Antibiotic therapy in Sepsis

Usman Hadi
DEFINITIONS
Sepsis Life-threatening organ disfunction caused by a dysregulated host
response to infection

Organ dysfunction:
Acute change in total SOFA score ≥ 2 points consequent to the
infection
Quick SOFA score: Respiratory rate ≥ 22/min.; Altered mentation;
Systolic blood pressure ≥ 100 mm Hg.
Septic shock Sepsis in which underlying circulatory and cellular/metabolic
abnormalities are profound enough to substantially increase
mortality

Septic shock can be identified with: persisting hypotension requiring

vasopressors to maintain MAP ≥ 65 mm Hg and having serum
lactate > 2 mmol /L (18 mg/dL) despite adequate volume resusitation

(Singer et al., JAMA 2016)

SOFA (Sequential <sepsis related> Organ Failure Assessment)

 Patient with suspected
infection

No No Monitor clinical condition;

qSOFA Sepsis stil re-evaluate for possible
2? suspected sepsis if clinical indicated
Yes ?
Yes
Assess for evidence of
organ dysfunction

No Monitor clinical condition;

SOFA2 re-evaluate for possible
? sepsis if clinical indicated
Yes

Sepsis

Despite adequate fluid resuscitation,

1. Vasopressors required to maintain No
MAP  65 mmHg
2. Serum lactatete level >2 mmol/L?
Yes

Septic shock
(Singer et al., JAMA 2016)
 Management
Sepsis

Diagnosis Therapy

Supportive
Lab routine
lnitial resuscitation Specific
Blood/other spec.
cultures Fluid therapy
Antibiotics
Radiologic exam Steroids
Source control
Biochemical Vasopressors/inotropic
Modification of
markers: PCT, CRP Mechanical ventilation inflammation
Blood tranfusion
Dialysis, glucose
control, RRT
 ANTIMICROBIAL REGIMEN SELECTION

Choosing an antimicrobial agent to treat infection → far more complicated than

matching a drug to a known or suspected pathogen
Initial selection of antimicrobial therapy → nearly always empiric
Empiric therapy is based on:
• Patient’s history: the presence of specific immune defects, comorbidities
• Physical examination:  source of infection
• Results of Gram stains or of rapidly performed tests on specimens from
infected site
• Local map of antibiotic
• Prevalent pathogens within the community and hospital
Antimicrobial agents
Intravenous antibiotic should be started within the 1st hour
of severe sepsis, after appropriate cultures be obtained

Initial empirical anti-infective agents should include ≥ 1 drug

against the likely pathogens. The choice of drugs is guided
by susceptibility patterns in the community & hospital

Assessment should be done after 48-72 hrs based on

microbiological & clinical data. If causative pathogen is
identified  no reason for combination therapy

If the presenting clinical syndrome is not due to infectious

cause  stop antimicrobial therapy
Empiric Therapy is More Difficult
Hidden of infection location

Antimicrobial Resistance

Poly Microbial
COMMON APPROACH EMPIRIC
THERAPY:
• Antimicrobial width spectrum

• Culture (+)  Narrowing spectrum

• Map of Bacterial
 PK/PD antibiotic therapy
Pharmacokinetic: absorption, distribution, metabolism,
elimination.
Pharmacodinamic: correlations between serum & tissue
concentration with MIC
Parameters:
Time dependent ab: t > MIC
Concentration depend: ratio C max/MIC > 10 X
ratio AUC/MIC
ANTIBIOTIC SELECTION BASE ON
SITE OF INFECTION

 Pulmonary infection
 Intra abdominal infections
 Intravascular infections
 Genitourinary infections
 Wound and skin-related infections
Pulmonary infection

 Nosocomial & VAP is most infection

 50%  MODS
 Risk factor Nosocomial:

 Aspiration, prolong ventilator, older, immune

suppressant, prolong immobilization
Classification of Pneumonia
Early Pneumonia :

• Occur in a week

• Sepsis & MODS <<<

• Because of CAP & Pneumonia Aspiration

Late Pneumonia :

• Gram Positive & Negative Bacterial

Because of intubation  colonization in 4 hour

Microbiology of Pulmonary Infections
Time Bacteria First-line agents Second-line
agents

Early: Strept. pneumoniae Third-generation

Legionella spp.
cephalosporins:
Mycoplasma pneumoniae
Community Chlamydia pneumoniae Quinolones
acquired Staphylococcus aureus •Ceftriaxone
Haemophilus spp. Macrolides
Klebsiella spp. •Cefotaxime
Neisseria spp. •Ceftizoxime
Aspiration-polymicrobial
Anaerobic bacteria
Microbiology of Pulmonary Infections
Time Bacteria First-line agents Second-line
agents

Late: Pseudomonas Anti- Anti-pseudomonal

aeruginosa pseudomonal
Nosocomial β-lactam
Enterobacter spp. β-lactam +/- quinolone
Klebsiella spp. +/- Carbapenem
aminoglycoside
Escherichia coli +/- aminoglycoside

Acinetobacter spp. Fourth-generation

cephalosporin
Intra Abdominal Infections

Classification Intra Abdominal infection

Primer: Spontaneus Bacterial Peritonitis

Secondary: Trauma, Perforation, Post op Abdomen

Tertiary: Persistent & Recurrent infection

 Microbiology of intra-abdominal
infections
Type Bacteria First line agent Second-line
agents

