[Activity of tigecycline against pathogen bacteria isolated in respiratory infectious disease in Europe. TEST study 2004-2007]. / Activité in vitro de la tigécycline vis-à-vis des germes pathogènes isolés d'infections respiratoires en Europe. Le Programme TEST 2004-2007.

Tigecycline (TGC), a semisynthetic glycylcycline, has a documented activity on Gram+ and Gram- pathogens including oxacillin-resistant (MRSA) and an extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae. Tigecycline Evaluation and Surveillance Trial (TEST) is an international surveillance study designed to assess the in vitro activity of TGC and 11 comparators against a range of important clinical pathogens from both the community and the hospital. The aim of this study was to assess efficacy of TGC, using this database, against pathogens implicated in community or hospital pneumonia and sinusitis. A total of 4163 isolates were consecutively collected in 21 European countries during three years (2004-2007). In all center, minimum inhibitory concentration (MIC) were determinated with the same Microscan panel (Dade-Behring). Tigecycline exhibited a good activity against respiratory pathogens, with the exception of Pseudomonas aeruginosa. Hundred percent of cocci Gram+ (Streptococcus pneumoniae, Staphylococcus aureus, Enterococcus sp.) and 100% of Haemophilus sp. are inhibited with 0.5 mg/L, without effect of an associated beta-lactam resistance mechanism. TGC is active in vitro on 89% of Enterobacteriaceae, with MIC 90 less or equal to 2mg/L. Eighty-nine percent of Enterobacter sp. and 77% of Serratia sp. are susceptible with range of MIC 90 from 2 to 4 mg/L. These interesting results obtained in vitro are to be strengthened by clinical studies.

[Meaning of the Quantiferon TB Gold tube test in tuberculosis screening among the hospital staff in case of very old or recent positive skin tests]. / Signification de Quantiféron TB Gold en tube en dépistage de la tuberculose parmi le personnel hospitalier en cas d'intradermoréactions positives très anciennes ou récentes.

UNLABELLED: The tuberculin skin test or PPD performed on health professionals evaluates delayed hypersensitivity to a Mycobacterium tuberculosis (Mt) antigen mixture. A very positive or increased area of induration indicates latent tuberculosis. Yet, prescribing a treatment is often difficult because of the test's poor specificity. OBJECTIVE: To determine if the T-lymphocytes of the proband exposed to specific Mt antigens to secrete interferon-gamma (IFN-gamma) can be measured; observe an immunizing response to cellular mediation improves T it this specificity? PATIENTS AND METHODS: The Department of Occupational Health at CHR of Metz performed a Quantiferon TB Gold (tube method, Cellestis) test on three groups of employees distributed according to the anteriority of a very positive IDR (>15mm). The test measures by method ELISA, the quantity of IFN-gamma secreted by the lymphocytes T collected in 1ml of total blood, after in vitro stimulation by antigens ESAT-6, CFP-10 and TB7.7. Group I is composed of 53 people (46 women [W] and 7 men [M]) and related to a recent discovery of October 2006 and June 2007, whereas group II, includes 28 of them (25W and 3M), is made of subjects with known very positive PPD for eight to 27 years. The age (41 years on average) and the sex-ratio are identical for these two groups. Group III is made of employees having made a tuberculosis there is more than 30 years. In the group I, the rate of IFN was supervised at the end of the treatment among patients who received it. RESULTS: The test Quantiferon TB Gold was positive at 15 subjects of group I (13W and 2M), that is to say 28.3%, and unspecified in one case (1.9%); positive at nine subjects of group II (9W), that is to say 32.1%. These rates of positivity are not significantly different. According to the experts consulted in group I, an antituberculosis treatment was proposed 11 times with 10 effective treatments (one refusal). A proportioning after treatment was carried out among six patients. The rate of IFN remained positive at five of the six supervised patients. This test made it possible to avoid the treatment of the 37 employees with test Quantferon TB negative Gold found over the nine months period of recruitment of group I. The choice not to treat was facilitated. CONCLUSION: The test Quantiferon indeed allows to eliminate the false positive of the skin test (1.6) so avoiding useless, expensive treatments and unwanted effects of antituberculosis medicines . On the other hand, the persistent positivity of this test 30 years after one firstly infection or after a contact does not allow to use it at present as certain control of a latent infection, unless having a negative value known about the hiring pa.

