scholarly journals 1259. Activity of eravacycline against staphylococci isolated from periprosthetic joint infections

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S646-S646
Author(s):  
Georg Zhuchenko ◽  
Suzannah Schmidt-Malan ◽  
Robin Patel ◽  
Robin Patel

Abstract Background Perirosthetic joint infections (PJIs) are costly and difficult to treat. The most common causes of PJIs are Staphylococcus aureus and Staphylococcus epidermidis. Eravacycline is a newer tetracycline with promising activity against Gram-positive and negative bacteria which is approved for treatment of complicated intraabdominal infections. Here, the in vitro activity of eravacycline was assessed against bacteria associated with PJI. Methods 185 staphylococcal isolates, including 38 methicillin-resistant S. aureus (MRSA), 64 methicillin-susceptible S. aureus (MSSA), 62 methicillin-resistant S. epidermidis (MRSE) and 21 methicillin-susceptible S. epidermidis (MSSE) strains were studied. Minimum inhibitory concentrations (MICs) were determined according to Clinical and Laboratory Standards Institute guidelines (range of 0.06-64 µg/ml tested). Results were analyzed using susceptible breakpoints from EUCAST (≤0.25 µg/ml) and the FDA (≤0.06 µg/ml). Minimum biofilm bactericidal concentrations (MBBCs) were determined using a modification of the Calgary biofilm method. Briefly, biofilms were formed on pegged lids in trypticase soy broth, after which the pegged lids were rinsed in phosphate buffered saline (PBS), transferred to a plate containing dilutions of eravacycline in cation-adjusted Mueller Hinton broth (CAMHB) and incubated for 20-24h. Finally, the pegged lids were again rinsed in PBS and transferred to a plate containing CAMHB and incubated for 24h. The MBBC was the lowest concentration with no visible growth. Results MIC50/90 (range) in µg/ml for MRSA, MSSA, MRSE, and MSSE were 0.125/0.125 (≤0.06-0.25), ≤0.06/0.125 (≤0.06-0.25). 0.125/1 (≤0.06-2), and 0.25/1 (≤0.06-1), respectively. Using the EUCAST susceptible breakpoint, 100% of isolates would be considered susceptible, whereas only 54% would be considered susceptible using the FDA breakpoint. MBBC50/90 (range) in µg/ml for MRSA and MSSA were both 8/16 (4-16); for MRSE and MSSE, the values were 4/16 (2-32) and 8/16 (2-32), respectively. Conclusion Our data suggest that the FDA susceptible breakpoint may need re-evaluation. Eravacycline has low anti-staphylococcal biofilm activity. Disclosures Robin Patel, MD, Accelerate Diagnostics (Grant/Research Support)CD Diagnostics (Grant/Research Support)Contrafect (Grant/Research Support)Curetis (Consultant)GenMark Diagnostics (Consultant)Heraeus Medical (Consultant)Hutchison Biofilm Medical Solutions (Grant/Research Support)Merck (Grant/Research Support)Next Gen Diagnostics (Consultant)PathoQuest (Consultant)Qvella (Consultant)Samsung (Other Financial or Material Support, Dr. Patel has a patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic, and a patent on an anti-biofilm substance issued.)Selux Dx (Consultant)Shionogi (Grant/Research Support)Specific Technologies (Consultant)

2007 ◽  
Vol 8 (4) ◽  
pp. 262-267 ◽  
Author(s):  
T.A. Takla ◽  
S.A. Zelenitsky ◽  
L.M. Vercaigne

Purpose This in vitro study tested the effectiveness of a novel 30% ethanol/4% trisodium citrate (TSC) lock solution against the most common pathogens causing hemodialysis catheter-related infections. Methods Clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) (n=4), methicillin-sensitive S. aureus (MSSA) (n=8), methicillin-resistant Staphylococcus epidermidis (MRSE) (n=8), Pseudomonas aeruginosa (n=4) and Escherichia coli (n=4) were tested in duplicate. Bacterial suspensions of each isolate were made in a control solution of normal saline and Mueller-Hinton broth (MHB), and in a lock solution of ethanol 30%, TSC 4% and MHB. Suspensions were incubated at 37 °C for 48 h. Colony counts were determined from samples collected at t=0 h (before exposure to the ethanol/TSC lock), t=1 h (one hour after exposure to the ethanol/TSC lock), t=24 h and t=48 h. To confirm the absence of viable organisms in the lock solution, the remaining volume at 48 h was filtered through a 0.45 μm filter. The filter was rinsed with 15 mL sterile water and plated on tryptic soy agar (TSA). Results All controls demonstrated significant growth over 48 h. In the lock solutions, initial inocula were reduced to 0 viable colonies by t=1 h (6-log kill), and there was no growth at t=24 and 48 h. Filtering of lock solutions also showed no growth. These results were consistent among duplicates of all isolates. Conclusions The 30% ethanol/4% TSC lock solution consistently eradicated MRSA, MSSA, MRSE, P. aeruginosa and E. coli within 1 h of exposure. Experiments are currently underway to test this novel lock solution on preventing biofilm production by these pathogens.


