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Biomedical subjects

E Bergogne-Berezin

Publications and source records attributed to E Bergogne-Berezin.

At least 19 recordsLinked to original sources

Interactions among antibiotics, bacteria and the human immune system: the clinical relevance of in vitro testing.

The role of interactions of the host immune system with antibacterial activities of antibiotics is extremely complex and its analysis is still at an early stage. Standard in vitro trests of antibiotic susceptibilities of pathogens provide only limited information since they do not take into account either the potential interaction of immunomodulating activities of antibiotics in vivo or the participation of the host immune response in the infection outcome. The understanding of these complex relationships is of major importance in treating immunocompromised patients, but this approach is still under investigation and much work remains to be done in order to confer more significance on in vitro testing.

Anti-Bacterial Agents↗

European multicentre evaluation of a commercial system for identification of methicillin-resistant Staphylococcus aureus.

A commercial system for the rapid detection of methicillin-resistant Staphylococcus aureus, the BBL Crystal MRSA test (C-MRSA ID; Becton Dickinson, USA), was evaluated prospectively and compared with a polymerase chain reaction test for the presence of the mecA gene. Ten European centres tested a total of 676 isolates of Staphylococcus aureus from blood cultures. The system correctly identified 661 (97.8%) isolates within 4 h. All but three mecA gene-negative isolates (99.4% specificity) yielded a negative C-MRSA ID reaction, and 158 of 170 mecA gene-positive isolates were accurately detected (92.9% sensitivity). After repeated testing of discrepant results, sensitivity and specificity increased to 99% and 100%, respectively.

Bacteriological Techniques↗

Activity of beta-lactamase inhibitor combinations on Escherichia coli isolates exhibiting various patterns of resistance to beta-lactam agents.

The efficacy of the clinically available beta-lactam/beta-lactamase inhibitor combinations (amoxicillin/clavulanic acid (CA), ticarcillin/CA, amoxicillin/sulbactam, and piperacillin/tazobactam) was evaluated on 300 amoxicillin-resistant Escherichia coli isolates having the main patterns of beta-lactam resistance. The patterns, which reflect the production of various beta-lactamase enzymes, were analyzed by a principal component analysis of susceptibility to 11 beta-lactam antibiotics or beta-lactam/beta-lactamase inhibitor combinations. Sixty-two percent of strains were not very susceptible to penicillins, cephalothin, or any beta-lactam/beta-lactamase inhibitor combinations except for piperacillin/tazobactam; these strains may represent high-level broad-spectrum beta-lactamase (so-called penicillinase) production phenotype or inhibitor-resistant TEM-like enzyme production phenotype. Of the strains, 14.7% were resistant to amoxicillin and ticarcillin compatible with low-level broad-spectrum beta-lactamase production phenotype; 5.7% were cefoxitin resistant and were postulated to present a high-level cephalosporinase production phenotype; and 2.6% were resistant to cephalothin only, attributable to a low-level cephalosporinase production phenotype. Three percent of strains were intermediate or resistant to cefotaxime and may produce an extended-spectrum beta-lactamase, and the remaining strains (12 %), resistant to all tested antibiotics except for cefotaxime and piperacillin/tazobactam, were hypothesized to produce both broad-spectrum beta-lactamase plus cephalosporinase. The minimal inhibitory concentration (MIC) for these phenotype patterns indicated that combinations of CA plus amoxicillin or ticarcillin, or sulbactam plus amoxicillin, restored the activity of penicillins against phenotype 1 strains, whereas these combinations remained inactive against the other phenotype strains. Piperacillin plus tazobactam showed the best in vitro effect against the strains of all resistance phenotypes.

Amoxicillin↗

Diagnosis of tuberculosis by Amplicor Mycobacterium tuberculosis test: a multicenter study.

The Amplicor Mycobacterium tuberculosis test is a new PCR assay for the direct detection of Mycobacterium tuberculosis from clinical samples. A multicenter study that included six laboratories was done to evaluate the Amplicor test in comparison with direct microscopy and culture (solid or radiometric media), and the culture method was used as the "gold standard." A total of 2,073 specimens, i.e., 1,749 respiratory specimens and 324 other specimens, were tested. A total of 184 cultures yielded M. tuberculosis. Of these 184 cultures, 77 (42%) were smear negative and 23 (12.5%) concerned extrapulmonary specimens. The sensitivity of the Amplicor test for all of the specimens and for extrapulmonary, smear-positive, and smear-negative specimens was 86, 83, 94.5, and 74%, respectively. The sensitivity of direct microscopy in comparison with that of culture was 58%. A total of 95% of patients with culture-proven tuberculosis were diagnosed by the Amplicor test, whereas direct microscopy detected mycobacteria in only 72% of these patients. The Amplicor test exhibited a high degree of specificity (98%). The assay was very rapid and easy to perform.

