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Biomedical subjects

J H Darrell

Publications and source records attributed to J H Darrell.

At least 19 recordsLinked to original sources

Comparative in vitro activity of daptomycin (LY146032) and vancomycin against gram-positive cocci determined using a pharmacokinetic model.

The activity of daptomycin (LY146032) and vancomycin was compared for methicillin-sensitive and methicillin-resistant (MRSA) strains of Staphylococcus aureus and for Enterococcus faecalis, using a semi-automated model that allows examination of time-kill curves with diminishing drug concentrations, thus reflecting in vivo pharmacokinetics. Exposure to daptomycin resulted in rapid killing of all strains of staphylococci and Enterococcus faecalis tested. Methicillin-sensitive staphylococcal strains appeared marginally more susceptible than MRSA. By contrast, the activity of vancomycin appeared much reduced. For all strains, greater than 90% kill was not observed within 24 h. Enterococcus faecalis was uniformly less susceptible to both agents than were staphylococci. The results suggest that despite similar values for MICs, the activity of daptomycin against strains of Staphylococcus aureus and Enterococcus faecalis is comparable to and may exceed that of vancomycin, although the significance of such differences is uncertain.

Daptomycin

Ceftazidime as first-line therapy for fever in acute leukaemia.

Fifty patients with acute non-lymphocytic leukaemia were treated by random allocation with either ceftazidime alone or a combination of piperacillin, netilmicin and cefotaxime for 65 febrile neutropenic episodes. Nineteen of 33 patient episodes (58%) responded to ceftazidime alone compared with 21 of 32 episodes (66%) treated with the combination. There was one infective death in a patient given the combination; rates of documented superinfection were low. The treatment groups appeared identical in terms of patient demography, underlying disease and other risk factors, though patients with a clinical site of infection responded more slowly than those without. Bacteraemia per se did not appear to influence outcome. Bactericidal serum concentrations greater than or equal to 8 X the minimum bactericidal concentration were predictive of a rapid response (within 4 days) to antibiotics. Furthermore, serum from patients treated with ceftazidime maintained adequate cidal activity against Pseudomonas aeruginosa for longer than that obtained from patients treated with the three-drug combination. Ceftazidime was shown to be a safe and effective alternative to the three-drug combination for the initial management of febrile neutropenic episodes in leukaemic patients.

Adolescent

Oral ketoconazole and amphotericin B for the prevention of yeast colonization in patients with acute leukaemia.

Forty-eight neutropenic patients with acute leukaemia were randomly allocated to receive, as antifungal prophylaxis, either ketoconazole, 400 mg once daily (K), or amphotericin B tablets and lozenges (A), or both ketoconazole and amphotericin B together (K + A). Antifungal prophylaxis was considered to have failed if (1) there was evidence of increasing colonization of the oropharynx or faeces with Candida spp. or other yeasts, or (2) if systemic antifungal therapy was begun empirically. Prophylaxis failed in nine of 17 patients given K, in four of 19 given A, and in four of 12 given K + A. The differences between the three regimens were not statistically significant, neither was there any significant difference in the mean duration of neutropenia before prophylaxis failed. The absorption of ketoconazole was impaired when patients were neutropenic. We conclude that ketoconazole was neither more nor less effective than amphotericin B in the prevention of yeast colonization in neutropenic patients.

Adolescent

Use of the Phoenix system for bacteriology.

A dedicated microbiology data processing system with remote batched job entry to an obsolete computer, has been superseded by the inclusion of bacteriology in an on-line interactive clinical pathology system which had previously incorporated chemical pathology and haematology. The original Phoenix system has been adapted to allow for the entry of bacteriology data using mnemonic codes and to deal with the problems caused by the longer processing time of bacteriology specimens. Particular advantages of the new system include the immediate linkage of all specimens for each patient and an easy recall and display of results in the laboratories and on the wards.

Bacteriology

Contamination of specimen container surfaces during sputum collection.

Sputum specimens from culture-positive tuberculosis patients were examined for the presence of Myobacterium tuberculosis on container surfaces. Although specimens were in transit for several days, M tuberculosis was isolated from 18 (6.5%) of 279 containers examined. Sputum specimens from local patients were examined for evidence of upper respiratory bacterial flora on the outside of containers as an indicator of contamination with sputum. Of 300 containers examined, 41 (14%) were contaminated. A technique for disinfecting specimen containers from tuberculosis patients has been evaluated and recommendations are made for handling sputum containers.

