C J Soussy

Publications (105)253.57 Total impact

• Article: [Activity of doripenem against anaerobic bacteria].

  L Dubreuil, C Neut, S Mahieux, C Muller-Serieys, H Jean-Pierre, H Marchandin, C J Soussy, A Miara
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  ABSTRACT: This study examines the activity of doripenem, a new carbapenem compound compared with amoxicillin-clavulanic acid, piperacillin+tazobactam, imipenem, clindamycin and metronidazole against 316 anaerobes. Inoculum preparation and agar dilution method were performed according to the CLSI method for anaerobes (M11A7). At a concentration of 4μg/ml doripenem and imipenem (IMP) inhibited 122 (96 %) and 126 (99 %) strains of the Bacteroides fragilis group, respectively. In contrast, doripenem appeared more potent than IMP against Gram-positive anaerobes inhibiting at the same concentration of 4μg/ml 145/145 strains (100 %) versus 115/145 for IMP (79.3 %). Against 316 anaerobic strains, the carbapenem doripenem had an MIC(50) of 0.25μg/ml and an MIC(90) of 2μg/ml. Results were similar to those for imipenem (MIC(50) of 0.125μg/ml and MIC(90) of 4μg/ml). If we consider the resistant breakpoints of the two carbapenems as defined by EUCAST, the resistance rate for doripenem (MIC>4μg/ml) 1.6 % is similar to that of imipenem (MIC>8μg/ml) 1.3 %. Thus independently of the PK/PD parameters the two carbapenems demonstrated very close activity; doripenem was more potent on Gram-positive anaerobes and slightly less potent against Gram-negative anaerobes mainly the B. fragilis group. Further clinical studies are needed to assess its usefulness in patients.
  Pathologie Biologie 04/2011; 59(2):102-7. · 1.53 Impact Factor
• Article: In vitro antibacterial activity of ceftobiprole against clinical isolates from French teaching hospitals: proposition of zone diameter breakpoints.

  C Lascols, P Legrand, A Mérens, R Leclercq, C Muller-Serieys, H B Drugeon, M D Kitzis, M E Reverdy, M Roussel-Delvallez, C Moubareck, S Brémont, A Miara, M Gjoklaj, C-J Soussy
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  ABSTRACT: The aims of this study were to determine the in vitro activity profile of ceftobiprole, a pyrrolidinone cephalosporin, against a large number of bacterial pathogens and to propose zone diameter breakpoints for clinical categorisation according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) minimum inhibitory concentration (MIC) breakpoints. MICs of ceftobiprole were determined by broth microdilution against 1548 clinical isolates collected in eight French hospitals. Disk diffusion testing was performed using 30 μg disks according to the method of the Comité de l'Antibiogramme de la Société Française de Microbiologie (CA-SFM). The in vitro activity of ceftobiprole, expressed by MIC(50/90) (MICs for 50% and 90% of the organisms, respectively) (mg/L), was as follows: meticillin-susceptible Staphylococcus aureus, 0.25/0.5; meticillin-resistant S. aureus (MRSA), 1/2; meticillin-susceptible coagulase-negative staphylococci (CoNS), 0.12/0.5; meticillin-resistant CoNS, 1/2; penicillin-susceptible Streptococcus pneumoniae, ≤ 0.008/0.03; penicillin-resistant S. pneumoniae, 0.12/0.5; viridans group streptococci, 0.03/0.12; β-haemolytic streptococci, ≤ 0.008/0.016; Enterococcus faecalis, 0.25/1; Enterococcus faecium, 64/128; Enterobacteriaceae, 0.06/32; Pseudomonas aeruginosa, 4/16; Acinetobacter baumannii, 0.5/64; Haemophilus influenzae, 0.03/0.12; and Moraxella catarrhalis, 0.25/0.5. According to the regression curve, zone diameter breakpoints could be 28, 26, 24 and 22 mm for MICs of 0.5, 1, 2 and 4 mg/L respectively. In conclusion, this study confirms the potent in vitro activity of ceftobiprole against many Gram-positive bacteria, including MRSA but not E. faecium, whilst maintaining a Gram-negative spectrum similar to the advanced-generation cephalosporins such as cefepime. Thus ceftobiprole appears to be well suited for the empirical treatment of a variety of healthcare-associated infections.
  International journal of antimicrobial agents 03/2011; 37(3):235-9. · 3.03 Impact Factor
• Article: In vitro antibacterial activity of doripenem against clinical isolates from French teaching hospitals: proposition of zone diameter breakpoints.

