scholarly journals In Vitro Activities of the Rx-01 Oxazolidinones against Hospital and Community Pathogens

2008 ◽  
Vol 52 (5) ◽  
pp. 1653-1662 ◽  
Author(s):  
Laura Lawrence ◽  
Paul Danese ◽  
Joe DeVito ◽  
Francois Franceschi ◽  
Joyce Sutcliffe

ABSTRACT Rx-01_423 and Rx-01_667 are two members of the family of oxazolidinones that were designed using a combination of computational and medicinal chemistry and conventional biological techniques. The compounds have a two- to eightfold-improved potency over linezolid against serious gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), multidrug-resistant streptococci, and vancomycin-resistant enterococci. This enhanced potency extends to the coverage of linezolid-resistant gram-positive microbes, especially multidrug-resistant enterococci and pneumococci. Compounds from this series expand the spectrum compared with linezolid to include fastidious gram-negative organisms like Haemophilus influenzae and Moraxella catarrhalis. Like linezolid, the Rx-01 compounds are bacteriostatic against MRSA and enterococci but are generally bactericidal against S. pneumoniae and H. influenzae.

2005 ◽  
Vol 49 (6) ◽  
pp. 2498-2500 ◽  
Author(s):  
Eun Jeong Yoon ◽  
Yeong Woo Jo ◽  
Sung Hak Choi ◽  
Tae Ho Lee ◽  
Jae Keol Rhee ◽  
...  

ABSTRACT In vitro and in vivo activities of DA-7867 were assessed against methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, and penicillin-resistant Streptococcus pneumoniae. All isolates were inhibited by DA-7867 at ≤0.78 μg/ml, a four-times-lower concentration than that of inhibition by linezolid. For murine infection models, DA-7867 also exhibited greater efficacy than linezolid against all isolates tested.


2016 ◽  
Vol 54 (9) ◽  
pp. 2225-2232 ◽  
Author(s):  
Matthew P. Crotty ◽  
Tamara Krekel ◽  
Carey-Ann D. Burnham ◽  
David J. Ritchie

The growing problem of antimicrobial resistance among bacterial pathogens, including methicillin-resistantStaphylococcus aureus(MRSA) and vancomycin-resistant enterococci (VRE), has reached a critical state. Tedizolid phosphate, dalbavancin, and oritavancin have recently been approved by the U.S. Food and Drug Administration (FDA) for the treatment of acute bacterial skin and skin structure infections (ABSSSI) and represent the next generation of oxazolidinones and lipoglycopeptides. All three agents exhibitin vitroactivity and clinical efficacy against MRSA. Tedizolid phosphate and oritavancin demonstratein vitroactivity against VRE. These new Gram-positive agents are reviewed here.


2004 ◽  
Vol 48 (7) ◽  
pp. 2771-2777 ◽  
Author(s):  
Laurel S. Almer ◽  
Jennifer B. Hoffrage ◽  
Erika L. Keller ◽  
Robert K. Flamm ◽  
Virginia D. Shortridge

ABSTRACT In vitro activities of ABT-492, ciprofloxacin, levofloxacin, trovafloxacin, moxifloxacin, gatifloxacin, and gemifloxacin were compared. ABT-492 was more potent against quinolone-susceptible and -resistant gram-positive organisms, had activity similar to that of ciprofloxacin against certain members of the family Enterobacteriaceae, and had comparable activity against quinolone-susceptible, nonfermentative, gram-negative organisms. Bactericidal activity of ABT-492 was also evaluated.


2020 ◽  
Vol 9 (4) ◽  
pp. e34-e34
Author(s):  
Babak Hadian ◽  
Azita Zafarmohtashami ◽  
Mahdi Razani

Introduction: Proper care of vascular access in hemodialysis patients is important. Catheter-related bloodstream infection (CRBSI), is a life-threatening complication of hemodialysis. Objectives: Sufficient data about microorganisms and their susceptibility to antibiotics in hemodialysis patients is necessary for handling of CRBSI; therefore, this study performed for better management of patients. Patients and Methods: All hemodialysis patients from March 2015 to March 2018 who had cultures of catheter and blood samples were studied. Clinical records of 122 patients were reviewed for variables such as catheter and blood culture microorganism types, antibiotic resistance, age, gender, site, comorbidities, and various clinical signs. Results: Eighty-four cases of catheter cultures were positive for bacteria. Staphylococcus epidermidis was the most common organism (36%) since Staphylococcus aureus was the second one (28%). In some cases, multidrug resistant organisms such as Enterobacter baumannii or methicillin-resistant Staphylococcus aureus (MRSA) organisms were grown. Twenty-one percent of S. aureus organisms were MRSA. No significant association between important diagnostic data (fever, chills or WBC count) and bacteremia were shown. Gender of patients had a significant statistical association with CRBSI. Conclusion: Given the necessity of proper management, physicians must empirically initiate antibiotic therapy as soon as possible, until receiving definite culture results, in hemodialysis patients suspected of bacteremia. In our study, both gram-positive and gram-negative organisms were common. Hence, when initial empirical treatment is indicated, the coverage of both gram positive and gram negative organisms must be considered. Vancomycin or other antibiotics that are effective on MRSA must be included in empirical treatment.


