scholarly journals The Monte Carlo Simulation of Three Antimicrobials for Empiric Treatment of Adult Bloodstream Infections With Carbapenem-Resistant Enterobacterales in China

2021 ◽  
Vol 12 ◽  
Author(s):  
Dongna Zou ◽  
Guangyue Yao ◽  
Chengwu Shen ◽  
Jinru Ji ◽  
Chaoqun Ying ◽  
...  
Keyword(s):  
Monte Carlo Simulation ◽  
Monte Carlo ◽  
Drug Exposure ◽  
Bacterial Resistance ◽  
Bloodstream Infections ◽  
Polymyxin B ◽  
Pharmacodynamic Modeling ◽  
Susceptibility Data ◽  
Carbapenem Resistant ◽  
Optimal Drug

Introduction: The aim of this study was to predict and evaluate three antimicrobials for treatment of adult bloodstream infections (BSI) with carbapenem-resistant Enterobacterales (CRE) in China, so as to optimize the clinical dosing regimen further.Methods: Antimicrobial susceptibility data of blood isolates were obtained from the Blood Bacterial Resistance Investigation Collaborative Systems in China. Monte Carlo simulation was conducted to estimate the probability target attainment (PTA) and cumulative fraction of response (CFR) of tigecycline, polymyxin B, and ceftazidime/avibactam against CRE.Results: For the results of PTAs, tigecycline following administration of 50 mg every 12 h, 75 mg every 12 h, and 100 mg every 12 h achieved > 90% PTAs when minimum inhibitory concentration (MIC) was 0.25, 0.5, and 0.5 μg/mL, respectively; polymyxin B following administration of all tested regimens achieved > 90% PTAs when MIC was 1 μg/mL with CRE; ceftazidime/avibactam following administration of 1.25 g every 8 h, 2.5 g every 8 h achieved > 90% PTAs when MIC was 4 μg/mL, 8 μg/mL with CRE, respectively. As for CFR values of three antimicrobials, ceftazidime/avibactam achieved the lowest CFR values. The highest CFR value of ceftazidime/avibactam was 77.42%. For tigecycline and ceftazidime/avibactam, with simulated regimens daily dosing increase, the CFR values were both increased; the highest CFR of tigecycline values was 91.88%. For polymyxin B, the most aggressive dosage of 1.5 mg/kg every 12 h could provide the highest CFR values (82.69%) against CRE.Conclusion: This study suggested that measurement of MICs and individualized therapy should be considered together to achieve the optimal drug exposure. In particular, pharmacokinetic and pharmacodynamic modeling based on local antimicrobial resistance data can provide valuable guidance for clinicians for the administration of empirical antibiotic treatments for BSIs.

Disease Severity Is an Independent Risk Factor of Mortality and Outcomes in Critically Ill Patients With Carbapenem-resistant Klebsiella Pneumoniae Bloodstream Infections: a 5-year Retrospective Analysis

2021 ◽  
Author(s):  
Yuzhen Qiu ◽  
Wen Xu ◽  
Yunqi Dai ◽  
Ruoming Tan ◽  
Jialin Liu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Septic Shock ◽  
Klebsiella Pneumoniae ◽  
Critically Ill Patients ◽  
Bloodstream Infections ◽  
Polymyxin B ◽  
Mortality Rates ◽  
Carbapenem Resistant ◽  
All Cause Mortality ◽  
Independent Risk Factors

Abstract Background: Carbapenem-resistant Klebsiella pneumoniae bloodstream infections (CRKP-BSIs) are associated with high morbidity and mortality rates, especially in critically ill patients. Comprehensive mortality risk analyses and therapeutic assessment in real-world practice are beneficial to guide individual treatment.Methods: We retrospectively analyzed 87 patients with CRKP-BSIs (between July 2016 and June 2020) to identify the independent risk factors for 28-day all-cause mortality. The therapeutic efficacies of tigecycline-and polymyxin B-based therapies were analyzed.Results: The 28-day all-cause mortality and in-hospital mortality rates were 52.87% and 67.82%, respectively, arising predominantly from intra-abdominal (56.32%) and respiratory tract infections (21.84%). A multivariate analysis showed that 28-day all-cause mortality was independently associated with the patient’s APACHE II score (p = 0.002) and presence of septic shock at BSI onset (p = 0.006). All-cause mortality was not significantly different between patients receiving tigecycline- or polymyxin B-based therapy (55.81% vs. 53.85%, p = 0.873), and between subgroups mortality rates were also similar. Conclusions: Critical illness indicators (APACHE II scores and presence of septic shock at BSI onset) were independent risk factors for 28-day all-cause mortality. There was no significant difference between tigecycline- and polymyxin B-based therapy outcomes. Prompt and appropriate infection control should be implemented to prevent CRKP infections.

