Biomedical subjects

A S Beale

Publications and source records attributed to A S Beale.

29 records · Page 2Linked to original sources

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↗

PubMed1987

Response of Streptococcus pyogenes to therapy with amoxicillin or amoxicillin-clavulanic acid in a mouse model of mixed infection caused by Staphylococcus aureus and Streptococcus pyogenes.

The response of Streptococcus pyogenes to amoxicillin or amoxicillin-clavulanic acid (Augmentin; Beecham Group) therapy of a mixed streptococcal-staphylococcal infection was studied in a surgical wound in mice. A superficial wound was produced on the backs of anesthetized mice, and a suture infected with S. pyogenes, Staphylococcus aureus, or a mixed inoculum of both organisms was inserted. Oral therapy was started 4 h after infection and continued for 3 days. Both amoxicillin and amoxicillin-clavulanic acid were effective in eliminating the streptococci from the pure wound infection. In contrast, amoxicillin failed to eliminate the streptococci from a mixed infection in which a beta-lactamase-producing strain of S. aureus was also present, wound counts reaching 10(7) streptococci per wound by 80 h, whereas amoxicillin-clavulanic acid reduced the count to less than 33 streptococci per wound by 24 h. Numbers of S. aureus were also reduced by amoxicillin-clavulanic acid therapy, controlling the infection, whereas amoxicillin was ineffective. Also of significance was the fact that successful therapy was achieved with blood and tissue concentrations of amoxicillin and clavulanic acid of the same order as those measured in humans. These results show that amoxicillin therapy failed to eliminate S. pyogenes from a wound infection in the presence of a beta-lactamase-producing strain of S. aureus and suggest the potential of amoxicillin-clavulanic acid in the treatment of mixed bacterial skin infections involving beta-lactamase-producing organisms.

Amoxicillin↗

PubMed1986

Antibacterial effects of ticarcillin/clavulanic acid in animal models of infection.

The therapeutic effects produced by ticarcillin plus clavulanic acid were compared with those of ticarcillin and clavulanic acid separately against infections in the mouse caused by beta-lactamase-producing bacteria. The infections studied included a pneumonia model, a local tissue infection and pyelonephritis. The distribution of ticarcillin and clavulanic acid in infected animals was evaluated by measurement of the concentrations of the substances present at sites of infection. The results showed that both ticarcillin and clavulanic acid were well-distributed in the mouse and at the doses employed were present at the sites of infection at concentrations of the same order as those obtained in man after administration of ticarcillin/clavulanic acid formulations (Timentin). The protection of ticarcillin by clavulanic acid from inactivation by the beta-lactamases produced in vivo by Bacteroides fragilis, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa was demonstrated by the pronounced bactericidal effects produced by the ticarcillin/clavulanic acid combination against the ticarcillin-refractory infections studied.

Animals↗

PubMed1986

Bactericidal effects of ticarcillin-clavulanic acid against beta-lactamase-producing bacteria in vivo.

The comparative efficacies of ticarcillin and ticarcillin plus clavulanic acid have been determined in the mouse against experimental infections caused by ticarcillin-resistant bacteria. The infections studied comprised an intraperitoneal infection, local tissue infections, pyelonephritis, and pneumonia. Both ticarcillin and clavulanic acid penetrated readily to the sites of infection studied and at the doses employed were present at concentrations of the same order as those obtained in humans after the administration of ticarcillin-clavulanic acid formulations (Timentin; Beecham). At these concentrations, the ticarcillin-clavulanic acid combination caused significant bactericidal effects at the sites of infection against the ticarcillin-resistant strains of Bacteroides fragilis, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus investigated. The efficacy of ticarcillin plus clavulanic acid against the infections resistant to therapy with ticarcillin demonstrated the beta-lactamase-inhibitory activity of clavulanic acid in vivo.

Animals↗

PubMed1985

Antibacterial activity of ticarcillin in the presence of clavulanate potassium.

The antibacterial effects produced by ticarcillin disodium plus clavulanate potassium, a combination of the broad-spectrum penicillin ticarcillin, and the beta-lactamase inhibitor clavulanic acid as the potassium salt, have been measured in vitro and in experimental infection studies. The presence of clavulanic acid resulted in a significant enhancement of the activity of ticarcillin against a wide range of beta-lactamase-producing bacteria. These included ticarcillin-resistant strains of Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, P. vulgaris, Yersinia enterocolitica, and the anaerobe Bacteroides fragilis. In addition, beta-lactamase-producing isolates of Hemophilus influenzae, Branhamella catarrhalis, Neisseria gonorrhoeae, and Staphylococcus aureus were susceptible to ticarcillin and clavulanate. Clavulanic acid did not influence the activity of ticarcillin against ticarcillin-susceptible bacteria. The bactericidal effects of the antibiotic combination were measured in an in vitro kinetic model in which the drug concentrations were varied to simulate those measured in humans after intravenous dosing with ticarcillin (3.0 g) and clavulanate potassium (100 mg clavulanic acid). In these tests, ticarcillin plus clavulanic acid had pronounced bactericidal activity against ticarcillin-resistant bacteria. The protection of ticarcillin by clavulanic acid from inactivation by bacterial beta-lactamases in vivo was demonstrated in experimental infection models in which the efficacy of the ticarcillin plus clavulanic acid combination against infections caused by beta-lactamase-producing bacteria was correlated with the presence of effective concentrations of both antibiotic and inhibitor at the site of infection.

