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Biomedical subjects

D S Reeves

Publications and source records attributed to D S Reeves.

At least 37 records · Page 2Linked to original sources

The pharmacokinetics of intravenous ciprofloxacin 400 mg 12 hourly in patients with severe sepsis: the effect of renal function and intra-abdominal disease.

Serum concentrations of ciprofloxacin were reviewed in 22 patients given ciprofloxacin 400 mg intravenously 12 hourly for severe infection. No dosage modifications were made in patients with renal impairment. Patients who had either bowel or liver pathology in addition to renal failure had significantly higher serum concentrations than all other patients. Dosage reduction of ciprofloxacin in patients with severe sepsis and impaired renal function is not required unless they have co-existent intra-abdominal disease.

Abdomen↗

A comparison of the penetration of cefuroxime and cephamandole into bone, fat and haematoma fluid in patients undergoing total hip replacement.

Twelve patients undergoing total hip anthroplasty received, at the induction of anaesthesia, cephamandole (1 g) and cefuroxime (1.5 g); further doses of cephamandole (1 g) and cefuroxime (750 mg) were given at 8 and 16 h after the operation. Routine total hip arthroplasty was performed and at timed intervals during operation samples of bone, fat and blood were collected for assay for HPLC analysis. Samples of the haematoma fluid that formed around the operation site and further blood samples were also collected at 7 and 15 h after the operation. Although considerable variation was observed in the bone and fat concentrations of both agents, the cefuroxime levels were substantially higher than those of cephamandole, with mean values for bone of cefuroxime 36.0 mg/L (95% CI 29.0-43.0 mg/L) and cephamandole 18.3 mg/L (95% CI 14.2-22.4 mg/L) and for fat of cefuroxime 15.0 mg/L (95% CI 11.1-18.9 mg/L) and cephamandole 11.2 mg/L (95% CI 7.2-15.2 mg/L). When corrected for blood concentrations the penetration of both agents was similar (bone, 43.6% cefuroxime and 37.8% cephamandole; fat, 16.0% cefuroxime and 19.2% cephamandole). Cefuroxime concentrations in haematoma drain fluid were higher than those of cephamandole 6-8 h after the operation (17.8 versus 8.3 mg/L) but lower at 14-16 h (7.7 versus 9.6 mg/L). We conclude that there are no significant differences between the bone, fat or haematoma penetration of cefuroxime and cephamandole and that any differences in the absolute levels of the two agents are due to differences in the total drug administered rather than their ability to penetrate into these sites. Time-kill curves for cefuroxime and cephamandole against five clinical isolates of Staphylococcus aureus failed to identify any significant differences between the rates of kill for the two agents at the concentrations seen in bone, fat or haematoma fluid. For both prophylaxis regimens antibiotic concentrations exceeded the MICs for potential pathogens for the duration of the operation and also in the haematoma which surrounds the operation site for up to 24 h after the operation.

Adipose Tissue↗

Bay 12-8039, a new 8-methoxy-quinolone: comparative in-vitro activity with nine other antimicrobials against anaerobic bacteria.

The in-vitro activity of a new 8-methoxy-quinolone, Bay 12-8039, was assessed against 218 anaerobic bacteria. Ninety-eight per cent of strains belonging to the Bacteroides fragilis group (n = 65) were inhibited by < or = 2 mg/L of Bay 12-8039 whereas 97%, 94%, 94% and 100%, respectively, of Gram-negative bacilli (n = 93), non-sporing Gram-positive bacilli (n = 36), endospore-forming Gram-positive bacilli (n = 34) and Gram-positive cocci (n = 45) were also inhibited by < or = 2 mg/L. Eighty-three per cent of all anaerobes tested were inhibited by < or = 1 mg/L Bay 12-8039 and 99.5% by < or = 4 mg/L. When compared with ciprofloxacin, clinafloxacin, ofloxacin and trovafloxacin, Bay 12-8039 was more active than ciprofloxacin and ofloxacin, equipotent to trovafloxacin but not as active as clinafloxacin.

Anti-Infective Agents↗

Microbiologically proven bacterial infections in AIDS.

We have reviewed the incidence, type and site of microbiologically proven bacterial infection occurring in 52 patients with the acquired immunodeficiency syndrome (AIDS) who presented to Southmead Hospital, Bristol between 1990 and 1994. A total of 30 (58%) patients had significant bacterial isolates. The majority of infections were community acquired. Overall, more infections were caused by Gram-negative organisms but Gram-positive organisms predominated in bacteraemia. Mycobacterium avium intracellulare (MAI) caused infection in the largest number of patients, followed by Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas sp, and Campylobacter sp. When individual episodes of infection were considered, after MAI, Haemophilus influenzae, Streptococcus pneumoniae and Pseudomonas sp were the organisms most frequently isolated; often these same organisms caused recurrent chest infection. Bacterial infections in AIDS patients are common and although they generally respond well to antimicrobial chemotherapy there is a high recurrence rate, particularly in the respiratory tract, which is the commonest site of infection.

