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Biomedical subjects

A Andremont

Publications and source records attributed to A Andremont.

At least 91 records · Page 5Linked to original sources

Use of beta-lactamase-producing anaerobes to prevent ceftriaxone from degrading intestinal resistance to colonization.

Six adult volunteers were given 1 g/d of intravenous ceftriaxone for 5 d (consecutive). Ceftriaxone and beta-lactamase activities were assayed in fecal samples obtained before and during drug administration, and anaerobic bacteria, Enterobacteriaceae, and fungi were counted. In two volunteers, no fecal beta-lactamase activity was detected, but ceftriaxone was present during treatment at concentrations of 1.8-2.0 mg/g of feces. Concomitantly, fecal counts of anaerobes in these volunteers dropped from 10.5 to less than 8 log10 colony-forming units (cfu)/g of feces, and those of Candida species increased more than 100-fold. However, in the feces of the four other volunteers, beta-lactamase activity was high during ceftriaxone administration, but no ceftriaxone was detected. In these volunteers, ceftriaxone administration was not followed by any significant change in counts of anaerobes or Candida species. This appeared to be due to the intraintestinal hydrolysis of ceftriaxone by resident beta-lactamase-producing anaerobes. In gnotobiotic mice associated with a human fecal flora containing no beta-lactamase-producing anaerobes, it was possible to prevent the deleterious effects of ceftriaxone on intestinal microbial composition and on colonization resistance (against a strain of Candida albicans and one of ceftriaxone-resistant Enterobacter cloacae) by feeding the animals with an association of four beta-lactamase-producing anaerobic strains.

Adult↗

Antibiotic treatment and intestinal colonization by Pseudomonas aeruginosa in cancer patients.

To determine whether antibiotic treatment increases the risk of colonization by Pseudomonas aeruginosa, we performed a case-control study comparing antibiotic exposure in cancer patients colonized by P. aeruginosa and in noncolonized controls. Of 88 patients, 76 had been exposed to at least one antibiotic, but colonization was not statistically associated with exposure to any specific antibiotic treatment, administered orally or parenterally, alone or in combination.

Adolescent↗

Treatment of experimental salmonellosis in mice with ampicillin-bound nanoparticles.

We tested the effectiveness of ampicillin bound to nanoparticles of polyisohexylcyanoacrylate (PIHCA) in treating C57BL/6 mice experimentally infected with Salmonella typhimurium C5. The diameter of the nanoparticles was 187 +/- 13 nm, and the ampicillin/PIHCA ratio was 0.2/1. The proportion of ampicillin bound was 90 +/- 3%. All control mice and all those treated with nonloaded nanoparticles died within 10 days of infection. By contrast, all mice treated with a single injection of 0.8 mg of nanoparticle-bound ampicillin survived. With free ampicillin, a similar curative effect required three doses of 32 mg each. Lower doses delayed but did not reduce mortality. The sharp increase in the therapeutic index of ampicillin after linkage to PIHCA nanoparticles was explained by studies of the distribution of ampicillin, which showed that when bound to nanoparticles, the ampicillin was concentrated mainly in the liver and spleen, the primary foci of infection in the experimental model that we used. These findings warrant further development of intracellular targeting of antibiotics on biodegradable polymeric carriers such as PIHCA.

Ampicillin↗

Effectiveness of nanoparticle-bound ampicillin in the treatment of Listeria monocytogenes infection in athymic nude mice.

The effectiveness of nanoparticle-bound ampicillin was tested in the treatment of experimental Listeria monocytogenes infection in congenitally athymic nude mice. Nanoparticles of polyisohexylcyanoacrylate (PIHCA) 187 +/- 13 nm in diameter were bound to ampicillin at an ampicillin/PIHCA ratio of 0.2:1. The proportion of ampicillin bound was 90% +/- 3%. After adsorption onto nanoparticles, the therapeutic activity of ampicillin increased dramatically over that in the free state. Thus, 2.4 mg of nanoparticle-bound ampicillin (three doses of 0.8 mg each) had a greater therapeutic effect than 48 mg of free ampicillin (three doses of 16 mg each). These results might provide an incentive for further development of intracellular targeting of antibiotics on biodegradable polymeric carriers.