Primary Enterobacteriaceae Third-generation Quinolones

peritonitis cephalosporin :
Streptococcus Carbapenem
pneumoniae Cefotaxime
Piperacillin-
Enterococcus Ceftriaxone tazobactam
faecalis
 Microbiology of intra-abdominal
infections (Cont’)
Type Bacteria First line Second-line
agent agents
2nd peritonitis Aerobic Gram- Carbapenem Antipseudomonal β-
negatives: lactam
causes
including Bacteroides fragilis Third-generation
perforate cephalosporin
d GI
tract + metronidazole
Quinolone +
metronidazole
causes Aerobic Gram- Carbapenem Antipseudomonal β-
including negatives: lactam
post-op +/-
abscess Bacteroides fragilis aminoglycoside Third-generation
anastom cephalosporin
otic leak Enterococcus spp.
+/- aminoglycoside
Pseudomonas
aeruginosa +/- amphotericin B
Candida spp.
 Microbiology of intra-abdominal
infections (Cont’)
Type Bacteria First line agent Second-line
agents
Tertiary Enterococcus spp. Carbapenem Antipseudomonal
β-lactam
peritonitis Candida spp. +/-
aminoglycoside Third-generation
Staphyloccus cephalosporin
epidermidis +/- amphotericin
+/-
aminoglycoside

+/- amphotericin B
Intra Vascular Infection
Intra venous  150.000 cases per year

Iatrogenic

Gram (+) bacterial most accident

If Culture (+) & Catheter  consider to bacteremia

Empiric terapy:
 Vancomycin & Cephalosporin Broad Spectrum
Wound & Skin-related Infection
• Contribute to the development of MODS <<

• Soft Tissue Infected Suspected :

• Empiric therapy : β lactam

• An aerobic organism (Clostridium perfringens or

septicum)  cellulitis, fasciitis, or myositis

• Empiric therapy : Carbapenem (imipenem) or

piperacillin – tazobactam + aminoglicoside
Genitourinary infections
• in place Catether > 10 days  colonization in bladder

• Obstruction is the major risk factor sepsis

• Aerobic Gram (-) bacterial is most frequent infection

• Empiric Antibiotic  single agent : Quinolone

• If persistent fever & sign sepsis :

Looking for evidence of obstruction or renal abxcess or
pyelonephritis
DISTRIBUSI ORGANISME BAKTERI
RSUD Dr. SOETOMO 2016

No Spesies D U S Lain2
GRAM NEGATIF
1 Acinetobacter 129 141 483 0
baumanii
2 Enterobacter 9 28 31
aerogenes
3 Enterobacter 47 118 129 2
cloacae
4 Escherichia colli 101 1285 168 4
5 Klebsiella 214 385 610 6
pneumoniae
6 Proteus mirabilis 4 61 13
7 Pseudomonas 58 246 314 3
aeruginosa
DISTRIBUSI ORGANISME BAKTERI
RSUD Dr. SOETOMO 2016

No Spesies D U S Lain2
GRAM POSITIF
1 Enterococcus 56 328(84%) 5
faecalis
2 Staphylococcus 190(57%) 64 65 15
aureus
3 Staphylococcus 208(87%) 13 8 10
epidermis
4 Staphylococcus 267(89%) 24 7 3
haemolyticus
5 Staphylococcus 333(96%) 5 9
hominis
 RESISTENCE RATE
Bacteria Ampi Cefo Cefepim Mero Sulbe

E coli 99,2% 58,2% 28,4% 4,8% 96,7%

K. pneumo 97,1% 66,9% 37% 3,4% 93,8%

Proteus 88,9% 27,8% 8,3% 5% 66,7%

Pseu aerug 100% 81,3% 48,3% 16,7% 72,1%

Pseu spp - 75% 51,5% 11,6% 90%

CN Staph 81,3% - - 25,3% -

Sta aureus 76,2% - - 17,6% -

 RESISTENCE RATE
Bacteria Cotri Cipro Fosfo Genta Amik
m
E coli 85,9% 46,5% 45,4% 89,7% 41,2%

Klebs 86,8% 49% 66,1% 37.9% 37,9%

Proteus 85% 18,8% 65% 26,7% 26,7%

Pseu aerug 88,2% 45,5% 89,4% 63,6% 43,4%

Pseu spp 93% 46,2% 66,7% 75% 44,4%

CN Staph 83,3% 36,2% 61,5% 75% -

Sta aureus - 21,1% - - -

 RESISTENCE RATE (%)
Bacteria Ery Peni Vanco Chlora Moxi Levo

CN Staph. 59,8 84 7,9 57,8 5,1 25

Staph. Aur 52,9 77,3 13,6 64,7 14,3 23,8

Summary
• Sepsis remains a serious problems that cause of high
morbidity & mortality

• Initial therapy  nearly always empiric

• Antibiotic selection base on site of infection

• Local map of antibiotics

• optimalize bacterial eradication by PK/PD antibiotics

• Antimicrobial BROAD spectrum  DEESCALATION

 narrowing spectrum