Unusual direct phycoerythrin labeling of B-cells from a splenic marginal zone lymphoma.

Flow cytometry is the most widely used method for lymphocyte subset characterization. Two types of antibodies, directly labeled with fluorochrome, are currently used for immunological diagnosis of B-cell lymphoproliferation: monoclonal antibodies against leukocyte differentiation antigens and polyclonal antibodies against immunoglobulins and light chains. In this study is described the case of a patient with an uncommon immunophenotyping of a B-cell lymphoproliferative disorder. B-cells from peripheral blood and from bone marrow reacted positively with all the tested phycoerythrin (PE)-conjugated antibodies, including the isotypic control. So we thought about a B-cell proliferation carrying a surface receptor recognizing PE: these B-cells were directly labeled with streptavidin-PE, indeed. Moreover, the immunodots from the patient were able to fix the streptavidin-PE. Finally, this unusual immunophenotyping was solved by using antibodies labeled with other fluorochromes than PE.

[A case of de novo acute basophilic leukaemia: diagnostic criteria and review of the literature]. / A propos d'un cas de leucémie à basophiles de novo: critères diagnostiques et revue de la littérature.

We report a case of a de novo acute basophilic leukaemia, revealed by an infectious pneumopathy in a 73 year old man. The full blood count revealed an hyperleucocytosis associated with an unregenerative normocytic normochrom anaemia and a thrombocytopenia. The blood and bone marrow smears showed a mixture of undifferentiated blast cells and basophiloblasts (high nucleo-cytoplasmic ratio, coarse basophilic cytoplasmic granules), along with basophilic precursors and basophilic polymorphonuclears. All the blasts were MPO negative but positive for the toluidine blue metachromatic coloration, which is considered as consistent with basophilic lineage. Immunophenotypic studies showed myeloid blasts, without maturity marker, CD 117 negative and CD203 cytoplasmic positive, the latter known to be highly representative of the basophilic lineage. This very clear-cut phenotype, associated with the morphology of cells, were arguments to ascertain the basophilic lineage of the blasts without the need of electron microscopic study. Cytogenetic and RNA analysis revealed the presence of a Philadelphia chromosome and of a BCR-ABL transcript with the unusual junction e6a2. Thus, imatinib was added to the conventional chimiotherapy and the patient is currently in complete remission. This clinical prompted allows us to review the literature on acute basophilic leukaemia and to state on the different diagnostic criteria of this rare disorder.

[Acquired Von Willebrand syndrome]. / Syndrome de Willebrand acquis.

We report a case of acquired von Willebrand syndrome in association with multiple myeloma, diagnosed in a 54 year-old man suffering from sudden onset of mucocutaneous bleeding. The acquired von Willebrand syndrome is a rare bleeding disorder with laboratory findings similar to those of inherited von Willebrand disease. Diagnosis, etiology and pathophysiology of acquired von Willebrand syndrome are reviewed to establish a differential diagnosis with inherited von Willebrand disease. Identification of the underlying disease responsible for the acquired von Willebrand factor defect and the bleeding diathesis is necessary to choose among the therapeutic options the appropriate treatment.

In vitro antibacterial activity of moxifloxacin against hospital isolates: a multicentre study.

