Exposure-Response Analyses of Tigecycline Efficacy in Patients with Complicated Intra-Abdominal Infections
| العنوان: | Exposure-Response Analyses of Tigecycline Efficacy in Patients with Complicated Intra-Abdominal Infections |
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| المؤلفون: | S. A. Van Wart, Julie A. Passarell, Brenda Cirincione, Paul G. Ambrose, Evelyn J. Ellis-Grosse, Timothy Babinchak, Alison K. Meagher, K. Liolios |
| المصدر: | Antimicrobial Agents and Chemotherapy. 52:204-210 |
| بيانات النشر: | American Society for Microbiology, 2008. |
| سنة النشر: | 2008 |
| مصطلحات موضوعية: | Adult, Male, medicine.medical_specialty, Adolescent, medicine.drug_class, Antibiotics, Minocycline, Microbial Sensitivity Tests, Tigecycline, Clinical Therapeutics, Biology, Gram-Positive Bacteria, Loading dose, Bacteria, Anaerobic, Double-Blind Method, Internal medicine, Gram-Negative Bacteria, medicine, Humans, Pharmacology (medical), Gram-Positive Bacterial Infections, Aged, Antibacterial agent, Aged, 80 and over, Pharmacology, Not evaluated, Abdominal Cavity, Middle Aged, biology.organism_classification, Anti-Bacterial Agents, Surgery, Clinical trial, Treatment Outcome, Infectious Diseases, Area Under Curve, Cohort, Female, Bacteroides fragilis, Gram-Negative Bacterial Infections, medicine.drug |
| الوصف: | Exposure-response analyses were performed to test the microbiological and clinical efficacies of tigecycline in complicated intra-abdominal infections where Escherichia coli and Bacteroides fragilis are the predominant pathogens. Data from evaluable patients enrolled in three clinical trials were pooled. Patients received intravenous tigecycline (100-mg loading dose followed by 50 mg every 12 h or 50-mg loading dose followed by 25 mg every 12 h). At the test-of-cure visit, microbiological and clinical responses were evaluated. Patients were prospectively classified into cohorts based on infection with a baseline pathogen(s): E. coli only (cohort 1), other mono- or polymicrobial Enterobacteriaceae (cohort 2), at least one Enterobacteriaceae pathogen plus an anaerobe(s) (cohort 3), at least one Enterobacteriaceae pathogen plus a gram-positive pathogen(s) (cohort 4), and all other pathogens (cohort 5). The cohorts were prospectively combined to increase sample size. Logistic regression was used to evaluate ratio of steady-state 24-hour area under the concentration-time curve (AUC) to MIC as a response predictor, and classification-and-regression-tree (CART) analyses were utilized to determine AUC/MIC breakpoints. Analysis began with cohorts 1, 2, and 3 pooled, which included 71 patients, with 106 pathogens. The small sample size precluded evaluation of cohorts 1 (34 patients, 35 E. coli pathogens) and 2 (16 patients, 24 Enterobacteriaceae ). CART analyses identified a significant AUC/MIC breakpoint of 6.96 for microbiological and clinical responses ( P values of 0.0004 and 0.399, respectively). The continuous AUC/MIC ratio was also borderline predictive of microbiological response ( P = 0.0568). Cohort 4 (21 patients, 50 pathogens) was evaluated separately; however, an exposure-response relationship was not detected; cohort 5 (31 patients, 60 pathogens) was not evaluated. The prospective approach of creating homogenous populations of pathogens was critical for identifying exposure-response relationships in complicated intra-abdominal infections. |
| تدمد: | 1098-6596 0066-4804 |
| DOI: | 10.1128/aac.00813-07 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::68f706835dd3268294641de2e94ba184 https://doi.org/10.1128/aac.00813-07 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....68f706835dd3268294641de2e94ba184 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10986596 00664804 |
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| DOI: | 10.1128/aac.00813-07 |