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Biomedical subjects

J Gisby

Publications and source records attributed to J Gisby.

11 recordsLinked to original sources
PubMed2000

Efficacy of a new cream formulation of mupirocin: comparison with oral and topical agents in experimental skin infections.

A new cream formulation of mupirocin developed to improve patient compliance was compared with systemic and topical antibiotics commonly used to treat primary and secondary skin infections. A mouse surgical wound model infected with Staphylococcus aureus or Streptococcus pyogenes was used. Topical treatment was applied at 4 and 10 h postinfection or oral treatment at a clinically relevant dose was administered 4, 8, and 12 h postinfection; treatments were continued three times daily for a further 3 days. Mupirocin cream was significantly more effective than (P < 0.01; two of eight studies) or not significantly different from (six of eight studies) mupirocin ointment in reducing bacterial numbers. Mupirocin cream was similar in efficacy to oral flucloxacillin but significantly more effective (P < 0.001) than oral erythromycin. It was also similar in efficacy to cephalexin against S. pyogenes but superior against S. aureus (P < 0.01). Mupirocin cream had a similar efficacy to fusidic acid cream against S. aureus but was significantly superior against S. pyogenes (P < 0.01). A hamster impetigo model infected with S. aureus was also used. Topical or oral treatment was administered at 24 and 30 h postinfection (also 36 h postinfection for oral therapy) and then three times daily for a further 2 days. On day 5, mupirocin cream was significantly more effective than mupirocin ointment in one study (P < 0.01) and of similar efficacy in the other two studies. Mupirocin cream was not significantly different from fusidic acid cream or neomycin-bacitracin cream, but it was significantly superior (P < 0.01) to oral erythromycin and cephalexin. Mupirocin cream was as effective as, or superior to, oral and other topical agents commonly used for skin infections.

Administration, Oral↗
PubMed1995

Evaluation of mupirocin E-test for determination of isolate susceptibility: comparison with standard agar dilution techniques.

Mupirocin E-test strips have been evaluated for their ease of use and accuracy in determining the susceptibilities of 171 strains of Staphylococcus spp., Streptococcus spp., Haemophilus influenzae, and Moraxella catarrhalis. The susceptibility of each strain was determined on two occasions, using parallel E-test and agar dilution methodologies each time. To ensure similar precisions for statistical analyses, E-test MICs were rounded up to a standard twofold agar dilution scale. Clear, elliptical zones were obtained against Staphylococcus spp. M. catarrhalis also gave clear zones, but the scale intercept was often difficult to interpret because of the irregular shape of the inhibition zone. Poor growth sometimes resulted in less-distinct zones of inhibition against Streptococcus spp. and H. influenzae. Excellent correlation was observed between the the E-test and agar dilution against Staphylococcus spp. and H. influenzae, with > 95% of the E-test values falling within one log2 dilution of the corresponding agar MIC. The correlation was lower for Streptococcus spp. and M. catarrhalis, with 86 and 83%, respectively, of E-test results falling within one log2 dilution of the agar MIC. When E-test MICs did not agree exactly with the corresponding agar MIC against Staphylococcus spp. or Streptococcus spp., there was a tendency for the E-test to give a lower MIC. This bias has little effect upon individual MICs in staphylococci or in the generation of susceptibility interpretation errors ( < 1.5% overall), but it could reduce population geometric mean MICs by factors of 0.78 to 0.83. This effect was more marked for Streptococcus spp., reducing the population mean by a factor of 0.73 and resulting in 0.7% major and 8% very major errors. In contrast, the E-test tended to give higher MICs against M. catarrhalis, resulting in 7.3% major errors and increasing the population geometric mean MIC by a factor of 1.60.

Anti-Bacterial Agents↗
PubMed1994

Staphylococcal osteomyelitis--a comparison of co-amoxiclav with clindamycin and flucloxacillin in an experimental rat model.

