[Fluoroquinolone use and MRSA rates in hospitalized patients].
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Biomedical subjects
Publications and source records attributed to R Leclercq.
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Of 233 erythromycin-resistant pneumococcal isolates collected in Belgium in 1999-2000, 89.7% carried the erm(B) gene, 6% the mef(A) gene, and 3.5%erm(B) plus mef(A). Two isolates contained neither erm(B) nor mef(A); one contained an erm(A) subclass erm(TR) gene, while the other contained an A2058G mutation in domain V of the 23S rRNA gene. Of 209 erm(B)-positive isolates, 191 had clindamycin MICs > 16 mg/L and 18 had MICs < or = 16 mg/L. Mef(A)-positive isolates all displayed the M resistance phenotype. Telithromycin remained active against erythromycin-resistant isolates, with the highest telithromycin MIC50 being found in mef(A)-positive isolates. No difference in the prevalence of different resistance mechanisms was observed compared to isolates collected in 1995-1997.
Exposure of populations to antibiotics is a condition for the emergence and the diffusion of bacteria resistant to antibiotics. Analysis of epidemiological causality between antibiotic exposure and expansion of antibiotic resistance in human pathogens requires the study of the basis for the emergence and the subsequent epidemic spread of the strains. Emergence of antibiotic resistance under the selective pressure of antibiotics is unavoidable. However, the rapidity of the emergence depends on several parameters including the biochemical mechanism and the genetic support of the resistance and on the couple bacteria/antibiotic considered. Several of these parameters may be studied and measured in vitro. In vivo, relationship between antibiotic exposure and risk for infection or colonisation by pneumococci resistant to beta-lactams or macrolides and methicillin-resistant staphylococci are among the best studied models. In particular for pneumococci, quantitative relationship between antibiotic consumption and resistance, including geographical correlations have been shown but do not allow to establish any causality relationship. Overall, there is no doubt on the question of the impact of antibiotic exposure and the risk of antibiotic resistance. However, the quantification of the risks remains to be accurately studied.
Exposure of populations to antibiotics is a condition for the emergence and the diffusion of bacteria resistant to antibiotics. Analysis of epidemiological causality between antibiotic exposure and expansion of antibiotic resistance in human pathogens requires the study of the basis for the emergence and the subsequent epidemic spread of the strains. Emergence of antibiotic resistance under the selective pressure of antibiotics is unavoidable. However, the rapidity of the emergence depends on several parameters including the biochemical mechanism and the genetic support of the resistance and on the couple bacteria/antibiotic considered. Several of these parameters may be studied and measured in vitro. In vivo, relationship between antibiotic exposure and risk for infection or colonisation by pneumococci resistant to beta-lactams or macrolides and methicillin-resistant staphylococci are among the best studied models. In particular for pneumococci, quantitative relationship between antibiotic consumption and resistance, including geographical correlations have been shown but do not allow to establish any causality relationship. Overall, there is no doubt on the question of the impact of antibiotic exposure and the risk of antibiotic resistance. However, the quantification of the risks remains to be accurately studied.
The bactericidal activity of quinupristin-dalfopristin was assessed by time-kill experiments against Staphylococcus aureus strains with characterized phenotypes and genotypes of MLS(B) resistance. A set of laboratory strains composed of isogenic pairs of S. aureus RN4220 derivatives containing or not the erm(A), erm(B) or erm(C) genes constitutively expressed and of 13 clinical isolates containing these genes inducibly or constitutively expressed were studied. Three of the clinical isolates with erm(B) or erm(A) genes had an unusual inducible MLS(B) cross resistance. The early bactericidal activity of quinupristin-dalfopristin was altered against strains expressing constitutive quinupristin resistance regardless of the erm(A), erm(B) or erm(C) type of gene. We conclude that the bactericidal activity of quinupristin-dalfopristin against staphylococci was dependent on the activity of quinupristin rather than on the erm genotype of the strain.
