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Biomedical subjects

J M Hamilton-Miller

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

At least 37 records · Page 2Linked to original sources

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↗

The effect of a component of tea (Camellia sinensis) on methicillin resistance, PBP2' synthesis, and beta-lactamase production in Staphylococcus aureus.

Extracts of tea (Camellia sinensis) can reverse methicillin resistance in methicillin-resistant Staphylococcus aureus (MRSA) and also, to some extent, penicillin resistance in beta-lactamase-producing S. aureus. These phenomena are explained by prevention of PBP2' synthesis and inhibition of secretion of beta-lactamase, respectively. Synergy between beta-lactams and tea extracts were demonstrated by disc diffusion, chequerboard titration and growth curves. Partition chromatography of an extract of green tea on Sephadex LH-20 yielded several fractions, one of which contained a virtually pure compound that showed the above-mentioned activities, at concentrations above about 2 mg/L. The observed activities are novel and distinct from the previously reported direct antibacterial activity of tea extracts. Prevention of PBP2' synthesis offers an interesting possible new approach for the treatment of infections caused by MRSA.

Bacterial Proteins↗

Efficacy and safety profile of long-term nitrofurantoin in urinary infections: 18 years' experience.

Case records from 219 female patients between 1975 and 1992 who were given long-term prophylaxis (1 year) with nitrofurantoin for the prevention of recurrent urinary infections have been reviewed. Patients' age ranged from 9 to 89 years (median 31-35 years, mode 26-30 years); most (61%) were < 40 years old. The median number of symptomatic episodes in the 12 months immediately before prophylaxis was six (mode 4, mean 6.9). 14.4% of the patients were allergic to an antibiotic, and 23.6% had an imaging abnormality. Three regimens were used: group A (43 patients), 50 mg microcrystalline nitrofurantoin, bd; group B (110 patients), 100 mg macrocrystalline nitrofurantoin (Macrodantin), od; group C (66 patients), 50 mg Macrodantin, od. There were no obvious differences in efficacy between the patient groups (173 assessable patients). The mean incidence of symptomatic episodes decreased 5.4-fold during prophylaxis. Four-fifths of the 43 breakthrough infections (mostly due to Escherichia coli), were caused by nitrofurantoin-sensitive strains. An important finding was that patients with an imaging abnormality responded as well as those with no such abnormalities. In 16% of patients, prophylaxis was not helpful, objectively or subjectively, for no obvious reasons. In most patients where prophylaxis was successful, clinical improvement was maintained for at least 6 months after the end of prophylaxis. Nausea was more common in group A (P < 0.001), as were 'all adverse events'. Of those in group A 25.6% stopped prematurely as a result of an adverse event of any type, compared with 13% of those taking Macrodantin (P < 0.01). Older patients (> 65 years) did not report more adverse events than younger patients. No adverse event was life-threatening. Faecal flora analysis showed neither overgrowth by nitrofurantoin-resistant bacteria nor elimination of sensitive coliforms. Thus, macrocrystalline nitrofurantoin 50 mg at bedtime is appropriate for use in the long-term (12 months) prophylaxis of recurrent urinary infections, in view of its efficacy and favourable safety and tolerability profile. Patients can be managed by their family doctor.

Adolescent↗

A pilot study of Salix SST (saliva-stimulating lozenges) in post-irradiation xerostomia.

Relief from the effects of radiation-induced xerostomia resulting from use of saliva-stimulating lozenges (Salix) has been subjectively evaluated. Ten patients took Salix as required for 7 days; and self-assessed using analogue scales before and after treatment. There was a marked and statistically significant improvement in the dryness and general comfort of the mouth, and beneficial effects on eating, sleeping and speech.

Adult↗

Microbiological activity of whole and fractionated crude extracts of tea (Camellia sinensis), and of tea components.

Aqueous extracts of teas (Camellia sinensis) of different types and from various sources inhibited a wide range of pathogenic bacteria, including methicillin-resistant Staphylococcus aureus. Tea extracts were bactericidal to staphylococci and Yersinia enterocolitica at well below 'cup of tea' concentrations. Activity was confined to one of four fractions obtained from a green tea extract by partition chromatography. Testing of pure tea compounds and closely related chemicals suggested that the antibacterial activity of extracts of green tea can be explained by its content of epigallocatechin, epigallocatechin gallate and epicatechin gallate. In black tea extracts, theaflavin and its gallates are additional antibacterially active components.