scholarly journals Clinical Characteristics of Carbapenem-Resistant Klebsiella Pneumoniaee Infections In A Tertiary Hospital In China

2021 ◽  
Author(s):  
Zhiwen Cui ◽  
Lirui Wang ◽  
Wei Chang ◽  
Minghui Li ◽  
Yuexia Li ◽  
...  
Keyword(s):  
Survival Time ◽  
Sofa Score ◽  
Clinical Characteristics ◽  
Bloodstream Infections ◽  
Polymyxin B ◽  
Apache Ii ◽  
Apache Ii Score ◽  
Drainage Fluid ◽  
Carbapenem Resistant ◽  
Antimicrobial Regimen

Abstract Background：The infections due to carbapenem-resistant Klebsiella pneumoniae (CR-KP) have become an important problem. The aim of the study is to evaluate the clinical characteristics of CR-KP.Methods: A retrospective cohort study has been made on all patients presenting with CR-KP infections. 615 patients with CR-KP humor infections diagnosed were identified. 135 patients who did not meet the requirements were excluded. Clinical characteristics, antimicrobial regimens, and outcomes of patients have been analyzed.Results: The CR-KP infections overall mortality was 37.3%, and bloodstream infections mortality was 66.2%. Survival analysis revealed that there were statistically significant differences between bloodstream infection and pulmonary and drainage fluid infection. Logistics regression analysis showed that hemopathy, age (>60 years), solid tumors, diabetes, septic shock, acute kidney injury and stroke were independent predictors associated with the 30-day mortality. Multivariate linear regression was performed in APACHE II score, SOFA score, lymphocyte absolute value (LYM) and survival time. Survival time was negatively correlated with APACHE II score and SOFA score, while positively correlated with LYM. Finally, we investigated different antimicrobial regimens for CR-KP infections. Chi-square test showed that antimicrobial regimen combined carbapenems, tigecycline with polymyxin B was superior the one combined carbapenems with polymyxin B. Ceftazidime avibactam-based antimicrobial regimens also had no advantage over other therapeutic regimens.Conclusions: Our study confirmed there is a high mortality rate in CR-KP infections, especially in the bloodstream infections. The outcome is greatly influenced by the patients’ clinical conditions. Antimicrobial regimen combined carbapenems, tigecycline with polymyxin B might be a better choice.

scholarly journals Clinical and epidemiological characteristics of carbapenem-resistant Klebsiella pneumoniae infections in a tertiary hospital in China

2021 ◽  
Author(s):  
Zhiwen Cui ◽  
Lirui Wang ◽  
Wei Chang ◽  
Minghui Li ◽  
Yuexia Li ◽  
...  
Keyword(s):  
Kidney Injury ◽  
Bloodstream Infections ◽  
Polymyxin B ◽  
Apache Ii Score ◽  
Klebsiella Pneumonia ◽  
Drainage Fluid ◽  
Carbapenem Resistant ◽  
Significant Difference ◽  
Epidemiological Characteristics ◽  
Antimicrobial Regimen

Abstract Background：The infections due to carbapenem-resistant Klebsiella pneumonia (CR-KP) have become an important problem. The aim of the study is to evaluate the clinical and epidemiological characteristics of CR-KP. Results: The CR-KP infections overall mortality was 37.3%, and bloodstream infections mortality was 66.2%. Survival analysis revealed that there were statistically significant differences between bloodstream infection and pulmonary and drainage fluid infection. Hemopathy, age (>60 years), tumors, diabetes, septic shock, acute kidney injury and stroke were independent predictors associated with the 30-day mortality. Multivariate linear regression showed that survival time was negatively correlated with APACHE II score and SOFA score, while positively correlated with LYM. Chi-square test showed that antimicrobial regimen combined carbapenems, tigecycline with polymyxin B was superior the one combined carbapenems with polymyxin B. But there was not statistically significant difference between carbapenems plus tigecycline and carbapenems plus polymyxin B. Ceftazidime avibactam-based antimicrobial regimens also had no advantage over other therapeutic regimens. Conclusions: Our study confirmed there is a high mortality rate in CR-KP infections, especially in the bloodstream infections. The outcome is greatly influenced by the patients’ clinical conditions. Antimicrobial regimen combined carbapenems, tigecycline with polymyxin B might be a better choice.

