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Tigecycline population pharmacokinetics in patients with community- or hospital-acquired pneumonia.

ABSTRACT: Tigecycline is a new-generation of tetracycline (glycylcyclines) and is active in vitro against bacteria that possess any of the classical genes that confer tetracycline resistance through ribosomal protection or efflux pumps. Herein, tigecycline disposition in patients with community- or hospital-acquired pneumonia was described using a population pharmacokinetic model. Additionally, the influence of covariates, such as body surface area, severity of illness, and clinical laboratory measures, on tigecycline disposition was evaluated. An intravenous loading dose of 100 mg was followed by 50 mg of tigecycline every 12 h. The final population pharmacokinetic model was a two-compartment model with linear elimination and with a relationship between tigecycline clearance and body surface area and creatinine clearance. The model was parameterized using total clearance (CL), the volume of the central compartment, distributional clearance from the central to the peripheral compartment, and volumes of distribution at steady state. Relationships between body surface area and creatinine clearance were identified as significant predictors of interindividual variability on CL. This model will serve as the basis for estimating tigecycline exposure for pharmacokinetic-pharmacodynamic analyses for efficacy and safety among patients with community- or hospital-acquired pneumonia.

SUBMITTER: Rubino CM

PROVIDER: S-EPMC2981274 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

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Tigecycline population pharmacokinetics in patients with community- or hospital-acquired pneumonia.

Rubino Christopher M CM Forrest Alan A Bhavnani Sujata M SM Dukart Gary G Cooper Angel A Korth-Bradley Joan J Ambrose Paul G PG

Antimicrobial agents and chemotherapy 20101004 12

Tigecycline is a new-generation of tetracycline (glycylcyclines) and is active in vitro against bacteria that possess any of the classical genes that confer tetracycline resistance through ribosomal protection or efflux pumps. Herein, tigecycline disposition in patients with community- or hospital-acquired pneumonia was described using a population pharmacokinetic model. Additionally, the influence of covariates, such as body surface area, severity of illness, and clinical laboratory measures, o ...[more]

PMID: 20921315

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Project description:Pharmacokinetic and clinical data from tigecycline-treated patients with hospital-acquired pneumonia (HAP) who were enrolled in a phase 3 clinical trial were integrated in order to evaluate pharmacokinetic-pharmacodynamic (PK-PD) relationships for efficacy. Univariable and multivariable analyses were conducted to identify factors associated with clinical and microbiological responses, based on data from 61 evaluable HAP patients who received tigecycline intravenously as a 100-mg loading dose followed by 50 mg every 12 h for a minimum of 7 days and for whom there were adequate clinical, pharmacokinetic, and response data. The final multivariable logistic regression model for clinical response contained albumin and the ratio of the free-drug area under the concentration-time curve from 0 to 24 h (fAUC(0-24)) to the MIC (fAUC(0-24):MIC ratio). The odds of clinical success were 13.0 times higher for every 1-g/dl increase in albumin (P < 0.001) and 8.42 times higher for patients with fAUC(0-24):MIC ratios of ?0.9 compared to patients with fAUC(0-24):MIC ratios of <0.9 (P = 0.008). Average model-estimated probabilities of clinical success for the albumin/fAUC(0-24):MIC ratio combinations of <2.6/<0.9, <2.6/?0.9, ?2.6/<0.9, and ?2.6/?0.9 were 0.21, 0.57, 0.64, and 0.93, respectively. For microbiological response, the final model contained albumin and ventilator-associated pneumonia (VAP) status. The odds of microbiological success were 21.0 times higher for every 1-g/dl increase in albumin (P < 0.001) and 8.59 times higher for patients without VAP compared to those with VAP (P = 0.003). Among the remaining variables evaluated, the MIC had the greatest statistical significance, an observation which was not surprising given the differences in MIC distributions between VAP and non-VAP patients (MIC(50)and MIC(90) values of 0.5 and 0.25 mg/liter versus 16 and 1 mg/liter for VAP versus non-VAP patients, respectively; P = 0.006). These findings demonstrated the impact of pharmacological and patient-specific factors on the clinical and microbiological responses.

