scholarly journals In Vitro Activities of Two Ketolides, HMR 3647 and HMR 3004, against Gram-Positive Bacteria

1999 ◽  
Vol 43 (4) ◽  
pp. 930-936 ◽  
Author(s):  
Kumthorn Malathum ◽  
Teresa M. Coque ◽  
Kavindra V. Singh ◽  
Barbara E. Murray

ABSTRACT 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 erythromycin-susceptible (Ems), 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 [MIC50] [HMR 3647 and HMR 3004], 0.03 μg/ml; range, 0.03 to 0.06 μg/ml; MIC50 [erythromycin], 0.25 μg/ml; range, 0.25 to 0.5 μg/ml). All methicillin-resistant S. aureus strains tested were resistant to erythromycin and had HMR 3647 and HMR 3004 MICs of >64 μg/ml. The ketolides were slightly more active against E. faecalis than against E. faecium, and MICs for individual strains varied with erythromycin susceptibility. The MIC50s of HMR 3647 and HMR 3004 against Ems enterococci (MIC ≤ 0.5 μg/ml) and those enterococcal isolates with erythromycin MICs of 1 to 16 μg/ml were 0.015 μg/ml. E. faecalis strains that had erythromycin MICs of 128 to >512 μg/ml showed HMR 3647 MICs in the range of 0.03 to 16 μg/ml and HMR 3004 MICs in the range of 0.03 to 64 μg/ml. In the group of E. faecium strains for which MICs of erythromycin were ≥512 μg/ml, MICs of both ketolides were in the range of 1 to 64 μg/ml, with almost all isolates showing ketolide MICs of ≤16 μg/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.

2011 ◽  
Vol 8 (3) ◽  
pp. 1120-1123 ◽  
Author(s):  
Bahram Letafat ◽  
Negar Mohammadhosseini ◽  
Ali Asadipour ◽  
Alireza Foroumadi

In the present study we report the synthesis and antibacterial activity of a new series 2-(1-methyl-4-nitro-1H-imidazol-5-ylsulfonyl)-1,3,4-thiadiazoles (6a-c). Compounds6a-cwere testedin vitroby the conventional agar dilution method against a panel of microorganisms including gram-negative and gram-positive bacteria. Compound6bwith 5-(5-nitrofuran-2-yl)-residue on 1,3,4-thiadiazole scaffold have shown promising antibacterial activities against gram-positive bacteria includingStaphylococcus aureus, Staphylococcus epidermidisandBacillus subtilis.


2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Séverine Boisard ◽  
Anne-Marie Le Ray ◽  
Anne Landreau ◽  
Marie Kempf ◽  
Viviane Cassisa ◽  
...  

During this study, thein vitroantifungal and antibacterial activities of different extracts (aqueous and organic) obtained from a French propolis batch were evaluated. Antifungal activity was evaluated by broth microdilution on three pathogenic strains:Candida albicans, C. glabrata, andAspergillus fumigatus. Antibacterial activity was assayed using agar dilution method on 36 Gram-negative and Gram-positive strains includingStaphylococcus aureus. Organic extracts showed a significant antifungal activity againstC. albicansandC. glabrata(MIC80between 16 and 31 µg/mL) but only a weak activity towardsA. fumigatus(MIC80= 250 µg/mL). DCM based extracts exhibited a selective Gram-positive antibacterial activity, especially againstS. aureus(SA) and several of its methicillin-resistant (MRSA) and methicillin-susceptible (MSSA) strains (MIC10030–97 µg/mL). A new and active derivative of catechin was also identified whereas a synergistic antimicrobial effect was noticed during this study.


2021 ◽  
Author(s):  
Shivalee N Duduskar ◽  
Mohamed Ghait ◽  
Martin Westermann ◽  
Huijuan Guo ◽  
Anuradha Ramoji ◽  
...  