scholarly journals In Vitro Activity Comparison of Ceftazidime–Avibactam and Aztreonam–Avibactam Against Bloodstream Infections With Carbapenem-Resistant Organisms in China

2021 ◽  
Vol 11 ◽  
Author(s):  
Wei Yu ◽  
Luying Xiong ◽  
Qixia Luo ◽  
Yunbo Chen ◽  
Jinru Ji ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Pseudomonas Aeruginosa ◽  
Bloodstream Infections ◽  
Polymyxin B ◽  
Resistance Rate ◽  
In Vitro Activity ◽  
Carbapenem Resistant ◽  
Resistance Rates ◽  
Activity Comparison

ObjectivesThe aim of this work was to investigate the activity of ceftazidime–avibactam (CZA) and aztreonam–avibactam (AZA) against bloodstream infections caused by carbapenem-resistant organisms (CROs).MethodsNon-duplicate CROs, including 56 carbapenem-resistant Escherichia coli (CR-Eco), 318 carbapenem-resistant Klebsiella pneumoniae (CR-Kpn), and 65 carbapenem-resistant Pseudomonas aeruginosa (CR-Pae), were collected using the Blood Bacterial Resistant Investigation Collaborative System (BRICS) program in China. The minimum inhibitory concentrations (MICs) of 24 antibiotics were tested. Carbapenemase genes were amplified for CZA-resistant CROs by PCR. The MICs of CZA and AZA were further determined with avibactam at 8 and 16 mg/L, respectively.ResultsThe resistance rate of polymyxin B against CROs was less than 5%. Only one CR-Kpn was resistant to tigecycline. The resistance rates of CZA against CR-Eco, CR-Kpn, and CR-Pae were 75.0%, 12.6%, and 18.5%, respectively. The MIC90 values of AZA against CR-Eco, CR-Kpn, and CR-Pae were 2/4, 1/4, and 64/4 mg/L, respectively. Among the CZA-resistant CROs, 42 (100%) CR-Eco, 24 (60%) CR-Kpn, and 1 (8.3%) CR-Pae isolates harbored metallo-β-lactamase genes. The increase of avibactam concentration enhanced the susceptibility of CZA and AZA against CROs, especially for CR-Eco and CR-Kpn.ConclusionsThe in vitro activity of AZA was superior to that of CZA against CR-Eco and CR-Kpn, whereas CZA showed better effect against CR-Pae.

scholarly journals Fosfomycin Dosing Regimens based on Monte Carlo Simulation for Treated Carbapenem-Resistant Enterobacteriaceae Infection

2020 ◽  
Vol 52 (4) ◽  
pp. 516
Author(s):  
Sukrit Kanchanasurakit ◽  
Wichai Santimaleeworagun ◽  
Charles E. McPherson ◽  
Napacha Piriyachananusorn ◽  
Benjawan Boonsong ◽  
...  
Keyword(s):  
Monte Carlo Simulation ◽  
Monte Carlo ◽  
Carbapenem Resistant ◽  
Dosing Regimens ◽  
Carbapenem Resistant Enterobacteriaceae

scholarly journals Clinical and Epidemiological Characteristics of Carbapenem-resistant Klebsiella Pneumoniae Infections in a Tertiary Hospital in China

2021 ◽  
Author(s):  
Zhiwen Cui ◽  
Lirui Wang ◽  
Wei Chang ◽  
Minghui Li ◽  
Yuexia Li ◽  
...  
Keyword(s):  
Mortality Rate ◽  
Sofa Score ◽  
Positive Culture ◽  
Bloodstream Infections ◽  
Polymyxin B ◽  
Apache Ii ◽  
Apache Ii Score ◽  
Carbapenem Resistant ◽  
Epidemiological Characteristics ◽  
Antimicrobial Regimen

