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.

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.

Tissue kinetics of telithromycin, the first ketolide antibacterial.

The potential efficacy of an antibacterial depends not only on its spectrum of activity but also on its concentration at the site of infection. The tissue kinetics of telithromycin-the first ketolide antibacterial-are reviewed here. Telithromycin accumulates rapidly in white blood cells, inflammatory fluid, and cells and tissues of the upper and lower respiratory tract, with mean concentrations above the MICs of key respiratory pathogens. Tissue kinetics of telithromycin support facilitated delivery to the site of infection, good efficacy against intracellular respiratory pathogens and respiratory pathogens at extracellular sites in the airways, and effectiveness in the treatment of upper and lower respiratory tract infections (RTIs). The tissue kinetics profile of telithromycin, together with its microbiological profile, makes it a promising new antibacterial for the treatment of community-acquired RTIs.

[Blood culture update]. / Actualités sur l'hémoculture.

BACKGROUND: Blood culture is one of the most important bacteriological examinations with important clinical and therapeutic consequences. Blood cultures should be ordered in all patients with signs suggesting septicemia, endocarditis or severe infection (pneumococcal pneumonia, bacterial meningitis with bloodstream dissemination). Blood culture methods have evolved considerably over the last twenty years. After using manual methods for many years, read by non-standardized visual methods, the development of media with defined compositions and supplemented to allow growth of bacteria difficult to culture has been associated with the development of automatic blood culture devices. AUTOMATIC DEVICES: These devices have undergone rapid improvement. Semi-automatic devices (Bactec NR-660) were rapidly followed by completely automatic techniques, including four devices currently available: since 1989 Bio-Argos (Rio-Rad) and Bact/Alert (Organon-Teknika) and in 1993, Bactec 9240 (Becton-Dickinson) and Vital (BioMérieux). All these devices allow automatic detection of CO2 produced during bacterial growth. Automatic reading systems provide continuous output avoiding the need for invasive methods and thus the risk of contamination in addition to saving time. Potential application to achieve quantitative blood cultures for intensive care units is in the development stage. CONSEQUENCES: The reliability of these devices is well recognized and their contribution to severe bacterial infection is undeniable. There are certain limitations however related to material cost and the non-identification of the pathogen involved. Molecular biology techniques open new perspectives in this field. The evolution of techniques, definitions, and pathogenic approach to septicemia must be revisited as new infectious situations have been identified at the same time as new investigation tools resulting from considerable technological progress. New methods of blood culture have largely contributed to this progress.

Multicenter evaluation of an automated system using selected bacteria that harbor challenging and clinically relevant mechanisms of resistance to antibiotics.

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.

Bronchopulmonary disposition of the ketolide telithromycin (HMR 3647).

Telithromycin (HMR 3647) is the first member of a new family of antimicrobials, the ketolides, developed specifically for the treatment of community-acquired respiratory tract infections. Telithromycin has proven in vitro activity against both common and atypical respiratory tract pathogens. The penetration of telithromycin into bronchopulmonary tissues and subsequent elimination from these sites were evaluated in four groups (groups A, B, C, and D) of six healthy male subjects who received telithromycin at 800 mg once daily for 5 days. Subjects in groups A, B, C, and D underwent fiberoptic bronchoscopy and bronchoalveolar lavage 2, 8, 24, and 48 h after receipt of the last dose, respectively. The concentration of telithromycin in the alveolar macrophages, epithelial lining fluid (ELF), and plasma was determined by the agar diffusion method with Bacillus subtilis ATCC 6633 as the test organism. The concentration of telithromycin in alveolar macrophages markedly exceeded that in plasma, reaching up to 146 times the concentration in plasma 8 h after dosing (median concentration, 81 mg/liter). Telithromycin was retained in alveolar macrophages 24 h after dosing (median concentration, 23 mg/liter), and it was still quantifiable 48 h after dosing (median concentration, 2.15 mg/liter). Telithromycin median concentrations in ELF also markedly exceeded concentrations in plasma (median concentration in ELF, 3.7 mg/liter 8 h after dosing). Telithromycin achieves high and sustained concentrations in ELF and in alveolar macrophages, while it maintains adequate levels in plasma, providing an ideal pharmacokinetic profile for effective treatment of community-acquired respiratory tract infections caused by either common or atypical, including intracellular, respiratory tract pathogens.

