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Biomedical subjects

W Brumfitt

Publications and source records attributed to W Brumfitt.

At least 19 recordsLinked to original sources

Comparison of the in-vitro activities of the topical antimicrobials azelaic acid, nitrofurazone, silver sulphadiazine and mupirocin against methicillin-resistant Staphylococcus aureus.

The in-vitro activities of the topical agents azelaic acid, nitrofurazone, silver sulphadiazine and mupirocin have been determined against 80 strains of MRSA collected from worldwide sources. MICs were determined by agar dilution (with an inoculum of approximately 5.0 x 10(5) cfu) in Iso-Sensitest agar, and MBCs were measured by replica-plating from MIC plates using velvet pads. The agents tested were uniformly active against MRSA, mupirocin being the most active (MIC50 0.15 mg/L) followed by nitrofurazone (MIC50 19 mg/L), silver sulphadiazine (MIC50 85 mg/L) and azelaic acid (MIC50 850 mg/L). Concentrations of azelaic acid, nitrofurazone and silver sulphadiazine close to the MIC were bactericidal, but mupirocin was only bactericidal at concentrations substantially greater than the MIC. In time-kill experiments, azelaic acid and nitrofurazone were gradually bactericidal, silver sulphadiazine was rapidly bactericidal and mupirocin was not bactericidal. Silver sulphadiazine killed sulphonamide-sensitive and sulphonamide-resistant strains equally rapidly. No resistant mutants were found to azelaic acid, nitrofurazone or silver sulphadiazine in an inoculum of 10(9) cfu, but two strains yielded (frequency: 1.0 x 10(-9)) mutants resistant to mupirocin. Our in-vitro results suggest azelaic acid, nitrofurazone and silver sulphadiazine could be of use for clearing staphylococcal carriage.

Anti-Bacterial Agents

In-vitro activity of RP 59500, a new semisynthetic streptogramin antibiotic, against gram-positive bacteria.

A study of the in-vitro activity of RP 59500, a semisynthetic derivative of pristinamycin, against a range of Gram-positive bacteria including erythromycin-resistant strains was undertaken. MICs were determined by plate dilution in IsoSensitest agar and MBCs by velvet pad replication. RP 59500 was found to have in-vitro activity almost identical to that of its parent compound, pristinamycin. Sixty methicillin-resistant Staphylococcus aureus (MRSA) and 60 methicillin-sensitive S. aureus (MSSA) were found to be sensitive to RP 59500, with MICs of 0.13-1 mg/L. All the MSSA and most MRSA showed an MBC less than 2 mg/L. Erythromycin-resistant S. aureus (62) were as sensitive to RP 59500 as were erythromycin-sensitive strains (58). RP 59500 was more active against MRSA than fusidate, vancomycin, amikacin, ciprofloxacin, imipenem or erythromycin. Forty strains of coagulase-negative staphylococci (11 were erythromycin-resistant) showed MICs of 0.25-1 mg/L, and RP 59500 was more active than methicillin, erythromycin, imipenem, cefotaxime or vancomycin. Sixty strains of streptococci (20 pneumococci and 40 of groups A, B, C, or G) and 20 enterococci were inhibited by 0.13-1 mg/L and 0.25-4 mg/L, respectively. Gram-positive bacilli (five each of diphtheroids, lactobacilli, Listeria monocytogenes and Bacillus spp., and 19 Clostridium spp.) were also sensitive, with MICs of between 0.06 and 4 mg/L. All 279 strains tested were judged to be sensitive to RP 59500, which was bactericidal and showed a small inoculum effect. The activity against MRSA, and against erythromycin-resistant strains of all species was particularly interesting.

Erythromycin

Differing prognostic significance of reinfection and relapse in CAPD peritonitis.