Decontamination

Prophylactic cefuroxime in total joint replacement.

Cefuroxime was given during operation to 95 patients undergoing 106 total joint replacements (hip 69: knee 37). Two regimes were used. Either 1 g was given intravenously with induction of anaesthesia and then two intramuscular injections of 1 g 6 and 12 h later, or 1.5 g was given intravenously with induction and two injections of 750 mg each intramuscularly 6 and 12 h later. The concentrations of cefuroxime in bone, capsule and blood were measured in 77 patients. The assays were carried out independently in two laboratories. In most instances concentrations in the bone were above the MICs for likely pathogens, even after allowing for any contaminating blood. Concentrations in synovial capsule were generally higher than in bone. After a follow-up period of 2 years, two patients developed deep infections. The overall infection rates are comparable with the best results reported in the literature using other prophylactic antibiotics or with ultra-clean air systems.

Adult

Extrapulmonary tuberculosis: a potential source of laboratory-acquired infection.

A three-year retrospective study has demonstrated the effect of extrapulmonary tuberculosis on safety within a routine bacteriology laboratory. The investigation showed that, from 112 patients, 162 specimens considered to present a risk to laboratory staff were processed outside of the B1 protective area. However, it was estimated that only 51 of those specimens were heavily positive. Of these 57% were sputum 30% pus, and 10% urine. Specimens of pus and urine account for 50% of specimens received for non-tuberculosis investigations, and it would be impossible to process all specimens that might present a risk in B1 accommodation and still maintain a high degree of safety. It is recommended that request forms which accompany specimens should clearly indicate potential high-risk specimens.

Humans

Peroperative antibiotics in the prevention of chest infection following cardiac operations.

Seventy-nine patients about to undergo cardiac operations were randomly allocated to two treatment groups in an attempt to reduce postoperative chest infections. The group receiving a short peroperative course of cefamandole, an antibiotic effective against both the pneumococcus and Haemophilus influenzae, had a significantly lower postoperative chest infection rate than the group receiving a 3-day course of cephradine, an antibiotic previously chosen to prevent intracardiac infection during the operation. By selecting an appropriate antibiotic it is possible, using a short peroperative course, to reduce the postoperative chest infection rate in patients undergoing cardiac operations.

Adult

Amikacin dosage in the preterm newborn.

Twenty-two preterm infants of gestational age 26 to 34 weeks were treated with amikacin for suspected bacterial infection, using a dose of 7.5 mg/kg, 12-hourly, intra muscularly. Blood levels were measured using a radio-immunoassay kit capable of giving results within 4 h. One-hour peak levels showed wide variation and the mean level one hour after the first dose was 18.2 mg/1; in severe infections an initial loading dose of 10 mg/kg is therefore recommended. Trough levels in individual infants also varied considerably from day to day, but showed no overall accumulation. There was no obvious adverse effect on hepatic or renal function.

Amikacin

Urinary infection with coagulase-negative staphylococci in a teaching hospital.

In the eight-month period of study of all urine samples processed in our routine laboratory, only 85 out of 12 152 specimens yielded a bacteriologically significant growth of either Staphylococcus epidermidis or micrococci. Their growth on MacConkey medium was strictly comparable to that on cysteine lactose electrolyte-deficient (CLED) media. Most micrococci isolated were from urine samples of non hospitalised women patients, were resistant to a novobiocin (5 micrograms) disc, and belonged to Baird Parker type 3. Staph. epidermidis came mainly from postoperative surgical in-patients. Their antibiotic sensitivity patterns are variable whereas micrococci are fully sensitive to all urinary antibiotics. We agree that the use of a novobiocin (5 micrograms) disc for provisional identification of micrococci and Staph. epidermidis is simple and practical for a busy routine diagnostic laboratory. The use of more extensive systems to biotype these organisms in a routine laboratory is not practical and not relevant to patient management.

Bacteriuria

The skin as the source of Acinetobacter and Moraxella species occurring in blood cultures.

A study was made of the flora of the skin in hospital inpatients and healthy people to demonstrate the presence of non-fermenting Gram-negative rods of the Acinetobacter and Moraxella group. These organisms were found to be present on the skin of 34.3% of inpatients and occurred even more commonly in those patients with kidney disease. It was also present on the skin of 20% of a group of healthy members of staff. This rather high rate of skin carriage is thought to account for the not infrequent occurrence of this organism in blood cultures.

Acinetobacter