Project description:IntroductionCommunity-acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP) are common complications in idiopathic inflammatory myopathy (IIM) patients, and are frequently associated with unfavorable outcome as well as prolonged antibiotic therapy. In this study, we intended to clarify whether clinical pulmonary infection score (CPIS) and multiple serum biomarkers are valuable in predicting unfavorable outcomes and prolonged antibiotic therapy in adult IIM patients complicated with CAP or HAP.MethodsData of IIM patients with CAP or HAP who were admitted to three tertiary centers from December 2010 to November 2019 were retrospectively collected. Cox proportional hazards regression analysis and logistic regression analysis were adopted to identify risk factors for unfavorable outcomes and prolonged antibiotic therapy in these patients. The predictive values of potential predictors were assessed using receiver operating characteristic analysis.ResultsThe mortality rate was 60.6% in 109 IIM patients complicated with CAP or HAP. Myositis Disease Activity Assessment Visual Analogue Scales (MYOACT) score, CPIS and timely adjustment to antibiotics based on drug susceptibility test (DST-based antibiotic) were significantly associated with long-term outcome in these patients. With an optimal cutoff value of 6.5 and area under the curve (AUC) of 0.813, CPIS was a more satisfying predictor compared with MYOACT score. The peak C-reactive protein (CRP) level, DST-based antibiotics, and complication of interstitial lung disease (ILD) were also significantly correlated with prolonged antibiotic therapy.ConclusionsIIM patients complicated with CAP or HAP frequently suffer from unfavorable outcomes. Compared with IIM disease activity, CPIS worked as a better predictor of outcome in these patients. Also, the peak CRP level during hospitalization might be valuable in predicting prolonged antibiotic therapy. The existence of ILD might impede early discontinuation of antibiotics. Timely adjustment to antibiotics based on drug susceptibility testing would decrease the mortality rate and reduce the incidence of prolonged antibiotic therapy.

Project description:ObjectivesSARS-CoV-2 may cause acute lung injury, and secondary infections are thus relevant complications in patients with COVID-19 pneumonia. However, detailed information on community- and hospital-acquired infections among patients with COVID-19 pneumonia is scarce.MethodsWe identified 220 SARS-CoV-2-positive patients hospitalized at the University Hospital Basel, Switzerland (between 25 February and 31 May 2020). We excluded patients who declined the general consent (n = 12), patients without clinical evidence of pneumonia (n = 29), and patients hospitalized for < 24 h (n = 17). We evaluated the frequency of community- and hospital-acquired infections using respiratory and blood culture materials with antigen, culture-based, and molecular diagnostics. For ICU patients, all clinical and microbial findings were re-evaluated interdisciplinary (intensive care, infectious disease, and clinical microbiology), and agreement reached to classify patients with infections.ResultsIn the final cohort of 162 hospitalized patients (median age 64.4 years (IQR, 50.4-74.2); 61.1% male), 41 (25.3%) patients were admitted to the intensive care unit, 34/41 (82.9%) required mechanical ventilation, and 17 (10.5%) of all hospitalized patients died. In total, 31 infections were diagnosed including five viral co-infections, 24 bacterial infections, and three fungal infections (ventilator-associated pneumonia, n = 5; tracheobronchitis, n = 13; pneumonia, n = 1; and bloodstream infection, n = 6). Median time to respiratory tract infection was 12.5 days (IQR, 8-18) and time to bloodstream infection 14 days (IQR, 6-30). Hospital-acquired bacterial and fungal infections were more frequent among ICU patients than other patients (36.6% vs. 1.7%). Antibiotic or antifungal treatment was administered in 71 (43.8%) patients.ConclusionsCommunity-acquired viral and bacterial infections were rare among COVID-19 pneumonia patients. By contrast, hospital-acquired bacterial or fungal infections were frequently complicating the course among ICU patients.

Dataset Information

Tigecycline population pharmacokinetics in patients with community- or hospital-acquired pneumonia.

Publications

Tigecycline population pharmacokinetics in patients with community- or hospital-acquired pneumonia.

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