Interactions of beta-lactam antibiotics and antineoplastic agents

Ueda, Yusuke; Saito, Atushi; Fukuoka, Yoshikazu; Yamashiro, Yoshiko; Ikeda, Yoshito; Taki, Hideo; Yasuda, Takashi; Saikawa, Isamu

doi:10.1128/aac.23.3.374

Cited by 22 publications

(10 citation statements)

References 7 publications

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“…Synergy between 5-FU and cephalosporins has been noticed against gram-negative bacteria in studies using the checkerboard dilution method and determinations of fractional inhibitory concentrations [23,24]. In the present study, ceftazidime showed an indifferent bactericidal effect in combination with the tested antineoplastic agents.…”

Section: Discussionmentioning

confidence: 63%

Bactericidal Effect of Combinations of Antibiotic and Antineoplastic Agents against Staphylococcus aureus and Escherichia coli

Nyhlén¹,

Ljungberg²,

Nilsson-Ehle³

et al. 2002

Chemotherapy

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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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Section: Discussionmentioning

confidence: 63%

Bactericidal Effect of Combinations of Antibiotic and Antineoplastic Agents against Staphylococcus aureus and Escherichia coli

Nyhlén¹,

Ljungberg²,

Nilsson-Ehle³

et al. 2002

Chemotherapy

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“…Changes in the composition of the oral micro-organisms have been reported for chemotherapy treatment in human studies (Lucas et al, 1997;Napeñas et al, 2010) and for 5-FU specifically in a rat study (Von Bültzingslöwen et al, 2003), with a shift towards more Gram-negative rods and bacterial translocation to cervical and mesenteric lymph nodes following treatment with 5-FU. A number of studies have been looking at the antibacterial effect of 5-FU on monocultures of mainly pathogenic strains such as Pseudomonas, Klebsiella and Staphylococcus (Wright & Matsen, 1980;Ueda et al, 1983;Bodet et al, 1985;Takahata et al, 1986). Although 5-FU was shown to have substantial antibacterial effects, the tested concentrations in these studies were much higher than what is usually present in vivo.…”

Section: Introductionmentioning

confidence: 90%

5-Fluorouracil sensitivity varies among oral micro-organisms

Vanlancker

Vanhoecke

Smet

et al. 2016

Journal of Medical Microbiology

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5-Fluorouracil (5-FU), a commonly used chemotherapeutic agent, often causes oral mucositis, an inflammation and ulceration of the oral mucosa. Micro-organisms in the oral cavity are thought to play an important role in the aggravation and severity of mucositis, but the mechanisms behind this remain unclear. Although 5-FU has been shown to elicit antibacterial effects at high concentrations (>100 µM), its antibacterial effect at physiologically relevant concentrations in the oral cavity is unknown. This study reports the effect of different concentrations of 5-FU (range 0.1-50 µM) on the growth and viability of bacterial monocultures that are present in the oral cavity and the possible role in the activity of dihydropyrimidine dehydrogenase (DPD), an enzyme involved in 5-FU resistance. Our data showed a differential sensitivity among the tested oral species towards physiological concentrations of 5-FU. Klebsiella oxytoca, Streptococcus salivarius, Streptococcus mitis, Streptococcus oralis, Pseudomonas aeruginosa and Lactobacillus salivarius appeared to be highly resistant to all tested concentrations. In contrast, Lactobacillus oris, Lactobacillus plantarum, Streptococcus pyogenes, Fusobacterium nucleatum and Neisseria mucosa showed a significant reduction in growth and viability starting from very low concentrations (0.2-3.1 µM). We can also provide evidence that DPD is not involved in the 5-FU resistance of the selected species. The observed variability in response to physiological 5-FU concentrations may explain why certain microbiota lead to a community dysbiosis and/or an overgrowth of certain resistant micro-organisms in the oral cavity following cancer treatment.

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“…Treatment with bleomycin, an antibiotic used against gramnegative bacteria (55) and with chemotherapeutic properties (5,27), leads to pulmonary fibrosis in ϳ18% of patients (40,47). Therefore, bleomycin has become the primary substance used to model pulmonary fibrosis in small rodents (36,37,46).…”

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confidence: 99%

Lung volume quantified by MRI reflects extracellular-matrix deposition and altered pulmonary function in bleomycin models of fibrosis: effects of SOM230

Egger

Gérard

Vidotto

et al. 2014

American Journal of Physiology-Lung Cellular and Molecular Phys

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Lung volume quantified by MRI reflects extracellular-matrix deposition and altered pulmonary function in bleomycin models of fibrosis: effects of SOM230. Am J Physiol Lung Cell Mol Physiol 306: L1064 -L1077, 2014. First published April 11, 2014 doi:10.1152/ajplung.00027.2014.-Idiopathic pulmonary fibrosis is a progressive and lethal disease, characterized by loss of lung elasticity and alveolar surface area, secondary to alveolar epithelial cell injury, reactive inflammation, proliferation of fibroblasts, and deposition of extracellular matrix. The effects of oropharyngeal aspiration of bleomycin in Sprague-Dawley rats and C57BL/6 mice, as well as of intratracheal administration of ovalbumin to actively sensitized Brown Norway rats on total lung volume as assessed noninvasively by magnetic resonance imaging (MRI) were investigated here. Lung injury and volume were quantified by using nongated or respiratory-gated MRI acquisitions [ultrashort echo time (UTE) or gradient-echo techniques]. Lung function of bleomycin-challenged rats was examined additionally using a flexiVent system. Postmortem analyses included histology of collagen and hydroxyproline assays. Bleomycin induced an increase of MRIassessed total lung volume, lung dry and wet weights, and hydroxyproline content as well as collagen amount. In bleomycin-treated rats, gated MRI showed an increased volume of the lung in the inspiratory and expiratory phases of the respiratory cycle and a temporary decrease of tidal volume. Decreased dynamic lung compliance was found in bleomycin-challenged rats. Bleomycin-induced increase of MRI-detected lung volume was consistent with tissue deposition during fibrotic processes resulting in decreased lung elasticity, whereas influences by edema or emphysema could be excluded. In ovalbumin-challenged rats, total lung volume quantified by MRI remained unchanged. The somatostatin analog, SOM230, was shown to have therapeutic effects on established bleomycin-induced fibrosis in rats. This work suggests MRI-detected total lung volume as readout for tissue-deposition in small rodent bleomycin models of pulmonary fibrosis.

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Interactions of beta-lactam antibiotics and antineoplastic agents

Cited by 22 publications

References 7 publications

Bactericidal Effect of Combinations of Antibiotic and Antineoplastic Agents against <i>Staphylococcus aureus</i> and <i>Escherichia coli</i>

Bactericidal Effect of Combinations of Antibiotic and Antineoplastic Agents against <i>Staphylococcus aureus</i> and <i>Escherichia coli</i>

5-Fluorouracil sensitivity varies among oral micro-organisms

Lung volume quantified by MRI reflects extracellular-matrix deposition and altered pulmonary function in bleomycin models of fibrosis: effects of SOM230

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