scholarly journals Synergy of Linezolid with Several Antimicrobial Agents against Linezolid-Methicillin-Resistant Staphylococcal Strains

Antibiotics ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 496
Author(s):  
María-José Valderrama ◽  
María Alfaro ◽  
Icíar Rodríguez-Avial ◽  
Elvira Baos ◽  
Carmen Rodríguez-Avial ◽  
...  
Keyword(s):  
Antimicrobial Agents ◽  
Synergistic Effects ◽  
Ribosomal Subunit ◽  
Antagonistic Effect ◽  
Prolonged Treatment ◽  
Synergistic Activity ◽  
Methicillin Resistant ◽  
Resistant Strains ◽  
Time Kill ◽  
Selection Of

Linezolid is a synthetic oxazolydinone active against multi-resistant Gram-positive cocci that inhibits proteins synthesis by interacting with the 50S ribosomal subunit. Although linezolid-resistant strains are infrequent, several outbreaks have been recently described, associated with prolonged treatment with the antibiotic. As an alternative to monotherapy, the combination of different antibiotics is a commonly used option to prevent the selection of resistant strains. In this work, we evaluated combinations of linezolid with classic and new aminoglycosides (amikacin, gentamicin and plazomicin), carbapenems (doripenem, imipenem and meropenem) and fosfomycin on several linezolid- and methicillin-resistant strains of Staphylococcus aureus and S. epidermidis, isolated in a hospital intensive care unit in Madrid, Spain. Using checkerboard and time-kill assays, interesting synergistic effects were encountered for the combination of linezolid with imipenem in all the staphylococcal strains, and for linezolid–doripenem in S.epidermidis isolates. The combination of plazomicin seemed to also have a good synergistic or partially synergistic activity against most of the isolates. None of the combinations assayed showed an antagonistic effect.

scholarly journals Assessment by Time-Kill Methodology of the Synergistic Effects of Oritavancin in Combination with Other Antimicrobial Agents against Staphylococcus aureus

2008 ◽  
Vol 52 (10) ◽  
pp. 3820-3822 ◽  
Author(s):  
Adam Belley ◽  
Eve Neesham-Grenon ◽  
Francis F. Arhin ◽  
Geoffrey A. McKay ◽  
Thomas R. Parr ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Agents ◽  
Synergistic Effects ◽  
Clinical Development ◽  
Synergistic Activity ◽  
Gram Positive ◽  
Vancomycin Resistant ◽  
Time Kill

ABSTRACT Oritavancin is a semisynthetic lipoglycopeptide in clinical development for serious gram-positive infections. This study describes the synergistic activity of oritavancin in combination with gentamicin, linezolid, moxifloxacin, or rifampin in time-kill studies against methicillin-susceptible, vancomycin-intermediate, and vancomycin-resistant Staphylococcus aureus.

scholarly journals In Vitro Synergy of Pongamia pinnata Extract in Combination with Antibiotics for Inhibiting and Killing Methicillin-Resistant Staphylococcus aureus

Antibiotics ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 103 ◽  
Author(s):  
Po-An Su ◽  
Shun-Lai Li ◽  
Hung-Jen Tang ◽  
Chi-Chung Chen ◽  
Ying-Chen Lu ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Seed Coat ◽  
Antimicrobial Agents ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Inhibitory Concentration ◽  
Synergistic Effects ◽  
Pongamia Pinnata ◽  
Multiple Drug ◽  
Methicillin Resistant ◽  
Time Kill

