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Biomedical subjects

J M Hamilton-Miller

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

At least 19 recordsLinked to original sources
PubMed1995

Activity of the semi-synthetic kanamycin B derivative, arbekacin against methicillin-resistant Staphylococcus aureus.

Arbekacin (1-N-((S)-4-amino-2-hydroxybutyryl)-3',4'-dideoxykanamycin B) was active against 54 strains of methicillin-resistant Staphylococcus aureus from 16 different countries, all of which were resistant to > or = 32 mg/L amikacin. MICs of arbekacin ranged from 1 to 16 mg/L, the MIC50 was 3.2 mg/L and the mode geometric mean MICs were 4 and 4.5 mg/L respectively.

Aminoglycosides↗
PubMed1995

Errors arising from incorrect orientation of E test strips.

Major errors arise if E test strips are placed upside down. Asymmetric zones, or no zone at all, may result. MICs indicated by upside-down tests were almost always considerably higher than true values. This situation differs markedly from that for conventional testing, where orientation of disks is not important.

Bacteria↗
PubMed1995

Natural history of bacteriuria in women with primary biliary cirrhosis and the effect of antimicrobial therapy in symptomatic and asymptomatic groups.

Primary biliary cirrhosis (PBC) patients have an increased incidence of recurrent urinary tract infection compared with patients with other chronic liver diseases. The course of significant asymptomatic and symptomatic bacteriuria in women with PBC was evaluated: consecutive patients were screened for bacteriuria at their outpatient appointments. Bacteriuric patients who were asymptomatic (n = 21) were randomised to receive antimicrobial therapy (n = 11), or no therapy (n = 10). Bacteriuric patients who were symptomatic (n = 13) were treated. All were followed up by weekly dipslide examination of urine. The course of bacteriuria in the 13 symptomatic and 11 asymptomatic treated patients was similar in terms of the medium interval between successive infective episodes (three and four weeks respectively), the number of relapses (six and seven) and reinfections (14 and 18). Most untreated asymptomatic patients became abacteriuric spontaneously but became reinfected with a different organism during the study period. A separate group of 24 PBC patients with no previous bacteriologically proved urinary tract infection was followed weekly in a similar fashion: seven (29%) became bacteriuric for two to four weeks during a three month period. This study suggests that treatment of recurrent bacteriuric episodes in PBC patients does not alter the natural history of their infection. The long term implication of periodically infected urine in these patients is currently unknown.

Adult↗
PubMed1995

Combinations of sulphonamides with diaminopyrimidines: how, when and why?

Co-trimoxazole is still widely used for indications where trimethoprim alone is equally effective. The pharmacological rationale of the combination of trimethoprim and sulphamethoxazole involves synergistic action of the two drugs. This is true only from a laboratory point of view; several considerations have led to the conclusion that the synergism between the two components is of only in vivo marginal importance in determining the clinical efficacy of co-trimoxazole. This is due to a greater tissue affinity of trimethoprim compared to that of sulphamethoxazole and, therefore, to the different tissue concentration ratios obtained in vitro and in vivo. Another claim sustaining the combination is the prevention of developing resistance to trimethoprim; however, there is no substantial clinical evidence to support this claim. It does seem likely that trimethoprim has protected against the emergence of that sulphonamide resistance. This slight benefit is outweighed by the disadvantages of the combination, mainly consisting of the occurrence of adverse events due to the sulphonamide moiety. Consequently, the incidence and severity of the adverse events seen with co-trimoxazole should be reduced by using trimethoprim alone. There are only a few cases where co-trimoxazole is better than trimethoprim: toxoplasmosis, brucellosis, nocardiosis, chancroid and pneumonia due to Pneumocystis carinii. For the other and many common infections, scientific rationale, economic and clinical reasons dictate that trimethoprim is superior to co-trimoxazole.

Dihydropteroate Synthase↗
PubMed1994

Activity of the fourth generation cephalosporin FK-037 against methicillin-resistant Staphylococcus aureus under conditions maximizing PBP2' production.

