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1.
MICs of CB-183,315, a novel lipopeptide antibiotic, vancomycin, and metronidazole were determined for intestinal anaerobes and Enterobacteriaceae. The MIC(90)s for Gram-negative anaerobes were >8,192, 8,192, and 4 μg/ml for CB-183,315, vancomycin, and metronidazole, respectively. Against Enterobacteriaceae, the MIC(90)s were >8,192 μg/ml, 1,024 μg/ml, and 1,024 μg/ml, respectively. The CB-183,315 MIC(90) for Clostridium difficile was 0.5 μg/ml. Its lack of activity against normal fecal organisms makes it a promising new agent for treating C. difficile.  相似文献   

2.
A 10-day course of oral fidaxomicin (200 mg twice a day [b.i.d.]), a potent new macrocyclic drug, was compared to vancomycin (125 mg four times a day [q.i.d.]) in 1,164 adults (1,105 in the modified intent-to-treat [mITT] population) with Clostridium difficile infection in two phase III randomized, double-blind trials at sites in North America and 7 European countries. Of 1,105 mITT patients, 792 (71.7%), including 719/999 (72.0%) in the per-protocol (PP) population, provided a C. difficile strain at baseline, of whom 356 received fidaxomicin with 330 cures (92.7%) and 363 received vancomycin with 329 cures (90.6%). The susceptibilities (MIC(90)) of baseline isolates did not predict clinical cure, failure, or recurrence for fidaxomicin (MIC(90), 0.25 μg/ml for both; range, ≤ 0.007 to 1 μg/ml), but there was a one-dilution difference in the MIC(90) (but not the MIC(50)) for vancomycin (MIC(90), 2 μg/ml [range, 0.25 to 8 μg/ml] for cure and 4.0 μg/ml [range, 0.5 to 4 μg/ml] for failures). A total of 65 (7.9%) "rifaximin-resistant" (MIC > 256 μg/ml) strains were isolated in both treatment groups on enrollment, which increased to 25% for failures at the end of therapy. No resistance to either fidaxomicin or vancomycin developed during treatment in either of the phase III studies, although a single strain isolated from a cured patient had an elevated fidaxomicin MIC of 16 μg/ml at the time of recurrence. All isolates were susceptible to ≤ 4 μg/ml of metronidazole. When analyzed by restriction endonuclease analysis (REA) type, 247/719 (34.4%) isolates were BI group isolates, and the MICs were generally higher for all four drugs tested (MIC(90)s: fidaxomicin, 0.5; vancomycin, 2.0; metronidazole, 2.0; and rifaximin, >256 μg/ml) than for the other REA types. There was no correlation between the MIC of a baseline clinical isolate and clinical outcome. MIC(90)s were generally low for fidaxomicin and vancomycin, but BI isolates had higher MICs than other REA group isolates.  相似文献   

3.
We evaluated the in vitro antianaerobic activity of razupenem (SMP-601, PTZ601), a new parenterally administered carbapenem, against 70 reference strains and 323 clinical isolates. Razupenem exhibited broad-spectrum activity against anaerobes, inhibiting most of the reference strains when used at a concentration of ≤1 μg/ml. Furthermore, it exhibited strong activity, comparable to those of other carbapenems (meropenem and doripenem), against clinically isolated non-fragilis Bacteroides spp. (MIC90s of 2 μg/ml), with MIC90 values of 0.06, 0.03, and 0.5 μg/ml against Prevotella spp., Porphyromonas spp., and Fusobacterium spp., respectively. Clinical isolates of anaerobic Gram-positive cocci, Eggerthella spp., and Clostridium spp. were highly susceptible to razupenem (MIC90s, 0.03 to 1 μg/ml).  相似文献   