OBJECTIVE: To evaluate the in vitro antibacterial activity of moxifloxacinin in comparison to that of other fluoroquinolones (ciprofloxacin, ofloxacin and trovafloxacin). METHODS: A total of 2,196 strains was collected in 11 French hospitals in 1998. Minimum inhibitory concentrations (MICs) (mg/L) were determined by agar dilution and agar diffusion was performed with 5-microg discs. Internal quality control was carried out with genetically defined strains. RESULTS: MIC50s and MIC90s of moxifloxacin against nalidixic acid (NAL)-susceptible Enterobacteriaceae (n = 663) were 0.12 and 0.5. As for other quinolones, the activity of moxifloxacin (4-32) was reduced against NAL-intermediate and NAL-resistant strains (n = 222). MIC50s and MIC90s of moxifloxacin were 2 and 4 for ciprofloxacin-susceptible P. aeruginosa (n = 128); moxifloxacin had no activity against ciprofloxacin-resistant strains (n = 56). The activity of moxifloxacin was maintained against NAL-susceptible A. baumannii (n = 11; 0.032-0.125), but reduced against NAL-resistant strains (n = 30; 16-32). H. influenzae (n = 97) and M. catarrhalis (n = 40) were inhibited by low concentrations (0.03-0.06 and 0.06-0.25, respectively). Moxifloxacin had better activity (0.06-0.12) than other tested quinolones against methicillin-susceptible S. aureus strains (n = 110); ciprofloxacin-resistant strains (n = 85) (2-8) were usually methicillin-resistant. Moxifloxacin was moderately active against enterococci (n = 149) (E. faecalis: 0.5-16; E. faecium: 2-4). Streptococci (n = 194) and pneumococci (n = 136), including 70 penicillin G-intermediate or G-resistant strains, were inhibited by low concentrations (0.25-0.5 for each species). Based on the regression curve, tentative zone diameter breakpoints could be > or =21 and <18 mm for MIC breakpoints of < or =1 and >2 mg/L, respectively. CONCLUSIONS: While retaining activity against Enterobacteriaceae, moxifloxacin was moderately active against P. aeruginosa. Its activity was inferior to that of ciprofloxacin for these species. This study confirmed the comparatively high in vitro activity of moxifloxacin against Gram-positive cocci and other pathogens isolated from community-acquired respiratory tract infections.

[Susceptibility of Pseudomonas aeruginosa to antibiotics isolated from patients of intensive care units in France in 1998. Resistant phenotypes to beta-lactams]. / Sensibilité de Pseudomonas aeruginosa aux antibiotiques, isolés chez des malades de soins intensifs français en 1998. Phénotypes de résistance aux beta-lactamines. Etude ESCRIME.

Pseudomonas aeruginosa is responsible for nosocomial infections and demonstrates many types of resistance mechanisms to antibiotics. Thus, in vitro susceptibility survey are frequently required. In this study, susceptibility has been assessed on 105 non redundant consecutive strains isolated from ICU's in 18 general hospitals, from 01.02.98 to 30.06.98. Only clinically significant samples have been considered. MICs have been measured for nine beta-lactams, three aminoglycosides, one fluoroquinolone and colistine. For ticarcilline resistant strains, phenotype has been assessed on Mueller-Hinton medium supplemented with beta-lactamases inhibitor. Transferable beta-lactamases has been identified using pl and PCR. MIC 50 and MIC 90 (mg/L) for beta-lactams are the following (MIC 50-->90): ticarcilline (16-->512), ticarcilline + clavulanic acid (16-->512), piperacilline (4-->512), pipéracilline + tazobactam (4-->64), aztreonam (4-->16), cefsulodine (4-->32), ceftazidime (2-->16), cefepime (4-->16), imipeneme (1-->8). For aminoglycosides: gentamicine (2-->32), tobramycine (1-->32), amikacine (4-->16). For ciprofloxacine (0.25-->32) and colistine (0.5-->2). According to CA-SFM break points recommendations, 50% of isolated strains are resistant to gentamicine, one out of three for ticarcilline + clavulanic acid (29%), one out of four for tobramycine (25%) and ciprofloxacine (25%), one out of ten for amikacine (9%), tazocilline (8%) and imipeneme (9%). Resistance to ceftazidime and aztreonam is uncommon (respectively 2%-1%) and never observed for cefepim. For ticarcilline resistant strains, (38% of total isolates) the following phenotypes have been detected: 6.7% non enzymatic resistance, 15.2% transferable beta-lactamase (TEM 4.8%, CARB 4.8%, TEM + CARB 4.8% and OXA-10 and derivated 0.9%) and 16.2% high level cephalosporinase. Extended-spectrum beta-lactamase has never been detected. TEM beta-lactamase is associated with resistance to amikacine and ciprofloxacine.

