Monte Carlo simulation evaluation of tigecycline dosing for bacteria with raised minimum inhibitory concentrations in non-critically ill adults

Kispal, Brianna; Walker, Sandra A N

doi:10.1007/s00228-020-02998-7

Cited by 5 publications

(3 citation statements)

References 29 publications

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“…Only a few patients could provide complete pharmacokinetic parameters, which was difficult to support the complex model. Thus, we chose a one-compartment model to describe the PK data ( Kispal and Walker, 2021 ). Correlation analysis was performed, and the correlation coefficient was calculated for each covariate.…”

Section: Resultsmentioning

confidence: 99%

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

et al. 2021

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BackgroundThe widespread use of antibiotics has led to the emergence of multidrug-resistant (MDR) bacteria such as multidrug-resistant Acinetobacter baumannii (AB). Tigecycline (TGC), as the first glycylcycline antibiotic approved by FDA, is a broad-spectrum antibiotic which remains highly effective to treat AB infections.ObjectiveTo confirm the TGC treatment dosage and effectiveness to treat AB infections in the Chinese population by performing therapeutic drug monitoring (TDM).MethodsThis study was performed from October 2018 through March 2019 at the PLA General Hospital. A high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was validated and employed to determine the plasma concentrations of TGC in patients with infectious diseases. The minimum inhibitory concentration (MIC) of TGC to clinically isolated AB was determined by broth microdilution method, agar dilution method, and disk diffusion method. Moreover, a model of population pharmacokinetics/pharmacodynamics (PPK/PD) was constructed.ResultsA total of 186 plasma samples from 67 patients were detected by the validated HPLC-MS/MS method. The MIC values determined by the broth microdilution method were more sensitive and accurate than the other two methods. The microbial and clinical PK/PD breakpoints were reached when the maintenance dose of TGC was 100 mg.ConclusionOur study established a validated HPLC-MS/MS method to monitor the plasma concentrations of TGC. In view of the MIC range to AB isolates in our hospital and the PPK/PD modeling results, we recommend a relatively high dose of 100 mg q12h regimen to achieve the optimal clinical efficacy and antimicrobial response.

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Section: Resultsmentioning

confidence: 99%

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

et al. 2021

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“…Monte Carlo simulation study indicated that high dose tigecycline may be appropriate for patients with MIC >0.48μg/mL. 29 …”

Section: Discussionmentioning

confidence: 97%

Clinical Efficacy, Antibiotic Resistance Genes, Virulence Factors and Outcome of Hospital-Acquired Pneumonia Induced by Klebsiella pneumoniae Carbapenemase 2-Producing with Tigecycline Treatment in the ICU

Bai¹,

Cao²,

Wang³

et al. 2022

IDR

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Purpose Tigecycline is an agent for carbapenemase-producing Klebsiella pneumonia (KPC-KP), given its penetration into lung tissues. Our study focused on the molecular and clinical efficacy of tigecycline for hospital-acquired pneumonia (HAP) in the ICU. Patients and Methods A retrospective cohort study of 52 adult KPC-KP HAP patients by searching hospital medical records from January 2018 to December 2020 was established to investigate the epidemiology of KPC-KP infections for tigecycline treatment and the associated clinical efficacy of tigecycline. The KPC-KP isolates underwent multilocus sequence typing. Molecular typing, antimicrobial resistance, and virulence profiling were also analyzed by whole-genome sequencing of KPC-KP. Results Among 52 patients with KPC-KP, the ICU mortality rate was 14/52 (27%), and there was no significant statistical difference in mortality between the effective group and failure group ( p = 0.754). However, the duration of tigecycline was statistically different between the two groups of patients (14.4 vs 10 days, p =0.046). The total bacterial clearance rate was 6/52 (11.5%). There was no significant statistical difference in both groups ( p =0.416). Antibiotic resistance genes ( aac3iia ) and virulence gene ( AREO-iutA, Capsule-wzc ) were negatively correlated with clinical efficacy ( p = 0.011, OR = 1.237). Conclusions Bla kpc was the main carbapenemase in all K. pneumoniae strains. ST11-KL64 KPC-KP was the most common virulence factors in KPC-KP isolates. This study suggested that antibiotic resistance genes ( aac3iia ) and virulence gene ( AREO-iutA, Capsule-wzc ) were independent mortality risk factors for patients with Klebsiella pneumoniae carbapenemase-2 producing K. pneumoniae infections, when during the tigecycline treatment. Molecular analysis of K. pneumoniae may provide an option when choosing the antimicrobial treatment.

