Pharmacodynamic and pharmacokinetic considerations in the treatment of critically Ill patients infected with carbapenem-resistant Enterobacteriaceae.
Ontology highlight
ABSTRACT:
SUBMITTER: Neuner EA
PROVIDER: S-EPMC5477717 | biostudies-other | 2017 May
REPOSITORIES: biostudies-other
Similar Datasets
Project description:The growing number of infections caused by multidrug-resistant pathogens has prompted a more rational use of available antibiotics given the paucity of new, effective agents. Monte Carlo simulations were utilized to determine the appropriateness of several doripenem dosing regimens based on the probability of attaining the critical drug exposure metric of time that drug concentrations remain above the drug MIC (T>MIC) for 35% (and lower thresholds) of the dosing interval in >80 to 90% of the population (T>MIC 35% target). This exposure level generally correlates with in vivo efficacy for carbapenems. In patients with creatinine clearance of >50 ml/min, a 500-mg dose of doripenem infused over 1 h every 8 h is expected to be effective against bacilli with doripenem MICs of < or =1 microg/ml based on a T>MIC 35% target and MICs of < or =2 microg/ml based on lower targets. A longer, 4-hour infusion time improved target attainment in most cases, such that the T>MIC was adequate for pathogens with doripenem MICs as high as 4 microg/ml. Efficacy is expected for infections caused by pathogens with doripenem MICs of < or =2 microg/ml in patients with moderate renal impairment (creatinine clearance, 30 to 50 ml/min) who receive doripenem at 250 mg infused over 1 h every 8 h and in patients with severe impairment (creatinine clearance between 10 and 29 ml/min) who receive doripenem at 250 mg, infused over 1 h or 4 h, every 12 h. Results of pharmacokinetics/pharmacodynamics (PK/PD) modeling can guide dose optimization, thereby potentially increasing the clinical efficacy of doripenem against serious Gram-negative bacterial infections.
| S-EPMC2876367 | biostudies-other
Project description:Infections due to carbapenem-resistant Enterobacteriaceae (CRE) are increasingly prevalent in children and are associated with poor clinical outcomes. Optimal treatment strategies for CRE infections continue to evolve. A lack of pediatric-specific comparative effectiveness data, uncertain pediatric dosing regimens for several agents, and a relative lack of new antibiotics with pediatric indications approved by the US Food and Drug Administration (FDA) collectively present unique challenges for children. In this review, we provide a framework for antibiotic treatment of CRE infections in children, highlighting relevant microbiologic considerations and summarizing available data related to the evaluation of FDA-approved antibiotics (as of September 2019) with CRE activity, including carbapenems, ceftazidime-avibactam, meropenem-vaborbactam, imipenem/cilastatin-relebactam, polymyxins, tigecycline, eravacycline, and plazomicin.
| S-EPMC7047006 | biostudies-literature
Project description:Antimicrobial resistance poses a significant threat to our ability to treat infections. Especially concerning is the emergence of carbapenem-resistant Enterobacteriaceae (CRE). In the new 2019 United States Centers for Disease Control and Prevention Antibiotic Resistance Report, CRE remain in the most urgent antimicrobial resistance threat category. There is good reason for this concerning designation. In particular, the combination of several resistance elements in CRE can make these pathogens untreatable or effectively untreatable with our current armamentarium of anti-infective agents. This article reviews recently approved agents with activity against CRE and a range of modalities in the pipeline, from early academic investigation to those in clinical trials, with a focus on structural aspects of new antibiotics. Another article in this series addresses the need to incentive pharmaceutical companies to invest in CRE antimicrobial development and to encourage hospitals to make these agents available in their formularies. This article will also consider the need for change in requirements for antimicrobial susceptibility testing implementation in clinical laboratories to address practical roadblocks that impede our efforts to provide even existing CRE antibiotics to our patients.
