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J M Hamilton-Miller

Publications and source records attributed to J M Hamilton-Miller.

At least 19 recordsLinked to original sources

Sir Edward Abraham's contribution to the development of the cephalosporins: a reassessment.

This paper is based on an invited lecture given at the 21st International Congress of Chemotherapy in July 1999, as part of a Symposium entitled '50 years of cephalosporins: their use the next 50 years', (Hamilton-Miller JMT, Cephalosporins: from mould to drug. Sardinia to Oxford and beyond, J Antimicr Chemother 1999;44(A):26). Celebration of this Golden Anniversary was made more poignant by the death of the last major participant, Sir Edward Abraham, in May 1999. This history has been told before, but mainly by Sir Edward, who being a very modest man (to which his obituaries graphically attest) consistently underplayed the role that he and Newton had in the discovery of cephalosporin C, that led to all the cephalosporins now in use. I had the privilege of working at the Dunn School from 1967 to 1970, with Abraham and Newton, where I met Brotzu, Florey and Dorothy Hodgkin, all of whom had important roles in this story. Other workers at the Dunn School at that time, e.g. Heatley, Sanders and Jennings (who became Lady Florey), helped develop penicillin. Such a galaxy of stars of the antibiotic firmament will never again be assembled. "Let us now praise famous men... these were honoured in their generation, and were the glory of their times" - Ecclesiasticus XLIV. vv 1.7.

Cephalosporins↗

Patterns of phenotypic resistance to the macrolide-lincosamide-ketolide-streptogramin group of antibiotics in staphylococci.

Phenotypes of resistance to the macrolide-lincosamide-ketolide-streptogramin (MLKS) group of antibiotics have been determined in 540 clinical isolates of staphylococci (210 Staphylococcus aureus and 330 coagulase-negative species). Results of disc diffusion tests using erythromycin A, oleandomycin, rokitamycin, clindamycin, telithromycin, quinupristin and dalfopristin delineated four main groups corresponding to those defined classically using erythromycin and clindamycin only, but with sub-divisions. Resistance to erythromycin was more common in coagulase-negative strains (56%) than in S. aureus (16%); telithromycin, clindamycin, quinupristin-dalfopristin and rokitamycin were active against >97% of S. aureus strains and >88% of the coagulase-negative strains. The commonest resistance phenotype was 'inducible MLS(B)' (12% in S. aureus, 31% in coagulase-negative strains); this group could be divided in terms of the different inducing abilities of erythromycin and oleandomycin. 'Constitutive MLS(B)' and 'MS' phenotypes were more often found in coagulase-negative strains (11 and 13%, respectively) than in S. aureus (2 and 1%). Novel phenotypes were found during the isolation of constitutively resistant mutants from inducible strains, and of resistant mutants from 'MS' strains. This extended phenotyping scheme has revealed further complexities and evolutionary possibilities in patterns of resistance to this group of antibiotics.

Anti-Bacterial Agents↗

Disorganization of cell division of methicillin-resistant Staphylococcus aureus by a component of tea (Camellia sinensis): a study by electron microscopy.

A component of aqueous extracts of green tea (Camellia sinensis), known to reverse methicillin-resistance in staphylococci, causes extensive morphological changes in methicillin-resistant but not in methicillin-sensitive Staphylococcus aureus. Clumps of partly divided cocci, consisting of up to 14 individuals, with thickened internal but normal external cell walls were seen by electron microscopy in cultures of methicillin-resistant S. aureus grown in the presence of the active principle. The morphological changes observed were consistent with selective inhibition of penicillin-binding proteins.

Anti-Bacterial Agents↗

Susceptibility testing of linezolid by two standard methods.

To determine to what extent methodological differences affect susceptibility testing parameters for linezolid, MICs and disk inhibition zones were compared using the methods described by the National Committee for Clinical Laboratory Standards and the British Society for Antimicrobial Chemotherapy for 198 strains of gram-positive cocci. Zones were 4-5 mm larger by the British Society for Antimicrobial Chemotherapy method, but MICs did not differ, except for pneumococci, which were more sensitive when the British Society for Antimicrobial Chemotherapy method was used. This is because incubation in CO2 depresses the activity of linezolid against this species only. Breakpoints for linezolid may need adjusting when testing is by other than National Committee for Clinical Laboratory Standards methods.

Acetamides↗

Public health issues arising from microbiological and labelling quality of foods and supplements containing probiotic microorganisms.

