Comparative in vitro activities of ABT-773 against aerobic and anaerobic pathogens isolated from skin and soft-tissue animal and human bite wound infections

We studied the comparative in vitro activities of ABT-773, a new ketolide, against 268 aerobic and 148 anaerobic recent isolates from clinical bites using an agar dilution method and inocula of 10(4) CFU/spot for aerobes and 10(5) CFU for anaerobes. The following are the MIC ranges and MICs at which 90% of isolates are inhibited (MIC(90)s) of ABT-773 for various isolates, respectively: Pasteurella multocida and Pasteurella septica, 0.125 to 2 and 1 microg/ml; other Pasteurella species, 0.125 to 1 and 0.5 microg/ml; Corynebacterium spp., 0.015 to 0.06 and 0.015 microg/ml; Staphylococcus aureus, 0.03 to 0.06 and 0.06 microg/ml; coagulase-negative staphylococci, 0.015 to >32 and 32 microg/ml; streptococci, 0.015 to 0.03 and 0.03 microg/ml; Eikenella corrodens, 0.25 to 1 and 1 microg/ml; and Bergeyella zoohelcum, 0.03 to 0.25 and 0.06 microg/ml. For anaerobes the MIC ranges and MIC(90)s of ABT-773 were as follows, respectively: Prevotella heparinolytica, 0. 06 to 0.125 and 0.125 microg/ml; Prevotella spp., 0.015 to 0.125 and 0.06 microg/ml; Porphyromonas spp., 0.015 to 0.03 and 0.015 microg/ml; Fusobacterium nucleatum, 0.5 to 8 and 8 microg/ml; other Fusobacterium spp., 0.015 to 8 and 0.5 microg/ml; Bacteroides tectum, 0.015 to 0.5 and 0.06 microg/ml; and Peptostreptococcus spp., 0.015 to 0.25 and 0.03 microg/ml. ABT-773 was more active than all macrolides tested against S. aureus, E. corrodens, and anaerobes, but all compounds were poorly active against F. nucleatum. The activity of ABT-773 was within 1 dilution of that of azithromycin against Pasteurella spp., and ABT-773 was four- to eightfold more active than clarithromycin against Pasteurella spp. ABT-773 may offer a therapeutic alternative for bite wound infections.     

In vitro antibacterial activity of modithromycin, a novel 6,11-bridged bicyclolide, against respiratory pathogens, including macrolide-resistant Gram-positive cocci

The in vitro activities of modithromycin against Gram-positive and -negative respiratory pathogens, including macrolide-resistant cocci with different resistance mechanisms, were compared with those of other macrolide and ketolide agents. MICs were determined by the broth microdilution method. All 595 test strains used in this study were isolated from Japanese medical facilities. The erm (ribosome methylase) and/or mef (efflux pump) gene, which correlated with resistance to erythromycin as well as clarithromycin and azithromycin, was found in 81.8%, 21.3%, and 23.2% of Streptococcus pneumoniae, Streptococcus pyogenes, and methicillin-susceptible Staphylococcus aureus (MSSA) strains, respectively. Modithromycin showed MIC(90)s of 0.125 μg/ml against these three cocci, including macrolide-resistant strains. In particular, the MIC of modithromycin against ermB-carrying S. pyogenes was ≥ 32-fold lower than that of telithromycin. The activities of modithromycin as well as telithromycin were little affected by the presence of mefA or mefE in both streptococci. Against Gram-negative pathogens, modithromycin showed MIC(90)s of 0.5, 8, and 0.031 μg/ml against Moraxella catarrhalis, Haemophilus influenzae, and Legionella spp., respectively. The MICs of modithromycin against M. catarrhalis and H. influenzae were higher than those of telithromycin and azithromycin. However, modithromycin showed the most potent anti-Legionella activity among the macrolide and ketolide agents tested. These results suggested that the bicyclolide agent modithromycin is a novel class of macrolides with improved antibacterial activity against Gram-positive cocci, including telithromycin-resistant streptococci and intracellular Gram-negative bacteria of the Legionella species.     