Amphiphilic diblock dendrimers: synthesis and incorporation in Langmuir and Langmuir-Blodgett films.

A new dendron with peripheral long alkyl chains and containing five C(60) units in the branching shell has been prepared and attached to a Fréchet-type dendron functionalized with ethylene glycol chains. The peripheral substitution of the resulting globular dendrimer with hydrophobic chains on one hemisphere and hydrophilic groups on the other provides the perfect hydrophobic/hydrophilic balance allowing the formation of stable Langmuir films. Furthermore, a perfect reversibility has been observed in successive compression/decompression cycles. The diblock structure of the dendrimer has been also crucial for the efficient transfer of the Langmuir films in order to obtain well-ordered multilayered Langmuir-Blodgett films. This approach appears particularly interesting since functional groups not well adapted for the preparation of Langmuir and Langmuir-Blodgett films such as fullerenes can be attached into the branching shell of the dendritic structure and, thus, efficiently incorporated in thin ordered films.

[Antibiotic sensitivity of enterobacteria in intensive care units]. / Sensibilité des entérobactéries aux antibiotiques en unités de soins intensifs.

Antibiotic therapy of intensive care patients is usually undocumented. The treatment is chosen according to epidemiologic and susceptibility data from microbiological laboratories. The aim of our study is to determine antibiotic susceptibility of enterobacteria isolated from intensive care patients during a five-month multicenter study in 18 French hospitals. Numerous (n = 1,113) strains were studied: 447 enterobacteria isolated from urine (n = 229), blood cultures (n = 106), respiratory tract specimens (n = 72), peritoneal fluids (n = 22), pus (n = 15) and catheters (n = 2). MICs of group 2 and group 3 enterobacteria were determined using the dilution agar method and were interpreted according to the CASFM (Comité de l'antibiogramme de la société française de microbiology) recommendations. Group 1 enterobacteria were most frequently isolated (67%). Only one Escherichia coli strain produced ESBL (0.3%). Among group 2 enterobacteria, one Citrobacter koseri strain produced ESBL. We did not isolate Klebsiella pneumoniae ESBL. Isolation of group 3 enterobacteria was frequent (24%). Thirty-five percent of group 3 enterobacteria were resistant to cefotaxime, 26% to ceftazidime and 16% to cefepime and cefpirome. Fourteen strains of this group produced ESBL: 13 Enterobacter aerogenes and one E. amnigenus.

In vitro activity of teicoplanin against gram-positive cocci.

The glycopeptide susceptibility of 443 clinical isolates of gram-positive cocci collected from nine general hospitals in 1996 was determined according to the recommendations of the CA-SFM (the Antibiogram Committee of the French Society for Microbiology). In total, 234 isolates of Staphylococcus aureus, 84 isolates of coagulase-negative staphylococci (CNS), 98 enterococci and 27 streptococci were collected. The mecA gene confirming resistance to methicillin was found in 42.7% of S. aureus isolates and 51.2% of CNS isolates. No resistance to teicoplanin and vancomycin was found in S. aureus but four isolates of CNS had an MIC of teicoplanin > or = 8 mg/L. All isolates of Enterococcus faecalis tested were susceptible to both glycopeptides. This study confirms that teicoplanin has a very good in vitro activity against gram-positive cocci, isolated in France from nosocomial infections.

Bacteriological eradication of Streptococcus pneumoniae from patients with acute exacerbations of chronic bronchitis: cefuroxime axetil versus cefixime.

The bacteriological eradication rates of Streptococcus pneumoniae from sputum of patients experiencing acute exacerbations of chronic bronchitis (WHO definition) have been compared following therapy with either cefuroxime axetil 250 mg b.d. or cefixime 200 mg b.d. All patients were hospitalised for an acute exacerbation of chronic bronchitis. The study design was a multicentre, double-blind, randomised, parallel group with patients giving written informed consent initially. Patients were recruited to the study if they met the WHO definition of chronic bronchitis, were aged 30-75 years and had a high probability of S. pneumoniae infection based on initial sputum Gram stain. All S. pneumoniae isolates were serotyped and susceptibility tested at the National Reference Centre, Paris. S. pneumoniae was eradicated more rapidly following cefuroxime axetil administration than after cefixime and this difference was statistically significant (p = 0.002) at 2-4 days post-treatment. Clinical endpoints showed a similar trend--94% response to cefuroxime axetil compared with 71% response to cefixime (RR 6.39:1). Cefuroxime eradicated S. pneumoniae significantly more rapidly than cefixime and patients in the cefuroxime axetil arm had favourable clinical criteria. The data suggest that focused antibacterial studies may be helpful in evaluating antibiotics in acute exacerbation of chronic bronchitis.