Molecular mechanisms through which Gram-positive bacteria induce the canonical inflammasome are poorly understood. Here, we studied the effects of Group B streptococci (GBS) and Staphylococcus aureus (SA) on inflammasome activation in human macrophages. Dinucleotide binding small RNA aptamers released by SA and GBS were shown to trigger increased IL-1β generation by inflammasomes. The stimulator of interferon genes-STING as a central mediator of innate immune responses has been identified as the key target of pathogenic RNA. Multi-lamellar lipid bodies (MLBs) produced by SA function as vehicles for the RNA aptamers. Notably, expression of RNA aptamers is controlled by an accessory gene regulator quorum sensing system of the bacteria. These findings have been translated to patients with Gram-positive sepsis showing hallmarks of MLB-RNA-mediated inflammasome activation. Together our findings may provide a new perspective for the pathogenicity of Gram-positive bacterial infection in man.


2005 ◽  
Vol 73 (10) ◽  
pp. 6383-6389 ◽  
Author(s):  
Francis Michon ◽  
Samuel L. Moore ◽  
John Kim ◽  
Milan S. Blake ◽  
France-Isabelle Auzanneau ◽  
...  

ABSTRACT A number of epitope specificities associated with the cell wall polysaccharide antigen of group A streptococci were identified in a polyclonal rabbit antiserum induced in rabbits by whole group A streptococci and in polyclonal convalescent human antisera from children that had recovered from streptococcal A infections. The identification was achieved by using a series of synthetic oligosaccharides, glycoconjugates, and bacterial polysaccharide inhibitors to inhibit the binding of the group A helical polysaccharide to the polyclonal antisera. The exclusively dominant epitope expressed in the convalescent human antisera was the doubly branched extended helical hexasaccharide with the structure α-l-Rhap(1→2)[β-d-GlcpNAc(1→3)]α-l-Rhap(1→3)α-l-Rhap(1→2)[β-d-GlcpNAc(1→3)]α-l-Rhap. The hexasaccharide epitope also bound with the highest immunoreactivity to the rabbit antiserum. In contrast, the human antisera did not show significant binding to the singly branched pentasaccharide with the structure α-l-Rhap(1→2)α-l-Rhap(1→3)α-l-Rhap(1→2)[β-d-GlcpNAc(1→3)]α-l-Rhap or the branched trisaccharide α-l-Rhap(1→2)[β-d-GlcpNAc(1→3)]α-l-Rhap, although both these haptens bound significantly to the same rabbit antiserum, albeit with less immunoreactivity than the hexasaccharide. Inhibition studies using streptococcal group A and B rabbit antisera and the inhibitors indicated above also suggested that the group A carbohydrate, unlike the group B streptococcal polysaccharide, does not contain the disaccharide α-l-Rhap(1→2)α-l-Rhap motif at its nonreducing chain terminus, stressing the importance of mapping the determinant specificities of these two important streptococcal subcapsular group polysaccharides to fully understand the serological relationships between group A and group B streptococci.


2015 ◽  
Vol 59 (10) ◽  
pp. 6262-6265 ◽  
Author(s):  
Ko-Hung Chen ◽  
Yu-Tsung Huang ◽  
Chun-Hsing Liao ◽  
Wang-Hui Sheng ◽  
Po-Ren Hsueh

ABSTRACTTedizolid is a novel, expanded-spectrum oxazolidinone with potent activity against a wide range of Gram-positive pathogens. A total of 425 isolates of Gram-positive bacteria were obtained consecutively from patients with acute bacterial skin and skin structure infections (ABSSSIs) or pneumonia. These isolates included methicillin-susceptibleStaphylococcus aureus(MSSA) (n= 100), methicillin-resistantStaphylococcus aureus(MRSA) (n= 100),Streptococcus pyogenes(n= 50),Streptococcus agalactiae(n= 50),Streptococcus anginosusgroup (n= 75),Enterococcus faecalis(n= 50), and vancomycin-resistant enterococci (VRE) (Enterococcus faecium) (n= 50). The MICs of tedizolid and linezolid were determined by the agar dilution method. Tedizolid exhibited betterin vitroactivities than linezolid against MSSA (MIC90s, 0.5 versus 2 μg/ml), MRSA (MIC90s, 0.5 versus 2 μg/ml),S. pyogenes(MIC90s, 0.5 versus 2 μg/ml),S. agalactiae(MIC90s, 0.5 versus 2 μg/ml),Streptococcus anginosusgroup (MIC90s, 0.5 versus 2 μg/ml),E. faecalis(MIC90s, 0.5 versus 2 μg/ml), and VRE (MIC90s, 0.5 versus 2 μg/ml). The tedizolid MICs againstE. faecalis(n= 3) and VRE (n= 2) intermediate to linezolid (MICs, 4 μg/ml) were 1 μg/ml and 0.5 μg/ml, respectively. The tedizolid MIC90s against S. anginosus,S. constellatus, andS. intermediuswere 0.5, 1, and 0.5 μg/ml, respectively, and the rates of susceptibility based on the U.S. FDA MIC interpretive breakpoints to the isolates were 16%, 28%, and 72%, respectively. Tedizolid exhibited 2- to 4-fold betterin vitroactivities than linezolid against a variety of Gram-positive cocci associated with ABSSSIs and pneumonia. The lower susceptibilities of tedizolid against isolates ofS. anginosusandS. constellatusthan against those ofS. intermediusin Taiwan were noted.


