Comparative In Vitro Activities and Postantibiotic Effects of the Oxazolidinone Compounds Eperezolid (PNU-100592) and Linezolid (PNU-100766) versus Vancomycin against Staphylococcus aureus, Coagulase-Negative Staphylococci, Enterococcus faecalis, and Enterococcus faecium (original) (raw)
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Comparative activity of linezolid against staphylococci and enterococci isolated in Italy
Clinical Microbiology and Infection, 2002
The activity of linezolid, a new oxazolidinone, was tested against 862 Gram-positive cocci isolated in Italy and compared with the activities of 12 antibiotics. Overall, MIC 90 s for linezolid (2-4 mg/L) indicated an in vitro activity comparable to that of vancomycin in methicillin-resistant Staphylococcus aureus (4 mg/L), S. epidermidis (2 mg/L) and methicillin-susceptible strains. Enterococcus faecalis strains were susceptible to linezolid (MIC 90 2-4 mg/L), glycopeptides and b-lactams. In E. faecium, only glycopeptides (MIC 90 2 mg/ L) and linezolid (MIC 90 2 mg/L) were active. Linezolid was the only drug active against two strains of Enterococcus showing a VanA phenotype. Owing to its antibacterial profile, linezolid represents a promising drug for the treatment of Gram-positive infections.
1999
The emergence of resistance in gram-positive bacteria has necessitated a search for new antimicrobial agents. Linezolid is an oxazolidinone, a new class of antibacterial agents with enhanced activity against pathogens. We compared the activity of linezolid to those of other antimicrobial agents against 3,945 clinical isolates. Linezolid demonstrated potent activity against all isolates tested. For all vancomycin-susceptible enterococci, staphylococci, and streptococci, the activity of linezolid was comparable to that of vancomycin. Against oxacillin-resistant staphylococci and vancomycin-resistant enterococci, linezolid was the most active agent tested. In summary, linezolid appears to be a promising new antimicrobial agent for the treatment of gram-positive infections.
R E S U M E N El objetivo de este estudio fue investigar los efectos in vitro de linezolid en combinación con cinco antimicrobianos antiestafilocócicos (doxiciclina, fosfomicina, levofloxacino, rifampicina y vancomicina) en cepas de Staphylococcus aureus sensibles a meticilina (SASM). Se utilizaron cinco cepas de SASM (hf008, hf095, hf295, hf602 y hf946) aisladas de muestras procedentes de infecciones humanas. Se utilizó el método del damero para evaluar la sinergia entre linezolid y los cinco antimicrobianos, y se trazaron curvas de tiempo-muerte con las combinaciones más activas. El resultado más habitual para las combinaciones de linezolid con rifampicina, vancomicina y doxiciclina fue indiferencia. La combinación con levofloxacino produjo antagonismo en dos de las cinco cepas. Sin embargo, frente a cuatro cepas se observó sinergia con la combinación de linezolid y fosfomicina, con un índice de concentración inhibitoria fraccionada (ICIF) >0,5. Ni linezolid ni fosfomicina en solitario inhibieron el crecimiento a 1/4x CMI, pero la combinación de ambos fármacos a 1/4 de la CMI respectiva mostró un efecto bacteriostático sinérgico, un descenso de 2-3 log 10 respecto al antimicrobiano más activo en solitario. En resumen, la combinación de linezolid y fosfomicina a concentraciones subinhibitorias se mostró sinérgica, ejerciendo un efecto bacteriostático. P a l a b r a s c c l a v e : Oxazolidinona -Fosfomicina -Sinergia S U M M A R Y The objective of this paper was to investigate the in vitro effects of linezolid combined with five antistaphylococcal antibiotics -doxycycline, fosfomycin, levofloxacin, rifampicin and vancomycin -upon methicillin-susceptible Staphylococcus aureus (MSSA). Five MSSA isolates from clinical specimens of human infections -hf008, hf095, hf295, hf602 and hf946 -were used in this study. The checkerboard method was used to assess synergism between linezolid and the five antibiotics, and time-kill curves were carried out with the most active combinations. Indifference was the most common result achieved by the checkerboard method when linezolid was combined with rifampicin, vancomycin or doxycycline. The combination with levofloxacin yielded antagonism for two of the five isolates. However, four isolates showed synergy for the combination of linezolid plus fosfomycin with a fractional inhibitory concentration index (FICI) >0.5. Neither linezolid nor fosfomycin alone inhibited growth at 1/4x minimum inhibitory concentration (MIC); but the combination of both drugs at 1/4 the respective MIC showed a synergistic bacteriostatic effect, a 2-3 log 10 decrease with respect to the most active antibiotic alone. In summary, the combination of subinhibitory concentrations of linezolid and fosfomycin presented synergism, exerting a bacteriostatic effect. K e y w w o r d s : Oxazolidinone -Fosfomycin -Synergism 2006; Vol. 19 (Nº 3) In vitro activity of linezolid in combination against methicillin-susceptible S. aureus 253
Medical Principles and Practice, 2001