In vitro activities of ABT-773 and other antimicrobials against human mycoplasmas

The in vitro susceptibilities of 103 Mycoplasma pneumoniae isolates, 14 Mycoplasma hominis isolates, 12 Mycoplasma fermentans isolates, and 24 Ureaplasma species to ABT-773, an investigational ketolide, and seven other agents were determined. For M. pneumoniae, the ABT-773 MIC at which 90% of isolates are inhibited (MIC(90); or=16-fold lower than those of all three fluoroquinolones. Minimal bactericidal concentrations determined for a subgroup of organisms were 相似文献   

Antipneumococcal activity of ABT-773 compared to those of 10 other agents

MICs, time-kills, and postantibiotic effects (PAEs) of ABT-773 (a new ketolide) and 10 other agents were determined against 226 pneumococci. Against 78 ermB- and 44 mefE-containing strains, ABT-773 MICs at which 50% of the isolates tested were inhibited (MIC(50)s) and MIC(90)s were 0.016 to 0.03 and 0.125 microgram/ml, respectively. Clindamycin was active only against macrolide-resistant strains containing mefE (MIC(50), 0.06 microgram/ml; MIC(90), 0.125 microgram/ml). Activities of pristinamycin (MIC(90), 0.5 microgram/ml) and vancomycin (MIC(90), 0.25 microgram/ml) were unaffected by macrolide or penicillin resistance, while beta-lactam MICs rose with those of penicillin G. Against 19 strains with L4 ribosomal protein mutations and two strains with mutations in domain V of 23S rRNA, ABT-773 MICs were 0.03 to 0.25 microgram/ml, while macrolide and azalide MICs were all >/=16.0 microgram/ml. ABT-773 was bactericidal at twice the MIC after 24 h for 8 of 12 strains (including three strains with erythromycin MICs greater than or equal to 64.0 microgram/ml). Kill kinetics of erythromycin, azithromycin, clarithromycin, and roxithromycin against macrolide-susceptible strains were slower than those of ABT-773. ABT-773 had longer PAEs than macrolides, azithromycin, clindamycin, or beta-lactams, including against ermB-containing strains. ABT-773, therefore, shows promising in vitro activity against macrolide-susceptible as well as -resistant pneumococci.     

In vitro activities of the novel ketolide telithromycin (HMR 3647) against erythromycin-resistant Streptococcus species

The in vitro susceptibilities of 184 erythromycin-resistant streptococci to a novel ketolide, telithromycin (HMR 3647), were tested. These clinical isolates included 111 Streptococcus pyogenes, 18 group C streptococcus, 18 group G streptococcus, and 37 Streptococcus pneumoniae strains. The MICs for all but eight S. pyogenes strains were < or =0.5 microg/ml, indicating that telithromycin is active in vitro against erythromycin-resistant Streptococcus strains. All strains for which MICs were > or =1 microg/ml had an erm(B) resistance gene and six strains for which MICs were > or =4 microg/ml had a constitutive erm(B) gene (MIC range, 4 to 64 microg/ml). Interestingly, for S. pneumoniae strains with a constitutive erm(B) gene, MICs were < or =0.25 microg/ml (MIC range, < or =0.008 to 0.25 microg/ml). Our in vitro data show that for S. pyogenes strains which constitutively express the erm(B) methylase gene, MICs are so high that the strains might be clinically resistant to telithromycin.     