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Ketolides are a new class of antibacterials that have been specifically developed for the treatment of community-acquired respiratory tract infections in an era of increasing resistance among major etiologic pathogens. These agents possess several unique structural features, including a 3-keto function and a large aromatic side chain, that confer not only a mode of action that differentiates them from the macrolide class but also a reduced potential to induce--or select for--resistant strains. Studies also suggest that ketolides such as telithromycin have a lower ecologic impact on the body's microflora than agents such as clarithromycin and amoxicillin-clavulanate, potentially reducing the risk of emergence of resistant strains and the spread of such resistance to pathogenic species. Therefore, available evidence suggests that ketolides may not only provide important new treatment options in an era of increasing resistance but may also contribute to reducing the pressure for development of further resistance. Clearly, further studies are required to confirm this low resistance potential once the ketolide agents become more widely used in routine practice.
In total, 844 strains of Gram-positive cocci were collected from six university hospitals in France between September 1999 and January 2000. MICs of linezolid were determined: (i) for all strains by agar dilution (method A); (ii) by broth microdilution (method B) for staphylococci and enterococci; (iii) by Etest (method E) for beta-haemolytic streptococci and Streptococcus pneumoniae. Susceptibility to other antibiotics was determined by the disk diffusion method. MIC50 and MIC90 values were identical (2 mg/L) for methicillin-susceptible Staphylococcus aureus (n = 179) by methods A and B. Linezolid was active against methicillin-resistant S. aureus (n = 117), with an MIC90 of 2 mg/L (methods A and B), but with a lower MIC50 of 1 mg/L by method A. Of the 200 coagulase-negative staphylococci, 56.5% were methicillin-resistant and 43.5% were methicillin-susceptible. Linezolid had similar in-vitro activity by methods A and B (MIC50 and MIC90 values of 1-2 mg/L), irrespective of methicillin susceptibility. The MIC90 of linezolid for all enterococci (150 Enterococcus faecalis and 50 Enterococcus faecium) was 2 mg/L by both methods. MICs of linezolid for beta-haemolytic streptococci had a narrow range of 0.5-2 mg/L (method A) and 0.125-2 mg/L (method E). Pneumococci (n = 118), including 67 penicillin G-intermediate and -resistant strains, were all inhibited by linezolid 2 mg/L (MIC90 of 2 mg/L by methods A and E). No strain had an MIC of > 2 mg/L by agar dilution or Etest, or of > 4 mg/L by broth microdilution. Overall, the study confirmed the good in-vitro activity of linezolid and the very narrow range of MICs for Gram-positive cocci susceptible or resistant to other antibiotics, irrespective of the method used.
One thousand six hundred and fifty clinically significant, consecutive and non redundant strains of staphylococci, including 863 Staphylococcus aureus and 787 coagulase negative staphylococci (CNS), were isolated between October 1999 and March 2000 in 35 French hospital laboratories. Susceptibilities were determined in each center by a standard diffusion method according to the recommendations of CA-SFM. Strains with vancomycin zone size diameter <17 mm were sent to the central laboratory for MIC determination of vancomycin by agar dilution, as recommended by the CA-CSFM. Frequencies of resistance to oxacillin were 38.6% for S. aureus (MRSA), 54% for the CNS, all species and 62% for S. epidermidis, respectively. The antibiotics tested showed a good activity against strains of S. aureus susceptible to oxacillin, more than 95% of strains being susceptible except for erythromycin (82.6%). Against MRSA, vancomycin and prisitinamycin had the highest rates of susceptible strains, greater than 93% for the later antibiotic. More than 92% of strains of CNS susceptible or resistant to oxacillin were sensitive to pristinamycin. Pristinamycin displayed a good activity whether the strains were constitutively or inducibly resistant to MLS(B). It comes out from this in vitro study that the rate of resistance of staphylococci to pristinamycin remains weak and stable in France. Pristinamycin is a good alternative for oral treatment of staphylococcal infections.
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.
This report describes two cases of Osler's triad of pneumonia, meningitis, and endocarditis, as a result of Streptococcus pneumoniae infection, also called Austrian's syndrome. In the first patient, a 51 year old non-alcoholic man, the aortic valve was affected and needed to be replaced in an emergency operation. The mitral valve was affected in a 70 year old woman without underlying disease, who only benefited from medical treatment. Both patients received corticosteroids, either dexamethasone followed by low doses of hydrocortisone and fludrocortisone, or only hydrocortisone and fludrocortisone, at the onset of the illness, and their outcome was favourable. These case reports focus on the presentation, prognosis, and therapeutic options for this severe syndrome.
