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Biomedical subjects

B Heym

Publications and source records attributed to B Heym.

At least 19 recordsLinked to original sources
PubMed2006

Pasteurella multocida infection of a total knee arthroplasty after a "dog lick".

The patient we report here underwent a total knee arthroplasty (TKA) which got infected with P. multocida after her dog had licked a small wound at the third toe of the same foot. Despite a correct treatment comprising synovectomy and cleansing, and an active antibiotic treatment for 3 months, the patient was readmitted for persistent infection of the same knee 2 weeks after the end of the antibiotic treatment. Sampling during surgery allowed for the growth of a P. multocida isolate proven by a molecular method to be identical to the previously isolated strain. This recurrent P. multocida infection was treated by a two-step change of the TKA comprising a 2-month period of antibiotic treatment between the two surgical interventions.

Aged↗
PubMed2004

Bacteriological investigation of infected pressure ulcers in spinal cord-injured patients and impact on antibiotic therapy.

STUDY DESIGN: Retrospective. OBJECTIVES: To improve the use of bacteriological results for treating spinal cord-injured patients with infected pressure ulcers. SETTING: Microbiology and Orthopaedics Department, Ambroise Paré University Hospital, Boulogne-Billancourt, France. METHODS: Tissue specimens, sampled at the end of the surgical intervention from unbridled and cleaned ulcers were analysed. Drainage liquids were cultured at day 1 (D1) and day 5 (D5) postsurgery. For part of the patients, a presurgery superficial sample was analysed and compared with the surgical and postsurgical samples. RESULTS: In all, 168 surgical samples from 101 patients, 183 D1 and 104 D5 wound drainage liquids were included in this study. Out of the 168 surgical samples 17 (10%) had a negative culture, whereas 151 (90%) had a positive culture. For drainage liquids, the culture was negative in 48% and 56% of the samples at D1 and D5, respectively. The most frequently isolated species were enterobacteria, followed by staphylococci and streptococci. CONCLUSION: Culturing deep tissue specimens sampled from the surgically cleaned and unbridled ulcers allows for the isolation of the bacterial species that are really involved in the ulcer infection. As the identification of these bacteria and their antibiotic susceptibility are available, when the culture results of the D1 postsurgical drainage liquid is also available, it is easier to choose targeted antibiotic treatment.

Anti-Bacterial Agents↗
PubMed2003

[Re-infection with a different strain after prosthesis revision for bacterial infection: 13 cases].

PURPOSE OF THE STUDY: Treatment of an infected arthroplasty is always a delicate task. Multidisciplinary management involving surgeons, clinicians, bacteriologists, and the patient may be long and not always successful. Rare re-infections caused by a bacterial strain different from the initial strain may be a cause of failure. We analyzed cases of re-infection with a different strain in search of an explanation. MATERIAL AND METHODS: We reviewed 13 cases of re-infection in 12 patients with 7 hip and 5 knee arthroplasties. The causal germ had been clearly identified by the bacteriology laboratory during the first infection. The antibiotic regimens were confirmed by the medical team. All patients underwent surgery in our unit. At the time of the second infection, the implant had been removed, had been left in place, or had been changed. We recorded the new strains isolated and studied their antibiotic susceptibility profile. Treatment protocols and biological and functional results were analyzed. RESULTS: A mean 27 months after the re-infection, clinical and biological success had been achieved in 7 cases. The failures more frequently corresponded to cases where the first infection was caused by an aggressive germ and where the second germ was found during reimplantation. DISCUSSION: Theoretically a change in the causal germ could be explained by an insufficient initial biological analysis with an unrecognized or masked germ, by peroperative contamination subsequent to the difficulties observed in these hospitalized patients, and finally by secondary contamination. We recall the criteria of secondary infection (free interval, distant infectious focus, time sequence), measures taken to prevent peroperative infections, and conditions for optimal bacteriological sampling. If no resistance emerges after the first antibiotic treatment, there could nevertheless be a selection of conditions enabling growth of germs infrequently encountered. We stress that re-infection should not be considered necessarily as a failure of initial management but can, in certain cases, be considered as a de novo infection, and treated as such.

Adult↗
PubMed2002

Multilocus sequence typing (MLST) shows that the 'Iberian' clone of methicillin-resistant Staphylococcus aureus has spread to France and acquired reduced susceptibility to teicoplanin.

