| Background:Tigecycline is the first glycylcycline antibiotic approved by the US Food and Drug Administration (FDA), as an extended-spectrum antibiotic, it has demonstrated strong activity against the majority of gram-positive, gram-negative organisms and many anaerobic bacteria. It overcomes2major resistance mechanisms of tetracycline due to the unique9-tert-butyl-glycylamido moiety that occurs at the9th position of the D ring:drug-specific efflux pump acquisition and ribosomal protection. Tigecycline has little target organ toxicity and clinically relevant drug interactions. Furthermore, the drug is extensively distributed in tissues and needs no dosage adjustment for patients with hepatic or (and) renal impairment except severe hepatic impairment (Child-Pugh C) as well as hemodialysis, all these make tigecycline the most useful drug for serious infections, especially in critically ill patients. But so far most study data on clinical pharmacokinetics and pharmacodyna-mics of tigecycline have been acquired from healthy volunteers and common patients, therefore, the data is not applied to critically ill patients since they tend to be susceptible to infections due to their complicated underlying diseases, immunocom-promise, multiple comlications and invasive therapeutic procedures, meanwhile, the multi-drug resistant bacteria (MDRB) giving rise to less clinical effectiveness. Additionally, these critically ill patients almost accompany with special physiological states, such as hypoalbuminemia, edema, hyperdynamic circulation and so on which will complicate the disposition of therapeutic drugs. Consequently, clinical studies on tigecycline for critically ill patients are particularly necessary.Objective: This study was aimed to observe the clinical outcomes and side effects of tigecycline in critically ill patients with serious infections and investigated the reasonable therapeutic regimen to provide reference for clinical practice in curing infections with tigecycline.Method:This prospective, multicenter trial was carried on critically ill patients hospitali-zed in six teaching hospitals between January1,2011and December31,2012. If the pathogenic examination indicated multi-drug resistant bacteria sensitive to tigecycline, the patients with informed consent would be administrated with tigecycline. After data entry into a computerized database, statistical analyses were performed using the software SPSS17.0.Results:There were47subjects enrolled in our study, but only43ones were evaluable eventually including31men (72.1%) based on the selection criteria. Their indications for the administration of tigecycline consisted of CSSTIs (2.3%) and CIAIs (4.7%) which was approved by Food and Drug Administration, HAP (60.5%), bacteremia (4.7%) and multiple-site infections (25.6%). Most patients (90.7%) received tigecycline as combination therapy, and the clinical success rates were53.5%in total. Of the microbiologically evaluable cases, MDRAB predominated (46/61,75.4%) and the clinical success rate of infections with them was52.4%. Extended-spectrum beta-lactamases (ESBLs) were discovered in69.0%Enterobacteriaceae strains. The microbiological eradication rates varied at different infections sites, the rates of HAP, CSSIs and CIAIs patients were62.2%,100.0%and100.0%respectively while the microbiological eradication rate of bacteremia cases was only50.0%. Furthermore, only the clinical success rate of subjects with APACHE Ⅱ score over20was obvious-sly lower than the rest ones (33.3%vs68.0%, P=0.025) and the difference was statistically significant. Pseudomonas aeruginosa was detected from51.2%of all subjects during the therapy while39.4%carbapenem-resistant strains were reported.Conclusion:Tigecycline was safe and effective for critically ill patients with serious infections, appropriate administration occasion and sufficient dosage and duration were significant for clinical success. Pathogens maintained high sensitive to tigecycline and it was effective to use tigecycline for infections caused by multi-drug resistant pathogens that were difficult to treat clinically, no matter it was used alone or in combination with other antibiotic agents. However, the therapeutic effect was poorer compared with the previous studies and the severer conditions might be the main cause. In addition, tigecycline is an alternative for MDRAB infections in critically ill patients with quite limited therapy selections and high mortality rate. Owning to the great need for clinical trials monitoring on tigecycline for serious infections in critically ill patients and the limited drugs for serious infections recently, clinicians should weigh risk and benefit for prescribing tigecycline. |
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