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R Leclercq

Publications and source records attributed to R Leclercq.

At least 19 recordsLinked to original sources
PubMed1997

Enterococci acquire new kinds of resistance.

In recent years, enterococci have become increasingly resistant to a broad range of antimicrobial agents. The development of high-level resistance to aminoglycosides, penicillins, and glycopeptides singly and in combination has important clinical implications. Strains of Enterococcus faecium that are resistant to every useful available antibiotic have been described. Resistance to penicillin can be due to overproduction of penicillin-binding protein (which has low affinity for penicillins) or to production of beta-lactamase. High-level resistance of enterococci to gentamicin is due to the synthesis of a modifying enzyme. In this case, the synergistic activity of the combination of penicillin with any aminoglycoside (except for streptomycin) is totally abolished. Acquired resistance to glycopeptides is often plasmid-mediated and is associated with a major epidemic potential since certain plasmids are self-transferable from E. faecium to a variety of gram-positive organisms, including Staphylococcus aureus.

Cross Infection↗
PubMed1997

The VanS sensor negatively controls VanR-mediated transcriptional activation of glycopeptide resistance genes of Tn1546 and related elements in the absence of induction.

Transposon Tn1546 from Enterococcus faecium BM4147 encodes a histidine protein kinase (VanS) and a response regulator (VanR) that regulate transcription of the vanHAX operon encoding a dehydrogenase (VanH), a ligase (VanA), and a D,D-dipeptidase (VanX). These last three enzymes confer resistance to glycopeptide antibiotics by production of peptidoglycan precursors ending in the depsipeptide D-alanyl-D-lactate. Transcription of vanS and the role of VanS in the regulation of the vanHAX operon were analyzed by inserting a cat reporter gene into vanS. Transcription of cat and vanX was inducible by glycopeptides in partial diploids harboring vanS and vanS(omega)cat but was constitutive in strains containing only vanS(omega)cat. Promoters P(R) and P(H), located upstream from vanR and vanH, respectively, were cloned into a promoter probing vector to study transactivation by chromosomally encoded VanR and VanS. The promoters were inactive in the absence of vanR and vanS, inducible by glycopeptides in the presence of both genes, and constitutively activated by VanR in the absence of VanS. Thus, induction of the vanHAX operon involves an amplification loop resulting from binding of phospho-VanR to the P(R) promoter and increased transcription of the vanR and vanS genes. Full activation of P(R) and P(H) by VanR was observed in the absence of VanS, indicating that the sensor negatively controls VanR in the absence of glycopeptides, presumably by dephosphorylation. Activation of the VanR response regulator in the absence of VanS may involve autophosphorylation of VanR with acetyl phosphate or phosphorylation by a heterologous histidine protein kinase.

Anti-Bacterial Agents↗
PubMed1996

Consecutive isolation of homologous strains of methicillin-resistant and methicillin-susceptible Staphylococcus aureus from a hospitalized child.

A multiply resistant, methicillin-resistant Staphylococcus aureus was repeatedly isolated from the anterior nares of a premature neonate hospitalized in an intensive-care unit and treated with multiple courses of antibiotics. Two months following cessation of antibiotic therapy, a strain of S. aureus with a similar antibiotic resistance profile, but susceptible to methicillin, was isolated from three consecutive nasal swabs. Total DNA of the methicillin-susceptible and -resistant isolates was digested with SmaI and resolved by pulsed-field gel electrophoresis. The SmaI restriction profile of the susceptible isolate was similar to that of the resistant one except for the replacement of a 207-kb fragment by a 147-kb fragment. In Southern hybridization, a mecA-specific probe hybridized to the 207-kb SmaI fragment of the methicillin-resistant strain but not to DNA of the susceptible strain. These results suggest that loss of the mecA gene can occur in vivo when antibiotic selective pressure is removed.

Base Sequence↗
PubMed1996

Influence of oral glycopeptides on the fecal flora of human volunteers: selection of highly glycopeptide-resistant enterococci.

