Sepsis and septic shock

Wang Liping

Wechat：wlp306972254
Department of Infectious Diseases, Affiliated Hospital
of Xuzhou Medical University
 CASE
Ø Femal,53Y, complained of “fever lasted a half months”.
Ø Accompanied with chill, shiver, general malaise, and no
appetite. the highest temperature was 40.2 ℃ ，no cough,
no expectoration.
Ø Signs：T:38.6 ℃, herpes around the mouth ,
it was scarred
.
Mature NE increased
 Questions

Ø1. What is the reason of the patient's fever ?

Ø2. What is the patient's diagnosis? And what kand

of examination can we do to confirm diagnosis?
Streptococcus
equi
 Conception

ØPathogenic bacteria or conditional pathogenic

bacteria invade the bloodstream

ØGrow and produce toxins, enzymes and

metabolic products cause systemic infection of
the bloodstream.
 Conception
Ø Septicemia : a severe toxinemia ,systemic infection
Ø Manifestation:
Fever
rash
joints swelling
liver and spleen enlargement
Migrating lesions
septic shock
 Definitions
ØBacteremia
ØToxinemia
ØSepticemia
ØSystemic inflammatory response syndrome
（SIRS）: Infectious + Noninfectious
ØSepsis: septicemia + SIRS
ØSeptic shock: sepsis with hypotension
ØSIRS: infectious and noninfectious etiology.
Infectious: septicemia.
Noninfectious: acute pancreatitis, severe
trauma, major burns and hypoxemia.

ØSepsis: SIRS that has a proven or suspected

microbial etiology.
 Systemic inflammatory response syndrome
（SIRS）

It should be includes two or more ：

① fever (＞38℃) or hypothermia (＜36℃);

② heart rate ＞90 beats/min;

③ respiratory rate ＞ 20 /min) or PaCO2<32mmHg

④ WBC>12,000/mm3, or <4,000/mm3or immature WBC

>10%.
ØSepsis: septicemia + SIRS
ØSeptic shock: sepsis with hypotension ( arterial
BP<90 mmHg or 40mmHg less than normal BP).
ØMultiple-organ dysfunction syndrome (MODS) :
the terminal stage of septicemia.
 ETIOLOGY
ØGram-positive cocci
ØGram-negative bacilli
ØAnaerobe
ØFungus
ØOther bacteria: Complex bacteria, resistant
bacteria, opportunistic pathogens
 ETIOLOGY
Gram-positive cocci
ØStaphylococci :
Staphylococcus aureus
Staphylococcus epidermidis
ØStreptococci:
Streptococcus pneumoniae
hemolytic streptococcus
Ø Enterococcus
 ETIOLOGY
Common resistant cocci
Ø MRSA: Methicillin resistant staphylococcus aureus

Ø MRSE: Methicillin resistant S. epidermidis

Ø PRSP: Penicillin-resistant Streptococcus pneumoniae

Ø VRE: vancomycin resistant Enterococcus

 ETIOLOGY
Gram-negative bacilli
ØEscherichia coli
Øklebsiella pneumoniae
ØPseudomonas
ØProteus bacillus
Ø Acinetobacter
 ETIOLOGY
Common resistant bacilli
ØESBL: extended-spectrum beta-lactamase

ØMDR-PA ：multiple-drug resistant

Pseudomonas aeruginosa
ETIOLOGY

20
ETIOLOGY

Gram positive
Gram negative
 ETIOLOGY
Anaerobe
ØBacteriodes fragilis

Ø Bacillus perfringens
 ETIOLOGY
fungus
ØCandida albicans

ØAspergillus
 The changes of bacterial spectrum
• Periods Changes
pre-antibiotic G+ predominant (>85%)
<70s G+ decreased greatly
• 70s-80s G- predominated
since 80s G+ rise gradually again
and is more than G- now
 The changes of bacterial spectrum

Hospital-acquired septicemia: CNS(coagulase negative

staphylococci): S.aureus, Enterococci, Candida, E.coli, K.
pneumoniae, Enterobacter and Serratia

Community-acquired septicemia: S. pneumoniae, E.coli,

S.aureus, Salmonella, Haemophilus influenzae and many
types of Streptococci
 PATHOGENESIS
Ømicrobial virulence:
pathogens high in toxicity or large in number ,
septicemia is very likely to occur
ØHost factors (inducing factors)
Host response ( interaction between microbe
and host)
 The routes of infection
ØDifferent pathogens have different routines