AIDS-Related Opportunistic Infections↗

Three cases of meningococcal pneumonia.

Three cases of pneumonia due to Neisseria meningitidis are described. In all three cases the organism was isolated only from blood cultures, but in the presence of good clinical and radiological evidence of pneumonia. The isolates belonged to three different serogroups: B type 2b, C, and Y. The cases illustrate the fact that N meningitidis can cause pneumonia and that culture of blood plays an important part in the diagnosis. Clinically there is nothing to differentiate meningococcal pneumonia from other causes of community acquired pneumonia. Predisposing factors include aspiration, immunosuppression, influenza, and adenovirus infections. When diagnosed, pneumonia due to N meningitidis should be notified and prophylaxis given as for meningitis or septicaemia.

Adult↗

Therapeutic monitoring, the concentration-effect relationship and impact on the clinical efficacy of antibiotic agents.

Therapeutic monitoring is now technically feasible for a wide variety of antibiotic agents and data are accumulating on the relationship of blood levels and clinical efficacy. For each antibiotic a therapeutic range and dosage regimen can be based theoretically on its known pharmacokinetics, pharmacodynamics in vitro, and also use in animal and human treatment studies. Antibiotics can be characterised into types by their mechanism of kill, as either concentration-dependent (for which achieving a large post-dose concentration to MIC ratio appears important) or concentration-independent/time-dependent (where efficacy is related to maintain the overall concentration above the MIC). Hopefully, concentration-controlled trials will be performed when new antibiotics are introduced, to determine a therapeutic range which correlates with clinical efficacy, and so enable monitoring to lead to a more rational approach to antibiotic administration.

4-Quinolones↗

A new time-kill method of assessing the relative efficacy of antimicrobial agents alone and in combination developed using a representative beta-lactam, aminoglycoside and fluoroquinolone.

A time-kill curve employing nine sampling times over 6 h was used to provide data which were then used to develop a theoretical (best-fit) curve. From the theoretical curve parameters describing the rate of kill (alpha), time from addition of antibiotic to initiation of killing (d) and a function of the degree of killing observed (Ym/Yo) were defined. The area-under-the-curve (AUC) was calculated from the theoretical curve. The variability of each parameter was assessed using a theoretical curve to fit the data from experiments done on three occasions and in triplicate. In terms of the parameters alpha, d, Ym/Yo and AUC, no synergy was demonstrated with combinations of piperacillin/tazobactam plus ciprofloxacin or gentamicin when compared with single antibiotics. The AUC represents the best summary parameter of a time-kill curve but should be supported by other parameters describing the best-fit curve.

Acinetobacter↗

The in-vitro activity of trovafloxacin and nine other antimicrobials against 413 anaerobic bacteria.

The in-vitro activity of trovafloxacin and nine other antimicrobials was determined for 413 non copy anaerobic clinical isolates. Trovafloxacin was the most active quinolone tested with an MIC90 of 0.5 mg/L against Gram-positive cocci (n = 75); MIC90 of 4 mg/L against Gram-positive bacilli (n = 151); MIC90 of 0.5 mg/L for Gram-negative cocci (n = 12) and MIC90 of 1 mg/L for Gram-negative bacilli (n = 175). Overall the MIC90 of trovafloxacin was 1 mg/L which was equivalent to co-amoxiclav and one dilution higher than that of imipenem. The other seven comparators, including clindamycin and metronidazole, had higher MIC90 values than trovafloxacin. Trovafloxacin is likely to have clinically useful activity against anaerobes from human infection.

Anti-Bacterial Agents↗

Pharmacokinetics of once-a-day netilmicin (6 mg/kg) in neonates.

The pharmacokinetics of once a day netilmicin (6 mg/kg) was studied in 21 neonates. The babies were divided into three groups according to gestational age: group I aged > 36 weeks; group II between 34-36 weeks and group III < 34 weeks. Serum concentrations were variable between patients and the concentration 24 h after the first dose ranged from 0.8 to 3.8 mg/L with only two babies having concentrations of < 1 mg/L while seven had concentrations of > 2 mg/L. There were also large patient-to-patient variations in serum half-life, volume of distribution, area under the curve and relative plasma clearance such that these parameters could not be correlated to gestational age or weight. Absolute plasma clearance was correlated with both gestational age and weight. There was evidence of accumulation between the first and second dose for all three patient groups and for patients of gestational age < 34 weeks (group III) these observations were statistically significant. A netilmicin dosage of 4.5 mg/kg once a day may be more suitable for all neonates supported by assay of serum concentrations.

