ESGAB breakpoint determination: clarithromycin.
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Biomedical subjects
Publications and source records attributed to I Phillips.
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To determine the influence of intrinsic neurons of the dorsal hippocampus on dopamine (DA) turnover in other limbic areas, DA and its metabolites were assayed in several brain areas 14 and 28 days after bilateral ibotenic acid (IA) lesions of the dorsal hippocampus in the rat. The locomotor response to d-amphetamine was also assessed. Spontaneous locomotion was increased 14 but not 28 days postoperatively. There was no change in d-amphetamine-induced locomotion at any time. Presynaptic indices of DA turnover in the medial prefrontal cortex, anteromedial striatum and nucleus accumbens were not affected by the lesion. Unlike lesions of the medial prefrontal cortex, deefferentation of the dorsal hippocampus does not increase DA turnover in the basal ganglia.
Multiply antibiotic-resistant Staphylococcus aureus and Escherichia coli have both caused outbreaks in London in recent years, and for this reason have been referred to as E(epidemic)MRSA and EMREC respectively. In each case it has been questioned whether either organism has properties other than antibiotic resistance that distinguish them from other strains. Evidence is adduced to suggest that EMRSA has properties that enable it to spread particularly well, and that EMREC is particularly virulent. Both were introduced into our environment by chance, and were helped by their antibiotic resistance to become involved in a train of events--different in each case--that culminated in severe infection in a small number of patients, and thus to further investigation. The organisms involved in such outbreaks are worthy of investigation and control, if only because of the difficulty of treating clinical infections when they develop.
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On the basis of minimum inhibitory concentrations clarithromycin (6-O-methylerythromycin), a new macrolide, was found to be slightly more active than erythromycin against Staphylococcus aureus, enterococci. Moraxella catarrhalis, Gardnerella vaginalis, Bacteroides fragilis (sensu stricto) and B. ureolyticus and slightly less active against coagulase-negative staphylococci, alpha- and beta-haemolytic streptococci, Haemophilus influenzae, Campylobacter coli/jejuni and the B. melaninogenicus/oralis groups. There was complete cross-resistance between the two agents. Reports of potentiation of the activity against Haemophilus influenzae of clarithromycin by its own metabolite and by human serum appear to operate in vivo, and therefore the new agent shows great promise, especially for the treatment of respiratory tract infections.
The major complication of central venous catheterization for immediate access for haemodialysis is infection. The Quinton Permcath is a tunnelled, double lumen, flexible silastic catheter with a Dacron cuff, and is claimed to be associated with a low rate of infection. In a two-year study we have monitored all complications including catheter-associated infection related to this device in haemodialysis patients while following a simple aseptic programme for the care of the catheter exit wound. Thirty four Permcaths were inserted in 30 patients for a mean duration of 6.2 months (SD +/- 5.7; range 2 days to 23 months). Catheter use amounted to a total of 197 months. Of twenty-seven catheter wound infections, 6 (22%) were caused by Staphylococcus aureus, and 15 (56%) by coagulase-negative staphylococci or corynebacteria. These occurred in 19 patients, giving an exit site infection rate of one episode per 7.4 catheter months. Catheter-associated septicaemia occurred in three patients (two S. aureus, one S. epidermidis), at a rate of one episode per 66 months. It was possible to correlate three episodes of infection with breakdown in aseptic care. This study confirms the low rate of infection associated with the use of the Permcath, and we conclude that the design of the device and aseptic care of the catheter and its wound contribute to this.
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MICs of penicillin, methicillin, clindamycin, erythromycin, sodium fusidate and gentamicin were determined by an agar dilution method for 300 current isolates of Staphylococcus aureus and 100 of S. epidermidis, collected from four centres, and 38 stock strains of methicillin-resistant S. aureus (MRSA). All but one of the 300 current isolates of S. aureus were sensitive to clindamycin (MIC less than 0.5 mg/l), with an MIC90 of 0.12 mg/l. Of a total of 39 MRSA strains, 11 (28.2%) were resistant to clindamycin (MIC greater than 32 mg/l); all of these strains were also resistant to erythromycin. Ten of the 100 strains of S. epidermidis were resistant to clindamycin; they came from a reasonably equal geographical distribution and were also resistant to erythromycin. The results suggest that clindamycin might still be useful as a second-line agent for infections caused by S. aureus and S. epidermidis, although its activity against MRSA was limited to approximately two-thirds of the MRSA strains tested in this study.