ØIncluding infections in the lungs, abdomen,

urinary tract, genital tract,, biliary tract.
Ø The pathogenic bacteria vary with factors :
1. age
2. sex
3. site of primary infection
4. underlying diseases
5. hospital or community
6. host immunity
7. inhabiting regions.
 Microbial factors
Ø gram-negative bacteria : secondary to biliary tract，gastrointestinal or
urinary tract infections．
Ø S．aureus : secondary to skin pyogenic infections，burn，pneumonia，
otitis media，oropharyngeal or gynecologic infections．
Ø P．aeruginosa : secondary to urinary tract，respiratory or skin wound
Ø Anaerobic bacterial : intestinal，intra—abdominal or gynecologic
infections．
Ø fungal : oral，intestinal or respiratory
 Microbial factors
1.Gram-positive bacteria

Øproduce many enzymes and toxins(exotoxin)

Øhelpful for bacteria to grow and proliferate but

can cause severe septicemia or toxic shock
syndrome (TSS)
 2.Gram-negative bacteria: release
LPS(endotoxin).
1). Release cytokine and inflammatory mediator
2). myocardial and vascular endothelial injury
3). Initiate endogenous coagulations，activate
complements，impels release of vasoactive
substances
4). induce disorders of microcirculation and leads to
sepsis shock and DIC
 Host factors

1.Mucocutaneous defense :skin or mucosal lesion:

such as trauma、 inflammation et.al
 Host factors
2.Systemic inflammatory response:
① Neutropenia.
② Some drugs (Immunosuppressive, broad-spectrum
antibiotics, cytotoxic).
③ Invasive procedures ( tracheal intubation, tracheotomy,
mechanical ventilator, IV catheter, endoscopy)
④ Underlying diseases (cirrhosis, uremia, diabetes,
rheumatic diseases)
 PATHOLOGY

1. Degeneration, edema, necrosis of cells and

tissues of vital organs.

2. Vascular endothelium injury.

3. Hyperplasia of monocyte-macrophage
system ( hepatosplenomegaly)
CLINICAL MANIFESTATIONS
ØNo specific manifestation

ØNo confirmed incubation period

 Main clinical manifestations
ü Primary inflammation
ü Toxemic symptoms
ü Rash
ü Joint symptoms
ü Hepatosplenomegaly
ü Migrating lesions
 1. Toxinemia symptoms.
① Abrupt high fever, rigors, remittent or sustained patterns.
② Generalized myalgia, fatigue
③ Neurological symptoms such as headache, delirium,
lethargy even coma.
④ Tachycardia and tachypnea.
⑤ ARDS, shock and encephalopathy in severe cases.
⑥ No fever is common in neonates, elderly and patients with
uremia, cirrhosis
 2. Skin lesions.

1). Petechia is the commonest , can distribute to

trunk, extremities, mucus and even to soles
and nail beds.

2). Urticaria, scarlet-like eruption and pustule

also can develop.
Pustular rash
Urticaria
Varicella rash

Petechia necrotic rash

maculopapule
 3. Joint involvement

• It is common in Staphylococcus aureus,

• The main manifestation of joint involvement is

arthritis, arthralgia and joint effusion.
 4. Hepatosplenomegaly.

• In general, it is mildly enlarged.

• It can be apparent when toxic hepatitis or

liver abscess complicated.
 5. Metastasis

1). Result from spread of bacterial thrombus via

bloodstream.

2). Very common among S. aureus and anaerobe.

3). All the organs can be involved.

 6. Primary infection

1). Septicemia arises from primary local

infections. The pathogen varys with different
infection sites

2). This information is very importance on

clinical diagnosis and antibiotics selection.
Characteristics of different pathogens
 1. Gram positive: S. aureus
1). Risk factors(RF): catheters, indwelling mechanical devices,
trauma, major burns, IV drug users and valvular heart diseases.
2). Primary infections(PI): skin, otitis media, bones and joints.
3). Age: 20~50yr.
4). Fever: acute and high, sustained or remittent.
5). Skin lesion: common.
6). Metastasis: common.
7). Shock: infrequent except toxic shock syndrome( TSS,) late episode
 2. Gram negative: E. Coli.
1). Risk factors: diabetes, malignancy, cirrhosis ,uremia,
invasive procedures and neutropenia.
2). Primary infections: GI tract, bile duct and urogenital
tract.
3). Age: neonate, elderly.
4). Fever: rigors, intermittent even hypothermia.
5). Skin lesions: not very common
6). Metastasis: not very common.
7). Shock: common(30~60%) and refractory, early
episode.
 The comparison between G+ and G-.
G+ G-
Ø RF catheters, trauma, burns underlying diseases and
and drug users etc. invasive procedures