Abstract Background: The infections due to carbapenem-resistant Klebsiella pneumonia (CR-KP) have become an important problem and they are associated with a high mortality rate. The aim of the study is to evaluate the clinical and epidemiological characteristics of CR-KP.Methods: A retrospective cohort study has been made on all patients presenting with CR-KP infections. 615 patients with CR-KP humor infections diagnosed between January 2018 and December 2019 were identified. 135 patients who did not meet the requirements were excluded, and the remaining 480 patients were enrolled in the study. We have evaluated the mortality in 30 days from the first positive culture. Clinical characteristics, antimicrobial regimens, and outcomes of patients have been analyzed.Results: The CR-KP infections overall mortality was 37.3%, and bloodstream infections mortality was 66.2%. Survival analysis revealed that there were statistically significant differences between bloodstream infection and pulmonary and drainage fluid infection. The gender, wards, and endotracheal intubation or tracheotomy before positive culture did not differ between the non-survivor and survivor groups. Logistics regression analysis showed that hemopathy, age (>60 years), solid tumors, diabetes, septic shock, acute kidney injury and stroke were independent predictors associated with the 30-day mortality. Multivariate linear regression was performed in APACHE II score, SOFA score, lymphocyte absolute value (LYM) and survival time. Survival time was negatively correlated with APACHE II score and SOFA score, while positively correlated with LYM. In addition, ROC curves were also drawn for APACHE II score, SOFA score and LYM, with AUC of 0.825, 0.876 and 0.797, respectively. Finally, we investigated different antimicrobial regimens for CR-KP infections. Chi-square test showed that antimicrobial regimen combined carbapenems, tigecycline with polymyxin B was superior the one combined carbapenems with polymyxin B, and the difference had statistically significant. But there was not statistically significant difference between carbapenems plus tigecycline and carbapenems plus polymyxin B, and it seemed that polymyxin B and tigecycline have synergistic effect. Ceftazidime avibactam-based antimicrobial regimens also had no advantage over other therapeutic regimens.Conclusions: Our study confirmed there is a high mortality rate in CR-KP infections, especially in the bloodstream infections. The outcome is greatly influenced by the patients’ clinical conditions. Antimicrobial regimen combined carbapenems, tigecycline with polymyxin B might be a better choice.

scholarly journals In Vitro Activities of Various Antimicrobials Alone and in Combination with Tigecycline against Carbapenem-Intermediate or -Resistant Acinetobacter baumannii

2007 ◽  
Vol 51 (5) ◽  
pp. 1621-1626 ◽  
Author(s):  
Marc H. Scheetz ◽  
Chao Qi ◽  
John R. Warren ◽  
Michael J. Postelnick ◽  
Teresa Zembower ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Antimicrobial Susceptibility ◽  
Bloodstream Infections ◽  
Polymyxin B ◽  
In Vitro Susceptibility ◽  
Carbapenem Resistant ◽  
Susceptibility Profiles ◽  
Time Kill

ABSTRACT The activities of tigecycline alone and in combination with other antimicrobials are not well defined for carbapenem-intermediate or -resistant Acinetobacter baumannii (CIRA). Pharmacodynamic activity is even less well defined when clinically achievable serum concentrations are considered. Antimicrobial susceptibility testing of clinical CIRA isolates from 2001 to 2005 was performed by broth or agar dilution, as appropriate. Tigecycline concentrations were serially increased in time-kill studies with a representative of the most prevalent carbapenem-resistant clone (strain AA557; imipenem MIC, 64 mg/liter). The in vitro susceptibility of the strain was tested by time-kill studies in duplicate against the average free serum steady-state concentrations of tigecycline alone and in combination with various antimicrobials. Ninety-three CIRA isolates were tested and were found to have the following antimicrobial susceptibility profiles: tigecycline, MIC50 of 1 mg/liter and MIC90 of 2 mg/liter; minocycline, MIC50 of 0.5 mg/liter and MIC90 of 8 mg/liter; doxycycline, MIC50 of 2 mg/liter and MIC90 of ≥32 mg/liter; ampicillin-sulbactam, MIC50 of 48 mg/liter and MIC90 of 96 mg/liter; ciprofloxacin, MIC50 of ≥16 mg/liter and MIC90 of ≥16 mg/liter; rifampin, MIC50 of 4 mg/liter and MIC90 of 8 mg/liter; polymyxin B, MIC50 of 1 mg/liter and MIC90 of 1 mg/liter; amikacin, MIC50 of 32 mg/liter and MIC90 of ≥32 mg/liter; meropenem, MIC50 of 16 mg/liter and MIC90 of ≥128 mg/liter; and imipenem, MIC50 of 4 mg/liter and MIC90 of 64 mg/liter. Among the tetracyclines, the isolates were more susceptible to tigecycline than minocycline and doxycycline, according to FDA breakpoints (95%, 88%, and 71% of the isolates were susceptible to tigecycline, minocycline, and doxycycline, respectively). Concentration escalation studies with tigecycline revealed a maximal killing effect near the MIC, with no additional extent or rate of killing at concentrations 2× to 4× the MIC for tigecycline. Time-kill studies demonstrated indifference for tigecycline in combination with the antimicrobials tested. Polymyxin B, minocycline, and tigecycline are the most active antimicrobials in vitro against CIRA. Concentration escalation studies demonstrate that tigecycline may need to approach concentrations higher than those currently achieved in the bloodstream to adequately treat CIRA bloodstream infections. Future studies should evaluate these findings in vivo.