2003 ◽  
Vol 47 (11) ◽  
pp. 3667-3671 ◽  
Author(s):  
A. Liebetrau ◽  
A. C. Rodloff ◽  
J. Behra-Miellet ◽  
L. Dubreuil

ABSTRACT The antimicrobial activities of garenoxacin and eight other antibiotics against 641 anaerobic isolates were evaluated with the NCCLS agar dilution method. Overall, the MICs of garenoxacin for 50 and 90% of the strains tested (in micrograms per milliliter) were as follows: Bacteroides fragilis group, 0.5 and 2; Prevotella spp., 0.25 and 2; Fusobacterium spp., 0.25 and 0.5; Porphyromonas spp., 0.125 and 0.25; Bilophila wadsworthia, 0.5 and 1; Veillonella spp., 0.25 and 0.5; Clostridium spp., 0.25 and 1; Clostridium difficile, 2 and >64; Bifidobacterium spp., 1 and 2; Eggerthella lenta, 0.25 and 1; Propionibacterium spp., 0.5 and 0.5; gram-positive cocci, 0.125 and 0.25.


2006 ◽  
Vol 74 (7) ◽  
pp. 4200-4213 ◽  
Author(s):  
Shizhen Zhang ◽  
Nicole M. Green ◽  
Izabela Sitkiewicz ◽  
Rance B. LeFebvre ◽  
James M. Musser

ABSTRACT Group A Streptococcus (GAS) is a gram-positive human bacterial pathogen that causes infections ranging in severity from pharyngitis to life-threatening invasive disease, such as necrotizing fasciitis. Serotype M28 strains are consistently isolated from invasive infections, particularly puerperal sepsis, a severe infection that occurs during or after childbirth. We recently sequenced the genome of a serotype M28 GAS strain and discovered a novel 37.4-kb foreign genetic element designated region of difference 2 (RD2). RD2 is similar in gene content and organization to genomic islands found in group B streptococci (GBS), the major cause of neonatal infections. RD2 encodes seven proteins with conventional gram-positive secretion signal sequences, six of which have not been characterized. Herein, we report that one of these six proteins (M28_Spy1325; Spy1325) is a member of the antigen I/II family of cell surface-anchored molecules produced by oral streptococci. PCR and DNA sequence analysis found that Spy1325 is very well conserved in GAS strains of distinct M protein serotypes. As assessed by real-time TaqMan quantitative PCR, the Spy1325 gene was expressed in vitro, and Spy1325 protein was present in culture supernatants and on the GAS cell surface. Western immunoblotting and enzyme-linked immunosorbent assays indicated that Spy1325 was produced by GAS in infected mice and humans. Importantly, the immunization of mice with recombinant Spy1325 fragments conferred protection against GAS-mediated mortality. Similar to other antigen I/II proteins, recombinant Spy1325 bound purified human salivary agglutinin glycoprotein. Spy1325 may represent a shared virulence factor among GAS, GBS, and oral streptococci.


