Dalbavancin, Vancomycin and Daptomycin Alone and in Combination with Cefazolin against Resistant Phenotypes of Staphylococcus aureus in a Pharmacokinetic/Pharmacodynamic Model

Abdul‐Mutakabbir, Jacinda C.; Kebriaei, Razieh; Stamper, Kyle; Sheikh, Zain; Maassen, Philip; Lev, Katherine; Rybak, Michael J.

doi:10.3390/antibiotics9100696

Cited by 11 publications

(9 citation statements)

References 36 publications

(44 reference statements)

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“…Several in vitro studies showed the synergistic effect of dalbavancin in combination with ceftaroline, cefazolin, daptomycin, rifampicin, and linezolid in reducing the MIC for MRSA, daptomycin non-susceptible, and heterogeneous VISA strains. [86][87][88][89] However, real-world experiences are limited to a single case report of dalbavancin and linezolid combination therapy for the management of a prosthetic joint infection. 60…”

mentioning

confidence: 99%

Real-World Use of Dalbavancin in the Era of Empowerment of Outpatient Antimicrobial Treatment: A Careful Appraisal Beyond Approved Indications Focusing on Unmet Clinical Needs

Gatti

Andreoni

Pea

et al. 2021

DDDT

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Dalbavancin is a novel, long-acting lipoglycopeptide characterized by a long elimination half-life coupled with excellent in vitro activity against multidrug-resistant Gram-positives. Although it is currently approved only for the treatment of acute bacterial skin and skin structure infections, an ever-growing amount of evidence supports the efficacy of dalbavancin as a long-term therapy in osteomyelitis, prosthetic joint infections, endocarditis, and bloodstream infections. This article provides a critical reappraisal of real-world use of dalbavancin for off-label indications. A search strategy using specific keywords (dalbavancin, osteomyelitis, endocarditis, long-term suppressive therapy, bloodstream infection, pharmacokinetic/pharmacodynamic profile) until April 2021 was performed on the PubMed-MEDLINE database. As for other novel antibiotics, a conundrum between approved indications and potential innovative therapeutic uses has emerged for dalbavancin as well. The promising efficacy in challenging scenarios (i.e., osteomyelitis, endocarditis, prosthetic joint infections), coupled with the unique pharmacokinetic/pharmacodynamic properties, makes dalbavancin a valuable alternative to daily in-hospital intravenous or outpatient antimicrobial regimens in the treatment of long-term Gram-positive infections. This makes dalbavancin valuable in the current COVID-19 scenario, in which hospitalization and territorial medicine empowerment are unavoidable.

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confidence: 99%

Real-World Use of Dalbavancin in the Era of Empowerment of Outpatient Antimicrobial Treatment: A Careful Appraisal Beyond Approved Indications Focusing on Unmet Clinical Needs

Gatti

Andreoni

Pea

et al. 2021

DDDT

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“…Brain heart infusion agar (BHIA; Difco Laboratories, San Jose, CA, USA) supplemented with vancomycin was used to subculture VISA strains to maintain this phenotype. As a result of the calcium-dependent nature of DAP, MHB supplemented with a total of 50 mg/L of calcium was used for susceptibility tests and PK/PD models [ 16 – 18 , 20 ].…”

Section: Methodsmentioning

confidence: 99%

“…The data for DAL in combination with other agents utilized for the treatment of MRSA is minimal; nevertheless, DAL has been shown to have synergistic activity with oxacillin and β-lactams against methicillin-resistant S. aureus and VISA infections [ 16 – 18 ]. The synergy represented here hints at the possibility of DAL being dosed in combination with DAP, allowing for enhanced eradication of bacterial load at higher inoculums.…”