2001 ◽  
Vol 45 (6) ◽  
pp. 1919-1922 ◽  
Author(s):  
Arthur L. Barry ◽  
Peter C. Fuchs ◽  
Steven D. Brown

ABSTRACT The in vitro activity of daptomycin is affected by the concentration of calcium cations in the test medium. Mueller-Hinton broth is currently adjusted to contain 10 to 12.5 mg of magnesium per liter and 20 to 25 mg of calcium per liter, but for testing of daptomycin, greater concentrations of calcium (50 mg/liter) are recommended to better resemble the normal concentration of ionized calcium in human serum. Two levels of calcium were used for broth microdilution tests of 2,789 recent clinical isolates of gram-positive bacterial pathogens. MICs of daptomycin were two- to fourfold lower when the broth contained additional calcium. For most species, however, the percentages of strains that were inhibited by 2.0 μg of daptomycin per ml were essentially identical with the two broth media. Enterococci were the important exception; i.e., 92% were inhibited when tested in calcium-supplemented broth but only 35% were inhibited by 2.0 μg/ml without the additional calcium. This type of information should be considered when selecting criteria for defining in vitro susceptibility to daptomycin.


2015 ◽  
Vol 59 (12) ◽  
pp. 7571-7580 ◽  
Author(s):  
Wei-Tao Jia ◽  
Qiang Fu ◽  
Wen-Hai Huang ◽  
Chang-Qing Zhang ◽  
Mohamed N. Rahaman

ABSTRACTThere is growing interest in biomaterials that can cure bone infection and also regenerate bone. In this study, two groups of implants composed of 10% (wt/wt) teicoplanin (TEC)-loaded borate bioactive glass (designated TBG) or calcium sulfate (TCS) were created and evaluated for their ability to release TECin vitroand to cure methicillin-resistantStaphylococcus aureus(MRSA)-induced osteomyelitis in a rabbit model. When immersed in phosphate-buffered saline (PBS), both groups of implants provided a sustained release of TEC at a therapeutic level for up to 3 to 4 weeks while they were gradually degraded and converted to hydroxyapatite. The TBG implants showed a longer duration of TEC release and better retention of strength as a function of immersion time in PBS. Infected rabbit tibiae were treated by debridement, followed by implantation of TBG or TCS pellets or intravenous injection with TEC, or were left untreated. Evaluation at 6 weeks postimplantation showed that the animals implanted with TBG or TCS pellets had significantly lower radiological and histological scores, lower rates of MRSA-positive cultures, and lower bacterial loads than those preoperatively and those of animals treated intravenously. The level of bone regeneration was also higher in the defects treated with the TBG pellets. The results showed that local TEC delivery was more effective than intravenous administration for the treatment of MRSA-induced osteomyelitis. Borate glass has the advantages of better mechanical strength, more desirable kinetics of release of TEC, and a higher osteogenic capacity and thus could be an effective alternative to calcium sulfate for local delivery of TEC.


1996 ◽  
Vol 40 (11) ◽  
pp. 2671-2672 ◽  
Author(s):  
L Martínez-Martínez ◽  
A Pascual ◽  
K Bernard ◽  
A I Suárez

The in vitro activities of 16 antimicrobial agents against 86 strains of Corynebacterium striatum were evaluated by microdilution using cation-adjusted Mueller-Hinton broth. MICs at which 90% of strains were inhibited were 0.06 microgram/ml for teicoplanin, 1 microgram/ml for vancomycin, 0.03 to 8 micrograms/ml for beta-lactams, 8 micrograms/ml for sparfloxacin, 16 micrograms/ml for ciprofloxacin, 16/304 micrograms/ml for co-trimoxazole (trimethoprim-sulfamethoxazole), 64 micrograms/ml for tetracycline, 128 micrograms/ml for gentamicin, and > 128 micrograms/ml for amikacin, erythromycin, and rifampin.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S579-S580
Author(s):  
Louis D Saravolatz ◽  
Joan Pawlak

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.


