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Biomedical subjects

V Jarlier

Publications and source records attributed to V Jarlier.

At least 91 records · Page 5Linked to original sources
PubMed1994

Mycobacterial cell wall: structure and role in natural resistance to antibiotics.

Mycobacteria show a high degree of intrinsic resistance to most antibiotics and chemotherapeutic agents. The low permeability of the mycobacterial cell wall, with its unusual structure, is now known to be a major factor in this resistance. Thus hydrophilic agents cross the cell wall slowly because the mycobacterial porin is inefficient in allowing the permeation of solutes and exists in low concentration. Lipophilic agents are presumably slowed down by the lipid bilayer which is of unusually low fluidity and abnormal thickness. Nevertheless, the cell wall barrier alone cannot produce significant levels of drug resistance, which requires synergistic contribution from a second factor, such as the enzymatic inactivation of drugs.

Cell Wall↗
PubMed1994

Amplification and nucleotide sequence of the quinolone resistance-determining region in the gyrA gene of mycobacteria.

Chromosomal DNA of different species of mycobacteria, Mycobacterium tuberculosis, Mycobacterium leprae, Mycobacterium avium and Mycobacterium smegmatis, has been submitted to polymerase chain reaction using two oligonucleotide primers highly homologous to DNA sequences flanking the quinolone resistance-determining region in the gyrA gene of Escherichia coli and Staphylococcus aureus. For each of these mycobacterial species, a 150-bp DNA fragment hybridizing with an intragenic probe of the gyrA gene of E. coli K12 was obtained. The nucleotide sequences of the 108-bp fragments amplified from M. tuberculosis and M. avium were determined. The two sequences were 87% homologous. Except for one residue, their deduced amino acid sequences were identical and shared 67% homology with the quinolone resistance-determining region of the gyrase A subunits of E. coli and S. aureus. Sequencing of the 108-bp fragment amplified from an in vitro mutant of M. avium, highly resistant to fluoroquinolones, showed a point mutation leading to the substitution of Ala for Val at a position corresponding to residues involved in quinolone resistance in E. coli and S. aureus, i.e. Ser 83 for E. coli and Ser 84 for S. aureus.

Amino Acid Sequence↗
PubMed1994

Prevention of gram negative nosocomial bronchopneumonia by intratracheal colistin in critically ill patients. Histologic and bacteriologic study.

OBJECTIVE: To evaluate the efficiency of intratracheal colistin in preventing nosocomial bronchopneumonia (BPN) in the critically ill. DESIGN: Study evaluating the clinical incidence of nosocomial BPN in 2 groups of critically ill patients who receive or did not receive intratracheal colistin. BPN was assessed clinically in survivors and histologically in non-survivors. SETTING: A 14-bed surgical intensive care unit. PATIENTS: 598 consecutive critically ill patients were studied during a prospective non-randomized study over a 40-month period. INTERVENTIONS: 251 patients--31 non-survivors and 220 survivors--did not receive intratracheal colistin and 347-42 non-survivors and 305 survivors--received intratracheal colistin for a 2-week period (1,600,000 units per 24 h). MEASUREMENTS AND RESULTS: The incidence of nosocomial BPN was evaluated clinically in survivors, using repeated protected minibronchoalveolar lavages, and histologically in non-survivors via an immediate postmortem pneumonectomy (histologic and semi-quantitative bacteriologic analysis of one lung). The clinical incidence of nosocomial BPN was of 37% in coli (-) survivors and of 27% in coli (+) survivors (p < 0.01). This result was histologically confirmed in non-survivors, where the incidence of histologic BPN was of 61% in coli (-) patients and of 36% in coli (+) patients (p < 0.001). Emergence of BPN due to colistin-resistant micro-organisms was not observed. Because colistin was successful in preventing Gram-negative BPN and did not change the absolute number of Gram-positive BPN, the proportion of BPN caused by staphylococcus species was higher in group coli (+) patients (33% vs 16%). Mortality was not significantly influenced by the administration of colistin. CONCLUSION: This study suggests that the administration of intratracheal colistin during a 2-week period significantly reduces the incidence of Gram-negative BPN without creating an increasing number of BPN due to colistin-resistant micro-organisms.

