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R Leclercq

Publications and source records attributed to R Leclercq.

At least 19 recordsLinked to original sources
PubMed1992

New high-content disks for determination of high-level aminoglycoside resistance in clinical isolates of Enterococcus faecalis.

Disks impregnated with 500 and 1000 micrograms of streptomycin, 1000 micrograms of kanamycin and 250 and 500 micrograms of gentamicin were used for detection of high-level resistance to aminoglycosides in 120 clinical isolates of Enterococcus faecalis. Fifty-seven strains were highly resistant to streptomycin, 80 to kanamycin and 41 to gentamicin. Using disks containing 500 micrograms of streptomycin, 1000 micrograms of kanamycin and 500 micrograms of gentamicin strains resistant to high levels of these drugs (97.9%, 100% and 100%, respectively) were accurately detected. Better discrimination between high-level and low-level resistance was achieved with a 500 micrograms streptomycin or gentamicin disk. Zone-size breakpoints are proposed for detection of high-level resistance by disk diffusion.

Drug Resistance, Microbial↗
PubMed1992

Resistance of enterococci to aminoglycosides and glycopeptides.

High-level resistance to aminoglycosides in enterococci often is mediated by aminoglycoside-modifying enzymes, and the corresponding genes generally are located on self-transferable plasmids. These enzymes are similar to those in staphylococci but differ from the modifying enzymes of gram-negative bacteria. Three classes of enzymes are distinguished, depending upon the reaction catalyzed. All but amikacin and netilmicin confer high-level resistance to the antibiotics that are modified in vitro. However, the synergistic activity of these last two antibiotics in combination with beta-lactam agents can be suppressed, as has always been found in relation to high-level resistance to the aminoglycosides. Acquisition of glycopeptide resistance by enterococci recently was reported. Strains of two phenotypes have been distinguished: those that are resistant to high levels of vancomycin and teicoplanin and those that are inducibly resistant to low levels of vancomycin and susceptible to teicoplanin. In strains of Enterococcus faecium highly resistant to glycopeptides, we have characterized plasmids ranging from 34 to 40 kilobases that are often self-transferable to other gram-positive organisms. The resistance gene vanA has been cloned, and its nucleotide sequence has been determined. Hybridization experiments showed that this resistance determinant is present in all of our enterococcal strains that are highly resistant to glycopeptides. The vanA gene is part of a cluster of plasmid genes responsible for synthesis of peptidoglycan precursors containing a depsipeptide instead of the usual D-alanyl-D-alanine terminus. Reduced affinity of glycopeptides to these precursors confers resistance to the antibiotics.

Aminoglycosides↗
PubMed1992

Activity of RP 59500, a new parenteral semisynthetic streptogramin, against staphylococci with various mechanisms of resistance to macrolide-lincosamide-streptogramin antibiotics.

RP 59500 is a semisynthetic streptogramin (Sg) composed of two synergic components: RP 57669 and RP 54476. The activities of RP 59500, RP 57669 and RP 54476 were tested against 20 strains of staphylococci susceptible to macrolide, lincosamide and streptogramin antibiotics (MLS) and against strains exhibiting different MLS resistance mechanisms. RP 59500 was active against 14 strains harbouring emrA or ermC genes which were inducibly or constitutively resistant to erythromycin (MICs of 0.5-2 mg/L). Neither RP 59500, RP 57669 nor RP 54476 induced MLSB resistance. Constitutive mutants appeared at frequencies of 10(-7)-10(-8) when two MLSB-inducible strains of staphylococci were exposed to 40 mg/L each of clindamycin and RP 57669. No such mutants appeared on plates containing RP 59500 or RP 54476. The emergence of mutants was prevented if the cultures were exposed to RP 54476 (40 mg/L), indicating that such mutants are unlikely to be selected in vivo by RP 59500. However, for some constitutive mutants, MBCs of RP 59500 were as high as 8 mg/L. Strains producing acetyltransferase and hydrolase, inactivating SgA- and SgB-type antibiotics respectively, were resistant to RP 59500, RP 57669 and RP 54476. Production of Pincosamide nucleotidyltransferase-4, which inactivates lincosamides, had no effect on the MICs of RP 59500, RP 57669 and RP 54476.