A double-blind randomized trial comparing the efficacy and safety of a 5-day course of cefotiam hexetil with that of a 10-day course of penicillin V in adult patients with pharyngitis caused by group A beta-haemolytic streptococci.

A 10-day course of penicillin is the antibiotic regimen currently recommended by the American Heart Association (AHA) as treatment for patients with tonsillitis caused by group A beta-haemolytic streptococci (GABHS), with the aim of preventing both the suppurative and non-suppurative complications of this infection. This prospective, multicentre, randomized, double-blind, double-dummy clinical trial was undertaken in order to compare the efficacy of, tolerability of and compliance with a 5-day course of cefotiam hexetil (CTM) 200 mg bd with that of a 10-day course of penicillin V (PEV) 1 megaunit (600 mg) tds, to investigate the significance of recovering GABHS during or after treatment and to evaluate the potential economic advantages of short-term regimens. Two hundred and fifty ambulatory adult patients with a presumptive diagnosis (based on a positive rapid antigen detection test) of GABHS tonsillitis were recruited in 60 centres; the diagnosis was subsequently confirmed by a positive culture of a throat swab. At the time of entry into the trial there was no statistically significant difference between the groups in terms of clinical symptoms. In an intention-to-treat analysis, both the clinical and bacteriological response rates at days 10 and 30 were comparable for each group i.e. 106 of 119 (89.1%) patients and 90 of 109 (82.6%) patients respectively in the CTM group and 103 of 117 (88.0%) patients and 92 of 107 (86.0%) patients respectively in the PEV group. The times until defervescence and resolution of symptoms were also similar. Of the 115 patients in each group who were assessed at day 90, there were three clinical relapses in the CTM group and seven in the PEV group. No non-suppurative complications of GABHS infection were detected. Tolerance was significantly better in the CTM group than in the PEV group, 14 of 119 (11.8%) patients and 26 of 117 (22.2%) patients in the former and latter groups respectively reporting adverse events. In three cases in each group treatment was discontinued prematurely because of adverse events; none of these in the CTM group was serious but one patient in the PEV group experienced a severe allergic reaction. Compliance in both groups was good during the first 5 days of therapy but, by the end of each course, 93.6% of patients in the CTM group had completed treatment, compared with 73.0% in the PEV group.(ABSTRACT TRUNCATED AT 400 WORDS)

Single-dose amoxycillin-clavulanic acid vs. cefotetan for prophylaxis in elective colorectal surgery: a multicentre, prospective, randomized study. The PRODIGE Group.

A prospective, multicentre, randomized trial was carried out in 19 hospitals in order to compare the efficacy of amoxycillin-clavulanic acid with cefotetan as antibiotic prophylaxis in patients undergoing elective colorectal surgery. Since the main purpose of the study was to demonstrate equivalence between the two regimens, the protocol planned the inclusion of 200 patients. Eligible patients were randomly assigned to receive either amoxycillin-clavulanic acid (2.2 g) or cefotetan (2 g) in a single infusion on the induction of anaesthesia. Failure of prophylaxis was defined as occurrence of infection of intestinal origin, either minor (wound cellulitis) or major (abscess, peritonitis, septicaemia) within the 30-day postoperative period. Among 221 randomized patients, 208 (105 amoxycillin-clavulanic acid, 103 cefotetan) aged 66 +/- 12 years (mean +/- SD) were evaluated while 13 were withdrawn. Colorectal cancer was the indication for surgery in 73% of cases. Eleven (10 +/- 6%, 95% confidence interval) and 13 (13 +/- 7%) failures were observed in the amoxycillin-clavulanic acid and cefotetan groups (P = 0.63 chi-square test) respectively. Most infections occurred before the 10th postoperative day (8% failures at this time, estimated by the Kaplan-Meier method). The results of the trial demonstrate that amoxycillin-clavulanic acid and cefotetan have similar efficacy when used for prophylaxis of infection after elective colorectal surgery.

