Since combinations of fosfomycin and vancomycin or tobramycin and vancomycin could be of advantage in the therapy of staphylococcal infections, we studied renal tolerance of both combinations. The experimental animal was the rat and the parameters of nephrotoxicity were cyturia and enzymuria. The experiments showed that fosfomycin at dosages of 50 and 250 mg/kg protected against nephrotoxicity caused by vancomycin (dose: 50 mg/kg), whereas the administration of both tobramycin (dose: 2.5 mg/kg) and vancomycin (dose: 50 mg/kg) resulted in an increase of cyturia and enzymuria. However, repeated dosing of vancomycin (single dose: 50 mg/kg) led to renal accumulation when combined with fosfomycin (single dose: 250 mg/kg); renal vancomycin concentrations were lower. This study suggests similarities in the renal handling of vancomycin and aminoglycosides and demonstrates the possibility of reducing drug-associated nephrotoxicity.

Animals↗

PubMedDate not supplied

The microbiological efficacy of the combination of fosfomycin and vancomycin against clinically relevant staphylococci.

Infections with multiresistant strains of Staphylococcus aureus and Staphylococcus epidermidis pose severe clinical problems. The drug of choice in such cases, vancomycin, is potentially ototoxic and nephrotoxic and this may give rise to additional problems in the patient. Fosfomycin has been shown to be nephroprotective when given with vancomycin and with other nephrotoxic drugs. We report the inhibitory and bactericidal activity of fosfomycin and vancomycin alone and in combination against 26 clinically relevant strains of S. aureus and 48 strains of S. epidermidis. In most instances these two drugs showed indifferent or additive effects, synergism or antagonism was only rarely observed. Assessment of the bactericidal action of the combination revealed similar effects. The combination of fosfomycin and vancomycin may, therefore, be beneficial in clinical situations where the nephrotoxic effect of vancomycin cannot be tolerated.

Drug Combinations↗

PubMedDate not supplied

Relationship between the bactericidal and bacteriolytic activity of cephalosporins and changes in the cell volumes of Escherichia coli cultures.

The bactericidal effect of cefoxitin and cefotaxime in relation to concentration and exposure time, as demonstrated by the killing curve diagrams of Escherichia coli cultures, was compared with the degree of bacteriolysis and the cell volume increase measured by the coulter counter-channel analyser system. Human plasma ultrafiltrate was used as the growth medium. Cefoxitin has a higher bactericidal activity than cefotaxime. With increasing concentrations the bactericidal efficacy of cefoxitin increases more rapidly in the lower range of concentrations (2-10 mg/l) than in the higher range (10-40 mg/l). In contrast, the bactericidal effect of cefotaxime in the range 0.06-1.2 mg/l is virtually constant and can only be increased by high levels (10-40 mg/l). The morphometric effect of cefoxitin on E. coli cultures, as demonstrated by volume distribution curves, is characterized by intensive and rapidly appearing bacteriolysis 20 min after exposure to the antibiotic without a preceding increase in bacterial cell volume. Higher concentrations result in an earlier onset of bacteriolysis. In contrast, the application of cefotaxime reveals a massive increase in bacterial cell volume (more than five-fold) with a delayed (greater than 2 h) onset of bacteriolysis. High cefotaxime concentrations reduce the extent of bacterial cell volume increase, associated with an earlier and more intensive onset of bacteriolysis. With both cephalosporins, the bacterial cell alterations are particularly dependent on the exposure time. There is evidently a close correlation between bactericidal and bacteriolytic activity. This is valid both for the two cephalosporins and generally for the concentration-activity relationships.

Blood↗

PubMedDate not supplied

Carboxyhaemoglobin and methaemoglobin findings in burnt bodies.

The often observed absence of carboxyhaemoglobin in burnt (charred) bodies is re-discussed in the light of two new cases in which the inhalation of very hot gases obviously led to reflex breathing and circulation arrest. (Macro and microscopic evaluations of the upper respiratory tract can give significant information as to whether a person was still alive at the time of the fire outbreak.) In the cadaver blood of people who survived a given period after a fire, high methaemoglobin values (up to 37%) were found. This was caused by the inhalation of nitrogen oxides that were produced by burning plastic.

Adolescent↗

PubMedDate not supplied

Biogenic amines as predictors of response to clozapine treatment in early-onset schizophrenia.

The purpose of the present study was to assess the relationship between plasma monoamine levels and changes in psychopathology in a sample of children and adolescents with schizophrenia (DSM-III-R criteria) during conventional neuroleptic therapy and during short-term treatment with clozapine. After failing on conventional neuroleptics in open-labeled clinical trials lasting a mean of 1.6 years, 15 inpatients (aged 11-20 years) received clozapine. Weekly ratings of psychopathological symptoms using standard rating scales were performed in parallel to blood samplings for measurements of biogenic amines and serum levels of clozapine. These measures were obtained for 6 weeks during conventional neuroleptic treatment and for 6 weeks during the open-label clozapine trial. Serum levels of serotonin and plasma norepinephrine levels were significantly higher during treatment with clozapine than during pretreatment with typical neuroleptics. A comparison of plasma epinephrine levels in responders (n = 7) and non-responders (n = 8) to clozapine revealed that response to clozapine can be predicted by epinephrine levels prior to initiation of treatment with clozapine (responders ranging from 32.2-90.3 pg/ml; non-responders ranging from 92.5-473.5 pg/ml). Additionally, subjects who responded to clozapine showed increased mean plasma concentrations of methoxyhydroxyphenylglycol (MHPG) and epinephrine during treatment with this drug in comparison to the levels measured during pretreatment with typical neuroleptic medication. In conclusion, our results demonstrate that plasma epinephrine levels prior to initiation of clozapine therapy predict response to this atypical neuroleptic.

Adolescent↗

PubMedDate not supplied

Updating the Read Codes: user-interactive maintenance of a dynamic clinical vocabulary.

The Read Codes are a hierarchically-arranged controlled clinical vocabulary introduced in the early 1980s and now consisting of three maintained versions of differing complexity. The code sets are dynamic, and are updated quarterly in response to requests from users including clinicians in both primary and secondary care, software suppliers, and advice from a network of specialist healthcare professionals. The codes' continual evolution of content, both across and within versions, highlights tensions between different users and uses of coded clinical data. Internal processes, external interactions and new structural features implemented by the NHS Centre for Coding and Classification (NHSCCC) for user interactive maintenance of the Read Codes are described, and over 2000 items of user feedback episodes received over a 15-month period are analysed.

Computer Systems↗

PubMedDate not supplied

Computerised clinical decision support systems--Part II.

Explore the source record for details and available documents.

Australia↗

PubMedDate not supplied

System architectures.

Explore the source record for details and available documents.

Australia↗