Anti-Bacterial Agents↗
PubMed1992

Vancomycin resistance gene vanC is specific to Enterococcus gallinarum.

Nearly all strains of Enterococcus gallinarum are resistant to low levels of vancomycin. The glycopeptide resistance gene vanC from E. gallinarum BM4174 has recently been cloned and sequenced. A probe specific for vanC hybridized with a 2.7-kb EcoRI and a 4.5-kb HindIII fragment of total DNA from the 42 strains of E. gallinarum studied. No homology was detected with DNA of strains belonging to other species intrinsically resistant to vancomycin, including Enterococcus casseliflavus, a species that expresses a vancomycin resistance phenotype similar to that of E. gallinarum. No hybridization with DNA of enterococcal strains with acquired resistance to high or low levels of vancomycin was observed. The specificity of the vanC probe allowed us to distinguish E. gallinarum from 12 other species of enterococci, indicating that this probe is a useful tool for species identification within the genus Enterococcus.

Culture Media↗
PubMed1991

Circadian and sleep-related endocrine rhythms in schizophrenia.

Plasma levels of prolactin, growth hormone, corticotropin, and cortisol were measured at 15-minute intervals for 24 hours in nine unmedicated male schizophrenic patients and in nine age-matched normal male subjects. Each study was preceded by 3 days of habituation to the laboratory environment. Sleep was polygraphically recorded. The circadian and pulsatile variations present in each hormonal profile were quantitatively characterized with the use of computer algorithms specifically designed for analyses of hormonal fluctuations. The major abnormality of neuroendocrine release that was observed in the schizophrenic patients was an almost threefold enhancement of the sleep-related increase in the prolactin level, associated with an intensified frequency of nocturnal prolactin pulses. This increased stimulatory effect of sleep on prolactin secretion was evident immediately after sleep onset. The normal inhibition of cortisol secretion during early sleep was absent in schizophrenic patients. The major sleep abnormalities were a prolonged sleep latency and a reduction in total rapid eye movement stage sleep. During wakefulness, prolactin and cortisol levels were normal. The 24-hour profile of growth hormone was unaltered in schizophrenic patients, and a sleep-onset growth hormone pulse was observed in all patients. No abnormalities were noted in the levels or temporal organization of corticotropin secretion. Both the amplitude and the timing of the cortisol rhythm were normal. We conclude that, in schizophrenic men, pituitary-adrenal function and circadian time-keeping are normal but prolactin secretion is hyperresponsive to the physiologic stimulus of sleep onset. Schizophrenia thus appears to be characterized by a subset of neuroendocrine disturbances distinct from that observed in major endogenous depression.

Adrenocorticotropic Hormone↗
PubMed1991

Effects of combinations of beta-lactams, daptomycin, gentamicin, and glycopeptides against glycopeptide-resistant enterococci.

Activities of combinations of beta-lactams, daptomycin, gentamicin, teicoplanin, and vancomycin against 11 clinical isolates of Enterococcus faecium highly resistant to glycopeptides, three plasmid-cured derivatives, eight E. faecalis and E. faecium transconjugants, and two susceptible recipient strains were tested. A marked synergy between penicillins or imipenem and glycopeptides against the glycopeptide-resistant strains but not against the glycopeptide-susceptible strains was observed by the double-disk agar diffusion assay. The synergy of combinations of amoxicillin, imipenem, penicillin G, or piperacillin with vancomycin or teicoplanin against resistant strains was confirmed by the checkerboard technique. The fractional inhibitory concentration indexes were generally below 0.25, except for one strain of E. faecium resistant to high levels of penicillin G. However, the combinations were not bactericidal as tested by time-killing experiments, and high concentrations (64 micrograms/ml) of amoxicillin, penicillin G, or piperacillin combined with 8 micrograms of vancomycin or teicoplanin per ml tended to be antagonistic. Addition of 4 micrograms of gentamicin per ml to these combinations enhanced their bactericidal effect, but they occasionally remained slightly less effective than beta-lactams associated with gentamicin. The combination of 10 micrograms of daptomycin per ml with gentamicin was bactericidal after 6 h against 11 glycopeptide-resistant strains.

