Clinical Efficacy Of Tigecycline In The Treatment Of Drug-resistant Bacterial Infection And Risk Factors For Hypofibrinogenemia

Objective:Through the literature analysis of adverse drug reactions(adverse drug reaction,ADR)reported by tigecycline in recent years,to explore the characteristics and regularity of ADR occurrence of tigecycline.The efficacy of tigecycline and risk factors for hypofibrinogenemia were analyzed in groups based on the medical records of patients treated with tigecycline at two tertiary hospitals to help clinicians understand and treat the syndrome and more reasonably guide the clinical use of the tigecycline.Methods:1.Literature analysis of adverse reactions caused by tigecyclineUsing"tigecycline","adverse reaction",and other Chinese search terms,and"tigecycline","adverse reaction","case","induced",and"related"as English search terms,literature searches were conducted on databases such as CNKI,Vip,Wanfang,Pub Med,Web of Science,and EMbase.The search period was from January 2005 to August 2022.According to the established inclusion and exclusion criteria,valid information from the literature was extracted using a retrospective study approach,and the included literature cases were assessed for association using the international general Naranjo’s ADR evaluation scale.The characteristics and regularity of the ADR induced by tigecycline were analyzed based on the information contained.2.Clinical efficacy of tigecycline in the treatment of drug-resistant bacterial infectionsThe study included inpatients treated with tigecycline at two tertiary hospitals between October 2021 and December 2022.Patient-related demographic data and clinical variable data were collected based on inclusion and exclusion criteria,and the clinical efficacy of tigecycline was assessed based on the location of the infection,distribution of pathogens,dosage,and combination regimen.3.Study on risk factors of tigecycline-induced hypofibrinogenemiaThe second part of patients was further included and excluded.Patients were divided into a study group(HF group)and a control group(non-HF group)according to whether tigecycline had hypofibrinogenemia.The data were statistically analyzed to study the risk factors and clinical characteristics of tigecycline with hypofibrinogenemia.Results:1.Literature analysis of adverse reactions caused by tigecyclineA total of 91 papers related to ADR caused by tigecycline were included,and108 cases were extracted,of which 68 were male,37 were female,and in three cases the gender was unknown.The main age of the patients was≥60 years old(61 cases,accounting for 56.48%).The primary diseases of the patients were mainly pulmonary and abdominal infections.The occurrence time of ADR caused by tigecycline was from 10 min to 2.5 months after administration,and most ADR occurred within seven days after administration(72 cases,accounting for 66.67%).Tigecycline-induced ADR involved multiple organs and/or systems in 219 cases,of which digestive system damage(105 cases,47.95%)was the most common,followed by blood system damage(77 cases,35.16%).The correlation of ADR was evaluated by Naranjo’s ADR evaluation scale,and most patients were"likely"(76.85%).Most of the patients with ADR improved within a week after drug withdrawal or active symptomatic treatment(68 cases,accounting for 62.96%).2.Clinical efficacy of tigecycline in the treatment of drug-resistant bacterial infections(1)A total of 181 patients were included in this study,including 126 males and55 females,with a median age of 62.00(52.00-72.00).Pulmonary infection ranked first in patients using tigecycline,accounting for 69.61%of the total.Acinetobacter baumannii was the main pathogenic bacteria,accounting for 86.74%of the total population,and all were resistant to carbapenem.(2)Pulmonary infection and abdominal infection were the most effective sites,and the effective rates were 61.90%and 62.50%,respectively.After treatment with tigecycline,the infection indicators(white blood cell,neutrophil percentage,procalcitonin,and body temperature)in the effective group showed a downward trend compared to those before treatment,with statistical differences before and after treatment(P<0.05).There was no statistically significant difference in infection indicators between the effective group and the ineffective group before medication(P>0.05),but there was a statistically significant difference in infection indicators between the two groups after medication(P<0.05).(3)For patients with carbapenem resistant acinetobacter baumannii(CRAB)infection,the effective rate of the high-dose group was higher than that of the low-dose group(62.24%vs.43.90%,P<0.05).The response rate of combination therapy was higher than that of monotherapy(60.90%vs.37.50%,P<0.05).Among all patients with combined drug use,the top four were sulbactam and sulbactam compound preparation(33.76%),carbapenem(20.38%),fosfomycin(20.38%),and aminoglycosides(8.92%),among which the effective rate of sulbactam combination or sulbactam compound preparation was the highest(67.92%).3.Study on risk factors of tigecycline-induced hypofibrinogenemia(1)Basic information of patients:A total of 150 patients were enrolled,80 in the study group and 70 in the control group.There were 108 males and 42 females.There was no significant difference between the two groups.(2)Effects of tigecycline on coagulation function:The plasma FIB valley value of HF patients during medication was significantly lower than that before medication(P<0.001),and the FIB value of HF patients after medication withdrawal was higher than that before medication,which had statistical significance compared with that during medication(P<0.05).The decreased FIB was accompanied by prolonged PT,APTT,and increased INR.The peak values of PT,APTT,and INR during medication were higher than those before medication(P<0.001),and after drug withdrawal,PT,APTT,and INR showed a downward trend,which was statistically significant compared with that during medication(P<0.001).HF occurred 1-23 days after administration,with a median time of 6d.Spearman rank correlation analysis found that the degree of FIB decline was positively correlated with the baseline FIB level before medication(r_s=0.839,P<0.001).(3)Effects of tigecycline on liver and kidney function:There were no significant differences in TBIL,AST,and ALT in the HF group before and after treatment with tigecycline,with P values of 0.536,0.633,and 0.431,respectively,and Scr showed a downward trend(P<0.05).(4)Risk factors of tigecycline-induced hypofibrinogenemia:Variables with P<0.10 in univariate logistic regression analysis included course of treatment,PLT,PT,FIB,APTT,and INR before medication.Multivariate logistic regression analysis showed that the course of treatment and baseline FIB value of tigecycline may be independent risk factors for HF.Conclusion:(1)According to the literature analysis,tigecycline-induced ADR can involve multiple organs and/or systems,and the clinical manifestations are diverse,of which the digestive system is the most common,followed by the blood system.(2)Most of the patients in this study were pulmonary infections,and CRAB was the main pathogenic bacteria.Tigecycline has a good curative effect on pulmonary and abdominal infections,and has a certain control effect on infection indexes.High doses of tigecycline and different combination regimens may affect the therapeutic effect on patients with CRAB infection.(3)Most of the hypofibrinogenemia caused by tigecycline occurred within a week after administration.Hypofibrinogenemia occurred during drug use,accompanied by different degrees of extension of PT and APTT and an increase of INR.FIB rose PT,APTT,and INR decreased after drug withdrawal.The degree of decline in FIB positively correlated with baseline FIB level.(4)Course of treatment and baseline FIB level are independent risk factors for hypofibrinogenemia caused by tigecycline,which can predict the occurrence of hypofibrinogenemia.