Effects of various media on the activity of NXL103 (formerly XRP 2868), a new oral streptogramin, against Haemophilus influenzae.

The activity of NXL103 against 108 strains of Haemophilus influenzae was tested using Haemophilus test media (HTM) obtained from various sources. With the exception of those obtained with stored HTM, MICs did not differ significantly, with MIC(50) and MIC(90) values of 0.5 and 0.

Anti-MRSA agents: under investigation, in the exploratory phase and clinically available.

Staphylococcal infections are difficult to treat due to the rapid emergence of methicillin-resistant staphylococci and, unfortunately, vancomycin-intermediate or -resistant staphylococci. Numerous alternative treatments are urgently required. In this special report, intensive research of new molecules is highlighted--in known antibacterial families and new medicinal chemical entities.

New research in macrolides and ketolides since 1997.

Macrolide and ketolide antibacterials remain a very dynamically active group. To overcome erythromycin A resistance within Gram-positive cocci and bacteria, novel compounds have been semi-synthesised, such as ketolides and C-4'' carbamate erythromycylamine derivatives. The continual efforts of those studying macrolides have led to molecular level investigations into the mechanism of action of these antibacterials.

Novelties in the field of fluoroquinolones.

The field of fluoroquinolone research is rapidly expanding. Bacterial targets are constantly changing to meet the demands of resistance. At present, new compounds are targeting respiratory pathogens, such as Streptococcus pneumoniae.

Novelties in the field of macrolides.

Research in the field of macrolide antibiotics has continued. The aims of research efforts are quite different with 14-, 15- and 16-membered ring macrolides. A review of 14- and 15-membered ring macrolides covering the period up to 1995 was published in a previous issue of this journal.

Dual beta-lactam-fluoroquinolone compounds: a novel approach to antibacterial treatment.

Codrugs comprise a beta-lactam-fluoroquinolone antibacterial hybrid. These new agents have been developed with the aim of enhancing the antibacterial spectrum of current therapies, overcoming intrinsic and acquired resistance, and diminishing severe side-effects. A few compounds, including Ro 23-9424, have entered Phase I clinical trials.

Pharmacodynamics of an 800-mg dose of telithromycin in patients with community-acquired pneumonia caused by extracellular pathogens.

The pharmacodynamics of telithromycin, a new ketolide antibacterial, was examined in 115 patients with community-acquired pneumonia (CAP). Patients received telithromycin 800 mg qd for 7-10 days. Pharmacokinetic parameters were determined, and exposure was linked to microbiological outcome using logistic regression analysis.

In vitro evaluation of faropenem activity against anaerobic bacteria.

Faropenem, a new oral penem with broad spectrum activity, could be used as empirical treatment in infections due to unidentified anaerobes, but only a few investigations have been carried out on these bacteria. The aim of this study was to compare faropenem in vitro activity with that of positive antimicrobial controls (metronidazole, imipenem, meropenem, amoxicillin, amoxicillin-clavulanic acid, ticarcillin-clavulanic acid, cefotetan, cefoxitin and clindamycin) against 462 anaerobic bacterial strains. The reference agar dilution method was used according to the NCCLS standard.

Mechanisms of macrolide resistance in clinical pneumococcal isolates in a university hospital, Ankara, Turkey.

Macrolide resistance in Streptococcus pneumoniae is usually caused by the presence of the erm(B) or mef(A) resistance determinants. The aim of the present study was to identify the predominant macrolide resistance mechanisms among erythromycin-resistant S. pneumoniae isolated in a university hospital, Ankara, Turkey.

Comparative in vitro activities of XRP 2868, pristinamycin, quinupristin-dalfopristin, vancomycin, daptomycin, linezolid, clarithromycin, telithromycin, clindamycin, and ampicillin against anaerobic gram-positive species, actinomycetes, and lactobacilli.

A comparative study of the in vitro activities of XRP 2868, a new oral streptogramin, against 266 anaerobic gram-positive clinical isolates using the agar dilution method showed that the XRP 2868 MICs for 95% (254 of 266) of isolates were < or =0.5 microg/ml. XRP 2868 MICs for only two strains, one being Clostridium clostridioforme (MIC, 16 microg/ml) and the other being Clostridium difficile (MIC, 32 microg/ml), were >2 microg/ml.

The AcrAB-TolC pump is involved in macrolide resistance but not in telithromycin efflux in Enterobacter aerogenes and Escherichia coli.

The role of the AcrAB-TolC pump in macrolide and ketolide susceptibility in Escherichia coli and Enterobacter aerogenes was studied. Efflux pump inhibitor restored erythromycin, clarithromycin, and telithromycin susceptibilities to multidrug-resistant isolates. No modification of telithromycin accumulation was detected in E.

Treatment of acute Chlamydia pneumoniae infection with telithromycin in C57BL/6J mice.

Objectives: The efficacy of telithromycin, a new ketolide antibiotic, was investigated in the treatment of acute Chlamydia pneumoniae infection in a mouse model.

