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

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.

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.


Antibiotics ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 128 ◽  
Author(s):  
Ainal Mardziah Che Hamzah ◽  
Chew Chieng Yeo ◽  
Suat Moi Puah ◽  
Kek Heng Chua ◽  
Ching Hoong Chew

Staphylococcus aureus is an important nosocomial pathogen and its multidrug resistant strains, particularly methicillin-resistant S. aureus (MRSA), poses a serious threat to public health due to its limited therapeutic options. The increasing MRSA resistance towards vancomycin, which is the current drug of last resort, gives a great challenge to the treatment and management of MRSA infections. While vancomycin resistance among Malaysian MRSA isolates has yet to be documented, a case of vancomycin resistant S. aureus has been reported in our neighboring country, Indonesia. In this review, we present the antimicrobial resistance profiles of S. aureus clinical isolates in Malaysia with data obtained from the Malaysian National Surveillance on Antimicrobial Resistance (NSAR) reports as well as various peer-reviewed published records spanning a period of nearly three decades (1990–2017). We also review the clonal types and characteristics of Malaysian S. aureus isolates, where hospital-associated (HA) MRSA isolates tend to carry staphylococcal cassette chromosome mec (SCCmec) type III and were of sequence type (ST)239, whereas community-associated (CA) isolates are mostly SCCmec type IV/V and ST30. More comprehensive surveillance data that include molecular epidemiological data would enable further in-depth understanding of Malaysian S. aureus isolates.


2016 ◽  
Vol 54 (9) ◽  
pp. 2225-2232 ◽  
Author(s):  
Matthew P. Crotty ◽  
Tamara Krekel ◽  
Carey-Ann D. Burnham ◽  
David J. Ritchie

The growing problem of antimicrobial resistance among bacterial pathogens, including methicillin-resistantStaphylococcus aureus(MRSA) and vancomycin-resistant enterococci (VRE), has reached a critical state. Tedizolid phosphate, dalbavancin, and oritavancin have recently been approved by the U.S. Food and Drug Administration (FDA) for the treatment of acute bacterial skin and skin structure infections (ABSSSI) and represent the next generation of oxazolidinones and lipoglycopeptides. All three agents exhibitin vitroactivity and clinical efficacy against MRSA. Tedizolid phosphate and oritavancin demonstratein vitroactivity against VRE. These new Gram-positive agents are reviewed here.


2013 ◽  
Vol 57 (9) ◽  
pp. 4547-4550 ◽  
Author(s):  
Louis D. Saravolatz ◽  
Joan Pawlak ◽  
Stephanie N. Saravolatz ◽  
Leonard B. Johnson

ABSTRACTRetapamulin and six other antimicrobial agents were evaluated against 155 methicillin-resistantStaphylococcus aureus(MRSA) isolates, including strains resistant to vancomycin, linezolid, daptomycin, and mupirocin by microdilution tests. Time-kill assays were performed against representative MRSA, vancomycin-intermediateS. aureus(VISA), and vancomycin-resistantS. aureus(VRSA) isolates. Retapamulin and mupirocin demonstrated MIC90s of 0.12 μg/ml and 8 μg/ml, respectively, with resistance seen in 2.6% and 10% of isolates, respectively. Retapamulin maintained good activity against 94% (15/16) of mupirocin-resistant isolates.


2011 ◽  
Vol 55 (7) ◽  
pp. 3631-3634 ◽  
Author(s):  
David J. Farrell ◽  
Lisa C. Liverman ◽  
Douglas J. Biedenbach ◽  
Ronald N. Jones

ABSTRACTJNJ-Q2 is a broad-spectrum bactericidal fluoroquinolone with potent activity against Gram-positive and -negative pathogens. In this study, thein vitroactivity of JNJ-Q2 was evaluated against 511 selectedStaphylococcus aureussamples isolated in 2008-2009 from patients with acute bacterial skin and skin structure infections in the United States by using reference methodology. JNJ-Q2 was the most potent fluoroquinolone tested overall (MIC50and MIC90, 0.12 and 0.5 μg/ml, respectively) and against methicillin- and fluoroquinolone-resistant subgroups in direct comparisons to moxifloxacin, levofloxacin, and ciprofloxacin (each being ≥16-fold less potent than JNJ-Q2).


2010 ◽  
Vol 54 (12) ◽  
pp. 5369-5371 ◽  
Author(s):  
Adam Belley ◽  
Geoffrey A. McKay ◽  
Francis F. Arhin ◽  
Ingrid Sarmiento ◽  
Sylvain Beaulieu ◽  
...  

