Distribution and antimicrobial susceptibility of bacteria from adults with community-acquired pneumonia or complicated skin and soft tissue infections in France: the nationwide French PREMIUM study.

The empirical therapy of community-acquired pneumonia (CAP) and complicated skin and soft tissue infections (cSSTIs) must be based on updated bacterial distribution and susceptibility data. A nationwide study consecutively collected 1288 isolates from CAP (n=467) and cSSTIs (n=821) from 18 French hospitals between 2012 and 2013. The MIC values of commonly used antimicrobial agents, including ceftaroline, were determined. Bacterial distribution featured Pneumococcus, Haemophilus influenzae, and Staphylococcus aureus for CAPs and S. aureus, ß-hemolytic streptococci and Enterobacteriaceae for cSSTIs. Antimicrobial susceptibility testing indicated i) the sustained third-generation cephalosporins and levofloxacin activity against pneumococci and H. influenzae, ii) no methicillin-resistant Staphylococcus aureus emergence among respiratory pathogens, iii) the high in vitro activity of ceftaroline against staphylococci from cSSTIs (98.7% susceptibility), and iv) the worrisome decreasing fluoroquinolone and third-generation cephalosporin susceptibilities among Enterobacteriaceae. This laboratory-based survey depicts a contrasting situation and supports the scoring of patients for the resistant pathogen risk before empirical therapy.

EUCAST expert rules in antimicrobial susceptibility testing.

EUCAST expert rules have been developed to assist clinical microbiologists and describe actions to be taken in response to specific antimicrobial susceptibility test results. They include recommendations on reporting, such as inferring susceptibility to other agents from results with one, suppression of results that may be inappropriate, and editing of results from susceptible to intermediate or resistant or from intermediate to resistant on the basis of an inferred resistance mechanism. They are based on current clinical and/or microbiological evidence. EUCAST expert rules also include intrinsic resistance phenotypes and exceptional resistance phenotypes, which have not yet been reported or are very rare. The applicability of EUCAST expert rules depends on the MIC breakpoints used to define the rules. Setting appropriate clinical breakpoints, based on treating patients and not on the detection of resistance mechanisms, may lead to modification of some expert rules in the future.

The role of pharmacokinetics/pharmacodynamics in setting clinical MIC breakpoints: the EUCAST approach.

Clinical breakpoints are used in clinical microbiology laboratories to categorize microorganisms as clinically susceptible (S), intermediate (I) or resistant (R) dependent on the quantitative antimicrobial susceptibility as indicated by the MIC value determined in a well-defined standard test system. The laboratory report, with the designations of S, I or R for each antimicrobial agent, provides guidance to clinicians with respect to the potential use of agents in the treatment of patients, and clinical breakpoints should therefore distinguish between patients that are likely or unlikely to respond to antimicrobial treatment. In Europe, clinical breakpoints are set by the European Committee on Antimicrobial Susceptibility Testing (EUCAST), following a defined procedure. This includes evaluation of efficacy in experimental settings and clinical studies to derive pharmacodynamic targets such as the fAUC/MIC ratio or %fT > MIC required for efficacy, the pharmacokinetic properties of the agent, Monte Carlo simulations to estimate exposures of the antimicrobial agent in the target patient population and commonly used dosing regimens. The probability of target attainment is subsequently determined for a range of pharmacodynamic targets and the results from the Monte Carlo simulations. The breakpoints derived are subsequently evaluated with respect to the wild-type population of the target microorganisms, specific resistance mechanisms and other relevant data. In this paper, we provide an overview of the EUCAST process and considerations for setting pharmacokinetic/pharmacodynamic breakpoints. These are the breakpoints that in the EUCAST breakpoint tables are referred to as 'non-species-related breakpoints'.

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.

[Activity of doripenem against anaerobic bacteria]. / Activité du doripénème sur les bactéries anaérobies strictes.

AIMS OF THE STUDY: 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. METHODS: Inoculum preparation and agar dilution method were performed according to the CLSI method for anaerobes (M11A7). RESULTS: 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 %. CONCLUSION: 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.

