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Biomedical subjects

J M Hamilton-Miller

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

At least 73 records · Page 4Linked to original sources
PubMed1993

Antibiogram typing of methicillin-resistant Staphylococcus aureus: a comparison with phage typing, biotyping and API Staph.

68 strains of methicillin- and gentamicin-resistant Staphylococcus aureus (MRSA) have been characterized by four different methods. First, by their production of lecithinase, lipase, pigment and sheep haemolysin. Second, by API Staph code. Third, by their sensitivity to 9 antibiotics. Fourth, by phage typing using the International Set and Supplementary phages. The third method was the most discriminatory. The combination of the first three techniques provides a highly effective, cheap and simple system to type MRSA. 80 separate MRSA strains from 26 countries were found to belong to a wide variety of phage types. Most were of group III. The most commonly found types were 85 (6 strains), 84 (4 strains) and 47 (3 strains).

Bacterial Typing Techniques↗
PubMed1993

Effect of bacterial products including endotoxin on neutrophil function in infected urine.

Experiments were performed to determine the effects of products of bacterial growth (including endotoxin) on phagocytosis and intracellular killing by polymorphonuclear leucocytes (PMNL) in urine. Bacteriologically filtered supernates of two strains of Escherichia coli grown in urine were added in varying amounts to mixtures of PMNL and E. coli, also in urine. Phagocytosis of the two strains was reduced from > 90% in controls to 66% and 48%, respectively, in the presence of undiluted culture filtrate (containing endotoxin 2-2.5 micrograms/ml). Intracellular killing was also decreased and was abolished by dilutions corresponding to endotoxin concentrations of 0.6 and 0.75 micrograms/ml. When PMNL exposed to these inhibitory dilutions were resuspended in fresh urine, their phagocytic ability was fully restored and 13-24% of their killing activity was regained. A minimum concentration of commercially purified E. coli endotoxin of 200 micrograms/ml was required to abolished PMNL killing, with phagocytosis uninhibited. The results strongly suggest that bacterial growth metabolites, not endotoxin, are responsible for the depression of phagocytosis and intracellular killing in infected urine. A moderate dilution of the bacterial products in urine permits good PMNL function. Extrapolating this to the clinical situation, diluting the urine by water loading (as recommended for patients with urinary infections) should ensure efficient activity of PMNL under in-vivo conditions providing urinary pH and osmolality are not adversely affected.

Bacteriuria↗
PubMed1993

Enoxacin relieves symptoms of recurrent urinary infections more rapidly than cefuroxime axetil.

In patients with a history of recurrent infections, treatment with enoxacin (200 mg/12 h for 3 days) relieved symptoms of acute urinary infection significantly more rapidly than treatment with cefuroxime axetil (125 mg/12 h for 7 days). Other parameters, including clinical and bacteriological cure rates and patients' overall opinion of their treatment, did not differ significantly between the treatments.

Adult↗
PubMed1993

Effect of pH and osmolality on in vitro phagocytosis and killing by neutrophils in urine.

Phagocytosis and intracellular killing of two strains of Escherichia coli and a Staphylococcus saprophyticus by polymorphonuclear neutrophils (PMN) in pooled sterile urine at three osmolalities (800, 485, and 200 mosM/kg of H2O) between pHs 5 and 8 was investigated. Urine at 800 mosM virtually abolished phagocytosis of both E. coli strains, regardless of pH, and reduced the phagocytosis of S. saprophyticus to 30%; no killing of any organisms took place at this osmolality. On the other hand, phagocytosis was a good in urine as in Hanks balanced salt solution at both 485 and 200 mosM between pHs 6 and 8. Phagocytosis of all three strains was virtually abolished at pH 5. Killing of the strains by PMN was optimal between pHs 6.5 and 7.5 in urine at 485 mosM (being at least 90% of the control values in Hanks balanced salt solution), whereas at 200 mosM killing was reduced to 50 to 70% of these values. Reduced killing of all three strains occurred at pH 8, whereas at pH 6 only S. saprophyticus was killed. Thus, the bactericidal activity of PMN in urine was more sensitive than phagocytic function to alterations in pH. The dominant modulating factor affecting PMN function in urine of 500 mosM or less was pH, but osmolality had a greater influence at 800 mosM. Thus, raising the pH of urine and reducing the osmolality may increase the ability of natural defense mechanisms to eliminate infecting organisms.