Anti-Bacterial Agents↗

In-vitro microbiological assessment of a new penem, Men 10700.

The in-vitro antibacterial activity of Men 10700, a novel penem, has been compared with that of ritipenem, ciprofloxacin, amikacin, cefotaxime and co-amoxiclav against 539 strains taken from 17 genera. Men 10700 was most active against staphylococci and streptococci (MIC90 < 0.5 mg/L), slightly less active against Escherichia coli, Klebsiella pneumoniae, Enterobacter spp., Citrobacter spp., Moraxella catarrhalis and peptostreptococci (MIC90 0.5-2 mg/L), moderately active against Enterococcus faecalis, members of the tribe Proteae, Serratia marcescens, Acinetobacter spp., clostridia and Bacteroides spp. (MIC90 4-16 mg/L), and inactive against Pseudomonas aeruginosa, Stenotrophomonas maltophilia and Enterococcus faecium. Its antibacterial spectrum is thus slightly less broad than that of imipenem, but it compares favourably with an oral third-generation cephalosporin. Men 10700 was more active than ritipenem against many species, especially Enterobacter spp. and Citrobacter spp.

Anti-Bacterial Agents↗

Activity of quinupristin/dalfopristin against Staphylococcus epidermidis in biofilms: a comparison with ciprofloxacin.

Bactericidal effects of quinupristin/dalfopristin and ciprofloxacin have been studied against six strains of Staphylococcus epidermidis, with varying erythromycin resistance phenotypes and varying abilities to form slime and adhere, growing as biofilms. Ciprofloxacin and quinupristin/dalfopristin killed (2-3 log10 cfu/mL) planktonic and sessile cells slowly, but progressively, over the course of 48 h. Rates of killing by quinupristin/dalfopristin were independent of concentration over the range 5-30 mg/L, and were somewhat slower than those seen with ciprofloxacin. These findings suggest that quinupristin/dalfopristin may be useful in the treatment of line-associated infections.

Anti-Bacterial Agents↗

Antimicrobial activities in vitro and in vivo of transition element complexes containing gold(I) and osmium(VI).

Metal compounds have been used as antibacterial agents for centuries. The in-vitro activity of two metal containing complexes, one gold, the other osmium, was investigated using a panel of clinically isolated bacteria and Candida albicans. Twenty strains of each organism were used and MIC and MBC values determined using the agar plate dilution method. Protein binding effects on the activity of the compounds were also investigated using media supplemented with 5% human blood. In-vivo activity of the two compounds was subsequently determined in a hairless-obese mouse skin-surface activity model. Both compounds were highly active against the Gram-positive organisms and Candida albicans in vitro. The gold compound had some Gram-negative activity but the osmium complex was inactive against these organisms. Both were extensively protein bound. In the in-vivo experiment the gold compound achieved a 2-3 log reduction for all the test organisms and was at least as good as or superior to mupirocin in its eradication rate. The osmium compound was inactive.

Animals↗

Activity of glycylcyclines CL 329998 and CL 331002 against minocycline-resistant and other strains of methicillin-resistant Staphylococcus aureus.

Two glycylcyclines have been tested against 191 strains of methicillin-resistant Staphylococcus aureus, 72 of which were resistant to minocycline, isolated from many parts of the world. MICs of CL 329998 ranged from 0.06 to 4 mg/L, with MIC50 and MIC90 0.5 and 2 mg/L, respectively. CL 331002 was slightly less potent, having an MIC range 0.12-16 mg/L and MIC50 and MIC90 values of 1 and 4 mg/L, respectively.

Americas↗

Anomalous but helpful findings from the BBL Crystal ID kit with Haemophilus spp.

Fourteen strains of Haemophilus (12 H. influenzae, 1 H. parainfluenzae and 1 H. aphrophilus) were processed in BBL Crystal ID Enteric/Nonfermenter, API 20E and API 20NE kits, to determine whether the BBL kit misidentifies, as API kits may do, Haemophilus spp. as Pasteurella spp. The 13 H. influenzae and H. parainfluenzae strains produced uninterpretable colour reactions in the Crystal kit, thus signalling that an inappropriate species had been tested. On the other hand, the API kits (especially 20NE) often confidently "identified' Haemophilus spp. as Pasteurella spp., giving no warning that this was a misidentification.

Diagnostic Errors↗