Aged↗
PubMed1994

Selection of a gyrA mutant of Mycobacterium tuberculosis resistant to fluoroquinolones during treatment with ofloxacin.

A strain of Mycobacterium tuberculosis resistant to ofloxacin was selected in a patient with a long history of multidrug-resistant tuberculosis eventually treated by ofloxacin combined with other second-line drugs. A mutation in the gyrA gene was hypothesized to be the mechanism of acquired resistance to ofloxacin in this strain. Chromosomal DNA of strains MTB1, isolated before treatment and susceptible to ofloxacin (MIC, 1 microgram/mL), and MTB2, isolated during treatment and resistant to ofloxacin (MIC, 32 micrograms/mL), was amplified by polymerase chain reaction (PCR) using two oligonucleotide primers highly homologous to DNA sequences flanking the quinolone resistance-determining region in gyrA of mycobacteria. Comparison of the nucleotide sequences of the 150-bp fragments obtained by PCR revealed a point mutation in MTB2 leading to the substitution of histidine for aspartic acid at a position corresponding to residues involved in quinolone resistance in Escherichia coli (Asp87), Staphylococcus aureus (Glu88), and Campylobacter jejuni (Asp90).

Adult↗
PubMed1994

Use of cefotaxime or ceftazidime susceptibility tests for predicting susceptibility of Enterobacteriaceae and Pseudomonas aeruginosa.

To determine if susceptibility to aztreonam could be predicted from cefotaxime or ceftazidime disc diffusion testing, 919 Enterobacteriaceae and 187 Pseudomonas aeruginosa clinical strains were studied. The correlation coefficient between the diameters of inhibition zones was 0.9 for cefotaxime versus aztreonam and ceftazidime versus aztreonam comparisons in Enterobacteriaceae and 0.75 for ceftazidime versus aztreonam comparison in P. aeruginosa. For 99% of the Enterobacteriaceae, there was no risk in predicting susceptibility to aztreonam on the basis of cefotaxime or ceftazidime susceptibility tests. To minimize the risk of the remaining 1% of the strains being erroneously classified as susceptible to aztreonam, ceftoaxime should be tested in preference to ceftazidime, and the production of extended-spectrum beta-lactamases should be tested for using the cefotaxime-clavulanate disc synergy test. For P. aeruginosa strains, susceptibility to aztreonam could be accurately predicted from ceftazidime susceptibility tests for ticarcillin susceptible strains, but for ticarcillin resistant strains, susceptibility to aztreonam should be tested.

Aztreonam↗
PubMed1994

Characterization of mutations in Mycobacterium smegmatis involved in resistance to fluoroquinolones.

Fluoroquinolone-resistant mutants of Mycobacterium smegmatis have been obtained in vitro by using ofloxacin as a selecting agent. Two types of mutants were identified according to their quinolone resistance patterns. Type 1 showed a low level of resistance to ofloxacin (MIC of 8 micrograms/ml), whereas a high level of resistance to this drug (MICs of 32 to 64 micrograms/ml) characterized type 2. By using two oligonucleotide primers homologous to DNA sequences flanking the quinolone resistance-determining region (QRDR) in the gyrA gene of Escherichia coli and Staphylococcus aureus, a 150-bp DNA fragment was obtained by PCR amplification from total DNA of two wild-type and five mutant strains of M. smegmatis. The nucleotide sequences of the amplified fragments were determined. The deduced amino acid sequence from the wild-type strains showed ca. 79% similarity with the QRDR in the gyrase A subunit from other gram-positive and gram-negative bacteria. The DNA sequences obtained from the fluoroquinolone-resistant mutants of M. smegmatis exhibited nucleotide modifications compared with the wild-type QRDR. The QRDR from type 1 mutants had a C-T or an A-G transition leading to a change from Ala-83 to Val or Asp-87 to Gly, respectively. The QRDR from type 2 mutants had a Val-83 mutation or both Val-83 and Gly-87 mutations detected in the type 1 mutants. These results suggest that point mutations in the QRDR of the mycobacterial gyrA gene are responsible for acquired quinolone resistance in M. smegmatis.

Amino Acid Sequence↗
PubMed1993

Automated interpretation of disk diffusion antibiotic susceptibility tests with the radial profile analysis algorithm.

