Cost-effective use of liposomal amphotericin B.
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Biomedical subjects
Publications and source records attributed to H Ludlam.
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As the prevalence of resistant Gram-positive organisms in the critical care unit has increased, so have the associated morbidity and mortality and the cost of their treatment. As a result, more toxic and less active second-line agents and combinations of agents are used, often with limited evidence of clinical benefit. Although widely used, the role of glycopeptides is limited by increasing resistance and poor pharmacokinetics. New agents now in use, such as quinupristin/dalfopristin and Linezolid (Zyvox; Pharmacia & Upjohn, Kalamazoo, MI), show promise, as do diverse agents in development. The future is likely to bring greater therapeutic choice but, inevitably, further resistance.
BACKGROUND: antibiotic-associated diarrhoea caused by Clostridium difficile is increasing in hospitals, and older people are at particular risk. OBJECTIVE: to establish whether reducing patient exposure to injectable third-generation cephalosporins by substituting alternative antibiotics can produce a cost-effective reduction in the incidence of antibiotic-associated diarrhoea. DESIGN: we prospectively investigated 2157 patients admitted to the department of elderly medicine in the year before introduction of antibiotic restrictions and 2037 patients admitted in the following year. Patients admitted to other wards, where antibiotic prescribing was unchanged, acted as controls. SETTING: a 900-bed teaching hospital in Cambridge, UK. MEASUREMENTS: use and cost of injectable antibiotics prescribed in the department of elderly medicine and the other wards studied; occurrence of C. difficile-associated diarrhoea. RESULTS: in the wards for older people, consumption of injectable cephalosporins fell by 92% (compared with 8% on other wards) and cases of C. difficile-associated diarrhoea fell from 98 to 45 (cases in other wards rose from 213 to 253; P < 0.001). The Pound Sterling 8062 increase in injectable antibiotic costs on the elderly wards were offset by the release of 1087 wasted bed-days attributable to the 53 fewer cases, with potential savings of Pound Sterling 212,000. CONCLUSIONS: restricting the consumption of injectable third-generation cephalosporins is a cost-effective method of reducing the incidence of C. difficile-associated diarrhoea.
An outbreak of gastroenteritis affected 58 of 700 people served by a private water supply at a biological research institute located in a village. No cases were detected in 250 residents of the same village served by a public water supply over the same period. Consumer complaints of tainting and laboratory evidence of bacterial and chemical contamination were obtained for the private water supply, but not for the public water supply. The outbreak was probably caused by contamination from a nearby sewer of a borehole used for the private supply. The outbreak showed how a large, private water supply posed a substantial risk to public health. The regulatory framework for such water supplies should be modified to ensure their safer design and operation.
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We describe a case of acute symptomatic infection with Coxiella burnetii acquired between the 16th and 28th week of pregnancy. Oral ciprofloxacin therapy was started on diagnosis, at the 28th week of pregnancy, but symptoms were unabated after 3 weeks treatment, suggesting persisting infection of the products of conception. Caesarean section was therefore performed at 32 weeks gestation when a healthy infant was delivered, and subsequent investigations showed no evidence of transplacental spread of infection. Infection control measures were applied at the time of delivery to minimize the risk of infection to obstetricians and midwives from potentially infectious products of conception.
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The discriminative capacity of ribotyping was initially assessed without knowledge of results obtained for the same isolates by use of more established typing methods. Forty-eight isolates of coagulase-negative staphylococci (CNS) from peritoneal fluids were studied. They were collected prospectively during 31 consecutive episodes of infection associated with peritoneal dialysis in 17 patients. DNA was digested by the restriction endonucleases EcoRI or HindIII and ribotyped by means of a biotinylated cDNA probe to 16S + 23S staphylococcal ribosomal RNA gene sequences. These methods in combination produced a total of 27 types which compared well with numbers of groups distinguished by other typing methods: limited biotype-antibiotic resistogram (ARB; 28), antibiotic resistogram alone (25), API-Staph (12), phage typing (9) and plasmid analysis (22). Ribotyping was highly reproducible and typed all isolates, including those that were not phage-typable (35) or did not contain plasmids (4). When used in a hierarchical manner with ARB, ribotyping results produced 13 additional types in comparison with the other three methods. When used hierarchically with all other typing systems, a further five types were found among isolates from two patients. However, some of the differences observed as a result of ribotyping could have been due to subtle changes produced by mutation, lysogenisation or gene transposition. Since the method requires additional time, expense and technical expertise, it is likely to be useful only when answers to specific epidemiological problems are required or as an initial screen before using other methods of genetic analysis.