4.
BC-3781 is a novel semisynthetic pleuromutilin antimicrobial agent developed as an intravenous and oral therapy for acute bacterial skin and skin structure infections (ABSSSI) and respiratory tract infections (RTI). BC-3781 and comparator agents were tested by the broth microdilution method against 1,893 clinical Gram-positive organisms predominantly causing ABSSSI. BC-3781 exhibited potent activity against methicillin-resistant Staphylococcus aureus (MIC(50/90), 0.12/0.25 μg/ml), coagulase-negative staphylococci (MIC(50/90), 0.06/0.12 μg/ml), β-hemolytic streptococci (MIC(50/90), 0.03/0.06 μg/ml), viridans group streptococci (MIC(50/90), 0.12/0.5 μg/ml), and Enterococcus faecium (including vancomycin-nonsusceptible strains) (MIC(50/90), 0.12/2 μg/ml). Compared with other antibiotics in use for the treatment of ABSSSI, BC-3781 displayed the lowest MICs and only a minimal potential for cross-resistance with other antimicrobial classes.  相似文献   

5.
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.  相似文献   

6.
HMR 3647 (RU 66647) and HMR 3004 (RU 64004), two ketolides, had MICs at which 50% of the strains are inhibited (MIC50s) of 0.06 to 0.125 microg/ml and MIC90s of 16.0 microg/ml against 352 anaerobes. MIC50s and MIC90s of erythromycin, azithromycin, clarithromycin, and roxithromycin were 0.5 to 2.0 microg/ml and 32.0 to >64.0 microg/ml, respectively. HMR 3647 and HMR 3004 were more active against non-Bacteroides fragilis-group anaerobes (other than Fusobacterium mortiferum, Fusobacterium varium, and Clostridium difficile).  相似文献   

7.
Two novel lipoglycopeptides, dalbavancin and telavancin, and relevant comparative agents were tested for in vitro activity against clinical isolates of staphylococci and streptococci collected in the cross-Canada surveillance study, CANWARD, in 2007-2009. The rank order of potency (based on MIC(90) [μg/mL], i.e., the concentration of antimicrobial agent required to inhibit the growth of 90% of isolates tested) of glycopeptides against both Staphylococcus aureus and Staphylococcus epidermidis was dalbavancin (0.06 μg/mL) >telavancin (0.5 μg/mL) > vancomycin (1-2 μg/mL); concurrent susceptibility or resistance to oxacillin in staphylococci did not affect potency of glycopeptides. Dalbavancin and telavancin also demonstrated potent activity against Streptococcus pneumoniae, including penicillin-resistant isolates (MIC(90), ≤ 0.03 μg/mL; ≤ 0.06 μg/mL), and Streptococcus pyogenes (≤ 0.03 μg/mL; 0.06 μg/mL). Based on their robust in vitro activities, dalbavancin and telavancin have the potential to treat Gram-positive infections caused by methicillin-resistant Staphylococcus aureus and penicillin-resistant Streptococcus pneumoniae.  相似文献   

8.
We evaluated the activity of CB-183,315 against Clostridium difficile, including strains that are resistant to fluoroquinolones and metronidazole and with elevated MICs to vancomycin as well as other Gram-positive intestinal pathogens. The MICs of CB-183,315 against all C. difficile isolates were ≤ 1 μg/ml. CB-183,315 had greater activity than vancomycin and metronidazole against C. difficile isolates and was more active than the comparators against vancomycin-resistant enterococcus (VRE). CB-183,315 also had excellent activity against methicillin-resistant Staphylococcus aureus (MRSA), other Clostridium spp., and Peptostreptococcus spp.  相似文献   