A rat model of Staphylococcus aureus osteomyelitis was used to compare treatment with co-amoxiclav, flucloxacillin and clindamycin. Co-amoxiclav (amoxycillin/clavulanic acid 200/50 mg/kg), flucloxacillin (200 mg/kg) and clindamycin (50 mg/kg) were injected subcutaneously tds for 28 days, commencing 14 days after infection. Eight days after cessation of treatment, high numbers of staphylococci were recovered from the infected tibiae of all control rats. All treatments, at clinically achievable concentrations, significantly (P < 0.05) reduced the bone bacterial titres. However, 50% of tibiae from co-amoxiclav-treated animals were sterile, compared with 17% and 25% from flucloxacillin- or clindamycin-treated animals respectively. Histopathological examination of tibiae reflected the bacteriological results, and showed that the severity of the osteomyelitis was greatly reduced in antibiotic-treated animals compared with non-treated controls. Twenty-eight days after cessation of therapy, bacterial counts from co-amoxiclav and clindamycin-treated animals remained significantly (P < 0.05) lower than those of non-treated controls, although the gross and microscopic appearance of clindamycin and flucloxacillin-treated tibiae suggested that recrudescence of the infection may have occurred. The results of this study demonstrated that co-amoxiclav was as effective as flucloxacillin and clindamycin in the treatment of an experimental chronic staphylococcal osteomyelitis.

Amoxicillin↗
PubMed1991

Comparative efficacies of ciprofloxacin, amoxicillin, amoxicillin-clavulanic acid, and cefaclor against experimental Streptococcus pneumoniae respiratory infections in mice.

Experimental respiratory infections were established in mice by intranasal inoculation of Streptococcus pneumoniae. Inoculation of 10(7) CFU of either S. pneumoniae 1629 or S. pneumoniae 7 produced a fatal pneumonia in nontreated mice 2 to 3 days after infection. Oral therapy was commenced 1 h after infection and was continued three times a day for 2 days. The doses used in mice produced peak concentrations in serum and lung tissue similar to those measured in humans. Ciprofloxacin failed to eliminate either strain of pneumococcus from mouse lungs at any of the doses tested (40, 80, or 160 mg/kg of body weight) by the end of therapy (33 h). Mice that received ciprofloxacin at 160 mg/kg were clear of S. pneumoniae 7 5 days later, whereas persistence and regrowth of S. pneumoniae 1629 resulted in the death of 20% of animals treated with ciprofloxacin. Therapy with cefaclor (20 mg/kg) produced an effect similar to that of ciprofloxacin. In contrast, amoxicillin (10 and 20 mg/kg) and amoxicillin-clavulanic acid (10/5 and 20/10 mg/kg) were significantly (P less than 0.05) more effective in eliminating both strains of S. pneumoniae from the lungs by the end of therapy and, by 168 h, had prevented mortality in 80 to 100% of treated animals. The efficacy of ciprofloxacin against these experimental pneumococcal respiratory infections was poor, despite good penetration into lung tissue, and is a reflection of the low in vitro activity of the quinolone against S. pneumoniae, one of the most common pathogens in community-acquired pneumonia.

Amoxicillin↗
PubMed1989

Inactivation of cefuroxime and cefotaxime by Bacteroides fragilis in vitro, and its influence on the treatment of an experimental Escherichia coli/Bacteroides fragilis mixed infection.

The activity of amoxycillin/clavulanic acid was compared with that of cefuroxime and cefotaxime, alone and combined with metronidazole, in preventing the development of infections in the mouse caused by subcutaneous injection of a beta-lactamase-producing strain, Escherichia coli E96, or a mixed inoculum of E. coli E96 and Bacteroides fragilis VPI 8908. Amoxycillin/clavulanic acid, cefuroxime and cefotaxime were equally efficacious in preventing development of the E. coli E96 monoinfection at clinically achievable concentrations. However, the activity of cefuroxime against E. coli E96 in the mixed infection was markedly reduced as was, to a lesser extent, that of cefotaxime. Co-administration of metronidazole improved slightly the activity of cefuroxime against E. coli E96 in the mixed infection, but had no such enhancing effect on cefotaxime. In contrast, amoxycillin/clavulanic acid effectively prevented development of the mixed infection in all treated mice. Results of in-vitro studies showed that cefuroxime and cefotaxime were stable in a culture of E. coli E96, and were rapidly bactericidal against this strain. In contrast, both cephalosporins were hydrolysed in a mixed culture of E. coli E96/Bact. fragilis VPI 8908, which resulted in diminished bactericidal activity, particularly of cefuroxime, which was not restored by addition of metronidazole. Amoxycillin/clavulanic acid was stable in the mixed culture and caused a significant reduction in numbers of both organisms. These in-vitro data explain the findings of the in-vivo studies, and establish that the beta-lactamase activity of Bact. fragilis VPI 8908 was responsible for the diminished activity of cefuroxime and cefotaxime, combined with metronidazole, against a mixed E. coli/Bact. fragilis infection.

