[Triclocarban antibacterial activity on resistant staphylococci, streptococci, and enterococci]. / Activité antibactérienne du triclocarban sur les staphylocoques, entérocoques et streptocoques résistant.

Triclocarban is an antiseptic of the anilide family. Its antibacterial activity was re-assessed in vitro against various susceptible and antibiotic resistant staphylococcus, streptococcus, and enterococcus strains. The results of this study show that, in vitro, the effectiveness of triclocarban antibacterial is maintained at very low MICs ranging from 0.5 to 8 mg/L for the various resistant strains studied. Triclocarban remains still very effective for the treatment of either initially bacterial skin and mucosal infections, or skin and mucosal at risk of super infection.

In vitro antibacterial activity of ceftobiprole against clinical isolates from French teaching hospitals: proposition of zone diameter breakpoints.

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; ß-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.

In vitro antibacterial activity of doripenem against clinical isolates from French teaching hospitals: proposition of zone diameter breakpoints.

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), ß-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.

Correlation between the VITEK2 system and cefoxitin disk diffusion for the daily detection of oxacillin resistance in a large number of clinical Staphylococcus aureus isolates.

The aim of the present study was to compare the performance of the new VITEK2 AST-P551 card with the cefoxitin disk diffusion method for the daily detection of methicillin resistance with a high number of Staphylococcus aureus clinical isolates. Detection of the PBP2a protein or mecA gene was performed for each discordant case. Seventy (3.3%) isolates out of 2,107 clinical strains showed discordant results, two very major errors, four major errors and 64 minor errors. Fifty-nine (84%) discordant results were resolved, with a final overall agreement of 99.5%. Eleven (0.5%) strains remained discordant (minor error [mE]). Four of 370 MRSA strains were misclassified as susceptible in daily practice by the cefoxitin disk diffusion method. All of these strains were resistant to aminoglycosides and/or fluoroquinolones. The VITEK2 system is highly reliable for methicillin resistance detection at the routine level. Oxacillin-susceptible classified clinical strains with associated resistance patterns required attention.

Significance of Propionibacterium acnes-positive samples in spinal instrumentation.

STUDY DESIGN: A retrospective study about Propionibacterium acnes infections after Cotrel-Dubousset (CD) instrumentation. OBJECTIVES: To analyze the significance of P. acnes-positive deep samples after CD. SUMMARY OF BACKGROUND DATA: The diagnosis of spinal infections to P. acnes after CD is difficult. METHODS: Patients with revision surgery and at least 1 P. acnes-positive deep sample, between 2000 and 2006 were included. Group A had 1 revision surgery and group B had 2 successive revision surgeries, with P. acnes-positive deep samples. Group A was divided into 2 subgroups according to the peroperative macroscopic aspect, subgroup A1 with septic tissues, subgroup A2 without septic tissues. The biologic characteristics of the patients and the surgical and medical treatments were assessed. RESULTS: Sixty-eight patients were included, 60 in group A (A1 = 33, A2 = 27) and 8 in group B. Group A: 26 patients had 1 or 2 P. acnes-positive samples and 34 had at least 3 P. acnes-positive samples. Histology showed chronic inflammatory changes. C-reactive protein value median rate was 42 (A1) and 5 mg/L (A2). Twenty-two patients had a complete implant removal (14 with antibiotics, A1 = 12, A2 = 2). Nine patients had a total implant replacement (7 with antibiotics). Twenty-two patients had a partial implant removal (17 with antibiotics, A1 = 5, A2 = 12). Seven A1 patients had an irrigation and debridement (6 with antibiotics). The evolution was favorable for 28 patients. Seven patients had a documented sepsis. Group B: during the first revision, 8 patients had a partial implant removal (2 with antibiotics); during the second revision, all patients received antibiotics 4 of whom had a total implant removal. The long-term evolution was favorable for 6 patients. CONCLUSION: P. acnes infection of spinal instrumentation is difficult to diagnose. Results of at least 4 deep sample cultures, histology, and C-reactive protein values must be compared to the peroperative macroscopic aspect.

