Stop Sepsis

Save Lives
with Early
Appropriate and Adequate
Antibiotics
Sepsis : Introduction

➢ Definition : 1991

Sepsis is Bacteraemia accompanied by fever with or without hypotension1

➢ Definition 1992

In 1992, ‘‘sepsis’’ was formally defined as the presence of both

suspected infection and two of the four criteria of the systemic
inflammatory response syndrome (SIRS)2

1. Burke A. Cunha, Crit Care Clin 24 (2008) 313–334

2. Tupchong K. et al. African Journal of Emergency Medicine (2014) Page 1-9
SIRS and Sepsis

➢SIRS criteria

Tupchong K. et al. African Journal of Emergency Medicine (2014) Page 1-9

SIRS and Sepsis

➢Clinical Definition of Sepsis

Khilnani G.C. and Hadda V. Indian J Chest Dis Allied Sci 2009;51:27-36
5
6
Sepsis : a Complex Disease

Bacterimia
Other

Trauma
Fungemia
Infection SEPSIS SIRS Burns
Parasitimia

Pancreatitis
Viremia

Other

Bone RC et al. Chest. 1992;101:1644-55.

the 2016 Third International Consensus Definitions for Sepsis and Septic Shock defin

ing organ dysfunction due to a dysregulated host response to infection.

8
9
Sepsis : High Prevalence in UK

Daniels R J. Antimicrob. Chemother. 2011;66:ii11-ii23

Sepsis: The Future in US

1 800 000 600 000

Severe sepsis cases
1 600 000 US population
500 000

Total US population x 000

1 400 000
Sepsis cases

1 200 000 400 000

1 000 000
300 000
800 000

600 000 200 000

400 000
100 000
200 000

2001 2025 2050

Year

Angus et al. Crit Care Med 2001;27:1363–1310

Sepsis : a Disease Continuum

Infection/Trauma SIRS Sepsis Severe Sepsis Septic Shock

Mortality
40-70%2
Mortality
25-30%2
Mortality

9,3%1

1. Sharma S. et al. Clin Chest Med 29 (2008) 677–687

2. Khilnani G.C. and Hadda V. Indian J Chest Dis Allied Sci 2009;51:27-36
Mortality Rates of Sepsis in Indonesia

Teaching Hospital Surabaya 1996 Teaching Hospital Yogyakarta 2007

600 700

631
504
450 525
70%

354 49%
Patients

Patients
300 350

309

150 175

0 0
Sepsis Dead Sepsis Dead

13 Pradipta I.S. Et.al N Am J Med Sci. Jun 2013; 5(6): 344–352.

The Microbiology of Sepsis
Indonesian Hospital

Organisms isolated from various specimens (n=78)

14
Pradipta I.S. Et.al N Am J Med Sci. Jun 2013; 5(6): 344–352.
Hospital Mortality and Rates of Inadequate Antimicrobial Treatment

15 Emad H. Ibrahim et.al Chest. 2000; 118:146–155

The level of Antibiotic Resistance

16 Pradipta I.S. Et.al N Am J Med Sci. Jun 2013; 5(6): 344–352.

Pattern of Antibiotic Use in Sepsis
Indonesian Hospital n= 255

17 Pradipta I.S. Et.al N Am J Med Sci. Jun 2013; 5(6): 344–352.

Surviving Sepsis Campaign 2012

Delinger RP, et. Al CCM February 2013 • Volume 41 • Number 2

Surviving Sepsis Campaign 2012

Recommendations: Initial Resuscitation and Infection Issues

A. Initial Resuscitation

B. Screening for Sepsis and Performance Improvement

C. Diagnosis

D. Antimicrobial Therapy
E. Source Control

F. Infection Prevention

19

Delinger RP, et. Al CCM February 2013 • Volume 41 • Number 2

 Surviving Sepsis Campaign 2012
Sepsis Resuscitation Bundle
(To be started immediately and completed within 6 hours)
Antimicrobial Therapy

1. Administration of effective intravenous antimicrobials within the first hour of

recognition of septic shock (grade 1B) and severe sepsis without septic shock (grade
1C) as the goal of therapy.

