Copyright ©The Author(s) 2016.
World J Hepatol. Feb 28, 2016; 8(6): 307-321
Published online Feb 28, 2016. doi: 10.4254/wjh.v8.i6.307
Table 1 State of immune dysfunction in patients with cirrhosis
Natural barriersFragile, thin and/or edematous skin
Alteration of GI motility and mucosal permeability
Alteration of GI bacterial flora, bacterial overgrowth
↑ GI mucosal ulcerations
Hepatic RES activityPortosystemic shunting
Kupffer cells - ↓ number, impaired function
Cellular defense mechanismsRES - ↓ activation, ↓ chemotaxis, ↓ phagocytosis, ↓ production of pro-inflammatory cytokines (IL-1, IL-6, IL-18, TNF-α)
PMN - ↓ lifespan, ↓ intracellular killing activity, ↓ phagocytosis, ↓ chemotaxis
Serum factors↓ Complement levels (C3, C4, CH50)
↓ Opsonic activity
↓ Protein C activity
Iatrogenic and treatment-related factors↑ Invasive procedure and catheters
Frequent hospitalization
Immunosuppressive agents (autoimmune hepatitis, post-transplantation)
Interferon therapy (viral hepatitis)
Proton pump inhibitors
Other compelling factorsMalnutrition
Alcohol drinking
Table 2 Types of infection and suggested empirical antibiotic therapy in patients with cirrhosis
Types of infectionCommon responsible bacteriaSuggested empirical antibiotic
SBP, spontaneous bacteremia, SBEEnterobacteriaceae1st line: Cefotaxime or ceftriaxone or BL-BI IV
S. pneumoniaeOptions: Ciprofloxacin PO for uncomplicated SBP1; carbapenems IV for nosocomial
S. viridansinfections in areas with a high prevalence of ESBL
BL-BI may prefer in those with suspicious for enterococcal infection2
PneumoniaEnterococciCommunity-acquired: ceftriaxone or BL-BI IV + macrolide or levofloxacin IV/PO
S. pneumoniaeNosocomial and health care-associated infections: Meropenem or cetazidime IV +
H. infuenzaeciprofloxacin IV (IV vancomycin or linezolid should be added in patients with risk
M. pneumoniaefactors for MRSA3)
Legionella spp.
P. aeruginosa
S. aureus
Urinary tract infectionEnterobacteriaceae1st line: Ceftriaxone or BL-BI IV in patients with sepsis. Ciprofloxacin or
E. faecaliscotrimoxazole PO in uncomplicated infections
E. faeciumOptions: In areas with a high prevalence of ESBL, IV carbapenems for nosocomial infections and sepsis (+ IV glycopeptides for severe sepsis); and nitrofurantoin PO for uncomplicated cases
Skin and soft tissue infectionsS. aureusCommunity-acquired: Ceftriaxone + cloxacillin IV or BL-BI IV
S. pyogenesNosocomial: Meropenem or cetazidime IV + glycopeptides IV
P. aeruginosa
Vibrio vulnificus
Aeromonas spp.
MeningitisS. pneumoniaeCommunity-acquired: Cefotaxime or ceftriaxone IV + vancomycin IV
EnterobacteriaceaeAmpicillin IV should be added if L. monocytogenes is suspected4
L. monocytogenesNosocomial: Meropenem + vancomycin IV
N. meningitidis
Table 3 Common manifestations and risk factors of bacterial pathogens in patients with cirrhosis
PathogensCommon clinical syndromeRisk factorsRemarks
Aeromonas spp. (A. hydrophila, A. sobria, A. aquariorum)[120-126]SBP, bacteremia, SSTI, enterocolitisContaminated food and waterIncreased incidence
DiabetesHigh mortality (20%-60%), especially when
Most reports were from East Asiapresence of hypotension on admission
Campylobacter spp.[127,128]Bacteremia, SBPAlcoholicIncreased incidence
High mortality (10% in bacteremia)
Clostridium spp. (C. perfringens, C. bifermentans, C. septicum)[4,129,130]SSTIDiabetesIncreased incidence
Very high mortality (54%-65%)
Clostridium difficile[108,131-133]ATB-associated diarrhea and colitisBroad-spectrum ATBIncreased incidence
HospitalizationHigher mortality (14%) when compare to non-cirrhotics
PPIsIncreased cost and length of hospital stay
Enterococcus spp. (E. faecium, E. faecalis, E. galinarum)[134-136]SBP, bacteremia, UTI, endocarditis, biliary tract infectionHealthcare-associated infectionIncreased incidence
Quinolone prophylaxisHigh mortality (30% in bacteremia; 60% in SBP)
Increased incidence of VRE colonization and infection in liver transplant setting
Listeria monocytogenes[137,138]SBP, bacteremia, meningitisHemochromatosisIncreased incidence
Mycobacterium TB[2,139,140]Pulmonary TB, TB peritonitis, TB lymphadenitis, disseminated TBAlcoholicIncreased incidence, especially extrapulmonary forms (>
Developing countries50% of TB peritonitis cases in the United States had
Exposed to TB caseunderlying cirrhosis)
High mortality (22%-48%)
Increased risk for multi-drug resistant TB
Increased risk for anti-TB-induced hepatotoxicity
Pasteurella multocida[141-143]SBP, bacteremia septic arthritis, meningitisPresence of ascites (TB peritonitis)Increased incidence
Domestic animal (cats or dogs) bites or scratchesHigh mortality (10%-40% in bacteremia)
Staphylococcus aureus[45,144,145]SSTI, UTI, SBP, bacteremia, endocarditisAlcoholicIncreased incidence of MRSA carriage and infection