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Temafloxacin, like other 4-quinolones, was highly active against most isolates of Enterobacteriaceae. It was slightly less active than ciprofloxacin but approximately as active as ofloxacin and enoxacin. It was the most active of the quinolones against Acinetobacter spp. and Xanthomonas maltophilia but was slightly less active than ciprofloxacin against Pseudomonas spp. Temafloxacin was highly active against Haemophilus influenzae, Moraxella catarrhalis and Neisseria gonorrhoeae and was the most active of the quinolones against Gardnerella vaginalis and Campylobacter coli/jejuni. It was more active than ciprofloxacin against most staphylococci and equally active against streptococci and enterococci. Temafloxacin was the most active quinolone against anaerobic bacteria and, with the exception of a few isolates of Bacteroides spp. and some clostridia, all anaerobes were within the sensitive range (MIC less than or equal to 2 mg/l).
Ciprofloxacin at a dose of 25 mg/L of dialysate was administered intraperitoneally for five days as a single agent for the empirical treatment of CAPD peritonitis. One hundred and seventeen consecutive episodes of peritonitis occurred in 65 patients during the study period, and 100 episodes were entered in the study. This therapy was successful in 79% of episodes. Resistant organisms (MIC greater than 4 mg/L) all of them coagulase-negative staphylococci, were isolated in nine (7.8%) of the 117 episodes. Mean ciprofloxacin concentrations in dialysate and serum on the last day of treatment were 6.1 mg/L (range 0.3-15.7) and 0.3 mg/L (range 0-0.9) respectively. No adverse effects were reported.
Tosufloxacin was highly active in vitro against most isolates of Enterobacteriaceae. It was slightly less active than ciprofloxacin for most species but more active than temafloxacin. It was the most active agent against Acinetobacter spp., Xanthomonas maltophilia and some Pseudomonas spp. but was slightly less active than ciprofloxacin against the fluorescent pseudomonads. Tosufloxacin was highly active against strains of Haemophilus influenzae, Moraxella catarrhalis, Neisseria gonorrhoeae and Campylobacter coli/jejuni. It was the most active of the fluoroquinolones tested against staphylococci (MICs 0.016-0.25 mg/L), streptococci (MICs 0.06-1 mg/L) and enterococci (MICs 0.12-4 mg/L). Tosufloxacin was also the most active quinolone tested against anaerobic bacteria and, with the exception of a few isolates of Bacteroides spp. and some clostridia, all anaerobes had tosufloxacin MICs less than 1 mg/L.
The auxotype, serogroup and antimicrobial susceptibility of 977 clinical isolates of Neisseria gonorrhoeae obtained at St Thomas' Hospital, London, during 1989 were determined; 23 isolates from 15 patients were resistant to 4-quinolones. Twelve of the patients acquired their infection in the UK and these strains were generally sensitive to other antimicrobial agents; strains from 10 patients were of serogroup IB-6. Three patients acquired their strains outside the UK and these isolates were multi-resistant and of different serogroups.
Conventional biochemical and antibiotic sensitivity tests were used to allocate 87 clinical isolates of anaerobic gram-positive cocci to currently recognised species, in comparison with type and other authentic reference strains. Whole-cell protein electrophoresis was then performed with extracts of each strain. Allowing for difficulties of standardisation, it was possible to allocate most of the organisms to species-related groups on the basis of protein patterns. Organisms identified conventionally as Peptostreptococcus anaerobius and P. micros formed homogeneous groups by protein electrophoresis. There was evidence for heterogeneity amongst strains identified as P. asaccharolyticus (two groups, including P. indolicus), P. prevotii and P. magnus. However, aberrant P. prevotii strains were allocated to the P. asaccharolyticus groups, leaving a homogeneous P. prevotii group, and if P. variabilis were re-instated as a species, the remaining P. magnus strains could be divided into two groups. Of the anaerobic gram-positive cocci in the National Collection of Type Cultures deposited by Hare, Group IV is P. magnus, Group IX is P. micros and Groups I, III and VIII appear to be related to the butyrate-producing species P. asaccharolyticus and P. prevotii, but are strongly saccharolytic.
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In 1987 a preventive programme was initiated to address the problem of high hospital and community-acquired CAPD infection. It concentrated on reducing Staphylococcus aureus carriage, improving aseptic operative technique, intensive training for nursing staff and patients in stringent aseptic care of the exit site, and avoidance of contact of the exit site with unsterile water. This programme was associated with an overall 10-fold reduction in exit site infection, a 2-fold reduction in peritonitis, and a 4.5-fold reduction in catheter loss from infection. These reductions have been sustained. Preventing infection in CAPD patients requires persistence and commitment but improves the patient's quality of life and reduces the cost of treatment.