OBJECTIVE: To assess the accuracy and helpfulness of labelling on products containing probiotic bacteria. DESIGN AND SETTING: 52 such products - 44 from the UK (21 supplements, 15 fermented functional foods, eight 'health-care' products) and eight from continental Europe - have been tested for microbiological content, and results compared to the information available on their labels. Products were stored in the dark at 4 degrees C and analysed before their expiry or sell-by date. Careful note was taken of wording on labels, package inserts, packaging, promotional literature and catalogue descriptions, as applicable. Products were cultured on appropriate bacteriological media, and organisms grown were counted and identified. RESULTS: Bioyoghurts gave no indication of numbers, and only five accurately described their bacterial content; results of culture were usually satisfactory. 'Healthcare' products (mostly intended for the bowel) usually indicated the presence of bacteria, but the numerical content was hard to ascertain, and cultural results fell short of label claims. Supplements were sometimes incorrectly labelled in bacteriological terms, and often contained markedly reduced numbers and/or had extraneous strains and/or strains specified on the label were missing. Products from continental Europe (that were sold for specific medical indications) seemed of a higher microbiological standard. The potential pathogen Enterococcus faecium was found in nine products. The most successful of the new functional foods in Britain now contain probiotics, and probiotic preparations are prominent among the expanding range of nutritional supplements presently available to consumers. CONCLUSIONS: Our findings have public health implications, and suggest that improvements are needed in labelling and quality assurance procedures for products containing probiotic organisms. The presence of the potential pathogen Enterococcus faecium (intentionally or as a contaminant) in some products calls for a review of the value of this species as a probiotic.

Dietary Supplements↗

Cefaclor into the millennium.

We review the discovery and development of the cephalosporins and subsequently cefaclor. Cefaclor is active against a wide range of commonly encountered bacterial pathogens, acting by inhibiting cell wall synthesis. Its in vitro activity compares favourably with other beta-lactam antibiotics. Its pharmacokinetic properties indicate that an 8-hourly dosing schedule is appropriate. In addition a delayed release formulation allowing twice daily dosage has been developed. The efficacy of both formulations of cefaclor has been verified by many clinical trials. Cefaclor has been widely used in infections of the respiratory tract (including otitis media), urinary tract and soft tissues. The results of therapy are summarized. The low incidence of adverse events is highlighted and the beneficial influence of this on compliance is described. Finally, the pharmaco-economics of cefaclor are considered.

Bacterial Infections↗

Comparative anti-anaerobic activity of Men 10700, a penem antibiotic.

The in vitro activity of Men 10700, a new penem, has been compared with that of metronidazole, clindamycin, ciprofloxacin, co-amoxiclav, imipenem and three third generation cephalosporins against 120 strains of anaerobes. The organisms tested comprised Clostridium perfringens, Clostridium difficile, Bacteroides fragilis and speciated members of the genera Fusobacterium, Veillonella and Peptostreptococcus. Men 10700 showed activity similar to that of imipenem, and was more potent than metronidazole against all species except C. difficile and P. anaerobius. The spectrum of activity of Men 10700 suggests this agent may be useful for treating infections caused by anaerobes.

Amoxicillin-Potassium Clavulanate Combination↗

Vancomycin susceptibility as an aid to the identification of lactobacilli.

Forty strains of lactobacilli isolated from probiotic supplements or functional foods, and two clinical isolates, have been identified by API 50 CHL and tested for susceptibility to vancomycin. All the Lactobacillus acidophilus (16) and Lact. delbreuckii (two) strains were sensitive to vancomycin, while all the other strains (mainly Lact. rhamnosus, 15) were resistant. Susceptibility to other antibiotics was not species-specific. Differential susceptibility to vancomycin may be helpful in speciation of lactobacilli.

Anti-Bacterial Agents↗

Comparative in-vitro activity of ketolide HMR 3647 and four macrolides against gram-positive cocci of known erythromycin susceptibility status.

The in-vitro activity of the novel ketolide HMR 3647 was compared with four other macrolides against 335 strains of staphylococci, pneumococci and enterococci with predetermined susceptibility status to erythromycin. HMR 3647 was the most active agent against staphylococci (irrespective of methicillin resistance) of sensitive (MIC90 = 0.25 mg/L) or inducibly resistant phenotype (MIC90 = 2 mg/L), but was inactive against constitutively resistant strains. HMR 3647 was very active against erythromycin-sensitive enterococci (MIC90 = 0.06 mg/L), irrespective of vancomycin resistance, but less active against strains that were resistant to erythromycin (MIC90 = 32 mg/L). The ketolide was highly active against pneumococci (irrespective of penicillin resistance), both erythromycin sensitive (MIC90 = 0.03 mg/L) and erythromycin resistant (MIC90 = 0.25 mg/L). A bactericidal action was found against some erythromycin-sensitive staphylococci, pneumococci and Enterococcus faecium. The microbiological properties of HMR 3647 are thus superior to those of other macrolides.

Anti-Bacterial Agents↗