Thymosin alpha1- and ulinastatin-based immunomodulatory strategy for sepsis arising from intra-abdominal infection due to carbapenem-resistant bacteria.
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).
Zhang
Ying
Y
Key Laboratory of Infectious Diseases, Ministry of Public Health, First Affiliated Hospital, College of Medicine, Zhejiang University, Zhejiang, China.
Chen
Hao
H
Li
Yu-min
YM
Zheng
Shu-sen
SS
Chen
Ya-gang
YG
Li
Lan-juan
LJ
Zhou
Lin
L
Xie
Hai-yang
HY
Praseedom
Raaj Kumar
RK
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
D000900:Anti-Bacterial Agents; D015780:Carbapenems; D006023:Glycoproteins; D007155:Immunologic Factors; D013947:Thymosin; C028665:urinastatin; D000077596:Thymalfasin