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.

Delafloxacin activity against Staphylococcus aureus with reduced susceptibility or resistance to methicillin, vancomycin, daptomycin or linezolid

2020 ◽  
Vol 75 (9) ◽  
pp. 2605-2608
Author(s):  
Louis D Saravolatz ◽  
Joan M Pawlak ◽  
Corinne Wegner
Keyword(s):  
Staphylococcus Aureus ◽  
Good Activity ◽  
Limited Data ◽  
Skin Structure ◽  
Spectrum Activity ◽  
Resistant Strains ◽  
Vancomycin Resistant ◽  
Gram Negative Organisms ◽  
Susceptibility Rate ◽  
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 MRSA. There are limited data available against MRSA blood isolates (MRSABIs), vancomycin-intermediate strains (VISA), vancomycin-resistant strains (VRSA), daptomycin-non-susceptible strains (DNSSA) and linezolid-resistant Staphylococcus aureus (LRSA). Methods Antimicrobial activity of delafloxacin, levofloxacin, vancomycin, daptomycin and linezolid was determined against 110 MRSABIs, 15 VRSA, 35 VISA, 40 DNSSA and 6 LRSA. Microdilution testing using CAMHB was used to determine MIC according to CLSI guidelines. FDA breakpoints were used to determine delafloxacin susceptibility, and CLSI breakpoints were used for all other antibiotics. PCR testing for molecular markers was performed. Results Delafloxacin demonstrated activity against MRSABIs with an MIC90 of 1 mg/L and 68% susceptibility. Against the other groups the MIC90 and susceptibility were 1 mg/L and 40%, respectively, for VISA, 4 mg/L and 7% for VRSA and 1 mg/L and 38% for DNSSA. None of the LRSA isolates was susceptible to delafloxacin. Delafloxacin was active against 94% of MRSA blood isolates that were genotype SCC IVa. For MRSABIs with a levofloxacin MIC ≥8 mg/L (55/110), suggesting multiple mutations in the QRDR, delafloxacin MIC90 was 1 mg/L with a 36.4% susceptibility rate. Conclusions Delafloxacin demonstrates superior activity to levofloxacin against recent MRSA blood isolates, VISA, VRSA and DNSSA, and demonstrates good activity against blood isolates most commonly found in the community.

Antimicrobial Peptides: A Promising Avenue for Human Healthcare

2020 ◽  
Vol 21 (2) ◽  
pp. 90-96 ◽  
Author(s):  
Girish M. Bhopale
Keyword(s):  
Antimicrobial Peptides ◽  
Antimicrobial Peptide ◽  
Antimicrobial Agents ◽  
Current Status ◽  
Antimicrobial Drugs ◽  
Spectrum Activity ◽  
Low Levels ◽  
Human Healthcare ◽  
Broad Spectrum Activity ◽  
Promising Avenue

Antimicrobial drugs resistant microbes have been observed worldwide and therefore alternative development of antimicrobial peptides has gained interest in human healthcare. Enormous progress has been made in the development of antimicrobial peptide during the last decade due to major advantages of AMPs such as broad-spectrum activity and low levels of induced resistance over the current antimicrobial agents. This review briefly provides various categories of AMP, their physicochemical properties and mechanism of action which governs their penetration into microbial cell. Further, the recent information on current status of antimicrobial peptide development, their applications and perspective in human healthcare are also described.

Effect of Ethanol/Trisodium Citrate Lock on Microorganisms Causing Hemodialysis Catheter-Related Infections

2007 ◽  
Vol 8 (4) ◽  
pp. 262-267 ◽  
Author(s):  
T.A. Takla ◽  
S.A. Zelenitsky ◽  
L.M. Vercaigne
Keyword(s):  
In Vitro Study ◽  
Trisodium Citrate ◽  
Methicillin Resistant ◽  
Hemodialysis Catheter ◽  
E Coli ◽  
Lock Solution ◽  
Mueller Hinton ◽  
Mueller Hinton Broth ◽  
Made In

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.

scholarly journals Antimicrobial susceptibility pattern of Corynebacterium striatum.

