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- Hjerdt-Goscinski, Gunilla, 1942-
(author)
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Antibiotic-induced Bacterial Toxin Release – Inhibition by Protein Synthesis Inhibitors
- 2004
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Doctoral thesis (other academic/artistic)abstract
- Toxic products, such as endotoxin from the gram-negative and exotoxin from the gram-positive bacteria, are the most important initiators of the inflammatory host response in sepsis. In addition to antibacterial treatment, numerous attempts have been made to interfere with the exaggerated proinflammatory cascade initiated by the toxins. As most antitoxic and anti-inflammatory agents have shown no clear efficacy, an attractive alternative has been to prevent or minimise their release. Therefore, it was of interest to further study the antibiotic-induced release of toxins after exposure to antibiotics used for the treatment of the most severe infections, especially if protein synthesis inhibitors could reduce the release induced by PBP 3-specific β-lactam antibiotics.There were significant reductions in endotoxin release from gram-negative bacteria when the combination of the PBP 3-specific β-lactam antibiotic, cefuroxime, and the protein synthesis inhibitor, tobramycin, was compared with cefuroxime alone. Increasing doses of tobramycin reduced endotoxin release and increased the killing rate. In a kinetic in vitro model the endotoxin release from E.coli was higher after the second dose of cefuroxime. Nevertheless, it was reduced after addition of tobramycin.No binding of tobramycin to endotoxin was observed, either in vivo or in vitro. In a porcine sepsis model, a possible anti-inflammatory effect of ceftazidime and tobramycin, expressed as late cytokine inhibition, was seen.The protein synthesis inhibitor, clindamycin, released less streptococcal pyrogenic exotoxin A (SpeA) from a group A streptococcus strain than penicillin, and addition of clindamycin to penicillin resulted in less toxin production than penicillin alone. The SpeA production was dependent on the bacterial number at the start of treatment. Higher doses of penicillin also led to less SpeA. The choice of antibiotic class and dose may be important in the severely ill septic patient in whom an additional toxin release could be deleterious. A combination of a β-lactam antibiotic and a protein synthesis inhibitor seems beneficial but further investigations are needed.
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| 2. |
- Nyhlén, Anna, et al.
(author)
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Bactericidal Effect of Combinations of Antibiotic and Antineoplastic Agents against Staphylococcus aureus and Escherichia coli.
- 2002
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In: Chemotherapy. - : S. Karger AG. - 0009-3157 .- 1421-9794. ; 48:2, s. 71-77
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Journal article (peer-reviewed)abstract
- Background: The bactericidal effect of some antibiotic and antineoplastic agents commonly used in clinical practice was investigated to analyse whether the combinations act synergistically, have indifferent or antagonistic antibacterial effects compared to the effect of the antibiotics alone. Methods: The rate of killing of meropenem, ceftazidime and tobramycin was studied against six different strains of Staphylococcus aureus and Escherichia coli, and the results were compared to the rate of killing of the antibiotics in combination with the cytostatic drugs doxorubicin, etoposide and 5-fluorouracil (5-FU). Results: Tobramycin showed synergy against two strains of S. aureus after 3 h in the presence of 5-FU and against one strain of S. aureus in the presence of doxorubicin. Meropenem induced an antagonistic bactericidal effect against one isolate of S. aureus after 24 h. Ceftazidime expressed an indifferent bactericidal effect together with the cytostatic agents. The antineoplastic agents had no impact on the bacterial killing of any of the antibiotics against E. coli. Conclusions: Tobramycin expressed a significantly better bactericidal effect against S. aureus after 3 h in the presence of doxorubicin and 5-FU than tobramycin alone. Meropenem expressed antagonism against one clinical strain of S. aureus, but the cytostatic drugs did not affect the killing of other strains tested. Ceftazidime expressed indifferent bactericidal activity together with the antineoplastic agents.
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| 3. |
- Nyhlén, Anna, et al.
(author)
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Impact of combinations of antineoplastic drugs on intestinal microflora in 9 patients with leukaemia.
- 2002
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In: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 1651-1980 .- 0036-5548. ; 34:1, s. 17-21
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Journal article (peer-reviewed)abstract
- The impact of antineoplastic drugs on the intestinal microflora was studied in 9 patients with acute leukaemia during chemotherapy and in 5 patients also during chemotherapy-induced neutropenia. Quantitative and qualitative microbiological analyses of faecal samples obtained before and during chemotherapy showed significantly increased counts of Bacteroides spp. in 3/9 patients and, during neutropenia, significantly increased counts of yeasts in 2/5 patients; however, the intestinal microflora was stable in most patients.
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| 4. |
- Nyhlén, Anna, et al.
(author)
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Postantibiotic effect of meropenem and ciprofloxacin in the presence of 5-fluorouracil
- 2002
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In: Chemotherapy. - 0009-3157. ; 48:4, s. 182-188
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Journal article (peer-reviewed)abstract
- Background: The postantibiotic effect (PAE) of meropenem and ciprofloxacin was studied in the presence of the antineoplastic agent 5-fluorouracil (5-FU). The purpose of the study was to investigate whether the PAEs of the combinations differed from the PAEs of the antibiotics alone. Methods: The PAEs of the combinations of 5-FU plus meropenem or ciprofloxacin were determined with viable counts against four reference strains of Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, Escherichia coli and two clinical isolates of S. epidermidis. The results were compared with the PAEs of the antibiotics drugs and 5-FU alone. The gram-positive strains were tested for slime production, both alone and in the presence of 5-FU. Results: Against two of the three tested strains of S. epidermidis, the combination of ciprofloxacin and 5-FU gave a synergistic prolongation of the PAE in comparison with the PAEs induced by the drugs alone. The combinations showed indifference against the other bacteria. The combination of meropenem and 5-FU had a synergistic PAE against one of the three tested strains of S. epidermidis and an additive effect against E coli but showed indifference against the rest of the strains. Conclusions:The presence of 5-FU did not influence the PAEs of the antibiotics against most of the tested strains, but caused a synergistic prolongation of the PAEs induced by ciprofloxacin and meropenem against some of the tested strains of S. epidermidis. 5-FU inhibited slime production in the same S. epidermidis strains, which might have contributed to the longer PAE.
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