Female↗

The elution and binding characteristics of rifampicin for three commercially available protein-sealed vascular grafts.

Rifampicin was absorbed onto gelatin-sealed (Gelsoft and Unigraft) or collagen-sealed (Hemashield) vascular grafts by soaking for 15 min in a 1000 mg/L solution. Bound drug was then eluted from the grafts by incubation in phosphate buffered saline (PBS) at 37 degrees C and at timed intervals the concentration of rifampicin remaining in the grafts was determined. Although all three grafts contained high concentrations of rifampicin immediately after absorption of drug, rifampicin concentrations rapidly fell during elution with PBS to approximately 1.25 mg/kg of graft after 5 h incubation in PBS, indicating that most of the rifampicin absorbed to the grafts was only loosely bound. However, once this loosely bound fraction had been removed there was a much slower elution of the remaining rifampicin from the grafts, suggesting a second and much more tightly bound fraction. The tightly bound fraction eluted with an apparent half-life of 47-76 h, depending on the graft, and extrapolation back to time zero from this phase suggests that only a very small amount of the rifampicin is tightly bound to the graft after initial soaking (0.6-1.3 mg/kg).

Antibiotics, Antitubercular↗

The quality of clinical serum teicoplanin assays: an experimental European EQA distribution.

Two sets of six samples of human serum spiked with predetermined concentrations of teicoplanin were circulated, 6 months apart, to 22 European laboratories for the purposes of external quality assessment (EQA). The laboratories returned assay results using either bioassay, high-performance liquid chromatography (HPLC) or fluorescence polarization immunoassay (FPIA). FPIA was the most popular method and performance was generally satisfactory. Some laboratories using HPLC or microbiological assay performed satisfactorily but others did not. Only seven laboratories (32%) showed consistently satisfactory performance. There appears to be a need for continuing EQA of clinical teicoplanin assays.

Anti-Bacterial Agents↗

Bactericidal activity, post antibiotic effect and modified controlled effective regrowth time of meropenem at high concentrations.

The effect of increasing meropenem concentrations up to 250 mg/L, as might occur if 3 g was given as a single daily intravenous dose, was investigated in terms of bactericidal activity, post antibiotic effect (PAE) and modified controlled effective regrowth time (mCERT). Increasing the meropenem concentration above 50 mg/L did not result in increased bacterial killing, while concentrations over 75 mg/L did not result in longer PAE or mCERT.

Enterobacter↗

Trends in-original research published from the United Kingdom in the antimicrobial chemotherapy literature, 1980-1994.

There is a feeling that the contribution of researchers from the United Kingdom in the antimicrobial chemotherapy area is in decline, and we, therefore, reviewed publications in the Journal of Antimicrobial Chemotherapy (JAC) and Antimicrobial Agents and Chemotherapy (AAC) in 4 of the last 14 years. In absolute numbers the total number of UK first author publications in these two journals were 103, 78, 107 and 82 in 1980, 1985, 1990 and 1994 respectively. The percentage of first author papers from the UK in JAC was 35%, 21%, 24%, 23% and in AAC was 5.7%, 4.9%, 5.1% and 4.7% for the years 1980, 1985, 1990 and 1994 respectively. Within the UK there has been a relative decline in the number of publications produced by NHS hospital departments and an increase in those produced by universities. Ten institutions (four universities, two pharmaceutical companies and four NHS departments) produced almost half of the UK publications. There is no room for complacency about the state of British antimicrobial research and the relative decline in the NHS hospital sector's contribution, the largest contributor numerically, even before the full impact of the ongoing NHS reforms, is cause for concern.

Anti-Infective Agents↗

The effects of swaddling versus standard positioning on neuromuscular development in very low birth weight infants.

A randomized control design was used to compare the effect of swaddling to standard positioning on neuromuscular development in very low birth weight (VLBW) infants (< 1,250 gm). The outcome of neuromuscular development was measured at 34 weeks postconceptional age using the Morgan Neonatal Neurobehavioral Exam (MNNE). The sample included 50 infants who met criteria for birth weight, age and who were classified as appropriate for gestational age. Exclusion criteria were also used. The infants were randomly assigned to the experimental group or the comparison group. Data analysis included descriptive and inferential statistical techniques. The results demonstrated that swaddled infants had higher total scores on the MNNE as compared to infants with standard positioning. Swaddling appears to be a positioning technique that can enhance neuromuscular development of the very low birth weight infant.

Bedding and Linens↗