[Monitoring of antibiotic resistance of gram negative anaerobes]. / Surveillance de la résistance aux antibiotiques des anaérobies stricts à Gram négatif.

MATERIAL AND METHOD: Using an agar reference method (Norma M11-A5, National Committee for Clinical and Laboratory Standards) the minimal inhibitory concentrations of nine antibiotics were determined for 376 anaerobic strains. The following strains were investigated: 254 Bacteroides fragilis group (including 143 B. fragilis), 122 other gram-negative anaerobes (Bacteroides spp., Prevotella, Fusobacterium, Porphyromonas, Suterella, Desulfomonas, Veillonella). RESULTS: In the B. fragilis group resistance rates were: coamoxyclav 2.8%, ticarcillin 27.5%, ticarcillin-clavulanic acid 1.9%, piperacillin-tazobactam 1.9%, cefoxitin 6.2%, imipenem 0.8%, clindamycin 28.3%, respectively. Based on previous studies, resistance to imipenem remained low in 2003 and was only observed for B. fragilis. Resistance to clindamycin was maintained around 25%. No metronidazole resistance was observed, but decreased susceptibility was found for B. fragilis, B. merdae and Prevotella, as in 4.3% of gram-negative anaerobes. DISCUSSION: This study confirms the high resistance rate of gram-negative anaerobes to clindamycin, the efficient activity of imipenem, beta-lactam/beta-lactamase inhibitor combinations and metronidazole. However, reduced metronidazole susceptibility seems to be increasing.

Long-term evolution of a nosocomial outbreak of Pseudomonas aeruginosa producing VIM-2 metallo-enzyme.

From April 1996 to July 2004, an outbreak of metallo-beta-lactamase-positive (MBL) Pseudomonas aeruginosa occurred in the haematology ward at Nantes University Hospital in France. Fifty-nine patients were carriers of VIM-2-positive strains of whom 14 were infected (mostly urinary tract infections and pneumonia). Pulsed-field gel electrophoresis identified related isolates demonstrating resistance to all beta-lactams, aminoglycosides, fluoroquinolones, fosfomycin, rifampicin but not colistin. The bla(VIM-2) gene responsible for VIM-2 MBL was not plasmid-encoded but part of a novel type of class 1 integron. VIM-2-positive strains were mostly from urine samples and clinical data suggest that in the absence of therapeutic guidelines, piperacillin-tazobactam or aztreonam may be a reliable choice for treating infections with MBL-producing strains.

Biological cost of fluoroquinolone resistance in Escherichia coli implicated in polyclonal infection.

Polyclonal Escherichia coli strains were isolated in a transplanted patient who experienced successive septic shocks. Fluoroquinolone susceptible and resistant strains were corresponding to different PFGE fragment profiles. The gyrA S83L mutation was associated with a reduction in biological fitness. Resistant strain was selected by a long-term single use of ofloxacin.

[Clinical aspects and management of patients with tuberculous meningitis. Retrospective analysis from 1994 to 2005]. / Aspects cliniques et prise en charge thérapeutique des méningites tuberculeuses. Analyse rétrospective de 15 cas observés de 1994 à 2005.

Tuberculous meningitis remains a devastating disease with poor prognosis in terms of mortality or invalidating after-effects. Eighteen cases of tuberculous meningitis, occurred between 1994 and 2005, were re-examined retrospectively. Among the 18 patients, 13 were aged from 14 to 64 years, and 5 were older than 64. There was no gender dominance. Factors of risk were identified in 7 patients. British Medical Research Council staging was III in 9 patients, II in 2 patients and I in 7 patients. Protein and glucose levels in the cerebrospinal fluid sample were very variable ranging from 0.4 to 10.7 g/L and 0.4 to 3.7 mmol/L respectively. The cellular reaction was also very variable ranging from 0 to 250 elements, mostly lymphocytes. Antituberculous treatment was given to 15 patients, associated with corticosteroid therapy for 9 patients. Among the 18 patients, 11 died within 1 year, 4 were treated for a recurrence occurring up to 6 years after the diagnosis, 1 presented important neuropsychic after-effects and 2 patients survived without after-effects with a time ranging between 6 months and 1 year. The deceased patients were significantly older than the others. The risk of mortality was 4.5-fold greater among stage III patients than among stage I and II patients. The use of corticosteroids significantly reduced the risk of death.