All episodes of recurrent infection in a CAPD unit over a 26-month period have been analysed to discover whether relapse and reinfection have different prognostic importance. Relapse and reinfection were distinguished by detailed microbiological investigation. Prognosis was expressed in terms of outcome of treatment and the fate of the Tenckhoff catheter. Twenty-nine patients suffered recurrent infections (i.e. more than one infection during a 12-month period). Nine (6 male, 3 female, age range 42-73 years) had relapses, and 20 (16 male, 4 female, age range 42-74 years) reinfections. The characteristics of the two groups of patients were indistinguishable. Relapse was of graver prognostic consequence: patients who relapsed were significantly less likely to respond to antibiotic treatment (78% versus 20%) and have to have their catheters removed (78% versus 10%) than those with reinfections. Thus it is important to differentiate relapse from reinfection in CAPD peritonitis. In addition to being helpful for the management of individual patients, this is essential if results of therapeutic trials are to be interpreted correctly.

Adult

Comparative trials of cefaclor AF in uncomplicated cystitis and asymptomatic bacteriuria.

Two different doses of cefaclor advanced formulation (AF), a new sustained-release formulation of cefaclor, were compared with the regular formulation of cefaclor for efficacy and safety in the treatment of uncomplicated cystitis and asymptomatic bacteriuria. A 7-day course of treatment was used, and the trials were double-dummy and double-blind. In one trial, cefaclor AF 500 mg once daily (at night) was compared with cefaclor 250 mg three times a day. Satisfactory clinical and bacteriological responses were found in 179/189 (94.7%) and 160/191 (83.8%) patients, respectively, given cefaclor AF and in 82/87 (94.3%) and 74/90 (82.2%) patients given cefaclor, 5-9 days after the end of treatment. In the other trial, cefaclor AF 375 mg twice daily was compared with cefaclor 250 mg three times a day. Satisfactory clinical and bacteriological responses were obtained in 164/180 (91.1%) and 156/184 (84.8%) patients, respectively, given cefaclor AF, and in 86/92 (93.5%) and 81/93 (87.1%) patients taking cefaclor, 5-9 days after the end of treatment. Very similar results were found in both studies in those patients who were assessable 3-5 weeks later. Only 4.3% and 2.4% of patients treated with cefaclor AF (375 mg and 500 mg, respectively) and 2.2% of cefaclor patients discontinued therapy due to adverse events. The three most commonly reported events were vaginal moniliasis or vaginitis (8.6%), headache (5.0%) and nausea (4.8%). No significant differences were found between clinical efficacy and safety parameters in the different study groups, and it was concluded that cefaclor AF in a twice-daily or once-daily dosage is as effective and as safe as the currently recommened three-times-a-day dosage of cefaclor.

Adolescent

In-vitro activity of daptomycin against a worldwide collection of methicillin-resistant Staphylococcus aureus.

Minimum inhibitory and minimum bactericidal concentrations (MIC and MBC) of daptomycin and of vancomycin have been compared against 80 strains of methicillin-resistant Staphylococcus aureus isolated from many parts of the world. In the presence of 30 mg/l of Ca++, daptomycin at 4 mg/l killed all the strains tested, and was only slightly less active than vancomycin.

Anti-Bacterial Agents

Comparative efficacy and tolerability of cephradine and cefuroxime axetil in the treatment of acute dysuria and/or frequency in general practice.

One hundred and thirteen patients with dysuria and/or frequency were treated randomly with either 500 mg cephradine 12-hourly or 125 mg cefuroxime axetil 12-hourly, for seven days. A total of 71 patients were found to have urinary infection: bacteriological cure rates were 97% one week post-treatment, and 96% five weeks post-treatment, for both antibiotics. On direct questioning, adverse events were reported by eight patients out of 59 taking cephradine and by three of 54 who had received cefuroxime axetil. However, only three and one respectively stopped taking the antibiotic due to the adverse event. Analysis of diary cards, completed by 109 patients, showed a significantly higher incidence of increased frequency of bowel movements in those taking cefuroxime axetil. It is concluded that both antibiotics are of equal value in the treatment of simple acute urinary infections in general practice.

Adolescent

Cefaclor as a prophylactic agent for recurrent urinary infections: a comparative trial with macrocrystalline nitrofurantoin.