Comparison of selection for mutants with reduced susceptibility to ABT-773, erythromycin and rifampicin in respiratory tract pathogens

Attempts were made to select mutants on agar media containing the new ketolide ABT-773, erythromycin or rifampicin, at concentrations above the MICs, from Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes and Haemophilus influenzae, including erythromycin-resistant strains. ABT-773 did not select for mutants in four strains, whereas in eight strains the frequencies at 72 h were < or = 10(-9). ABT-773 MICs were 0.015-4 mg/L for mutants, except those selected from inducible Erm(A) S. aureus. Mutants selected on ABT-773 or erythromycin were cross-resistant to ABT-773, erythromycin and, sometimes, clindamycin. The susceptibility profiles indicate that different mutations were selected and that ABT-773 and erythromycin may interact with the ribosome differently.     

Comparative activity of cefditoren and other oral beta-lactams against nonpneumococcal streptococci

BACKGROUND: In vitro studies of cefditoren activity have focused primarily on Streptococcus pneumoniae and other bacterial species isolated from patients with respiratory infections, but relatively few reports have been published describing the activity of cefditoren against clinical isolates of nonpneumococcal streptococci. METHODS: Cefditoren activity was determined by broth microdilution (M7-A5, NCCLS, 2000) for 450 viridans group streptococci, 917 Streptococcus pyogenes and 800 other beta-hemolytic streptococci collected throughout the US during 1999-2000. RESULTS: Against viridans group streptococci, cefditoren (MIC(90), 0.5 microg/ml) was 4- to 32-fold more active than the other beta-lactams tested (penicillin ampicillin, amoxicillin-clavulanate, cefprozil and cefuroxime). The difference in activity between cefditoren and the other beta-lactams was greater for penicillin-nonsusceptible isolates (MIC(90s), 1 microg/ml versus 8-32 microg/ml) than among penicillin-susceptible isolates (MIC(90s), 0.12 versus 0.25- 1 microg/ml). Cefditoren also demonstrated potent activity against S. pyogenes (MIC(90), 0.015 microg/ml) and other beta-hemolytic streptococci (MIC(90), 0.06 microg/ml), comparable to that of the other beta-lactams. CONCLUSIONS: The activity demonstrated by cefditoren against nonpneumococcal streptococci, including beta-lactam- and macrolide-resistant isolates, suggests that this agent holds promise as therapy for infections caused by all clinically significant species of streptococci.     

Macrolide-Resistant Streptococcus pneumoniae in Canada during 1998–1999: Prevalence of mef(A) and erm(B) and Susceptibilities to Ketolides

In this study (1998-1999), we collected 215 macrolide-resistant Streptococcus pneumoniae isolates from an ongoing Canadian Respiratory Organism Surveillance Study involving 23 centers representing all regions of Canada. The prevalence of erythromycin-resistant S. pneumoniae was 8% (215 of 2,688). Of the 215 isolates, 48.8% (105 of 215) were PCR positive for mef(A) and 46.5% (100 of 215) were PCR positive for erm(B). The ketolides telithromycin and ABT-773 demonstrated excellent activity against both mef(A) (MIC for 90% of strains [MIC(90)], 0.06 and 0.03 microg/ml, respectively) and erm(B) (MIC(90), 0.06 and 0.03 microg/ml, respectively) strains of S. pneumoniae.     

Comparative activity of telithromycin against typical community-acquired respiratory pathogens

