Biomedical subjects
Publications and source records attributed to W Brumfitt.
We report five cases of continuous ambulatory peritoneal dialysis in which the mechanisms and sources of infection were established. We show how diligent enquiry and environmental investigation can explain the pathogenesis of infection and help in prevention by motivation of the patient.
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The evolution of the fluoroquinolones is described, and structure-activity relationships outlined. The in-vitro antimicrobial activities of ciprofloxacin, enoxacin, norfloxacin, ofloxacin and pefloxacin against a wide range of organisms are critically reviewed. In-vitro factors influencing fluoroquinolone activity are discussed. Reports of the acquisition of resistance to the fluoroquinolones are evaluated. Finally, possible future directions for this group of antibiotics are discussed.
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Eighty-eight female patients with a history of recurrent urinary tract infections were treated according to a randomization scheme with either 1 g of cephradine every 12 h (47 patients) or 375 mg of amoxicillin-clavulanate every 8 h (41 patients) for 7 days. The treatments were equally effective (cure rates of 89% for cephradine and 88% for amoxicillin-clavulanate) and showed similar relapse rates (cephradine, 14%; amoxicillin-clavulanate, 11%). Adverse effects were similar in both groups (cephradine, 23%; amoxicillin-clavulanate, 22%).
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The pH of urine samples from patients suffering symptoms suggesting urinary infection (e.g. dysuria, frequency, urgency) was measured while the patients were symptomatic and again when they had become asymptomatic. There was no correlation between the urine pH and the incidence or number of symptoms. No differences were observed between either the distribution or means of urine pH values in symptomatic and asymptomatic patients. There were also no significant differences in either symptomatology or urine pH between patients with significant bacteriuria and those without significant bacteriuria. These results cast doubt upon the traditional (but unproved) belief that alkalinizing the urine helps to reduce symptoms of dysuria and/or frequency, whether or not associated with urinary infection.
A clinical trial comparing 5 days' treatment with amoxycillin/clavulanate (group A) and a single dose of fosfomycin trometamol (group B) is presented. The study was done in symptomatic patients presenting to their family practitioner, with the microbiological testing being carried out in a university hospital laboratory. Of 62 patients with significant bacteriuria, 29 were given amoxycillin/clavulanate and 33 fosfomycin trometamol, in a randomized fashion. Cure rates 1 week and 5 weeks after the end of treatment were 72 and 65% in group A and 85 and 81% in group B. Adverse events assessed in 141 patients were unusual (10.1% in group A and 8.3% in group B) and were mild in nature. The results of this study suggest that single-dose treatment with fosfomycin trometamol is effective and acceptable as a conventional course of amoxycillin clavulanate for the treatment of simple acute dysuria and/or frequency with infection.
Strains of Staphylococcus aureus resistant to both methicillin and aminoglycosides (e.g. gentamicin) emerged during the late 1970s. They have now become established in hospitals throughout the world, and outbreaks of infection and colonization cause severe clinical and managerial problems. Therapeutic options are limited and clearance of the carrier state may be difficult. Much is known about the genetic and biochemical properties of the organisms but more work is necessary both to develop antibiotics active against these strains and to formulate effective measures for their control.
The authors have investigated the activity of ramoplanin against 162 isolates of MRSA from some twenty-six countries around the world. MICs were determined by the plate dilution method in isosensitest agar with an inoculum of 10(6) cfu. MBCs were measured by replication, using velvet pads, from MIC plates after 24 h incubation at 37 degrees C. Time-kill curves were determined from viable counts of cultures in Isosensitest broth (inoculum ca. 5.0 x 10(6) cfu/ml) taken at intervals during shaking culture at 37 degrees C for up to 24 h. Ciprofloxacin, mupirocin, rifampicin, teicoplanin and vancomycin were used as comparison compounds. The following MIC90 (MBC90) values (mg/l) were obtained against a selection of 60 strains: ciprofloxacin 0.8 (1.8), mupirocin 0.27 (19.0), ramoplanin 0.5 (1.0), rifampicin 0.007 (0.01), teicoplanin 1.2 (greater than 32) and vancomycin 2.2 (greater than 32.0). In time-kill experiments, ramoplanin at 20 mg/l and ciprofloxacin at 3.0 mg/l produced 99.9% killing in less than 4h. Mupirocin at 4.0 mg/l was only slowly bactericidal. No resistance was found to mupirocin, ramoplanin, teicoplanin or vancomycin in the 162 isolates tested, whereas ca. 20% resistance was found to ciprofloxacin and rifampicin. The absence of resistance, the high intrinsic activity and the rapid bactericidal effect of ramoplanin against this diverse group of MRSA are very encouraging, and suggest that clinical trials are indicated.
Material extracted from propolis (bee glue) by alkaline aqueous solvents or organic solvents showed weak inhibitory activity in vitro against certain species of Gram-positive bacteria. No antimicrobial activity was detected in urine from three volunteers who had taken 500 mg propolis three times a day for 3 days.
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Antibiotic resistance patterns were determined for 106 strains of methicillin-resistant Staphylococcus aureus (MRSA) from 21 countries. Resistance to gentamicin, tobramycin, netilmicin, amikacin, streptomycin, or erthromycin was recorded in more than 90% of strains. Resistance to the other compounds tested was as follows: tetracycline 86%, minocycline 76%, trimethoprim 69%, clindamycin 66%, neomycin 59%, chloramphenicol 39%, rifampicin 26%, fosfomycin 22%, ciprofloxacin 17%, fusidic acid 12%, bacitracin 2%, and novobiocin 1%. All the stains were sensitive to mupirocin, pristinamycin, ramoplanin, teicoplanin, and vancomycin. There were geographical patterns of resistance: MRSA from the UK and Australia were predominantly resistant to trimethoprim, whereas many strains from centres in Europe and the USA were sensitive. MRSA that were resistant to ciprofloxacin were of French and German origin. 15 strains, 12 of which came from France, Turkey, or Brazil, were resistant either to thirteen or to fourteen agents.
Sera from patients with primary biliary cirrhosis exhibit variable autoantibody reactivity against mitochondria, the commonest antigen (designated M2) including three structures of approximate M.W. 70, 50 and 40 kD. The nature of these antigens has only recently been established; the 70 and 50 kD are the transacetylase E2 and component X, respectively, of the pyruvate dehydrogenase complex and are distinct polypeptides. We have demonstrated, by immunoblotting, elution and rebinding of antibodies, unequivocal cross-reactivity between the major bands of the M2 antigen. In addition, cross-reactivity has been shown between antibodies binding to each of the three M2 bands of mitochondria and two major antigenic bands of both Gram-negative and Gram-positive bacteria. Conversely, antibodies eluted from these two bands of Escherichia coli were found to bind all three M2 bands of mitochondria. These results suggest that the antibodies of primary biliary cirrhosis contain both peptide-specific and cross-reacting antibodies, the latter recognizing a common "M2 epitope" that might include nonprotein components of the peptides. However, direct and competitive enzyme-linked immunosorbent assays failed to implicate the coenzyme of the pyruvate dehydrogenase complex, lipoic acid or its amide, as the common antigenic moiety.
A total of 112 Staphylococcus aureus strains resistant to methicillin and gentamicin were collected from 31 centres in 22 countries worldwide. Many strains were multi-resistant. In tests to determine the susceptibility of the organisms to ciprofloxacin 16 strains (14.3%), originating from France, the FRG, Israel and Italy, were shown to be resistant to this agent. To limit ciprofloxacin resistance, a reappraisal is necessary of fluoroquinolone usage against methicillin- and gentamicin-resistant Staphylococcus aureus.