Aims: Currently, we face the serious problem of multiple drug-resistant pathogens. The development of new antimicrobial agents is very costly and time-consuming. Therefore, the use of medicinal plants as a source of alternative antibiotics or for enhancing antibiotic effectiveness is important. Methods: The antibacterial effects of aqueous extracts of the seed coat of Pongamia pinnata (Linn.) Pierre in combination with several antibiotics against methicillin-resistant Staphylococcus aureus (MRSA) were tested by broth dilution, checkerboard, and time-kill methods. Results: For the combinations of P. pinnata with ampicillin, meropenem, cefazolin, cefotaxime, cefpirome, and cefuroxime, 70% to 100% were synergistic, with a fractional inhibitory concentration (FIC) index of < 0.5. For the time-kill method with 0.5× minimum inhibitory concentration (MIC) of P. pinnata in combination with 8, 4, 2, and 1 µg mL−1 of the various antibiotics, almost all of the combinations showed synergistic effects, even with the lowest concentrations of P. pinnata, except for aztreonam. No antagonistic effect was observed for these combinations. Conclusions: Based on these findings, aqueous seed coat extracts of P. pinnata have good potential for the design of new antimicrobial agents.

Antimicrobial Activity of Angelica Dahurica Ethanol Extract Against Oral Bacteria

2021 ◽  
Vol 5 (1) ◽  
Keyword(s):  
Antimicrobial Agents ◽  
Synergistic Effects ◽  
Ethanol Extract ◽  
Oral Bacteria ◽  
Antimutagenic Activity ◽  
Angelica Dahurica ◽  
Synergistic Activity ◽  
Protective Activity ◽  
Minimal Inhibitory Concentrations ◽  
Time Kill

Introduction: Angelica dahurica (A. dahurica) has the protective activity against dexamehasone-induced disorders, liver protective activity, antimutagenic activity, anti-inflammatory, anti-microbial, anti-oxidative, anti-asthmatic, and anti-cancer effects. Aims of the Study: This study aimed to investigate the synergistic antibacterial activity with existing antimicrobial agents against oral pathogen. Materials and Methods: The synergistic effects of 50% ethanol extract of A. dahurica (ADEE) were evaluated against oral bacteria, either alone or with antibiotics, via broth microdilution and time-kill method. Results: The minimal inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) values for ADEE, ampicillin and gentamicin against all the tested bacteria ranged between 62.5-1000/250-2000 μg/mL, 0.0625-16/0.25-32 μg/mL, and 4-128/16-256 μg/mL, respectively. The ADEE displayed synergism with ampicillin and gentamicin, with 8-fold reductions in the MIC/MBC. Furthermore, a time-kill study showed that the growth of the tested bacteria was completely attenuated after treatment with 1/2 MIC of ADEE with 1/2 MIC of antibiotics resulted from an increase of the rate of killing in units of CFU/mL to a greater degree than was observed with alone. Discussion and Conclusions: The results of this study demonstrate the antimicrobial and synergistic activity of ADEE and antibiotics against oral pathogens.

scholarly journals A Molecular Insight into the Synergistic Mechanism of Nigella sativa (Black Cumin) with β-Lactam Antibiotics against Clinical Isolates of Methicillin-Resistant Staphylococcus aureus

2021 ◽  
Vol 11 (7) ◽  
pp. 3206
Author(s):  
Lorina I. Badger-Emeka ◽  
Promise Madu Emeka ◽  
Hairul Islam M. Ibrahim
Keyword(s):  
Staphylococcus Aureus ◽  
Mechanism Of Action ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Nigella Sativa ◽  
Synergistic Effects ◽  
Diffusion Method ◽  
Methicillin Resistant ◽  
Cell Wall Disruption ◽  
Time Kill ◽  
Insight Into

Methicillin-resistant Staphylococcus aureus (MRSA) infection is detrimental to hospitalized patients. With diminishing choices of antibiotics and the worry about resistance to colistin in synergistic combined therapy, there are suggestions for the use of herbal derivatives. This investigation evaluated the synergistic effects of Nigella sativa (NS) in combination with beta-lactam (β-lactam) antibiotics on extreme drug-resistant (XDR) MRSA isolates. NS concentrations of 10, 7.5, 5.0, 2.5, 1.0, and 0.1 µg/mL, alone and in combination with β-lactam antibiotics, were used to determine the antimicrobial susceptibility of MRSA isolates by the well diffusion method. Time–kill assays were performed using a spectrophotometer, with time–kill curves plotted and synergism ascertained by the fractional inhibitory concentration (FIC). Scanning and transmission electron microscopy were used to gain insight into the mechanism of action of treated groups. Isolates were inhibited by the NS concentrations, with differences in the zones of inhibition being statistically insignificant at p < 0.05. There were statistically significant differences in the time–kill assay for the MRSA isolates. In addition, NS combined with augmentin showed better killing than oxacillin and cefuroxime. The mechanism of action shown by the SEM and TEM results revealed cell wall disruption, which probably created interference that led to bacterial lysis.