Infection by methicillin-resistant Staphylococcus aureus (MRSA) presents a serious problem, as these organisms are resistant to a wide range of antibiotics. Moreover, MRSA with reduced susceptibility to glycopeptides (GISA) have emerged in recent years. In our hospital we were faced with an outbreak of GISA between January and March 2000, involving six patients who were free of MRSA when the GISA isolate emerged, and five of whom had not been given glycopeptides. The initial GISA isolate from the six patients was compared with six 'historical' multiple-resistant MRSA isolates (1996-1999), which had not been found to be GISA by the routinely used method. Antibiotic susceptibility was studied through the disc diffusion method, and MICs of glycopeptides were determined by Etest, agar and broth dilution techniques. Molecular strain typing was done by PFGE and multilocus sequence typing (MLST). All 12 isolates that belonged to the gentamicin-resistant group of MRSA were susceptible to vancomycin, but showed reduced susceptibility to teicoplanin through at least one MIC method. PFGE typing yielded five different but closely related profiles, and eight of the 12 clinical isolates were classified into a single PFGE type. MLST yielded an identical allelic profile for all 12 isolates, corresponding to the profile (3-3-1-12-4-4-16) of the 'Iberian' clone HPV107 of MRSA. MLST allowed us to confirm the presence of the 'Iberian' MRSA clone HPV107 with the same allelic profile in our hospital for several years. We can now note that strains of this clone have acquired reduced susceptibility to teicoplanin.

Anti-Bacterial Agents↗
PubMed2001

Role of OxyS of Mycobacterium tuberculosis in oxidative stress: overexpression confers increased sensitivity to organic hydroperoxides.

Mycobacterial genomics has uncovered a novel regulatory gene, oxyS, belonging to the LysR family. There is extensive similarity in the DNA-binding domain of OxyS with that of OxyR, the oxidative stress response protein of many bacteria. Since the oxyR gene of Mycobacterium tuberculosis has been multiply inactivated during evolution it was conceivable that some of its functions could be effected by OxyS. It is shown here that OxyS is produced at low levels and that there are at least three different oxyS alleles present in clinical isolates of M. tuberculosis that are susceptible or resistant to isoniazid. Overproduction or depletion of OxyS did not affect susceptibility to isoniazid but increasing the concentration of the regulator lowered levels of the alkyl hydroperoxide reductase, AhpC, and rendered the tubercle bacillus more susceptible to organic hydroperoxides.

Amino Acid Sequence↗
PubMed2001

Familial outbreak of disseminated multidrug-resistant tuberculosis and meningitis.

Rapidly progressive multidrug-resistant tuberculosis (MDR-TB) is well documented in human immunodeficiency virus (HIV) positive subjects, but it is not fully recognised in HIV-negative subjects in the familial environment. We report three cases of MDR-TB in three young HIV-negative subjects from the same family. All the patients showed signs of meningitis during the course of their disease, and in two cases a resistant strain of Mycobacterium tuberculosis was isolated in cerebrospinal fluid. Two of the three subjects died from neurological complications; the other was successful treated utilising both systemic and intrathecal therapy for tuberculous meningitis. By a retrospective analysis of DNA obtained from Lowenstein-Jensen cultures, the strains were confirmed as M. tuberculosis resistant to rifampicin and isoniazid, and were closely related in the two cases where specimens were available for analysis. The resistance was acquired in two patients initially infected with a susceptible strain; in the other patient, the resistance was present on the first sensitivity test for which results were available. This report demonstrates the high risk of fatality from MDR-TB for HIV-negative subjects in the absence of reliable early diagnostic and preventive tools. It also reinforces the concept that genetic susceptibility to M. tuberculosis may be an important factor in the clinical presentation and outcome of MDR-TB.

Adolescent↗
PubMed2000

Epidemiological survey of amoxicillin-clavulanate resistance and corresponding molecular mechanisms in Escherichia coli isolates in France: new genetic features of bla(TEM) genes.