[Efficacy and safety of extended-release clarithromycin (5-day short-course) vs telithromycin, in acute bacterial exacerbation of chronic bronchitis]. / Efficacité et tolérance de la clarithromycine, forme à libération modifiée en traitement court de cinq jours dans les exacerbations aiguës de bronchite chronique, comparativement à la télithromycine.

BACKGROUND: The extended-release formulation of clarithromycin (CLA-ER) allows using this macrolide as a single daily dose. The purpose of this study was to evaluate the efficacy and safety of the CLA-ER formulation (500 mgx2) vs telithromycin (TELI) (400 mgx2) as a short course 5-day treatment, once a day, in patients with AECB. METHOD: This randomized double-blind study was conducted in patients with AECB without severe airflow limitation (FEV1>35%), with sputum purulence (mandatory criterion), and with either increased sputum volume or increased dyspnea, or both (Anthonisen criteria I or II). RESULTS: Three hundred sixty-two patients were assessed (62.6 years of age+/-12.9, men: 58.8%) positive culture on inclusion for 53.8%, with Haemophilus influenzae (N=57), Moraxella catarrhalis (N=42), and Streptococcus pneumoniae (N=41). In the per protocol population, the clinical success rate at day 8 was 97% (161/166) vs 97% (146/151), 97.5% CI=[-4.12 -4.71], the clinical cure rate at day 30 was 78% (129/166) versus 77% (116/151), P=0.85, and mean time without recurrence was 62 days versus 61 days (P=0.51), in CLA-ER and TELI groups, respectively. Fourteen patients in the CLA-ER group (8.2%) and 20 patients in the TELI group (12.4%) experienced at least one treatment-related adverse event (P=0.21), upon which gastrointestinal events were the most commonly reported treatment-related ones. CONCLUSION: CLA-ER (1000 mg once a day) for 5 days is at least as effective as telithromycin in the treatment of AECB without severe airflow limitation and is well tolerated.

Correlation of agar dilution and VITEK2 system for detection of resistance to macrolides, lincosamides and pristinamycin among Staphylococcus aureus and Staphylococcus epidermidis: association with genotypes.

The performance of the VITEK2 system was evaluated against the agar dilution reference procedure for testing susceptibility of Staphylococcus aureus and Staphylococcus epidermidis to macrolides, lincosamides and streptogramins (MLS). Eighty clinical isolates were selected according to their resistance phenotype and genotype. Results for erythromycin and clindamycin showed 100% agreement; results for lincomycin showed agreement of 78%, with one very major error and 17 minor errors; and results for pristinamycin showed agreement of 46%, with one major error and 43 minor errors. Most isolates resistant to lincomycin and streptogramin A (L SgAr phenotype) were falsely susceptible to lincomycin, and intermediately-resistant or resistant to pristinamycin, with the VITEK2 system. No resistance gene was detected. Most (80%) isolates resistant constitutively to MLS (MLS(r)BC phenotype) were falsely intermediately-resistant to pristinamycin with the VITEK2 system. The erm(A) gene was more common than erm(C) in MLS(r)BC strains. Resistance to pristinamycin alone (SgA SgB PTr phenotype), or associated with either lincomycin resistance (L SgA SgB PTr phenotype) or constitutive MLS(B) resistance (MLS(BC) SgA PTr phenotype), was well-characterised without discordant results. Resistance to pristinamycin was always associated with resistance to streptogramin A, encoded by the vga(A), vga(B), vgb(A) and vat(A) genes in association with the erm(A) or erm(C) genes.

