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Biomedical subjects

W Brumfitt

Publications and source records attributed to W Brumfitt.

231 records · Page 13Linked to original sources
PubMedDate not supplied

Rifaprim (rifampicin plus trimethoprim): pharmacokinetics and effects on the normal flora of man.

Ten healthy volunteers were given 'Rifaprim' in the dosage recommended for the treatment of urinary infections in man (rifampicin 300 mg + trimethoprim 80 mg in the morning and double these amounts at night, for 7 days). Levels of both drugs in the serum and urine were determined on the first and last days. The results show that trimethoprim was always present in the serum in amounts sufficient to suppress the emergence of resistance to rifampicin. In the urine, inhibitory concentrations of each drug were present throughout the course of treatment. Aerobic organisms were largely eliminated from the gut and reappeared after treatment still sensitive to both antibiotics: the anaerobic moiety persisted and became resistant to rifampicin. Changes in nasopharyngeal flora were relatively minor. Thus, this dosage regimen of "Rifaprim' contains enough trimethoprim to prevent the emergence of resistance to rifampicin among urinary pathogens under normal circumstances (i.e. provided the organisms are initially sensitive to trimethoprim).

Adult↗
PubMedDate not supplied

Bioavailability in human volunteers of three intramuscular formulations of cefonicid: a long-acting cephalosporin.

Three different intramuscular formulations of cefonicid (a new long acting cephalosporin) have been tested for bioavailability in 12 healthy volunteers, using a triple crossover design. No significant differences were detectable between the bioequivalence of the three formulations in terms of area-under-curve and 24-h urinary excretion. However, one of the formulations (A) was absorbed significantly more rapidly from the site of injection, causing higher serum levels for up to 1.5 h after administration. A significantly greater urinary excretion was also found up to 8 h after administration of formulation A. All three formulations were well tolerated, and no side-effects or significant changes in laboratory tests were observed.

Adult↗
PubMedDate not supplied

Comparative trial of trimethoprim and co-trimoxazole in recurrent urinary infections.

Eighty-nine patients with a history of recurrent urinary infection who required immediate treatment for significant bacteriuria were treated with either trimethoprim (300 mg at night) or with the standard course of co-trimoxazole (two tablets 12-hourly) for seven days. Cure rates one week after the end of treatment were 74.4% and 80.4%, respectively. During the following month the relapse rate was lower in the group given trimethoprim than among those who had received co-trimoxazole. Consequently, the cure rates six weeks after the start of treatment were 71.4% in the trimethoprim group and 58.5% in the co-trimoxazole group. These results suggest that in this type of patient, it may be possible to reduce the incidence of bacteriological relapse by giving antibiotics in larger doses and at less frequent intervals than are at present generally recommended.

Adult↗
PubMedDate not supplied

Single dose and conventional treatment for acute bacterial and non-bacterial dysuria and frequency in general practice.

A five day course of clavulanate-potentiated amoxicillin (Augmentin) has been compared with a single oral dose of fosfomycin trometamol in the treatment of patients complaining of symptoms suggesting urinary tract infection. The study took place in a single urban general practice of 15,000 patients in Cheshire. The microbiology was performed at a London Teaching Hospital. 141 patients entered the trial. 65 had a significant bacteriuria, 62 of which were assessable for the ability of the trial drugs to eradicate bacteriuria: 29 patients received clavulanate-potentiated amoxicillin and 33 fosfomycin trometamol. The cure rates, assessed at five to ten days and at four to six weeks post treatment, were 72% and 65%, respectively for clavulanate-potentiated amoxicillin and 85% and 81%, respectively for fosfomycin trometamol. Side effects, assessed in all 141 patients, occurred in 11.6% receiving clavulanate-potentiated amoxicillin and in 8.3% receiving fosfomycin. Statistically there is no difference between any of these findings and the effect of sample size is discussed. 69 patients were symptomatic but did not have a significant bacteriuria ("urethral syndrome"). These patients were assessed for the effect of treatment in relieving symptoms: 33 received fosfomycin trometamol and 36 clavulanate-potentiated amoxicillin. The success and speed of relieving the symptoms were very similar in the two groups. The finding that both groups responded equally well appears to refute an aetiological role for lactobacilli and diphtheroids in the "urethral syndrome", since these organisms are resistant to fosfomycin but sensitive to clavulanate-potentiated amoxicillin.

Adolescent↗
PubMedDate not supplied

In vitro activity of combinations of antibiotics against Staphylococcus aureus resistant to gentamicin and methicillin.

Twenty clinical isolates of Staphylococcus aureus, resistant to both gentamicin and methicillin, were tested in vitro for sensitivity to rifampicin, novobiocin, fusidic acid, vancomycin, teicoplanin and an extended range of aminoglycosides. Rifampicin was the most active compound tested, having an MIC of less than 0.02 mg/l. All the strains were inhibited by 1 mg/l of novobiocin, vancomycin and teicoplanin, and only one strain was resistant to fusidic acid. 50% of the strains were inhibited by less than 1 mg/l of amikacin and netilmicin, but other aminoglycosides were of poor activity. Resistant mutants were selected when strains were grown in the presence of rifampicin, novobiocin or fusidic acid alone, but this did not occur when rifampicin was combined with either novobiocin or vancomycin. Pharmacokinetic and other considerations suggest that a combination of rifampicin and novobiocin deserves further assessment for the treatment of infections caused by this type of organism.