An original algorithm referred to as the radial profile analysis algorithm was implemented on a Macintosh Quadra 700 computer to provide an automatic determination of the inhibition zone diameters of antibiotic susceptibility tests performed with the disk diffusion method. After digitization of the petri plate image, each antibiotic disk is recognized and labeled. Pixels of the local zone around each disk are then used for generating a profile pattern that is subjected to decision rules. The resulting estimate of the inhibition zone diameter is then automatically compared with conventional breakpoints for classifying the tested strain in one of the clinical categories of antibiotic susceptibility. The program is also able to request a human reading for some rare plates difficult to interpret. The algorithm accuracy was tested by comparing the results with a combination of independent human measurements performed on the tested plates. The test sample was composed of 98 strains, and 2,552 tests of 40 distinct antibiotics were subjected to the analysis. The difference between the automatic and human diameter estimates was less than 4 mm in 90% of the tests. The agreement between the automatic and human clinical categorizations amounted to 95.5%, and severe (major and very major) disagreements were found in 5.6% of the tests performed with staphylococci but only 0.3% of the tests with gram-negative rods. We conclude that the radial profile analysis algorithm is a solid backbone for an automatic system dedicated to the clinical interpretation of disk diffusion antibiotic susceptibility tests.

Algorithms↗
PubMed1992

Porins in the cell wall of mycobacteria.

The cell wall of mycobacteria is an efficient permeability barrier that makes mycobacteria naturally resistant to most antibiotics. Liposome swelling assays and planar bilayer experiments were used to investigate the diffusion process of hydrophilic molecules through the cell wall of Mycobacterium chelonae and identify the main hydrophilic pathway. A 59-kilodalton cell wall protein formed a water-filled channel with a diameter of 2.2 nanometers and an average single-channel conductance equal to 2.7 nanosiemens in 1 M potassium chloride. These results suggest that porins can be found in the cell wall of a Gram-positive bacterium. A better knowledge of the hydrophilic pathways should help in the design of more effective antimycobacterial agents.

Bacterial Proteins↗
PubMed1992

Nosocomial bronchopneumonia in the critically ill. Histologic and bacteriologic aspects.

To provide a comprehensive description of the histologic and bacteriologic characteristics of human nosocomial bronchopneumonia (BPN), the lungs of 83 critically ill patients decreased after a period of mechanical ventilation were examined in the immediate postmortem period. In addition, the accuracy of the protected minibronchoalveolar lavage (BAL) technique in the diagnosis of nosocomial BPN was evaluated. In each patient, a surgical pneumonectomy was performed at the bedside within 30 min following death. Each pulmonary lobe was sampled and bacteriologically analyzed using semiquantitative cultures in 50 patients and quantitative cultures in 33 patients. The entire lung was histologically analyzed using 5 to 10 slices per lung segment. In 69 patients, the bacteriologic result of a protected mini-BAL performed within 48 h preceding death was compared with histologic and bacteriologic results of study of the lung tissue itself. Histologic lesions of BPN were found in 43 of the 83 lungs examined. These lesions were (1) severe in the majority of patients (confluent BPN, n = 23; lung abscess, n = 6), (2) preferentially found in dependent lung segments, (3) often associated with nonspecific alveolar damage, (4) associated with positive lung cultures in 65% of patients (53% with gram-negative bacteria), (5) polymicrobial in 28% of patients, (6) characterized by a lobar bacterial burden greater than 10(3) cfu/g in 32% of cases. Using semiquantitative bacteriologic analysis, the sensitivity and the specificity of the protected mini-BAL in the diagnosis of nosocomial BPN were found to be 70 and 69%, respectively. Protected mini-BAL identified 77% of causative microorganisms of BPN.(ABSTRACT TRUNCATED AT 250 WORDS)

Bronchoalveolar Lavage Fluid↗
PubMed1991

Interplay of cell wall barrier and beta-lactamase activity determines high resistance to beta-lactam antibiotics in Mycobacterium chelonae.