Changes in fecal flora were evaluated in 22 healthy volunteers administered oral vancomycin or teicoplanin in 1989-1991 in Belgium. Evaluation of 5 colonies per subject revealed no glycopeptide-resistant enterococci in the predominant flora before glycopeptide administration; however, large numbers (mostly Enterococcus faecium) emerged by the end of the study in 14 (64%) of the subjects. Pediococci and lactobacilli also increased in number. In 1992, 40 healthy volunteers and 33 cancer patients were evaluated by plating stool samples directly onto selective media containing vancomycin; low numbers of vancomycin-resistant enterococci (< 50 cfu/g) were found in 11 (28%) of the 40 and 4 (12%) of the 33 samples, respectively. DNA restriction fragment length polymorphism analysis showed that most isolates were different, but all contained vanA in Tn1546-like elements. These results indicate that vanA and Tn1546-like elements were common in Belgium as early as 1989 and that community-based individuals in that location likely form a major reservoir for glycopeptide-resistant enterococci.

Adult↗
PubMed1996

Use of the coagulase gene typing method for detection of carriers of methicillin-resistant Staphylococcus aureus.

Strains of Staphylococcus aureus can be typed on the basis of the polymorphism of the coagulase gene. DNA fragments generated after amplification by polymerase chain reaction (PCR) of the variable region of this gene and digested with the restriction enzyme HaeIII can be compared by their restriction fragment length polymorphism (RFLP). Seventy-nine of 86 (91.8%) methicillin-resistant S. aureus (MRSA) strains isolated in various hospitals had a characteristic RFLP pattern. This pattern differed from those of 32 methicillin-susceptible S. aureus (MSSA). Only one MSSA shared with MRSA the same RFLP pattern. After modification, we applied this method to the rapid detection of MRSA from 255 nasal swabs from patients hospitalized in intensive care units. When screened by plating on Chapman agar, 55 of these samples contained MRSA, whereas 40/55 yielded the expected restriction profile after amplification by PCR. No DNA was amplified by PCR in 9/55 samples and restriction profiles were uninterpretable in six cases. When compared to culture, the positive and negative predictive values of the PCR test were 100% and 93%, respectively. The specificity was 100% and the sensitivity was 72.7%. Since control of spread of MRSA strains in hospitals is based in part on rapid isolation of carriers, this method which allows detection of epidemic MRSA in nasal swabs within a day could be helpful, though culture would still be necessary to confirm the result.

Bacterial Typing Techniques↗
PubMed1996

Survey of enterococcal susceptibility patterns in Belgium.

A national surveillance study was performed in order to identify the enterococci causing important infections, to determine their susceptibilities to first-choice agents for treatment, and to characterize the phenotypes and genotypes of the glycopeptide-resistant strains. A total of 472 isolates were collected between 15 January and 15 April 1993. The ability of the API rapid ID 32 STREP gallery to identify enterococci was evaluated. The majority of the Belgian enterococci were identified as E. faecalis (89.4%). E. faecium and other enterococci were present in small percentages only (9.1 and 1.5%, respectively). The API rapid ID 32 STREP system identified 88.6% of the strains with an excellent or very good identification score. For the majority of the strains with uncertain identification scores, the results of a single test only were aberrant. Only 2.3% of the strains remained unidentified. High-level aminoglycoside resistance was widespread in E. faecalis (streptomycin, 50.8%; gentamicin, 8.7%), and the emergence of ciprofloxacin resistance was found to be associated with aminoglycoside resistance. E. faecium is generally more resistant to a wide range of antibiotics, but glycopeptide-resistant strains (1.5%) have not yet become widespread.

Belgium↗
PubMed1996

[Bacterial resistance and management of nosocomial infections: relations to hematology].