Amoxicillin-clavulanate resistance (MIC >16 microg/ml) and the corresponding molecular mechanisms were prospectively studied in Escherichia coli over a 3-year period (1996 to 1998) in 14 French hospitals. The overall frequency of resistant E. coli isolates remained stable at about 5% over this period. The highest frequency of resistant isolates (10 to 15%) was observed, independently of the year, among E. coli isolated from lower respiratory tract samples, and the isolation rate of resistant strains was significantly higher in surgical wards than in medical wards in 1998 (7.8 versus 2.8%). The two most frequent mechanisms of resistance for the 3 years were the hyperproduction of the chromosomal class C beta-lactamase (48, 38.4, and 39.7%) and the production of inhibitor-resistant TEM (IRT) enzymes (30.4, 37.2, and 41.2%). By using the single-strand conformational polymorphism-PCR technique and sequencing methods, we determined that 59 IRT enzymes corresponded to previously described IRT enzymes whereas 8 were new. Three of these new enzymes derived from TEM-1 by only one amino acid substitution (Ser130Gly, Arg244Gly, and Asn276Asp), whereas three others derived by two amino acid substitutions (Met69Leu and Arg244Ser, Met69Leu and Ile127Val, and Met69Val and Arg275Gln). The two remaining new IRTs showed three amino acid substitutions (Met69Val, Trp165Arg, and Asn276Asp and Met69Ile, Trp165Cys, and Arg275Gln). New genetic features were also found in bla(TEM) genes, namely, bla(TEM-1B) with either the promoters Pa and Pb, P4, or a promoter displaying a C-->G transversion at position 3 of the -35 consensus sequence and new bla(TEM) genes, notably one encoding TEM-1 but possessing the silent mutations originally described in bla(TEM-2) and then in some bla(TEM)-encoding IRT enzymes.

Amino Acid Substitution↗
PubMed2000

Updated sequence information and proposed nomenclature for bla(TEM) genes and their promoters.

The nucleotide sequences of 59 bla(TEM) genes encoding inhibitor-resistant TEM enzymes showed great genetic variability and were associated with different types of promoters. These findings led us to suggest an updated bla(TEM) gene nomenclature based on the origin of the bla(TEM) gene (bla(TEM-1A), bla(TEM-1B), bla(TEM-1C), bla(TEM-1D), bla(TEM-1E), and bla(TEM-1F)) and the promoter type.

Genetic Variation↗
PubMed1999

Evidence for a small anion-selective channel in the cell wall of Mycobacterium bovis BCG besides a wide cation-selective pore.

Two channels were observed in extracts of whole Mycobacterium bovis BCG cells using organic solvents and detergents. The channels derived from organic solvent treatment had a single-channel conductance of about 4.0 nS in 1 M KCl in lipid bilayer membranes with properties similar to those of the channels discovered previously in Mycobacterium smegmatis and Mycobacterium chelonae. The channel was in its open configuration only at low transmembrane potentials. At higher voltages it switched to closed states that were almost impermeable for ions. Lipid bilayer experiments in the presence of detergent extracts of whole cells revealed another channel with a single-channel conductance of only 780 pS in 1 M KCl. Our results indicate that the mycolic acid layer of M. bovis BCG contains two channels, one is cation-selective and its permeability properties can be finely controlled by cell wall asymmetry or potentials. The other one is anion-selective, has a rather small single-channel conductance and is voltage-insensitive. The concentration of channel-forming proteins in the cell wall seems to be small, which is in agreement with the low cell wall permeability for hydrophilic solutes.

Anions↗
PubMed1998

Discriminatory detection of inhibitor-resistant beta-lactamases in Escherichia coli by single-strand conformation polymorphism-PCR.

Plasmid-mediated mechanisms, comprising TEM hyperproduction, TEM derivative production, and OXA production, lead to amoxicillin-clavulanic acid resistance in enterobacteria. The ability of the single-strand conformation polymorphism (SSCP)-PCR method to differentiate the genes encoding inhibitor-resistant beta-lactamases was evaluated with three bla(TEM) primer pairs. The bla(TEM) genes, which were known to be different on the basis of their nucleotide sequences (bla[TEM-1A], bla[TEM-1B], bla[TEM-2], bla[TEM-30], bla[TEM-32], and bla[TEM-35]), were identified as different by their electrophoretic mobilities. The bla(TEM-33), bla(TEM-34), bla(TEM-36), bla(TEM-37), bla(TEM-38), and bla(TEM-39) genes, whose sequence differences have been established by oligotyping, displayed different SSCP profiles for different fragments, suggesting genetic differences in addition to those defined by oligotyping. Confirmed by sequencing, these additional genetic events concerned silent mutations at certain positions and, notably, a G-->T transversion at position 1 of the -10 consensus sequence in bla(TEM-34), bla(TEM-36), bla(TEM-37), and bla(TEM-39). Applied to eight clinical isolates of Escherichia coli resistant to amoxicillin-clavulanic acid, the SSCP method detected TEM-1 in three strains and TEM-30, TEM-32, and TEM-35 in three other strains, respectively. A novel TEM derivative (TEM-58) was detected in another strain, and the deduced amino acid sequence showed two substitutions: Arg244Ser, which is known to confer amoxicillin-clavulanic acid resistance in TEM-30, and Val261Ile, which has not been described previously. The eighth strain produced an OXA beta-lactamase. Given the discriminatory power and the applicability of SSCP-PCR, this method can be proposed as a means of following the evolution of the frequencies of the different inhibitor-resistant beta-lactamases.

