In Vitro Activities of Ketolide HMR 3647, Macrolides, and Clindamycin against Coryneform Bacteria (original) (raw)
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The in-vitro activity of HMR 3647, a new ketolide antimicrobial agent
Journal of Antimicrobial Chemotherapy, 1998
The in-vitro activity of HMR 3647, a novel ketolide, was investigated in comparison with those of erythromycin A, roxithromycin, clarithromycin (14-membered ring macrolides), amoxycillin-clavulanate and ciprofloxacin against 719 recent clinical Gram-positive, Gramnegative and anaerobic isolates and type cultures. HMR 3647 generally demonstrated greater activity than the other compounds with MIC 90 s of 0.5 mg/L, except for Staphylococcus epidermidis (MIC 90 > 128 mg/L), Haemophilus influenzae (MIC 90 = 2 mg/L), Enterococcus faecalis (MIC 90 = 2 mg/L), Enterococcus faecium (MIC 90 = 1 mg/L) and the anaerobes, Bacteroides fragilis (MIC 90 = 2 mg/L) and Clostridium difficile (MIC 90 = 1 mg/L). In general, an increase in the size of the inoculum from 10 4 to 10 6 cfu on selected strains had little effect on the MICs of HMR 3647. Additionally, the in-vitro activity of HMR 3647 was not affected by the presence of either 20 or 70% (v/v) human serum. The antichlamydial activity of HMR 3647 was generally greater than that of commonly used antichlamydial antimicrobials.
In Vitro Activities of Two Ketolides, HMR 3647 and HMR 3004, against Gram-Positive Bacteria
1999
The in vitro activities of two new ketolides, HMR 3647 and HMR 3004, were tested by the agar dilution method against 280 strains of gram-positive bacteria with different antibiotic susceptibility profiles, including Staphylococcus aureus, Enterococcus faecalis, Enterococcus faecium, Streptococcus spp. (group A streptococci, group B streptococci, Streptococcus pneumoniae, and alpha-hemolytic streptococci). Seventeen erythromycinsusceptible (Em s ), methicillin-susceptible S. aureus strains were found to have HMR 3647 and HMR 3004 MICs 4-to 16-fold lower than those of erythromycin (MIC at which 50% of isolates were inhibited [MIC 50 ] [HMR 3647 and HMR 3004], 0.03 g/ml; range, 0.03 to 0.06 g/ml; MIC 50 [erythromycin], 0.25 g/ml; range, 0.25 to 0.5 g/ml). All methicillin-resistant S. aureus strains tested were resistant to erythromycin and had HMR 3647 and HMR 3004 MICs of >64 g/ml. The ketolides were slightly more active against E. faecalis than against E. faecium, and MICs for individual strains varied with erythromycin susceptibility. The MIC 50 s of HMR 3647 and HMR 3004 against Em s enterococci (MIC < 0.5 g/ml) and those enterococcal isolates with erythromycin MICs of 1 to 16 g/ml were 0.015 g/ml. E. faecalis strains that had erythromycin MICs of 128 to >512 g/ml showed HMR 3647 MICs in the range of 0.03 to 16 g/ml and HMR 3004 MICs in the range of 0.03 to 64 g/ml. In the group of E. faecium strains for which MICs of erythromycin were >512 g/ml, MICs of both ketolides were in the range of 1 to 64 g/ml, with almost all isolates showing ketolide MICs of <16 g/ml. The ketolides were also more active than erythromycin against group A streptococci, group B streptococci, S. pneumoniae, rhodococci, leuconostocs, pediococci, lactobacilli, and diphtheroids. Time-kill studies showed bactericidal activity against one strain of S. aureus among the four strains tested. The increased activity of ketolides against gram-positive bacteria suggests that further study of these agents for possible efficacy against infections caused by these bacteria is warranted.
In vitro activity of linezolid and 12 other antimicrobials against coryneform bacteria
International Journal of Antimicrobial Agents, 2007
Methods: Minimum inhibitory concentrations (MICs) and time-death curves were carried out according to the recommendations of the Clinical and Laboratory Standards Institute (CLSI). Results: Linezolid was very active against the 130 strains of the Corynebacterium species studied. Only the glycopeptides showed similar efficacy. In contrast, penicillin G, ampicillin, macrolides, lincosamides, fluoroquinolones and aminoglycosides showed generally high MICs. Among the -lactams, only imipenem was active against the majority of strains of C. striatum and C. amycolatum, and, approximately half of the C. jeikeium and C. urealyticum isolates. Both Dermabacter hominis and Brevibacterium casei showed marked resistance against most of the antimicrobials tested, while Turicella otitidis only showed high MICs against macrolides and clindamycin. For all of them, linezolid, vancomycin and teicoplanin proved effective. The time-death curves showed linezolid to behave as a bacteriostatic agent (approximately 90% death rate). Such activity was more accentuated for C. amycolatum and C. striatum (reduction of 1.3 and 1.7 log 10 CFU/mL, respectively) than for C. jeikeium and C. urealyticum (reduction of 1.0 and 0.8 log 10 , respectively). Conclusions: Our results indicate that linezolid is active against coryneform bacteria. The efficacy of linezolid is equal to or even superior to that of the glycopeptides.