An outbreak of imipenem-resistant Acinetobacter baumannii in critically ill surgical patients.

OBJECTIVE: To describe an outbreak of imipenem-resistant Acinetobacter baumannii (IR-Ab) and the measures for its control, and to investigate risk factors for IR-Ab acquisition. DESIGN: An observational and a case-control study. SETTING: A surgical intensive care unit (ICU) in a university tertiary care hospital. METHODS: After admission to the ICU of an IR-Ab-positive patient, patients were prospectively screened for IR-Ab carriage upon admission and then once a week. Environmental cleaning and barrier safety measures were used for IR-Ab carriers. A case-control study was performed to identify factors associated with IR-Ab acquisition. Cases were patients who acquired IR-Ab. Controls were patients who were hospitalized in the ICU at the same time as cases and were exposed to IR-Ab for a similar duration as cases. The following variables were investigated as potential risk factors: baseline characteristics, scores for severity of illness and therapeutic intervention, presence and duration of invasive procedures, and antimicrobial administration. RESULTS: Beginning in May 1996, the outbreak involved 17 patients over 9 months, of whom 12 acquired IR-Ab (cases), 4 had IR-Ab isolates on admission to the ICU, and 1 could not be classified. Genotypic analysis identified two different IR-Ab isolates, responsible for three clusters. Ten of the 12 nosocomial cases developed infection. Control measures included reinforcement of barrier safety measures, limitation of the number of admissions, and thorough environmental cleaning. No new case was identified after January 1997. Eleven of the 12 cases could be compared to 19 controls. After adjustment for severity of illness, a high individual therapeutic intervention score appeared to be a risk factor for IR-Ab acquisition. CONCLUSION: The outbreak ended after strict application of control measures. Our results suggest that high work load contributes to IR-Ab acquisition.

[Streptpcoccus pneumoniae: current status of its resistance to antibiotics]. / Streptococcus pneumoniae: état actuel de la résistance aux antibiotiques.

A WORLDWIDE ISSUE: Streptococcus pneumoniae is an important pathogen implicated in many illnesses. The susceptibility of this bacteria has greatly changed since 1967 when it was the leading strain resistant to penicillin G. Since that time, the resistance of S. pneumoniae has become a worldwide problem leading to the development of schemes to monitor resistance in different countries. The analysis of these "observation" studies points out the wide variability of resistance to antibiotics depending on the concerned country and region. Amoxicillin, cefotaxim, the new fluoroquinolones and vancomycin have exhibited the best preservation of efficacy worldwide. RESISTANCE IN FRANCE: Pneumococcal resistance is high in France against penicillin, third-generation cephalosporins, and erythromycin. Resistance has however appeared to stabilize since 1997, with the exception of invasive strains which have shown a rising level of penicillin G resistance. A NEW THREAT: Several authors have reported that vancomycin-tolerant strains have a significant clinical importance and must be carefully monitored. Reasonable prescription of antibiotics appears to be more than ever necessary to reduce the selection pressure of antibiotics.

[Ketolides and oxazolidinones. Mechanisms of action and antibacterial spectrum]. / Kétolides et oxazolidinones. Mécanisme d'action et spectre antibactérien.

