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Biomedical subjects

A S Beale

Publications and source records attributed to A S Beale.

At least 19 recordsLinked to original sources
PubMed1997

Does Chlamydia trachomatis MoPn enter a microbiologically-inapparent state during experimental infection of the mouse genital tract?

Microbiologically-inapparent chlamydial infection may contribute towards the immunopathogenesis of these diseases. Although morphologically and physiologically aberrant non-cultivable chlamydiae can be induced reversibly in cell culture, evidence for these forms in infections of animals and humans is indirect. A mouse model of salpingitis caused by the mouse pneumonitis biovar of Chlamydia trachomatis (MoPn) was used to determine the existence of non-cultivable organisms in vivo. Following intravaginal inoculation, mice yielded high chlamydial counts for 7-14 dyas, with a decline in culture-positivity by 21-28 days. A significant elevation of IFN gamma production in infected tissues was measured for 21 days and, from 28-70 days, all mice were culture-negative and developed characteristic hydrosalpinges. MoPn was detected by PCR in vaginal swabs of 80% and 69% respectively of culture-negative animals at 21 and 28 days. In a second study, 100%, 63% and 50% of culture-negative genital tissue homogenates were PCR-positive at 21, 28 and 42 days. Immunosuppression with either cyclophosphamide or hydrocortisone failed to regenerate cultivable chlamydiae. Tissues were disrupted by homogenization and inoculated intranasally to MF1 mice which are extremely susceptible to MoPn, but all culture-negative specimens were non-infectious. The significance of the PCR-positive culture-negative specimens requires further investigation, since these may represent a non-cultivable state in the deeper tissues of the mouse genital tract which may be beyond the reach of reactivating triggers.

Animals↗
PubMed1995

Relevance of Chlamydia pneumoniae murine pneumonitis model to evaluation of antimicrobial agents.

A mouse model of Chlamydia pneumoniae pneumonitis was established in outbred MF1 mice immunosuppressed with cyclophosphamide. Following intranasal inoculation with 2.2 x 10(3) inclusion-forming units of C. pneumoniae TW-183 per mouse, chlamydiae were culturable from the lungs for at least 29 days. Progressive subacute pneumonitis with perivascular and peribronchial lymphoid cell hyperplasia was observed, and C. pneumoniae organisms were located in consolidated areas of tissue by immunocytochemistry. Mice were treated orally, commencing at 8 days after infection, with clinically achievable concentrations of amoxicillin-clavulanate or ciprofloxacin (three times daily for 7 days), ofloxacin, doxycycline, or erythromycin (twice daily for 7 days), or azithromycin (once daily for 4 days). Despite disparate antichlamydial activity in cell culture and different pharmacokinetic properties in infected animals, all treatments reduced the chlamydial load in the lungs (P < 0.05) when the loads were evaluated by culture at 1 and 10 days after the cessation of dosing, and this was reflected in the histopathological and immunocytochemistry scores. There was no significant difference between these treatments, and C. pneumoniae TW-183 was eradicated from the majority but not from all mice. These results confirm the limited clinical data available to date. In conclusion, a range of oral antimicrobial agents commonly used for the treatment of community-acquired respiratory infection was found to be efficacious in this experimental model of C. pneumoniae pneumonitis, which may therefore be of utility in chemotherapy and follow-up studies.

Animals↗
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↗
PubMed1994

Characteristics of murine model of genital infection with Chlamydia trachomatis and effects of therapy with tetracyclines, amoxicillin-clavulanic acid, or azithromycin.

Following intravaginal inoculation of progesterone-treated outbred mice with Chlamydia trachomatis MoPn, 4 to 6 log10 inclusion-forming units were recovered in vaginal swabs for 21 days but all animals were culture negative after 28 days. Serum antibody titers were elevated and remained high for at least 70 days. Between 28 and 70 days, upper tract infection (inflammation and distension of the uterine horns, occlusion of oviducts with inflammatory exudate, pyosalpinx, and hydrosalpinx) was seen in > 80% of the animals. Mice were dosed orally, commencing at 7 days after infection, with minocycline, doxycycline, or amoxicillin-clavulanate. Further groups received azithromycin either as a single high dose or as lower once-daily doses. In addition, minocycline and amoxicillin-clavulanate were administered at 24 h after infection, and this early treatment prevented elevation of antibody titers whereas delayed therapy did not. Vaginal swabs from mice in all treatment regimens were culture negative except for 25% of mice receiving either early amoxicillin-clavulanate or low-dose azithromycin, which yielded low numbers (20 to 70 inclusion-forming units) of chlamydiae. Numbers of fertile mice in the early treatment regimens and their litter sizes were similar to those of noninfected controls, although 25% of amoxicillin-clavulanate-treated mice had unilateral hydrosalpinges. In comparison, 88% of untreated mice developed hydrosalpinges and only 25% conceived. Delayed dosing did not affect the outcome of amoxicillin-clavulanate therapy but did diminish the protective efficacy of minocycline such that 50% of treated mice had either unilateral hydrosalpinges or ovarian abscesses. Doxycycline and azithromycin were highly effective in restoring fertility. This model makes possible the study of both short- and long-term outcomes of chlamydial infection.