Animals↗

PubMed1985

Efficacy of topical mupirocin against an experimental Staphylococcus aureus surgical wound infection.

The efficacy of topically-applied mupirocin was evaluated against an experimental surgical staphylococcal wound infection in the guinea-pig. A suture impregnated with Staphylococcus aureus was inserted into a superficial wound, and topical therapy with mupirocin ointment was started 24 h after infection. In non-treated wounds, the bacterial counts increased to greater than 10(6) organisms/wound in the majority of animals at 24 h, remaining at this level for up to seven days. Therapy with placebo ointment (polyethylene glycol base) was ineffective, whereas twice daily application of mupirocin ointment resulted in elimination of the staphylococci. Mupirocin was as effective as topically-applied fusidic acid cream in reducing the bacterial counts of infected wounds.

Administration, Topical↗

PubMed1985

Studies with temocillin in a hamster model of antibiotic-associated colitis.

Hamsters given the new penicillin temocillin, either orally or by injection, did not develop antibiotic-associated colitis, whereas animals given the control antibiotics cefoxitin or clindamycin developed the disease, which is characterized by marked hemorrhagic cecitis and high cecal levels of Clostridium difficile cytotoxin.

Administration, Oral↗

PubMed1985

Studies with temocillin in the hamster model of antibiotic-associated colitis.

The studies reported here were designed to ascertain whether or not the new beta-lactam antibiotic, temocillin, would produce antibiotic-associated colitis in the hamster. The experiments were controlled with clindamycin and cefoxitin, which are known to induce antibiotic-associated colitis experimentally and clinically. All three antibiotics were administered to groups of animals both parenterally and orally. Clindamycin, at 1 mg/hamster, caused a slow onset of antibiotic-associated colitis by both routes, with death occurring at between 4 and 8 days. 80 to 100% of the animals had diarrhoea and showed signs of haemorrhage and caecal distension, with the caecal contents being Clostridium difficile toxin-positive. The onset of antibiotic-associated colitis after administration of cefoxitin was less marked at the 1 mg parenteral dose, with only 40% of the hamsters showing signs of colitis. At the higher doses of cefoxitin, colitis was more severe and the animals exhibited dramatic weight loss, with death occurring at between 3 and 5 days. The majority of animals had diarrhoea and were C. difficile toxin-positive; 60 to 80% also showed signs of haemorrhage and caecal distension. In contrast, the hamsters receiving temocillin remained healthy with no signs of diarrhoea, and showed consistent weight gain. No pathological abnormalities were observed and the caecal contents were toxin-negative. These results suggest that temocillin therapy in humans is unlikely to cause significant disturbance of the gastrointestinal flora.

Administration, Oral↗

PubMed1982

Distribution of amoxicillin and clavulanic acid in infected animals and efficacy against experimental infections.

The therapeutic effects produced by formulations of amoxicillin plus clavulanic acid (BRL 25 000A and BRL 25 000G) were compared with those of amoxicillin and clavulanic acid separately against a variety of infections produced by amoxicillin-susceptible and beta-lactamase-producing (amoxicillin-resistant) bacteria. The infection models studied included intraperitoneal infections, a mouse pneumonia, experimental pyelonephritis, and local lesions caused by Staphylococcus aureus and Bacteroides fragilis. The distribution of amoxicillin and clavulanic acid in infected animals after the administration of amoxicillin-clavulanic acid was evaluated by measurement of the concentrations of the substances present in specimens collected at the sites of infection. The results showed that both amoxicillin and clavulanic acid were well distributed in the animal body after the administration of amoxicillin-clavulanic acid formulations, being present in significant concentrations at various sites of infection, e.g., peritoneal washings, pleural fluid, pus, and infected tissue homogenates. In a number of cases, the amoxicillin concentrations measured after the administration of BRL 25000 were higher than those found after treatment with amoxicillin alone, presumably as a result of inhibition of bacterial beta-lactamases by clavulanic acid at the site of infection. The ability of clavulanic acid to protect amoxicillin in vivo was confirmed by the efficacy of amoxicillin-clavulanic acid formulations in the treatment of the infections studied, most of which were refractory to therapy with amoxicillin.

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↗