scholarly journals Trans-Cinnamaldehyde Exhibits Synergy with Conventional Antibiotic against Methicillin-Resistant Staphylococcus aureus

2021 ◽  
Vol 22 (5) ◽  
pp. 2752
Author(s):  
Shu Wang ◽  
Ok-Hwa Kang ◽  
Dong-Yeul Kwon
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Synergistic Effects ◽  
Regulatory Gene ◽  
Western Blot Assay ◽  
Methicillin Resistant ◽  
Wide Range ◽  
Kill Curve ◽  
Conventional Antibiotics ◽  
Time Kill

Methicillin-resistant Staphylococcus aureus (MRSA) is a major nosocomial pathogen worldwide and has acquired multiple resistance to a wide range of antibiotics. Hence, there is a pressing need to explore novel strategies to overcome the increase in antimicrobial resistance. The present study aims to investigate the efficacy and mechanism of plant-derived antimicrobials, trans-cinnamaldehyde (TCA) in decreasing MRSA’s resistance to eight conventional antibiotics. A checkerboard dilution test and time–kill curve assay are used to determine the synergistic effects of TCA combined with the antibiotics. The results indicated that TCA increased the antibacterial activity of the antibiotics by 2-16-fold. To study the mechanism of the synergism, we analyzed the mecA transcription gene and the penicillin-binding protein 2a level of MRSA treated with TCA by quantitative RT-PCR or Western blot assay. The gene transcription and the protein level were significantly inhibited. Additionally, it was verified that TCA can significantly inhibit the biofilm, which is highly resistant to antibiotics. The expression of the biofilm regulatory gene hld of MRSA after TCA treatment was also significantly downregulated. These findings suggest that TCA maybe is an exceptionally potent modulator of antibiotics.

scholarly journals Novel Antibiotic Combinations of Diverse Subclasses for Effective Suppression of Extensively Drug-Resistant Methicillin-Resistant Staphylococcus aureus (MRSA)

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Shumyila Nasir ◽  
Muhammad Sufyan Vohra ◽  
Danish Gul ◽  
Umm E Swaiba ◽  
Maira Aleem ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Clavulanic Acid ◽  
Antimicrobial Agents ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Multidrug Resistant ◽  
Methicillin Resistant ◽  
Development Of Resistance ◽  
Amoxicillin Clavulanic Acid ◽  
Combination Antibiotics ◽  
Time Kill

The emergence of multidrug-resistant pathogens such as methicillin-resistant Staphylococcus aureus (MRSA), the chief etiological agent for a range of refractory infections, has rendered all β-lactams ineffective against it. The treatment process is further complicated with the development of resistance to glycopeptides, primary antibiotics for treatment of MRSA. Antibiotic combination therapy with existing antimicrobial agents may provide an immediate treatment option. Minimum inhibitory concentrations (MICs) of 18 different commercially available antibiotics were determined along with their 90 possible pairwise combinations and 64 triple combinations to filter out 5 best combinations. Time-Kill kinetics of these combinations were then analyzed to find collateral bactericidal combinations which were then tested on other randomly selected MRSA isolates. Among the top 5 combinations including levofloxacin-ceftazidime; amoxicillin/clavulanic acid-tobramycin; amoxicillin/clavulanic acid-cephradine; amoxicillin/clavulanic acid-ofloxacin; and piperacillin/tazobactam-tobramycin, three combinations were found to be collaterally effective. Levofloxacin-ceftazidime acted synergistically in 80% of the tested clinical MRSA isolates. First-line β-lactams of lower generations can be used effectively against MRSA infection when used in combination. Antibiotics other than glycopeptides may still work in combination.

