Emergence of dalbavancin non-susceptible, vancomycin-intermediate Staphylococcus aureus (VISA) after treatment of MRSA central line-associated bloodstream infection with a dalbavancin- and vancomycin-containing regimen

Werth, Brian J.; Jain, Rupali; Hahn, Abigail; Cummings, Lisa A.; Weaver, Tatiana; Waalkes, Adam; SenGupta, Dhruba J.; Salipante, Stephen J.; Rakita, Robert M.; Butler-Wu, Susan M.

doi:10.1016/j.cmi.2017.07.028

Cited by 80 publications

(58 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This issue was simulated and confirmed in vitro, although the development of resistance was not clinically important in an experiment involving nasal colonizers in patients treated with oritavancin for unrelated infections 63,64 . On the other hand, at least two cases of significant treatment‐emergent resistance have been reported in the literature for dalbavancin 65,66 …”

Section: Considerations For Selection Of Dalbavancin Versus Oritavancinmentioning

confidence: 90%

Advantages of Outpatient Treatment with Long‐Acting Lipoglycopeptides for Serious Gram‐Positive Infections: A Review

et al. 2020

View full text Add to dashboard Cite

Treatment of serious gram-positive infections presents multiple challenges. Treatment often results in prolonged hospitalization for administration of intravenous antimicrobials and presents an inefficient use of hospital resources. Prolonged hospitalization is typically also unfavorable to patient preferences and potentially subjects patients to additional health care-associated complications. Current strategies of transition to outpatient settings-outpatient parenteral antimicrobial therapy and use of oral antibiotics-often do not adequately serve vulnerable populations for whom there is often no alternative to inpatient therapy. Specifically, people who use drugs, those who cannot reliably adhere to unsupervised treatment (poor mental or physical health), people with complicating life circumstances (e.g., homelessness, incarceration, rural location), and those with inadequate health insurance remain hospitalized for weeks longer than persons without such conditions. We suspected that long-acting lipoglycopeptides (laLGP), such as dalbavancin and oritavancin, may be useful in patient transitions to outpatient settings. Thus, we conducted a search of the peer-reviewed literature using the PubMed, Google Scholar, and MEDLINE databases. Based on accumulating literature, it appears that laLGPs offer a reliable alternative therapeutic strategy that addresses many of the personal and systemic barriers to the traditional transitioning approaches. Current evidence also suggests that these agents may be cost-effective from patient, payer, and hospital perspectives. Barriers to broader use of laLGPs include, among others, a relative lack of prospective data regarding efficacy in serious infections, a narrow United States Food and Drug Administration-approved indication restricted to only acute bacterial skin and skin structure infections, and lack of reimbursement infrastructure for inpatient settings.

show abstract

Section: Considerations For Selection Of Dalbavancin Versus Oritavancinmentioning

confidence: 90%

Advantages of Outpatient Treatment with Long‐Acting Lipoglycopeptides for Serious Gram‐Positive Infections: A Review

et al. 2020

View full text Add to dashboard Cite

show abstract

Section: Introductionmentioning

confidence: 99%

“…To date, in vivo induced lipoglycopeptide resistance was only described in a single S. aureus urine isolate after long-term therapy with vancomycin followed by dalbavancin 8 . Genetic alterations in the yvqF gene were considered to be the most likely cause based on the previously reported implication in a vancomycin resistance pathway 8 , 9 . Other frequently identified mutations found in clinical isolates with reduced glycopeptide susceptibility were graRS , rpoB, vraRS , or walKR which are mostly involved in the biosynthesis or metabolism of the staphylococcal cell wall 10 – 15 .…”

Section: Introductionmentioning

confidence: 99%

Emergence of a dalbavancin induced glycopeptide/lipoglycopeptide non-susceptible Staphylococcus aureus during treatment of a cardiac device-related endocarditis