  C Lascols, P Legrand, A Mérens, R Leclercq, L Armand-Lefevre, H B Drugeon, M D Kitzis, C Muller-Serieys, M E Reverdy, M Roussel-Delvallez, C Moubareck, A Lemire, A Miara, M Gjoklaj, C-J Soussy
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  ABSTRACT: The aims of the study were to determine the in vitro activity of doripenem, a new carbapenem, against a large number of bacterial pathogens and to propose zone diameter breakpoints for clinical categorization in France according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) minimum inhibitory concentration (MIC) breakpoints. The MICs of doripenem were determined by the broth microdilution method against 1,547 clinical isolates from eight French hospitals. The disk diffusion test was performed (10-μg discs) according to the Comité de l'Antibiogramme de la Société Française de Microbiologie (CASFM) method. The MIC(50/90) (mg/L) values were as follows: methicillin-susceptible Staphylococcus aureus (MSSA) (0.03/0.25), methicillin-resistant Staphylococcus aureus (MRSA) (1/2), methicillin-susceptible coagulase-negative staphylococci (MSCoNS) (0.03/0.12), methicillin-resistant coagulase-negative staphylococci (MRCoNS) (2/8), Streptococcus pneumoniae (0.016/0.25), viridans group streptococci (0.016/2), β-hemolytic streptococci (≤0.008/≤0.008), Enterococcus faecalis (2/4), Enterococcus faecium (128/>128), Enterobacteriaceae (0.06/0.25), Pseudomonas aeruginosa (0.5/8), Acinetobacter baumannii (0.25/2), Haemophilus influenzae (0.12/0.25), and Moraxella catarrhalis (0.03/0.06). According to the regression curve, the zone diameter breakpoints were 24 and 19 mm for MICs of 1 and 4 mg/L, respectively. This study confirms the potent in vitro activity of doripenem against Pseudomonas aeruginosa, Acinetobacter, Enterobacteriaceae, MSSA, MSCoNS, and respiratory pathogens. According to the EUCAST MIC breakpoints (mg/L) ≤1/>4 for Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter, and ≤1/>1 for streptococci, pneumococci, and Haemophilus, the zone diameter breakpoints could be (mm) ≥24/<19 and ≥24/<24, respectively.
  European Journal of Clinical Microbiology 11/2010; 30(4):475-82. · 2.86 Impact Factor
• Article: Occurrence of qnrA-positive clinical isolates in French teaching hospitals during 2002-2005.

  E Cambau, C Lascols, W Sougakoff, C Bébéar, R Bonnet, J-D Cavallo, L Gutmann, M-C Ploy, V Jarlier, C-J Soussy, J Robert
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  ABSTRACT: Bacteria harbouring the novel qnrA plasmid-mediated mechanism of quinolone resistance have been described in different countries, but the frequency of their occurrence has not been investigated. In total, 1,468 clinical isolates of Enterobacteriaceae with quinolone resistance or extended-spectrum beta-lactamase (ESBL) phenotypes were collected from eight teaching hospitals in France during 2002-2005 and screened for qnrA. Overall, 28 isolates (22 Enterobacter cloacae, three Klebsiella pneumoniae, one Citrobacter freundii, one Klebsiella oxytoca and one Proteus mirabilis) were positive for qnrA, representing 1.9% of all isolates, 3.3% of ESBL-producing isolates (22% of the E. cloacae isolates) and 0% of non-ESBL-producing isolates. The prevalence of qnrA among consecutive ESBL-producing isolates in 2004 from the eight hospitals was 2.8% (18/639). Of the qnrA-positive isolates, 100% were intermediately-resistant or resistant to nalidixic acid, and 75% to ciprofloxacin. Twenty-one of the 22 qnrA-positive E. cloacae isolates were obtained from two hospitals in the Paris area, and molecular typing and plasmid content analysis showed clonal relationships for five, three and two isolates, respectively. The qnrA genetic environment was similar to that of the In36 integron. The remaining two isolates had qnrA variants (30 and 29 nucleotide differences, respectively, compared with the original sequence) and an unknown genetic environment. The ESBL gene associated with qnrA was bla(SHV-12) in most of the isolates, but bla(PER-1) and bla(SHV-2a) were found in two isolates. In France, it appears that qnrA-positive isolates are predominantly E. cloacae isolates producing SHV-12, and may be associated with the dissemination of an In36-like integron.
  Clinical Microbiology and Infection 11/2006; 12(10):1013-20. · 4.54 Impact Factor
• Article: [Investigation of the new QNR-based mechanism of quinolone resistance among enterobacterial strains isolated in Henri-Mondor hospital 2002-2005].