scholarly journals 1588. Delafloxacin Activity Against Staphylococcus aureus with Reduced Susceptibility or Resistance to Methicillin, Vancomycin, Daptomycin, or Linezolid

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S579-S580
Author(s):  
Louis D Saravolatz ◽  
Joan Pawlak
Keyword(s):  
Antimicrobial Agents ◽  
Minimal Bactericidal Concentration ◽  
Limited Data ◽  
Methicillin Resistant ◽  
Mueller Hinton ◽  
Spectrum Activity ◽  
Resistant Strains ◽  
Gram Negative Organisms ◽  
Mueller Hinton Broth ◽  
Broad Spectrum Activity

Abstract Background Delafloxacin is a recently approved anionic fluoroquinolone antibiotic with broad-spectrum activity against Gram-positive and Gram-negative organisms. The drug has been approved for patients with acute bacterial skin and skin structure infections including those caused by methicillin-resistant S. aureus. There is limited data available against methicillin-resistant S. aureus blood isolates (MRSABI), vancomycin intermediate strains (VISA), vancomycin-resistant strains (VRSA), daptomycin non-susceptible strains (DNSSA) and linezolid-resistant S. aureus (LRSA). Methods Antimicrobial activity of delafloxacin, levofloxacin, vancomycin, daptomycin, ceftaroline, and linezolid was determined against recent (2016–2018) MRSABI (110), VRSA (15), VISA (35), DNSSA (40), and LRSA (6). Broth microdilution testing using Mueller–Hinton broth was used to determine minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) according to CLSI guidelines. FDA breakpoints were used to determine delafloxacin susceptibility, and CLSI breakpoints were used for all other antibiotics. Results Antimicrobial MIC90 expressed in mg/L and (% susceptible) None of the LRSA were susceptible to delafloxacin or levofloxacin. All strains that were susceptible to the antimicrobial agents above had an MBC that was the same as the MIC or one dilution greater except for linezolid which demonstrated an MBC that was more than eight-fold greater than the MIC. For MRSABI isolates with a levofloxacin MIC ≥ 8 mg/L (55/110) suggesting multiple mutations in the quinolone-resistant determining region, the delafloxacin MIC90 was 1 mg/L with a 36.4% susceptibility rate. Conclusion Delafloxacin demonstrates superior activity to levofloxacin against recent MRSA blood isolates, VISA, VRSA, and DNSSA. Disclosures All authors: No reported disclosures.

scholarly journals Synergistic Activity of Colistin-Containing Combinations against Colistin-ResistantEnterobacteriaceae

2018 ◽  
Vol 62 (10) ◽  
Author(s):  
Thea Brennan-Krohn ◽  
Alejandro Pironti ◽  
James E. Kirby
Keyword(s):  
Treatment Options ◽  
Multidrug Resistant ◽  
Synergistic Activity ◽  
Gram Negative ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Resistant Strains ◽  
Bacterial Outer Membrane ◽  
Time Kill ◽  
Synergistic Combinations

ABSTRACTResistance to colistin, a polypeptide drug used as an agent of last resort for the treatment of infections caused by multidrug-resistant (MDR) and extensively drug-resistant (XDR) Gram-negative bacteria, including carbapenem-resistantEnterobacteriaceae(CRE), severely limits treatment options and may even transform an XDR organism into one that is pan-resistant. We investigated the synergistic activity of colistin in combination with 19 antibiotics against a collection of 20 colistin-resistantEnterobacteriaceaeisolates, 15 of which were also CRE. All combinations were tested against all strains using an inkjet printer-assisted digital dispensing checkerboard array, and the activities of those that demonstrated synergy by this method were evaluated against a single isolate in a time-kill synergy study. Eighteen of 19 combinations demonstrated synergy against two or more isolates, and the 4 most highly synergistic combinations (colistin combined with linezolid, rifampin, azithromycin, and fusidic acid) were synergistic against ≥90% of strains. Sixteen of 18 combinations (88.9%) that were synergistic in the checkerboard array were also synergistic in a time-kill study. Our findings demonstrate that colistin in combination with a range of antibiotics, particularly protein and RNA synthesis inhibitors, exhibits synergy against colistin-resistant strains, suggesting that colistin may exert a subinhibitory permeabilizing effect on the Gram-negative bacterial outer membrane even in isolates that are resistant to it. These findings suggest that colistin combination therapy may have promise as a treatment approach for patients infected with colistin-resistant XDR Gram-negative pathogens.

