Dataset Information

In Vitro Study To Evaluate the Bioactivity of Freezing a Heparin-Based Dalbavancin Lock Solution.

ABSTRACT: The use of dalbavancin as a catheter lock solution must be addressed in depth before implementation in clinical practice. We assessed whether a heparin-based dalbavancin lock solution could be frozen in single-dose vials for 6 months without affecting its bioactivity against biofilms of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant Staphylococcus epidermidis (MRSE). Over 6 months, we tested the bioactivity of a frozen solution of dalbavancin (≈1 mg/ml) plus heparin (60 IU) in terms of CFU counts and metabolic activity against biofilms of Staphylococcus aureus ATCC 43300 (MRSA) and Staphylococcus epidermidis ATCC 35984 (MRSE). The Anti-Xa assay was also performed to assess whether the anticoagulant activity of heparin was reduced under freezing. Every month, we compared the mean value of each variable with that obtained at baseline (before freezing, month 0) using both clinical criteria (values were within 25% of the baseline value) and statistical criteria (linear mixed models). At the end of the experiment (month 6), neither a clinically nor a statistically significant reduction in the bioactivity of dalbavancin-heparin solution was observed in terms of CFU counts and metabolic activity against biofilm of MRSA. Regarding MRSE, considering the clinical criteria, neither CFU counts nor metabolic activity decreased significantly. However, the reduction was statistically significant for all variables. Anti-Xa values (mean [standard deviation] international units per milliliter) for heparin in combination with dalbavancin were within 25% of the heparin-water value. A heparin-based dalbavancin lock solution can be frozen for up to 6 months with no effect on its bioactivity against MRSA and MRSE biofilms.

SUBMITTER: Rubia M

PROVIDER: S-EPMC7674050 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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In Vitro Study To Evaluate the Bioactivity of Freezing a Heparin-Based Dalbavancin Lock Solution.

Rubia Marta M Cordero Andrea A Pérez-Granda María Jesús MJ Cercenado Emilia E Pascual Cristina C Muñoz Patricia P Guembe María M

Antimicrobial agents and chemotherapy 20201117 12

The use of dalbavancin as a catheter lock solution must be addressed in depth before implementation in clinical practice. We assessed whether a heparin-based dalbavancin lock solution could be frozen in single-dose vials for 6 months without affecting its bioactivity against biofilms of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant Staphylococcus epidermidis (MRSE). Over 6 months, we tested the bioactivity of a frozen solution of dalbavancin (≈1 mg/ml ...[more]

PMID: 32988823

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Project description:ObjectivesDalbavancin is a lipoglycopeptide active against methicillin-resistant Staphylococcus aureus (MRSA). Its long half-life (8.5-16 days) allows for once-weekly or single-dose treatments but could prolong the mutant selection window, promoting resistance and cross-resistance to related antimicrobials such as vancomycin. The objective of this study was to evaluate the capacity of post-distributional pharmacokinetic exposures of dalbavancin to select for resistance and cross-resistance in MRSA.MethodsWe simulated average, post-distributional exposures of single-dose (1500 mg) dalbavancin (fCmax 9.9 μg/mL, β-elimination t1/2 204 h) in an in vitro pharmacokinetic/pharmacodynamic (PK/PD) model for 28 days (672 h) against five MRSA strains and one methicillin-susceptible strain (MSSA). Samples were collected at least daily, and surviving colonies were enumerated and screened for resistance on drug-free and dalbavancin-supplemented medium respectively. Isolates from resistance screening plates were subjected to whole-genome sequencing (WGS) and susceptibly testing against dalbavancin, vancomycin, daptomycin, and six β-lactams with varying penicillin-binding protein (PBP) affinities.ResultsDalbavancin was bactericidal against most strains for days 1-4 before regrowth of less susceptible subpopulations occurred. Isolates with eight-fold increases in dalbavancin MIC were detected as early as day 4 but increased 64-128-fold in all models by day 28. Vancomycin and daptomycin MICs increased 4-16-fold, exceeding the susceptibly breakpoints for both antibiotics; β-lactam MICs generally decreased by two-to eight-fold, suggesting a dalbavancin-β-lactam seesaw effect, but increased by eight-fold or more in certain isolates. Resistant isolates carried mutations in a variety of genes, most commonly walKR, apt, stp1, and atl.ConclusionsIn our in vitro system, post-distributional dalbavancin exposures selected for stable mutants with reduced susceptibility to dalbavancin, vancomycin, and daptomycin, and generally increased susceptibility to β-lactams in all strains of MRSA tested. The clinical significance of these findings remains unclear, but created an opportunity to genotype a unique collection of dalbavancin-resistant strains for the first time. Mutations involved genes previously associated with vancomycin intermediate susceptibility and daptomycin non-susceptibility, most commonly walKR-associated genes.

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In Vitro Study To Evaluate the Bioactivity of Freezing a Heparin-Based Dalbavancin Lock Solution.

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<i>In Vitro</i> Study To Evaluate the Bioactivity of Freezing a Heparin-Based Dalbavancin Lock Solution.

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