1996 ◽  
Vol 40 (11) ◽  
pp. 2671-2672 ◽  
Author(s):  
L Martínez-Martínez ◽  
A Pascual ◽  
K Bernard ◽  
A I Suárez
Keyword(s):  
Antimicrobial Susceptibility ◽  
Antimicrobial Agents ◽  
Susceptibility Pattern ◽  
Beta Lactams ◽  
Antimicrobial Susceptibility Pattern ◽  
Mueller Hinton ◽  
Corynebacterium Striatum ◽  
Mueller Hinton Broth

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.

scholarly journals Scope and Predictive Genetic/Phenotypic Signatures of Bicarbonate (NaHCO3) Responsiveness and β-Lactam Sensitization in Methicillin-Resistant Staphylococcus aureus

2020 ◽  
Vol 64 (5) ◽  
Author(s):  
Selvi C. Ersoy ◽  
Mariam Otmishi ◽  
Vanessa T. Milan ◽  
Liang Li ◽  
Youngju Pak ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Clonal Complex ◽  
Population Analysis ◽  
Methicillin Resistant ◽  
Content Type ◽  
Mueller Hinton ◽  
Testing Medium ◽  
Mrsa Strains ◽  
Mueller Hinton Broth

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.

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 Durlobactam, a New Diazabicyclooctane β-Lactamase Inhibitor for the Treatment of Acinetobacter Infections in Combination With Sulbactam

2021 ◽  
Vol 12 ◽  
Author(s):  
Adam B. Shapiro ◽  
Samir H. Moussa ◽  
Sarah M. McLeod ◽  
Thomas Durand-Réville ◽  
Alita A. Miller
Keyword(s):  
First Generation ◽  
Multidrug Resistant ◽  
Class A ◽  
Carbapenem Resistant ◽  
Medical Need ◽  
Spectrum Activity ◽  
Resistant Strains ◽  
Direct Acting ◽  
Lactamase Inhibitor ◽  
Broad Spectrum Activity

Durlobactam is a new member of the diazabicyclooctane class of β-lactamase inhibitors with broad spectrum activity against Ambler class A, C, and D serine β-lactamases. Sulbactam is a first generation β-lactamase inhibitor with activity limited to a subset of class A enzymes that also has direct-acting antibacterial activity against Acinetobacter spp. The latter feature is due to sulbactam’s ability to inhibit certain penicillin-binding proteins, essential enzymes involved in bacterial cell wall synthesis in this pathogen. Because sulbactam is also susceptible to cleavage by numerous β-lactamases, its clinical utility for the treatment of contemporary Acinetobacter infections is quite limited. However, when combined with durlobactam, the activity of sulbactam is effectively restored against these notoriously multidrug-resistant strains. This sulbactam-durlobactam combination is currently in late-stage development for the treatment of Acinectobacter infections, including those caused by carbapenem-resistant isolates, for which there is a high unmet medical need. The following mini-review summarizes the molecular drivers of efficacy of this combination against this troublesome pathogen, with an emphasis on the biochemical features of each partner.

scholarly journals Efficacy and Safety of Levonadifloxacin in the Management of Community-Acquired Bacterial Pneumonia (CABP): Findings of a Retrospective, Real-World, Multi-centre Study

2021 ◽  
Vol 6 (12) ◽  
pp. 919-925
Author(s):  
Dr. Prahlad Prabhudesai ◽  
Dr. Ashish Jain ◽  
Dr. Prashant Borade ◽  
Dr. Abhijeet Khandelwal ◽  
Kapil Mehta ◽  
...  
Keyword(s):  
Real World ◽  
Bacterial Pneumonia ◽  
Antimicrobial Agents ◽  
Global Public Health ◽  
Efficacy And Safety ◽  
Multi Centre Study ◽  
Healthcare Facilities ◽  
Post Marketing ◽  
Spectrum Activity ◽  
Broad Spectrum Activity