Increasing frequency in antibiotic resistance in Staphylococcus aureus is worrying. In this review, we briefly describe the mechanisms of resistance to antibiotics in staphylococci and we report the current incidence of antibiotic resistance in France. Methicillin-resistance is mostly confined to hospitals. However, spread of multiply resistant strains of staphylococci to the community is a putative threat. Strains with diminished susceptibility to glycopeptides are rare but possibly underestimated because of the in vitro difficulties to detect glycopeptide resistance. A continuous resistance survey is necessary. The problem of multiresistance is different for hospital and community staphylococci. The later strains still remain susceptible to many antibiotics, apart from some exceptions. By contrast, incidence of multiply resistance in hospitals remains high. After a recent decrease, incidence of oxacillin resistance seems to be stabilized. A new and recent feature is the great variety of resistance phenotypes which can be found in methicillin-resistant strains, in particular with gentamicin susceptibility.
Between February and June 2000, 2345 consecutive strains of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus and Klebsiella pneumoniae were isolated from 2088 adult patients suffering from community-acquired respiratory tract infections, in 97 hospital laboratories. Of the 1037 S. pneumoniae isolates, 48.3% were intermediately or highly penicillin resistant. For invasive isolates, the MIC90s of penicillin G, amoxycillin, cefuroxime, ceftriaxone, erythromycin, ofloxacin, ciprofloxacin and moxifloxacin were 2, 2, 4, 0.5, 1024, 2, 2 and 0.25 mg/l, respectively. All but one invasive strain were susceptible to moxifloxacin whereas 97.5% were susceptible to levofloxacin. The MIC90s of clinical isolates with intermediate susceptibility or high resistance to penicillin G, were 2, 2, 4, 1, 1024, 2, 2 and 0.25 mg/l. About 98.1, 97.0, and 83.1% of strains were inhibited by concentrations < or = 1 mg/l of moxifloxacin, levofloxacin and ciprofloxacin, respectively (E-test). Eight of the 1037 S. pneumoniae strains were not susceptible to moxifloxacin and had mutations in gyrA (eight strains), parC (four strains) or parE (three strains). Against H. influenzae (32.7% were beta-lactamase producers) and M. catarrhalis (96.3% were beta-lactamase producers), the MIC90s of moxifloxacin, amoxycillin and co-amoxiclav were 0.094 and 0.125 mg/l, 64 and 8 mg/l, and 1.5 and 0.25 mg/l, respectively. Against oxacillin-susceptible S. aureus and K. pneumoniae, the MIC90s of moxifloxacin were 0.125 and 0.84 mg/l respectively. Moxifloxacin had the highest in vitro activity of all antibiotics tested.
Recent data from surveillance studies suggest that levels of resistance to macrolide, lincosamide and streptograminB (MLSB) antibacterials in respiratory tract pathogens, particularly Streptococcus pneumoniae, are rising and limiting the usefulness of these drugs. New agents that do not select for resistance are essential to safeguard the future of antibacterial efficacy. The ketolides, of which telithromycin is the first to be registered for clinical use, represent a new class of antibacterials developed specifically for optimal empirical treatment of respiratory tract infections (RTIs). Although derived chemically from macrolides, the ketolides, which possess innovative structural modifications, form a unique class in the macrolide family. A keto function at position 3 of the erythronolide A ring replaces the L-cladinose moiety, generating a class of compounds that, unlike 14- and 15-membered ring macrolides, will not induce MLSB resistance in vitro. A large aromatic N-substituted C11,12-carbamate side chain allows a more effective interaction with domain II of the 23S rRNA, enhancing binding to bacterial ribosomes and allowing binding to MLSB-resistant ribosomes. This novel structure allows ketolides to exert intrinsic activity against respiratory tract pathogens, avoid induction of MLSB resistance, and retain activity against MLS(B)-resistant strains. Furthermore, ketolides have a low potential to select for resistance and cross-resistance both in vitro and in vivo, making them an attractive option for the empirical treatment of RTIs.
