Valediction--a personal view from Professor Francis O'Grady, Chief Scientist of the Department of Health 1986-1990.
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Health Policy↗
Biomedical subjects
F O'Grady
Publications and source records attributed to F O'Grady.
Death and other notable events in the course of infection.
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Bacterial Adhesion↗
Comparative growth of Bacteroides species in various anaerobic culture media.
The growth of five species of Bacteroides in four anaerobic culture media was continuously monitored turbidimetrically. Interspecies differences were observed in the growth of Bacteroides spp. in the various media, but growth in Brain Heart Infusion broth supplemented with yeast extract, haemin and menadione, was consistently better than in Wilkins-Chalgren, Thioglycollate or Schaedler broths. Microscopy of cultures grown overnight in Brain Heart Infusion broth showed that the bacteria exhibited normal morphology but most species grown in the other media displayed filamentation or chain formation. Four of the five species grown in Schaedler broth also exhibited spheroplast formation. This morphological change occurred in the stationary phase of growth, was reduced by inclusion of NaCl in the medium and was abolished in Schaedler broth prepared at double the recommended strength.
Anaerobiosis↗
A micro-chamber for continuous microscopic monitoring of anaerobic bacteria.
A recently developed apparatus is described that allows continuous microscopic monitoring of bacteria grown in anaerobic conditions. Four species of Bacteroides were tested using this equipment and normal and reproducible growth rates were obtained in all cases.
Bacteriological Techniques↗
Strategies for potentiating chemotherapy in severe sepsis: some experimental pointers.
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Anti-Infective Agents↗
Continuous opacity monitoring of the growth of bacteria under strict anaerobic conditions.
A newly designed instrument is described which generates continuous records of the opacities of six bacterial cultures growing under strict anaerobic conditions. Additions (for example, of antibacterial agents) or withdrawal of culture (for example, for viable counting) can be made at any time without breach of anaerobiosis. Use of the instrument is illustrated by growth curves obtained from small inocula of two strict anaerobes, Bacteroides asaccharolyticus and Peptostreptococcus anaerobius and by the effects on the growth curve of Bacteroides fragilis of adding various concentrations of metronidazole at different times.
Anaerobiosis↗
Semiautomated determination of minimum bactericidal concentrations of antibiotics.
Using a newly devised 50-channel photometer which records the opacity of growing bacterial cultures, it was shown that the time taken by cultures diluted 1/1000 in fresh broth to reach 50% of the opacity of a fully grown culture was inversely related to the concentration of organisms in the original culture. This relation was used to determine the numbers of survivors after exposure to benzylpenicillin and gentamicin alone and in combination. The procedure is commended as a labour-saving and potentially rapid method of obtaining comprehensive information on the bactericidal action and interaction of antibiotics.
Dose-Response Relationship, Drug↗
Therapeutic significance of nocardicin A stimulation of phagocyte function in experimental Pseudomonas aeruginosa infection.
Nocardicin A, a monocyclic beta-lactam antibiotic with modest anti-pseudomonal activity in vitro, controlled an otherwise fatal Pseudomonas infection in mice when given in doses which produced blood levels well below the minimum bactericidal concentration. In even smaller doses, it converted the partial protection afforded by modest doses of carbenicillin into full protection. Human polymorphonuclear leucocytes exposed to low concentrations of the drug in vitro and peritoneal macrophages recovered from mice treated with nocardicin A exhibited an unusually specific form of enhanced activity. Chemotaxis and phagocytosis were not affected, but intracellular killing of Ps. aeruginosa was significantly increased. This was shown to be due to an effect on the phagocyte and not to facilitated killing of organisms damaged by extracellular exposure to the antibiotic. It is argued that the effect on phagocyte function is sufficient to contribute materially to the therapeutic effect of nocardicin A.
Animals↗
In-vitro activity of the novel oxa-beta-lactam antibiotic moxalactam (LY 127935) against dense populations of selected Gram-negative bacilli.
The activity of moxalactam, a new beta-lactam antibiotic with a novel molecular structure, was examined against dense populations of a variety of Gram-negative bacilli. The lytic activity of moxalactam against ampicillin-sensitive strains was similar to ampicillin, but the activity was maintained against ampicillin-resistant strains, including Pseudomonas aeruginosa, irrespective of whether the ampicillin resistance was 'intrinsic' (non-enzymic) or due to beta-lactamase. Of the 18 strains tested only one, a Hafnia sp., failed to respond to moxalactam.
Ampicillin↗
Increasing importance of plasmid-mediated trimethoprim resistance in enterobacteria: two six-month clinical surveys.
All clinical isolates of enterobacteria received at the laboratory were monitored for trimethoprim resistance over six months in 1978. The survey was repeated in 1979 and the incidence of trimethoprim resistance showed a slight decrease, but the proportion of resistant strains owing their trimethoprim resistance to transferable R plasmids had almost trebled. There was also a large increase in the proportion of resistant strains exhibiting high-level non-transferable trimethoprim resistance. These findings suggest transposition of genes conferring trimethoprim resistance from plasmids to the bacterial chromosome.
Drug Resistance, Microbial↗
Treatment of acute bacterial cystitis: economy versus efficacy.