Amoxicillin↗
PubMed1988

Efficacy of amoxycillin/clavulanic acid in experimental Bacteroides fragilis/Escherichia coli mixed infections.

The efficacy of amoxycillin/clavulanic acid was compared with those of metronidazole, cefuroxime, metronidazole/ampicillin, metronidazole/gentamicin and metronidazole/cefuroxime, in experimental mixed infections produced in mice by subcutaneous inoculation of amoxycillin-resistant strains of Bacteroides fragilis and Escherichia coli. The combination of metronidazole/ampicillin failed to inhibit the growth of E. coli, and exerted only a transient effect on the numbers of Bact. fragilis in the groin abscesses. In contrast, amoxycillin/clavulanic acid prevented the development of the infection, eliminating both organisms. Metronidazole and cefuroxime, alone and in combination, were less effective than amoxycillin/clavulanic acid in inhibiting the growth of the infecting organisms. These results demonstrate the clinical potential of amoxycillin/clavulanic acid in prophylaxis, or in the therapy of mixed aerobe/anaerobe infections.

Amoxicillin↗
PubMed1988

Comparative efficacies of amoxicillin-clavulanic acid and ampicillin-sulbactam against experimental Bacteroides fragilis-Escherichia coli mixed infections.

Amoxicillin-clavulanic acid was compared with ampicillin-sulbactam in preventing the development of mixed infections produced in mice by subcutaneous inoculation of amoxicillin-resistant strains of Bacteroides fragilis and Escherichia coli. At doses designed to produce concentrations in mouse plasma similar to those obtained in humans, both amoxicillin-clavulanic acid and ampicillin-sulbactam were effective in preventing an infection caused by B. fragilis VPI 8908 mixed with E. coli E96, both strains being susceptible in vitro to each combination. However, ampicillin-sulbactam failed to arrest the progression of infections involving a more potent beta-lactamase-producing strain, E. coli 41548, even when a comparatively low inoculum was tested. In contrast, amoxicillin-clavulanic acid therapy effectively reduced the bacterial numbers at the site of infection. These data illustrate the need to treat polymicrobial infections with agents effective against the responsible aerobic as well as anaerobic bacteria.

Amoxicillin↗
PubMedDate not supplied

Comparative efficacies of ticarcillin, ticarcillin/clavulanic acid, piperacillin and cefoxitin against polymicrobial infections in mice caused by Escherichia coli and Bacteroides fragilis.

A model of localised abscess formation was used to establish mixed infections caused by Escherichia coli and Bacteroides fragilis. The beta-lactamase producing, ticarcillin-resistant strains E. coli E96 and B. fragilis VPI 8708 were used to produce one infection, and in another infection, a beta-lactamase hyperproducing strain E. coli 41548 was combined with a ticarcillin-susceptible strain, B. fragilis B3. Treatment, at doses producing clinically achievable concentrations in mouse serum, began 1 h after inoculation, and continued three times daily for four days. Bacterial numbers in infected tissue were measured at intervals. Against both infections, ticarcillin was ineffective in preventing bacterial growth and abscess formation in all mice. Piperacillin prevented abscess formation in 60% of the mice infected with E. coli E96/B. fragilis VPI 8708, and in 40% of those in the E. coli 41548/B. fragilis B3 group. Therapy with ticarcillin/clavulanic acid or cefoxitin reduced the number of both organisms at the site of infection, and thus prevented abscess formation in 100% treated animals.

Abscess↗