Cell Death↗
PubMed1993

Reassessment of the rationale for the combinations of sulphonamides with diaminopyrimidines.

Trimethoprim is the best known inhibitor of bacterial dihydrofolate reductase. Initially, this was always combined with sulphamethoxazole. It was later combined with other sulphonamides (eg. sulphamoxole, sulphadiazine or sulfametopyrazine), but the sulphonamide moiety as a contributor to clinical efficacy was increasingly questioned. Thus, in 1979 (in UK) trimethoprim alone was introduced. Justification for the combination was based on: (a) synergy occurs in vitro (b) bactericidal activity, while the two components are bacteriostatic (c) the emergence of resistance was claimed to be lower. However, these claims were not substantiated by studying the microbiological and pharmacokinetic properties of trimethoprim and the sulphonamides, but most importantly by the results of clinical trials. These show that in most indications, trimethoprim alone is as good, cheaper and causes considerably fewer adverse events than use with a sulphonamide. For urinary infections most agree that monotherapy is best. In respiratory infections diaminopyrimidines have relatively poor activity against important pathogens, eg pneumococci and especially Moraxella catarrhalis. It could be argued in these case that the addition of a sulphonamide may increase therapeutic efficacy. This can only be resolved by large clinical trials. In brucellosis and gonorrhoea, where sulphonamides are more microbiologically active than diaminopyrimidines, it is likely that combination with another antibiotic is needed. However, too much reliance must not be placed on extrapolating from trimethoprim to other diaminopyrimidines; conclusions should be drawn from work using the other compounds.

Anti-Bacterial Agents↗
PubMed1992

In vitro assessment of rokitamycin against problem gram-positive cocci.

Rokitamycin was more active than erythromycin against erythromycin-sensitive strains of Staphylococcus aureus and enterococci, but somewhat less active against coagulase-negative staphylococci. Strains with inducible resistance to erythromycin were uniformly resistant to erythromycin, while rokitamycin was active against such strains. Strains with constitutive resistance to erythromycin were also uniformly resistant to erythromycin, and most were also resistant to rokitamycin. However, 5 of 21 coagulase-negative staphylococci and 2 of 20 enterococci remained sensitive to rokitamycin. This is a novel finding, perhaps suggesting a new mechanism of macrolide resistance.

Coagulase↗
PubMed1992

In-vitro activities of 14-, 15- and 16-membered macrolides against gram-positive cocci.

The in-vitro activities of the 14-membered macrolides erythromycin, dirithromycin, roxithromycin, clarithromycin, the 15-membered compound azithromycin and the 16-membered macrolides (16 MM) josamycin, spiramycin and midecamycin acetate (MOM) have been compared against staphylococci, enterococci and streptococci. Results have been analysed separately according to the sensitivity status of the tested strains to erythromycin, namely sensitive (S), inducibly resistant (IR) or constitutively resistant (CR). 14- and 15-membered macrolides were active only against S strains; the order of potency in vitro was clarithromycin = erythromycin greater than azithromycin = roxithromycin greater than dirithromycin. The 16 MM were slightly less active against S strains than were the 14- and 15-membered compounds, and inhibited most IR strains; MOM and josamycin were about twice as potent as spiramycin. IR and S Staphylococcus aureus strains were equally sensitive to 16 MM, while IR strains of coagulase-negative staphylococci were less sensitive than were S strains. All CR strains of S. aureus were resistant to 16 MM, as were most of the other CR strains. However, 5/21 CR coagulase-negative staphylococci and 2/20 CR enterococci tested were sensitive to 16 MM. The seven CR strains showing anomalous sensitivity to the 16 MM (five Staphylococcus haemolyticus and two enterococci) were only 'moderately resistant' to erythromycin (MIC 8-64 mg/L), while all the other CR strains were 'highly resistant' (MIC greater than 128 mg/L). These results indicate that it may be difficult to predict the sensitivity of Gram-positive cocci to 16 MM, and therefore individual sensitivity testing to specific compounds is essential.

Anti-Bacterial Agents↗
PubMed1992

Comparison of the in-vitro activities of the topical antimicrobials azelaic acid, nitrofurazone, silver sulphadiazine and mupirocin against methicillin-resistant Staphylococcus aureus.

