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Biomedical subjects

A Andremont

Publications and source records attributed to A Andremont.

At least 73 records · Page 4Linked to original sources

Conjugal transfer of plasmid DNA from Enterococcus faecalis to Escherichia coli in digestive tracts of gnotobiotic mice.

We have studied the transfer of the conjugative shuttle plasmid pAT191, which confers resistance to kanamycin, from Enterococcus faecalis to Escherichia coli in the digestive tracts of six gnotobiotic mice. Colonies of E. coli resistant to kanamycin were isolated from the feces of two mice, respectively, on days 25 and 35 after the beginning of the experiment and never thereafter. The transfer frequency of pAT191, expressed as the number of transconjugants per donor cell isolated from intestines of sacrificed mice, was 3 x 10(-9). These results indicate that conjugation is a mechanism that could account for the resistance gene flux from gram-positive to gram-negative bacteria observed in nature.

Animals↗

Presence of Clostridium difficile and antibiotic and beta-lactamase activities in feces of volunteers treated with oral cefixime, oral cefpodoxime proxetil, or placebo.

Three groups of six healthy adult volunteers were randomly assigned to a treatment with 400 mg of oral cefpodoxime proxetil, oral cefixime, or placebo per day for 10 days. Informed consent was obtained from all volunteers. Clostridium difficile was not detected in the feces of any subject before treatment or at any time in the subjects in the placebo group. C. difficile was, however, detected in all subjects treated with cefpodoxime proxetil and in five of six treated with cefixime. Genomic DNA restriction patterns showed that the strains of C. difficile differed from one volunteer to another. Two subjects both shed different strains at different times during the 25-day surveillance period. All isolates were resistant to cefixime and cefpodoxime (MIC for 90% of strains, 256 and 512 mg/liter, respectively). Antibiotic activity was found in the feces of one volunteer treated with cefpodoxime proxetil and of four volunteers treated with cefixime. It was inversely correlated with the presence of fecal beta-lactamase activity. Intestinal side effects were limited to modifications of stool consistency, which occurred in only 3 of the 12 treated volunteers and did not lead to cessation of treatment. These modifications were significantly associated with the presence of fecal antibiotic activity (P less than 0.05) but not with the shedding of toxigenic or nontoxigenic strains of C. difficile or with the presence of toxin A in feces, which was detected only in one perfectly healthy treated volunteer.

Administration, Oral↗

Activity and specificity of a mouse monoclonal antibody to ferric aerobactin.

We isolated a monoclonal antibody directed against the ferric complex of aerobactin purified from Escherichia coli KH576. This antibody, which we designated MAb AERO1, was identified as an immunoglobulin G, subtype 2. A competitive enzyme-linked immunosorbent assay with MAb AERO1 had a limit of 10 nM for the detection of purified ferric aerobactin and allowed detection of the crude aerobactin produced by various members of the family Enterobacteriaceae isolated from cancer patients with bacteremia. The only two other structurally related siderophores recognized by MAb AERO1 were ferric arthrobactin and ferrioxamine B. These results suggest that the epitope recognized by MAb AERO1 was the lysyl moiety of ferric aerobactin. We also showed that MAb AERO1 reduced the growth of an aerobactin-producing strain of E. coli in newborn calf serum, which indicates that it might be effective in reducing the severity of infections caused by bacteria for which the production of aerobactin is an important virulence factor.

Animals↗

Detection of genes in feces by booster polymerase chain reaction.

A 321-bp fragment intragenic to the gene ereA carried by Escherichia coli BM2195 was used as a model target to study the conditions under which DNA amplification by booster polymerase chain reaction can be used to detect specific bacterial DNA sequences in fecal specimens. When target E. coli cells were mixed with 41 freshly obtained fecal specimens, the polymerase chain reaction detection limit varied from 4.5 to 7.1 log CFU/g of feces, depending on the individual fecal specimen used to prepare the test sample. These variations were not statistically related to the sex or age of the subject from whom the specimen was obtained. After storage of the samples for 4 weeks at room temperature on swabs or filter papers, no loss in sensitivity was observed.

Base Sequence↗

Infectious complications associated with granulocytopenia during the treatment of poor risk or relapsed germ cell tumors.