Ampicillin↗

Value of semiquantitative cultures of blood drawn through catheter hubs for estimating the risk of catheter tip colonization in cancer patients.

Colonization of central catheter tips has been associated with catheter-related infections. This colonization is defined as the presence of over 15 CFU in a semiquantitative catheter tip culture performed after catheter removal. Using a simple pour-plate technique, we determined the microbial concentrations in samples of blood collected via the hubs of 205 central catheters while they were in position in 179 cancer patients. All catheters were removed within three days of blood collection via the hub and cultured semiquantitatively. We then compared the results for the hub blood cultures and catheter tip cultures. Cultures from 18% of the hub samples and 29% of the tips were positive. When a cutoff limit of 1,000 CFU/ml was used for the blood cultures, the sensitivity was 20% and the specificity was 99% for estimating catheter tip colonization. These values did not seem to be related to the underlying disease, the site of catheter insertion, or the antibiotic treatment administered at catheter removal. We conclude that, if positive, cultures of blood sampled via the catheter hub can be useful in assessing the risk of catheter colonization in cancer patients.

Bacteria↗

Risk factors for candidemia in cancer patients: a case-control study.

Risk factors for candidemia were analyzed in a case-control study of 30 cancer patients with candidemia and 58 controls. In a univariate analysis, previous surgery, neutropenia, central catheterization, chemotherapy, specific antibiotic treatments, and peripheral cultures positive for Candida spp. were associated with a significantly increased risk of candidemia. In a multivariate logistic model, the significant risk factors for candidemia were positive peripheral cultures for Candida spp. (P = 0.02), central catheterization (P = 0.03), and neutropenia (P = 0.05). These results should help to identify cancer patients with a high risk of candidemia, who should be given early systemic antifungal therapy.

Adult↗

Effect of oral ofloxacin on fecal bacteria in human volunteers.

Intestinal members of the family Enterobacteriaceae were eliminated in five human volunteers treated with oral ofloxacin for 5 days. No emergence of resistant Enterobacteriaceae was observed. Counts of group D streptococci were significantly reduced. Colonization by Candida sp. was observed in all five volunteers during ofloxacin treatment. The anaerobic flora was fairly stable from one sample to another before treatment and was not substantially modified by ofloxacin.

Administration, Oral↗

Distribution of erythromycin esterase and rRNA methylase genes in members of the family Enterobacteriaceae highly resistant to erythromycin.

The distribution of nucleotide sequences related to ereA, ereB, and ermAM was studied by colony hybridization in 112 strains of members of the family Enterobacteriaceae that are highly resistant to erythromycin. The ereA and ereB genes encoding erythromycin esterases type I and II, respectively, were detected in strains inactivating the 14-membered macrolides erythromycin and oleandomycin. Because all 52 strains resisting these antibiotics by inactivation were detected by ereA (n = 23), ereB (n = 23), or both probes (n = 6), only two classes of genes accounted for this resistance phenotype. The ermAM gene encoding a streptococcal rRNA methylase was detected in 21 strains of Escherichia coli and two strains of Klebsiella spp. Determination of the MICs of macrolide, lincosamide, and streptogramin (MLS) antibiotics demonstrated a correlation between hybridization with ermAM and the so-called MLS resistance phenotype. The presence of 11 strains coresistant to MLS antibiotics that did not hybridize to the ermAM probe suggests that, as in gram-positive organisms, MLS resistance in members of the family Enterobacteriaceae involves more than one class of rRNA methylase. Numerous strains (n = 18) were found to produce both an erythromycin esterase type II and an rRNA methylase. Physical linkage between ereB and ermAM may be responsible for the codissemination of the genes. Despite their exogenous origin, ereB and ermAM are already disseminated in various genera of the Enterobacteriaceae.