We calculated the target access index, which reflects the probability that a drug will reach its target at an effective concentration, and the predictive MICs of cephaloridine, cephalothin, and cefazolin for Mycobacterium chelonae from the drug concentrations inhibiting the binding of benzylpenicillin to penicillin-binding proteins, the permeability coefficients, and the beta-lactamase properties. Despite a low level of beta-lactamase activity and because of a very effective permeability barrier, the target access indices were very low, e.g., 100 times lower than for penicillinase-producing Escherichia coli. The predicted MICs were within one to three twofold dilutions of the experimentally determined values (which ranged between 512 and greater than or equal to 2,048 micrograms/ml). These results demonstrate that the interplay of the cell wall barrier and beta-lactamase activity determines high resistance of M. chelonae to beta-lactam antibiotics.

Cefazolin↗
PubMed1990

[Listeria monocytogenes liver abscess. In a diabetic patient].

Most liver abscesses are caused by Enterobacteriaceae, sometimes associated with anaerobes. Listeriosis is an exceptional cause of liver abscess, usually in a context of disseminated infections. We report the case of a diabetic woman who had liver abscess due to Listeria monocytogenes. The organism was isolated after guided needle aspiration, and there was no other site of infection. The course of the disease gradually moved towards recovery under an antibiotic therapy that was based on sensitivity tests. A search for immunodeficiency proved negative. A review of the literature showed that the rare cases of listerial liver abscess share a common factor, diabetes mellitus, the importance of which has not yet been noticed.

Diabetes Mellitus, Type 2↗
PubMed1990

Permeability barrier to hydrophilic solutes in Mycobacterium chelonei.

In order to define the permeability barrier to hydrophilic molecules in mycobacteria, we used as a model a smooth, beta-lactamase-producing strain of Mycobacterium chelonei. The rates of hydrolysis of eight cephalosporins by intact and sonicated cells were measured, and the permeability coefficient (P) was calculated from these rates by the method of Zimmermann and Rosselet (W. Zimmermann and A. Rosselet, Antimicrob. Agents Chemother. 12:368-372, 1977). P ranged from (0.9 +/- 0.3) x 10(-8) (benzothienylcephalosporin) to (10 +/- 3.3) x 10(-8) cm/s (cephaloridine); i.e., the P values were lower than those reported for Pseudomonas aeruginosa and Escherichia coli by 1 and 3 orders of magnitude, respectively. The permeability barrier was shown to reduce drastically the stream of drug molecules entering the cell, allowing the rather low level of beta-lactamase (0.1 U/mg of protein with penicillin G) to decrease radically the concentration of the drug at the target; this explains the poor in vitro activities of the beta-lactams against M. chelonei. We also estimated P for small, hydrophilic molecules (glucose, glycerol, glycine, leucine), by studying their uptake kinetics. The values found, ranging from 15 x 10(-8) to 490 x 10(-8) cm/s, were consistent again with a very low permeability of M. chelonei cell wall. The permeation of cephalosporins was not very dependent on the hydrophobicity of the molecules or on the temperature, suggesting a hydrophilic pathway of penetration for these molecules.

Biological Transport↗
PubMed1989

[Antibacterial effect of cefixime in the presence of the type of beta-lactamases produced by Enterobacteriaceae].