PURPOSE OF THE STUDY: Malignant metastases are rarely located in skeletal muscles. We report a case of lung adenocarcinoma disclosed by metastatic dissemination to the infraspinatus muscle. CASE REPORT: A 66-year-old man consulted for a painful stiff right shoulder. Pain had developed progressively and did not respond to class 2 antalgesics. There was a complete loss of passive and active medial rotation while the other shoulder amplitudes were normal. A discrete tumefaction was palpated in the infraspinatus fossa. Magnetic resonance imaging alone was able to evidence an intramuscular tumoral formation within the infraspinatus. Surgical excision led to the diagnosis of metastatic adenocarcinoma of the lung and provided rapid pain relief. Nearly normal medial rotation amplitude was recovered. The patient died at 10 months from complications related to the lung adenocarcinoma. DISCUSSION: This is the first report of metastatic lung carcinoma located in the infraspinatus muscle. The clinical presentation was very exceptional, no similar cases being reported in the literature. In bloc surgical resection appears to be the best therapeutic approach, allowing positive diagnosis and relief of pain and stiffness.
A multicenter study was carried out to evaluate the performance of a new commercial automated system in comparison with that of the reference agar dilution method. Ten clinical microbiology laboratories tested a collection of 61 strains of gram-negative bacilli (49 Enterobacteriaceae and 12 Pseudomonas aeruginosa), and 6 other laboratories tested a collection of 55 strains of gram-positive cocci (10 enterococci and 45 staphylococci) against 10-20 antimicrobial agents. The strains were selected on the basis that they harbored challenging and characterized mechanisms of resistance. In comparison with the agar reference method, the automated system gave an overall essential agreement (+/-1 dilution) of 94.5%, 93.5%, and 97% for the gram-negative bacilli, enterococci, and staphylococci, respectively. According to the interpretive standards of the National Committee for Clinical Laboratory Standards, the category agreement ranged from 96 to 96.4% for the three sets of organisms. The accuracy of the automated system, as determined by the kappa test, ranged from 0.80 to 0.88, reflecting an almost perfect agreement with the reference technique. Very major, major, and minor errors obtained with the automated system were 0.3%, 2.9%, and 6.6% for gram-negative bacilli, 3.4%, 0%, and 5% for enterococci, and 1%, 1.6%, and 2.7% for staphylococci, respectively. The high rate of very major errors in enterococci was mostly due to a single strain of multidrug-resistant Enterococcus faecium, which was found susceptible to several antibiotics in a majority of participant laboratories. The use of a heavy inoculum and of a broth test medium by the automated system might account for a better expression of certain resistance mechanisms, including beta-lactamases, as compared to the agar dilution reference method. The interlaboratory reproducibility was acceptable, as shown by the narrow dispersion of MICs and by the results of quality control.
Fifty-seven methicillin resistant S. epidermidis with decreased susceptibility to teicoplanin were obtained from 14 neutropenic patients on a period of 11 months (19 February-31 December 1998) from essentially blood culture (30 strains) and ORL specimens (21 strains). The MIC90 of methicillin, gentamicin, ofloxacin and telcoplanin were respectively 1024, 1024, 512 and 32 mg/l. We applied pulsed field gel electrophoresis (PFGE) after Smal digestion to 21 isolates choosed between eight patients with multiple isolates (> two strains). For epidemiological control, a MetiR and TeicoR S. epidermidis isolated from blood culture taken from Caen CHU was include in study. Twenty-one isolates were separated by PFGE into eight group, from I to VIII. The control strain was classed in group IX. Group I include 14 strains which can be subdivised on three sub-types (differed by a single to three bands): seven strains have the pulsotype Ia and obtained respectively from five strains in transplantation unit and two strains in hematology unit. Two strains have the pulsotype Ib and isolated in the two units. Five strains have the pulsotype Ic and obtained also from transplantation unit (four strains) and hematology unit (one strain). All the other pulsotypes were identified in only one strain, frequently in association with the pulsotype I. Until recently, infections due to coagulase negative staphylococci have been regarded as endogenous in origin, these results with some pulsotype of S. epidermidis MetiR and TeicoR in the two separate units suggered a nosocomial origin, probably by medical staff transmission because no S. epidermidis TeicoR was isolated from environmental control during all the period.