Sepsis journal club

1. EFFICACY AND SAFETY OF INJECTION SEPSIVAC IN GRAM
NEAGTIVE SEPSIS ADMINISTERED via AN INTRAVENOUS ROUTE
MODERATOR :- DR.JITENDRA H
STUDENT:-DR.TEJESHWINI C

2. INTRODUCTION
 Sepsis is a potentially fatal disorder of the immune system that arises when the body’s defensive
responses to infection cause harm to its tissues and organs
Even today, septic shock (28.3%), the most severe subset of sepsis, has a death rate of 18.1% as
reported by an INDICAPS study involving 124 Indian ICUs.
Sepsis remains an important and life-threatening problem and the most common cause of death in the
ICU, with mortality between 20 and 50% for severe sepsis and 45–80% for septic shock
Mycobacterium w (Mw) is an immunomodulator. It is known to contain multiple antigens. Its
administration is associated with the antigen-specific generation of cell-mediated immunity

3. INTRODUCTION(cont.)
Mw has been approved by the Drug Controller General of India for use in the treatment of gram-
negative sepsis along with the standard of care treatment
The traditional route of administration for Mw is ID, which is limited to administering 0.1 mL per Inj
Mw’s IV administration has not been explored in severe sepsis patients
Based on the efficacy and safety data of Mw, as observed in previous clinical studies, we hypothesize
that using Mw as an adjuvant to standard treatment in sepsis via the IV route will be safe as well as
effective in decreasing complications, hasten the organ function recovery, and reducing the mortality
associated with sepsis

4. NEED FOR THE STUDY
 To justify the advantage of Mycobacterium w as an immunomodulator in Sepsis
 To prove the safety and efficacy of Mw in septic shock including the geriatric patient
population.

5. METHODOLOGY
•STUDY DESIGN:-
The present observational study was performed on 30 patients of >18 years of age, presumed to
have gram-negative sepsis with one organ dysfunction and on single vasopressor support.
Those with a history of allergic reactions attributed to Inj Sepsivac or any of its excipients,
pregnant and lactating women, and those with generalized septic skin conditions were excluded
 Informed consent was taken from all the patients

6. METHODOLOGY
•STUDY POPULATION:-
Inclusion criteria :-
•Patients of >18 years of age, presumed to have gram-negative sepsis with one organ dysfunction
and on single vasopressor support.

7. METHODOLOGY
•STUDY POPULATION:-
Exclusion criteria:-
•History of allergic reactions attributed to Inj Sepsivac
•Pregnant and lactating women
• Generalized septic skin conditions

8. RESULT
The mean age of patients with gram-negative sepsis was 62.67 ± 12.77 years, ranging from 32 to
88 years.
The majority of the patients had pneumonia [12 (40.1%)] followed by intraabdominal infection [8
(26.7%)] and urinary tract infection [5 (16.7%)]. Other less common sites of infections were
blood (n = 1), joint (n = 1), skin and soft tissue (n = 3).
 All vital parameters showed significant change from day 2 onward. Respiratory rate, heart rate,
temperature, and blood pressure had a significant change from day 2 onward from baseline
posttreatment
The mean SOFA score was 13 at baseline (Fig. 1). At the end of day 1, the mean SOFA score did
not significantly change from the baseline. At the end of day 2, the mean SOFA score showed a
significant change till the end of treatment from baseline

9. Trend in mean SOFA score among the study cases

13. DISCUSSION
The use of Mw via IV route combined with standard care has shown significant improvement in all vital
parameters and mean SOFA score from day 2 onward in patients with severe gram-negative. Similar
improvement was observed for AST,
Similar improvement was observed for AST, ALT, blood urea, and C-reactive protein from day 4 onward.
A significant improvement in TLC was observed from day 7 onward compared to the baseline. None of the
patients developed any major adverse event and Mw was well-tolerated in all patients
Results obtained in the present study are comparable to previous research of Mw using the ID route. A
randomized clinical trial by Sehgal et al. on 50 patients with severe sepsis reported a significant reduction in
days on mechanical ventilation, ICU, and hospital length of stay, lower incidence of nosocomial infection,
and delta SOFA score with the use of Mw along with standard care compared to standard care alone