Because they receive many infected patients with various degrees of immunosuppression, the haematology departments have a high consumption of antibiotics. The possible relationship between antibiotic consumption and bacterial resistance is discussed in many specialities, especially for some classes like quinolones. This possible relationship has to be evocated in haematology where patients are at high risk of severe sepsis because of neutropenia. In Henri Mondor hospital, we studied the evolution of bacterial susceptibility and of antibiotic consumption in the haematology unit on a 6 year period. We found that this susceptibility was finally stable over time. The main factors which may influence the evolution of the bacterial susceptibility in our study, and in the literature are discussed.

4-Quinolones↗
PubMed1995

Evolution of bacterial susceptibility to antibiotics during a six-year period in a haematology unit.

A knowledge of the bacterial ecology of a haematology unit should help in the management of the febrile patient with or without neutropenia. We studied the prevalence and the susceptibility profiles of bacteria isolated during a six-year period among patients hospitalized in a 44-bed haematology unit. Antibiotic use over this period was also studied. The most prevalent bacteria were coagulase-negative staphylococci (CNS) (35.1%), Escherichia coli (11.4%), Staphylococcus aureus (9.9%), Enterococcus spp. (8.2%), and Pseudomonas aeruginosa (7.5%). The susceptibility of CNS to oxacillin decreased from 67-44% over six years, while that of enterobacteriaceae to amoxycillin and piperacillin was reduced by about 50%. P. aeruginosa susceptibility to ceftazidime remained remarkably stable at around 90%, despite extensive empirical use. Imipenem and ciprofloxacin were used restrictively and ceftazidime-resistant P. aeruginosa remained susceptible to these two agents in most cases. Our antibiotic policy was found to be compatible with the frequency of the bacterial strains isolated in our department and with their susceptibility profiles.

Anti-Bacterial Agents↗
PubMed1995

Critical influence of resistance to streptogramin B-type antibiotics on activity of RP 59500 (quinupristin-dalfopristin) in experimental endocarditis due to Staphylococcus aureus.

In order to determine the microbiological and pharmacokinetic parameters that best predicted the in vivo antistaphylococcal activity of the streptogramin RP 59500 (quinupristin-dalfopristin), we evaluated the activity in rabbit aortic endocarditis of three regimens of quinupristin-dalfopristin against five strains of Staphylococcus aureus with various streptogramin B-type antibiotic resistance phenotypes and susceptible to streptogramin A-type antibiotics. Quinupristin-dalfopristin was as active as vancomycin against three strains that were susceptible to its streptogramin B component quinupristin, including one strain that was inducibly resistant to erythromycin, but had a significantly decreased activity against two strains that were resistant to quinupristin, for all quinupristin-dalfopristin regimens tested (P < 0.05). The area under the concentration-time curve for quinupristin-dalfopristin in plasma divided by the MIC of quinupristin was the only parameter retained by multilinear regression that predicted the in vivo activity of quinupristin-dalfopristin (P = 0.0001), emphasizing the importance of determining the susceptibility to quinupristin in order to predict the in vivo activity of quinupristin-dalfopristin against S. aureus.

Animals↗
PubMed1995

[Bactericidal activity of combinations of ticarcillin-clavulanic acid or other beta-lactams (amoxicillin, piperacillin-tazobactam, ticarcillin) with gentamicin against Enterococcus faecalis and E. faecium].

MICs of amoxicillin, piperacillin-tazobactam, ticarcillin and ticarcillin-clavulanic acid were determined against 52 clinical strains of E. faecalis and E. faecium. Modal MICs (mg/l) of these antibiotics were 1, 4, 64 and 64, respectively. Bactericidal activity of the beta-lactams was tested at two concentrations (1/2 MIC and 100 mg/l) alone or combined with gentamicin (4 mg/l) against 10 clinical strains of Enterococcus spp. Activity of ticarcillin was not modified by the addition of clavulanic acid (4 mg/l). Time-kill curves showed that all beta-lactams at 100 mg/l were bactericidal after 18 h of incubation (decrease in bacterial counts > or = 3 log10 CFU/ml) against 6 strains of E. faecalis, with MICs of amoxicillin at 1 mg/l and 2 strains of E. faecium with MICs of amoxicillin at 1 and 2 mg/l. Addition of gentamicin resulted in a bactericidal effect at 3 or 6 hours for the great majority of the combinations studied, except against the two strains highly resistant to gentamicin. Combination of every beta-lactam at 1/2 MIC with gentamicin was synergistic (except in case of high level resistance to gentamicin) and prevented bacterial growth but was not bactericidal. Against two strains of E. faecium with high MICs of amoxicillin (8 mg/l), piperacillin-tazobactam (64 mg/l) and ticarcillin-clavulanic acid (512 mg/l), only combinations of amoxicillin 100 mg/l and gentamicin were always bactericidal. In conclusion, against E. faecalis strains, ticarcillin-clavulanic acid tested at 100 micrograms/ml had a bactericidal activity similar to that of the other beta-lactams tested, alone or combined with gentamicin.(ABSTRACT TRUNCATED AT 250 WORDS)