Anti-Bacterial Agents↗
PubMed1991

Influence of low-level resistance to vancomycin on efficacy of teicoplanin and vancomycin for treatment of experimental endocarditis due to Enterococcus faecium.

Emergence of vancomycin-resistant strains among enterococci raises a new clinical challenge. Rabbits with aortic endocarditis were infected with Enterococcus faecium BM4172, a clinical strain resistant to low levels of vancomycin (MIC, 16 micrograms/ml) and susceptible to teicoplanin (MIC, 1 micrograms/ml), and against its susceptible variant E. faecium BM4172S obtained in vitro by insertional mutagenesis (MICs, 2 and 0.5 micrograms/ml, respectively). Control animals retained 8 to 10.5 log10 CFU/g of vegetation. We evaluated in this model the efficacy of vancomycin (30 mg/kg of body weight; mean peak and trough serum levels, 27 and 5 micrograms/ml, respectively), teicoplanin (standard dose, 10 mg/kg; mean peak and trough levels, 23 and 9 micrograms/ml, respectively; and high dose, 20 mg/kg; mean peak and trough levels, 63 and 25 micrograms/ml, respectively), gentamicin (6 mg/kg; mean peak and trough levels, 8.6 and less than 0.1 micrograms/ml, respectively), alone or in combination, given every 12 h intramuscularly for 5 days. Teicoplanin standard dose was as active as vancomycin against both strains. Vancomycin was not effective against E. faecium BM4172 but was highly effective against E. faecium BM4172S (7.5 +/- 1.1 log10 CFU/g of vegetation versus 4.9 +/- 1.0 log10 CFU/g of vegetation for vancomycin against E. faecium BM4172 and E. faecium BM4172S, respectively; P = 0.0012). A high dose of teicoplanin was more effective than vancomycin against E. faecium BM4172 (4.4 +/- 1.8 log10 CFU/g of vegetation versus 7.5 +/- 1.1 log10 CFU/g of vegetation for teicoplanin high dose and vancomycin, respectively; P less than 0.05). Against E. faecium BM4172 glycopeptide-gentamicin combinations were the most effective regimens in vitro and in vivo (2.8 +/- 0.7 and 3.5 +/- 1.3 log10 CFU/g of vegetation for vancomycin plus gentamicin and teicoplanin standard dose plus gentamicin, respectively; P < 0.05 versus single-drug regimens). We concluded that high-dose teicoplanin or the combination of a glycopeptide antibiotic plus gentamicin was effective against experimental infection due to E. faecium with low-level resistance to vancomycin.

Animals↗
PubMed1991

Urine protein excretion and swimming events.

To determine total urinary protein, albumin (ALB), and beta 2-microglobulin (beta 2m) excretion rates in relation to different speeds, 12 males were studied while swimming distances of 100, 600, and 2,000 m at maximal speed. Venous blood lactate concentrations rose to 16.1, 11.6, and 4.5 mmol.l-1 after the 100, 600, and 2,000 m events, while plasma volumes were reduced by 11.3, 7.7, and 5.5%, respectively. ALB urine excretion increased to 110-120 micrograms.min-1 after the 100 and 600 m swims and to 56 micrograms.min-1 after 2,000 m (resting values: 9 micrograms.min-1). In the meantime, the beta 2m excretion rate increased 21 and 10 times the resting values, respectively, for the two shorter swims, with no change for the longer one. Progressive plasma volume reduction was associated with the increase of the protein excretion rate. As evidenced by the creatinine clearance, the glomerular filtration rate did not change for the 100 m swim but dropped by 23 and 35% for the 600 and 2,000 m ones, respectively. On the other hand, the ALB clearance increases were elevated for the three swims, while the beta 2m clearance increases were inversely related to the swimming speeds. The data showed a relationship between the rate of protein excretion and the speed of the swim, and the reduction of plasma volume. The findings could indicate a renal glomerular alteration, with an additional dysfunction of the tubular reabsorption process when the exercise load is high during swimming events.

Albuminuria↗
PubMed1990

Hematological variations at rest and during maximal and submaximal exercise in a cold (0 degree C) environment.