Amoxicillin-Potassium Clavulanate Combination↗
PubMed1997

On the catalase-peroxidase gene, katG, of Mycobacterium leprae and the implications for treatment of leprosy with isoniazid.

The toxicity of the potent tuberculocidal agent, isoniazid, is mediated by the heme-containing enzyme, catalase-peroxidase, encoded by the katG gene. Although isoniazid has been used for the treatment of leprosy, it is shown here that the katG gene of Mycobacterium leprae is a pseudogene, which has probably been inactivated by multiple mutations. Inactive genes were detected by the polymerase chain reaction in several isolates of M. leprae, of different geographical origins, and attempts to complement an isoniazid-resistant strain of Mycobacterium smegmatis with the katG pseudogene were unsuccessful. Isoniazid is thus likely to be of no therapeutic benefit to leprosy patients.

Antitubercular Agents↗
PubMed1997

Typing of Clostridium perfringens strains by use of Random Amplified Polymorphic DNA (RAPD) system in comparison with zymotyping.

The definition of strain clonality postulates that strains showed identical phenotypic and genetic traits are likely to descend from a common ancestor even if they were isolated from different sources and locations. Regarding this definition, non-epidemiologically linked strains might be clonal strains. To overcome this ambiguity, the discriminatory capability of RAPD typing was assessed firstly on eight Clostridium perfringens strains proven to be chromosomally different with one being the mutant of another one. Thirteen primers were tested but only two were able to differentiate seven of the eight strains. With none of the used primers it was possible to differentiate the parental strain and its mutant harboring an insertion of 180 kb. The four most discriminant primers were retained to determine the RAPD fingerprints of a further 20 previously zymotyped strains from which seventeen were unrelated. To compare the two typing systems, the zymotype of the eight chromosomally different strains was determined. Thus, the discriminatory index was calculated on the basis of 25 unrelated C. perfringens strains. This was 0.97 with RAPD typing and 0.99 with zymotyping. From these results we conclude that the RAPD typing which is less fastidious than zymotyping can be used as an epidemiological marker for C. perfringens.

Journal Article↗
PubMed1997

Effects of overexpression of the alkyl hydroperoxide reductase AhpC on the virulence and isoniazid resistance of Mycobacterium tuberculosis.

Mutations to the regulatory region of the ahpC gene, resulting in overproduction of alkyl hydroperoxide reductase, were encountered frequently in a large collection of isoniazid (INH)-resistant clinical isolates of Mycobacterium tuberculosis but not in INH-susceptible strains. Overexpression of ahpC did not seem to be important for INH resistance, however, as most of these strains were already defective for catalase-peroxidase, KatG, the enzyme required for activation of INH. Transformation of the INH-susceptible reference strain, M. tuberculosis H37Rv, with plasmids bearing the ahpC genes of M. tuberculosis or M. leprae did not result in a significant increase in the MIC. Two highly INH-resistant mutants of H37Rv, BH3 and BH8, were isolated in vitro and shown to produce no or little KatG activity and, in the case of BH3, to overproduce alkyl hydroperoxide reductase as the result of an ahpC regulatory mutation that was also found in some clinical isolates. The virulence of H37Rv, BH3, and BH8 was studied intensively in three mouse models: fully immunocompetent BALB/c and Black 6 mice, BALB/c major histocompatibility complex class II-knockout mice with abnormally low levels of CD4 T cells and athymic mice producing no cellular immune response. The results indicated that M. tuberculosis strains producing catalase-peroxidase were considerably more virulent in immunocompetent mice than the isogenic KatG-deficient mutants but that loss of catalase-peroxidase was less important when immunodeficient mice, unable to produce activated macrophages, were infected. Restoration of virulence was not seen in an INH-resistant M. tuberculosis strain that overexpressed ahpC, and this finding was confirmed by experiments performed with appropriate M. bovis strains in guinea pigs. Thus, in contrast to catalase-peroxidase, alkyl hydroperoxide reductase does not appear to act as a virulence factor in rodent infections or to play a direct role in INH resistance, although it may be important in maintaining peroxide homeostasis of the organism when KatG activity is low or absent.