Ø PI skin, otitis media, GI tract, urogenital tract

bones and joints. and bile duct.
Ø Age 20～50yr neonate, elderly
Ø Fever acute, high, sustained rigors, intermittent
or remittent. even hypothermia
Ø Skin common less
Ø Metastasis common less
Ø Shock rare, late common, early
Ø BR WBC↑↑ N↑↑ WBC↑ /- N↑
Ø limulus test negative positive
 3 . Anaerobe: B. fragilis

1). Polymicrobial infections are common.

2). Hyperbilirubinemia (10~40%).

3). Thrombophlebitis

4). Metastatic abscess.

 4. Fungus: C. albicans

1). Its incidence increased. Most are hospital—

acquired infections
2). The patients are often immunocompromised.
3). As a superinfection, it is often covered by
primary infection.
4). Part of the cases were diagnosed by autopsy.
 LABORATORY FINDINGS

Blood routine test：

Ø Leukocytosis (10000-30000/ul)
Neutrophils (N) rise
Ø Eosinophils (E) decrease or disappear
Ø Normal WBC count ,even leukopenia can present
in gram negative septicemia, but N still elevated.
 Etiologic culture

Ø blood, bone marrow， cerebrospinal fluid（CSF）

ascites and aspirate of skin lesions, etc.

Ø blood culture: before antibiotics, draw blood

during rigors and high fever, multiple samples,
>5ml for neonate and infant, >10ml for adult
 The others:
• Limulus Lysate Test (LLT): has limited diagnostic
value for gram negative septicemia.

X-ray for suppurative arthritis.

Echocardiography when bacterial endocarditis
suspected
 DIAGNOSIS

ØSepticemia: acute febrile illness with leukocytosis

and elevated neutrophils can’t be explained by
local or single organ’ s infection.

ØHighly suspicious: there is primary local infection,

but general response is not good after effective
antibiotics treatment against it.
 Clinical diagnosis

Ødevelop rash, hepatomegaly splenomegaly

and metastatic abscess during illness.
 Definite diagnosis:
Østablished by positive blood or bone marrow
culture results
 Differential diagnosis:
1. Adult onset still’s disease
2. Typhoid fever
3. Miliary tuberculosis
4. Malignant histocytosis
5. Rheumatic fever
 Prognosis

1. Total mortality rate: 30%-40%.

2. It varies with different pathogens and

underlying diseases.
 TREATMENT
Ø Antimicrobial agents (most important)
1. Principles
1).Initiate empirical treatment
2). Combination therapy
3). Intravenous route
4). Prolonged period
 2. Antibiotics selection for specific pathogen

1). Unknown bacteria:

antibiotics covering both G+ and G-

2). Staphylococcus aureus: Penicillin sensitive(rare):

Penicillin , Penicillin resistant(common): Oxacillin
MRSA, MRSE: Vancomycin， Linezolid

3). Streptococci: Penicillin G

4). Enterococci: resistant to many antibiotics,
combination necessary:
A. Penicillin or ampicillin + aminoglycoside
B. 3rd generation cephalosporin + aminoglycoside
C. Vancomycin + aminoglycoside
D. Imipenem + cilastatin
5). Gram-negative bacteria: resistance common,
combination necessary： Enzyme resistant
compound preparation ；Quinolone
antibiotics； carbapenem
6). Anaerobes: metronidazole, clindamycin,
lincomycin
7). Fungi: amphotericin B, fluconazole
 Remove the source of infection
(also essential!)

1. Completely drain local abscesses

2. Remove indwelling IV catheters

3. Removal of prosthetic joint and valve may be

needed

4. Sometimes surgery inevitable

 Symptomatic and supportive treatment

Ømaintain water, electrolytes balance; correct

acidosis and alkalosis

Øcorrect shock if present.

ØSupportive: nutrition supplementation; infuse

albumin, immunoglobulin, and FFP if necessary.
 Other measures

1. Corticosteroid: remains controversial

2. Granulocyte infusion

3. GSF administration
 PREVENTION

1. Reduce the invasive procedures;

2. Replace IV catheters timely;

3. Avoid indiscriminate use of antibiotics;

4. Stick to infection control measures.