  S Honoré, C Lascols, D Malin, R Targaouchi, V Cattoir, P Legrand, C-J Soussy, E Cambau
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  ABSTRACT: To assess the prevalence of the novel plasmid-mediated resistance to quinolones in enterobacteria isolated in our hospital. We have screened 737 enterobacterial strains isolated in Henri-Mondor hospital between 2002 and 2005 for the presence of the qnr gene by PCR using specific primers. Among them, 282 had a phenotype in concordance with extended spectrum betalactamase (ESBL). Qnr-positive strains were phenotypically and genetically characterized, and epidemiological link between the cases was investigated. Five qnr+ strains were described. The global prevalence was 0.7% but 5/282 among ESBL producing strains and 0/437 among quinolone-resistant enterobacteria non producing ESBL. The sequences of the PCR products were identical to qnrA in the environment of the integron In36. All the strains harboured also the ESBL SHV-12 gene. Transfer of qnr by conjugation raised quinolone MICs from 2 to 24 times. However clinical strains harboured a higher level of quinolone resistance and harboured also DNA gyrase and topoisomerase IV mutations. Two strains were epidemiologically related by molecular typing and contact tracing revealed that the patients have been previously hospitalized in the same tertiary care center. We described the first investigation of qnr-positive strains in one hospital in France over 4 years. Although the qnr gene prevalence is low, nosocomial transmission is already shown and the transfer of the qnr containing integron among ESBL producing strains may predict future epidemic. Surveillance will be necessary to confirm this low prevalence rate of qnr in France.
  Pathologie Biologie 06/2006; 54(5):270-9. · 1.53 Impact Factor
• Article: Activity of linezolid against Gram-positive cocci isolated in French hospitals as determined by three in-vitro susceptibility testing methods.

  C Muller-Serieys, H B Drugeon, J Etienne, C Lascols, R Leclercq, J Nguyen, C J Soussy
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  ABSTRACT: 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.
  Clinical Microbiology and Infection 03/2004; 10(3):242-6. · 4.54 Impact Factor
• Article: In vitro antibacterial activity of moxifloxacin against hospital isolates: a multicentre study.

  C-J Soussy, J Nguyen, F Goldstein, H Dabernat, A Andremont, R Leclercq, H Drugeon, P Cavallo, H Chardon, J Etienne, Y Rio, P Courvalin
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  ABSTRACT: To evaluate the in vitro antibacterial activity of moxifloxacinin in comparison to that of other fluoroquinolones (ciprofloxacin, ofloxacin and trovafloxacin). 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. 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. 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.
  Clinical Microbiology and Infection 10/2003; 9(10):997-1005. · 4.54 Impact Factor
• Article: [In vitro activity of the pristinamycin against the isolated staphylococci in the french hospitals in 1999-2000].

  R Leclercq, C J Soussy, Ph Weber, N Moniot-Ville, C Dib
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  ABSTRACT: 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.
  Pathologie Biologie 09/2003; 51(7):400-4. · 1.53 Impact Factor
• Article: Susceptibility of Enterobacteriaceae to β‐lactam agents and fluoroquinolones: a 3‐year survey in France