2020 ◽  
Vol 64 (5) ◽  
Author(s):  
Selvi C. Ersoy ◽  
Mariam Otmishi ◽  
Vanessa T. Milan ◽  
Liang Li ◽  
Youngju Pak ◽  
...  

ABSTRACT Addition of sodium bicarbonate (NaHCO3) to standard antimicrobial susceptibility testing medium reveals certain methicillin-resistant Staphylococcus aureus (MRSA) strains to be highly susceptible to β-lactams. We investigated the prevalence of this phenotype (NaHCO3 responsiveness) to two β-lactams among 58 clinical MRSA bloodstream isolates. Of note, ∼75% and ∼36% of isolates displayed the NaHCO3 responsiveness phenotype to cefazolin (CFZ) and oxacillin (OXA), respectively. Neither intrinsic β-lactam MICs in standard Mueller-Hinton broth (MHB) nor population analysis profiles were predictive of this phenotype. Several genotypic markers (clonal complex 8 [CC8]; agr I and spa t008) were associated with NaHCO3 responsiveness for OXA.


1976 ◽  
Vol 4 (3) ◽  
pp. 165-175 ◽  
Author(s):  
Jose Ximenes ◽  
Orlando Natale Bassoi ◽  
Jairo Perche de Menezes ◽  
Wilson Fry

The activity of amikacin, gentamicin and kanamycin was tested in vitro against clinical isolates of Pseudomonas aeruginosa. Concentrations of the antibiotics in serum and in saline solution were prepared according to serum levels produced in volunteers 15 minutes, 1, 2, and 6 hours after a single intramuscular injection of 500 mg amikacin, 80 mg gentamicin and 500 mg kanamycin. Following isolation of the Pseudomonas strains in cultures, they were incubated and seeded in Mueller-Hinton broth, then 107 dilutions of the organisms were kept in contact with the prepared antibiotic solutions in serum and in saline solution for three hours, the approximate half-life of the antibiotics in serum. Amikacin was active at concentrations seen six hours post-dose, inhibiting growth in a total of 72·5% of seeded plates. Gentamicin was active for only two hours and inhibited growth in 2·5% of the plates. Kanamycin showed no anti-pseudomonal activity.


2003 ◽  
Vol 47 (12) ◽  
pp. 3764-3767 ◽  
Author(s):  
Elizabeth D. Hermsen ◽  
Laurie B. Hovde ◽  
John R. Hotchkiss ◽  
John C. Rotschafer

ABSTRACT Peritoneal dialysate fluid (PDF) is a bacteriostatic medium that compromises the antibacterial activity of cell wall-active agents. By use of an in vitro static model, methicillin-resistant Staphylococcus aureus (MRSA), methicillin-susceptible S. aureus (MSSA), methicillin-susceptible Staphylococcus epidermidis (MSSE), and Streptococcus sanguis were exposed to daptomycin at concentrations of 10, 30, and 100 mg/liter, cefazolin at 125 mg/liter, and vancomycin at 25 mg/liter in cation-adjusted Mueller-Hinton Broth or Todd Hewitt Broth (for S. sanguis) and PDF at pHs of 5.5 and 7.4. The pH had no effect on antibacterial activity. Neither cefazolin nor vancomycin produced a bactericidal or a bacteriostatic effect versus MRSA, MSSA, MSSE, or S. sanguis in PDF, while all concentrations of daptomycin were bactericidal against all organisms in PDF. Daptomycin did not exhibit concentration-dependent activity in PDF. Daptomycin appears to be a promising agent for use in peritoneal dialysis-associated peritonitis, producing bacterial kill to a greater extent and at a higher rate than cefazolin or vancomycin in PDF.


Author(s):  
Nisheeth C. Desai ◽  
Bonny Y. Patel ◽  
Bharti P. Dave

The present study is in the interest of some synthesized novel derivatives containing 4-(1,3-diphenyl-1H-pyrazol-4-yl)-N-(morpholinomethyl)-6-arylpyrimidin-2-amines pooled with different bio-active heterocycles such as pyrazole, pyrimidine and morpholine derivatives. The structures of newly synthesized compounds were elucidated by IR, 1H NMR, 13C NMR and mass spectral data. The synthesized compounds were evaluated for their in vitro antimicrobial activity against different bacterial and fungal strains using Mueller-Hinton Broth dilution method. On the basis of SAR studies, it was observed that the presence of electron withdrawing groups remarkably enhanced the antimicrobial activity of synthesized compounds.


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