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“…No antimicrobial with in vitro results showing resistance may be considered as adequate. In addition, doses are also not considered in the evaluation of appropriateness of therapy, with the exception of tigecycline, where an adapted breakpoint considering the minimal inhibitory concentration and dose was considered in this evaluation, based on data from previous studies [41][42][43][44].…”

Section: Strengths and Limitationsmentioning

confidence: 99%

A Randomized, Open-Label, Non-inferiority Clinical Trial Assessing 7 Versus 14 Days of Antimicrobial Therapy for Severe Multidrug-Resistant Gram-Negative Bacterial Infections: The OPTIMISE Trial Protocol

Arns,

Horvath,

Rech

et al. 2023

Infect Dis Ther

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Introduction Shorter courses of antimicrobials have been shown to be non-inferior to longer, “traditional” duration of therapies, including for some severe healthcare-associated infections, with a few exceptions. However, evidence is lacking regarding shorter regimes against severe infections by multidrug-resistant Gram-negative bacteria (MDR-GNB), which are often caused by distinct strains and commonly treated with second-line antimicrobials. In the duratiOn of theraPy in severe infecTIons by MultIdrug-reSistant gram-nEgative bacteria (OPTIMISE) trial, we aim to assess the non-inferiority of 7-day versus 14-day antimicrobial therapy in critically ill patients with severe infections caused by MDR-GNB. Methods This is a randomized, multicenter, open-label, parallel controlled trial to assess the non-inferiority of 7-day versus 14-day of adequate antimicrobial therapy for intensive care unit (ICU)-acquired severe infections by MDR-GNB. Adult patients with severe infections by MDR-GNB initiated after 48 h of ICU admission are screened for eligibility. Patients are eligible if they proved to be hemodynamically stable and without fever for at least 48 h on the 7th day of adequate antimicrobial therapy. After consenting, patients are 1:1 randomized to discontinue antimicrobial therapy on the 7th (± 1) day or to continue for a total of 14th (± 1) days. Planned Outcomes The primary outcome is treatment failure, defined as death or relapse of infection within 28 days after randomization. Non-inferiority will be achieved if the upper edge of the two-tailed 95% confidence interval of the difference between the clinical failure rate in the 7-day and the 14-day group is not higher than 10%. Conclusion The OPTIMISE trial is the first randomized controlled trial specifically designed to assess the duration of antimicrobial therapy in patients with severe infections by MDR-GNB. Trial Registration ClinicalTrials.gov, NCT05210387. Registered on 27 January 2022. Seven Versus 14 Days of Antibiotic Therapy for Multidrug-resistant Gram-negative Bacilli Infections (OPTIMISE). Supplementary Information The online version contains supplementary material available at 10.1007/s40121-023-00897-9.

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Monte Carlo simulation evaluation of tigecycline dosing for bacteria with raised minimum inhibitory concentrations in non-critically ill adults

Cited by 5 publications

References 29 publications

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

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

Clinical Efficacy, Antibiotic Resistance Genes, Virulence Factors and Outcome of Hospital-Acquired Pneumonia Induced by Klebsiella pneumoniae Carbapenemase 2-Producing with Tigecycline Treatment in the ICU

A Randomized, Open-Label, Non-inferiority Clinical Trial Assessing 7 Versus 14 Days of Antimicrobial Therapy for Severe Multidrug-Resistant Gram-Negative Bacterial Infections: The OPTIMISE Trial Protocol

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