Amoxicillin↗
PubMed1994

The 24-hour profiles of cortisol, prolactin, and growth hormone secretion in mania.

OBJECTIVE: To characterize sleep and the 24-hour profiles of cortisol, prolactin (PRL), and growth hormone (GH) secretion in mania. METHODS: Blood was sampled at 15-minute intervals, and sleep was polygraphically recorded in eight unmedicated male patients with pure mania and the results compared with those from a group of 14 healthy age-matched controls. The circadian, sleep-related, and pulsatile hormonal variations were quantitatively characterized using specifically designed computer algorithms. RESULTS: The manic state was associated with alterations of corticotropic activity and circadian rhythmicity partially overlapping those previously observed in acute endogenous depression, consisting of an elevation of nocturnal cortisol levels and an early timing of the nadir of the circadian variation. Sleep onset was delayed and the sleep period was reduced. A trend for short rapid eye movement latencies was apparent in the adult patients. Both the amount and the temporal organization of PRL and GH secretion were normal. CONCLUSION: The manic state seems to be characterized by similar but less severe neuroendocrine and circadian abnormalities, compared with major depression.

Acute Disease↗
PubMed1994

In vivo activities and penetration of the two components of the streptogramin RP 59500 in cardiac vegetations of experimental endocarditis.

We evaluated the in vivo activity and the diffusion of radiolabelled RP 57669 (RPI) and RP 54476 (RPII), the two components of the injectable streptogramin RP 59500, alone or in combination, in aortic vegetations from experimental endocarditis in rabbits. RPI and RPII demonstrated in vitro bacteriostatic and bactericidal synergy against a clinical strain of Staphylococcus aureus resistant to methicillin and susceptible to erythromycin. In experimental staphylococcal endocarditis, RP 59500 was as effective as vancomycin and significantly more effective than RPI (P < 0.01) and RPII (P < 0.05). Autoradiography studies showed different patterns of distribution into cardiac vegetations infected with Streptococcus sanguis for [14C]RPI and [14C]RPII. [14C]RPI was homogeneously distributed throughout the vegetations whereas [14C]RPII showed a decreasing gradient of concentration between the periphery and the core of the vegetation, with an approximately 2:1 ratio. [14C]RPI diffused approximately 2 to 4 times more than [14C]RPII into the core of the vegetations. Since the injected ratio of RPI and RPII is 30:70 in RP 59500, the actual RPI:RPII ratio in the core of the vegetation may range from 0.8 to 1.7, a ratio which remains compatible with the in vivo synergism demonstrated between the two components.

Animals↗
PubMed1993

Overproduction of 3'-aminoglycoside phosphotransferase type I confers resistance to tobramycin in Escherichia coli.