| S-EPMC7293954 | biostudies-literature
Project description:BackgroundCarbapenem-resistant Enterobacteriaceae (CRE) have emerged as an urgent public health threat. Intestinal colonization with CRE has been identified as a risk factor for the development of systemic CRE infection, but has not been compared to colonization with third and/or fourth generation cephalosporin-resistant (Ceph-R) Enterobacteriaceae. Moreover, the risk conferred by colonization on adverse outcomes is less clear, particularly in critically ill patients admitted to the intensive care unit (ICU).MethodsWe carried out a cohort study of consecutive adult patients screened for rectal colonization with CRE or Ceph-R upon ICU entry between April and July 2013. We identified clinical variables and assessed the relationship between CRE or Ceph-R colonization and subsequent systemic CRE infection within 30 days (primary outcome) and all-cause mortality within 90 days (secondary outcome).ResultsAmong 338 ICU patients, 94 (28%) were colonized with either Ceph-R or CRE. 26 patients developed CRE infection within 30 days of swab collection; 47% (N = 17/36) of CRE-colonized and 3% (N = 2/58) of Ceph-R colonized patients. 36% (N = 13/36) of CRE-colonized patients died within 90 days compared to 31% (N = 18/58) of Ceph-R-colonized and 15% (N = 37/244) of non-colonized patients. In a multivariable analysis, CRE colonization independently predicted development of a systemic CRE infection at 30 days (aOR 10.8, 95% CI2.8-41.9, p = 0.0006); Ceph-R colonization did not (aOR 0.5, 95% CI0.1-3.3, p = 0.5). CRE colonization was associated with increased 90-day mortality in a univariable analysis (p-value 0.001), in a multivariable model, previous hospitalization and medical ICU admission were independent predictors of 90-day mortality whereas CRE colonization approached significance (aOR 2.3, 95% CI1.0-5.3, p = 0.056).ConclusionsOur study highlights the increased risk of CRE infection and mortality in patients with CRE colonization at the time of ICU admission. Future studies are needed to assess how CRE colonization can guide empiric antibiotic choices and to develop novel decolonization strategies.
| S-EPMC5638409 | biostudies-literature
Project description:Imipenem-Relebactam Susceptibility and Genotypic Characteristics of Carbapenem Resistant Enterobacterales (CRE) Identified during Population-Based Surveillance
| PRJNA748096 | ENA
Project description:Whole genome and metagenomic sequencing of isolates and samples from a patient who tested positive for carbapenem-resistant organisms following stem cell transplant Genome sequencing and assembly
| PRJNA513350 | ENA
Project description:Carbapenem-resistant Enterobacteriaceae (CRE) are an emerging global public health threat. Infections due to CRE are associated with significant morbidity and mortality. Few therapeutic options are available for treatment of these infections, and optimal antibiotic treatment regimens are unclear. Along with the rapidly increasing prevalence of CRE in the USA and worldwide, several studies have described the epidemiology of CRE in the adult population. While CRE are now also reported sporadically in children, there is a significant lack of data on the epidemiology, risk factors, treatment, and outcomes in this population. This article provides a comprehensive review of what is known to date about CRE, including clinical and molecular epidemiology, microbiologic diagnosis, antibiotic treatment options, and outcomes. In particular, this review will focus on the available data on CRE in the pediatric population.