  J. Sirot, M. H. Nicolas-Chanoine, H. Chardon, J. L. Avril, C. Cattoen, J. C. Croix, H. Dabernat, T. Fosse, J. C. Ghnassia, E. Lecaillon, A. Marmonier, M. Roussel-Delvallez, C. J. Soussy, A. Trevoux, F. Vandenesch, C. Dib, N. Moniot-Ville, Y. Rezvani
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  ABSTRACT: Objective To assess trends in the susceptibility to β-lactam agents and to fluoroquinolones of clinically relevant Enterobacteriaceae isolated over a 3-year period in 14 French hospital laboratories.Methods During the second quarter of 1996, 1997 and 1998, 180 consecutive non-duplicate isolates of Enterobacteriaceae were collected in each center. Sixteen β-lactams and four quinolones were tested by the disk diffusion method. In addition, the double-disk synergy test was used to screen for the production of extended-spectrum β-lactamase (ESBL).Results Totals of 2507, 2312 and 2506 clinical isolates were obtained in each period, respectively. The distribution of Enterobacteriaceae species according to clinical specimens and wards was similar in each study period. No significant variation in the susceptibility rates to β-lactams and fluoroquinolones was observed, except in Klebsiella pneumoniae and Enterobacter aerogenes. The prevalence of ESBL-producing isolates decreased from 18% to 9% in the former, while it increased from 32% to 54% in the latter. At the same time, the susceptibility to ofloxacin and pefloxacin increased for K. pneumoniae (P < 0.003) and cephalosporinase-producing species (P < 0.05), except Enterobacter spp.Conclusion Over the 3-year study period β-lactams and fluoroquinolones remained highly active against Enterobacteriaceae clinical isolates, with the exception of E. aerogenes, probably as a result of the dissemination of multiresistant clones in French hospitals.
  Clinical Microbiology and Infection 05/2002; 8(4):207 - 213. · 4.54 Impact Factor
• Article: Susceptibility of Enterobacteriaceae to beta-lactam agents and fluoroquinolones: a 3-year survey in France.

  J Sirot, M H Nicolas-Chanoine, H Chardon, J L Avril, C Cattoen, J C Croix, H Dabernat, T Fosse, J C Ghnassia, E Lecaillon, A Marmonier, M Roussel-Delvallez, C J Soussy, A Trevoux, F Vandenesch, C Dib, N Moniot-Ville, Y Rezvani
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  ABSTRACT: To assess trends in the susceptibility to beta-lactam agents and to fluoroquinolones of clinically relevant Enterobacteriaceae isolated over a 3-year period in 14 French hospital laboratories. During the second quarter of 1996, 1997 and 1998, 180 consecutive non-duplicate isolates of Enterobacteriaceae were collected in each center. Sixteen beta-lactams and four quinolones were tested by the disk diffusion method. In addition, the double-disk synergy test was used to screen for the production of extended-spectrum beta-lactamase (ESBL). Totals of 2507, 2312 and 2506 clinical isolates were obtained in each period, respectively. The distribution of Enterobacteriaceae species according to clinical specimens and wards was similar in each study period. No significant variation in the susceptibility rates to beta-lactams and fluoroquinolones was observed, except in Klebsiella pneumoniae and Enterobacter aerogenes. The prevalence of ESBL-producing isolates decreased from 18% to 9% in the former, while it increased from 32% to 54% in the latter. At the same time, the susceptibility to ofloxacin and pefloxacin increased for K. pneumoniae (P < 0.003) and cephalosporinase-producing species (P < 0.05), except Enterobacter spp. Over the 3-year study period beta-lactams and fluoroquinolones remained highly active against Enterobacteriaceae clinical isolates, with the exception of E. aerogenes, probably as a result of the dissemination of multiresistant clones in French hospitals.
  Clinical Microbiology and Infection 04/2002; 8(4):207-13. · 4.54 Impact Factor
• Article: Effect of pH on the susceptibility of Helicobacter pylori to the ketolide telithromycin (HMR 3647) and clarithromycin.

  C Lascols, A Bryskier, C J Soussy, J Tanković
  Journal of Antimicrobial Chemotherapy 12/2001; 48(5):738-40. · 5.07 Impact Factor
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  Article: Clarithromycin resistance of Helicobacter pylori has a major impact on the efficacy of the omeprazole-amoxicillin-clarithromycin therapy.