CHANGING RESISTANCE OF GRAM-POSITIVE COCCI: Several new families of antibiotics are under development in response to the changing resistance of Gram-positive cocci. Linezolide, the leading member of the oxazolidinone family and telithromycin and ABT-773, leading members of the ketolide family have reached an advanced stage of development. INHIBITION OF PROTEIN SYNTHESIS: Oxazolidinones and ketolides inhibit protein synthesis at different levels. Oxazolidinones inhibit formation of the 70S initiation complex and ketolides block the protein elongation step by inhibiting peptidyl transferase. MECHANISMS OF RESISTANCE: To date, no cross resistance of linezolide with other antibiotic families used for the treatment of Gram-positive bacteria has been observed. It is quite difficult to obtain resistant mutants in the laboratory but two point mutations on the 23S ribosome fraction have been described in vivo. Resistance of Gram-positive cocci to macrolides occur via mechanisms altering the target (methylation of 23S rRNA or ribosome protein mutations) or via mechanisms involving active efflux. LINEZOLIDE: Linezolide is highly active in vitro against meticillin-resistant Staphylococcus aureus (MRSA), against Streptococcus including resistant pneumococcal strains, and against glycopeptide-resistant E. faecium and E. faecalis strains. TELITHROMYCIN AND ABT-773: These ketolides are active against Streptococcus and Pneumococcus strains exhibiting erythromycin-inducible resistance and resistance by active efflux. In addition, these antibiotics are highly active against other bacteria causing respiratory tract infections (Moraxella and Haemophilus), anaerobic germs and intracellular germs (Legionella).

[Epidemiology of resistance to antibiotics in respiratory tract infections]. / Epidémiologie de la résistance aux antibiotiques dans les infections respiratoires.

AN EVOLVING PROBLEM: Antibiotic resistance currently concerns H. influenzae, S. pneumoniae, S. pyogenes, M. catarrhalis, all species which are particularly susceptible to beta-lactamines, fluoroquinolones and macrolides. Incidence of resistance has reached high levels in many countries, including France in certain instances. BETA-LACTAMINE RESISTANCE: Penicillin-resistant pneumococci (partial and total resistance) are unequally distributed over the globe. In France the frequency is high, particularly in children. S. pyogenes strains remain sensitive to peni-G. Amino-penicillin resistance of H. influenzae and M. catarrhalis results from enzymatic processes (penicillinase production) and concerns an important proportion of the strains, particularly for M. catarrhalis. FLUOROQUINOLONE-RESISTANCE: Fluoroquinolone resistance is now described for H. influenzae. Though rare, this is a serious problem as it proves that this bacterial species can adapt to new antibiotics used for the treatment of respiratory tract infections. Resistance is acquired by modifying the antibiotic target, DNA gyrase and/or topo-isomerases, enzyme implicated in bacterial DNA. The presence of multiple mutations in the genes coding for these enzymes raises the MIC for fluoroquinolones, including those for the most recent compounds. Streptococci resistance to fluoroquinolones is increasing but no new mechanisms of resistance have been described. MACROLIDE-RESISTANT STREPTOCOCCI: Acquired resistance results either from the presence of erm genes causing a modification in the bacterial ribosome by methylation or by the presence of mef genes coding for efflux proteins. Incidence of macrolide resistance and the distribution of these different mechanisms vary greatly from one country to another. EMPIRICAL TREATMENT OF RESPIRATORY TRACT INFECTIONS: Epidemiological data and the locoregional bacterial ecology must be considered when prescribing an empirical treatment for respiratory tract infections.

Levofloxacin: serum bactericidal activity against methicillin-resistant Staphylococcus aureus isolates.

The aim of this study was to assess the serum bactericidal activity (SBA) of levofloxacin compared with that of ofloxacin against methicillin-resistant Staphylococcus aureus (MRSA) isolates. Serum from 10 healthy volunteers (seven females, three males) was collected after a single oral dose of either levofloxacin (500 mg) or ofloxacin (400 mg). Subjects were allocated randomly to treatment after at least a 1 week interval between antibiotic regimens. Three well-defined MRSA strains were tested, each susceptible to levofloxacin and ofloxacin, with different levels of resistance to methicillin (HBD 456, HBD 3 and HBD 2; class 1, 2 and 3 Tomasz heterogeneous resistance, respectively) together with a methicillin-susceptible (MSSA) reference strain (S. aureus ATCC 25,923). SBA was tested in vitro by a microtitration method 15 min before dosing and at 1, 4, 8 and 12 h after drug absorption. Levofloxacin was significantly more bactericidal than ofloxacin against all strains of S. aureus tested (SBA > or = 1:2). An SBA was recorded for only a short period with ofloxacin, and thereafter only bacteriostatic activity remained. This study, therefore, confirms the superior activity of levofloxacin over that of ofloxacin against MSSA and MRSA.