Author(s):  
Kyle J. Gontjes ◽  
Kristen E. Gibson ◽  
Bonnie Lansing ◽  
Marco Cassone ◽  
Lona Mody

Abstract Perianal screening can be intrusive. The sensitivities of multianatomical, nonperianal surveillance were 92.3% for methicillin-resistant Staphylococcus aureus (MRSA), 58.7% for vancomycin-resistant enterococci (VRE), and 54.9% for resistant Gram-negative bacilli (R-GNB). Sensitivities improved upon adding environmental surveillance (95.5%, 82.9%, and 67.9%, respectively). Multianatomical, nonperianal screening and room environment surveillance may replace perianal screening and reduce healthy participant bias in nursing homes.


2016 ◽  
Vol 60 (4) ◽  
pp. 2352-2358 ◽  
Author(s):  
Jordan R. Smith ◽  
Juwon Yim ◽  
Animesh Raut ◽  
Michael J. Rybak

ABSTRACTOritavancin possesses activity against vancomycin-resistant enterococci (VRE) and methicillin-resistantStaphylococcus aureus(MRSA).In vitrodata suggest synergy between beta-lactams (BLs) and vancomycin or daptomycin, agents similar to oritavancin. We evaluated the activities of BLs combined with oritavancin against MRSA and VRE. Oritavancin MICs were determined for 30 strains, 5 each of MRSA, daptomycin-nonsusceptible (DNS) MRSA, vancomycin-intermediate MRSA (VISA), heteroresistant VISA (hVISA), vancomycin-resistantEnterococcus faecalis, and vancomycin-resistantEnterococcus faecium. Oritavancin MICs were determined in the presence of subinhibitory concentrations of BLs. Oritavancin combined with ceftaroline, cefazolin, or nafcillin was evaluated for lethal synergy against MRSA, and oritavancin combined with ceftaroline, ampicillin, or ertapenem was evaluated for lethal synergy against VRE in 24-h time-kill assays. Oritavancin at 0.5× the MIC was combined with BLs at 0.5× the MIC or the biological free peak concentration, whichever one was lower. Synergy was defined as a ≥2-log10-CFU/ml difference between the killing achieved with the combination and that achieved with the most active single agent at 24 h. Oritavancin MICs were ≤0.125 μg/ml for all MRSA isolates except three VISA isolates with MICs of 0.25 μg/ml. Oritavancin MICs for VRE ranged from 0.03 to 0.125 μg/ml. Oritavancin in combination with ceftaroline was synergistic against all MRSA phenotypes and statistically superior to all other combinations against DNS MRSA, hVISA, and MRSA isolates (P< 0.02). Oritavancin in combination with cefazolin and oritavancin in combination with nafcillin were also synergistic against all MRSA strains. Synergy between oritavancin and all BLs was revealed against VRE strain 8019, while synergy between oritavancin and ampicillin or ertapenem but not ceftaroline was demonstrated against VRE strain R7164. The data support the potential use of oritavancin in combination with BLs, especially oritavancin in combination with ceftaroline, for the treatment of infections caused by MRSA. The data from the present study are not as strong for oritavancin in combination with BLs for VRE. Further study of both MRSA and VRE in more complex models is warranted.


1996 ◽  
Vol 40 (3) ◽  
pp. 720-726 ◽  
Author(s):  
R N Jones ◽  
D M Johnson ◽  
M E Erwin