  J Tankovic, D Lamarque, C Lascols, C J Soussy, J C Delchier
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  ABSTRACT: Clarithromycin resistance of Helicobacter pylori is relatively frequent in France and is assumed to be the main cause of failure of the proton pump inhibitor-amoxicillin-clarithromycin (PPI-AC) therapy, which is the first-line regimen in our country. We determined the respective effects of clarithromycin primary and secondary resistances on efficacy of the PPI-AC regimen and examined whether failures were associated with persistence of the same strain or with emergence of a new one. Hundred and twenty three H. pylori-infected patients were treated for seven days with omeprazole 20 mg b.d., amoxicillin 1 g b.d., and clarithromycin 500 mg b.d. Eradication was assessed by breath test in 102 patients. MICs of clarithromycin were determined by E-test. Strain genotyping was performed by random amplified polymorphic DNA. The pre-treatment and post-treatment prevalences of clarithromycin resistance were 18.7% (23/123) and 69.2% (9/13), respectively. The rates of eradication were 67.6% (69/102), 78.8% (67/85), and 11.8% (2/17) for all, susceptible and resistant strains, respectively. The post-treatment isolate was available for six patients with a susceptible pre-treatment isolate and a persistent infection; resistance emerged in two patients and was associated with persistence of the pre-treatment strain in one and with selection of a new strain in the other. In conclusion, in our hospital, failures of the PPI-AC therapy are related to both clarithromycin primary and secondary resistances but emergence of secondary resistance does not explain all failures in the initial clarithromycin-susceptible group. In that group a new strain can emerge after failure.
  Pathologie Biologie 10/2001; 49(7):528-33. · 1.53 Impact Factor
• Article: Impact of Helicobacter pylori resistance to clarithromycin on the efficacy of the omeprazole-amoxicillin-clarithromycin therapy.

  J Tankovic, D Lamarque, C Lascols, C J Soussy, J C Delchier
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  ABSTRACT: Helicobacter pylori resistance to clarithromycin is relatively frequent in France and is assumed to be the main cause of failure of the proton pump inhibitor-amoxicillin-clarithromycin (proton pump inhibitor-AC) therapy, which is the first-line regimen in France. To determine the respective effects of clarithromycin primary and secondary resistances on efficacy of the proton pump inhibitor-AC regimen and to determine whether failures are associated with persistence of the same strain or with emergence of a new one. A total of 123 H. pylori-infected patients were treated for 7 days with omeprazole 20 mg b.d., amoxicillin 1 g b.d., and clarithromycin 500 mg b.d. Eradication was assessed by breath test in 102 patients. Minimal inhibitory concentrations of clarithromycin were determined by E-test. Strain genotyping was performed by random amplified polymorphic DNA. The pre-treatment and post-treatment prevalences of clarithromycin resistance were 19% (23 out of 123) and 69% (nine out of 13), respectively. The rates of eradication were 68% (69 out of 102), 79% (67 out of 85), and 12% (two out of 17) for all, susceptible and resistant strains, respectively. The post-treatment isolate was available for six patients with a susceptible pre-treatment isolate and a persistent infection. Resistance emerged in two patients and was associated with persistence of the pre-treatment strain in one and with selection of a new strain in the other. In our hospital, failures of the proton pump inhibitor-AC therapy are related to both clarithromycin primary and secondary resistances, but the emergence of secondary resistance does not explain all of the failures in the initial clarithromycin-susceptible group. In that group a new strain can emerge after failure.
  Alimentary Pharmacology & Therapeutics 06/2001; 15(5):707-13. · 3.77 Impact Factor
• Article: Single or double mutational alterations of gyrA associated with fluoroquinolone resistance in Campylobacter jejuni and Campylobacter coli.

  R Bachoual, S Ouabdesselam, F Mory, C Lascols, C J Soussy, J Tankovic
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  ABSTRACT: We looked for the presence of gyrA mutations in seven fluoroquinolone-resistant French clinical isolates of Campylobacter jejuni and Campylobacter coli. Three of the five isolates of C. jejuni and the two isolates of C. coli had high-level resistance to nalidixic acid (MICs 128-256 microg/ml) and ciprofloxacin (MICs 32 microg/ml). A gyrA mutation was found in all these isolates leading to the following substitutions: Thr86-Ile in four cases and Asp90-Tyr for one C. coli strain. One isolate had high-level resistance to nalidixic acid (MIC 64 microg/ml) but low-level resistance to ciprofloxacin (MIC 2 microg/ml) and also carried a gyrA mutation leading to a Thr86-Ala substitution. The last isolate of C. jejuni studied displayed an atypical resistance phenotype: It was resistant to high levels of ciprofloxacin (MIC 64 microg/ml) but remained fully susceptible to nalidixic acid (MIC 2 microg/ml). This phenotype was not explained by the presence of peculiar mutations in gyrA or gyrB. It carried a gyrA mutation leading to a Thr86-Ile substitution and was devoid of gyrB mutation. Despite numerous attempts with various degenerate oligonucleotide primers deduced from conserved regions of known parC genes, we were unable to amplify a corresponding sequence in C. jejuni or C. coli. First-step and second-step in vitro mutants, derived from reference strain C. coli ATCC 33559 with ciprofloxacin or moxifloxacin as selecting agents, were found to carry one and two mutations in gyrA, respectively. In contrast with the results obtained with clinical isolates, a variety of gyrA mutations were obtained in vitro.
  Microbial Drug Resistance 02/2001; 7(3):257-61. · 2.15 Impact Factor
• Article: [Antibiogram Committee of the French Microbiology Society. Report 2000-2001].