Efficacy and tolerance of cefpodoxime proxetil compared with ceftriaxone in vulnerable patients with bronchopneumonia.

This multicentre, randomized study compared the efficacy and tolerance of cefpodoxime proxetil and ceftriaxone in vulnerable patients with bronchopneumonia. Patients received cefpodoxime proxetil 200 mg bd orally or ceftriaxone 1 g daily im for a ten-day period. They were evaluated at days 10 and 30. Ninety-six patients were evaluated for tolerance, 85 for clinical efficacy and 65 for bacteriological efficacy. At entry all patients had radiographic evidence of pneumonia and 74% of bacteriological samples were positive. The percentage of overall success (cured or improved) was 97.7% (43/44) in the cefpodoxime proxetil group and 95.1% (39/41) in the ceftriaxone group. The bacteriological efficacy was 94.3% in the cefpodoxime proxetil group and 97.4% in the ceftriaxone group. Clinical tolerance was satisfactory in both groups. In this study, the clinical and bacteriological results obtained with cefpodoxime proxetil were comparable with those obtained with ceftriaxone in the treatment of community-acquired bronchopneumonia in patients with additional risk factors.

[Diffusion of ceftriaxone in healthy and infected peritoneal tissue]. / Etude de la diffusion de la ceftriaxone dans le tissu péritonéal sain et infecté.

The authors studied the peritoneal diffusion of ceftriaxone in the four quadrants of the abdomen (right and left inguinal and right and left hypochondrium) in 50 adult patients divided into 4 groups: pre-operative IVD administration of ceftriaxone in patients with healthy peritoneum, 1 g (group I), 2 g (group II): pre-operative IVD administration of ceftriaxone in patients presenting peritonitis 1 g (group III), 2 g (group IV). After laparotomy, a fragment of peritoneal membrane was resected from each of the four quadrants, the product was extracted from the peritoneum by a crushing technique and the assayed by HPLC with concomitant blood level assay. The mean assayed concentrations in situ are respectively in groups I to IV: 27.2, 31.2, 31.36 and 43.65 micrograms/g, with a rapid time of appearance (30 minutes) and a homogeneous topographic distribution for all peritoneal sample sites. In cases of peritonitis, the concentrations are higher by a factor of 1.15 and 1.39 for the dosages of 1 and 2 g as compared to healthy peritoneum. Beyond the third hour after injection, peritoneal concentrations remained high at 9.8 micrograms/g in patients having received 1 g of ceftriaxone and very high at 22.6 micrograms/g in patients having received 2 g. These levels are therefore effective whatever the posology in antibioprophylaxis, taking into account the MIC of the product on Gram- bacilli.

[Treatment of septicemias and skin infections in burn patient by teicoplanin. Study of its skin diffusion]. / Traitement des septicémies et infections cutanées chez le brûlé par la téicoplanine. Etude de sa diffusion cutanée.

In this study, teicoplanin was administered to burnt patients by IV and IM route in monotherapy or in association with other antibiotics. 12 cases of septicaemia and 8 severe cutaneous cocci Gram + infections were treated. Dosage varied from 5 mg/kg to 14 mg/kg. Clinical cure was observed in 89% of cases, and eradication of cocci Gram + in 83%. The MICs of Staphylococcus were between 0.25 micrograms/ml and 4 micrograms/ml, with a majority of methicillin-resistant Staphylococcus at 1. Average through serum concentrations were 7.4 micrograms/ml, and peak serum concentrations were 26 micrograms/ml (1 hour after injection). Tolerance was good in 19 of the 20 cases (95%). Skin levels of teicoplanin were found to be 1.6 times the through serum level. It was noted that in burnt patients whose UBS is superior to 100, the dose should be increased by about 50%.