Dirithromycin concentrations in bronchial mucosa and secretions.

Since a high tissue penetration of dirithromycin (D) has been assessed in early studies, the aims of this study were to determine D concentrations in bronchial mucosa and secretions in patients suffering from an acute exacerbation of chronic bronchitis (AECB), to compare intra-individual bronchial mucosa and secretion concentrations and to relate bronchial concentrations of D and clinical efficacy. The main inclusion criteria were comprised of (1) AECB, defined by the presence of an increase in dyspnea, sputum production and change in sputum purulence, and (2) clinical indication of fiberoptic bronchoscopy allowing performance of bronchial biopsies. All patients were treated with a 500-mg once-daily D dose for 5 days. Patients were randomly divided into three groups, according to sampling times (24, 48 and 72 h after the last dose). Tissue concentration analyses were performed by one blinded microbiologist (microbiological agar diffusion assay). The results showed: (1) 37 out of the 46 patients (80.4%) had a favorable response to treatment at the time of fiberoptic bronchoscopy (14 cured, 23 improved); (2) bronchial mucosa concentrations were high in all groups, and (3) mean values at 24, 48 and 72 h after the last dose were respectively 6.51 +/- 1.44, 6. 61 +/- 2.7, 5.67 +/- 1.02 mg.kg-1; no statistical difference was observed between the groups. In bronchial secretions collected simultaneously, concentrations were lower, i.e. 1.26 +/- 0.3, 0.61 +/- 0.12, 0.84 +/- 0.12. Significant associations were observed between bronchial mucosa and secretion concentrations (r = 0.71, p = 0.0001), and between clinical response and bronchial concentrations (p = 0.03, Kruskall-Wallis test). In conclusion, these results may confirm the clinical significance of tissue concentrations measured in bronchial tissues of patients with AECB.

[Bacterial resistance and new therapeutic perspectives]. / Résistance bactérienne et nouvelles perspectives thérapeutiques.

A PROGRESSING PHENOMENON: Concern about bacterial resistance to antibiotics is growing steadily as new mechanisms of resistance are regularly detected. Cocci have generally remained very antibiotic-sensitive, but resistance is developing. MACROLIDE-RESISTANT STREPTOCOCCI: Streptococci resistance to macrolides is related either to a change in the target, the bacterial ribosome (usually the case), or to an efflux mechanism pushing the antibiotic out of the bacteria before it reaches the target (a mechanism which has been confirmed in different parts of the world). QUINOLONE RESISTANCE: Resistance to quinolones results from a modification of the target, bacterial topo-isomerases, or via an efflux mechanism described in several Gram positive and Gram negative bacteria. HOPES FOR THE FUTURE: New families of antibiotics are currently under evaluation, particularly compounds directed against bacteria resistant to classically used antibiotics. Likewise, several fluoroquinolones are under development. Most have a wide spectrum including Gram positive cocci, particularly enterococci and strict anaerobic bacteria. A rigorously applied antibiotic prescription policy is however required to control bacterial resistance to antibiotics.

European multicentre evaluation of a commercial system for identification of methicillin-resistant Staphylococcus aureus.

A commercial system for the rapid detection of methicillin-resistant Staphylococcus aureus, the BBL Crystal MRSA test (C-MRSA ID; Becton Dickinson, USA), was evaluated prospectively and compared with a polymerase chain reaction test for the presence of the mecA gene. Ten European centres tested a total of 676 isolates of Staphylococcus aureus from blood cultures. The system correctly identified 661 (97.8%) isolates within 4 h. All but three mecA gene-negative isolates (99.4% specificity) yielded a negative C-MRSA ID reaction, and 158 of 170 mecA gene-positive isolates were accurately detected (92.9% sensitivity). After repeated testing of discrepant results, sensitivity and specificity increased to 99% and 100%, respectively.

