The clinical treatment outcomes and side effects of tigecycline in infectious diseases

• Main Authors: Chang-Hsueh Wu, 吳昌學
• Other Authors: 張上淳
• Format: Others
• Language: zh-TW
• Published: 2012
• Online Access: http://ndltd.ncl.edu.tw/handle/764zdf

碩士 === 國立臺灣大學 === 臨床藥學研究所 === 100 === Background: Tigecycline is approved by the USA Food and Drug Administration（FDA） for the treatment of complicated intra-abdominal infections（cIAIs）, complicated skin and skin structure infections（cSSSIs）, and community acquired pneumonia（CAP）. Tigecycline is active against many resistant pathogens in in-vivo study, and it can be used for the antibiotic-resistant bacterial infections. However, FDA imposed a black box warning on tigecycline in 2010. Concerning the increasing mortality rate of tigecycline, especially in the treatment of hospital-acquired pneumonia, in clinical trials and retrospective studies. In addition, patients treated by tigecycline have significant more treatment failure and septic shock. Therefore, tigecycline is not recommended in critically ill patients. Objective: The goal of this study is to evaluate the clinical response and mortality of patients receiving tigecycline treatment in Taiwan. The clinical response and mortality of patients with pneumonia only are analyzed in sub-group analysis, identifying the risk factors for treatment failure and the indicated pathogens assessed. We also evaluate the adverse drug reactions of tigecycline. Methods: This retrospective study included patients hospitalized in a 2500-bed medical center with infection-related diagnosis and received tigecycline between January 2010 and June 2011. Patients younger than 20 years old or with incomplete data are excluded. We reviewed the medical records including baseline characteristics, comorbidities, disease severity, clinical presentations, laboratory data, culture results, pathogens of secondary infection, clinical response, and adverse drug reactions of tigecycline. Treatment outcomes in different groups were analyzed by chi-square test. We also identified the risk factors for treatment failure in all patients and in patients with pneumonia only by logistic regression. Results: Among 137 patients, 61（44.5%）patients had multiple-site infection, 71（51.8%） patients had pneumonia with other infections, 76（55.5%）patients had mono-site infection, 60 patients had pneumonia only, 11（8%） patients had cIAIs, and 5（3.6%） patients had cSSSIs. Most patients had comorbid respiratory diseases（80%）, renal diseases（71%）, and cardiovascular diseases（61%）. The most common indicated pathogens were multidrug-resistant Acinetobacter baumannii（MDRAB）（71%）, and Stenotrophomonas maltophilia（7%）. The susceptibility of MDRAB was approximately 67% in this study. Overall clinical response was 50%. Clinical response in patients with pneumonia only was 45%, which is lower than patient with cIAIs or cSSSIs only（100% and 64%, respectively）.Patients with mono-microbial infection had higher clinical response than those with poly-microbial infection（59% vs 39%, P=0.0241）. Besides, the susceptible pathogens also had better clinical response（54% vs 32%, P=0.0414）. Fifty-one patients（37%） had secondary infections in total, and the most common pathogen was Pseudomonas aeruginosa（10%）. In total patients, blood sugar higher than 180 mg/dL during tigecycline treatment（OR 3.28, P=0.0395）, septic shock at the first day of tigecycline used（OR 3.34, P=0.002）, and acute kidney injury at the first day of tigecycline used（OR 2.40, P=0.0416） were independent risk factors for treatment failure. In patients with pneumonia only, the independent risk factors were septic shock at the first day of tigecycline used（OR 5.04, P=0.0078）. In this study, the most common side effects were gastrointestinal（GI） side effects（35%）, and diarrhea（21%） is the most frequently. In contrast to previous studies, nausea and vomiting were reported both only 4%in this study. Conclusion: Patients’ disease severity is correlated with treatment outcomes, regardless in all patients or in patients with pneumonia only. There would be more treatment failure in patients with severe disease status and in patients with hyperglycemia. However, the mortality rate is similar with other studies. The most adverse drug reactions of tigecycline are gastrointestinal tract side effects. Among gastrointestinal tract side effects, diarrhea is the most common side effects. Percentage of nausea and vomiting is less than prior studies.