Methods: C57BL/6J mice were inoculated intranasally, and the effects of three different doses of telithromycin (25, 50 and 100 mg/kg) were assessed after 5 and 10 days of treatment. Lungs for culture, PCR, histopathology, and blood for serum samples were collected immediately after each treatment period and at 3 weeks post-inoculation.

Clonal relatedness of erythromycin-resistant Streptococcus pyogenes isolates in Germany.

In a nationwide study in Germany, a total of 381 Streptococcus pyogenes were collected. Erythromycin A-resistant strains were characterized for the underlying resistance genotype, showing 55.6% had the efflux type mef(A), 31.

Preparation of stock solutions of macrolide and ketolide compounds for antimicrobial susceptibility tests.

Stock solutions of telithromycin, ABT-773, azithromycin, clarithromycin, erythromycin, roxithromycin and dirithromycin were each prepared with eight different combinations of solvents and diluents. Broth microdilution trays were then prepared and frozen at -60 degrees C. Standard quality control strains were evaluated periodically during a 12-week storage time.

Activities of a new oral streptogramin, XRP 2868, compared to those of other agents against Streptococcus pneumoniae and haemophilus species.

MIC methodology was used to test the antibacterial activity of XRP 2868, a new oral combination of two semisynthetic streptogramins, RPR 132552A and RPR 202868, compared to activities of other antibacterial agents against pneumococci, Haemophilus influenzae, and Haemophilus parainfluenzae. For 261 pneumococci, XRP 2868 and pristinamycin MICs were similar, irrespective of penicillin G and erythromycin A susceptibilities (MIC at which 50% of isolates were inhibited [MIC(50)], 0.25 micro g/ml; MIC(90), 0.

In vitro activities of a new lipopeptide, HMR 1043, against susceptible and resistant gram-positive isolates.

The purpose of this study was to compare the activity of HMR 1043 with those of daptomycin and teicoplanin against gram-positive isolates. Susceptibility tests were performed for 52 strains, 26 parental strains, including staphylococcal, streptococcal, enterococcal, and listerial strains, and 26 HMR 1043-resistant mutants obtained from parental strains by using the Szybalski method. Agar dilution and disk diffusion susceptibility tests were performed by the procedures outlined by the NCCLS.

In vivo pharmacodynamics of HMR 3270, a glucan synthase inhibitor, in a murine candidiasis model.

In vivo pharmacokinetic/pharmacodynamic characterization for numerous antibacterial compounds has had a significant impact upon optimal dosing regimen design and the development of in vivo susceptibility breakpoints. More recently, similar characterization has been undertaken for antifungal drug classes. Very little is known of these pharmacodynamic relationships for the new echinocandin class of compounds.

Macrolide-resistant Streptococcus pneumoniae and Streptococcus pyogenes in the pediatric population in Germany during 2000-2001.

In a nationwide study in Germany covering 13 clinical microbiology laboratories, a total of 307 Streptococcus pyogenes (mainly pharyngitis) and 333 Streptococcus pneumoniae (respiratory tract infections) strains were collected from outpatients less than 16 years of age. The MICs of penicillin G, amoxicillin, cefotaxime, erythromycin A, clindamycin, levofloxacin, and telithromycin were determined by the microdilution method. In S.

Activities of HMR 3787 and RU 64399 compared with those of four other agents against Haemophilus influenzae and Haemophilus parainfluenzae.

Activities of HMR 3787, a new 2-fluoroketolide, and its (des)-fluor derivative, RU 64399, were tested against 111 Haemophilus influenzae and 26 H. parainfluenzae strains and compared with those of telithromycin, erythromycin, azithromycin, and clarithromycin. HMR 3787 and RU 64399 MICs were comparable with those of azithromycin but were less affected by incubation in CO(2).

Bacillus anthracis and antibacterial agents.

Anthrax is one of the oldest threats to humankind, and remains endemic in animals in many parts of the world. Human cases are infrequent, and some result from biological warfare. This review summarizes the current knowledge on the antibacterial activity of available antibiotics.

Antibiotic susceptibilities of Parachlamydia acanthamoeba in amoebae.

Parachlamydia acanthamoeba are intracellular bacteria of amoebae and are considered potential etiological agents of human pneumonia. We have determined the in vitro antibiotic susceptibilities of two strains (strain Bn(9) and Hall's coccus) in Acanthamoeba polyphaga. The two strains were susceptible to tetracyclines, macrolides, and rifampin, but resistant to fluoroquinolones.

Viridans group streptococci: a reservoir of resistant bacteria in oral cavities.

The worldwide spread of erythromycin A-resistant streptococci, including Streptococcus pneumoniae, is of concern. Many studies have demonstrated that the viridans group streptococci can be a reservoir of erythromycin A resistance. Within oral streptoccoci, an important difference in the susceptibility pattern has been noted.