[In vitro antibacterial activity of a new fluoroquinolone, sparfloxacin, against nosocomial bacteria, and concordance curve]. / Activité anti-bactérienne in vitro d'une nouvelle fluoroquinolone, la sparfloxacine sur les bactéries hospitalières et courbe de concordance.

Minimal inhibitory concentrations (MICs) of sparfloxacin (SFX) were determined by agar dilution for 3,164 bacterial strains isolated in 10 university hospitals; in addition, antibiograms by agar diffusion were performed with 5 micrograms disks. Activity of SFX against nalidixic acid (NAL) susceptible (S) Enterobacteriaceae was close to that of other fluoroquinolones (FQ) (MIC 50 and 90: 0.06-0.5 microgram/ml); like for other FQ, this activity was reduced against NAL intermediate and resistant (R) Enterobacteriaceae (2-16). MICs of SFX against P. aeruginosa were between 0.12 and 16 (1-32). SFX had also a good activity against NAL-S A. baumannii (CMI < or = 0.25) but this activity is reduced against NAL-R Acinetobacter (16). SFX was highly active against Haemophilus (0.016-0.06) gonococci (0.008), meningococci (0.008) and B. catarrhalis (0.008-0.03). SFX showed activity superior to the currently available FQ against methicillin susceptible staphylococci (0.06); the resistant strains [8] are usually methicillin resistant. SFX is more effective against enterococci (0.5), streptococci (0.25-0.5) and particularly pneumococci (0.25-0.5) including penicillin-resistant strains. The coefficient correlation of the regression curve is 0.876; for MIC breakpoints of 1 and 2 micrograms/ml, zone diameter breakpoints should be 20 and 16 mm.

Activity of beta-lactamase inhibitor combinations on Escherichia coli isolates exhibiting various patterns of resistance to beta-lactam agents.

The efficacy of the clinically available beta-lactam/beta-lactamase inhibitor combinations (amoxicillin/clavulanic acid (CA), ticarcillin/CA, amoxicillin/sulbactam, and piperacillin/tazobactam) was evaluated on 300 amoxicillin-resistant Escherichia coli isolates having the main patterns of beta-lactam resistance. The patterns, which reflect the production of various beta-lactamase enzymes, were analyzed by a principal component analysis of susceptibility to 11 beta-lactam antibiotics or beta-lactam/beta-lactamase inhibitor combinations. Sixty-two percent of strains were not very susceptible to penicillins, cephalothin, or any beta-lactam/beta-lactamase inhibitor combinations except for piperacillin/tazobactam; these strains may represent high-level broad-spectrum beta-lactamase (so-called penicillinase) production phenotype or inhibitor-resistant TEM-like enzyme production phenotype. Of the strains, 14.7% were resistant to amoxicillin and ticarcillin compatible with low-level broad-spectrum beta-lactamase production phenotype; 5.7% were cefoxitin resistant and were postulated to present a high-level cephalosporinase production phenotype; and 2.6% were resistant to cephalothin only, attributable to a low-level cephalosporinase production phenotype. Three percent of strains were intermediate or resistant to cefotaxime and may produce an extended-spectrum beta-lactamase, and the remaining strains (12 %), resistant to all tested antibiotics except for cefotaxime and piperacillin/tazobactam, were hypothesized to produce both broad-spectrum beta-lactamase plus cephalosporinase. The minimal inhibitory concentration (MIC) for these phenotype patterns indicated that combinations of CA plus amoxicillin or ticarcillin, or sulbactam plus amoxicillin, restored the activity of penicillins against phenotype 1 strains, whereas these combinations remained inactive against the other phenotype strains. Piperacillin plus tazobactam showed the best in vitro effect against the strains of all resistance phenotypes.