ABSTRACT Oritavancin is an investigational lipoglycopeptide in clinical development for the treatment of acute bacterial skin and skin structure infections. In this study, we demonstrate that oritavancin causes bacterial membrane depolarization and permeabilization leading to cell death of Gram-positive pathogens and that these effects are attributable to the 4′-chlorobiphenylmethyl group of the molecule.


2021 ◽  
Vol 12 ◽  
Author(s):  
Adam B. Shapiro ◽  
Samir H. Moussa ◽  
Sarah M. McLeod ◽  
Thomas Durand-Réville ◽  
Alita A. Miller

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.


2008 ◽  
Vol 52 (4) ◽  
pp. 1221-1229 ◽  
Author(s):  
Michael J. Noto ◽  
Paige M. Fox ◽  
Gordon L. Archer

ABSTRACT Treatment of infections caused by Staphylococcus aureus is often confounded by the bacterium's ability to develop resistance to chemotherapeutic agents. Methicillin-resistant S. aureus (MRSA) arises through the acquisition of staphylococcal chromosomal cassette mec (SCCmec), a genomic island containing the methicillin resistance determinant, mecA. In contrast, resistance to vancomycin can result from exposure to the drug, a mechanism that is not dependent upon a gene acquisition event. Here we describe three MRSA strains that became resistant to vancomycin during passage in the presence of increasing concentrations of the drug. In each case two derivative strains were isolated, one that had lost mecA and one that retained mecA during passage. Strain 5836VR lost mecA by the site-specific chromosomal excision of SCCmec, while the other two strains (strains 3130VR and VP32) deleted portions of their SCCmec elements in a manner that appeared to involve IS431. Conversion to vancomycin resistance caused a decrease in the growth rate that was partially compensated for by the deletion of mecA. In mixed-culture competition experiments, vancomycin-resistant strains that lacked mecA readily outcompeted their mecA-containing counterparts, suggesting that the loss of mecA during conversion to vancomycin resistance was advantageous to the organism.


2004 ◽  
Vol 48 (8) ◽  
pp. 3043-3050 ◽  
Author(s):  
Sharath S. Hegde ◽  
Noe Reyes ◽  
Tania Wiens ◽  
Nicole Vanasse ◽  
Robert Skinner ◽  
...  

ABSTRACT Telavancin (TD-6424) is a novel lipoglycopeptide that produces rapid and concentration-dependent killing of clinically relevant gram-positive organisms in vitro. The present studies evaluated the in vivo pharmacodynamics of telavancin in the mouse neutropenic thigh (MNT) and mouse subcutaneous infection (MSI) animal models. Pharmacokinetic-pharmacodynamic studies in the MNT model demonstrated that the 24-h area under the concentration-time curve (AUC)/MIC ratio was the best predictor of efficacy. Telavancin produced dose-dependent reduction of thigh titers of several organisms, including methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA), penicillin-susceptible and -resistant strains of Streptococcus pneumoniae, and vancomycin-resistant Enterococcus faecalis. The 50% effective dose (ED50) estimates for telavancin ranged from 0.5 to 6.6 mg/kg of body weight (administered intravenously), and titers were reduced by up to 3 log10 CFU/g from pretreatment values. Against MRSA ATCC 33591, telavancin was 4- and 30-fold more potent (on an ED50 basis) than vancomycin and linezolid, respectively. Against MSSA ATCC 13709, telavancin was 16- and 40-fold more potent than vancomycin and nafcillin, respectively. Telavancin, vancomycin, and linezolid were all efficacious and more potent against MRSA ATCC 33591 in the MSI model compared to the MNT model. This deviation in potency was, however, disproportionately greater for vancomycin and linezolid than for telavancin, suggesting that activity of telavancin is less affected by the immune status. The findings of these studies collectively suggest that once-daily dosing of telavancin may provide an effective approach for the treatment of clinically relevant infections with gram-positive organisms.


2017 ◽  
Vol 61 (9) ◽  
Author(s):  
Timothy E. Long

ABSTRACT Thiram and disulfiram were evaluated as antibacterial agents against multidrug-resistant Staphylococcus aureus. Against a 30-member panel comprised of vancomycin-susceptible, vancomycin-intermediate, and vancomycin-resistant S. aureus strains, the MIC90 values of the respective test agents were 4 and 16 μg/ml. Additional analyses revealed that thiram and disulfiram are rapid-acting bacteriostatic agents with narrow, Gram-positive-bacterium spectrum activity. Synergy studies further determined that disulfiram increases the vancomycin susceptibility of three clinical vancomycin-resistant S. aureus strains in vitro, thus establishing a potential use in combination therapy.


Sign in / Sign up

Export Citation Format

Share Document