Infectious complications associated with granulocytopenia during the treatment of poor risk or relapsed germ cell tumors were studied in order to assess the frequency, morbidity and characteristics of these complications. Thirty-three cases were investigated at the Institut Gustave-Roussy; 63 episodes of granulocytopenia were observed (mean duration 7.5 days). Twenty-four (38%) of the episodes of granulocytopenia were associated with fever. In 11/24 episodes (46%), fever was associated with a documented infection. Eighteen organisms were isolated. Ten were found to be Gram-positive, 7 Gram-negative, and one Candida. The major site of infection was the lungs. One death from septicaemia occurred. In conclusion, post-chemotherapy granulocytopenia during the treatment of germ cell tumors is associated with fever in less than 50% of cases. Bacterial infection was diagnosed in only 46% of febrile neutropenic episodes and rarely appears to be associated with a fatal outcome.

Adolescent↗

[Value of the combination of piperacillin and pefloxacin possibly followed by vancomycin in the treatment of febrile neutropenia in nephrotoxic chemotherapy].

We evaluated the efficacy and safety of piperacillin-pefloxacin potentially associated to vancomycin as a non nephrotoxic antimicrobial therapy in febrile neutropenic cancer patients, treated with nephrotoxic chemotherapy. Fifty-seven patients: 49 with solid tumors and 8 non-Hodgkin lymphomas, were treated during 85 episodes with: piperacillin 4 g IV every 8 h pefloxacin 400 mg IV every 12 h. If the patient remained febrile after 72 h, 1 g of vancomycin IV was added every 12 h. The mean duration of neutropenia was 7 days (3-14 days). In 44 episodes, the granulocyte nadir was < 100/mm3. Infection was microbiologically documented in 17 episodes (20%) with ten Gram-positive cocci and 11 Gram-negative bacilli. There were 64 apyrexia with piperacillin-pefloxacin (75%) and further 14 were resolved by the addition of vancomycin (total success = 92%); three early changes because of clinical deterioration (two episodes) or germ resistance (one episode); three protocol violations, and one apyrexia by addition of amphotericin. Neither septic death nor toxicity were observed. We conclude that this empirical treatment is active and safe and avoids nephrotoxicity in cancer patients heavily treated with nephrotoxic chemotherapy.

Adolescent↗

Liposomes and nanoparticles in the treatment of intracellular bacterial infections.

The treatment of infections caused by obligate or facultative intracellular microorganisms is difficult because most of the available antibiotics have either poor intracellular diffusion and retention or reduced activity at the acidic pH of the lysosomes. The need for antibiotics with greater intracellular efficacy led to the development of endocytosable drug carriers, such as liposomes and nanoparticles, which mimic the entry path of the bacteria by penetrating the cells into phagosomes or lysosomes. This Review assesses the potential of liposomes and nanoparticles in the targeted antibiotic therapy of intracellular bacterial infections and diseases and the pharmaceutical advantages and limitations of these submicron delivery systems.

Anti-Bacterial Agents↗

Effect of oral spiramycin on the faecal and oral bacteria in human volunteers.

Six healthy adult volunteers were treated with 1 g of oral spiramycin twice daily for five days, and their oral and faecal microbial flora were studied. Mean saliva and serum concentrations of the antibiotic never exceeded 2.1 +/- 1.1 mg/l. The number of volunteers whose oral cavity was colonized by Enterobacteriaceae, group D streptococci, staphylococci, and fungi remained unchanged following treatment. The mean count of anaerobic faecal bacteria was 10.3 +/- 0.6 log10 cfu/g initially. This did not change significantly during the treatment, nor did the composition of the predominant anaerobic flora. Mean counts of group D streptococci were 1000 times lower than those of anaerobes before treatment, and also remained unchanged during therapy. No overgrowth of fungi, staphylococci, or Pseudomonas aeruginosa was observed. No significant modifications occurred in the mean total count of faecal Enterobacteriaceae (7.9 +/- 0.4 versus 7.4 +/- 1.0 log10 cfu/g of faeces before and during treatment respectively). However, faecal concentrations of highly spiramycin-resistant Enterobacteriaceae (MIC greater than or equal to 512 mg/l) increased from 4.8 +/- 1.2 to 7.0 +/- 1.8 log10 cfu/g during treatment. The MIC50 value of spiramycin for anaerobes, Enterobacteriaceae, and group D streptococci were 0.125, 64, and 0.5 mg/l respectively before treatment, and these increased to 1024, 512 and 1024 mg/l respectively during treatment. This was attributed to the rise in the faecal concentrations of spiramycin, which reached 689 +/- 48 micrograms/g of faeces on the fifth day of treatment. These concentrations decreased rapidly on cessation of treatment.

Administration, Oral↗

Inducible transfer of conjugative transposon Tn1545 from Enterococcus faecalis to Listeria monocytogenes in the digestive tracts of gnotobiotic mice.