  C J Soussy, G Carret, J D Cavallo, H Chardon, C Chidiac, P Choutet, P Courvalin, H Dabernat, H Drugeon, L Dubreuil, F Goldstein, V Jarlier, R Leclercq, M H Nicolas-Chanoine, A Philippon, C Quentin, B Rouveix, J Sirot
  Pathologie Biologie 12/2000; 48(9):832-71. · 1.53 Impact Factor
• Article: Roles of gyrA mutations in resistance of clinical isolates and in vitro mutants of Bacteroides fragilis to the new fluoroquinolone trovafloxacin.

  R Bachoual, L Dubreuil, C J Soussy, J Tankovic
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  ABSTRACT: We determined whether gyrA mutations were present in fluoroquinolone-resistant laboratory mutants derived from the Bacteroides fragilis reference strain ATCC 25285 and in clinical isolates of B. fragilis. The two first-step mutants selected on ciprofloxacin (CIP) were devoid of gyrA mutations, whereas two of the three CIP-selected second-step mutants studied presented the same gyrA mutation leading to a Ser82Phe change. Unusual GyrA alterations, Asp81Asn or Ala118Val, were detected in two of the three first-step mutants selected on trovafloxacin (TRO), Mt3 and Mt1, respectively. The Ala118Val change had no effect on the susceptibility of Mt1 to CIP. No second-step mutant could be obtained with TRO as a selector. For the 12 clinical isolates studied, a Ser82Phe change in GyrA was found only in the 3 strains which showed the highest levels of TRO resistance (MIC, 4 microgram/ml). Thus, the resistance phenotypes and genotypes observed in fluoroquinolone-resistant clinical isolates of B. fragilis were similar to those found in CIP-selected laboratory mutants, whereas peculiar mutational events could be selected in vitro with TRO.
  Antimicrobial Agents and Chemotherapy 08/2000; 44(7):1842-5. · 4.84 Impact Factor
• Article: Frequent association between alteration of the rdxA gene and metronidazole resistance in French and North African isolates of Helicobacter pylori.

  J Tankovic, D Lamarque, J C Delchier, C J Soussy, A Labigne, P J Jenks
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  ABSTRACT: Mutations in the rdxA gene have been associated with the acquisition of resistance to metronidazole in Helicobacter pylori. This gene encodes an NADPH nitroreductase whose expression is necessary for intracellular activation of the drug. We wished to examine whether mutations in rdxA were present in resistant H. pylori isolates infecting either French or North African patients. We determined the complete nucleotide sequences of the rdxA genes from seven French and six North African patients infected with paired resistant and sensitive strains. Genotyping by random amplified polymorphic DNA analysis confirmed the close genetic relatedness of the susceptible and resistant isolates from individual biopsies. Eight French and five North African individual resistant strains were also studied. For the French strains, an alteration in rdxA most probably implicated in resistance was found in 10 cases (seven frameshift mutations, two missense mutations, and one deletion of 211 bp). One to three putative missense mutations were identified in four cases, and a missense mutation possibly not implicated in resistance was discovered in the last case. For the North African strains, an alteration in rdxA was found in eight cases (three frameshift mutations, three missense mutations, one deletion of 6 bp, and one insertion of a variant of IS605). Two strains contained putative missense mutations, and no change was observed in rdxA of the last strain. Thus, inactivation of the rdxA gene is frequently, but not always, associated with resistance to metronidazole in French and North African clinical isolates of H. pylori. In addition, a variety of alterations of rdxA are associated with the resistant phenotype.
  Antimicrobial Agents and Chemotherapy 04/2000; 44(3):608-13. · 4.84 Impact Factor
• Article: [Methicillin-resistant Staphylococcus aureus: factors responsible for its incidence].

