Therapeutic Drug Monitoring of Tigecycline in 67 Infected Patients and a Population Pharmacokinetics/Microbiological Evaluation of A. baumannii Study

Yang, Tianli; Mei, Hekun; Wang, Jin; Cai, Yun

doi:10.3389/fmicb.2021.678165

Cited by 9 publications

(13 citation statements)

References 19 publications

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“…As a time-dependent antimicrobial agent with delayed post-antibiotic effect (PAE), the pharmacokinetics/pharmacodynamics (PK/PD) parameter associated with the clinical efficacy of tigecycline is AUC/MIC. For tigecycline-resistant hvKp, the increased MIC and the limited tigecycline dosage were the main reasons for the poor clinical efficacy 55 . The MIC reduction endow by TTCT would be beneficial for maximizing the efficacy and minimizing the drug-related adverse events of tigecycline.…”

Section: Discussionmentioning

confidence: 99%

TPGS-based and S-thanatin functionalized nanorods for overcoming drug resistance in Klebsiella pneumonia

Wang

Zhang

et al. 2022

Nat Commun

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Tigecycline is regarded as the last line of defense to combat multidrug-resistant Klebsiella pneumoniae. However, increasing utilization has led to rising drug resistance and treatment failure. Here, we design a D-alpha tocopheryl polyethylene glycol succinate-modified and S-thanatin peptide-functionalized nanorods based on calcium phosphate nanoparticles for tigecycline delivery and pneumonia therapy caused by tigecycline-resistant Klebsiella pneumoniae. After incubation with bacteria, the fabricated nanorods can enhance tigecycline accumulation in bacteria via the inhibitory effect on efflux pumps exerted by D-alpha tocopheryl polyethylene glycol succinate and the targeting capacity of S-thanatin to bacteria. The synergistic antibacterial capacity between S-thanatin and tigecycline further enhances the antibacterial activity of nanorods, thus overcoming the tigecycline resistance of Klebsiella pneumoniae. After intravenous injection, nanorods significantly reduces the counts of white blood cells and neutrophils, decreases bacterial colonies, and ameliorates neutrophil infiltration events, thereby largely increasing the survival rate of mice with pneumonia. These findings may provide a therapeutic strategy for infections caused by drug-resistant bacteria.

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Section: Discussionmentioning

confidence: 99%

TPGS-based and S-thanatin functionalized nanorods for overcoming drug resistance in Klebsiella pneumonia

Wang

Zhang

et al. 2022

Nat Commun

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“…However, previous clinical studies with XDR-AB infections, have shown that when tigecycline MIC is >2 μg/mL, significantly higher therapeutic failures and mortality were observed either when tigecycline was used as monotherapy or as part of a combination therapy with colistin [ 8 , 9 ]. In addition, the clinical efficacy of tigecycline is reached when ƒ AUC 0–24h /MIC ratios are greater than 0.9, which cannot be achieved, especially in bloodstream infections, even with high doses of tigecycline (200 mg loading dose followed by maintenance dose 100 mg b.i.d) [ 10 ]. The therapeutic regimen used in each patient was defined after infectious diseases consultation.…”

Section: Methodsmentioning

confidence: 99%

Efficacy of Fosfomycin-Containing Regimens for Treatment of Bacteremia Due to Pan-Drug Resistant Acinetobacter baumannii in Critically Ill Patients: A Case Series Study

et al. 2023

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Acinetobacter baumannii (AB) has evolved over the last decades as a major problem in carbapenem-resistant gram-negative nosocomial infections, associated with high mortality rates especially in the intensive care unit (ICU). Recent reports highlight the increasing prevalence of resistance to colistin, a last resort therapeutic option for carbapenem-resistant AB. We retrospectively evaluated the characteristics, treatment regimens and outcomes of twenty patients with pan-drug resistant (PDR) AB primary bacteremia hospitalized in the ICU of the University General Hospital of Patras, during a two-year period (October 2020–September 2022). The 28-day mortality reached 50%. Between survivors and non-survivors, no differences were found regarding age, gender, and Charlson comorbidity index (CCI). However, non-survivors had higher APACHE II scores and higher prevalence of septic shock and COVID-19 infection. A significantly higher percentage in the survivor group received Fosfomycin as part of the combination regimen. Inclusion of fosfomycin in the combination therapeutic regimen was associated with significantly better survival as compared to non-fosfomycin-containing regimens. In view of the increasing prevalence of PDR-AB infections in ICUs, its associated high rates of mortality and the lack of effective treatment options, the observed survival benefit with fosfomycin inclusion in the therapeutic regimen merits further validation in larger prospective studies.