Antimicrobial agents and chemotherapy, 1998
Ninety-four erythromycin-susceptible and 107 erythromycin-resistant enterococcal strains (MIC of >/=512 microgram/ml) were inhibited by the ketolide HMR3647 at MICs of </=0.007 to 0.06 and 0.03 to 8 microgram/ml, respectively. Eighteen vanA-positive isolates and 29 high-level-penicillin-resistant isolates, all of them erythromycin resistant, were inhibited by HMR3647 at an MIC range of 0.015 to 4 microgram/ml. The new ketolide has excellent activity against Enterococcus species.
Antimicrobial Agents and Chemotherapy, 2004
Telavancin is a new semisynthetic glycopeptide anti-infective with multiple mechanisms of action, including inhibition of bacterial membrane phospholipid synthesis and inhibition of bacterial cell wall synthesis. We determined the in vitro activities of telavancin, vancomycin, daptomycin, linezolid, quinupristin-dalfopristin, imipenem, piperacillin-tazobactam, and ampicillin against 268 clinical isolates of anaerobic gram-positive organisms and 31 Corynebacterium strains using agar dilution methods according to National Committee for Clinical Laboratory Standards procedures. Plates with daptomycin were supplemented with Ca 2؉ to 50 mg/liter. The MICs at which 90% of isolates tested were inhibited (MIC 90 s) for telavancin and vancomycin were as follows: Actinomyces spp. (n ؍ 45), 0.25 and 1 g/ml, respectively; Clostridium difficile (n ؍ 14), 0.25 and 1 g/ml, respectively; Clostridium ramosum (n ؍ 16), 1 and 4 g/ml, respectively; Clostridium innocuum (n ؍ 15), 4 and 16 g/ml, respectively; Clostridium clostridioforme (n ؍ 15), 8 and 1 g/ml, respectively; Eubacterium group (n ؍ 33), 0.25 and 2 g/ml, respectively; Lactobacillus spp. (n ؍ 26), 0.5 and 4 g/ml, respectively; Propionibacterium spp. (n ؍ 34), 0.125 and 0.5 g/ml, respectively; Peptostreptococcus spp. (n ؍ 52), 0.125 and 0.5 g/ml, respectively; and Corynebacterium spp. (n ؍ 31), 0.03 and 0.5 g/ml, respectively. The activity of TD-6424 was similar to that of quinupristin-dalfopristin for most strains except C. clostridioforme and Lactobacillus casei, where quinupristin-dalfopristin was three-to fivefold more active. Daptomycin had decreased activity (MIC > 4 g/ml) against 14 strains of Actinomyces spp. and all C. ramosum, Eubacterium lentum, and Lactobacillus plantarum strains. Linezolid showed decreased activity (MIC > 4 g/ml) against C. ramosum, two strains of C. difficile, and 15 strains of Lactobacillus spp. Imipenem and piperacillin-tazobactam were active against >98% of strains. The MICs of ampicillin for eight Clostridium spp. and three strains of L. casei were >1 g/ml. The MIC 90 of TD-6424 for all strains tested was <2 g/ml. TD-6424 has potential for use against infections with gram-positive anaerobes and deserves further clinical evaluation.
Antimicrobial Agents and Chemotherapy, 1999
Testing of susceptibility to 13 antibiotics was performed with 90 isolates of Lactobacillus , Leuconostoc , and Pediococcus . MICs at which 90% of the isolates tested were inhibited by HMR3647, erythromycin, and ciprofloxacin were 0.015, 0.125 and 32 μg/ml, respectively. The penicillin MIC was ≥16 μg/ml against 26.2% of the studied Lactobacillus sp. isolates and 50% of Lactobacillus plantarum . HMR3647 showed excellent activity against these genera.
Antimicrobial Agents and Chemotherapy, 2001
The in vitro activities of gemifloxacin, ciprofloxacin, ampicillin, doxycycline, gentamicin, and vancomycin were evaluated against 15Listeria monocytogenes strains and 205 coryneform bacteria isolated from clinical samples. The percentages of strains inhibited by gemifloxacin at 0.5 μg/ml were 100% (L. monocytogenes), 93.3% (Brevibacterium spp.), 90% (Corynebacterium minutissimum), 42.5% (Corynebacterium amycolatum), 20% (Corynebacterium striatum), 12.5% (Corynebacterium jeikeium), and 10% (Corynebacterium urealyticum). One hundred percent of the L. monocytogenes strains were inhibited by 0.25 μg of gemifloxacin per ml, whereas 0% of the strains were inhibited by 0.25 μg of ciprofloxacin per ml. Vancomycin at 2 μg/ml inhibited all strains. Doxycycline and gentamicin at 4 μg/ml inhibited 94 and 49% of the strains, respectively, while ampicillin at 0.5, 2, and 8 μg/ml inhibited 24, 61, and 66% of the strains, respectively. It is concluded that gemifloxacin shows good in vitro activity...