Escherichia coli HM69, isolated from urine, was resistant to high levels of kanamycin (MIC, > 1,000 micrograms/ml) and a low level of tobramycin (MIC, 8 micrograms/ml). Phosphocellulose paper-binding assays and molecular cloning indicated that resistance to both aminoglycosides was due to synthesis of a 3'-aminoglycoside phosphotransferase type I, an enzyme that phosphorylates kanamycin but not tobramycin. The structural gene for the enzyme was borne by an 80-kb conjugative plasmid, pIP1518, and was nearly identical to aphA1 of Tn903. Incubation of extracts of resistant cells with tobramycin or kanamycin led to a decrease (> 80%) of antibiotic activity as determined by a microbiological assay. Heat treatment showed that loss of activity was reversible and dependent upon the native enzyme. In the presence of ATP, only inactivation of kanamycin was reversible. These results suggest that resistance to low levels of tobramycin was due to formation of a complex between the enzyme and the antibiotic.

Aminoglycosides↗
PubMed1993

Identification of the satA gene encoding a streptogramin A acetyltransferase in Enterococcus faecium BM4145.

Enterococcus faecium BM4145, a clinical isolate from urine, was resistant to streptogramin group A antibiotics by inactivation. The strain harbored a plasmid containing a gene, satA, responsible for this resistance; this gene was cloned and sequenced. It encoded SatA, a protein deduced to be 23,634 Da in mass and homologous with a new family of chloramphenicol acetyltransferases described in Agrobacterium tumefaciens, Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. The similarity of SatA to other acetyltransferases, LacA (thiogalactoside acetyltransferase) and CysE (serine acetyltransferase) from E. coli, and to two putative acetyltransferases, NodL from Rhizobium leguminosarum and Urf1 from E. coli, was also observed in a region considered to be the enzyme's active site. Acetylation experiments indicated that acetyl coenzyme A was necessary for SatA activity and that a single acetylated derivative of pristinamycin IIA was produced. Other members of the streptogramin A group such as virginiamycin M and RP54476 were also substrates for the enzyme. We conclude that resistance to the streptogramin A group of antibiotics in E. faecium BM4145 is due to acetylation by an enzyme related to the novel chloramphenicol acetyltransferase family.

Acetylation↗
PubMed1993

Fusidic acid alone or in combination with vancomycin for therapy of experimental endocarditis due to methicillin-resistant Staphylococcus aureus.

The usefulness of fusidic acid, alone or combined with vancomycin, was investigated for the therapy of experimental endocarditis caused in rabbits by a methicillin-resistant strain of Staphylococcus aureus. In vitro killing curves showed an indifferent interaction between the two antibiotics. In vivo, vancomycin alone was as effective as a vancomycin-fusidic acid combination (P < 0.05 versus control animals). No resistance to fusidic acid emerged during combination therapy. Fusidic acid alone was not effective. Resistance emerged in 5 of 12 animals treated with fusidic acid alone and was responsible for antibacterial failure. Fusidic acid alone was effective (P < 0.001) and did not select resistant strains if therapy was started when animals retained a smaller inoculum. We concluded that the vancomycin-fusidic acid combination exhibited no advantage over vancomycin alone in this model.

Animals↗
PubMed1993

Antimicrobial susceptibility of Pediococcus spp. and genetic basis of macrolide resistance in Pediococcus acidilactici HM3020.

We determined the MICs of 28 antimicrobial agents against 36 clinical strains of Pediococcus spp. (25 P. acidilactici, 9 P. pentosaceus, and 2 P. urinaeequi strains). Penicillin G, imipenem, gentamicin, netilmicin, erythromycin, clindamycin, rifampin, chloramphenicol, daptomycin, and ramoplanin were the most active. All strains of P. acidilactici were susceptible to novobiocin, whereas all isolates of P. pentosaceus were resistant. Novobiocin could therefore be helpful for differentiation of these two closely related species. P. acidilactici HM3020 was inducibly resistant to macrolide, lincosamide, and streptogramin B-type (MLS) antibiotics. Resistance was due to a determinant homologous to ermAM and carried by a nontransferable 46-kb plasmid, pVM20. This plasmid was structurally distinct from two enterococcal MLS resistance plasmids, pIP819 and pAM beta 1. The 34 strains of P. acidilactici and P. pentosaceus were resistant to tetracycline, and total DNA of these strains did not hybridize to probes specific for tetK, tetL, tetM, and tetO.

Anti-Bacterial Agents↗