scholarly journals 204. Antagonistic Effect of Colistin on Vancomycin Activity Against Methicillin-Resistant Staphylococcus aureus in in vitro and in vivo Studies

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S120-S121
Author(s):  
Sungim Choi ◽  
Taeeun Kim ◽  
Seongman Bae ◽  
Eunmi Yang ◽  
Su-Jin Park ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Antagonistic Effect ◽  
In Vivo Studies ◽  
Infection Model ◽  
Methicillin Resistant ◽  
Checkerboard Assay ◽  
Mrsa Strains ◽  
Time Kill

Abstract Background There is a concern that the vancomycin MIC of methicillin-resistant Staphylococcus aureus (MRSA) could be increased by concomitant colistin administered against multidrug-resistant gram-negative pathogen. Methods We confirmed the molecular genotypes of MRSA blood isolates collected in a tertiary hospital in Seoul, South Korea, and selected representative strains from the community-associated MRSA strains (CA-MRSA, ST72-SCCmec IV) and hospital-acquired MRSA strains (HA-MRSA, ST5-SCCmec II). USA CA-MRSA (USA300, ST8-SCCmec IV) and MRSA standard strain (ATCC 43300, ST39-SCCmec II) were also used for comparison with representative. We identified changes of the vancomycin MIC in MRSA by colistin exposure in a checkerboard assay and performed a time-kill assay to evaluate the combined effect of vancomycin and colistin on MRSA. In addition, we administered vancomycin, colistin, and combination of two antibiotics, respectively, to a neutropenic murine thigh infection model to evaluate the in vivo antagonistic effect of colistin on vancomycin treatment. Results In the checkerboard assay, all 4 MRSA strains showed a tendency for the vancomycin MIC to increase along with increasing concentrations of colistin. However, the time-kill assay showed the antagonism of vancomycin and colistin only against ST5-MRSA, when vancomycin concentration was 2 times the vancomycin MIC (Figure 1). No antagonism was observed in other strains. In the murine thigh infection model of ST5-MRSA, vancomycin monotherapy showed a significant log CFU reduction compared with a combination of vancomycin and colistin at 24 hours, demonstrating the antagonistic effect of vancomycin and colistin combination (Figure 2). Conclusion This study showed that exposure of colistin to certain MRSA strains may reduce the susceptibility to vancomycin. Combination therapy with vancomycin and colistin for MDR pathogens infections might result in treatment failure for concurrent MRSA infection. Disclosures All authors: No reported disclosures.

scholarly journals In vitro activities of oxazolidinone compounds U100592 and U100766 against Staphylococcus aureus and Staphylococcus epidermidis.

1996 ◽  
Vol 40 (3) ◽  
pp. 799-801 ◽  
Author(s):  
G W Kaatz ◽  
S M Seo
Keyword(s):  
Staphylococcus Aureus ◽  
Staphylococcus Epidermidis ◽  
Inhibitory Activity ◽  
Antimicrobial Agents ◽  
Methicillin Resistant ◽  
Clinical Strains ◽  
Time Kill

The new oxazolidinone antimicrobial agents U100592 and U100766 demonstrated good in vitro inhibitory activity against clinical strains of Staphylococcus aureus and Staphylococcus epidermidis regardless of methicillin susceptibility. Both agents appeared bacteriostatic by time-kill analysis. Stable resistance to low multiples of the MIC of either drug could be produced only in methicillin-resistant S. aureus.

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