| S-EPMC4975038 | biostudies-literature
Project description:The purpose was to explore the optimal dosage regimen of colistin using Monte Carlo simulations, for the treatment of carbapenem-resistant Klebsiella pneumoniae and carbapenem-resistant Escherichia coli based on PK/PD targets in critically ill patients. A total of 116 carbapenem-resistant K. pneumoniae and E. coli were obtained from various clinical specimens at Siriraj Hospital in Bangkok, Thailand. Minimum inhibitory concentrations (MICs) of colistin were determined by broth microdilution method. Monte Carlo simulation was used to calculate the cumulative fraction of response (CFR) for European Medicine Agency (EMA), US-Food and Drug Administration (FDA), Nation et al., Siriraj Hospital and our study regimens. The targeted CFR was 90%. For colistin-susceptible K. pneumoniae, all of the dosage regimens achieved ?90% CFR in patients with creatinine clearance <80 mL/min except the FDA-approved regimens for patients with creatinine clearance 51-79 and 11-29 mL/min, respectively. While, patients with creatinine clearance ?80 mL/min, CFR ?90% was observed in Siriraj Hospital and our study regimen. For colistin-susceptible E. coli, all of the dosage regimens achieved ?90% CFR regardless of renal function. In contrast, the currently approved regimens achieved CFR target in only 10-50% for colistin-resistant isolates subgroup. These results suggest that currently approved regimens still recommended for colistin-susceptible CRE. For colistin-resistant CRE, alternative approaches such as high dose or combination therapy should be considered.
| S-EPMC6784242 | biostudies-literature
Project description:IntroductionCarbapenem-resistant Enterobacteriaceae (CRE) has emerged as a global threat to hospitalization patients. Infected pancreatic necrosis (IPN) leads to high risks of CRE infections with increasing mortality. Our study aims to determine the predictors related to 90-day overall mortality of CRE IPN.MethodsWe retrospectively reviewed the drug resistance rates and clinical characteristics of CRE IPN patients from January 1, 2016, to January 1, 2021. Independent predictors of mortality were identified via univariate and multivariate analyses.ResultsDuring the 5-year period, 75 IPN patients suffered from 135 episodes of CRE infections with mortality up to 50.7%. CRE strains were highly resistant (> 50%) to nine of ten common antibiotics, except tigecycline (18%). The most common pathogen was carbapenem-resistant Klebsiella pneumoniae (84 of 135). Lung was the main site of extrapancreatic infections, followed by bloodstream and biliary tract. The independent predictors of mortality were Sequential Organ Failure Assessment (SOFA) score > 2 (hazard ratio 3.746, 95% confidence interval 1.209-11.609, P = 0.022) and procalcitonin > 6 ng/l (hazard ratio 2.428, 95% confidence interval 1.204-4.895, P = 0.013).ConclusionCRE is widespread as a global challenge with a high mortality rate among IPN patients due to limited therapeutic options. Carbapenem-resistant K. pneumoniae is the leading category of CRE which requires more attention in clinical practice. High SOFA score and procalcitonin level represent two independent predictors of mortality in CRE IPN patients. Greater efforts are needed toward timely therapeutic intervention for CRE IPN.
| S-EPMC8322183 | biostudies-literature
Project description:Infections caused by gram-negative bacteria (GNB) resistant to multiple classes of antibiotics are increasing in many hospitals. Extended-spectrum β-lactamase (ESBL)-producing and carbapenem-resistant Enterobacteriaceae in particular are now endemic in many parts of the world and represent a serious public health threat. In this era, antimicrobial stewardship programs are essential as targeted and responsible use of antibiotics improves patient outcomes and hopefully limits the selective pressure that drives the further emergence of resistance. However, some stewardship strategies aimed at promoting carbapenem-sparing regimens remain controversial and are difficult to implement when resistance rates to non-carbapenem antibiotics are increasing. Coordinated efforts between stewardship programs and infection control are essential for reversing conditions that favor the emergence and dissemination of multidrug-resistant GNB within the hospital and identifying extra-institutional "feeder reservoirs" of resistant strains such as long-term care facilities, where colonization is common despite limited numbers of serious infections. In settings where ESBL resistance is endemic, the cost-effectiveness of expanded infection control efforts and antimicrobial stewardship is still unknown. Once a patient has been colonized, selective oral or digestive decontamination may be considered, but evidence supporting its effectiveness is limited in patients who are already colonized or in centers with high rates of resistance. Moreover, temporary success at decolonization may be associated with a higher risk of relapse with strains that are resistant to the decolonizing antibiotics.
| S-EPMC4569644 | biostudies-literature