Eighty women with recurrent urinary infections (a median of seven episodes per year) were randomized to twelve months prophylaxis with cefaclor 250 mg or macrocrystalline nitrofurantoin 50 mg, at night. Seventy-three patients (37 given cefaclor and 36 given macrocrystalline nitrofurantoin) were assessable for efficacy. The incidence of radiological abnormalities in the two treatment groups was 23% and 30% respectively. Ninety-five percent of the patients taking cefaclor were symptomatically improved during the twelve months of prophylaxis and 86% remained abacteriuric; corresponding figures in the group taking macrocrystalline nitrofurantoin were 86% and 85% respectively. There were 88 breakthrough infections in patients taking cefaclor (6 resistant strains), and 9 in those patients taking macrocrystalline nitrofurantoin (6 by resistant strains). The mean interval between symptomatic episodes on prophylactic therapy increased by 5.6-fold in patients taking cefaclor, and 4.3-fold in those taking macrocrystalline nitrofurantoin. Resistant coliforms were found in only 3 out of 37 patients studied after twelve months prophylaxis; these organisms did not proceed to cause infections. All 80 patients were assessable for adverse events: 5 out of 39 taking cefaclor (12.8%) reported an event "probably" associated with the antibiotic, and 3 (7.7%) stopped taking the drug for various reasons; corresponding figures for macrocrystalline nitrofurantoin were 17.1% and 9.8% respectively. Patients with a radiological abnormality responded well to long-term low-dose prophylaxis with either agent. Cefaclor seems to offer an alternative to macrocrystalline nitrofurantoin for the prophylaxis of recurrent urinary infections in women.

Adult

Pre-opsonisation of Escherichia coli induces resistance to neutrophil killing in serum and urine: relationship to growth phase.

Tests of phagocytosis and killing by polymorphonuclear neutrophil leucocytes (PMNL) are usually done with pre-opsonised organisms. Phagocytosis of 11 strains of Escherichia coli, pre-opsonised, and in the stationary phase, resulted in the killing of only one strain although all the organisms were phagocytosed. However, when the same strains were added unopsonised to a PMNL-serum mixture, eight were killed after phagocytosis. With two of these strains, the amount of killing was inversely proportional to the time of pre-oposonisation. E. coli incubated for 30 min in dilute peptone water in Hanks's Balanced Salts Solution before phagocytosis also became resistant to killing; bacterial division did not occur during this period. Experiments with bacteria in urine confirmed these findings and showed that E. coli exposed to serum or urine before phagocytosis became resistant to killing by PMNL. E. coli rapidly changes its sensitivity to phagolysosome killing during transition from stationary to lag phase in a nutrient medium. This resistance is retained through the exponential phase but is lost during the stationary phase. The killing of Pseudomonas, Enterobacter, and Acinetobacter by PMNL was unaffected by varying the method of opsonisation or the phase of growth. If this phenomenon occurs in vivo it may affect the outcome of infections caused by strains of E. coli that survive killing by PMNL.

Blood Bactericidal Activity

Differing activities of quinolones against ciprofloxacin-susceptible and ciprofloxacin-resistant, methicillin-resistant Staphylococcus aureus.

The in vitro activities of nine quinolones (seven fluoroquinolones, nalidixic acid, and acrosoxacin) against methicillin-resistant Staphylococcus aureus (MRSA) were compared with those of the glycopeptides teicoplanin and vancomycin. MICs against 160 strains of ciprofloxacin-susceptible (MIC, less than 2.0 micrograms/ml) MRSA and 40 strains of ciprofloxacin-resistant (MIC, greater than or equal to 2.0 micrograms/ml) MRSA were determined. The following MICs for 50% of the strains tested (in micrograms per milliliter) were obtained for ciprofloxacin-susceptible and -resistant strains, respectively: tosufloxacin, 0.06 and 2.0; ofloxacin, 0.25 and 16; ciprofloxacin, 0.5 and 16; pefloxacin, 0.5 and 32; acrosoxacin, 1.0 and greater than 256; enoxacin, 1.0 and 64; fleroxacin, 1.0 and 32; norfloxacin, 2.0 and 64; nalidixic acid, 64 and 512; teicoplanin, 1.0 and 1.0; vancomycin, 2.0 and 2.0. In mutation rate studies using a range of antibiotic concentrations to reflect those achievable in vivo, resistant mutants grew only on plates containing nalidixic acid (rate of mutation to resistance, 10(-7) to 10(-8) and on plates containing low concentrations of ciprofloxacin, enoxacin, and norfloxacin (rate of mutation to resistance, 10(-8) to 10(-9). In time-kill studies, 99.9% killing was found within 8 h for all of the quinolones tested (norfloxacin and nalidixic acid were not tested). Teicoplanin and vancomycin were less rapidly bactericidal. For the clinical isolates of ciprofloxacin-resistant MRSA, different levels and patterns of quinolone resistance were found. Generally, cross-resistance among the fluoroquinolones was complete; however, incomplete cross-resistance did occur with the nonfluorinated quinolone acrosoxacin.