The in-vitro activities of the topical agents azelaic acid, nitrofurazone, silver sulphadiazine and mupirocin have been determined against 80 strains of MRSA collected from worldwide sources. MICs were determined by agar dilution (with an inoculum of approximately 5.0 x 10(5) cfu) in Iso-Sensitest agar, and MBCs were measured by replica-plating from MIC plates using velvet pads. The agents tested were uniformly active against MRSA, mupirocin being the most active (MIC50 0.15 mg/L) followed by nitrofurazone (MIC50 19 mg/L), silver sulphadiazine (MIC50 85 mg/L) and azelaic acid (MIC50 850 mg/L). Concentrations of azelaic acid, nitrofurazone and silver sulphadiazine close to the MIC were bactericidal, but mupirocin was only bactericidal at concentrations substantially greater than the MIC. In time-kill experiments, azelaic acid and nitrofurazone were gradually bactericidal, silver sulphadiazine was rapidly bactericidal and mupirocin was not bactericidal. Silver sulphadiazine killed sulphonamide-sensitive and sulphonamide-resistant strains equally rapidly. No resistant mutants were found to azelaic acid, nitrofurazone or silver sulphadiazine in an inoculum of 10(9) cfu, but two strains yielded (frequency: 1.0 x 10(-9)) mutants resistant to mupirocin. Our in-vitro results suggest azelaic acid, nitrofurazone and silver sulphadiazine could be of use for clearing staphylococcal carriage.

Anti-Bacterial Agents↗
PubMed1992

In-vitro activity of RP 59500, a new semisynthetic streptogramin antibiotic, against gram-positive bacteria.

A study of the in-vitro activity of RP 59500, a semisynthetic derivative of pristinamycin, against a range of Gram-positive bacteria including erythromycin-resistant strains was undertaken. MICs were determined by plate dilution in IsoSensitest agar and MBCs by velvet pad replication. RP 59500 was found to have in-vitro activity almost identical to that of its parent compound, pristinamycin. Sixty methicillin-resistant Staphylococcus aureus (MRSA) and 60 methicillin-sensitive S. aureus (MSSA) were found to be sensitive to RP 59500, with MICs of 0.13-1 mg/L. All the MSSA and most MRSA showed an MBC less than 2 mg/L. Erythromycin-resistant S. aureus (62) were as sensitive to RP 59500 as were erythromycin-sensitive strains (58). RP 59500 was more active against MRSA than fusidate, vancomycin, amikacin, ciprofloxacin, imipenem or erythromycin. Forty strains of coagulase-negative staphylococci (11 were erythromycin-resistant) showed MICs of 0.25-1 mg/L, and RP 59500 was more active than methicillin, erythromycin, imipenem, cefotaxime or vancomycin. Sixty strains of streptococci (20 pneumococci and 40 of groups A, B, C, or G) and 20 enterococci were inhibited by 0.13-1 mg/L and 0.25-4 mg/L, respectively. Gram-positive bacilli (five each of diphtheroids, lactobacilli, Listeria monocytogenes and Bacillus spp., and 19 Clostridium spp.) were also sensitive, with MICs of between 0.06 and 4 mg/L. All 279 strains tested were judged to be sensitive to RP 59500, which was bactericidal and showed a small inoculum effect. The activity against MRSA, and against erythromycin-resistant strains of all species was particularly interesting.

Erythromycin↗
PubMed1992

Differing prognostic significance of reinfection and relapse in CAPD peritonitis.

All episodes of recurrent infection in a CAPD unit over a 26-month period have been analysed to discover whether relapse and reinfection have different prognostic importance. Relapse and reinfection were distinguished by detailed microbiological investigation. Prognosis was expressed in terms of outcome of treatment and the fate of the Tenckhoff catheter. Twenty-nine patients suffered recurrent infections (i.e. more than one infection during a 12-month period). Nine (6 male, 3 female, age range 42-73 years) had relapses, and 20 (16 male, 4 female, age range 42-74 years) reinfections. The characteristics of the two groups of patients were indistinguishable. Relapse was of graver prognostic consequence: patients who relapsed were significantly less likely to respond to antibiotic treatment (78% versus 20%) and have to have their catheters removed (78% versus 10%) than those with reinfections. Thus it is important to differentiate relapse from reinfection in CAPD peritonitis. In addition to being helpful for the management of individual patients, this is essential if results of therapeutic trials are to be interpreted correctly.

