteristatic antibiotics and no substantial difference was noted between the effectiveness of bacteristatic and bactericidal agents except that bacteristatic antibiotics were more influenced by alteration of the conditions of "diuresis" and "frequency of micturition". The response of dense bacterial populations to high concentrations of 3 beta-lactam antibiotics varied markedly under the different hydrokinetic conditions. Possible reasons for these variations are discussed.

Ampicillin↗

An electro-optic study of the effect of certain aminoglycoside antibiotics on the electrical polarizability of sensitive, dependent and resistant strains of Escherichia coli.

A study has been made of the effect of certain aminoglycoside antibiotics on the electrical properties of the surfaces of one sensitive, two resistant and one dependent form of E. coli K-12. The method employed was to observe the change in scattered light produced when the bacteria in suspension are orientated by an applied a. c. electric field. The effect of the antibiotics has been analysed in terms of drug accumulation at the bacterial surface. Differences have been noted in the responses of the sensitive form to different aminoglycosides and an attempt has been made to correlate these differences with mimimum inhibitory concentrations. Differences have also been noted in the response of certain resistant and dependent forms of E. coli to streptomycin.

Anti-Bacterial Agents↗

Resistance categories of enterobacteria to beta-lactam antibiotics.

The activities of cephaloridine, cephalothin, and ampicillin against dense cultures of 103 ampicillin-resistant gram-negative bacilli were compared in a turbidimetric system. The organisms were divided into two groups according to their behavior in conventional minimal inhibitory concentration titrations: those fully resistant to ampicillin at a concentration of 500 mug/ml and those inhibited by 32-500 mug of ampicillin/ml. Of the 83 strains in the first group, most were more sensitive to cephalothin than to cephaloridine, whereas the 20 strains in the second group exhibited a number of interesting properties peculiar to them. On the basis of these and previous results, six distinct categories of resistance to beta-lactam antibiotics have been detected among enterobacteria.

Ampicillin↗

Lysis enhancement: a novel form of interaction between beta-lactam antibiotics.

A novel form of synergy has been observed to occur between cephalexin and certain other beta-lactam antibiotics. In the presence of cephalexin a reduction was found in the concentration of other beta-lactam agents needed to induce lysis of Escherichia coli; the effect was particularly marded when cephalexin was allowed to act for a short time before the addition of the second agent. The basis of this type of synergy--which is not likely to be of therapeutic value--is discussed in terms of a theroy perviously put forward, whcih suggests that penicillins and cephalosporins have two distinct sites of action in Gram-negative bacilli.

Ampicillin↗

Activity of cefazolin against dense populations of enterobacteria.

The in vitro activity of cefazolin was assessed by continuous turbidimetric monitoring of cultures of gram-negative bacilli and the results were compared with those previously obtained with other beta-lactam agents using the same strains and methods. Cefazolin was found to induce rapid lysis of ampicillin-susceptible and -resistant strains of Escherichia coli at a lower concentration than any other beta-lactam agent tested; its stability to beta-lactamase, as judged by regrowth studies, was generally considerably greater than that of other antibiotics of this group. Tested against 103 ampicillin-resistant enterobacteria, cefazolin was found to be more active than cephalothin against E. coli, but no systematic increase in susceptibility to cefazolin was seen with other species. A study of cefazolin in an in vitro model which simulates the hydrokinetic features of the urinary bladder showed it to be as active as ampicillin against ampicillin-susceptible E. coli and as active as cephalothin against ampicillin-resistant E. coli.

Cefazolin↗

Assessment of susceptibility of ampicillin-resistant enterobacteria to cephalosporins.

The susceptibility of 103 ampicillin-resistant strains of enterobacteria to two cephalosporins was assessed by turbidimetric monitoring and disk diffusion tests. The results obtained suggest that in most cases a correlation exists between the suppression of growth of a dense bacterial culture for a therapeutically acceptable period by a fixed, high concentration of cephalosporin and a large zone of inhibition (>/=24 mm) using a high potency disk. This correlation was found to hold good when a moderate, subconfluent inoculum and commercially obtained blood-agar plates were used for the disk test, but not when the stringent conditions required by the Kirby-Bauer test (which demands a dense inoculum on Mueller-Hinton agar) were employed. Better correlation was obtained with cephaloridine than with cephalothin. This approach to the interpretation of disk diffusion tests gives a grossly different picture of the susceptibility of ampicillin-resistant enterobacteria to cephalosporins than do conventional minimal inhibitory concentration-based correlations.

Ampicillin↗

Potent combinations of beta-lactam antibiotics using the beta-lactamase inhibition principle.

Several penicillins known to be stable to enterobacterial beta-lactamases were tested in combination with beta-lactamase-sensitive penicillins and cephalosporins in a turbidimetric system. Nafcillin was found to be the best beta-lactamase inhibitor amongst agents presently available commercially, but the related, new semi-synthetic penicillin BRL 1437 (2-isopropoxy-1-naphthylpenicillin) was consistently found to be superior. Using 103 ampicillin-resistant coliform bacilli and antibiotic levels achievable in urine, cephalothin or cephaloridine alone achieved long-term suppression of growth (greater than 20 h) of 16 and 13% of strains, respectively, while the additional presence of BRL 1437 suppressed growth for longer than 20 h of 81% of the remaining strains. Even where 'success' was not achieved according to these stringent criteria, regrowth was significantly delayed by the presence of BRL 1437. Suppression of growth for longer than 20 h by BRL 1437 plus cephalothin was achieved with all of the 46 Escherichia coli strains tested. Antibiotic combinations were also studied in an in vitro model which stimulates the hydrokinetic features of the urinary bladder. Suppression of the growth of two highly resistant E. coli strains was achieved in this system, for therapeutically acceptable periods of time, with combinations of cephalothin or cephaloridine with BRL 1437, but not nafcillin.

Ampicillin↗