Carboxylic Ester Hydrolases↗

Comparative translocation of enteropathogenic Campylobacter spp. and Escherichia coli from the intestinal tract of gnotobiotic mice.

In C3H gnotobiotic mice, no significant difference was observed between the translocation of nine clinical isolates of enteropathogenic Campylobacter spp. and that of seven nonisogeneic Escherichia coli strains with or without various determinants of pathogenicity. In addition, there was no correlation found between the intensity of translocation of Campylobacter strains and the signs of invasiveness in the patients from whom the strains had been isolated.

Animals↗

Pseudoepidemic of aspergillosis after development of pulmonary infiltrates in a group of bone marrow transplant patients.

During February and March 1985, seven patients in the pediatric bone marrow transplant unit (PBMTU) of a 350-bed cancer hospital developed pulmonary infiltrates. Five of the patients had Aspergillus spp. isolated from the respiratory tract, and two of these patients had histologic evidence of aspergillosis. Between 26 February and 22 April, Aspergillus spp. were isolated in a total of 70 cultures from 39 hospitalized patients. Of the 70 cultures, 14 (group 1) were from respiratory specimens of PBMTU patients with pulmonary infiltrates and were submitted to the laboratory intermittently over the 56-day period. However, of the other 56 Aspergillus-positive cultures (group 2), 41 (73%) were submitted on six days during this period (P less than 0.001, chi-square goodness of fit), including 8 blood cultures submitted on one day. When Aspergillus sp. was recovered from group 1 cultures early during this period, the isolates were stored in the culture-processing room. Aspergillus isolates were not handled in a biological safety cabinet, and blood cultures were done by using a system which requires opening of an evacuated bottle to room air. The presence of stored Aspergillus isolates was associated with a markedly elevated concentration of airborne fungi in the culture-processing room. After removal of the stored Aspergillus isolates from the culture-processing room, the concentration of airborne fungi returned to background level and there were no further Aspergillus-positive cultures. These findings suggested that group 2 cultures had been contaminated by stored Aspergillus isolates. No evidence for a common source of infection was found in the PBMTU patients with pulmonary infiltrates.

Air Microbiology↗

Severe gram-negative infections in neutropenic children cured by imipenem/cilastatin in combination with an aminoglycoside.

Nine severe Gram-negative septicaemias in neutropenic (less than 500 neutrophils/mm3) children with neoplastic diseases were treated with imipenem/cilastatin (75 mg/kg/day) in combination with an aminoglycoside. The bacterial strains (Pseudomonas aeruginosa 7, P. putida 1, Enterobacter cloacae 1) were resistant to penicillins and cephalosporins, or were isolated during treatment with a broad-spectrum penicillin to which the bacterial strain was sensitive in vitro. The mean duration of neutropenia was 18.5 (3-51) days and duration of treatment 20 (8-51) days. Pyrexia was controlled in 2.8 (1-10) days and eradication of the pathogen from blood in one day. No clinical and biological adverse reaction was observed. These results show imipenem/cilastatin to be an effective treatment of infections in severely immunocompromised patients.

Adolescent↗

Plasmid-mediated high-level resistance to erythromycin in Escherichia coli.

Escherichia coli BM2195 was found to be resistant to high levels of erythromycin. This new resistance phenotype was due to the constitutive synthesis of an erythromycin esterase which inactivates the antibiotic. The gene conferring resistance to erythromycin in this strain is carried on a 61-kilobase self-transferable plasmid, pIP1100, belonging to incompatibility group X.

Drug Resistance, Microbial↗

Selective antimicrobial modulation of the intestinal tract by norfloxacin in human volunteers and in gnotobiotic mice associated with a human fecal flora.