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.

[Diagnosis and treatment of acute uncomplicated urethritis of men: guidelines from the French committee of infectious disease of the French association of urology (CIAFU)]. / Recommandations de bonnes pratiques cliniques : diagnostic et traitement des uréthrites aiguës non compliquées de l'homme, par le comité d'infectiologie de l'Association française d'urologie (CIAFU).

Resistance progression of the Neisseria gonorrhoeae to quinolones and the decreasing sensitivity to cephalosporin implicate to actualise the guidelines for managing urethritis. We present the guidelines from the committee of infectious diseases of the French Association of Urology to manage acute urethritis.

[Recommendations of the Infectious Disease Committee of the French Association of Urology (AFU): antibiotic prophylaxis for urological procedures]. / Recommandations de bonnes pratiques cliniques: l'antibioprophylaxie en chirurgie urologique, par le Comité d'infectiologie de l'association française d'urologie (CIAFU).

The French Association of anesthesiology (SFAR) has published in 1999 the Antibiotic prophylaxis guidelines. Antibiotic resistance has increased and new procedures appeared so new recommendations were needed. We present the antibiotic prophylaxis guidelines from the committee of infectious diseases of the French Association of Urology.

[Diagnosis, treatment and follow-up of community-acquired bacterial infections of the urinary system of men and women (acute cystitis and acute pyelonephritis) and of the genital system of men (acute prostatitis): general remarks]. / Généralités.

Urinary tract infections are frequent. The aim of these guidelines is to improve the management of urionary tract infections. Increasing antibiotic prescriptions may increase bacterial drug resistance. Asymptomatic bacteriuria, bacterial count, pyuria are defined and the clinical value of the bacterial culture and urinary dipstick test are discussed. The good antibiotic use depends on bacteriological, pharmaceutical, patient characteristics and economic findings which are precised in these guidelines.

[Acute cystitis]. / Cystites aiguës.

The management of uncomplicated lower urinary tract infections (UTI) implicate to look for risk factors and complications. Bacterial or radiological exams are not recommanded and short course of antibiotic is effective for treating uncomplicated UTI. Complicated UTI needs clinical, bacteriological and radiological exams, longer treatments are recommanded. Recurrent UTI definition is precised in these guidelines.

[Acute pyelonephritis]. / Pyélonéphrites aiguës.

The initial management of pyelonephritis needs to look for complicating factors. Ultrasound and X ray of the abdomen are able to rule out a urinary dilatation or a stone. The treatment is then surgical with renal drainage. Additional investigations such as a CT scan should be performed in patients with complicating factors or recurrence. In uncomplicated pyelonephritis a ambulatory treatment with 2 weeks of fluoroquinolones or cephalosporine Gr3 is sufficient. More severe cases should be admitted to a hospital and treated with initial cephalosporin Gr 3 plus aminoside for 3 to 6 weeks.

[Acute prostatitis]. / Prostatites aiguës.

A urinary infection in a febrile man is classiquely defined as a prostatitis. Investigation exams look for complicating factors or post voiding residual which should be drained. Antibiotic treatment should begin with a fluroquinolone or cephalosporin gr 3 for 3 to 6 weeks.

[In vitro activity of levofloxacin against Escherichia coli strains in acute pyelonephritis, in France in 2005]. / Activité in vitro de la lévofloxacine vis-à-vis de souches de Escherichia coli responsables de pyélonéphrites aiguës communautaires en France en 2005.