Transfer of conjugative transposon Tn1545 from Enterococcus faecalis to Listeria monocytogenes was studied in vitro and in vivo. Tn1545 transferred following filter mating at a frequency of 2.5 x 10(-7) transconjugants per donor colony. A 20-fold increase in transfer frequency was observed when matings were performed in the presence of a subinhibitory concentration of tetracycline. The frequency of in vivo transfer of Tn1545, expressed as the number of transconjugants per donor cell extracted from the intestines of the gnotobiotic mice after 35 days of experiment, was 1.1 x 10(-8). Presence of a low concentration of tetracycline in the drinking water increased this frequency 10-fold.

Animals↗

Effects of roxithromycin on fecal bacteria in human volunteers and resistance to colonization in gnotobiotic mice.

The ecological impact of roxithromycin given orally at 300 mg/day on the intestinal floras in six human volunteers was studied. The resulting fecal concentrations of active roxithromycin were in the range of 100 to 200 micrograms/g of feces. Consecutive modifications in the composition of the fecal floras were limited to a decrease in counts of total members of the family Enterobacteriaceae. The rest of the intestinal floras, including the predominant anaerobic floras, changed little. No overgrowth of Pseudomonas aeruginosa, staphylococci, fungi, or highly erythromycin-resistant strains of the family Enterobacteriaceae was observed. The strains of Enterobacteriaceae and of anaerobes isolated during treatment were not markedly more resistant to roxithromycin than those isolated before treatment started. Changes in intestinal resistance to colonization by exogenous microorganisms in gnotobiotic mice inoculated with human fecal flora were studied and were also found to be minimal. The impact of oral roxithromycin on the intestinal microbiota appears to be weaker than that previously observed with oral erythromycin, perhaps because the concentrations of roxithromycin in the feces were lower than those previously found for erythromycin.

Administration, Oral↗

Liposome-entrapped ampicillin in the treatment of experimental murine listeriosis and salmonellosis.

The tissue distribution of ampicillin entrapped in liposomes was studied in normal noninfected mice and showed that ampicillin concentrated mostly in the liver and spleen. Liposomate ampicillin was significantly more effective than free ampicillin in reducing splenic and hepatic bacterial counts in C57BL/Ka nude mice chronically infected with Listeria monocytogenes EGD. It was also significantly more effective than free ampicillin in reducing mortality in C57BL/6 mice acutely infected with Salmonella typhimurium C5. Comparison of the results with those previously obtained in the same experimental models with the same amounts of ampicillin bound to polyisohexylcyanoacrylate nanoparticles showed that liposomes were more effective than nanoparticles (M. Youssef, E. Fattal, M. J. Alonso, L. Roblot-Treupel, J. Sauzières, C. Tancrède, A. Omnès, P. Couvreur, and A. Andremont, Antimicrob. Agents Chemother. 32:1204-1207, 1988) in targeting ampicillin to the spleen but were less effective than nanoparticles in targeting ampicillin to the liver and reducing mortality in acute salmonellosis.

Ampicillin↗

Kinetics of Saccharomyces cerevisiae elimination from the intestines of human volunteers and effect of this yeast on resistance to microbial colonization in gnotobiotic mice.

When healthy volunteers were given a daily dose of 3 x 10(8) life-dehydrated Saccharomyces cerevisiae cells for 5 days, the volunteers excreted 10(5) living yeast cells per g of feces at first, but the yeast cells disappeared within 5 days of the end of treatment. In gnotobiotic mice, S. cerevisiae administered alone colonized the intestinal tract but did not interfere with previous or subsequent colonization by a variety of potentially enteropathogenic microorganisms. When these microorganisms were present, the intestinal counts of S. cerevisiae were greatly reduced.

Adult↗

Streptococcal septicaemia following autologous bone marrow transplantation in children treated with high-dose chemotherapy.

A total of 251 patients were given 326 courses of high-dose chemotherapy followed by autologous bone marrow transplantation between February 1979 and August 1988. Ninety-one cases of septicaemia developed in 84 patients, 33 of these cases (36%) were due to streptococci. The outcome was fatal for four patients (12.1%). No specific risk factors were identified which might account for this septicaemia and no clinical feature was significantly associated with these cases of bacterial infection. Pulmonary and neurologic septic complications, however, were of very poor prognosis since all patients with these complications died. The high rate of streptococcal septicaemia and the poor outcome for patients with prolonged and profound neutropenia led us to modify our choice of initial broad-spectrum antibiotic therapy.