Invasive proceduresHigh mortality (30% in bacteremia)
HospitalizationRemoval of the eradicable focus was associated with
decreased mortality
Streptococcus bovis[146,147]Bacteremia, SBP meningitis, endocarditis, septic arthritisQuinolone prophylaxisIncreased incidence
Colonic lesion(s): Adenoma orHigh mortality (up to 40% in bacteremia with
adenocarcinoma (presence inadvanced cirrhosis)
18%-40% of cases)Colonic lesion(s) was present in 18%-40% of cases
Streptococcus group B[148-150]SSTI, bacteremia, SBP, meningitis, pneumoniaPost endoscopic sclerotherapy and banding ligationIncreased incidence
High mortality (10%-25% in SBP and bacteremia;
45% in meningitis)
Streptococcus pneumoniae[89-92]Pneumonia, SBP bacteremia, SSTI, meningitisAlcoholicIncreased incidence of invasive pneumococcal disease
Post-splenectomyHigh mortality (10%-20%)
Not vaccinated
Vibrio spp. (V. vulnificus, non-o1 V. cholera, V. parahemolyticus)[151-153]SSTI, bacteremia, gastroenteritis, diarrhea, SBPHemochromatosisIncreased incidence
Exposed to seawater and undercooked seafoodsVery high mortality (50%-60% in bacteremia; 24% in SSTI)
Most reports were from East Asia
Yersinia spp. (Y. enterocolitica, Y. pseudotuberculosis)[154,155]Bacteremia, SBP, hepatosplenic abscessesHemochromatosisIncreased incidence (in hemochromatosis)
Exposed to animals andHigh mortality (50% in bacteremia)
contaminated foods
Table 4 Vaccinations and other preventive measures for bacterial infections in patients with cirrhosis
Raw/uncooked foods, especially seafood
Close contact to at-risk animals or sick people
Wound exposure to flood or seawater
InfluenzaRecommended yearly for all patients with chronic liver disease
Pneumococcal (polysaccharide)Recommended for all cirrhotic patient
Booster dose after 3-5 yr
Hepatitis ARecommended for all non-immune, cirrhotic patient, 2 injections 6-12 mo apart
Anti-HAV should be checked 1-2 mo after the second dose
Hepatitis BRecommended for all cirrhotic patient without serological markers of HBV (e.g., negative HBsAg, anti-HBs, and anti-HBc antibodies)
3 injections (at month 0, 1 and 6)
Anti-HBs should be checked 1-2 mo after the last dose
Patients with advanced cirrhosis should receive 1 dose of 40 μg/mL (Recombivax HB) administered on a 3-dose schedule or 2 doses of 20 μg/mL (Engerix-B) administered simultaneously on a 4-dose schedule at 0, 1, 2 and 6 mo
Other vaccines, e.g., Td, Tdap, MMR, varicellaRecommendations are as same as general adult population
Prophylactic antibiotics
Secondary prophylaxis for SBP[32,41]Recommended for all cirrhotic patients who recovered from SBP
Norfloxacin 400 mg PO daily
Alternatives: TMP/SMX 1 double-strength tablet or ciprofloxacin 500 mg PO daily
Primary prophylaxis in GI bleeding[32,41]Recommended for all cirrhotic patients with GI hemorrhage
Norfloxacin 400 mg PO twice daily or ceftriaxone 1 g IV daily for 7 d
IV ceftriaxone is preferred, in patients with advanced cirrhosis as defined by the presence of at least two of the following: Ascites, severe malnutrition, encephalopathy or bilirubin > 3 mg/dL
Primary prophylaxis in patients with low ascitic fluid protein[32,41]Recommended for cirrhotic patients with ascitic fluid protein < 1.5 g/dL and at least one of the following is present: Serum creatinine > 1.2 mg/dL, blood urea nitrogen > 25 mg/dL, serum sodium < 130 mEq/L or Child-Pugh > 9 points with bilirubin > 3 mg/dL
Prophylaxis before undergoing endoscopic and surgical proceduresProphylactic antiobiotics are recommended for the moderate-high risk invasive endoscopic or surgical procedures (choice of antibiotics should be individualized)
Prophylactic antibiotics are not routinely recommended for diagnostic endoscopy, elective variceal band ligation or sclerotherapy, and abdominal paracentesis
Table 5 Studies demonstrated risk of bacterial infections in cirrhotic patients receiving proton pump inhibitors
Campbell et al[116]Case-control116NS for SBP (OR = 1.05; 95%CI: 0.43-2.57)
Bajaj et al[108]Case-control83230PPI use were significantly higher in those with CDAD (74% vs 31%, P = 0.0001)
Bajaj et al[112]Retrospective, propensity-matched1268↑ Serious infections (HR = 1.66; 95%CI: 1.31-2.12)
de Vos et al[119]Case-control102PPI were more frequently used in SBP patients than in controls, but did not influence prognosis of SBP
Min et al[113]Retrospective cohort1554↑ SBP (HR = 1.39; 95%CI: 1.057-1.843)
Mandorfer et al[117]Retrospective607PPI neither predisposes to SBP (HR = 1.38; 95%CI: 0.63-3.01) or other infections (HR = 1.71; 95%CI: 0.85-3.44)
Terg et al[118]Prospective770PPI therapy was not associated with a higher risk of SBP and other infections
Merli et al[114]Cross-sectional400↑ Bacterial infections (OR = 2; 95%CI: 1.2-3.2)
O'Leary et al[115]Prospective188↑ Infections: CDAD and SBP (OR = 2.94; 95%CI: 1.39-6.20)