Adult↗
PubMed1992

Comparative trials of cefaclor AF in uncomplicated cystitis and asymptomatic bacteriuria.

Two different doses of cefaclor advanced formulation (AF), a new sustained-release formulation of cefaclor, were compared with the regular formulation of cefaclor for efficacy and safety in the treatment of uncomplicated cystitis and asymptomatic bacteriuria. A 7-day course of treatment was used, and the trials were double-dummy and double-blind. In one trial, cefaclor AF 500 mg once daily (at night) was compared with cefaclor 250 mg three times a day. Satisfactory clinical and bacteriological responses were found in 179/189 (94.7%) and 160/191 (83.8%) patients, respectively, given cefaclor AF and in 82/87 (94.3%) and 74/90 (82.2%) patients given cefaclor, 5-9 days after the end of treatment. In the other trial, cefaclor AF 375 mg twice daily was compared with cefaclor 250 mg three times a day. Satisfactory clinical and bacteriological responses were obtained in 164/180 (91.1%) and 156/184 (84.8%) patients, respectively, given cefaclor AF, and in 86/92 (93.5%) and 81/93 (87.1%) patients taking cefaclor, 5-9 days after the end of treatment. Very similar results were found in both studies in those patients who were assessable 3-5 weeks later. Only 4.3% and 2.4% of patients treated with cefaclor AF (375 mg and 500 mg, respectively) and 2.2% of cefaclor patients discontinued therapy due to adverse events. The three most commonly reported events were vaginal moniliasis or vaginitis (8.6%), headache (5.0%) and nausea (4.8%). No significant differences were found between clinical efficacy and safety parameters in the different study groups, and it was concluded that cefaclor AF in a twice-daily or once-daily dosage is as effective and as safe as the currently recommened three-times-a-day dosage of cefaclor.

Adolescent↗
PubMed1992

In-vitro activity of daptomycin against a worldwide collection of methicillin-resistant Staphylococcus aureus.

Minimum inhibitory and minimum bactericidal concentrations (MIC and MBC) of daptomycin and of vancomycin have been compared against 80 strains of methicillin-resistant Staphylococcus aureus isolated from many parts of the world. In the presence of 30 mg/l of Ca++, daptomycin at 4 mg/l killed all the strains tested, and was only slightly less active than vancomycin.

Anti-Bacterial Agents↗
PubMed1992

Comparative efficacy and tolerability of cephradine and cefuroxime axetil in the treatment of acute dysuria and/or frequency in general practice.

One hundred and thirteen patients with dysuria and/or frequency were treated randomly with either 500 mg cephradine 12-hourly or 125 mg cefuroxime axetil 12-hourly, for seven days. A total of 71 patients were found to have urinary infection: bacteriological cure rates were 97% one week post-treatment, and 96% five weeks post-treatment, for both antibiotics. On direct questioning, adverse events were reported by eight patients out of 59 taking cephradine and by three of 54 who had received cefuroxime axetil. However, only three and one respectively stopped taking the antibiotic due to the adverse event. Analysis of diary cards, completed by 109 patients, showed a significantly higher incidence of increased frequency of bowel movements in those taking cefuroxime axetil. It is concluded that both antibiotics are of equal value in the treatment of simple acute urinary infections in general practice.

Adolescent↗
PubMed1992

In vitro activity of fosfomycin against 'problem' gram-positive cocci.

Fosfomycin was active in vitro against 54 of 60 'problem' Gram-positive cocci (20 methicillin-resistant Staphylococcus aureus, 20 coagulase-negative staphylococci and 20 enterococci). Its activity was significantly greater under anaerobic conditions, especially against coagulase-negative staphylococci. Mutants resistant to fosfomycin were readily demonstrated, but their growth was prevented by rifampicin or ciprofloxacin. The combinations rifampicin+fosfomycin and ciprofloxacin+fosfomycin showed MIC synergy. It is concluded that fosfomycin in an appropriate combination would be a valuable addition to the small and dwindling range of antibiotics active against problem Gram-positive cocci.

Ciprofloxacin↗