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Biomedical subjects

D A Leigh

Publications and source records attributed to D A Leigh.

At least 19 recordsLinked to original sources
PubMed1992

An 11-month incidence study of infections in wards of a district general hospital.

Between March 1988 and January 1989, an incidence study of infections in patients occupying 122 beds in a district general hospital was undertaken. Nursing notes, medical notes, temperature charts, drug prescription charts and laboratory information were reviewed three times a week to determine if patients had infection which met strict case definitions. In addition, the surveyor consulted with ward nursing and medical staff for clarification of symptoms and signs indicative of infection. During the study, 668 infections were identified amongst 3326 patients. Three hundred and thirty-eight (51%) were community-acquired infections (CAI) and 330 hospital-acquired infections (HAI). Excluding 24 HAI acquired in other hospitals, the incidence rates were 9.2 HAI per 100 discharges, and 1.1 HAI per 100 patient days. The common types of CAI were pneumonia, abdominal infection and urinary tract infection. The main types of HAI were urinary tract infection, surgical wound infection and pneumonia. The microorganisms most frequently associated with CAI and HAI were Gram-negative bacilli.

Adolescent↗
PubMed1991

An investigation into Clostridium perfringens enterotoxin-associated diarrhoea.

An investigation was carried out to establish the incidence of diarrhoea associated with the presence of enterotoxigenic Clostridium perfringens. The results indicate a high risk group, namely elderly hospitalized patients, who should be investigated for this organism in a similar way to Clostridium difficile if symptoms occur. The significance of antibiotic association is suggested and cross-infection was shown to be a possibility. Detection of the enterotoxin was accompanied in all cases by the presence of high faecal counts of enterotoxigenic strains of C. perfringens.

Adolescent↗
PubMed1991

Antibacterial activity of lomefloxacin.

Lomefloxacin has marked activity against Gram-negative bacilli including Enterobacteriaceae, non-fermenting strains and Haemophilus influenzae with 98% of all isolates tested having MICs of 0.25 mg/l or less. Sixty-eight per cent of Pseudomonas aeruginosa strains were sensitive to 1 mg/l with a few strains resistant to 8 or 16 mg/l. Gram-positive cocci were more resistant, particularly streptococci, where the MICs vary between 1 and 8 mg/l. Bactericidal activity was similar to inhibitory activity and the effect of increasing serum concentrations and bacterial inocula was minimal. The MIC and MBC were increased in the presence of urine, particularly at an acid pH 5. Comparative MICs showed that lomefloxacin was more active than ofloxacin and pefloxacin, similar to norfloxacin but less active than ciprofloxacin for Gram-negative bacteria but not for Gram-positive cocci. Comparative studies with sensitivity disc concentrations showed that a 5 micrograms disc was more satisfactory than the 10 micrograms disc as the zone sizes were more suitable for routine testing. Solutions of lomefloxacin showed instability in bright sunlight when 52% of activity was lost in 1 h. Similar instability was shown in impregnated discs which lost up to 40% activity in 6 h exposure. Lomefloxacin showed a wide range of activity against Gram-negative bacteria including multiresistant strains and Pseudomonas spp. Gram-positive bacteria were less susceptible, with streptococci more resistant than staphylococci. Lomefloxacin is well absorbed after oral administration giving high blood and urine concentrations and its prolonged half-life means once daily dosing in the treatment of many types of bacterial infection may be possible.

4-Quinolones↗
PubMed1991

Pharmacokinetic study of lomefloxacin and its effect on the faecal flora of volunteers.

In a volunteer pharmacokinetic study mean peak serum concentrations of lomefloxacin of 7.19 mg/l were obtained 1.5 h after an oral dose of 400 mg. Women had higher concentrations than men. Urinary excretion was 34% in 6 h and 63% in 24 h and the mean peak concentration was 699 mg/l. Saliva concentrations were 37% of those in serum. Lomefloxacin was detectable in the faeces up to seven days after the last dose. The major effect of lomefloxacin on the faecal flora of volunteers following a four day course of 400 mg once daily was the elimination of strains of Enterobacteriaceae and an increase in the numbers of Gram-positive cocci, mainly streptococci. There was no effect on anaerobic bacteria or yeasts. Lomefloxacin was well tolerated and no side effects were recorded. No bacterial resistance was detected after treatment.

4-Quinolones↗
PubMed1990

Activated Ki-ras proto-oncogene in spontaneously transformed and chemical tumor-derived cell lines related to the mouse lung alveologenic carcinoma.