Objectives: The increasing prevalence of resistant grampositive bacteria, emergence of vancomycin-resistant enterococci and the isolation of vancomycin-intermediate resistant Staphylococcus aureus have emphasized the need for new antimicrobial agents to treat infections caused by these organisms. We studied the comparative antimicrobial activities of linezolid, a new and totally synthetic oxazolidinone antibacterial agent and vancomycin against resistant gram-positive clinical isolates from four hospitals in Kuwait. Methods: The organisms were isolated from clinical samples including throat and wound swabs, urine and blood, and identified by cultural and biochemical characteristics. The minimum inhibitory concentration (MIC) of linezolid and vancomycin against S. aureus, coagulase-negative staphylococci, Streptococcus pneumoniae and enterococci was determined by the agar dilution method. Results: Linezolid demonstrated MIC ranges of 0.5-4 mg/l against methicillinresistant S. aureus (MRSA) and methicillin-susceptible S. aureus, 1-4 mg/l against methicillin-resistant coagulasenegative staphylococci (MR-CNS) and methicillin-sensitive coagulase-negative staphylococcal strains, and a narrow range of 0.5-1 mg/l against penicillin-resistant S. pneumoniae (PRSP). The range of vancomycin MICs against MRSA, MR-CNS and PRSP was 0.5-4, 0.5-1 and 0.25-0.5 mg/l, respectively. The MIC values of linezolid and vancomycin against vancomycin-susceptible enterococci were 1-2 and 0.5-4 mg/l, respectively. However, linezolid demonstrated a lower MIC of 2 mg/l against vancomycin-intermediate resistant enterococci and vancomycin-resistant enterococci than vancomycin (MICs of 8 and 1 512 mg/l, respectively). Conclusion: The results indicated that linezolid demonstrated activity comparable to vancomycin against all staphylococcal, vancomycin-susceptible enterococci and PRSP strains, but demonstrated superior activity against vancomycin-intermediate resistant enterococci and vancomycin-resistant enterococci. In addition, linezolid was highly effective against all multidrug-resistant gram-positive clinical isolates from hospitals in Kuwait.
Antimicrobial Agents and Chemotherapy, 2003
The in vitro activities of linezolid were determined alone and in combination with vancomycin, ciprofloxacin, gentamicin, fusidic acid, or rifampin against five methicillin-susceptible Staphylococcus aureus (MSSA) and five methicillin-resistant S. aureus (MRSA) strains. Similar responses were obtained against MSSA and MRSA. When combined with fusidic acid, gentamicin, or rifampin, linezolid prevented selection of resistant mutants but showed no synergy. When linezolid was combined with vancomycin and ciprofloxacin, a slight antagonism was observed. While the combination with linezolid may reduce the emergence of mutants resistant to the associated drugs, the absence of synergy, especially in the case of vancomycin and ciprofloxacin, does not argue in favor of such combinations.
In vitro efficacy of linezolid against vancomycin resistant Enterococci
Pakistan journal of pharmaceutical sciences, 2018
Vancomycin-resistance among Enterococci has been escalating in recent years in many countries. Linezolid, an oxazolidinone is one of the novel drug that promised effective therapy of infections caused by vancomycin-resistant Enterococci (VRE).However, like with most of the previous antimicrobial agents, the clinical benefit of linezolid is being threatened by the emergence of resistant strains of MRSA and vancomycin resistant enterococci VRE, being reported in many countries. This study was conducted to establish linezolid susceptibility of VRE isolates by determining the in vitro activity of linezolid against vancomycin resistant Enterococci, isolated in our setup using fifty VRE isolates. The data collected from this study conclude that the vancomycin resistant Enterococci are 100% linezolid susceptible and presently there is no significant resistance against this unique oxazolidinone in our setup.
Antimicrobial Agents and Chemotherapy, 2005
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.
Wiener Medizinische Wochenschrift, 2017
Background The increasing incidence of antimicrobial resistance has led to research on finding new antimicrobial agents or identifying drug combinations with synergistic effects. Enterococcal infections, particularly those associated with vancomycin-resistant enterococci (VREs), are therapeutic problems. Linezolid (LZD), an oxazolidinone antibiotic, shows good activity against Gram-positive bacteria including enterococci. To avoid the emergence of linezolid-resistant subpopulations and achieve enhanced activity or bactericidal effect, the use of combined therapy has been considered. Methods The in vitro activity of LZD in combination with five different antibiotics was evaluated using a microdilution checkerboard method and timekill study against 12 clinical enterococcus isolates. Results With the checkerboard method, LZD plus doxycycline (DX) had the highest frequency among all synergistic combinations. This combination and
In vitro antibacterial activities of a novel oxazolidinone, OCID0050
Journal of Antimicrobial Chemotherapy, 2009
Objectives: In the pursuit of developing a second-generation oxazolidinone, we have identified OCID0050 as a novel oxazolidinone with enhanced activity against bacterial strains resistant to methicillin, vancomycin and linezolid.