14. DISCUSSION
 Mw is also reported as being safe and effective when administered by IV as per data from other indications
The IV method of administration of Mw provides the following benefits—(1) ease of administration via a
secure ongoing IV line and capacity to administer the needed extra dose in a single Inj. ID administration
requires additional training/skills not needed in the ICU setting for IV administration
The highest dose provided via the ID method is 0.3 mL/day compared to a dose as high as 5.0 mL/day by
the IV route.
Findings of the present study provide more strength to observations of the previous series. It also paves the
way for evaluating Mw via the IV route in a larger study.
Bacterial endotoxin joins with toll-like receptor (TLR) 4 on the host leukocyte and other immune cells in
gram-negative sepsis to activate pro-inflammatory and anti-inflammatory pathways simultaneously

15. DISCUSSION
While beneficial in the first few hours, the anti-inflammatory mechanism may be harmful, resulting in
immunosuppression, which is counterproductive
. Its administration is associated with the antigen-specific generation of cell-mediated immunity, including
generation of strong Type 1 T helper (Th1) response (TLR2 agonistic activity), suppression of cytokine
production (poly TLR- 4,5,7, and 9 antagonist activit y), macrophage activation, T cell proliferation, the
release of cytokines IL-2, interferon-gamma and genetic expression modulation

16. LIMITATIONS
Small sample size
 Lack of randomization
Absence of a comparator arm (ID route)
Large multicentric randomized trials are required to confirm the findings

17. STRENGTHS OF THE STUDY
 This is the first study that has proved the safety and efficacy of Mw in septic shock including the
geriatric patient population
Use of Intravenous administration of Mw immunomodulator when compared to other studies
which used Intradermal route as it gives more favourable immune response in lung parenchyma

18. CONCLUSION
The use of an immunomodulator Mw in Septic shock in addition to the standard of care was
found to be well tolerated and efficacious
Its improved survival is evident from the improvement in clinical and biochemical parameters.

19. FUNDING
NIL

20. REFERENCES
1) Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions
for sepsis and septic shock (sepsis-3). JAMA 2016;315:801–810
2) Jarczak D, Kluge S, Nierhaus A. Use of intravenous immunoglobulins in sepsis therapy—a
clinical view. Int J Mol Sci 2020;21:5543
3) Divatia JV, Amin PR, Ramakrishnan N, et al. Intensive care in India: the Indian intensive care
case-mix and practice patterns study. Indian J Crit Care Med 2016;20:216–225
4) Gritte RB, Souza-Siqueira T, Curi R, et al. Why septic patients remain sick after hospital
discharge? Front Immunol 2021;11:605666

21. REFERENCES(cont..)
5) Surbatovic M, Popovic N, Vojvodic D, et al. Cytokine profile in severe gram-positive and gram-
negative abdominal sepsis. Sci Rep 2015;5:11355.
6) Xu XJ, Tang YM, Liao C, et al. Inflammatory cytokine measurement quickly discriminates
gram-negative from gram-positive bac teremia in pediatric hematology/oncology patients with
septic shock. Intensive Care Med 2013;39(2):319–326
7) Ingale A, Ingale F, Kunwar B, et al. Role of Mycobaterium w for the treatment of COVID-19:
an observational study. J Assoc Physicians India 2021;69(1):19–22.
8) Sehgal IS, Agarwal R, Aggarwal AN, et al. A randomized trial of Mycobacterium w in severe
sepsis. J Crit Care 2015;30(1):85–89

22. APPLICABILITY IN OUR SETUP
NO

23. CRITICAL ANALYSIS:
TITLE
SAMPLE SIZE
METHODOLOGY
RESULT
CONCLUSION

24. REFERENCES(cont..)
9) Sehgal IS, Basumatary NM, Dhooria S, et al. A randomized trial of mycobacterium w in severe
presumed gram-negative sepsis. Chest 2021;160(4):1282–1291
10) Darrah PA, Zeppa JJ, Maiello P, et al. Prevention of tuberculosis in macaques after
intravenous BCG immunization. Nature 2020;577:95–102.

25. THANK YOU