OBJECTIVES: Respiratory tract infections (RTIs) remain a significant cause of morbidity and mortality. Major bacterial pathogens in RTIs, such as Streptococcus pneumoniae, have exhibited increasing resistance to a variety of antibiotics during the past decades. Telithromycin, the first ketolide, was designed especially to overcome this resistance. The present study was conducted to assess the comparative activity of telithromycin against typical RTI pathogens in Austria. METHODS: A total of 1,015 bacterial isolates was tested, including S. pneumoniae, Streptococcus pyogenes, Staphylococcus aureus and Haemophilus influenzae. MICs of the following antimicrobials: penicillin G, ampicillin (for H. influenzae), azithromycin, clarithromycin, erythromycin A and telithromycin were determined using the NCCLS broth microdilution method. RESULTS: Telithromycin showed excellent activity against S. pneumoniae, with 99.8% of all isolates being susceptible. Penicillin remained active with an MIC50 and MIC90 of 0.007 mg/L. Nevertheless, a notable increase in penicillin intermediate-resistant and resistant isolates, from 4.9% in 1996 to the present rate of 10%, was observed. There was also a distinct rise in the resistance levels of S. pneumoniae against the macrolides. All tested isolates of S. pyogenes were susceptible to penicillin and telithromycin, and only low levels of resistance against telithromycin were found in S. aureus (2.2%, MIC90 of 0.5 mg/L). No telithromycin-resistant isolate of H. influenzae could be detected. CONCLUSIONS: This study demonstrates the rising prevalence of resistance among S. pneumoniae not only to penicillin but also to other antimicrobials. It also shows the value of telithromycin as an attractive option for the empirical treatment of community-acquired RTIs in an era of widespread antibacterial resistance.     

Antimicrobial resistance among clinical isolates of Streptococcus pneumoniae in Canada during 2000

A total of 2,245 clinical isolates of Streptococcus pneumoniae were collected from 63 microbiology laboratories from across Canada during 2000 and characterized at a central laboratory. Of these isolates, 12.4% were not susceptible to penicillin (penicillin MIC, >or=0.12 microg/ml) and 5.8% were resistant (MIC, >or=2 microg/ml). Resistance rates among non-beta-lactam agents were the following: macrolides, 11.1%; clindamycin, 5.7%; chloramphenicol, 2.2%; levofloxacin, 0.9%; gatifloxacin, 0.8%; moxifloxacin, 0.4%; and trimethoprim-sulfamethoxazole, 11.3%. The MICs at which 90% of the isolates were inhibited (MIC90s) of the fluoroquinolones were the following: gemifloxacin, 0.03 microg/ml; BMS-284756, 0.06 microg/ml; moxifloxacin, 0.12 microg/ml; gatifloxacin, 0.25 microg/ml; levofloxacin, 1 microg/ml; and ciprofloxacin, 1 microg/ml. Of 578 isolates from the lower respiratory tract, 21 (3.6%) were inhibited at ciprofloxacin MICs of >or=4 microg/ml. None of the 768 isolates from children were inhibited at ciprofloxacin MICs of >or=4 microg/ml, compared to 3 of 731 (0.6%) from those ages 15 to 64 (all of these >60 years old), and 27 of 707 (3.8%) from those over 65. The MIC90s for ABT-773 and telithromycin were 0.015 microg/ml for macrolide-susceptible isolates and 0.12 and 0.5 microg/ml, respectively, for macrolide-resistant isolates. The MIC of linezolid was 相似文献   

In Vitro Activity of the Ketolide ABT-773

The in vitro activities of ABT-773, azithromycin, erythromycin, and clindamycin were compared by testing 1,223 clinical isolates selected to represent different species and phenotypes. ABT-773 was particularly potent against staphylococci (the MIC at which 90% of the strains tested were inhibited [MIC(90)] was < or =0.06 microg/ml), including all strains that were macrolide resistant but clindamycin susceptible. Streptococcus pneumoniae and other streptococci were inhibited by low concentrations of ABT-773, and that included most erythromycin-resistant strains. Against Haemophilus influenzae, ABT-773 and azithromycin were similar in their antibacterial potency (MIC(90), 4.0 and 2.0 microg/ml, respectively).     