1978 ◽  
Vol 8 (5) ◽  
pp. 480-488
Author(s):  
S M Gubash

A new phenomenon of synergistic hemolysis by Clostridium perfringens alpha-toxin and the streptococcal CAMP factor on human and guinea pig erythrocytes is described. A possible mode of action of the CAMP factors is suggested. On human blood agar all of the tested isolates of group B streptococci gave an arrowhead-shaped zone of hemolysis; 74% of group A gave a crescent-shaped lytic zone, whereas all isolates of groups C and G and the remaining 26% of group A streptococci gave a bullet-shaped lytic zone. By comparison, in the CAMP test incubated aerobically and anaerobically, 70 and 91%, respectively, of streptococci other than group B gave positive, arrowhead-shaped lytic zones. If all intermediate positive reactions in the CAMP tests were read as negative after aerobic incubation, only 89% of group B streptococci would be properly identified. The synergistic hemolysis phenomenon, using an alpha-toxin-producing C. perfringens and human blood agar, provided a reliable test for presumptive identification of group B streptococci, with promising potential to differentiate in the same test group A streptococci from other groups.


2003 ◽  
Vol 47 (6) ◽  
pp. 1968-1971 ◽  
Author(s):  
Ellie J. C. Goldstein ◽  
Diane M. Citron ◽  
C. Vreni Merriam ◽  
Yumi Warren ◽  
Kerin Tyrrell ◽  
...  

ABSTRACT Dalbavancin is a novel semisynthetic glycopeptide with enhanced activity against gram-positive species. Its comparative in vitro activities and those of nine comparator agents, including daptomycin, vancomycin, linezolid, and quinupristin-dalfopristin, against 290 recent gram-positive clinical isolates strains, as determined by the NCCLS agar dilution method, were studied. The MICs of dalbavancin at which 90% of various isolates tested were inhibited were as follows: Actinomyces spp., 0.5 μg/ml; Clostridium clostridioforme, 8 μg/ml; C. difficile, 0.25 μg/ml; C. innocuum, 0.25 μg/ml; C. perfringens, 0.125 μg/ml; C. ramosum, 1 μg/ml; Eubacterium spp., 1 μg/ml; Lactobacillus spp., >32 μg/ml, Propionibacterium spp., 0.5 μg/ml; and Peptostreptococcus spp., 0.25 μg/ml. Dalbavancin was 1 to 3 dilutions more active than vancomycin against most strains. Dalbavancin exhibited excellent activity against gram-positive strains tested and warrants clinical evaluation.


1959 ◽  
Vol 109 (6) ◽  
pp. 589-600 ◽  
Author(s):  
Hutton D. Slade ◽  
Yoshitami Kimura

Heat-killed cells of Group A streptococci caused death of the adrenalectomized rat. While the adrenalectomized rat readily succumbed to intraperitoneal infection with living cells, death was due primarily to toxicity. The normal rat was highly resistant under either condition. For studies on the toxic materials, the cells of numerous serological types of group A streptococci, and of a Group B and a Group D streptococcus, were extracted with 0.1 N HCl at 100°C. or by sonic oscillation. The extracts, containing macromolecular components, were subjected to chemical fractionation and purification. C substance and M protein of Group A streptococci released from the cell by sonic oscillation were toxic to the adrenalectomized rat in quantities of 1 mg./100 gm. rat. Death usually occurred within 2 hours. On the other hand, C substance and M protein released from the cell with HCl at 100°C. were relatively non-toxic to the adrenalectomized rat. The sonic-extracted C substance of streptococcal Groups B, C, and D was also toxic. The toxic property of the C and M preparations was neutralized in vitro in each case by group and type-specific rabbit antiserum. Heterologous antiserum was without effect. Adrenalectomized rats which received homologous antiserum 18 hours before challenge were also resistant to the toxicity of the C and M preparations. Trypsin destroyed the toxic effect of the M protein preparations and was without effect on the toxicity of the C substance. The R antigen and a nucleoprotein component of Group A streptococci, preparations of protein from Groups B and D streptococci, and coagulase from Staphylococcus aureus were all found to be essentially non-toxicic for the adrenalectomized rat. Large quantities of peptone, crystalline albumin, and rabbit serum were also without effect.


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