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Acute Disease↗
Response of Escherichia coli to Beta-lactam antibiotics: effect of the concomitant presence of staphylococci exhibiting inducible Beta-lactamase activity.
The response to Beta-lactam antibiotics of mixed cultures of Escherichia coli and Staphylococcus epidermidis was studied in static culture and in an in vitro model which simulates the dynamic conditions in which bacteria are exposed to antibiotics in the treatment of urinary infection. In static cultures, the concomitant presence of staphylococci exhibiting inducible Beta-lactamase activity substantially reduced the efficacy of benzylpenicillin and ampicillin (but not cefuroxime) against E. coli. In the conditions of the bladder model some interference with the activity of Beta-lactam antibiotics by Beta-lactamase producing staphylococci was also demonstrated. Nevertheless, relatively modest doses of ampicillin were still able to suppress growth of susceptible E. coli for periods exceeding the normal interdose interval, even in the presence of enzyme-producing staphylococci.
Ampicillin↗
An in vitro model for assessing optimum antibiotic dosage in urinary tract infection.
Experimental and clinical data from which dosage regimens can be rationally deduced are generally lacking. As an approach to this problem, an in vitro model of the urinary bladder has been constructed in which the conditions of exposure of bacteria to antibacterial drugs which exist in the treatment of cystitis are simulated. Results obtained so far correlate well with such clinical information as we possess and have helped to define more accurately the conditions which govern successful therapy of urinary infection. The most recent data suggest that much lower doses of some beta-lactam antibiotics than have been contemplated hitherto may be effective in the treatment of uncomplicated cystitis.
Anti-Bacterial Agents↗
Uropathogenic properties of Escherichia coli in recurrent urinary-tract infection.
Properties of Escherichia coli considered to be important in the pathogenesis of urinary-tract infection were investigated. The following properties were more common in E. coli strains isolated from urinary infections than in periurethral strains from healthy individuals: (i) O serogroups 2, 4, 6, 8, 18ab and 75; (ii) high K-antigen titre; (iii) production of haemolysin; (iv) production of fimbriae; (v) fermentation of salicin. The correlation between isolation of a strain from the urinary tract and possession of any single property was not strong; however, strains rich in a combination of these pathogenic properties were rarely isolated from the periurethral area of healthy subjects but were common in urinary infections. Nevertheless, a significant proportion of urinary strains had few pathogenic properties. Strains rich in pathogenic properties were more commonly isolated from upper urinary-tract infections than from lower-tract infections; this indicates that the properties of the invading organism may influence the localisation of infection.
Antigens, Bacterial↗
Comparative in vitro activities of cefotaxime and ceftizoxime (FK749): new cephalosporins with exceptional potency.
Cefotaxime and its desacetoxymethyl derivative, ceftizoxime (previously known as FK749), are both extremely active against a wide spectrum of bacteria. In the present comparative study, the activity of ceftizoxime exceeded that of cefotaxime by a factor of four or more for strains of Klebsiella, Enterobacter, Providencia, Serratia, and Bacteroides; the only species for which the activity of cefotaxime exceeded that of ceftizoxime by a factor of four was Vibrio cholerae. Against other species, the activity of the two drugs was roughly comparable. Both showed outstanding activity against Haemophilus influenzae and Neisseria gonorrhoeae. Comparative turbidimetric and morphological studies revealed that ceftizoxime was able to induce spheroplast formation and rapid lysis in Escherichia coli strains at lower concentrations than cefotaxime. This difference was not found, however, when E. coli strains resistant to ampicillin by an intrinsic (nonenzymic) mechanism were tested.
Bacteria↗
Thiamphenicol and chloramphenicol: an in vitro comparison with particular reference to bactericidal activity.
Chloramphenicol is bacteristatic for most species but bactericidal for Haemophilus influenzae and Neisseria meningitidis. Despite its generally lower activity, thiamphenicol exhibited equal or greater activity against these two species than did chloramphenicol. It is suggested that a particular place might be defined for thiamphenicol in the treatment of infection due to these two organisms.
Bacteria↗
A microcomputer-based research system for the optical analysis of agar-cultured micro-organism colonies.
A system which has been developed for the automatic of agar-cultured microorganism colonies is described. A camera of the line-scanning type is used to scan the plates and details of the hardware and software development are explained. Flow diagrams are included which illustrate the operation of the system, but, as yet, no results are available. The prototype machine is undergoing evaluation testing.
Agar↗
Resistance to antimicrobial agents of Vibrio cholerae E1 Tor strains isolated during the fourth cholera epidemic in the United Republic of Tanzania.
Isolates of Vibrio cholerae obtained immediately after the outbreak of the fourth recorded epidemic of cholera in the United Republic of Tanzania were sensitive to tetracycline, but after five months of its extensive therapeutic and prophylactic use, 76% of the isolates were observed to be resistant to this and other antimicrobial agents. The appearance of resistance was found to be due to the rapid spread of antibiotic resistance plasmids belonging to the C incompatibility complex. Although most plasmid incompatibility groups have been shown to be unstable in V. cholerae, the strains found in the present epidemic seem to carry a plasmid belonging to one of the few relatively stable groups. These findings emphasize the importance of monitoring any emergence of bacterial resistance that may occur when mass prophylaxis programmes are in operation and also the importance of determining the genetic basis of the resistance mechanism.
Alanine↗