Comparative in vitro activities of ABT-773 against 362 clinical isolates of anaerobic bacteria

The activity of ABT-773, a novel ketolide antibiotic, against clinical isolates of anaerobic bacteria was determined and compared to the activities of other antimicrobial agents. MICs at which 90% of isolates were inhibited (MIC(90)s) were 32 microg/ml, respectively, for Eubacterium spp., Lactobacillus spp., Clostridium difficile, and Clostridium ramosum. The MIC(90) for Bilophila wadsworthia, Bacteroides ureolyticus, and Campylobacter gracilis was 1 microg/ml, and that for Prevotella bivia and other Prevotella spp. was 0.5 microg/ml. The MIC(90) for Fusobacterium nucleatum was 8 microg/ml, and that for Fusobacterium mortiferum and Fusobacterium varium was >32 microg/ml. The MIC(90)s for the Bacteroides fragilis group were as follows: for B. fragilis, 8 microg/ml; for Bacteroides thetaiotaomicron, Bacteroides ovatus, Bacteroides distasonis, and Bacteroides uniformis, >32 microg/ml; and for Bacteroides vulgatus, 4 microg/ml. Telithromycin MICs for the B. fragilis group were usually 1 to 2 dilutions higher than ABT-773 MICs. For all strains, ABT-773 was more active than erythromycin by 4 or more dilutions, and for some strains this drug was more active than clindamycin.     

Time-kill study of the activity of telithromycin against macrolide-resistant Streptococcus pneumoniae Isolates with 23S rRNA mutations and changes in ribosomal proteins L4 and L22

By use of a time-kill methodology, the antipneumococcal activity of telithromycin was determined against macrolide-resistant S. pneumoniae isolates having mutations in the 23S rRNA gene and changes in the ribosomal proteins L4 and L22. Telithromycin had MICs ranging between 0.03 and 0.25 microg/ml and was bactericidal against four of seven strains after 24 h at two times the MIC.     

Activity of retapamulin (SB-275833), a novel pleuromutilin, against selected resistant gram-positive cocci

Retapamulin (SB-275833), the first pleuromutilin to be developed for human topical use, was tested against a selected population of staphylococci and beta-hemolytic streptococci. The MIC90 results for retapamulin were 0.12 microg/ml for Staphylococcus aureus and < or = 0.03 microg/ml for Streptococcus pyogenes; no cross-resistance was observed for organism subsets resistant to oxacillin, erythromycin, or mupirocin.     

Contemporary re-evaluation of the activity and spectrum of grepafloxacin tested against isolates in the United States

Grepafloxacin potency and spectrum of activity were re-evaluated against contemporary pathogens collected from clinical infections in 2001-2002. A total of 995 isolates were tested for grepafloxacin by the reference agar dilution method and these results were compared to those of 25 other antimicrobial agents. Grepafloxacin activity remained comparable to that of ciprofloxacin, levofloxacin and gatifloxacin against Escherichia coli, Klebsiella pneumoniae and Enterobacter cloacae (MIC(90), 0.03-2 microg/ml; 0.0-7.7% resistance rates). For Pseudomonas aeruginosa, grepafloxacin was active against ciprofloxacin-susceptible (MIC(90), 2 microg/ml), but not against ciprofloxacin-resistant (MIC(90), >8 microg/ml) isolates. Against methicillin-susceptible Staphylococcus aureus, grepafloxacin susceptibility rate was 91.4%, equal to that of levofloxacin. None of the fluoroquinolones showed reasonable activity against methicillin-resistant staphylococci. Gatifloxacin and grepafloxacin had the same MIC(90) against beta-hemolytic streptococci (0.25 microg/ml) and penicillin-susceptible Streptococcus pneumoniae (0.25 microg/ml). Grepafloxacin and other fluoroquinolone activities were not influenced by penicillin resistance in S. pneumoniae. Grepafloxacin was very active against Haemophilus influenzae (MIC(90), 0.03 microg/ml), Moraxella catarrhalis (MIC(90), 0.03 microg/ml) and Legionella spp. (MIC(90), 0.5 microg/ml). These results on recently isolated organisms indicate that grepafloxacin has a sustained potency and spectrum against most clinically important and indicated pathogens.     