The susceptibility of isolates or Enterobacteriaceae to orally absorbed beta-lactams (amoxicillin, cephalexin, cefaclor, cefuroxime, and cefixime), was maximum for the iminomethoxy-aminothiazolyl-cephalosporin but variable according to bacterial species. For E. coli, P. mirabilis, Salmonella, Shigella, K. pneumoniae, K. oxytoca (group 1) MIC50 were congruent to 0.06 mg/l, and MIC90 congruent to 0.12 mg/l. Finally for C. freundii, E. aerogenes, E. cloacae, S. marcescens, M. morganii, MIC50 were higher, congruent to 1, and MIC90 16 mg/l. The slight increase reported between MIC50 ans MIC90 of cefixime against isolates belonging to group 1 was related to stability towards beta-lactamases (TEM, SHV) unlike groups 2 and 3, where the drug was less stable to chromosomal type 1 enzyme. The discovery of extended-spectrum beta-lactamases (ESB) (e.g. SHV-2, CTX-1 or TEM-3), mainly in K. pneumoniae, led to further investigations of the behavior of cefixime. The in vitro activity of cefixime (CFM), amoxicillin (AMX) combined or not with clavulanate (AMC, 2 mg/l), ticarcillin (TIC), cephalothin (CF), cefotaxime (CTX), ceftazidime (CAZ) and aztreonam (AZM) was determined by the agar dilution method (inoculum 10(5) cfu/ml) against clinical isolates: E. coli (26), K. pneumoniae (42), K. oxytoca (9), Salmonella (3) producing several types of beta-lactamases, chromosomal (cephalosoporinase, broad-spectrum) or plasmid-encoded (TEM-1, TEM-2, CTX-1, SHV-2, SHV-3, SHV-4). The geometric mean MIC values of AMX, AMC, TIC, CF, CTX, CAZ, AZM and CFM were as follows: greater than 480, 21.6, greater than 285, 45.6, 0.53, 1.12, 0.51, and 0.77 respectively. An MIC increase of oxyimino beta-lactams (CTX, CAZ, AZM, CFM) was observed against over-producing isolates of K. oxytoca and isolates producing ESB (CTX-1, SHV-2, SHV-3, SHV-4). The comparative behavior of cefixime was determined after transfer by conjugation to E. coli K-12. Sixty-one derivatives were constructed producing TEM-1, TEM-2, SHV-1, CTX-1, TEM-4, CAZ-2, SHV-2, SHV-3, SHV-4, the MICs of cefixime were stable against derivatives producing a penicillinase (TEM-1, TEM-2, SHV-1), but not against those producing an ESB. The MIC increases of undigestible beta-lactams ranged from 1 to 135 fold (CFM), 40 to 200 fold (CTX) 12 to 232 fold (CAZ), and 4 to 240 fold (AZM).

Anti-Bacterial Agents↗
PubMed1989

Detection of extended broad-spectrum beta-lactamases in Enterobacteriaceae in four French hospitals.

In 210 strains of Enterobacteriaceae which were isolated in four hospitals and which showed reduced susceptibility to cefotaxime, high synergy was demonstrated between amoxicillin (20 micrograms) + clavulanate (10 micrograms) and cefotaxime (30 micrograms) using a simple double-disk test. Isoelectric focusing on gel and specific iodometric detection using ceftriaxone identified four extended broad-spectrum beta-lactamases (isoelectric points 7.6, 6.3, 7.0 and 5.9) produced by the strains.

Amoxicillin↗
PubMed1989

In-vitro activity of FCE 22101 and other beta-lactam antibiotics against Enterobacteriaceae resistant to third generation cephalosporins.

The in-vitro activity of FCE 22101 was compared with those of imipenem, aztreonam, cefotaxime, ceftriaxone and latamoxef against 225 Enterobacteriaceae (209 clinical isolates and 16 derivatives of Escherichia coli K12) chosen for their resistance (MIC greater than or equal to 8 mg/l) to third-generation cephalosporins. The beta-lactamases produced by the strains of Enterobacter cloacae, Klebsiella pneumoniae and Esch. coli were identified. The mean MICs of FCE 22101 were 2-8 mg/l for Ent. cloacae, Citrobacter freundii and Morganella morganii. For Ent. cloacae, the MICs were slightly higher for the cephalosporinase non overproducing (5.5-8 mg/l) than for the cephalosporinase overproducing (4.5 mg/l) strains. The mean MIC was 9 mg/l for Serratia spp. but for half of the strains the MICs were greater than or equal to 16 mg/l. The MICs of FCE 22101 were 0.5-1 mg/l for the resistant clinical isolates or isogenic derivatives of K. pneumoniae and Esch. coli producing extended broad-spectrum beta-lactamases (SHV-2, SHV-3 or CTX-1), whether measured in the presence of clavulanate or not, and against the sensitive controls. This showed that the compound was not affected by these new beta-lactamases. The MICs of imipenem, on the average four to five times lower than those of FCE 22101, were found to be very similar for resistant and sensitive strains. The MICs of aztreonam were high (32-128 mg/l) for C. freundii, K. oxytoca and cephalosporinase overproducing strains of Ent. cloacae. There was cross-resistance between the third-generation cephalosporins, but the MICs of latamoxef remained low (1 mg/l) against M. morganii, Klebsiella spp. and Esch. coli.

Carbapenems↗