An in vitro cell model of mouse lung alveologenic carcinoma consisting of preneoplastic nonmalignant cells, spontaneously transformed cells, and urethane-induced malignant cells was analyzed for phenotypic and genotypic changes associated with the transition to neoplasia. The polymerase chain reaction (PCR) was used to amplify the cDNA derived from the c-Ki-ras mRNA corresponding to exons 1 and 2 of the proto-oncogene. This approach allowed analysis of the gene transcription product rather than potentially unexpressed DNA. Direct sequencing of the PCR product identified a common single point mutation, alone or together with wild-type mRNA for c-Ki-ras, in all of the malignant clones. An A----G transition in the second base position of codon 61 was common to spontaneously malignant and chemical tumor-derived cell lines and to lines selected for lung metastatic behavior. The absence of the mutation in the nonmalignant cells suggests that the Ki-ras mutation may be a factor in onset or maintenance of the malignant phenotype and, at least in vitro, may be a late event in the transformation process.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed1990

Post-operative urinary tract infection and wound infection in women undergoing caesarean section: a comparison of two study periods in 1985 and 1987.

In 1985 and 1987 women undergoing Caesarean section were studied for the development of post-catheterization bacteriuria, urinary tract infection and wound infection. In 1985, 34% developed bacteriuria compared to 25% in 1987. Post-catheterization bacteriuria within two days was reduced by improved catheterization techniques. Late urinary tract infection after 5 days occurred in 2% of women in 1985 and 6% in 1987. The commonest bacteria were Escherichia coli and enterococci. Post-catheterization bacteriuria was only confirmed in a second urine specimen in 53%. The incidence of wound infection was 20% in 1985 and 15.8% in 1987 but bacterial pathogens were only isolated from 12.5% and 5.1% respectively. Staphylococcus aureus was isolated in 60% of infected women. Antimicrobial usage was high in this group of women at 41% in 1985 and 27% in 1987. A significant reduction of usage from 37% to 16% was seen in bacteriologically confirmed infections where the laboratory reports were only issued after examination of a second specimen. However most symptomatic women received treatment. The incidence of post-operative infective complications is high in women having Caesarean section. Careful urethral catheterization techniques are necessary to prevent bacteriuria.

Adolescent↗
PubMed1990

The effect of cefuroxime axetil on the faecal flora of healthy volunteers.

The effect on the faecal flora of cefuroxime axetil, an oral ester of cefuroxime, was examined in ten healthy volunteers following a dose of 250 mg twice a day for 41/2 days. The mean blood concentration 2 h after the ninth dose was 3.6 mg/l and the urinary excretion was approximately 40% in 6 h and 50% in 24 h. Two volunteers developed mild diarrhoea and one candida vaginitis. Although there was variation between volunteers in the changes found in the faecal flora, the major effects were a reduction in the total anaerobic bacterial count, particularly where high levels of cefuroxime were present in the faeces and a significant decrease or elimination of strains of Enterobacteriaceae plus an increase in the streptococcal count. Six volunteers showed an increase in the candida count. Clostridium difficile was not isolated from any volunteer and toxin was not present in the two volunteers who developed diarrhoea. Four volunteers showed high levels of cefuroxime in the faeces on the fourth or fifth days of treatment.

Bacteria, Aerobic↗
PubMed1989

Treatment of acute uncomplicated urinary tract infections with single daily doses of cefuroxime axetil.

Cefuroxime axetil in a single daily dose of 250 mg for ten days was given to 75 women with symptoms of acute uncomplicated urinary tract infections. Fifty-nine women were found to have significant bacteriuria but one was excluded as urethral catheterization was required. The dose was taken at night with a milk drink. Ninety-five per cent of women had a clear urine during treatment. Compliance studies showed that antimicrobial activity was detectable in early morning urines up to 8-10 h after the dose. Post treatment, 93% of women were clear of their original infecting organism but five women had become reinfected with a different strain of Escherichia coli. At the six week follow up 98% of women were still clear although one further reinfection had occurred. The overall cure rate was 86%, including 11% reinfection. Adverse events developed in 17 (23%) of the 75 women with candida vaginitis (8) and diarrhoea (4) being most common. Cefuroxime axetil is a valuable therapy for the treatment of urinary tract infection particularly when due to beta-lactamase producing bacteria.

Acute Disease↗
PubMed1989

Determination of serum and bone concentrations of cephradine and cefuroxime by HPLC in patients undergoing hip and knee joint replacement surgery.

Bone and serum concentrations of cephradine and cefuroxime were measured by HPLC in 21 patients undergoing hip and knee joint replacement surgery. An intravenous dose of 750 mg of each cephalosporin was given to patients at induction of anaesthesia. The serum and bone concentrations of both compounds were similar in individual patients although there was considerable interpatient variation. The mean concentrations in the femoral head bone supernatant in hip replacements were 7.2 mg/kg of cephradine and 8.0 mg/kg of cefuroxime. In knee replacement the femoral condyle bone concentrations were 5.1 mg/kg of cephradine and 4.2 mg/kg of cefuroxime, and for tibial bone 5.6 and 4.6 mg/kg respectively. Both cephradine and cefuroxime diffuse well into bone giving bone concentrations effective against common pathogens such as Staphylococcus aureus and S. epidermidis.

