scholarly journals Beneficial Influence of Platelets on Antibiotic Efficacy in an In Vitro Model of Staphylococcus aureus-Induced Endocarditis

2004 ◽  
Vol 48 (7) ◽  
pp. 2551-2557 ◽  
Author(s):  
Renee-Claude Mercier ◽  
Robert M. Dietz ◽  
Jory L. Mazzola ◽  
Arnold S. Bayer ◽  
Michael R. Yeaman
Keyword(s):  
Staphylococcus Aureus ◽  
In Vitro Model ◽  
Antimicrobial Effect ◽  
Human Platelets ◽  
Inhibitory Effects ◽  
Activated Platelets ◽  
Vitro Model ◽  
Antibiotic Efficacy ◽  
Chamber Fluid

ABSTRACT Platelets contribute to antimicrobial host defense against infective endocarditis (IE) by releasing platelet microbicidal proteins (PMPs). We investigated the influence of thrombin-stimulated human platelets on the evolution of simulated IE in the presence and absence of vancomycin or nafcillin. Staphylococcus aureus strains differing in intrinsic susceptibility to PMPs or antibiotics were studied: ISP479C (thrombin-induced PMP-1 [tPMP-1] susceptible; nafcillin and vancomycin susceptible), ISP479R (tPMP-1 resistant; nafcillin and vancomycin susceptible), and GISA-NJ (tPMP-1 intermediate-susceptible; vancomycin intermediate-susceptible). Platelets were introduced and thrombin activated within the in vitro IE model 30 min prior to inoculation with S. aureus. At 0 to 24 h postinoculation, bacterial densities in chamber fluid and simulated endocardial vegetations (SEVs) were quantified and compared among groups. Activated platelets alone, or in combination with antibiotics, inhibited the proliferation of ISP479C in chamber fluid or SEVs over the initial 4-h period (P < 0.05 versus controls). Moreover, nafcillin-containing regimens exerted inhibitory effects beyond 4 h against ISP479C in both model phases. By comparison, activated platelets inhibited GISA-NJ proliferation in SEVs but not in chamber fluid. The combination of platelets plus nafcillin or vancomycin significantly inhibited proliferation of the GISA-NJ strain in SEVs compared to the effect of platelets or antibiotics alone (P < 0.05). In contrast, platelets did not significantly alter the antistaphylococcal efficacies of nafcillin or vancomycin against ISP479R. These data support our hypothesis that a beneficial antimicrobial effect may result from the interaction among platelets, PMPs, and anti-infective agents against antibiotic-susceptible or -resistant staphylococci that exhibit a tPMP-1-susceptible or -intermediate-susceptible phenotype.

scholarly journals β-Naphthoflavone and Ethanol Reverse Mitochondrial Dysfunction in A Parkinsonian Model of Neurodegeneration

2020 ◽  
Vol 21 (11) ◽  
pp. 3955
Author(s):  
Jesus Fernandez-Abascal ◽  
Elda Chiaino ◽  
Maria Frosini ◽  
Gavin P. Davey ◽  
Massimo Valoti
Keyword(s):  
Complex I ◽  
In Vitro Model ◽  
Inhibitory Effects ◽  
Cyp Induction ◽  
Cyp Isoforms ◽  
Vitro Model ◽  
Complex I Activity ◽  
Cyp 2D6

The 1-methyl-4-phenylpyridinium (MPP+) is a parkinsonian-inducing toxin that promotes neurodegeneration of dopaminergic cells by directly targeting complex I of mitochondria. Recently, it was reported that some Cytochrome P450 (CYP) isoforms, such as CYP 2D6 or 2E1, may be involved in the development of this neurodegenerative disease. In order to study a possible role for CYP induction in neurorepair, we designed an in vitro model where undifferentiated neuroblastoma SH-SY5Y cells were treated with the CYP inducers β-naphthoflavone (βNF) and ethanol (EtOH) before and during exposure to the parkinsonian neurotoxin, MPP+. The toxic effect of MPP+ in cell viability was rescued with both βNF and EtOH treatments. We also report that this was due to a decrease in reactive oxygen species (ROS) production, restoration of mitochondrial fusion kinetics, and mitochondrial membrane potential. These treatments also protected complex I activity against the inhibitory effects caused by MPP+, suggesting a possible neuroprotective role for CYP inducers. These results bring new insights into the possible role of CYP isoenzymes in xenobiotic clearance and central nervous system homeostasis.

scholarly journals Pharmacodynamics of once- or twice-daily levofloxacin versus vancomycin, with or without rifampin, against Staphylococcus aureus in an in vitro model with infected platelet-fibrin clots.

