Experimental intestinal microflora in mice with a changeable population size of E. coli.
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Biomedical subjects
Publications and source records attributed to A Andremont.
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The effect of erythromycin base was studied on intestinal resistance to colonization of gnotobiotic mice inoculated with a human fecal flora and challenged with six microbial strains potentially pathogenic for immunocompromised patients. Fecal concentrations of erythromycin were greater than 1,000 micrograms/g in the human donor and in mice. Total intestinal bacterial counts were not significantly different in the human donor and in the recipient mice and were not affected by erythromycin treatment. Strains of various species from the dominant flora (greater than 10(9) colony-forming units/g) and resistant to greater than 1,000 micrograms of erythromycin/ml were present before and persisted during treatment. Strains sensitive to such concentrations - particularly all enterobacteria-were eliminated. Treatment did not reduce colonization resistance against Candida albicans, Clostridium perfringens, and erythromycin-sensitive Escherichia coli. It reduced but did not eliminate some colonization resistance against Pseudomonas aeruginosa, Clostridium difficile, and erythromycin-resistant E coli.
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A relationship between the gut flora level, particularly gram-negative enterobacilli, and the in vivo flucytosine conversion to fluorouracil has been observed in humans from the fluorine-19 magnetic resonance spectroscopy analysis of urine from two patients treated with the flucytosine- (6 to 9 g/day) amphotericin B (1 mg/kg/day) combination. Indeed the percentage of fluorouracil metabolites was extremely low (less than 0.6% of total fluorinated compounds excreted) when the number of enterobacillary colonies was low (less than 10(3] and higher (3.5 to 8.8%) when enterobacillary colonies were under reconstitution or in the normal range (10(5) to 10(8]. The intestinal microflora assessment may therefore be of high interest to predict the risk of an additive flucytosine-induced myelotoxicity suspected to be due to fluorouracil during flucytosine chronic therapy.
We have constructed a probe specific for the gene ereA of plasmid pIP1100, which confers high-level resistance to erythromycin in Escherichia by production of an erythromycin esterase. The distribution of the gene ereA in enterobacteria highly resistant to erythromycin isolated from human faeces was studied by colony hybridization. The gene ereA was detected in strains of E. coli belonging to various biotypes, in Klebsiella pneumoniae, in Enterobacter agglomerans and in one strain of a "coliform". Moreover, our results indicated the existence of at least two classes of genes specifying resistance to erythromycin by inactivation of the antibiotic in enterobacteria.
Between 1983 and 1987 the overall incidence of candidemia at the Institut Gustave Roussy, a tertiary care referral hospital for patients with cancer, increased from 0.1% (7 of 6,801) to 0.32% (24 of 7,515) (P = .009). Because acute lymphocytic leukemia (ALL) was the most common underlying disease in patients with candidemia, risk factors for candidemia were analyzed in this subset of patients. A case-control study comparing the eight ALL patients who had candidemia with 18 ALL control patients revealed that previous bacteremia, prolonged neutropenia, prolonged fever, prolonged administration of antimicrobial agents, treatment with multiple antimicrobial agents, and a relatively high concentration of Candida organisms in stool were significant risk factors for candidemia. In a logistic regression analysis, however, only receipt of vancomycin and/or imipenem was identified as an independent risk factor for candidemia. Further analysis showed that administration of vancomycin promoted proliferation of Candida organisms in the gastrointestinal tract and that this proliferation was associated with an increased risk of candidemia.
In this paper, we report the physico-chemical properties of negatively charged liposomes and of polyisohexylcyanoacrylate nanoparticles loaded with ampicillin. Although the carriers were of the same size (200 nm), drug-loading capacity was 20 times higher for nanoparticles than for liposomes. After freeze-drying or storage at +4 degrees C, no drug escaped from polymeric nanoparticles. On the other hand, in the same conditions, ampicillin leaked rapidly from liposomes. Drug release in foetal calf serum was gradual (of zero order) with nanoparticles, whereas it was rapid with liposomes. Finally, the antimicrobial activity of ampicillin-entrapped liposomes or nanoparticles was studied in vitro.
One-hundred and fifteen infants aged 1 to 31 days from two intensive-care units were grouped into 6 classes according to clinical criteria (enterocolitis with or without anatomopathological examination and pneumatosis intestinalis, "haemorrhagic colitis", acute diarrhoea or absence of intestinal disorders). The total number of viable bacteria, the number of Clostridium and, in some cases, the presence of rota- and/or coronavirus were determined in their stools. The incidence of Clostridium in the stools of infants with enterocolitis (with or without pneumatosis intestinalis) or haemorrhagic colitis was not significantly different from that of infants without intestinal disorders, whereas stools of infants with acute diarrhoea less often contained Clostridium than those of other infants. C. butyricum, C. difficile, C. perfringens, C. tertium, and C. sordellii were identified. Correspondence analysis comparing the variable, "clinical profile", with 23 other variables, suggested that the variables of gemellity, a birthweight below 1900 g, a gestational age of less than 35 weeks, respiratory distress, umbilical catheterization and a Clostridium count above 10(7)/g at the onset of clinical signs, i.e. between 8 to 12 days of age, were linked to the clinical profile of necrotizing enterocolitis with pneumatosis intestinalis. Conversely, the absence of gemellity, a high birthweight and gestational age, the absence of respiratory distress or umbilical catheterization, the onset of diarrhoea within 8 days, and the presence of rota- and/or coronavirus in the stools were linked with a clinical profile of acute diarrhoea.
Traveller's diarrhea is mostly due to aerobic Gram-negative bacterial species, especially enterotoxigenic Escherichia coli. Until today no fully satisfactory prophylactic regimen has been designed. We have previously reported that erythromycin can eliminate Enterbacteriaceae from the human faecal flora during several weeks without recolonization by highly resistant Gram-negative aerobic organisms. This effect has been reproduced in 17 out of 18 volunteers taking 1, 2 or 3 g per day of oral erythromycin base during 5 days. This effect is due to the very high faecal concentrations of the antibiotic (2,000-4,000 micrograms/g) compared to the MIC of erythromycin on aerobic Gram-negative species (10-500 micrograms/ml). MIC of erythromycin on bacterial species which cause traveller's diarrhea are within the same range. These considerations led us to perform a double-blind, randomized, placebo-controlled clinical trial of the efficacy of 1 g daily intake of erythromycin base in preventing traveller's diarrhea. Fourty-eight US citizens travelling to Acapulco (Mexico) were enrolled in the study. Mean duration stay was 5.87 days. Seven out of 24 subjects of the placbo group experienced diarrhea and non (p=0.0047) in the treated group. Study should be undertaken to evaluate the efficacy of oral erythromycin in preventing traveller's diarrhea in other parts of the world.