Amoxicillin↗
PubMed1991

Bactericidal effects of amoxycillin/clavulanic acid against a Legionella pneumophila pneumonia in the weanling rat.

Amoxycillin/clavulanic acid and clavulanic acid have been previously reported to demonstrate bactericidal activity in tissue culture studies against intracellular Legionella pneumophila. A rat model of legionellosis was therefore developed for the purpose of assessing the efficacy of these agents against L. pneumophila in vivo. Therapy by the subcutaneous route was started 12 h after infection when the majority of the bacteria observed in lavage fluid were residing in alveolar macrophages. Treatment with amoxycillin was ineffective in reducing the bacterial counts of L. pneumophila in lung homogenates whereas amoxycillin/clavulanic acid displayed bactericidal effects of the same order as the control antibiotic, erythromycin. Further in-vivo studies are planned to assess the clinical relevance of these findings.

Age Factors↗
PubMed1991

Comparative activities of amoxycillin, amoxycillin/clavulanic acid and tetracycline against Chlamydia trachomatis in cell culture and in an experimental mouse pneumonitis.

The activity of amoxycillin, amoxycillin/clavulanic acid and two tetracycline antibiotics was investigated against three strains of Chlamydia trachomatis in vitro. McCoy cells were infected and single doses of antibiotic administered 24 h after infection. The percentage of infected cells was calculated at intervals up to 72 h after infection. Amoxycillin and clavulanic acid, alone and in combination, reduced the incidence of inclusion formation of all three strains. Particularly good activity was observed against the laboratory-adapted strain C. trachomatis Sa2f and a clinical isolate C. trachomatis LB1, where a progressive reduction in numbers of inclusions was observed with time. Minocycline and oxytetracycline were the most active agents tested. In an experimental animal model, mice were inoculated intranasally with C. trachomatis MoPn (ATCC VR123) which caused a fatal pneumonia within 16 days, and treated orally for four days commencing at 24 h after infection. At doses producing clinically achievable serum concentrations, amoxycillin (10 mg/kg), amoxycillin/clavulanic acid (10 + 5 mg/kg) and minocycline (5 mg/kg) all protected the mice over a 21-day period. The majority of the animals treated with clavulanic acid alone (20 mg/kg) survived the infection. Treatment with oxytetracycline was less effective, a dose of 160 mg/kg being required to protect 70% of the mice. The results indicate that amoxycillin and amoxycillin/clavulanic acid were more effective against C. trachomatis MoPn in vivo than might be predicted from in-vitro data, suggesting that amoxycillin/clavulanic acid may have potential for the treatment of polymicrobial infections involving C. trachomatis.

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↗
PubMed1991

Bactericidal effects of ticarcillin-clavulanic acid against Legionella pneumophila pneumonia in immunocompromised weanling rats.

A model of acute Legionella pneumophila pneumonia in neutropenic weanling rats was developed as a means of assessing the efficacies in vivo of the beta-lactams ticarcillin, ticarcillin-clavulanic acid, and clavulanic acid, agents active against the organism in vitro. Weanling rats were dosed with cyclophosphamide 3 days before and immediately prior to infection by intrabronchial intubation with L. pneumophila. The bacteria persisted in the lungs of untreated animals at high counts (5.0 to 7.0 log10 CFU/g of lung tissue) for up to 168 h after infection, and the histological characteristics of the infection were similar to those of the disease in humans. Transmission electron micrography revealed the presence of L. pneumophila multiplying within alveolar macrophages. Therapy with ticarcillin was ineffective in reducing the bacterial numbers in the lung tissue, whereas ticarcillin-clavulanic acid and clavulanic acid were active, producing bactericidal effects similar to those of erythromycin. The ticarcillin-clavulanic acid combination was significantly more efficacious (P less than 0.01) than corresponding doses of clavulanic acid alone. Synergistic activity between ticarcillin and clavulanic acid against L. pneumophila has been demonstrated in vivo, and the combination showed activity similar to that of erythromycin.

Animals↗
PubMed1990

Influence of clavulanic acid on the activity of amoxicillin against an experimental Streptococcus pneumoniae-Staphylococcus aureus mixed respiratory infection.

An experimental respiratory infection caused by Streptococcus pneumoniae was established in weanling rats by intrabronchial instillation. Treatment of this infection with amoxicillin rapidly eliminated the pneumococci from the lung tissue. A beta-lactamase-producing strain of Staphylococcus aureus, when inoculated in a similar manner, did not persist adequately in the lungs long enough to permit a reasonable assessment of the therapy, but staphylococcal survival was extended in the lungs of rats infected 24 h previously with S. pneumoniae. Amoxicillin therapy was relatively ineffective against the pneumococci in this polymicrobial infection and had no effect on the growth of S. aureus. In contrast, amoxicillin-clavulanic acid eliminated the pneumococci from the lung tissue and brought about a reduction in the numbers of staphylococci. The data illustrate the utility of this model for the study of polymicrobial lung infections and demonstrate the role of amoxicillin-clavulanic acid in the treatment of polymicrobial infections involving beta-lactamase-producing bacteria.

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↗