  H Aubry-Damon, C J Soussy
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  ABSTRACT: INTRODUCTION: How can we explain that the proportion of methicillin-resistant Staphylococcus aureus (MRSA) varies between the European countries, ranging from < 1% in Scandinavia to > 30% in Spain, France and Italy? This paper is aimed at attempting to determine factors at the origin of the spreading of endemic MRSA strains as of the early 1980s. Those strains are characterized by their ability to develop resistance to current antibiotics and make treatment of severe and deep infections more complex. CURRENT KNOWLEDGE AND KEY POINTS: Differences in the virulence of MRSA strains and that of susceptible strains appear unlikely. MRSA prevalence seems to be a growing problem, especially in Southern Europe where rates of resistance to other anti-staphylococcal antibiotics are high. General policies for antibiotic therapy as well as the implementation of strategies for prevention and control of MRSA might be responsible for such rates. Indeed, once MRSA is introduced into a facility without control program, this multiresistant bacteria rapidly spreads within the hospital and becomes endemic, expanding its reservoir. FUTURE PROSPECTS ET PROJECTS: Due to the introduction of new methods in microbiology and communication, infection control measures including procedures for isolation and identification of MRSA reservoirs are still feasible; however, their implementation requires human and material resources. Areas requiring improvement in the detection of MRSA outbreaks are identified in this paper, with particular emphasis on the need for national surveillance of MRSA prevalence and reappraisal of MRSA control strategies in French hospitals.
  La Revue de Médecine Interne 04/2000; 21(4):344-52. · 0.61 Impact Factor
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  Available from: oxfordjournals.org

  Article: Case of false-positive results of the urinary antigen test for Legionella pneumophila.

  L Deforges, P Legrand, J Tankovic, C Brun-Buisson, P Lang, C J Soussy
  Clinical Infectious Diseases 11/1999; 29(4):953-4. · 9.15 Impact Factor
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  Available from: oxfordjournals.org

  Article: In-vitro antibacterial activity of levofloxacin against hospital isolates: a multicentre study.

  C J Soussy, M Cluzel, M C Ploy, M D Kitzis, C Morel, A Bryskier, P Courvalin
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  ABSTRACT: The objective of this study was to evaluate the activity of the fluoroquinolone, levofloxacin, against hospital isolates of bacteria. MICs of levofloxacin were determined for 2154 strains by agar dilution. Breakpoints for susceptibility testing were calculated using the agar diffusion technique with 5 micrograms discs. The activity of levofloxacin against nalidixic acid- and pefloxacin-susceptible Enterobacteriaceae (n = 668) was higher (MIC50/90 0.06-0.12 mg/L) than previously reported for ofloxacin. As seen with other fluoroquinolones, this activity was reduced against nalidixic acid-resistant and pefloxacin-intermediate and -resistant strains (MIC 1-8 mg/L). MICs for Pseudomonas aeruginosa (n = 104) were between 0.12 and 128 mg/L. Levofloxacin had good activity against nalidixic acid- and pefloxacin-susceptible Acinetobacter baumannii (n = 12; MIC 0.06-0.25 mg/L), but the activity was reduced against nalidixic acid- and pefloxacin-resistant strains (n = 80; MIC 1-32 mg/L). Haemophilus influenzae (n = 70), Haemophilus parainfluenzae (n = 47) and Moraxella catarrhalis (n = 64) were inhibited by low concentrations of levofloxacin (MICs 0.016-0.03 mg/L, 0.03-0.12 mg/L) and 0.03-0.12 mg/L, respectively). Clostridium perfringens (n = 23; MIC 0.25-1 mg/L) was more susceptible than Bacteroides fragilis (n = 60; MIC 0.5-4 mg/L). Levofloxacin showed superior activity compared with ofloxacin against methicillin-susceptible staphylococci (n = 107; MIC 0.03-0.5 mg/L); the resistant strains (MICs 2-32 mg/L) were usually also resistant to methicillin. Levofloxacin was less effective against enterococci (n = 105; MIC 1-32 mg/L), but streptococci (n = 192) and pneumococci (n = 129), including 58 penicillin-non-susceptible strains, were inhibited by low concentrations (MICs 0.5-2 mg/L). According to the regression curve, zone diameters were usually 20-22 mm, 17-19 mm and 15-16 mm for MICs of 1, 2 and 4 mg/L, respectively. In conclusion, this study, performed on a large number of strains, confirms the superior anti-bacterial activity of levofloxacin compared with ofloxacin, especially against pathogens isolated from respiratory tract infections.
  Journal of Antimicrobial Chemotherapy 07/1999; 43 Suppl C:43-50. · 5.07 Impact Factor