Anti-Bacterial Agents

Comparative trial of norfloxacin and macrocrystalline nitrofurantoin (Macrodantin) in the prophylaxis of recurrent urinary tract infection in women.

Eighty-eight women with a history of recurrent urinary tract infection (at least four attacks in the preceding 12 months) were randomized to take either norfloxacin 200 mg at night (45 patients) or macrocrystalline nitrofurantoin 100 mg at night (43 patients) for 12 months. A decrease in the number of symptomatic attacks while taking this prophylaxis was observed in 94 per cent of the patients and this improvement was maintained during the 6 months following the end of prophylaxis in 69 per cent. The mean interval between symptomatic episodes while taking prophylaxis was 7.2-fold and 6.9-fold greater, respectively, than in the 12 months before starting prophylaxis. There were only nine breakthrough infections during 74 patient-years of prophylaxis, four in patients taking norfloxacin (two enterococci, one Staphylococcus epidermidis, one Escherichia coli), and five in those taking macrocrystalline nitrofurantoin (four E. coli, one Klebsiella pneumoniae). Adverse events caused four patients taking norfloxacin (8 per cent) and seven taking macrocrystalline nitrofurantoin (14 per cent) to stop prophylaxis. Norfloxacin had a marked suppressive effect on the coliform part of the faecal flora, with no emergence of resistance. Thus, norfloxacin appears to be an excellent alternative agent to macrocrystalline nitrofurantoin for the prevention of recurrent urinary infections.

Adolescent

Comparative in vitro activity of cefixime, cefaclor and loracarbef against urinary pathogens.

Minimum inhibitory concentrations of cefixime, cefaclor and loracarbef have been determined against 200 strains of bacteria, representing a wide selection of species causing urinary infections. Cefixime was poorly active against Gram-positive species, but was active (MIC90 less than 2 mg/l) against almost all the Gram-negative pathogens tested (except Pseudomonas aeruginosa), and particularly so against Klebsiella pneumoniae and members of the tribe Proteae. Cefaclor and loracarbef were more active against the Gram-positive species than was cefixime, but had a less broad spectrum against the Gram-negative species. Cefixime use seems more appropriate in nosocomial than in domiciliary urinary infections.

Anti-Infective Agents, Urinary

Urinary infection in the 1990's: the state of the art.

Growing points and problem areas in the field of urinary tract infections are critically surveyed. It is concluded that there is a particular need for advances in rapid tests for bacteriuria (to distinguish between symptomatic patients who are infected and those who are not) and for the determination of antibiotic sensitivity of infecting organisms. The aetiology of the "urethral syndrome" (dysuria and/or frequency without a significant bacteriuria) is still obscure although it is becoming clear what suggested possible causes are not responsible for it. Another unresolved problem is whether or not to treat asymptomatic bacteriuria in all groups of patients especially the elderly, and in the absence of pyuria. Similarly it is still not decided what are the optimal lengths of time and dosages of antibiotics to treat various types of urinary infections. Finally, difficulties involved in preventing infections of in-dwelling catheters, and the possibility of obtaining a protective vaccine are discussed.

Anti-Infective Agents, Urinary