NEW GENERATION

ANTIBIOTIC
IN SEPSIS

Umar Zein
Tropical Medicine
Department of Internal Medicine
Faculty of Medicine
Universitas Islam Sumatera Utara
Data di RSUP H. Adam Malik
Medan
• The most aetiology diagnosis of sepsis were:
• pneumonia (70,84%), UTI (10,28%), IAI (4,11%), and
SSTI(3,93%).
The gram-negative bacteria was the most common bacteria
• Acinetobacter baumanii (26,6%), Klebsiella pneumonia
(22,8%), and
• Escherichia coli (18,8%).
The gram-positive bacteria were
• Staphylococcus sp. (54,2%), Enterococcus sp. (33,6%),
and Streptococcus sp. (8,4%).
AMR for sepsis patient in non-ICU for gram-negative bacteria were
Amikasin (19,1%), Meropenem (30,6%), and Cefoperazone
sulbactam (33,5%) while for gram-positive bacteria was only
vancomycin with the resistance level below 20% (18,3%). In the
ICU patients, the AMR prevalence was higher than the non-ICU.
INFECTION INFECTION

SEPSIS INFECTION

SEVERE SEPSIS
SEPSIS
 HISTORICAL PERSPECTIVE

SIRS Criteria ( > 2)

• Temperature > 38 C < 36 C
• Heart rate > 90 bpm
• Respiratory rate > 20 /min or
a PaCO2 < 32 mmHg
• White blood cell count >
12,000 / cu mm or < 4,000 /
cu mm, or > 10 bands
Source: CHEST 1992
 NEW SEPSIS DEFINITION

“Sepsis is a life threatening

organ dysfunction caused
by a dysregulated host
response to an infection.”

The European Society of Intensive Care Medicine/Society of Critical Care

Medicine Third International Consensus definitions for Sepsis and Septic
Shock task force (the Sepsis-3 task force)
 SEPSIS SCORING TOOL

Quick SOFA / qSOFA

> 22/ min SBP

≤100mmHg

In patients with infection a qSOFA score >

2 is associated with higher mortality and
prolonged ICU stay.
 SEP-1 TWO CLOCKS

SEP-1: EARLY MANAGEMENT BUNDLE

Severe

3 hr.

6 hr.
Sepsis

Time Zero
Interventions Required:
 Blood culture before Interventions Required:
antibiotics  Lactate level repeated (If
 Antibiotics elevated)
 Lactate level

Set Measure ID # SEP-1-8; Early Management Bundle, Severe Sepsis/Septic Shock

 SEP-1 TWO CLOCKS
TO BE COMPLETED WITHIN 3 HOURS OF TIME
OF PRESENTATION:
1. Obtain blood cultures prior to administration of
antibiotics.
2. Measure lactate level.
3. Administer broad spectrum antibiotics.
4. Administer 30ml/kg crystalloid for hypotension,
defined as a “mean arterial pressure” MAP<65 or
lactate ≥4mmol/L.

2012 NQF: SEPSIS 0500

 SEP-1 Two Clocks

“Delays in administering all

four guidelines
recommendations, even
when they did not exceed 3
hours, were associated with
a significant increase in
in-hospital mortality.”
SCCM journal April 2018. Volume 46. Number 4
 SEPTIC SHOCK ONLY
3 hr.
Time Zero
Interventions Required:
ALL of Severe Sepsis +
 Fluid 30 ml/kg
(NO exclusionary
criteria)
Shock Assessment
Physical Exam (ALL)
• Vital Signs (T, HR, RR, BP)
• Cardiopulmonary exam
• Capillary refill evaluation
• Peripheral Pulse evaluation
• Skin evaluation
6 hr.
Interventions Required:
Persistent Hypotension
 Within 1 hour of fluid add
VASOPRESSOR
Persistent Hypotension
OR Lactate > 4
 Shock Assessment (1 of 2)
Hemodynamics (2 of 4)
• CVP
• SVO2
• Bedside cardiovascular ultrasound
• Passive leg raise / fluid challenge
a 6Rs rule for sepsis and septic
shock management:

This rule encompasses rational decisions

right patients,
regarding the timing of treatment, the
right time, identification of the correct pathogen, the
right target, selection of appropriate antibiotics, the
right antibiotics, formulation of a scientifically based
antibiotic dosage regimen, and the adequate
right dose, and
control of infectious foci.
right source
control.
 ANTIBIOTIC CHEMOTHERAPY

- - FACTORS IN EMPIRIC ANTIBIOTIC CHOICE

a) SITE OF INFECTION, b) ENVIRONMENTAL EXPOSURE
c) IMMUNOSUPPRESSION, d) DRUG ALLERGY
e) REVIEWING EMPIRIC THERAPY

• - ANTIBIOTIC INDUCED ENDOTOXIN RELEASE

- DETECTION AND REMOVAL OF INFECTED
MATERIAL
a) DRAIN ABSCESSES,
b) RESECT DEAD TISSUE
c) REMOVE INFECTED FOREIGN MATERIAL

16
Time to Antibiotics Following Onset Septic Shock

Kumar A, et al. Crit Care Med 2006; 34:1589-1596

 IMPORTANT POINTS TO CONSIDER WHEN USING THE
GUIDELINE:

• The selection of appropriate antibiotic therapy is complex -

this guideline is not intended to cover all possible scenarios
• Prompt administration of antibiotics and resuscitation fluids
is vital in the management of the patient with sepsis.
• In patients diagnosed with septic shock the goal is to
commence antibiotic therapy within the first hour.
• Obtain at least two sets of blood cultures and other clinical
specimens (e.g. urine, cerebrospinal fluid, wound swabs) as
appropriate PRIOR TO antibiotic commencement.
• Do not delay antibiotic administration to wait for results of
investigations.
• If agents listed are not available in your hospital, consult
the Attending Medical Officer and seek expert advice.
• Patients must be weighed to ensure correct dosage of
medications
 
 IMPORTANT POINTS TO CONSIDER WHEN USING THE
GUIDELINE:

• Clinicians must document the indication,

drug name, dose, route of administration
and review date for antibiotics in the patient’s
health record
• Antibiotic therapy should be reviewed by the
treating team 24 hours and 48 hours
after commencement.
• Antibiotics should be reviewed once
microbiology results are available, and
continued, changed or ceased as required

 
New Antibiotics
• delafloxacin,
omadacycline,
lefamulin,
solithromycin,
nemonoxacin, and
ceftaroline.
• Their major advantages
include activity against
methicillin-
resistant Staphylococcu
s aureus and
macrolide-
resistant Strep.
pneumoniae.
The New Antibiotics
• Fluoroquinolone: Delafloxacin
• Tetracycline: Omadacycline IV
• Pleuromutilin: Levamulin, IV and oral for
pneumonia
• Macrolide: Solithromycine
• Nonfluorinated quinolone: Nemonoxacine
• Cephalosphorin generasi ke 5:
Ceftaroline, Cephtobiprole
• Derivate Vancomycin: Telavancin
• Aminoglikoside: Tobramycin
Thank You