Background: Community-acquired bacterial pneumonia (CABP) remains a global public health threat and is a leading cause of hospitalization and infection-linked mortality. Levonadifloxacin is a novel benzoquinolizine antibiotic with a broad-spectrum activity including methicillin-resistant Staphylococcus aureus (MRSA) and CABP-pathogens. Methods: This multi-centre, retrospective, post-marketing, real-world study assessed the efficacy and safety of levonadifloxacin oral and/or intravenous therapy in the treatment of CABP. Data from 338 patients above 17 years-of-age who received levonadifloxacin (oral or intravenous or both) was collected from 89 healthcare facilities across India. Information on clinical condition, comorbidities, complications, and details of concurrent therapy (including antimicrobial agents) was also collected. Study outcomes were clinical and microbial success at the end of therapy while safety was assessed based on clinical and laboratory adverse events. Results: Of the 338 patients, 244 (72.2%) were male, 93 (27.5%) were female and 1 (0.43%) was a transgender. About 294 (87.0%) patients were hospital-treated and 44 (13%) received outpatient treatment. About 248 (73.4%) patients received intravenous levonadifloxacin treatment, 79 (23.4%) received oral and 11 (3.3%) received intravenous followed by oral levonadifloxacin therapy. The common comorbid conditions were diabetes (14.2%) and hypertension (8.6%). Mean duration of levonadifloxacin therapy was 6.4 days. Clinical and microbial success in levonadifloxacin-treated patients was 95.0% (321/388) and 96.8% (150/155), respectively. Conclusions: Levonadifloxacin showed promising clinical outcomes and safety when used as an intravenous and/or oral for the treatment of CABP, both in outpatients as well as hospitalized patients.

scholarly journals In VivoPharmacodynamic Study of Cefiderocol, a Novel Parenteral Siderophore Cephalosporin, in Murine Thigh and Lung Infection Models

2019 ◽  
Vol 63 (9) ◽  
Author(s):  
Rio Nakamura ◽  
Tsukasa Ito-Horiyama ◽  
Miki Takemura ◽  
Shinsuke Toba ◽  
Shuhei Matsumoto ◽  
...  
Keyword(s):  
Lung Infection ◽  
Infection Model ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Mueller Hinton ◽  
Infection Models ◽  
Resistant Strains ◽  
The Mean ◽  
Mueller Hinton Broth

ABSTRACTThe pharmacokinetic (PK) and pharmacodynamic (PD) parameters which correlated with thein vivoefficacy of cefiderocol were evaluated using neutropenic murine thigh and lung infection models in which the infections were caused by a variety of Gram-negative bacilli. The dose fractionation study using the thigh infection model in which the infection was caused byPseudomonas aeruginosashowed that the cumulative percentage of a 24-h period that the free drug concentration in plasma exceeds the MIC (%fT>MIC) rather than the free peak level divided by the MIC (fCmax/MIC) and the area under the free concentration-time curve over 24 h divided by the MIC (fAUC/MIC) was the PK/PD parameter that best correlated with efficacy. The study with multiple carbapenem-resistant strains revealed that the %fT>MICdetermined in iron-depleted cation-adjusted Mueller-Hinton broth (ID-CAMHB) better reflected thein vivoefficacy of cefiderocol than the %fT>MICdetermined in cation-adjusted Mueller-Hinton broth (CAMHB). The mean %fT>MICof cefiderocol required for a 1-log10reduction against 10 strains ofEnterobacteriaceaeand 3 strains ofPseudomonas aeruginosain the thigh infection models were 73.3% and 77.2%, respectively. The mean %fT>MICforEnterobacteriaceae,P. aeruginosa,Acinetobacter baumannii, andStenotrophomonas maltophiliain the lung infection model were 64.4%, 70.3%, 88.1%, and 53.9%, respectively. These results indicate that cefiderocol has potent efficacy against Gram-negative bacilli, including carbapenem-resistant strains, irrespective of the bacterial species, in neutropenic thigh and lung infection models and that thein vivoefficacy correlated with thein vitroMIC under iron-deficient conditions.

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
Keyword(s):  
Research Support ◽  
Methicillin Resistant ◽  
Joint Infections ◽  
Mueller Hinton ◽  
Common Causes ◽  
Visible Growth ◽  
Phosphate Buffered Saline ◽  
Mueller Hinton Broth ◽  
Intraabdominal Infections

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)

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