Optimizing the Dosing Regimens of Daptomycin Based on the Susceptible Dose-Dependent Breakpoint against Vancomycin-Resistant Enterococci Infection

Santimaleeworagun, Wichai; Changpradub, Dhitiwat; Thunyaharn, Sudaluck; Hemapanpairoa, Jatapat

doi:10.3390/antibiotics8040245

Cited by 7 publications

(5 citation statements)

References 33 publications

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“…According to the controversial data, further research is needed to determine the role of colistin-based combinations in the management of infections caused by CRAB. Finally, newer antibiotics have been launched for CRAB treatment, including everacycline, cefiderocol, and plazomicin, and they might represent interesting therapeutic options for CRAB infections [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Colistin plus Sulbactam or Fosfomycin against Carbapenem-ResistantAcinetobacter baumannii: Improved Efficacy or Decreased Risk of Nephrotoxicity?

et al. 2021

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Background Acinetobacter baumannii has been recognized as a cause of nosocomial infection. To date, polymyxins, the last-resort therapeutic agents for carbapenem-resistant A. baumannii (CRAB). Thus, the small number of effective antibiotic options against CRAB represents a challenge to human health. This study examined the appropriate dosage regimens of colistin alone or in combination with sulbactam or fosfomycin using Monte Carlo simulation with the aims of improving efficacy and reducing the risk of nephrotoxicity. Materials and Methods Clinical CRAB isolates were obtained from patients admitted to Phramongkutklao Hospital in 2014 and 2015. The minimum inhibitory concentration (MIC) of colistin for each CRAB isolate was determined using the broth dilution method, whereas those of sulbactam and fosfomycin were determined using the agar dilution method. Each drug regimen was simulated using the Monte Carlo technique to calculate the probability of target attainment (PTA) and the cumulative fraction of response (CFR). Nephrotoxicity based on RIFLE (Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease) criteria was indicated by colistin trough concentration exceeding ≥3.3 µg/mL. Results A total of 50 CRAB isolates were included. The MIC 50 and MIC 90 were 64 and 128 µg/mL, respectively, for sulbactam, 256 and 2,048 µg/mL, respectively, for fosfomycin, and 1 and 4 µg/mL, respectively, for colistin. In patients with creatinine clearance of 91 – 130 m/min, the dosing regimens of 180 mg every 12 h and 150 mg every 8 h achieved ≥ 90% of target of the area under the free drug plasma concentration–time curve from 0 to 24 hr ( f AUC24)/MIC ≥25 against isolates MICs of ≤0.25 and ≤0.5 µg/mL, respectively, and their rates of colistin trough concentration more than ≥3.3 µg/mL were 35 and 54%, respectively. Colistin combined with sulbactam or fosfomycin decreased the colistin MIC of CRAB isolates from 1 – 16 µg/mL to 0.0625 – 1 and 0.0625 – 2 µg/mL, respectively. Based on CFR ≥ 90%, no colistin monotherapy regimens in patients with creatinine clearance of 91 – 130 mL/min were effective against all of the studied CRAB isolates. For improving efficacy and reducing the risk of nephrotoxicity, colistin 150 mg given every 12 h together with sulbactam (≥6 g/day) or fosfomycin (≥18 g/day) was effective in patients with creatinine clearance of 91 – 130 mL/min. Additionally, both colistin combination regimens were effective against five colistin-resistant A. baumannii isolates. Conclusion Colistin monotherapy at the maximum recommended dose might not cover some CRAB isolates. Colistin combination therapy appears appropriate for achieving the pharmacokinetic/pharmacodynamic targets of CRAB treatment.

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Section: Discussionmentioning

confidence: 99%

Colistin plus Sulbactam or Fosfomycin against Carbapenem-ResistantAcinetobacter baumannii: Improved Efficacy or Decreased Risk of Nephrotoxicity?

et al. 2021

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“…Despite its good activity against VREs in both the present and previous studies [ 16 - 19 ], tigecycline only has bacteriostatic effects on enterococcal isolates at any concentration exceeding the MIC [ 20 ]. Not surprisingly, antibiotics such as cell wall-targeting agents ( e.g.…”

Section: Discussionmentioning

confidence: 81%

“…This unfavorable tigecycline level was documented by a meta-analysis indicating that patients with baseline bacteremia had a higher risk of mortality [ 23 ]. Daptomycin as alternative option is clinically used for VRE treatment by using the loading and maintenance doses with 8 mg/kg/day determined to be optimal and safe [ 19 ]. Lastly, this study only suggested the possible dose of tigecycline to meet the current PK/PD target.…”