Kussmann

Karer

Obermueller

et al. 2018

Emerging Microbes & Infections

View full text Add to dashboard Cite

In the present study, we demonstrated the emergence of dalbavancin non-susceptible and teicoplanin-resistant Staphylococcus aureus small colony variants which were selected in vivo through long-term treatment with dalbavancin. A 36-year-old man presented with a cardiac device-related S. aureus endocarditis and received long-term therapy with dalbavancin. Consecutively, two glycopeptide/lipoglycopeptide susceptible and two non-susceptible S. aureus isolates were obtained from blood cultures and the explanted pacemaker wire. The isolates were characterized by: standard typing methods, antimicrobial susceptibility testing, auxotrophic profiling, proliferation assays, scanning and transmission electron microscopy, as well as whole genome sequencing. The isolated SCVs demonstrated a vancomycin-susceptible but dalbavancin non-susceptible and teicoplanin-resistant phenotype whereof the respective MICs of the last isolate were 16- and 84-fold higher than the susceptible strains. All four strains were indistinguishable or at least closely related by standard typing methods (spa, MLST, and PFGE), and whole genome sequencing revealed only eight sequence variants. A consecutive increase in cell wall thickness (up to 2.1-fold), an impaired cell separation with incomplete or multiple cross walls and significantly reduced growth rates were observed in the present study. Therefore, the mutations in pbp2 and the DHH domain of GdpP were identified as the most probable candidates due to their implication in the biosynthesis and metabolism of the staphylococcal cell wall. For the first time, we demonstrated in vivo induced dalbavancin non-susceptible/teicoplanin resistant, but vancomycin and daptomycin susceptible S. aureus SCVs without lipopeptide or glycopeptide pretreatment, thus, indicating the emergence of a novel lipoglycopeptide resistance mechanism.

show abstract

“…Inadequate drug exposure may encourage the selection of resistant subpopulations, 175 providing treatment failure, as was recently reported for dalbavancin 5 . 75 The physicochemical properties leading to improved half-lives compared to vancomycin also leads to different tissue penetration properties, which may result in reduced efficacy in some types of infections, as potentially seen with the failure of dalbavancin in an off-label endocarditis case study. The need for more potent antibiotics that can treat resistant Gram-positive infections, yet maintain a good safety profile, means that new glycopeptide antibiotics will continue to play an important role in the ongoing fight against drug resistant infections into the future.…”

Section: Discussionmentioning

confidence: 99%

“…46 By virtue of its long half-life, concerns 74 have been raised about the potential for resistance to develop during the course of treatment, as there is extended exposure to subtherapeutic levels; the recent emergence of a dalbavancin nonsusceptible VISA strain in a patient with a MRSA central line-associated bloodstream infection supports this hypothesis. 75 …”

Section: Recently Approved Glycopeptidesmentioning

confidence: 99%

Developments in Glycopeptide Antibiotics

et al. 2018

View full text Add to dashboard Cite

Glycopeptide antibiotics (GPAs) are a key weapon in the fight against drug resistant bacteria, with vancomycin still a mainstream therapy against serious Gram-positive infections more than 50 years after it was first introduced. New, more potent semisynthetic derivatives that have entered the clinic, such as dalbavancin and oritavancin, have superior pharmacokinetic and target engagement profiles that enable successful treatment of vancomycin-resistant infections. In the face of resistance development, with multidrug resistant (MDR) S. pneumoniae and methicillin-resistant Staphylococcus aureus (MRSA) together causing 20-fold more infections than all MDR Gram-negative infections combined, further improvements are desirable to ensure the Gram-positive armamentarium is adequately maintained for future generations. A range of modified glycopeptides has been generated in the past decade via total syntheses, semisynthetic modifications of natural products, or biological engineering. Several of these have undergone extensive characterization with demonstrated in vivo efficacy, good PK/PD profiles, and no reported preclinical toxicity; some may be suitable for formal preclinical development. The natural product monobactam, cephalosporin, and β-lactam antibiotics all spawned multiple generations of commercially and clinically successful semisynthetic derivatives. Similarly, next-generation glycopeptides are now technically well positioned to advance to the clinic, if sufficient funding and market support returns to antibiotic development.

show abstract

Emergence of dalbavancin non-susceptible, vancomycin-intermediate Staphylococcus aureus (VISA) after treatment of MRSA central line-associated bloodstream infection with a dalbavancin- and vancomycin-containing regimen

Cited by 80 publications

References 32 publications

Advantages of Outpatient Treatment with Long‐Acting Lipoglycopeptides for Serious Gram‐Positive Infections: A Review

Advantages of Outpatient Treatment with Long‐Acting Lipoglycopeptides for Serious Gram‐Positive Infections: A Review

Emergence of a dalbavancin induced glycopeptide/lipoglycopeptide non-susceptible Staphylococcus aureus during treatment of a cardiac device-related endocarditis

Developments in Glycopeptide Antibiotics

Contact Info

Product

Resources

About