Intestinal endogenous members of the family Enterobacteriaceae were eliminated in 12 human volunteers treated with 400 or 800 mg of oral norfloxacin per day for 5 days. No clones resistant to quinolone derivatives were isolated. Counts of aerotolerant streptococci were affected to various degrees, depending on their susceptibility to norfloxacin. During treatment, counts of anaerobes remained above 9.8 log10 CFU/g of feces. A total of 932 anaerobic isolates from the predominant flora (over 10(9) CFU/g) in fecal samples obtained before or during norfloxacin treatment were classified by a simple morphological and physiological scheme. The composition of this flora was fairly stable from one sample to another before treatment and was not substantially modified by norfloxacin. Intestinal resistance to colonization by exogenous microorganisms was studied in gnotobiotic mice associated with a human fecal flora. The composition of the fecal flora of the human donor and the fecal concentrations of norfloxacin in the volunteers were reproduced in the intestine of the mice. Resistance to colonization by exogenous microorganisms was reduced by norfloxacin for only 2 of 14 (14%) of the strains tested. These results suggest that norfloxacin is a good candidate for selective antimicrobial modulation of the intestinal tract in humans.

Animals↗

Epidemiology of intestinal colonization by members of the family Enterobacteriaceae highly resistant to erythromycin in a hematology-oncology unit.

Intestinal colonization by highly erythromycin-resistant members of the family Enterobacteriaceae was surveyed for 4 years in a hematology-oncology unit. Fifty-four of 555 patients (9.7%) were colonized, each with a different strain. The incidence of intestinal carriage was not correlated with erythromycin consumption in the ward but was strongly associated with individual exposure to erythromycin.

Carrier State↗

Epidemiology of intestinal colonization by members of the family Enterobacteriaceae resistant to cefotaxime in a hematology-oncology unit.

Intestinal colonization by members of the family Enterobacteriaceae resistant to cefotaxime was surveyed for 3 years in a hematology-oncology unit. Of 416 patients, 66 (15.9%) were colonized, each with a different strain. The incidence of intestinal carriage was not correlated with cefotaxime consumption in the ward but was strongly associated with individual exposure to cefotaxime.

Agranulocytosis↗

In vivo activity of nifurzide and nifuroxazide in intestinal bacteria in man and gnotobiotic mice.

Although Gram-negative enteropathogenic bacteria are the target strains of nifurzide and nifuroxazide treatments, neither drug affected faecal counts of in vitro-susceptible Enterobacteriaceae in healthy volunteers. This absence of activity was shown to be due to the poor solubility of the drugs tested. Therefore, effect of high doses of nifurzide was investigated in gnotobiotic mice. Activity against in vitro susceptible enteropathogens was then observed. Normal bacterial cells were replaced in the faeces by elongated, nonseptate and unflagellated mutants. Moreover, the resistance to colonization by enterotoxigenic Escherichia coli and Shigella flexeri of an anaerobic flora of human origin was sharply decreased.

Animals↗

Plasmid-mediated susceptibility to intestinal microbial antagonisms in Escherichia coli.

Self-transferable plasmid pIP1100 confers to Escherichia coli an unusually high level of resistance (1 to 2 mg/ml) to erythromycin by production of an erythromycin esterase. The effect of pIP1100 on the destiny of E. coli strains in the intestines of gnotobiotic mice was studied. In germfree mice, pIP1100 was efficiently transferred to a plasmid-free E. coli recipient. Intestinal counts of the donor, the recipient, and the transconjugants were greater than 8.5 log CFU/g of feces. When erythromycin was added to the diet of the mice, counts of the plasmid-bearing strains were only slightly lowered and partial inactivation of erythromycin was observed in the feces. Transfer of pIP1100 also occurred in human-flora-associated mice. In this model all the E. coli strains were subject to microbial antagonisms caused by the anaerobic components of the flora. However, strains harboring pIP1100 were strongly inhibited (less than 2.5 log CFU/g of feces), whereas their plasmid-free counterparts persisted at much higher population levels (greater than 5.2 log CFU/g of feces). The ecological disadvantage conferred by pIP1100 to E. coli when a complex human flora was concomitantly present in the intestine of the mice persisted during erythromycin administration. These results provide an explanation for the low incidence of isolation of highly erythromycin-resistant E. coli strains despite the extensive use of the antibiotic.

Animals↗