scholarly journals Colistin Dosing Regimens against Pseudomonas aeruginosa in Critically Ill Patients: An Application of Monte Carlo Simulation

Antibiotics ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 595
Author(s):  
Van Thi Khanh Nguyen ◽  
Preecha Montakantikul ◽  
Pramote Tragulpiankit ◽  
Jantana Houngsaitong ◽  
Mohd Fazli Shuib
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Monte Carlo Simulation ◽  
Monte Carlo ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Pharmacokinetic Parameters ◽  
Infection Model ◽  
Carbapenem Resistant ◽  
Dosing Regimens ◽  
Microbiological Data

Our aims are to assess various colistin dosing regimens against Pseudomonas aeruginosa (P. aeruginosa) infection in critically ill patients and to propose an appropriate regimen based on microbiological data. A Monte Carlo simulation was performed using the published colistin’s pharmacokinetic parameters of critically ill patients, the published pharmacodynamic target from a mouse thigh infection model, and the minimum inhibitory concentration (MIC) results from a Vietnamese hospital. The probability of target attainment (PTA) of 80% and cumulative fraction of response (CFR) of 90% were used to evaluate the efficacy of each regimen. Of 121 P. aeruginosa laboratory datasets, the carbapenem-resistant P. aeruginosa (CRPA) and the colistin- resistant P. aeruginosa rates were 29.8% and 0.8%, respectively. MIC50,90 were both 0.5 mg/L. The simulated results showed that at MIC of 2 mg/L, most regimens could not reach the PTA target, particularly in patients with normal renal function (Creatinine clearance (CrCl) ≥ 80 mL/min). At MIC of 0.5 mg/L and 1 mg/L, current recommendations still worked well. On the basis of these results, aside from lung infection, our study recommends three regimens against P. aeruginosa infection at MIC of 0.5 mg/L, 1 mg/L, and 2 mg/L. In conclusion, higher total daily doses and fractionated colistin dosing regimens could be the strategy for difficult-to-acquire PTA cases, while a less aggressive dose might be appropriate for empirical treatment in settings with low MIC50/90.

scholarly journals Pharmacodynamics of Voriconazole for Invasive Pulmonary Scedosporiosis

2018 ◽  
Vol 62 (5) ◽  
pp. e02516-17 ◽  
Author(s):  
Helen Box ◽  
Clara Negri ◽  
Joanne Livermore ◽  
Sarah Whalley ◽  
Adam Johnson ◽  
...  
Keyword(s):  
Monte Carlo Simulation ◽  
Monte Carlo ◽  
Drug Exposure ◽  
Complete Suppression ◽  
Scedosporium Apiospermum ◽  
Maximal Effect ◽  
Time Curve ◽  
Content Type ◽  
Wide Range

ABSTRACT Scedosporium apiospermum is a medically important fungal pathogen that causes a wide range of infections in humans. There are relatively few antifungal agents that are active against Scedosporium spp. Little is known about the pharmacodynamics of voriconazole against Scedosporium. Both static and dynamic in vitro models of invasive scedosporiosis were developed. Monoclonal antibodies that target a soluble cell wall antigen secreted by Scedosporium apiospermum were used to describe the pharmacodynamics of voriconazole. Mathematical pharmacokinetic-pharmacodynamic models were fitted to the data to estimate the drug exposure required to suppress the release of fungal antigen. The experimental results were bridged to humans using Monte Carlo simulation. All 3 strains of S. apiospermum tested invaded through the cellular bilayer of the in vitro models and liberated antigen. There was a concentration-dependent decline in the amount of antigen, with near maximal antifungal activity against all 3 strains being achieved with voriconazole at 10 mg/liter. Similarly, there was a drug exposure-dependent decline in the amount of circulating antigen in the dynamic model and complete suppression of antigen, with an area under the concentration-time curve (AUC) of approximately 80 mg · h/liter. A regression of the AUC/MIC versus the area under the antigen-time curve showed that a near maximal effect was obtained with an AUC/MIC of approximately 100. Monte Carlo simulation suggested that only isolates with an MIC of 0.5 mg/liter enabled pharmacodynamic targets to be achieved with a standard regimen of voriconazole. Isolates with higher MICs may need drug exposure targets higher than those currently recommended for other fungi.

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