Animals↗
PubMed1997

Genotypic assessment of isoniazid and rifampin resistance in Mycobacterium tuberculosis: a blind study at reference laboratory level.

Progress in understanding the basis of resistance to isoniazid (INH) and rifampin (RMP) has allowed molecular tests for the detection of drug-resistant tuberculosis to be developed. Consecutive isolates (n = 95) of Mycobacterium tuberculosis, from a Spanish reference laboratory investigating outbreaks of multidrug-resistant tuberculosis, were coded and sent to two external laboratories for genotypic analysis of INH and RMP resistance by PCR-single-strand conformation polymorphism (SSCP) analysis of specific regions of four genes: part of the coding sequence of katG and the promoter regions of inhA and ahpC for INH and the RMP resistance region of rpoB. After correction for the presence of outbreak strains and multiple isolates from single patients, RMP resistance was detected successfully by PCR-SSCP in > 96% of the RMP-resistant strains. PCR-SSCP had a sensitivity of 87% for INH resistance detection, and mutations in katG, inhA, katG-inhA, ahpC, and katG-ahpC were identified in 36.8, 31.6, 2.6, 13.2, and 2.6%, respectively, of the unique strains. Specificity was 100%. Molecular detection of resistance to the two main antituberculous drugs, INH and RMP, can be accomplished accurately by using a strategy which limits analysis to four genetic regions. This may allow the expedient analysis of drug resistance by reference laboratories.

Antibiotics, Antitubercular↗
PubMed1996

An integrated map of the genome of the tubercle bacillus, Mycobacterium tuberculosis H37Rv, and comparison with Mycobacterium leprae.

An integrated map of the genome of the tubercle bacillus, Mycobacterium tuberculosis, was constructed by using a twin-pronged approach. Pulsed-field gel electrophoretic analysis enabled cleavage sites for Asn I and Dra I to be positioned on the 4.4-Mb circular chromosome, while, in parallel, clones from two cosmid libraries were ordered into contigs by means of fingerprinting and hybridization mapping. The resultant contig map was readily correlated with the physical map of the genome via the landmarked restriction sites. Over 165 genes and markers were localized on the integrated map, thus enabling comparisons with the leprosy bacillus, Mycobacterium leprae, to be undertaken. Mycobacterial genomes appear to have evolved as mosaic structures since extended segments with conserved gene order and organization are interspersed with different flanking regions. Repetitive sequences and insertion elements are highly abundant in M. tuberculosis, but the distribution of IS6110 is apparently nonrandom.

Chromosome Mapping↗
PubMed1996

The katE gene, which encodes the catalase HPII of Mycobacterium avium.

Disseminated Mycobacterium avium-Mycobacterium intracellulare disease is a prevalent opportunistic infection in patients with acquired immune deficiency syndrome (AIDS). These pathogens are generally resistant to isoniazid (INH), a powerful antituberculosis drug. It is now generally accepted that the INH susceptibility of Mycobacterium tuberculosis results from the transformation of the drug into a toxic derivative, as a result of the action of the enzyme catalase-peroxidase (HPI), encoded by the katG gene. It has been speculated that the presence of a second catalase (HPII) in some mycobacterial species, but lacking in M. tuberculosis, may impair the action of INH. In this report, the nucleotide sequence of the M. avium katE gene, encoding catalase HPII, is described. This enzyme shows strong similarity to Escherichia coli catalase HPII and eukaryotic catalases. All amino acids previously postulated as participating directly in catalysis by liver catalase and most of the amino acids binding the prosthetic group are conserved in M. avium catalase HPII. The enzyme is expressed in E. coli and is inhibited by 3-amino-1,2,4-triazole (AT). Furthermore, Southern blot hybridizations and polymerase chain reaction experiments demonstrate the distribution of katE gene in several mycobacterial species. To evaluate the potentially antagonistic effect of HPII catalase on INH susceptibility, the katE gene was transformed into M. tuberculosis H37Rv and the minimum inhibitory concentration (MIC) for INH was determined. Despite strong expression of the katE gene, no change in MIC was observed, thus ruling out a possible contribution of this enzyme to the natural resistance of M. avium to the drug. The availability of the gene probe, encoding the second mycobacterial catalase HPII, should open the way for the development of new drugs and diagnostic tests to combat drug-resistant pathogen strains.

Amino Acid Sequence↗