The in vitro activity of ABT773, a new ketolide antimicrobial agent

The in vitro activity of ABT773, a ketolide antimicrobial agent, was investigated and compared with those of seven other antibiotics. Type strains and 733 Gram-positive, Gram-negative and anaerobic isolates of clinical origin and four CHLAMYDIA: isolates were used. The activity of ABT773 was very similar to that of telithromycin, the other ketolide tested. The MIC(90) was < or = 0.5 mg/L for all bacteria examined except methicillin-resistant Staphylococcus aureus, Enterococcus faecalis, Enterococcus faecium, Haemophilus influenzae and BACTEROIDES: spp. The antichlamydial activity of ABT773 was greater than that of telithromycin, erythromycin and ciprofloxacin. Neither an increase in the size of the inoculm nor the addition of human serum had any marked affect on the in vitro activity of ABT773.     

Susceptibility to telithromycin in 1,011 Streptococcus pyogenes isolates from 10 central and Eastern European countries.

Among 1,011 recently isolated Streptococcus pyogenes isolates from 10 Central and Eastern European centers, the MICs at which 50% of isolates are inhibited (MIC(50)s) and the MIC(90)s were as follows: for telithromycin, 0.03 and 0.06 microg/ml, respectively; for erythromycin, azithromycin, and clarithromycin, 0.06 to 0.125 and 1 to 8 microg/ml, respectively; and for clindamycin, 0.125 and 0.125 microg/ml, respectively. Erythromycin resistance occurred in 12.3% of strains. Erm(A) [subclass erm(TR)] was most commonly encountered (60.5%), followed by mef(A) (23.4%) and erm(B) (14.5%). At <0.5 microg/ml, telithromycin was active against 98.5% of the strains tested.     

In vitro activities of a new ketolide, ABT-773, alone and in combination with amoxicillin, metronidazole, or tetracycline against Helicobacter pylori

The in vitro activity of ABT-773, a new ketolide, was compared with those of clarithromycin, amoxicillin, metronidazole, and tetracycline against 15 strains of Helicobacter pylori. The MIC of ABT-773 at which 90% of isolates were inhibited was 0.25 microg/ml, which was 3 dilutions higher than that of the most active agent, clarithromycin. Synergy and antagonism were not seen with any combinations. Additive activity was seen with tetracycline, metronidazole, and amoxicillin in 100, 60, and 40% of the combinations, respectively.     

In vitro activity of the new ketolide ABT-773 against community acquired respiratory tract isolates and Viridans Streptococci

A total of 230 isolates were collected from clinical specimens of patients attending five health centers of the Buenos Aires, Argentina. ABT-773 was compared to erythromycin, azithromycin and clindamycin against bacterial isolates responsible for community-acquired respiratory tract infections and viridans streptococci showing different resistance patterns. Time-kill curves were also performed against selected resistant isolates.All but one of the 105 pneumococcal isolates were susceptible to ABT-773. Among the erythromycin resistant S. pyogenes isolates, all the M type and inducible isolates were susceptible to ABT-773. ABT-773 showed excellent activity against macrolide, azalide, lincosamide (MAL) inducible S. aureus producers but was inactive against constitutive producers. ABT-773 activity against viridans streptococci was also excellent.ABT-773 exerted bactericidal activity against selected isolates of S. pneumoniae, M. catarrhalis and H. influenzae, however, it was only bacteriostatic against methicillin-susceptible S. aureus.     

In vitro activity of telavancin against gram-positive clinical isolates recently obtained in Europe

The in vitro activity of telavancin was tested against 620 gram-positive isolates. For staphylococci, MICs at which 50 and 90% of isolates were inhibited (MIC(50) and MIC(90)) were both 0.25 microg/ml, irrespective of methicillin resistance. MIC(50) and MIC(90) were 0.25 and 0.5 microg/ml for vancomycin-susceptible enterococci and 1 and 2 microg/ml for vancomycin-resistant enterococci, respectively. Streptococcus pneumoniae, group A and B beta-hemolytic streptococci, and viridans streptococci were inhibited by < or =0.12 microg/ml.