Antagonism of antibiotic activity by peritoneal dialysate has been postulated to be a cause of failure of treatment of peritonitis complicating continuous ambulatory peritoneal dialysis. We evaluated by a case-control study whether unexpected treatment failure could be attributed to such antagonism. Bacteria isolated from 34 patient episodes of peritonitis treated with the same regimen of ciprofloxacin monotherapy were studied. Ciprofloxacin was significantly less active in dialysate than in Iso-Sensitest broth (IB). The median MIC in IB was 0.5 microgram/ml, increasing to 2.0 micrograms/ml for both fresh dialysate (FD) (P = 0.003) and pooled dialysis effluent (PDE) (P = 0.03); the median MBC in IB was 8.0 micrograms/ml, increasing to 128.0 micrograms/ml in FD (P = 0.0002) and 64.0 micrograms/ml in PDE (P = 0.02). However, no significant differences were found in the results for patients suffering unexpected treatment failure (relapse of peritonitis) compared with the results for patients whose infection resolved without sequel. In IB the median MICs for relapsers and nonrelapsers were 1.0 and 0.5 microgram/ml, respectively (P = 0.88); median MBCs were 32.0 and 4.0 micrograms/ml (P = 0.19). In FD median MICs for relapsers and nonrelapsers were 2.0 and 1.0 micrograms/ml (P = 0.06); median MBCs were 128.0 micrograms/ml for both groups (P = 0.84). In PDE the median MICs were 2.0 micrograms/ml for both groups (P = 0.78); median MBCs were 256.0 and 64.0 micrograms/ml (P = 0.17). We therefore found no evidence to suggest that antagonism of antibiotic activity by dialysate is a cause of treatment failure or that conventional methods for laboratory susceptibility testing in peritonitis complicating continuous ambulatory peritoneal dialysis should be abandoned in favor of testing in media containing dialysate.
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Dialysate effluent from 41 patients presenting with 54 episodes of CAPD peritonitis was examined by four culture techniques, three employing methods for the lysis of peritoneal leucocytes. The most efficient method employed a distilled water lysis-centrifugation technique (81% of episodes culture-positive). Filtration (without leucocyte lysis) was less effective (74% culture-positive). The results of a mechanical leucocyte lysis technique were less satisfactory still, the culture positive rate of 74% being compromised by the recovery of the infecting organism in low numbers, and by an association with a high incidence of plate contamination. The results of a bile-salt lysis technique were the least satisfactory (67% culture-positive).
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In December, 1984, an outbreak of pyoderma affected five scrum players in the St Thomas' Hospital rugby team. The causative organism, Streptococcus pyogenes, was acquired during a match against a team experiencing an outbreak of impetigo, and was transmitted to two front row players of another team a week later, and to two girlfriends of affected St Thomas' players a month later. The strain was M-type 49, tetracycline-resistant, and virulent. It caused salpingitis in a girlfriend and acute glomerulonephritis in one rugby player. No case of subclinical glomerulonephritis was detected in eight patients with pyoderma. Screening of the St Thomas' Hospital team revealed four further cases of non-streptococcal skin infection, with evidence for contemporaneous spread of Staphylococcus aureus. Teams should not field players with sepsis, and it may be advisable to apply a skin antiseptic to traumatised skin after the match.
Tuberculous peritonitis is reported in an Asian immigrant undergoing continuous ambulatory peritoneal dialysis (CAPD). Unusual laboratory findings which resulted in delayed diagnosis are described.