2a. Initial empiric anti-infective therapy of one or more drugs that have
activity against all likely pathogens (bacterial and/or fungal or viral) and that penetrate in
adequate concentrations into tissues presumed to be the source of sepsis (grade 1B).

2b. Antimicrobial regimen should be reassessed daily for potential de-escalation

(grade 1B).

3. Use of low procalcitonin levels or similar biomarkers to assist the clinician in the
discontinuation of empiric antibiotics in patients who initially appeared septic, but have
no subsequent evidence of infection (grade 2C).

Delinger RP, et. Al CCM February 2013 • Volume 41 • Number 2

 Surviving Sepsis Campaign 2012
Sepsis Resuscitation Bundle
(To Antimicrobial Therapy
be started immediately Cont.
and completed within 6 hours)
4a. Combination empirical therapy for neutropenic patients with severe sepsis (grade 2B)
and for patients with difficult-to-treat, multi drug resistant bacterial pathogens
such as Acinetobacter and Pseudomonas spp. (grade 2B). For patients with severe infections
associated with respiratory failure and septic shock, combination therapy with an extended
spectrum beta-lactam and either an aminoglycoside or a fluoroquinolone is for P. aeruginosa
bacteremia (grade 2B). A combination of beta-lactam and macrolide for patients with septic shock
from bacteremic Streptococcus pneumoniae infections (grade 2B

4b. Empiric combination therapy should not be administered for more than 3–5 days.
De-escalation to the most appropriate single therapy should be performed as soon as the
susceptibility profile is known (grade 2B).

5. Duration of therapy typically 7–10 days; longer courses may be appropriate in

patients who have a slow clinical response, undrainable foci of infection, bacteremia with S.
aureus; some fungal and viral infections or immunologic deficiencies, including neutropenia (grade
2C).

6. Antiviral therapy initiated as early as possible in patients with severe sepsis or septic shock
of viral origin (grade 2C).

7. Antimicrobial agents should not be used in patients with severe inflammatory states
determined to be of non infectious cause (UG).

Delinger RP, et. Al CCM February 2013 • Volume 41 • Number 2

 Mortality in Patients with Septic Shock

1.0 survival fracton

cumulatve antbiotc initaton
Facton of total patents

For each hour’s

0.8 delay in
administering
0.6 antibiotics in
septic shock,
0.4 mortality
increases by
0.2
7.6%
0.0

6
5

12

-2

-3
0.

5-

+
2

36
12

24
0-

2-

3-

5-

6-
1-

4-

9-
0.

Time from hypotension onset (hrs)

Kumar et al. CCM. 2006:34:1589-96.

Mortality Rate in Patients with Sepsis
Appropriate vs Inappropriate Antimicrobial

Effects of inappropriate and appropriate antimicrobial therapy

on mortality in severe sepsis and septic shock

Matthew R.M et.al. Infect Dis Clin N Am 23 (2009) 485–501

 Early Adequate Antibiotics

Hospital mortality according to the adequacy of the initial antimicrobial

treatment prescribed for bloodstream infection

24 Kollef Chest 1999;115;462-474

The Choice of Empirical Antibiotics

• The patient’s history.

• Drug intolerances.
• Underlying disease.
• The clinical syndrome.
• Susceptibility/Resistance patterns of pathogens in the
community & hospital.
• Previously have been documented to colonize or infect the
patient.

International Surviving Sepsis Campaign Guidelines Committee.

Crit Care Med 2008; 36(1): 296–327.
Susceptibility of Meropenem
Main Pathogens Causes of Sepsis

Rhomberg PR. Jones RN. Diagnostic Microbiology and Infectious Disease 2009; 65 : 414–426
Antimicrobial Treatment of Sepsis

Cunha BA. Et al.Crit Care Clin 24 (2008) 313–334

Meropenem vs Imipenem in Sepsis

100
100 100

75
Response Rate (%)

Clinical
50 Bacteriologic
50
40

25

n=5 n=3 n=10 n=8

0
Meropenem Imipenem

Verwaest C. Clin Microbiol Infect. 2000; 6: 294-302

28
Thank You!