9.
The comparative in vitro activity of SMT19969, a novel, narrow-spectrum, nonabsorbable agent, was studied against 50 ribotype-defined Clostridium difficile strains, 174 Gram-positive and 136 Gram-negative intestinal anaerobes, and 40 Gram-positive aerobes. SMT19969 was one dilution more active against C. difficile isolates (MIC range, 0.125 to 0.5 μg/ml; MIC90, 0.25 μg/ml), including ribotype 027 strains, than fidaxomicin (range, 0.06 to 1 μg/ml; MIC90, 0.5 μg/ml) and two to six dilutions lower than either vancomycin or metronidazole. SMT19969 and fidaxomicin were generally less active against Gram-negative anaerobes, especially the Bacteroides fragilis group species, than vancomycin and metronidazole, suggesting that SMT19969 has a lesser impact on the normal intestinal microbiota that maintain colonization resistance. SMT19969 showed limited activity against other Gram-positive anaerobes, including Bifidobacteria species, Eggerthella lenta, Finegoldia magna, and Peptostreptococcus anaerobius, with MIC90s of >512, >512, 64, and 64 μg/ml, respectively. Clostridium species showed various levels of susceptibility, with C. innocuum being susceptible (MIC90, 1 μg/ml) and C. ramosum and C. perfringens being nonsusceptible (MIC90, >512 μg/ml). Activity against Lactobacillus spp. (range, 0.06 to >512 μg/ml; MIC90, >512 μg/ml) was comparable to that of fidaxomicin and varied by species and strain. Gram-positive aerobic cocci (Staphylococcus aureus, Enterococcus faecalis, E. faecium, and streptococci) showed high SMT19969 MIC90 values (128 to >512 μg/ml).  相似文献   

10.
JNJ-Q2 is a novel broad-spectrum bactericidal fluorinated 4-quinolone with potent activity against Gram-positive and -negative pathogens with a balanced potency against both DNA gyrase and topoisomerase IV targets. JNJ-Q2 is in clinical development for the treatment of acute bacterial skin and skin-structure infections (ABSSSIs) and community-acquired bacterial pneumonia. With the use of reference broth microdilution methods in a central reference laboratory design, MIC values were obtained for 3650 pathogens (44.4% were from patients diagnosed with ABSSSI) obtained during the 2010 SENTRY antimicrobial surveillance program. Isolates were collected from patients in 96 medical centers in 26 countries in North America, Europe, Latin America, and Asia Pacific. JNJ-Q2 demonstrated good activity overall (MIC(50/90), 0.015/0.5 μg/mL) and against 3081 Staphylococcus aureus with >95% of the isolates inhibited at a MIC of ≤0.5 μg/mL; against 1410 levofloxacin-resistant Staphylococcus aureus isolates, >90% were inhibited by MIC ≤0.5 μg/mL. All isolates were inhibited at a MIC of ≤2 μg/mL. In addition, JNJ-Q2 demonstrated excellent activity (MIC(90), 0.015 μg/mL) against 569 isolates of beta-hemolytic streptococci (including 278 Streptococcus pyogenes and 161 Streptococcus agalactiae). JNJ-Q2 was the most potent fluoroquinolone tested overall and against all pathogens when compared directly to moxifloxacin, levofloxacin, and ciprofloxacin.  相似文献   

11.
A total of 403 nonduplicate isolates of Clostridium difficile were collected at three major teaching hospitals representing northern, central, and southern Taiwan from January 2005 to December 2010. Of these 403 isolates, 170 (42.2%) were presumed to be nontoxigenic due to the absence of genes for toxins A or B or binary toxin. The remaining 233 (57.8%) isolates carried toxin A and B genes, and 39 (16.7%) of these also had binary toxin genes. The MIC(90) of all isolates for fidaxomicin and rifaximin was 0.5 μg/ml (range, ≤ 0.015 to 0.5 μg/ml) and >128 μg/ml (range, ≤ 0.015 to >128 μg/ml), respectively. All isolates were susceptible to metronidazole (MIC(90) of 0.5 μg/ml; range, ≤ 0.03 to 4 μg/ml). Two isolates had reduced susceptibility to vancomycin (MICs, 4 μg/ml). Only 13.6% of isolates were susceptible to clindamycin (MIC of ≤ 2 μg/ml). Nonsusceptibility to moxifloxacin (n = 81, 20.1%) was accompanied by single or multiple mutations in gyrA and gyrB genes in all but eight moxifloxacin-nonsusceptible isolates. Two previously unreported gyrB mutations might independently confer resistance (MIC, 16 μg/ml), Ser416 to Ala and Glu466 to Lys. Moxifloxacin-resistant isolates were cross-resistant to ciprofloxacin and levofloxacin, but some moxifloxacin-nonsusceptible isolates remained susceptible to gemifloxacin or nemonoxacin at 0.5 μg/ml. This study found the diversity of toxigenic and nontoxigenic strains of C. difficile in the health care setting in Taiwan. All isolates tested were susceptible to metronidazole and vancomycin. Fidaxomicin exhibited potent in vitro activity against all isolates tested, while the more than 10% of Taiwanese isolates with rifaximin MICs of ≥ 128 μg/ml raises concerns.  相似文献   