Bacteriological Techniques↗

Penetration of piperacillin-tazobactam into bronchial secretions after multiple doses to intensive care patients.

The penetration of piperacillin-tazobactam in eight mechanically ventilated intensive care patients (age, 56.0 +/- 12.2 years, and weight, 76.5 +/- 15.2 kg [means +/- standard deviations]) with bacterial pneumonia was investigated. They were given intravenous doses of piperacillin (4 g) and tazobactam (0.5 g) as 30-min infusions every 6 h. The kinetic study was performed after the fourth dose on day 2 of treatment. Samples of blood and bronchial secretions (BS) were collected before the fourth dosing and 0.5, 1, 2, 4, and 6 h after the end of infusion. Drug concentrations in both sera and BS were measured by high-performance liquid chromatography. Concentrations (in micrograms per milliliter) in serum were 184.80 +/- 63.03 and 40.03 +/- 30.79 for piperacillin and 23.05 +/- 7.53 and 4.86 +/- 4.54 for tazobactam at 0.5 and 6 h, respectively, after the end of infusion. The corresponding concentrations (in micrograms per milliliter) in BS were 29.33 +/- 25.08 and 20.25 +/- 19.11 for piperacillin and 6.86 +/- 4.25 and 4.25 +/- 2.78 for tazobactam. The percentages for the extent of penetration of piperacillin and tazobactam, as defined by the BS/serum area under the curve ratio, were 35.70 and 78.42%, respectively. These data indicate good penetration of both piperacillin and tazobactam into BS. The concentrations of tazobactam in BS are persistent and high enough to exceed the values found to be effective in vitro against the tazobactam-susceptible beta-lactamases produced by the most important pathogens responsible for nosocomial pneumonia.

Adult↗

Penetration of cefpodoxime proxetil in lung parenchyma and epithelial lining fluid of noninfected patients.

The pulmonary disposition of cefpodoxime was studied in 12 patients with pulmonary opacities after a single oral dose of 260 mg of cefpodoxime-proxetil, which is equivalent to 200 mg of cefpodoxime. Blood and lung tissue samples were collected during surgery, and bronchoalveolar lavage was carried out 3 h (group A) or 6 h (group B) after drug administration. Urea was used as an endogenous marker for measurement of the volume of epithelial lining fluid (ELF). Concentrations were measured by using a microbiological assay. The mean concentrations of cefpodoxime in plasma, ELF, and lung tissue were, respectively, 1.85 +/- 0.82 mg/liter, 0.22 +/- 0.13 mg/liter, and 0.89 +/- 0.80 mg/kg of body weight in group A and 1.40 +/- 1.25 mg/liter, 0.12 +/- 0.14 mg/liter, and 0.84 +/- 0.61 mg/kg in group B. Concentrations in lung parenchyma 6 h after dosing were at least equal to or above the MICs for 90% of the strains of most organisms commonly found in respiratory tract infections, whereas data for ELF suggest levels of drug insufficient to inhibit bacteria.

Administration, Oral↗

Susceptibility of Xanthomonas maltophilia to six quinolones and study of outer membrane proteins in resistant mutants selected in vitro.

The in vitro susceptibilities of 75 clinical isolates of Xanthomonas maltophilia to nalidixic acid, five fluoroquinolones, latamoxef, and doxycycline were determined. Spontaneous mutants were selected, at a frequency of about 10(-5) to 10(-7) from four strains by culturing the strains in the presence of each quinolone. Selection in the presence of nalidixic acid provided mutants that were either resistant only to that compound or that exhibited cross-resistance to all the fluoroquinolones tested. Cross-resistance was always observed for mutants selected on any of the five fluoroquinolones. It was always associated with chloramphenicol resistance and, frequently, with doxycycline resistance. The electrophoretic alterations of the outer membrane proteins of the mutants suggest that different mechanisms may be involved in quinolone resistance in X. maltophilia.

4-Quinolones↗

Methods for clinical assessment of expectorants: a critical review.