Section: Discussionmentioning

confidence: 99%

Optimizing the Dosing Regimens of Tigecycline against Vancomycin-Resistant Enterococci in the Treatment of Intra-abdominal and Skin and Soft Tissue Infections

et al. 2020

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Tigecycline was previously considered to have activity against vancomycin-resistant Enterococcus (VRE) isolates, but the optimal dose was not clarified. Thus, this study assessed the in vitro activity of tigecycline against clinical VRE isolates to determine its optimal regimens for complicated intra-abdominal (cIAIs) and complicated skin/soft tissue infections (cSSTIs). We used Monte Carlo simulation to calculate the probability of target attainment (PTA) and the cumulative fraction of response for the ratio of the free area under the curve to the minimum inhibitory concentration (MIC) (fAUIC 24), which were 17.9 and 6.9 for treating cSSTIs and cIAIs, respectively. All clinical isolates were Enterococcus faecium. Only a maintenance dose of 200 mg/day tigecycline gave the target attainment of fAUIC 24 >17.9, and PTA exceeded 90% for MIC ≤0.38 µg/mL. Meanwhile, this dose gave the target attainment of fAUIC 24 >6.9, and PTA exceeded 90% for MIC ≤1 µg/mL. All simulated tigecycline dosing regimens met the fAUIC 24 targets more than 90% of the cumulative fraction of response. Despite its apparent efficacy, a daily tigecycline dose of 200 mg is recommended for VRE isolates with MICs of ≤0.38 µg/mL and ≤1 µg/mL for treating cSSTIs and cIAIs, respectively.

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“…Higher rates of microbiological failure and mortality have been reported in BSIs caused by E. faecium strains with daptomycin MIC 3-4 mg/L when treated with daptomycin [20,21]. In fact, two recent studies found that no dose presented an acceptable PTA against a MIC of 4 mg/L in the Monte Carlo simulation [22,23]. When MICs of 2-4 mg/L were analysed, a fixed dose of 1500 mg daily was needed for ≥ 90% PTA, but this dosage carried an undue risk of toxicity as was associated with an increased 24.5-80.5% risk of achieving a Cmin ≥ 24.3 mg/L [24].…”

Section: Discussionmentioning

confidence: 99%

Daptomycin versus Glycopeptides for the Treatment of Enterococcus faecium Bacteraemia: A Cohort Study

Echeverría-Esnal

Sorlí

Prim³

et al. 2021

Antibiotics

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Background: Ampicillin resistant and glycopeptide susceptible Enterococcus faecium bloodstream infection (GSEF-BSI) incidence has risen. However, the treatment of choice remains unknown. Daptomycin use for the treatment of enterococcal infections has increased, despite effectiveness and safety concerns. The objective was to compare the effectiveness and safety of daptomycin and glycopeptides in the treatment of GSEF-BSI. Methods: This was a single-centre, retrospective observational cohort study performed at Hospital del Mar (Barcelona, Spain), from January 2006–May 2018. The primary outcome was clinical cure at the end of the therapy, and secondary outcomes included 14-day, 30-day, in-hospital mortality, and length of stay. Results: From a total of 192 patients with GSEF-BSI, 54 (28.1%) were treated with glycopeptides and 17 (8.9%) with daptomycin. Patients treated with daptomycin presented a lower clinical cure than patients treated with glycopeptides (58.8% vs. 83.3%, RR 0.416 (95% CI 0.189–0.915)). After controlling for confounding variables by means of multivariate analysis the significative difference was confirmed (aOR 4.313, 95% CI, 1.053–17.660). The need for treatment discontinuation due to adverse events was similar. Conclusions: Patients with GSEF-BSI treated with glycopeptides showed a higher clinical cure than those treated with daptomycin.

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Optimizing the Dosing Regimens of Daptomycin Based on the Susceptible Dose-Dependent Breakpoint against Vancomycin-Resistant Enterococci Infection

Cited by 7 publications

References 33 publications

Colistin plus Sulbactam or Fosfomycin against Carbapenem-ResistantAcinetobacter baumannii: Improved Efficacy or Decreased Risk of Nephrotoxicity?

Colistin plus Sulbactam or Fosfomycin against Carbapenem-ResistantAcinetobacter baumannii: Improved Efficacy or Decreased Risk of Nephrotoxicity?

Optimizing the Dosing Regimens of Tigecycline against Vancomycin-Resistant Enterococci in the Treatment of Intra-abdominal and Skin and Soft Tissue Infections

Daptomycin versus Glycopeptides for the Treatment of Enterococcus faecium Bacteraemia: A Cohort Study

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