Aminoglycosides↗
PubMedDate not supplied

A comparative trial of low dose cefaclor and macrocrystalline nitrofurantoin in the prevention of recurrent urinary tract infection.

One hundred and twenty women, aged between 18 and 90 years, with a history of at least four episodes of symptomatic urinary tract infection in the preceding 12 months, were randomized in an open, prospective study to prophylactic treatment with cefaclor 250 mg at bedtime or macrocrystalline nitrofurantoin 50 mg at bedtime for 12 months. Ninety-seven (49 taking cefaclor, 48 taking macrocrystalline nitrofurantoin) were assessed for efficacy; 80% of these were symptomatically improved and remained abacteriuric during the period of prophylaxis. Symptomatic attacks while patients were taking prophylaxis occurred at least five times less often than before prophylaxis had started. Seventy percent of the patients continued in an improved condition after having stopped prophylaxis. All 120 patients were assessed for adverse events; these were twice as frequent in patients taking macrocrystalline nitrofurantoin (20% vs. 10%), but only 11 patients (three taking cefaclor, eight taking macrocrystalline nitrofurantoin) withdrew from the study. Due to the small numbers of patients experiencing adverse events, these differences are not statistically significant. No significant changes in haematological or biochemical parameters were found during or after the end of the 12-month course. The 22 patients assessable for efficacy who had a non-obstructive radiological abnormality responded as well to prophylaxis as those with no detectable abnormality. Long-term, low-dose prophylaxis with a suitable antimicrobial agent is highly effective management for patients with recurrent urinary tract infections, and can appropriately be provided by the family doctor. Prophylaxis given for 1 year gives better results than when given for 6 months.

Adolescent↗
PubMedDate not supplied

Antibacterial oxazolidinones. In vitro activity of a new analogue, E3709.

The oxazolidinone compound E3709, which contains a 4-pyridyl group, was found to be more active in vitro than other members of this series, such as DuP 721. MIC90 for staphylococci(including methicillin-resistant isolates), streptococci (including Enterococcus faecalis), Clostridia, and diphtheroids was less than 0.5 micrograms/ml. Haemophilus influenzae, Moraxella catarrhalis, and Bacteroides fragilis were less susceptible, with an MIC90 between 2 and 8 micrograms/ml. E3709 MICs of Gram-negative species ranged from 100 to greater than 1000 micrograms/ml. At a concentration of 10 micrograms/ml, E3709 was bactericidal for selected Gram-positive species. A postantibiotic effect of 3 hr was observed against staphylococci. Resistance to E3709 was not detected.

Ampicillin↗
PubMedDate not supplied

Use of trimethoprim alone or in combination with drugs other than sulfonamides.

Experimental data, pharmacokinetic results, and clinical trials suggest that trimethoprim (TMP) is effective when used alone and is not associated with the toxicity and adverse effects caused by sulfonamides. Because an analysis of in vitro, pharmacokinetic, and clinical data suggested that the combination of rifampicin and TMP (Rifaprim) would be safe and highly active, an eight-year study of this combination for the treatment of urinary tract infection was done. The results were encouraging. Furthermore, a large multicenter trial of Rifaprim in 800 patients showed Rifaprim to be superior to trimethoprim-sulfamethoxazole for the treatment of chronic infections of the upper urinary tract. In another controlled trial, Rifaprim proved valuable for the treatment of urinary tract infections that resisted eradication and recurred frequently. Evidence suggests that Rifaprim may be useful in the treatment of other disease, such as staphylococcal osteitis (especially that caused by highly resistant organisms). Unlike antibiotics such as gentamicin, the use of which requires hospitalization of the patient and careful monitoring of levels in blood, Rifaprim can be used at home. Thus the danger of nosocomial infection is avoided.

Bacterial Infections↗
PubMedDate not supplied

Use of rifampin for the treatment of urinary tract infections.

The pharmacokinetic and microbiologic properties of rifampin are such that the antibiotic appears suitable for the treatment of urinary tract infections. However, its use alone for this indication is associated with an unacceptably high rate (approximately 30%) of acquisition of high-level resistance during therapy-an event that results in the failure of treatment. The combination of rifampin with another suitable antibiotic prevents this emergence of resistance. In vitro, pharmacokinetic, epidemiologic, and clinical studies with a combination of rifampin and trimethoprim (300 mg of rifampin: 80 mg of trimethoprim) both in England and in other countries have shown that this combination is effective and safe for the treatment of recurrent urinary tract infections. Provided that careful laboratory controls are used, the combination of rifampin and trimethoprim is a useful addition to the list of antibiotics available for the treatment of this condition.

Adult↗