12.
By using an agar dilution method, the in vitro activities of ramoplanin, teicoplanin, vancomycin, linezolid, and five other agents were determined against 300 gram-positive and 54 gram-negative strains of intestinal anaerobes. Ramoplanin was active at or=256 microg/ml. Ramoplanin displays excellent activity against C. difficile and other gram-positive enteric anaerobes, including vancomycin-resistant strains; however, it has poor activity against most gram-negative anaerobes and thus potentially has a lesser effect on the ecological balance of normal fecal flora.  相似文献   

13.
Tests of dalbavancin's in vitro activity against 209 aerobic and 120 anaerobic isolates from pretreatment diabetic foot infections showed an MIC(90) of < or =0.125 microg/ml against methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA), and 120 anaerobes (Clostridium perfringens, other clostridia, Peptoniphilus asaccharolyticus, Finegoldia magna, and Anaerococcus prevotii), compared to respective MIC(90)s for MSSA and MRSA of 0.5 and 1 microg/ml for vancomycin, 4 and 4 microg/ml for linezolid, 0.5 and 0.5 microg/ml for daptomycin, and 0.25 and >8 microg/ml for clindamycin.  相似文献   

14.
Ertapenem (MK-0826, L-749,345) is a 1-beta-methyl carbapenem with a long serum half-life. Its in vitro activity was determined by broth microdilution against 3,478 bacteria from 12 centers in Europe and Australia, with imipenem, cefepime, ceftriaxone, and piperacillin-tazobactam used as comparators. Ertapenem was the most active agent tested against members of the family Enterobacteriaceae, with MICs at which 90% of isolates are inhibited (MIC(90)s) of < or =1 microg/ml for all species. Ertapenem also was more active than imipenem against fastidious gram-negative bacteria and Moraxella spp.; on the other hand, ertapenem was slightly less active than imipenem against streptococci, methicillin-susceptible staphylococci, and anaerobes, but its MIC(90)s for these groups remained < or =0.5 microg/ml. Acinetobacter spp. and Pseudomonas aeruginosa were also much less susceptible to ertapenem than imipenem, and most Enterococcus faecalis strains were resistant. Ertapenem resistance, based on a provisional NCCLS MIC breakpoint of > or =16 microg/ml, was seen in only 3 of 1,611 strains of the family Enterobacteriaceae tested, all of them Enterobacter aerogenes. Resistance was also seen in 2 of 135 anaerobes, comprising 1 Bacteroides fragilis strain and 1 Clostridium difficile strain. Ertapenem breakpoints for streptococci have not been established, but an unofficial susceptibility breakpoint of < or =2 microg/ml was adopted for clinical trials to generate corresponding clinical response data for isolates for which MICs were as high as 2 microg/ml. Of 234 Streptococcus pneumoniae strains tested, 2 required ertapenem MICs of 2 microg/ml and one required an MIC of 4 microg/ml, among 67 non-Streptococcus pyogenes, non-Streptococcus pneumoniae streptococci, single isolates required ertapenem MICs of 2 and 16 microg/ml. These streptococci also had diminished susceptibilities to other beta-lactams, including imipenem as well as ertapenem. The Etest and disk diffusion gave susceptibility test results in good agreement with those of the broth microdilution method for ertapenem.  相似文献   