Two new fluorinated oxazolidinones, U-100592 and U-100766, were evaluated against more than 659 gram-positive and -negative organisms and compared with glycopeptides, erythromycin, clindamycin, clinafloxacin, and chloramphenicol. U-100592 and U-100766 were usually equally potent, but the MICs at which 90% of the isolates are inhibited (MIC90s) of U-100592 for some staphylococci and enterococci were slightly lower than those of U-100766 (1 versus 2 micrograms/ml). The MIC90 of U-100592 and U-100766 for oxacillin-resistant Staphylococcus aureus was 2 micrograms/ml, the same as observed for oxacillin-susceptible strains. The oxazolidinone MICs for other Staphylococcus spp. were < or = 2 micrograms/ml (MIC50, 0.5 to 1 microgram/ml). All enterococci were inhibited by < or = 4 and < or = 2 micrograms of U-100592 and U-100766 per ml, respectively. Against 152 vancomycin-resistant enterococci (five species), both compounds had a narrow range of MICs (0.25 to 2 micrograms/ml) and a MIC90 of 1 microgram/ml. Corynebacterium jeikeium, Bacillus spp., and all tested streptococci were inhibited (< or = 4 micrograms/ml). Members of the family Enterobacteriaceae and other gram-negative bacilli were not susceptible (MIC50, > 64 micrograms/ml) to either oxazolidinone. Three potencies of U-100592 and U-100766 disks were tested (5, 15, and 30 micrograms), and acceptable correlations (r = 0.81 to 0.90) with the measured MICs were observed. Best discrimination of the tentatively susceptible organisms (MICs, < or = 4 micrograms/ml) was demonstrated with the 30-micrograms disk concentration. The oxazolidinones demonstrated a dominant bacteristatic action. These oxazolidinones (U-100592 and U-100766) appear promising for treatment of gram-positive organisms that demonstrate resistance to contemporary therapeutic agents.


2019 ◽  
Vol 63 (3) ◽  
Author(s):  
Cecilia G. Carvalhaes ◽  
Michael D. Huband ◽  
Harald H. Reinhart ◽  
Robert K. Flamm ◽  
Helio S. Sader

ABSTRACTOmadacycline is a derivative of minocycline and the first agent of the aminomethylcycline class. A total of 3,282 organisms (1 per patient) were consecutively collected from patients hospitalized in China (including Hong Kong) and Taiwan. Susceptibility testing was performed by broth microdilution methods in a central laboratory (JMI Laboratories). The collection included Gram-positive and Gram-negative organisms from patients with pneumonia, bloodstream, skin, community-acquired respiratory, and other infections. Omadacycline was very potent againstStaphylococcus aureus(n= 689; MIC50/90, 0.12/0.25 mg/liter), including methicillin-resistantStaphylococcus aureus(MRSA;n= 299; MIC50/90, 0.12/0.5 mg/liter), and had similar activity across geographic regions. Omadacycline was very active againstStreptococcus pneumoniae(highest MIC, 0.25 mg/liter), β-hemolytic streptococci (highest MIC, 1 mg/liter), viridans group streptococci (highest MIC, 0.25 mg/liter), andEnterococcusspp. (highest MIC, 0.5 mg/liter) from all geographic regions. Overall, 53.8% ofS. pneumoniaeisolates were penicillin resistant (penicillin MIC, ≥2 mg/liter) and 10.7% of enterococci (21.2% amongE. faeciumisolates) were vancomycin resistant. Omadacycline was active againstHaemophilus influenzae(MIC50/90, 0.5/1 mg/liter) regardless of β-lactamase production and was active againstMoraxella catarrhalis(MIC50/90, ≤0.12/0.25 mg/liter). AgainstEnterobacteriaceae, omadacycline was most active againstEscherichia coli(MIC50/90, 1/2 mg/liter),Klebsiella oxytoca(MIC50/90, 1/4 mg/liter), andEnterobacter cloacae(MIC50/90, 2/4 mg/liter). Omadacycline had potentin vitroactivity against Gram-positive and Gram-negative pathogens isolated from China and Taiwan and retained activity against problem pathogens, such as MRSA, vancomycin-resistant enterococci (VRE), penicillin-resistantS. pneumoniae(PRSPN), and extended-spectrum β-lactamase-producingE. coli. The observed MIC profile in Chinese isolates was very similar to that seen in the U.S. and European surveillance studies.


2001 ◽  
Vol 45 (12) ◽  
pp. 3640-3643 ◽  
Author(s):  
Kavindra V. Singh ◽  
Kumthorn Malathum ◽  
Barbara E. Murray

ABSTRACT The in vitro activities of ABT-773 were evaluated against 324 strains of gram-positive bacteria, including multidrug-resistantStaphylococcus spp. and Enterococcus spp. ABT-773 had lower MIC ranges, MICs at which 50% of isolates are inhibited (MIC50s), and MIC90s than erythromycin or clindamycin for almost all isolates tested. The MICs of ABT-773 were also lower than those of quinupristin-dalfopristin (Q-D) for methicillin-susceptible Staphylococcus aureus,Rhodococcus spp., and Streptococcus spp., while the MICs of Q-D were lower than those of ABT-773 for methicillin-resistant S. aureus and Enterococcus faecium, including vancomycin-resistant isolates.


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