The affect of negative thermal stress on hematological variables at rest, and during submaximal (sub ex) and maximal exercise (max ex) were observed for young males who volunteered in two experimental sessions, performed in cold (0 degree C) and in normal room temperature (20 degrees C). At rest, hematological variables such as RBC and derivates Hb and Hct were significantly increased (P less than 0.05) during cold stress exposure, while plasma volume decreased. The findings of this study suggest that the major factor inducing hypovolemia during low thermal stress can be imputed to local plasma water-shift mechanisms and especially to a transient shift of plasma water from intra- to extravascular compartments. Rest values for WBC and platelets (Pla) were also slightly increased during cold stress exposure. However this increase can partly be related to hemoconcentration but also to the cold induced hyperventilation activating the lung circulation. Maximal exhaustive exercise induced, in both experimental temperatures, significant (P less than 0.05) increments of RBC, Hb, Hct, and WBC while plasma volume decreased. However, Pla increase was less marked. On the other hand, cold stress raised slightly the observed variations of the different hematological variables. Submaximal exercise induced a similar, though non-significant, pattern for the different hematological variables in both experimental conditions. Observed plasma volume (delta PV%) reduction appears during exercise. However cold stress induced resting plasma volume variations that are transferred at every exercise level. Neither exercise nor cold inducement significantly modified the hematological indices (MCH, MCV, MCHC). In conclusion hematological variables are affected by cold stress exposure, even when subjects perform a physical activity.

Acclimatization↗
PubMed1990

Bactericidal activity of vancomycin, daptomycin, ampicillin and aminoglycosides against vancomycin-resistant Enterococcus faecium.

Daptomycin, vancomycin, ampicillin and aminoglycosides, alone or in combination, were tested for their bactericidal activity against 15 isolates of vancomycin-resistant Enterococcus faecium from immunocompromised children. The kill-kinetic studies at clinically achievable concentrations demonstrated that daptomycin alone or in combination with ampicillin had the greatest bactericidal activity.

Aminoglycosides↗
PubMed1990

Phenotypic and genotypic heterogeneity of glycopeptide resistance determinants in gram-positive bacteria.

Gram-positive glycopeptide-resistant bacteria isolated in various hospitals in Europe and in the United States between 1986 and 1988 were collected. Three resistance phenotypes could be distinguished. Thirty-one enterococci were highly resistant to vancomycin and teicoplanin. Resistance was transferable to other enterococci by conjugation for 16 of the 22 isolates that were tested. Homology was detected by hybridization between a probe specific for the vanA gene, which encodes an inducible high-level glycopeptide resistance protein in Enterococcus faecium BM4147, and DNA of the 31 clinical isolates and the 16 corresponding transconjugants. This indicates that a single class of resistance determinants accounts for high-level glycopeptide resistance in enterococci. The strains differed in their biotypes and resistance phenotypes and harbored resistance plasmids of various sizes, suggesting that spread of this resistance phenotype is due to dissemination of a gene rather than of a bacterial clone or of a single plasmid. Four enterococcal isolates were resistant to low levels of vancomycin and susceptible to teicoplanin. Twenty-three coagulase-negative staphylococcal isolates were resistant to teicoplanin and susceptible to vancomycin. These two groups of strains did not hybridize with the vanA probe and did not transfer resistance at a detectable frequency. The vanA gene was not detected in the glycopeptide-producing strains of Amycolatopsis orientalis (vancomycin) and Actinoplanes teichomyceticus (teicoplanin) or in various gram-positive bacteria intrinsically resistant to glycopeptides.

Anti-Bacterial Agents↗
PubMed1990

Cloning and heterospecific expression of the resistance determinant vanA encoding high-level resistance to glycopeptides in Enterococcus faecium BM4147.

Fragments of plasmid pIP816, which confers high-level glycopeptide resistance in Enterococcus faecium BM4147, were cloned into a conjugative gram-negative-gram-positive shuttle vector. The resulting hybrids were transferred by conjugation from Escherichia coli to Enterococcus faecalis and Bacillus thuringiensis. A 4-kilobase EcoRI fragment from pIP816 was found to confer vancomycin resistance in these hosts but not in E. coli or Bacillus subtilis.

Cloning, Molecular↗
PubMed1989

Transferable vancomycin and teicoplanin resistance in Enterococcus faecium.