To investigate the in vitro activity of the fourth generation cephalosporin FK-037, MICs were determined for 80 strains of methicillin-resistant Staphylococcus aureus from 11 countries. Methicillin and cefamandole served as comparators. The method ensured good expression of PBP2' by use of a large inoculum, salt supplement and incubation for 48 hours at 30 degrees C. FK-037 was twice as active as cefamandole against both strains with high-level and strains with low-level methicillin resistance (geometric mean MICs 23.4 and 10.8 mg/l, respectively).

Bacterial Proteins↗
PubMed1994

Opsonophagocytosis in infected urine: relation to pH and osmolality.

Polymorphonuclear neutrophils (PMN) in freshly voided urines from 20 symptomatic bacteriuric patients were examined. Although the PMN were viable (median 85%), in only 2 cases could phagocytosis of the infecting organisms be demonstrated, even after the addition of serum opsonins. Polymorphonuclear neutrophils from urines of 12 patients were also unable to phagocytose added opsonized Staphylococcus aureus. These urines were found to be of pH < 6.0 and/or osmolality > 700, or < 180 mOsm. However, the phagocytic function of these PMN was restored when transferred to Hanks balanced salt solution (HBSS). By contrast, most PMN in urines of suitable pH (> or = 6.0) and osmolality (between 200 to 700 mOsm.) phagocytosed the opsonized S. aureus. When bacteria cultured from the infected urine were incubated in the same urine and then transferred to HBSS, in 17 of 19 cases opsonization occurred and the organisms were phagocytosed when PMN, isolated from blood, were added. IgG appeared to be the prime opsonin in the urines, and heat-stable opsonins for S. aureus were also present. It is concluded that lack of opsonization is not a major cause of the absence of phagocytosis by urinary PMN. Low pH and adverse osmolality are largely responsible, correction of which may restore PMN function in vivo.

Antibody-Coated Bacteria Test, Urinary↗
PubMed1994

Limitations of and indications for the use of co-trimoxazole.

Co-trimoxazole is still widely used for indications where trimethoprim alone is equally effective. Microbiological and pharmacokinetic considerations reveal that trimethoprim alone provides adequate anti-microbial activity for treatment of conditions for which co-trimoxazole is often given. Synergy may be shown in vitro, but in clinical practice is an unusual occurrence. There is no evidence from clinical studies that the sulphonamide moiety fo co-trimoxazole prevents the development of resistance to trimethoprim. The adverse event profile of co-trimoxazole is a summation of that of sulphonamide and of trimethoprim. Thus, using trimethoprim alone should reduce both the incidence and potential severity of adverse events seen when co-trimoxazole is used. Clinical trials have shown trimethoprim to be as effective as co-trimoxazole in many of the common bacterial infections of the urinary and respiratory tracts. However, there are a few specific varieties of infection for which co-trimoxazole can be shown to be superior to trimethoprim: these include toxoplasmosis, brucellosis, nocardiosis, chancroid and pneumonia caused by Pneumocystis carinii. For many common infections, scientific, rational, economic and clinical reasons dictate that trimethoprim is preferable to co-trimoxazole.

Clinical Trials as Topic↗
PubMed1994

Consensus viewpoint on management of urinary infections.

Twenty-four general practitioners completed a questionnaire on behalf of their partners in the practices before attending the symposium. The main points that emerged were that trimethoprim was the most popular antibiotic for treatment of acute urinary infection and that the most common duration of treatment was 5 to 7 days. A panel discussion, with audience participation, covered duration of treatment, antibiotic resistance, specimen collection, management of different patient groups and availability of information concerning resistance patterns. Nineteen of the original 24 general practitioners returned the post-meeting questionnaire, and stated that, as a result of what they had heard at the symposium, they were contemplating changing the way in which they managed urinary infections. Information concerning bacteriuria in pregnancy and changing patterns of bacterial resistance to antibiotics were of particular interest.

Anti-Infective Agents, Urinary↗
PubMed1994

The urethral syndrome and its management.

