Are bacterial infection a problem in

cirrhosis?

Hospitalized cirrhotic patients are concerned by bacterial infections

30 to 50 %

In cirrhotics at admission or during hospitalization: 32%

In hospitalized non-cirrhotics: 5% - 7%

Bacterial infections

Bacterial infections are well described complications of cirrhosis that greatly increase life-threatening complications& mortality rates in cirrhotic patients.

Recognition of infection is made more difficult by the absence of the normal clinical feature

of infection that is:

fever, rigors, hypotension, and leucocytosis in which:

case the only clues may be deterioration of hepatic precoma or coma or renal function

Factors play important roles in the development of bacterial infections in

cirrhosis : 1-The severity of liver disease

2 -gastrointestinal haemorrhage 3-Invasive technique:

catheter,canula,endoscopy,ryle,sungestakenLiver biopsy?&paracentesis

4-Admission to ICU5-Low acitic albumin

6-Increase total serum bilirubin

bacterial infections in patients with cirrhosis, spontaneous bacterial peritonitis was the most common infection (31%),

followed by urinary tract infection (25%), pneumonia(21%), and skin infections (11%).

Gram-negative enteric organisms, especially E coli, are the most commonly identified

pathogens.

This increased susceptibility is due to multiple immune system defects(humoral&cell mediated including:

1-complement deficiency(impaired opsonic activity)

2-Reduced chemoattractant activity,

3-decreased polymorphonuclear leukocyte activity.

4-Impaired bactericidial function of IgM for certain strains of Escherichia coli,

5-Reduced reticuloendothelial activity and kupffer cell activity

Sepsis is a systemic inflammatory response to the presence of infection, mediated via the production of many cytokines, including

tumour necrosis factor (TNF-), interleukin (IL)-6, and IL-1, which cause changes in the circulation and in the coagulation cascade. There is stagnation of blood flow and poor oxygenation, Subclinical coagulopathy with elevated D-dimers, and Increased production of superoxide from nitric oxide synthase

All of these changes favour

1-Endothelial apoptosis and necrosis 2-Increased oxidant stress .

3-Reduced levels of activated protein C, which is normally anti-inflammatory and antiapoptotic.

All these can lead to further tissue injury and organ failure

Studies of serum complement in patients with liver disease

Type of liver disease finding mechanism

1-Acute liver disease(a )Acute viral hepatitis Deficiency of classical pathway Reduced

synthesis and increasedfactors, especially in acute stage catabolism

and with serum sickness ‘(b )Fulminant hepatic failure Severe deficiency of classical and

Predominantly decreasedalternate pathways irrespective of synthesis

aetiology

2- Chronic liver disease(a( Alcoholic cirrhosis and/or hepatitis Generally minor deficiencies of

Mainly,classical and alternate pathways

. Most severe if liver disease decompansated.unrelated to HBsAg status

(b( Chronic active JepatI

Mainly reduced synthesis, but

)c( Cryptogenic cirrhosis increased catabolism a factor in chronic active hepatitis hbsag +ve

( d )Primary biliary cirrhosis

Normal or increased levels, with Increased

synthesis and increased

catabolism

evidence of compliment

activation, especially of the

classical pathway

•

Problems of bacterial infection in patients with liver disease

Bacteria + Complement Neutrophil

)antibody (Complement activation

Bacterial Opsonic factor Chemotactic factorIysis (C3b) (C5a). Activated neutrophils

)adhere to vascularendothelium and moveTo the site of infection (

Opsonised Bacteria + neutrophil

PhagocytosisKilling

Bacteria in mesenteric lymph nodes

Systemic circulation

Urinary infections

Dysfunction of innate defenders

SBP

Infections and cirrhosisPathophysiology

Pulmonary infections

Reticuloendothelial system depression

Gut permeability Bacterial overgrowth

Enteric bacteria

Bacteremia

Spontaneous Bacterial Peritonitis (SBP) (± bacteremia)

Urinary Tract Infection (UTI) (± bacteremia)

Pulmonary infection

+bacteremia

Others (peritoneal

tuberculosis)

25-50 % of death directly due to bacterial infection

Mortality rate

In decompansated cirrhotics during hospitalization :

46.5% for patients with bacterial infection .

22.7% for patients without infection.

Mortality rate according to type of infection:

25% with urinary infections.

50% with pulmonary infection

80% with bacteraemia.

Types of organisms responsible for bacteraemia in patients with liver disease

Chronic liver disease58% Fulminatit hepatic failure 61%Gram positive 21% 26%StaphylococciStreptococci

Group B haemolytic Pneumoniae

ViridansBacillus sp- .Clostridium welchii-

Other gram positive sp. Gram negative 42% 39% Escherichia coliPseudomonas aeruginosaKlebsiella pneumoniae

Clinical presentationBacterial infections in cirrhotics hav few

symptoms.

So, They need an active search through:

1 .Chest X-ray.

2 .Urine culture.

3 .Blood culture.

4 .Paracentesis, if there is ascites.

Urinary tract infections

Urinary tract infections (UTIs) in cirrhosis are usually asymptomatic, and bacteriuria alone is found in a high proportion of UTI episodes in

cirrhotics .

Its potential role in causing bacteremia may be underestimated.

The incidence is markedly higher in cirrhotics with indwelling catheters and female cirrhotic

Pneumonia

Community-acquired pneumonia is a frequent

complication in subjects with active alcoholism.

Streptococcus pneumoniae is the causative organism in most lower respiratory tract infections in alcoholics.

However, other pathogens normally present in the oropharyngeal area, especially anaerobic bacteria or

Haemophilus influenzae, Klebsiella pneumoniae,

mycoplasma pneumonia, or Legionella spp., have also been reported

Endocarditis

Endocarditis complicating the course of cirrhosis

usually arises from a previously normal

endocardium.