[Vaccination failure: case report of Haemophilus influenzae b meningitis in a 14-month-old child]. / Echec de la vaccination contre Haemophilus influenzae b: cas d'une méningite chez un enfant de 14 mois.

BACKGROUND: The generalization of the vaccination against H. influenzae b (Hib), according to its integration in the French vaccinal calendar, led to the incidence decrease of the purulent meningitis with Hib in young children, which became a so rare event. CASE REPORT: We described the case of a 14-months-old child showing a bacterial purulent meningitis with Hib, despite of a well driven vaccination. DISCUSSION: The epidemiology of bacterial meningitis was upset by the generalization of the anti-H. influenzae b vaccination. The use of combined vaccines specially reduced the incidence and the gravity of this pathology. Nevertheless, in spite of the excellent vaccinal coverage, the limited but real persistence of epiglottis or meningitis due to H. influenzae b should keep in mind of the biologists and the clinicians. Indeed, the chronic nasopharyngal carriage, the existence of not vaccinated or not answering people allow to consider the persistent risk of H. influenzae b bacterial meningitis.

[An example of simulation for a better understanding of PK/PD relationship of antibiotics]. / Un exemple de modélisation permettant une meilleure compréhension de la relation PK/PD des antibiotiques.

The interpretation of PK/PD indices is specific to each class of antibiotics. In order to illustrate this, we developed a multidisciplinary tutorial program based on simulation of clinical cases. Three drugs were included in this software: tobramycin, vancomycin and azithromycin. From the dosage regimen proposed by the user, the model simulates a plotting of antibiotic plasma concentrations vs. time (tobramycin, vancomycin and azithromycin) and tissue concentrations (azithromycin). Peak and trough concentrations are calculated at steady-state. A commentary is provided to evaluate the efficacy of treatment and to assist the user in improving his prescription of tobramycin or vancomycin. T(> MIC) (time the concentration remains above the MIC) and AUC(24) (area under the concentration-time curve) are calculated in plasma and tissues for azithromycin. In order to create a link between theoretical pharmacokinetics and clinical practice, we propose this model as a simulation of antibiotic monitoring. We put the emphasis on interactivity and simulation, leading to applied reasoning and decision making. It illustrates (i) the influence of pharmacokinetic parameters, location of infection and bactericidal kinetics on the use of three different classes of antibiotics, (ii) the role of route of administration, dosing and intervals between administrations on therapeutic response and (iii) the influence of erratic administrations on clinical efficacy.

[Treatment of exacerbations of chronic obstructive pulmonary disease with pristinamycin]. / Traitement des exacerbations de broncho-pneumopathie chronique obstructive (BPCO) par la pristinamycine.

BACKGROUND: Pristinamycin is a bactericidal antibiotic whose spectrum covers the main respiratory pathogens including S. pneumoniae poorly sensitive to penicillin. It has not yet been evaluated in short course treatment of acute exacerbations of chronic obstructive bronchitis (AECB). METHODS: 476 patients suffering from an AECB were randomised to either a short course of pristinamycin, 3 G daily for 4 days, or conventional treatment with co-amoxiclav (AAC) 2G daily for 8 days. The duration of follow-up was 6 months. RESULTS: The clinical success rate at 21 days was the same in both groups at 87.2% and 87.9%, CI95% [-7.0%, 6.0%], in the protocol population (FEV1<80%). Among the 120 patients in whom a bacterial pathogen was isolated at the time of inclusion a satisfactory bacteriological response was obtained in 84.6% of the PRI patients against 78.2% of the AAC patients. The time to relapse was comparable with a relapse rate of 25% reached in 128 days in the PRI group and 125 days in the AAC group. Treatment related side effects occurred in 9.2% of the PRI group and in 10.6% of the AAC group. CONCLUSION: Pristinamycin 3 G daily for 4 days is as effective and well tolerated as co-amoxiclav 2G daily for 8 days in the treatment of AECB.

Activity of linezolid against Gram-positive cocci isolated in French hospitals as determined by three in-vitro susceptibility testing methods.

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.

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.