title: Thymosin alpha1- and ulinastatin-based immunomodulatory strategy for sepsis arising from intra-abdominal infection due to carbapenem-resistant bacteria.
abstract: OBJECTIVE
  The aim of this study was to evaluate the potential efficacy of therapy with thymosin alpha(1) and ulinastatin for patients with sepsis due to carbapenem-resistant bacteria.
  
  
  METHODS
  Prospective, randomized, parallel controlled clinical study.
  
  
  METHODS
  A total of 120 patients received a diagnosis of sepsis caused by infection with carbapenem-resistant bacteria and satisfied the study enrollment criteria. Sixty patients received carbapenems combined with thymosin alpha(1) and ulinastatin (the CTU group), and the other 60 patients were treated with carbapenems and placebo (the CP group). For both groups, flow cytometry was used to enumerate lymphocyte subsets, and ELISA was used to determine cytokine concentrations.
  
  
  RESULTS
  When the 2 groups were compared, the CTU group exhibited a better performance with respect to organ failure scores such as the Acute Physiology and Chronic Health Evaluation II score, the Multiple Organ Failure Score, and the Glasgow Coma Scale. The CTU group also showed significant improvements in CD4(+)CD8(+) count after initiation of treatment. In addition, compared with the CP group, in the CTU group the balance between proinflammatory mediators (such as tumor necrosis factor-alpha, interleukin [IL]-1beta, IL-6, and IL-8) and anti-inflammatory cytokines (including IL-4 and IL-10) was better modulated, and the cumulative survival rate of the CTU group exceeded that of the CP group by 17.8% at day 28, 25.9% at day 60, and 27.4% at day 90.
  
  
  CONCLUSIONS
  Immunomodulatory therapy that combines thymosin alpha(1) and ulinastatin appears to improve the survival rate for patients infected with carbapenem-resistant bacteria. The number of patients in this study was relatively small, and although the same number of patients was initially enrolled in each study group, the groups were not the same size at the end of the study. Therefore, a larger clinical trial should be conducted to validate this conclusion.
  
  
  BACKGROUND
  The trial was registered with the Chinese State Food and Drug Administration (Peking Science and Technology Development Plan, 2002[641]), (registration number 2007Y0211).
authors.affiliation: Key Laboratory of Infectious Diseases, Ministry of Public Health, First Affiliated Hospital, College of Medicine, Zhejiang University, Zhejiang, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Hao
authors.initials: H
authors.lastname: Chen
authors.forename: Yu-min
authors.initials: YM
authors.lastname: Li
authors.forename: Shu-sen
authors.initials: SS
authors.lastname: Zheng
authors.forename: Ya-gang
authors.initials: YG
authors.lastname: Chen
authors.forename: Lan-juan
authors.initials: LJ
authors.lastname: Li
authors.forename: Lin
authors.initials: L
authors.lastname: Zhou
authors.forename: Hai-yang
authors.initials: HY
authors.lastname: Xie
authors.forename: Raaj Kumar
authors.initials: RK
authors.lastname: Praseedom
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D015780:Carbapenems / Q000494:pharmacology* / Q000627:therapeutic use; D002761:Cholangitis / Q000150:complications; D024901:Drug Resistance, Multiple, Bacterial; D004359:Drug Therapy, Combination; D005260:Female; D006023:Glycoproteins / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology* / Q000627:therapeutic use; D007415:Intestinal Obstruction / Q000150:complications; D008100:Liver Abscess / Q000150:complications; D008297:Male; D008875:Middle Aged; D010195:Pancreatitis / Q000150:complications; D010538:Peritonitis / Q000150:complications; D018805:Sepsis / Q000188:drug therapy* / Q000382:microbiology; D000077596:Thymalfasin; D013947:Thymosin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; D006023:Glycoproteins; D007155:Immunologic Factors; D013947:Thymosin; C028665:urinastatin; D000077596:Thymalfasin