Streptococcus spp. (Streptococcus viridans, Streptococcus

enterococcus, Streptococcus bovis) and Staphylococcus aureus are the most common

causative organisms, but

the possibility of endocarditis caused by enterobacteria should not be underestimated

Soft tissue infections

are found in 2%to 11% of cirrhotic patients,

with gram-positive cocci, primarily

staphylococci and streptococci, being the most prevalent pathogens.

fulminant gram-negative cellulitis associated with septic shock and death

was reported .

Early recognition of this complication of cirrhosis is extremely important because

its course is usually rapid and fatal

Figure 1. Case 4. Hemorrhagic bulla and cellulitis on the medialaspect of the inner thigh. Note patchy areas of edema, necrosis,

and inflammation.

Figure 2. Case 4. Bullous cellulitis on the inner aspect of the leftcalf. Cultures were obtained from this large bulla.

Bacterial meningitis

Bacterial meningitis is also rare in patients with liver disease.

There being isolated reports of pneumococcal

meningitis in patients with alcoholic cirrhosis

and primary biliary cirrhosis.

TuberculosisDespite the decline in the incidence of tuberculosis in the general population ,

studies from several countries, with similar life styles and incidences oftuberculosis, show increasing numbers of alcoholics among patients withtuberculosis. " Alcoholics tend to have more advanced tuberculosis at thetime of presentation, more adverse effects from chemotherapy, poorercompliance, and increased incidence of drug failure. Fortunately, whenadequate therapy has been completed there is no significant difference inrelapse rates between patients with and without a history of alcoholism.Recent reviews of abdominal tuberculosis make no mention of alcoholics orcirrhotics, and only sporadic cases are reported in series of patients with liver disease and spontaneous bacterial peritonitis." Immunosuppressivetherapy administered to patients with liver disease may result in development of tuberculosis either de novo or by reactivation .

Patients with liver disease, particularly those with evidence of past infection with tuberculosis,should be monitored regularly for evidence of reactivation especially while receiving immunosuppressive therapy.

Bacteraemia in cirrhosis

The incidence of bacteremia in patients with

chronic liver disease is 5 to 7 times higher

than that in other hospitalized patients

Sepsis ensues when there is overactivation

of pathways involved in the development of

the sepsis syndrome, associated with

complications such as

Renal failure

Encephalopathy ,

Gastrointestinal bleeding

Shock

with decreased survival

BACTERIAL INFECTION AND VARICEAL HAEMORRHAGE

Bacterial infections are frequently associated with upper gastrointestinal bleeding in cirrhotic

patients .

About two thirds of these infections are present at hospital admission .

Moreover, bacterial infections are more common in cirrhotic patients with acute variceal bleeding than in those admitted to hospital with other forms of decompensation, such as encephalopathy.

Variceal bleeding is a life-threatening complication of cirrhosis

Potential risk factors include:

Clinical

Endoscopic

Haemodynamic factors.

Why bleeding occurs unpredictably in individual patients is not known.

Bacterial infections in patients with variceal haemorrhage may be the critical factor that triggers bleeding In patients with large varices and a high wall tension

Recently,bacterial infections and/or endotoxaemia are associated with 1-variceal bleeding

2-Failure to control variceal bleeding 3-More early variceal rebleeding due toabnormalities in coagulation,

vasodilatation of the systemic vasculature and

worsening of the liver function.

Bacterial infection or a surrogate of its presence (use of antibiotics) had the strongest independent association with failure to control bleeding in cirrhotic patients

with variceal bleeding .

Even stronger than active bleeding at endoscopy and severity of liver disease

Endotoxaemia secondary to bacterial infection may be indeed the critical trigger for variceal haemorrhage as it produces a wide series of effects: Impairment of

1-primary and secondary haemostasis, 2-increase in portal pressure and

3-worsening of liver functions.

This occurred through:

1 -the release of endotoxin into the systemic circulation during episodes of bacterial infection results in a further increase in portal pressure through a-the induction of endothelin and

b- possibly vasoconstrictive cyclo-oxygenase products.

The subsequent contraction of hepatic stellate cells causes a rise in intrahepatic vascular resistance.

2-Furthermore, endotoxin-induced nitric oxide and prostacyclin, and prostacyclin induced by endothelin could inhibit platelet aggregation, which may result in a further deterioration of primary haemostasis at the level of varix.

3-Endotoxins and inflammation due to

infection can release heparinoids from the

endothelium and mast cells

The combination of these effects leads to the onset of variceal haemorrhage

Recent advances in management strategies

of infections early in cirrhosis have helped

to prevent the development and downward

spiral of the sepsis syndrome& improve the

prognosis of these patients.

These include:

.The use of prophylactic antibiotics in patients with gastrointestinal bleed to prevent infection and

.The use of albumin in patients with spontaneous bacterial peritonitis to reduce the incidence of renal impairment

The use of antibiotics has to be judicious, as

their indiscriminate use can lead to

antibiotic resistance with potentially

disastrous consequences

Short term Primary prophylaxis

-To prevent infection after GI bleeding.

-Selective decontamination by oral norfloxacin.

-The regimen is 800 mg/day for 7 days.

-It resulted in significant decrease in:

The incidence of infection (14% vs 45%)

The mortality rate (15%-24)

Long term Secondary prophylaxis

-For patients recovered from an episode of

SBP.

-Oral norfloxacin, 400 mg/day.

-Till absence of ascites, transplantation or

death.

-Decreased recurrence of SBP (20% vs 68%).

-May lead to quinolone resistant infection.