Adolescent↗

Influence of colonizing micro-flora on the mucin histochemistry of the neonatal mouse colon.

Mucin histochemistry on sections of colon from germ-free and conventional mouse pups showed that all goblet cell mucins were sulphated at birth. During the first two weeks of post natal development, the pattern of mucin production in the ascending colon changed to a distribution of non-sulphated mucins towards the apical zone of the crypts and sulphated sialomucins basally. In conventional animals during the third postnatal week when the complex micro-flora of the colon was becoming established, the typical adult mucin distribution pattern developed, with sulphated mucins now confined to the upper third of the crypt. However, in the absence of a colonizing micro-flora crypt mucins become more and more sulphated until at weaning, most goblet cells of the ascending colon were producing fully or partially sulphated mucins, except for one or two cells at the very base of the crypt.

Animals↗

Effectiveness of simple measures to control an outbreak of nosocomial methicillin-resistant Staphylococcus aureus infections in an intensive care unit.

Between June 1985 and March 1986, 14 cases of severe nosocomial methicillin-resistant Staphylococcus aureus (MRSA) infection, including septicemia, were observed in the intensive care unit (ICU) of a 400-bed cancer reference center. Simple control measures including contact isolation of colonized patients and reinforcement of handwashing practices among personnel were followed by a sharp decrease in the rate of infection and colonization. An epidemiological investigation showed that a single serophage variant MRSA strain was involved; peak incidence of infection was 17 per 100 ICU patient discharges; the index case was identified as a patient admitted from another hospital and the epidemic strain was then transmitted from patient-to-patient in the ICU; risk factors for acquiring infection were length of prior hospitalization, invasive procedures and number of antibiotic treatments; dissemination of the strain to other wards was only anecdotal. These results stress the effectiveness of simple measures to control outbreaks of MRSA nosocomial infections even in immunocompromised cancer patients.

Cancer Care Facilities↗

Faecal excretion of ciprofloxacin after a single oral dose and its effect on faecal bacteria in healthy volunteers.

High concentrations of ciprofloxacin have been shown to persist in the faeces of volunteers for several days after a week of oral treatment with this drug, which was also found to have a prolonged effect on aerobic Gram-negative intestinal bacteria. To determine whether a shorter course of ciprofloxacin would have the same prolonged effect, we treated ten healthy adult volunteers with a single oral dose of 750 mg ciprofloxacin and found that this was not followed by any significant changes in the counts of anaerobes or streptococci, but that there was a mean decrease of 2.5 log10 cfu/ml in the counts of faecal Enterobacteriaceae, which lasted for a full week. We attributed this to the persistence of high faecal ciprofloxacin concentrations for several days in all the volunteers. We did not observe any significant increase in the MICs of ciprofloxacin for faecal Enterobacteriaceae, or any faecal overgrowth of staphylococci, fungi, Pseudomonas aeruginosa or Clostridium difficile.

Adult↗

Prospective multicenter study of vascular-catheter-related complications and risk factors for positive central-catheter cultures in intensive care unit patients.

To determine the incidence rate of complications associated with vascular catheters in intensive care unit patients and to analyze risk factors for a positive vascular culture, we performed a multicenter study of intensive care unit patients at eight French hospitals. During the study period, 865 intravenous catheters were inserted in 566 patients; 362 (41.8%) were peripheral catheters, and 503 (58.2%) were central catheters. Local complications (i.e., infiltration) occurred significantly more often with peripheral than with central catheters (P less than 0.001); in contrast, fever and bacteremia were significantly more often associated with central than with peripheral catheters (P less than 0.01 and P less than 0.05, respectively). The culture of the vascular-catheter tip was positive for 24% of central catheters (32 of 1,000 catheters days) and for 9% of peripheral catheters (21 of 1,000 catheters days). Staphylococcus epidermidis was the most common microorganism isolated from both peripheral and central catheters, followed by Staphylococcus aureus and Pseudomonas aeruginosa. No significant risk factor associated with positive cultures for peripheral catheters was found by univariate analysis. In contrast, the purpose of the cannula (nutrition and monitoring of central venous pressure), the insertion site (jugular), the dressing type (semipermeable transparent dressing), the antiseptic used to prepare the insertion site (povidone iodine), and routine changing of the intravenous administration set were significantly associated with positive cultures of central catheters. Three factors, duration of catheterization, use of a semipermeable transparent dressing, and the jugular insertion site, were found to be independently associated with positive cultures of central catheters by multivariate analysis.

Catheterization↗