The objective of this study was to assess the in vitro activity of levofloxacin compared to other antibiotics against Escherichia coli strains isolated from female patients with acute pyelonephritis in 23 French hospitals in 2005. Minimal inhibitory concentrations (MICs) were determined in a central laboratory, by agar dilution method in compliance with the recommendations of the Comité de l'antibiogramme de la Société française de Microbiologie (CA-SFM). The percentages of susceptible strains were calculated according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints approved by the CA-SFM (2005) for ciprofloxacin, levofloxacin, and ofloxacin and according to the CA-SFM breakpoints for the other antibiotics. Amongst the 231 strains collected, 46.3% of strains were isolated from urinary samples, 10.8% from blood culture, and 42.9% from both. Concerning fluoroquinolones, the percentages of susceptibility were 93.1%, 90.5%, and 92.7% for levofloxacin, ofloxacin, and ciprofloxacin, respectively. For the other antibiotics, a higher percentage of susceptibility was observed with ceftriaxone (99.6%) and amikacin (94.8%), whereas a lower percentage of susceptibility was observed with amoxiclav (68.8%), and cotrimoxazole (65.4%). Levofloxacin exhibited a good in vitro activity against E. coli strains isolated from acute pyelonephritis with 93.1% of susceptible strains.

Occurrence of qnrA-positive clinical isolates in French teaching hospitals during 2002-2005.

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.

Long-term efficacy of mupirocin in the prevention of infections with meticillin-resistant Staphylococcus aureus in a gastroenterology unit.

The long-term efficacy (55 months) of eradication of nasal carriage of meticillin-resistant Staphylococcus aureus (MRSA) by mupirocin was assessed for MRSA infections in a gastroenterology unit receiving patients for long hospital stays. In total, 2242 patients were included in the study; 92% had been hospitalized in another hospital before admission to the study department, 64% had chronic liver diseases (LD), 25% had miscellaneous medical conditions and 11% were admitted following gastroenterological surgery. Three consecutive periods were considered in the analysis. Nasal carriage at admission was similar in all three periods (10.9 vs 7.5 vs 8.6% in Periods 1, 2 and 3, respectively), while acquired nasal carriage decreased in the whole population (14.3 vs 16.2 vs 10.2% in Periods 1, 2 and 3, respectively, P=0.006) and in LD patients (15.8 vs 18.7 vs 11.9% in Periods 1, 2 and 3, respectively, P=0.018). The incidence of MRSA infections (N per total number of hospitalization-days) was 1.41 per 1000 in the year before initiation of eradication, 1.40 in Period 1, 0.74 in Period 2 and 0.59 in Period 3 (P=0.022). The incidence of MRSA infections among patients was 7.0% in Period 1, 3.7% in Period 2 and 3.1% in Period 3 in LD patients (P=0.0062). The corresponding figures were 5.5, 3.0 and 2.4% for the whole population (P=0.0024). The mortality caused by MRSA was 0.31, 0.19 and 0.13% (P=0.035) in Periods 1, 2 and 3, respectively. The numbers of resistant strains among those acquired during hospitalization were 12 in Period 1, four in Period 2 and six in Period 3. Long-term intranasal mupirocin treatment in MRSA carrier patients with long hospital stay is associated with a decrease in acquired carriage and MRSA infections, while resistance of the strains to mupirocin does not increase provided that colonized patients are only treated once.

European Committee on Antimicrobial Susceptibility Testing (EUCAST) Technical Notes on antimicrobial susceptibility testing.

The main objectives of the European Committee on Antimicrobial Susceptibility Testing (EUCAST) are to harmonise breakpoints for antimicrobial agents in Europe, and to act as the breakpoint committee for the European Medicines Agency (EMEA) during the registration of new antimicrobial agents. Detailed EUCAST procedures for harmonising and setting breakpoints for antimicrobial agents are available on the EUCAST website. Beginning with the current issue, a series of EUCAST Technical Notes will be published in CMI, based on the rationale documents produced by EUCAST for each of the antimicrobial agents studied, with the aim of highlighting important background information underlying decisions on breakpoints made by EUCAST.

[Investigation of the new QNR-based mechanism of quinolone resistance among enterobacterial strains isolated in Henri-Mondor hospital 2002-2005]. / Emergence et diffusion chez les entérobactéries du nouveau mécanisme de résistance plasmidique aux quinolones Qnr (résultats hôpital Henri-Mondor 2002-2005).

AIM OF THE STUDY: To assess the prevalence of the novel plasmid-mediated resistance to quinolones in enterobacteria isolated in our hospital. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

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.