Optimal tigecycline dosage regimen is urgently needed: results from a pharmacokinetic/pharmacodynamic analysis of tigecycline by Monte Carlo simulation

Xie, Jiao; Wang, Taotao; Sun, Jing; Chen, Siying; Cai, Jie; Zhang, Weipeng; Dong, Haiyan; Hu, Sasa; Zhang, Di; Wang, Xue; Dong, Yalin

doi:10.1016/j.ijid.2013.09.008

Cited by 47 publications

(26 citation statements)

References 39 publications

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“…However, studies conducted over 24 h were unable to ascertain whether the suppression of resistant bacterial subpopulations is sustained beyond 24 h at the studied concentrations. In an attempt to optimise tigecycline regimens, Xie et al concluded that the clinical effectiveness of current standard tigecycline dosing was less than adequate given the continued resistance and reduced AUC in vivo against MDR A. baumannii strains with enhanced MICs [15]. Therefore, bacterial density and duration of in vitro studies are important to consider when evaluating these polymyxin combinations.…”

Section: Discussionmentioning

confidence: 99%

Combinatorial pharmacodynamics of polymyxin B and tigecycline against heteroresistant Acinetobacter baumannii

Rao

Ly²,

Diep

et al. 2016

International Journal of Antimicrobial Agents

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The prevalence of heteroresistant Acinetobacter baumannii is increasing. Infections due to these resistant pathogens pose a global treatment challenge. Here, the pharmacodynamic activities of polymyxin B (PMB) (2–20 mg/L) and tigecycline (0.15–4 mg/L) were evaluated as monotherapy and in combination using a 4 × 4 concentration array against two carbapenem-resistant and polymyxin-heteroresistant A. baumannii isolates. Time Kill Experiments was employed at starting inocula of 106 and 108 CFU/mL over 48 h. Clinically relevant combinations of PMB (2 mg/L) and tigecycline (0.90 mg/L) resulted in greater reductions in the bacterial population compared with polymyxin alone by 8 h (ATCC 19606, −6.38 vs. −3.43 log10 CFU/mL; FADDI AB115, −1.38 vs. 2.08 log10 CFU/mL). At 10× the clinically achievable concentration (PMB 20 mg/L in combination with tigecycline 0.90 mg/L), there was bactericidal activity against FADDI AB115 by 4 h that was sustained until 32 h, and against ATCC 19606 that was sustained for 48 h. These studies show that aggressive polymyxin-based dosing in combination with clinically achievable tigecycline concentrations results in early synergistic activity that is not sustained beyond 8 h, whereas combinations with higher tigecycline concentrations result in sustained bactericidal activity against both isolates at both inocula. These results indicate a need for optimised front-loaded polymyxin-based combination regimens that utilise high polymyxin doses at the onset of treatment to achieve good pharmacodynamic activity whilst minimising adverse events.

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Section: Discussionmentioning

confidence: 99%

Combinatorial pharmacodynamics of polymyxin B and tigecycline against heteroresistant Acinetobacter baumannii

Rao

Ly²,

Diep

et al. 2016

International Journal of Antimicrobial Agents

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“…Thirdly, current tigecycline dosing strategies (especially monotherapy) may not be optimal for treating multidrug-resistant bacteria such as CRKP. 29 Lastly, tigecycline was also shown in murine models to promote the intestinal overgrowth of CRKP. 22 In subgroup analysis, the association between tigecycline treatment and CRKP readmission was observed in both the group of patients with CRKP infection as well as the group with CRKP colonization.…”

Section: Discussionmentioning

confidence: 99%

Hospital Readmissions in Patients With Carbapenem-ResistantKlebsiella pneumoniae

Messina

Cober

Richter

et al. 2015

Infect. Control Hosp. Epidemiol.

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Background Various transmission routes contribute to spread of Carbapenem-resistant Klebsiella pneumoniae (CRKP) in hospitalized patients. Patients with readmissions during which CRKP is again isolated (“CRKP readmission”) potentially contribute to transmission of CRKP. Objective Evaluate CRKP readmissions in the Consortium on Resistance against Carbapenems in K. pneumoniae (CRaCKle). Design Cohort study from 12/24/2011 to 7/1/2013 Setting CRaCKle is a multicenter consortium of acute care hospitals in the Great Lakes region. Patients All patients who were discharged alive during the study period were included. Each patient was included only once at the time of the first CRKP positive culture. Methods All readmissions within 90 days of discharge from the index hospitalization during which CRKP was again found were analyzed. Risk factors for CRKP readmission were evaluated in multivariable models. Results Twenty percent of patients who were discharged alive (56/287) had a CRKP readmission. A history of malignancy was associated with CRKP readmission (aOR 3.00, 95% CI 1.32-6.65, p<0.01). During the index hospitalization, 160 (56%) patients received antibiotic treatment targeted against CRKP. The choice of antibiotic regimen was associated with CRKP readmission (p=0.02). Receipt of tigecycline-based therapy (aOR 5.13, 95% CI 1.72-17.44, using aminoglycoside-based therapy as a reference in those treated with anti-CRKP antibiotics) was associated with CRKP readmission. Conclusion Hospitalized patients with CRKP – specifically those with a history of malignancy – are at high risk of readmission with recurrent CRKP infection or colonization, which may contribute to transmission of CRKP in healthcare systems. Treatment during the index hospitalization with a tigecycline-based regimen increases this risk.

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“…More specifically, the optimum therapeutic choices can also be based on the pharmacokinetic/pharmacodynamic model or Monte-Carlo simulation to obtain the most effective treatment. 18 This study has some limitations. The long-term monitoring period is still warranted to comprehensively investigate crossresistance or relation between other classes of antimicrobial agents and the resistance in AB.…”

Section: Discussionmentioning

confidence: 91%

Modeling and forecasting Acinetobacter baumannii resistance to set appropriate use of cefoperazone-sulbactam: Results from trend analysis of antimicrobial consumption and development of resistance in a tertiary care hospital

Xie

Wang

Zheng

et al. 2015

American Journal of Infection Control

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Optimal tigecycline dosage regimen is urgently needed: results from a pharmacokinetic/pharmacodynamic analysis of tigecycline by Monte Carlo simulation

Abstract: In the absence of new drugs on the horizon, rather than using a single fixed dosing regimen, tigecycline dosing needs to be optimized in order to achieve the desired successful clinical response and to prevent an escalation in drug resistance.

Cited by 47 publications

References 39 publications

Combinatorial pharmacodynamics of polymyxin B and tigecycline against heteroresistant Acinetobacter baumannii

Combinatorial pharmacodynamics of polymyxin B and tigecycline against heteroresistant Acinetobacter baumannii

Hospital Readmissions in Patients With Carbapenem-ResistantKlebsiella pneumoniae

Modeling and forecasting Acinetobacter baumannii resistance to set appropriate use of cefoperazone-sulbactam: Results from trend analysis of antimicrobial consumption and development of resistance in a tertiary care hospital

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