1996 ◽  
Vol 40 (3) ◽  
pp. 701-705 ◽  
Author(s):  
S M Palmer ◽  
M J Rybak
Keyword(s):  
In Vitro Model ◽  
Area Under The Curve ◽  
Human Platelets ◽  
Inoculum Size ◽  
Human Pharmacokinetics ◽  
Development Of Resistance ◽  
Vitro Model ◽  
Better Than ◽  
Fibrin Clots

We compared the pharmacodynamic activities of levofloxacin versus vancomycin, with or without rifampin, in an in vitro model with infected platelet-fibrin clots simulating vegetations. Infected platelet-fibrin clots were prepared with human cryoprecipitate, human platelets, calcium, thrombin, and approximately 10(9) CFU of organisms (MSSA 1199 and MRSA 494) per g and then were suspended via monofilament line into the in vitro model containing Mueller-Hinton growth medium. Antibiotics were administered by bolus injection into the model to simulate human pharmacokinetics; the regimens simulated included levofloxacin at dosages of 800 mg every 24 h (q24h) and 400 mg q12h, vancomycin at 1 g q12h, and rifampin at 600 mg q24h. Each model was run in duplicate over a 72-h period. Infected platelet-fibrin clots were removed in duplicate from each model, weighed, homogenized, serially diluted with sterile 0.9% saline, and plated on tryptic soy agar plates and plates containing antibiotics at 3, 6, and 12 times the MIC to evaluate the emergence of resistance. Time-kill curves were constructed by plotting the inoculum size versus time. Residual inoculum at 72 h was used to compare regimens. All levofloxacin regimens were significantly better than vancomycin monotherapy against both isolates (P < 0.002). Against MSSA 1199, levofloxacin q24h was significantly better than all other regimens, including levofloxacin q12h (P < 0.002); however, no difference between the levofloxacin monotherapy and combination therapy (with rifampin) regimens against MRSA 494 was seen. Killing activity for levofloxacin appeared to correlate better with the peak/MIC ratio than with the area under the curve/MIC ratio. The addition of rifampin significantly enhanced the activity of vancomycin but had little effect upon the activity of levofloxacin. For MRSA 494, vancomycin plus rifampin resulted in the greatest killing (P < 0.05). Development of resistance was not detected with any regimen. Levofloxacin may be a useful therapeutic alternative in the treatment of staphylococcal endocarditis, and further study with animal models of endocarditis or clinical trials are warranted.

Pharmacokinetically-based prediction of the effects of antibiotic combinations on resistant Staphylococcus aureus mutants: in vitro model studies with linezolid and rifampicin

2016 ◽  
Vol 29 (4) ◽  
pp. 220-226 ◽  
Author(s):  
Alexander A. Firsov ◽  
Maria V. Golikova ◽  
Elena N. Strukova ◽  
Yury A. Portnoy ◽  
Svetlana A. Dovzhenko ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
In Vitro Model ◽  
Model Studies ◽  
Vitro Model

scholarly journals In Vitro Evaluation of the Activities of Telavancin, Cefazolin, and Vancomycin against Methicillin-Susceptible and Methicillin-Resistant Staphylococcus aureus in Peritoneal Dialysate

2007 ◽  
Vol 51 (12) ◽  
pp. 4521-4524 ◽  
Author(s):  
Frances L. Clouse ◽  
Laurie B. Hovde ◽  
John C. Rotschafer
Keyword(s):  
Staphylococcus Aureus ◽  
Peritoneal Dialysis ◽  
In Vitro Model ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Dialysis Fluid ◽  
Methicillin Resistant ◽  
Peritoneal Dialysate ◽  
Peritoneal Dialysis Fluid ◽  
Vitro Model

ABSTRACT This study compared the ability of telavancin to the ability of cefazolin and vancomycin to eliminate staphylococci from peritoneal dialysis fluid by using a static in vitro model to simulate the conditions of peritoneal dialysis. The results showed that telavancin exhibited statistically significantly better kill (P < 0.05) against both methicillin-susceptible and methicillin-resistant Staphylococcus aureus.

scholarly journals Impact of sarA on Antibiotic Susceptibility of Staphylococcus aureus in a Catheter-Associated In Vitro Model of Biofilm Formation

2009 ◽  
Vol 53 (6) ◽  
pp. 2475-2482 ◽  
Author(s):  
Elizabeth C. Weiss ◽  
Horace J. Spencer ◽  
Sonja J. Daily ◽  
Brian D. Weiss ◽  
Mark S. Smeltzer
Keyword(s):  
Staphylococcus Aureus ◽  
Clinical Isolate ◽  
Antimicrobial Susceptibility ◽  
Antibiotic Susceptibility ◽  
Biofilm Formation ◽  
In Vitro Model ◽  
Susceptibility Testing ◽  
Specific Context ◽  
Vitro Model

ABSTRACT Mutation of the staphylococcal accessory regulator (sarA) in Staphylococcus aureus limits but does not abolish the capacity of the organism to form a biofilm. As a first step toward determining whether this limitation is therapeutically relevant, we carried out in vitro studies comparing the relative susceptibility of an S. aureus clinical isolate (UAMS-1) and its isogenic sarA mutant (UAMS-929) in the specific context of a catheter-associated biofilm. The antibiotics tested were daptomycin, linezolid, and vancomycin, all of which were evaluated by using concentrations based on the MIC defined as the breakpoint for a susceptible strain of S. aureus (≤1.0, ≤2.0, and ≤4.0 μg/ml for daptomycin, vancomycin, and linezolid, respectively). Mutation of sarA had no significant impact on the MIC of UAMS-1 for any of the targeted antibiotics, as defined by Etest antimicrobial susceptibility testing. However, mutation of sarA did result in a significant increase in antimicrobial susceptibility to all targeted antibiotics when they were tested in the specific context of a biofilm. Additionally, whether susceptibility was assessed by using UAMS-1 or its sarA mutant, daptomycin was found to be more effective against established S. aureus biofilms than either linezolid or vancomycin.

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