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“…[32][33][34] Typical MICs were taken into consideration based on related studies and the latest guidelines of European Committee on Antimicrobial Susceptibility Testing (EUCAST). [35][36][37] 3 | RESULTS The estimated PK parameters for the plasma/sputum of each patient are shown in Tables 2 and 3. In plasma, The C max and AUC 0-12h were 2.21 ± 0.17 mg/L and 15.29 ± 1.13 h mg/L, respectively (Table 2).…”

Section: Measurement Methodsmentioning

confidence: 99%

“…Crystal Ball software was used to carry out Monte Carlo simulations and to calculate the probability of target attainments (PTAs) at different MIC values (0.25–16 mg/L) in 10,000 patients 32–34 . Typical MICs were taken into consideration based on related studies and the latest guidelines of European Committee on Antimicrobial Susceptibility Testing (EUCAST) 35–37 …”

Section: Methodsmentioning

confidence: 99%

Pharmacokinetic/pharmacodynamic analysis of high‐dose tigecycline, by Monte Carlo simulation, in plasma and sputum of patients with hospital‐acquired pneumonia

Qin

Kong

et al. 2022

Clinical Pharmacy Therapeu

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What is Known and Objective To Investigate the pharmacokinetic/pharmacodynamic (PK/PD) parameters of high‐dose tigecycline in plasma and sputum of patients with hospital‐acquired pneumonia (HAP), and provide a therapeutic regimen of multidrug‐resistant bacteria (MDRB) infections. Methods Blood/sputum samples were collected at intervals after tigecycline had reached a steady‐state. Tigecycline concentrations in specimens were determined by high‐performance liquid chromatography (HLPC), PK parameters were evaluated by WinNonlin software using a non‐compartment model. The probability of target attainments (PTAs) at different minimal inhibitory concentrations (MICs) were calculated for achieving the PK/PD index with Crystal Ball software by 10,000‐patient Monte Carlo Simulation. Results In plasma, the maximum concentration (Cmax) and area under the concentration–time curve from 0 to 12 h (AUC0–12h) were 2.21 ± 0.17 mg/L and 15.29 ± 1.13 h mg/L, respectively. In sputum, they were 2.48 ± 0.21 mg/L and 19.46 ± 1.82 h mg/L, respectively. The mean lung penetration rate was 127.27%. At the MIC ≤4 mg/L, the PTAs in plasma and sputum were 100.00%. When the MIC increased to 8 mg/L, the PTAs in plasma and sputum mostly were < 90.00% according to two criteria. What is New and Conclusion In this study, we explored PK/PD of high‐dose tigecycline in plasma and sputum. From a PK/PD perspective, high‐dose tigecycline had greater therapeutic outcomes in HAP treatment caused by MDRB. Antimicrobial‐drug concentrations should be determined to optimize their clinical use.

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Therapeutic Drug Monitoring of Tigecycline in 67 Infected Patients and a Population Pharmacokinetics/Microbiological Evaluation of A. baumannii Study

Cited by 9 publications

References 19 publications

TPGS-based and S-thanatin functionalized nanorods for overcoming drug resistance in Klebsiella pneumonia

TPGS-based and S-thanatin functionalized nanorods for overcoming drug resistance in Klebsiella pneumonia

Efficacy of Fosfomycin-Containing Regimens for Treatment of Bacteremia Due to Pan-Drug Resistant Acinetobacter baumannii in Critically Ill Patients: A Case Series Study

Pharmacokinetic/pharmacodynamic analysis of high‐dose tigecycline, by Monte Carlo simulation, in plasma and sputum of patients with hospital‐acquired pneumonia

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