The purpose of the paper is to discuss some aspects of the methods that are most appropriate for the clinical assessment of new expectorants. Expectorants are drugs devised to help in the removal of bronchial secretions. The evaluation of these drugs is aimed at demonstrating, in controlled trials, their efficacy, safety and, if possible, mechanism of action. Unfortunately, there is no universally accepted assessment technique available. Evaluation of symptoms with the use of self-reported measures is imprecise. Studies of quality of life can assist as a means of assessing the usefulness of this class of drug for patients. Lung function tests evaluate only the possible indirect effects of expectorants; the changes observed are often minor and they do not correlate with other methods of evaluation. Mucociliary clearance studies evaluate bronchial drainage by mucociliary transport and cough. They are a useful pharmacological approach but they cannot replace therapeutic trials. In vitro and ex vivo studies of bronchial secretion, while improving knowledge of the mechanisms of bronchial secretion, fail to predict the modifications of bronchial drainage produced in vivo by cough or mucociliary transport. To be considered efficient, expectorants should not only ease the removal of bronchial secretions, but also improve the patient's condition for the duration of treatment.

Animals↗

Cefpodoxime proxetil in upper respiratory tract infections.

Cefpodoxime proxetil is a new third generation oral cephalosporin, which shows potent antibacterial activity against both Gram-positive and Gram-negative bacteria, and high stability in the presence of beta-lactamases. Low concentrations of cefpodoxime inhibit most respiratory pathogens, including Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella (Branhamella) catarrhalis. Cefpodoxime reaches concentrations of 0.24 +/- 0.06 mg/kg in tonsils, 0.89 +/- 0.80 mg/kg in lung parenchyma, and 0.91 +/- 0.01 mg/kg in bronchial mucosa; these values exceed by far the minimum inhibitory concentrations (MICs) of cefpodoxime for respiratory pathogens. Preliminary clinical studies were carried out in 181 patients with upper respiratory tract infections: the results indicated an overall clinical response in 88.4% of patients; in 30% the clinical efficacy was excellent and in 58.5% it was good. Further studies showed clinical cure in 90.3% of patients with pharyngotonsillitis, and clinical efficacy (cure plus improvement) in 95% of those with acute sinusitis. Moreover, bacterial eradication was obtained in 78 to 96.7% of cases, most of which involved H. influenzae, streptococci, or M. catarrhalis. Cefpodoxime appears to be an effective new antibacterial that can be recommended as a drug of first choice in the treatment of most upper respiratory tract infections.

Ceftizoxime↗

Prosthetic valve endocarditis due to Thermomyces lanuginosus Tsiklinsky--first case report.

The first case of Thermomyces lanuginosus endocarditis occurring on a porcine heterograft prosthesis, secondary to a Staphylococcus aureus infection of the aortic valve, is reported. The diagnosis was made post-mortem by direct examination of the prosthesis and culture of surgical samples on Sabouraud's agar. Identification was based on the presence of warty, dark brown aleurioconidia. The route of contamination could not be established but the most likely cause was the air of the operating room or the insertion of a contaminated graft.

Adult↗

[Comparative activity of imipenem, ceftazidime and cefotaxime against Acinetobacter calcoaceticus].

The authors compared the in vitro activity of imipenem, ceftazidime and cefotaxime against 100 strains of Acinetobacter calcoaceticus isolated in 1986 and 1987. The minimal inhibitory and bactericidal concentrations (MICs and MBCs) were determined by the agar dilution and broth microdilution methods respectively, with and without 50 per cent of human serum in the medium to evaluate the possible influence of protein binding. Imipenem was the most active of the three drugs against Acinetobacter, including beta-lactamase producing strains. The MICs 50 and 90 of imipenem were 0.18 micrograms/ml and 0.48 micrograms/ml respectively, as opposed to 5.16 and 14.61 micrograms/ml for ceftazidime, 16 and 75.6 micrograms/ml for cefotaxime. No change was noted in the susceptibility of Acinetobacter to imipenem from 1981 to 1987. The geometric mean MIC of imipenem was 0.25 micrograms/ml. Susceptibility remained unchanged for ceftazidime and cefotaxime but the geometric mean MICs were higher, being 7.29 and 22.8 micrograms/ml respectively. Imipenem had the highest bactericidal activity, with a mean MBC/MIC ratio of 1.16. The presence of human serum did not influence the results, due to the low protein binding of all three antibiotics. It is concluded that imipenem is one of the major antibiotics available for the treatment of nosocomial Acinetobacter infections. However, a few resistant strains have recently been isolated, confirming the need for epidemiological surveillance of bacterial resistance to this antibiotic.

Acinetobacter↗

[Epidemiology of Acinetobacter and resistance to antibiotics at hospitals. A 5-year evaluation].