Adult↗
PubMed1988

Pharmacokinetics of ofloxacin and the effect on the faecal flora of healthy volunteers.

Pharmacokinetic studies using a new oral quinolone ofloxacin were carried out in 12 healthy volunteers. The mean Cmax was 2.7 mg/l after the first dose of 200 mg ofloxacin rising to 3.4 mg/l after the seventh dose. The Tmax was between 1-2 h and the serum half life 5 h. Saliva concentrations matched serum levels but the absolute values were lower. Urinary concentrations ranged from 141 to 330 mg/l and the 12 h excretion was 62% after the seventh dose. Faecal concentrations were high and persisted for up to five days after the last dose. The major effect of ofloxacin on the faecal flora was the rapid and complete elimination of aerobic Gram-negative bacilli. Streptococci were generally increased but there was no change in the total anaerobic bacterial count. Pre-treatment composition of the faecal flora was re-established between 3 and 26 days after the last dose. Ofloxacin was well tolerated by the volunteers and only two complained of significant side effects, gastrointestinal disturbance and insomnia. Ofloxacin is a valuable addition to the range of antimicrobial agents available for the oral treatment of bacterial infection.

Adult↗
PubMed1988

Economic implications of oral treatment replacing parenteral therapy in antimicrobial chemotherapy.

The cost of antimicrobial chemotherapy is a major part of the total hospital pharmacy cost. Parenteral administration is considerably more expensive than oral and until recently was the only available therapy for nosocomial and resistant bacterial infections. Apart from the cost of the antimicrobial agent itself, many other factors such as the infusion sets, catheters and cannulae, monitoring of blood to avoid toxicity and other laboratory investigations will influence the costs. The introduction of ciprofloxacin, a new quinolone, with a wide range of bacterial activity which can be prescribed orally, will have economic advantages in the treatment of hospital infections.

Administration, Oral↗
PubMed1986

Serum and bone concentrations of cefuroxime in patients undergoing knee arthroplasty.

Concentrations of cefuroxime were measured in the serum and femoral and tibial bone of 12 patients undergoing knee arthroplasty, following cefuroxime 1.5 g iv. The mean serum cefuroxime concentration was 112.4 mg/l at the time of application of the mid thigh tourniquet. The mean femoral bone concentration was 18.6 mg/kg and tibial bone was 15.5 mg/kg. These concentrations of cefuroxime appear adequate for prophylaxis against post-operative infection in knee arthroplasty.

Arthroplasty↗
PubMed1986

Ciprofloxacin therapy in complicated urinary tract infections caused by Pseudomonas aeruginosa and other resistant bacteria.

Thirty courses of ciprofloxacin were given to 28 patients with complicated urinary tract infections mainly caused by Pseudomonas aeruginosa. All patients had severe underlying abnormalities and infection usually followed urethral catheterization. The infecting organisms were eradicated from the urine of all patients during therapy and 89% were still clear five to nine days after treatment. At one month follow up the cure rate had fallen to 64%. An increase in resistance to ciprofloxacin was seen in three of the ten failures in infections caused by Ps. aeruginosa. Therapy was well tolerated and few side effects were seen. Ciprofloxacin is a valuable addition to the range of antimicrobial agents available for the treatment of Ps. aeruginosa urinary tract infections particularly in domiciliary practice.

Adult↗
PubMed1985

Pharmacokinetic study of ceftazidime in bone and serum of patients undergoing hip and knee arthroplasty.

Twenty-eight patients undergoing hip arthroplasty and 15 undergoing knee arthroplasty, received chemoprophylaxis with ceftazidime 1.0 g administered intravenously at the time of induction of anaesthesia, followed by two doses of 500 mg given intramuscularly 6 and 12 h later. The mean bone concentration in hip arthroplasty showed a general rise towards a maximum of approximately 20 mg/kg when the exposure time (interval between antibiotic injection and removal of bone sample) was 35-40 min, with values ranging from 4.4 to 21.2 mg/kg (mean 14.4 mg/kg). The patients undergoing knee arthroplasty present a complicated pharmacokinetic problem, as the use of a tourniquet limits the exposure time. Bone concentrations of ceftazidime were highest at sampling times greater than 20 min in these patients (mean level of 15.9 mg/kg for femoral bone and 13.1 mg/kg for tibial bone).

Adult↗