Section: Introductionmentioning

confidence: 99%

Targeting Dalbavancin Inoculum Effect: Adjunctive Single Dose of Daptomycin

Kebriaei,

Abdul-Mutakabbir,

Stamper

et al. 2023

Infect Dis Ther

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Introduction Daptomycin (DAP) has proven to be a viable alternative amid vancomycin resistance; however, the use of DAP post vancomycin treatment has led to the development of DAP non-susceptible (DNS) strains. Dalbavancin (DAL), a novel single-dosed lipoglycopeptide, has shown enhanced activity against highly resistant Staphylococcus aureus strains. However, on the basis of previous reports and our observations, DAL does not demonstrate similar activity at high versus low inoculum levels. Therefore, we hypothesized that addition of DAP even at minimal concentrations (single dose on day 1) will lower the inoculum to the level that can be cleared by dalbavancin. Methods Isolates from methicillin-resistant S. aureus (MRSA)-infected patients with varying susceptibility profiles were evaluated using broth microdilution methods. Two DNS–VISA strains (vancomycin intermediate resistant S. aureus ) and one MRSA strain were further evaluated in a one-compartment PK/PD model using a high starting initial inoculum of 10 9 CFU/mL as well as low initial inoculum of 10 7 CFU/mL over 168 h to assess the activity of DAL and DAP monotherapy and in combination. Results Single therapies were not bactericidal when evaluated in the 168 h in vitro one-compartment model with an initial inoculum of 10 9 ; however, the combination of DAL plus single dose of DAP resulted in enhanced killing at the end of the 168-h exposure. DAL single therapy caused reduction in colony counts down to detection limit (2 log 10 CFU/ml) at a lower inoculum but did not show enhancement (< 2 log 10 CFU/ml) at higher initial inoculums ( P < 0.01) for all three strains. Similarly, DAP caused initial bacterial reduction up to 4 log 10 CFU/ml with regrowth at about 32 h of exposure, which stayed at initial inoculum levels for the duration of the model for all three strains. Conclusions Dalbavancin inoculum effect is a major issue in bacterial infections with high bacterial loads and the combination of DAL plus single dose of DAP showed promise in eradicating resistant S. aureus strains at high inoculums.

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“…Notwithstanding the important (if not essential) value of clinical evaluation, the immediate future for the progression of candidates for MRSA chemotherapy will largely be empirical prioritization. This empirical exploration surely will include further evaluation of β-lactam synergy known additional synergistic pairings identified by in vitro study against multistrain MRSA include ceftaroline-dalbavancin and imipenem-linezolidas well as answers as to whether the lipoglycopeptides (such as dalbavancin and oritavancin) are intrinsically superior to vancomycin ,− or whether fundamentally different approaches to MRSA therapy, such as the use of “metabolism” adjuvants ,− (some as simple as bicarbonate) or lysin (enzymatic) adjuvants. − …”

Section: Against the Fortressmentioning

confidence: 99%

β-Lactams against the Fortress of the Gram-Positive Staphylococcus aureus Bacterium

Fisher

Mobashery

2020

Chem. Rev.

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The biological diversity of the unicellular bacteriawhether assessed by shape, food, metabolism, or ecological nichesurely rivals (if not exceeds) that of the multicellular eukaryotes. The relationship between bacteria whose ecological niche is the eukaryote, and the eukaryote, is often symbiosis or stasis. Some bacteria, however, seek advantage in this relationship. One of the most successfulto the disadvantage of the eukaryoteis the small (less than 1 μm diameter) and nearly spherical Staphylococcus aureus bacterium. For decades, successful clinical control of its infection has been accomplished using β-lactam antibiotics such as the penicillins and the cephalosporins. Over these same decades S. aureus has perfected resistance mechanisms against these antibiotics, which are then countered by new generations of β-lactam structure. This review addresses the current breadth of biochemical and microbiological efforts to preserve the future of the β-lactam antibiotics through a better understanding of how S. aureus protects the enzyme targets of the β-lactams, the penicillin-binding proteins. The penicillin-binding proteins are essential enzyme catalysts for the biosynthesis of the cell wall, and understanding how this cell wall is integrated into the protective cell envelope of the bacterium may identify new antibacterials and new adjuvants that preserve the efficacy of the β-lactams.

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Dalbavancin, Vancomycin and Daptomycin Alone and in Combination with Cefazolin against Resistant Phenotypes of Staphylococcus aureus in a Pharmacokinetic/Pharmacodynamic Model

Cited by 11 publications

References 36 publications

Real-World Use of Dalbavancin in the Era of Empowerment of Outpatient Antimicrobial Treatment: A Careful Appraisal Beyond Approved Indications Focusing on Unmet Clinical Needs

Real-World Use of Dalbavancin in the Era of Empowerment of Outpatient Antimicrobial Treatment: A Careful Appraisal Beyond Approved Indications Focusing on Unmet Clinical Needs

Targeting Dalbavancin Inoculum Effect: Adjunctive Single Dose of Daptomycin

β-Lactams against the Fortress of the Gram-Positive Staphylococcus aureus Bacterium

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