The urethral syndrome and its management are reviewed. Urethral syndrome is defined as 'symptoms suggestive of a lower tract urinary infection but in the absence of significant bacteriuria with a conventional pathogen' with three provisos concerning symptomatology and the definition of significant bacteriuria and conventional pathogens. The urethral syndrome is a very common condition; about half the patients visiting their General Practitioner by reason of frequency and/or dysuria do not have significant bacteriuria. Both infective causes (such as lactobacilli and sexually-transmitted pathogens) and non-infective causes (such as trauma, allergies, anatomical features and co-existing medical conditions) have been suggested as causes and are discussed. Treatment options include antibiotics in the case of acute urethral syndrome, since it is not possible to distinguish between urinary infection and the urethral syndrome in the consulting room. For those with chronic urethral syndrome, treatment depends upon whether attacks are associated with bacteriuria or if urological investigations reveal any abnormalities.

Humans↗
PubMed1994

The challenge of methicillin-resistant Staphylococcus aureus.

Staphylococcus aureus strains resistant both to methicillin and aminoglycosides emerged during the late 1970s. These have become endemic in hospitals all over the world. Outbreaks of infection and colonization may cause severe clinical and managerial problems, as therapeutic options are limited and it may be difficult to clear the carrier state. The genetics and biochemistry of these organisms are well studied, but additional antibiotics active against these strains are needed. The most urgent requirement is for rational and effective policies for control of their spread.

Animals↗
PubMed1993

Anomalous growth of Staphylococcus epidermidis in the presence of Silastic and glycopeptide antibiotics.

In the presence of supra-inhibitory concentrations of the glycopeptide antibiotics vancomycin and teicoplanin, biofilms of Staphylococcus epidermidis on a Silastic surface produce anomalous growth. This takes the form of macroscopic, cohesive aggregates of cocci bound together with slime. This phenomenon was intermittent, independent of antibiotic concentrations between 20 and 50 micrograms ml-1, occurred more often with teicoplanin, and was found both with slime-positive and slime-negative strains.

Microscopy, Electron, Scanning↗
PubMed1993

M2 mitochondrial antibodies and urinary rough mutant bacteria in patients with primary biliary cirrhosis and in patients with recurrent bacteriuria.

Primary biliary cirrhosis (PBC) patients have a higher incidence of recurrent urinary tract infection and an increased prevalence of rough forms (mutants) of E. coli in their stool samples than other chronic liver disease patients. PBC patients exhibit autoantibody reactivity against mitochondria, the most common antigen (M2) being a family of antigens with the major components having approximate molecular weights of 74, 56, 52 and 48 kD. Cross-reactivity between M2 antigen components and corresponding antigenic bands of bacteria has been demonstrated with PBC sera. Patients with recurrent urinary tract infections, all of whom had normal liver function and were taking prophylactic antibiotic treatment, had weak anti-mitochondrial antibody (AMA) reactivity (69%), with reactivity against the 74-kD antigen alone being the most common. When antibody to the 74-kD band was eluted, it was found to cross-react with bacterial membrane fractions. In the controls, 12/77 chronic liver disease patients and 2/24 normals possessed AMA. Rough forms of bacteria were found in the urine of patients with significant bacteriuria: 39% PBC, 5.3% chronic liver disease and 41% of the recurrent urinary tract infection group. M2 antibodies may be induced by urinary organisms in 'normal' women with recurrent bacteriuria and in females with PBC.

Autoantibodies↗
PubMed1993

Continuing the search for bacterial urovirulence factors.

Bacteria that commonly cause infections of the normal urinary tract (eg Escherichia coli, Proteus mirabilis and Staphylococcus saprophyticus) do so because they possess specific urovirulence factors. Adhesions of various types (often fimbriae) seem to be the most important of these. In E. coli several other factors have been recognized, and sub-sets of defined uropathogenic clones exist. On the other hand, urovirulence determinants are less easy to distinguish in species such as S. epidermidis and Klebsiella pneumoniae, that rarely cause such infections, or are pathogenic only in the presence of some abnormality or deficiency in host defences.

Animals↗
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↗