The growing number of Acinetobacter strains in hospitals and the rapid increase of their resistance to antibiotics have prompted us to undertake a long-term epidemiological study of this resistance at the Bichat hospital, Paris. Between 1971 and 1984, the resistance of Acinetobacter to antibiotics had already progressed, with only some antibiotics (imipenem, ceftazidime, tobramycin and amikacin) remaining active. During the following 5 years (1984-1988) a study of 1056 strains demonstrated a further increase of resistance and showed how serious the problem was in intensive care units. During the last few years, there has been a considerable increase in the proportion of multiresistant strains, reaching 84 per cent with beta-lactam antibiotics and 64 per cent with aminoglycosides. At present, in most cases the only effective treatment is imipenem, and no antibiotic is active in 5.5 per cent of the cases. Studies of lysotypes, enzymes and phenotypic resistance of bacterial strains completed the epidemiological approach, showing the presence of dominant lysotypes. Two predominant lysotypes are associated with multiresistance of Acinetobacter strains responsible for nosocomial infections.

Acinetobacter Infections↗

[Development of antibiotherapy and new trends].

During the last 10 years antimicrobials have been produced in almost limitless numbers by the pharmaceutical industry, and some have been marketed. The main objectives of these new drugs were to overcome the ever expanding problems of bacterial resistance and to fill the gaps in the spectra of previous agents. These objectives are progressively reached by new B-lactams, penems and fluoroquinolones, while new oral cephalosporins are becoming available to general practitioners. To overcome toxicity problems new concepts in antibiotic usage, such as intermittent aminoglycoside regimens, have been suggested. Research in antibiotics, the discovery of new compounds or the re-evaluation of older drugs constitute dynamic trends in antibiotic therapy.

Aminoglycosides↗

A study of the relationships between antibiotic resistance phenotypes, phage-typing and biotyping of 117 clinical isolates of Acinetobacter spp.

Two typing systems were used to conduct an epidemiological study of Acinetobacter and to establish their relationship to antibiotic resistance phenotypes. Biotyping was performed with biochemical tests according to the new definition of Acinetobacter baumannii (18 biotypes). Phage typing included two complementary systems: 125 phage-types and 25 subtypes. Resistance phenotype analysis included 11 antibiotics. The results of the study showed that: (1) nine phage-types or subtypes (67%) and two groups of atypical phage-types (5%) or of untypable strains (28%), could be defined; (2) all strains that were resistant to carboxy/ureido-penicillins and cephalosporins (62%) belonged to biotypes 6 or 9; among them 70% belonged to phage-types 17 or 124; (3) imipenem resistance was observed in five isolates of biotype 9 and one of biotype 6; (4) a phenotype including resistance to third generation cephalosporins (but not carboxypenicillins) and to amikacin (but not tobramycin) represented 8.5% of the isolates; 90% of them belonged to biotype 1 and were not phage-typable; (5) 15% of the isolates were not identified as A. baumannii; among them five Acinetobacter haemolyticus strains all had the same resistance phenotype: amikacin-tobramycin-kanamycin-netilmicin resistant; they were however, susceptible to beta-lactams and to gentamicin. There was a clear relationship between biotypes 6 and 9 and phage-types 17 and 124 which were the strains most resistant to beta-lactams and aminoglycosides and were predominant in the survey. The three typing systems were complementary but it seems that antibiotic resistance phenotypes and one of the two other typing systems would be required in parallel to provide suitable information for epidemiological purposes.

Acinetobacter↗

Identification of coagulase-negative staphylococci by electrophoretic profile of total proteins and analysis of penicillin-binding proteins.

Analyses of total solubilized proteins and penicillin-binding proteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis were demonstrated to be accurate methods for the identification of coagulase-negative staphylococci. However, penicillin-binding protein profiles were found to be much clearer for the identification of these organisms to species level than was examination of the total solubilized proteins. By using the former technique, 13 reference strains were found to have species-specific penicillin-binding protein profiles, and 150 of 160 randomly collected clinical isolates were identified as belonging to eight of these species. A group of three clinical strains probably represents the recently described species Staphylococcus lugdunensis; the other seven clinical isolates belonging to five species remained unclassified.

Bacterial Proteins↗

[From the parenchyma to the mucosa biopsy: significance and importance of local assays of antibiotics. A critical study].

The authors discussed the relevance of antibiotic concentrations as measured in tissues and fluids of the respiratory tract. They analysed theoretical factors which influence tissue distribution of antibiotics as well as the results of studies carried out in animal and in human tissues. Various factors may interfere with the results of antibiotic assays: but the data published by various groups were usually convergent: this confirms the significance of "tissue pharmacokinetics". New protocols based on more refined and reliable techniques were proposed recently, which underlines the attention payed to these studies.

Animals↗