15.
LFF571 is a novel semisynthetic thiopeptide and potent inhibitor of Gram-positive bacteria. We report that the antibacterial activity of LFF571 against Clostridium difficile is due to inhibition of translation. Single-step mutants of C. difficile with reduced susceptibility to LFF571 were selected at frequencies of <4.5 × 10(-11) to 1.2 × 10(-9). Sequencing revealed a G260E substitution in the thiopeptide-binding pocket of elongation factor Tu. Importantly, this mutation did not confer cross-resistance to clinically used antimicrobials. These results support the development of LFF571 as a treatment for C. difficile infection.  相似文献   

16.
TD-1792 is a new multivalent glycopeptide-cephalosporin antibiotic with potent activity against Gram-positive bacteria. The in vitro activity of TD-1792 was tested against 527 Staphylococcus aureus isolates, including multidrug-resistant isolates. TD-1792 was highly active against methicillin-susceptible S. aureus (MIC(90), 0.015 μg/ml), methicillin-resistant S. aureus, and heterogeneous vancomycin-intermediate S. aureus (MIC(90), 0.03 μg/ml). Time-kill studies demonstrated the potent bactericidal activity of TD-1792 at concentrations of ≤ 0.12 μg/ml. A postantibiotic effect of >2 h was observed after exposure to TD-1792.  相似文献   

17.
The in vitro activity of SCH27899, a novel oligosaccharide antimicrobial agent, was compared with those of representatives of six classes of antimicrobial agents (piperacillin, clarithromycin, clindamycin, vancomycin, sitafloxacin and metronidazole) against clinical isolates of anaerobic bacteria and Propionibacterium acnes. Against Peptostreptococcus: spp. and Clostridium difficile, SCH27899 was the most potent (MIC(90) < 0.125 mg/L) of the agents examined. Besides these Gram-positive anaerobes, SCH27899 showed a moderate level of activity against Prevotella bivia, Prevotella intermedia and Porphyromonas: spp. (MIC(90)< or = 4 mg/L).  相似文献   

18.
The in vitro activity of ceftobiprole was evaluated against 15 011 clinical isolates obtained from patients in Canadian hospitals between 2007 and 2009. All Staphylococcus aureus were susceptible to ceftobiprole (MIC(90)'s for methicillin-susceptible Staphylococcus aureus and methicillin-resistant Staphylococcus aureus of ≤ 1 μg/mL and 2 μg/mL, respectively). Ceftobiprole was active against penicillin-susceptible Streptococcus pneumoniae (MIC(90), ≤ 0.06 μg/mL), penicillin-resistant Streptococcus pneumoniae (MIC(90), 0.5 μg/mL), Streptococcus pyogenes (MIC(90), ≤ 0.06 μg/mL), Staphylococcus epidermidis (MIC(90), ≤ 1 μg/mL), and Enterococcus faecalis (MIC(90), ≤ 1 μg/mL). Over 90% of Escherichia coli, Klebsiella pneumoniae, Enterobacter aerogenes, Citrobacter freundii, Proteus mirabilis, and Serratia marcescens isolates were inhibited by a ceftobiprole concentration of ≤ 1 μg/mL. Ceftobiprole was not active against extended-spectrum β-lactamase-producing Escherichia coli and K. pneumoniae. The in vitro activity of ceftobiprole versus Pseudomonas aeruginosa was similar to that of cefepime (MIC(90), 16 μg/mL). The broad spectrum of activity by ceftobiprole would support further study of this agent in the treatment of hospital-acquired infections.  相似文献   

19.
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.  相似文献   

20.
The susceptibility of 69 clinical isolates of Clostridium difficile from the Minneapolis Veterans Administration Medical Center and 29 C. difficile strains from other hospitals to efrotomycin, ciprofloxacin, and six other antimicrobials was tested in vitro by agar dilution. Ciprofloxin (MIC50 and MIC90 = 8 mcg/ml) was only moderately active whereas efrotomycin (MIC50 = 0.125, MIC90 = 0.25 mcg/ml) was highly active against C. difficile.  相似文献   

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