Enterococcus faecium BM4165 and BM4178, isolated from immunocompromised patients, one treated with vancomycin, were inducibly resistant to high levels of the glycopeptide antibiotics vancomycin and teicoplanin but susceptible to the new lipopeptide daptomycin (LY146032). Strain BM4165 was also resistant to macrolidelincosamide-streptogramin B-type (MLS) antibiotics. The genes conferring resistance to glycopeptides and to MLS antibiotics in strain BM4165 were carried on plasmids pIP819 and pIP821, respectively; pIP819 also carried genes that encoded resistance to MLS antibiotics. The two plasmids, which were distinct although related, were self-transferable to other E. faecium strains. Plasmid pIP819 could also conjugate to E. faecalis, Streptococcus sanguis, S. pyogenes, S. lactis, and Listeria monocytogenes, in which it conferred inducible glycopeptide resistance, but not to S. aureus. Glycopeptide-inactivating activity was not detected, and the biochemical mechanism of resistance remains unknown. Based on this first report of transferable resistance to glycopeptides, we anticipate dissemination of resistance to these antibiotics in gram-positive cocci and bacilli in which it can be phenotypically expressed.

Adult↗
PubMed1989

[In vitro antibacterial activity of a new fluoroquinolone, fleroxacin as a function of the sensitivity or resistance to nalidixic acid and to pefloxacin].

Minimal inhibitory concentrations (MIC) of fleroxacin (FLE) were evaluated by agar dilution for 375 bacterial strains. For Enterobacteriaceae, MIC of FLE were (microgram/ml): nalidixic acid (NAL), susceptible (S), pefloxacin (PEF), susceptible (S) strains: 0.032 to 0.5; NAL, resistant (R), PEF S: 0.25 to 1; NAL R, PEF R: 1 to 32; NAL R, PEF R strains were particularly observed among Serratia marcescens and Providencia stuartii, Pseudomonas aeruginosa was less susceptible to FLE (MIC 1 to 4), as to PEF; two PEF R strains were inhibited by 32 micrograms/ml of FLE. FLE was active on A. baumannii PEF S strains (0.5), but this activity was reduced on PEF R strains (2 to 64). H. influenzae and N. meningitidis (0.03 to 0.06), N. gonorrhoeae (0.016 to 0.03) and L. pneumophila (0.03 to 0.25) were very susceptible to FLE. MIC of FLE on S. aureus were 0.25 to 1 for PEF S strains and greater than or equal to 16 for PEF R strains, also resistant to methicillin. Enterococci, Streptococci and Pneumococci were less susceptible to FLE (2 to 8). C. perfringens (0.5 to 1) appeared susceptible to FLE whereas B. fragilis was inhibited by higher concentrations (4 to 8). So, antibacterial properties of FLE are very similar to that of PEF; PEF R strains appear generally resistant to FLE.

Anti-Infective Agents↗
PubMed1989

[Selection of constitutive mutants of gram-positive cocci inducible resistant to macrolides, lincosamides and streptogramins (MLS): comparison of the selective effects of the MLS].

Mutation frequencies to constitutive resistance were determined for 7 strains inducible resistant to the MLS antibiotics (5 Staphylococcus aureus, 1 group G Streptococcus and 1 Streptococcus sanguis). In the 5 staphylococcal strains, mutants were generally selected at a frequency of 10(-9) to 10(-10) (ranging from 4.10(-8) to 9.10(-11) on plates containing 50 mg/l of the following non-inducer MLS: spiramycin, josamycin, midecamycin, miocamycin, lincomycin, clindamycin, and pristinamycin factor I (PI). No mutant was selected by 50 mg/l of pristinamycin factor II (PII) or by pristinamycin complex (P). Absence of selection of constitutive mutant by P was due to the low MICs of the antibiotic against the constitutively resistant strains and to the effect of PII: the emergence of the mutants constitutively resistant to PI was prevented by a 6-hour contact of the culture with PII (50 mg/l). MICs and MBCs of the pristinamycin against 9 constitutive mutants were respectively 2 to 4-fold and 2 to 8-fold greater than that against the wild-strains. In the streptococci, no constituvely resistant mutant was selected. Therefore, the risk of selection of resistant mutants by a non inducer MLS in the course of the treatment of infections due to inducible resistant staphylococcus appeared to be low, especially in the case of pristinamycin.

Aminoglycosides↗